Respiratory Diseases and the Fire Service - IAFF

U.S. Fire Administration 

Mission Statement 

As an entity of the Department of Homeland Security’s Federal Emergency Management 

Agency, the mission of the USFA is to reduce life and economic losses due to fire and 

related emergencies, through leadership, advocacy, coordination and support. We 

serve the Nation independently, in coordination with other Federal agencies, and in 

partnership with fire protection and emergency service communities. With a commitment 

to excellence, we provide public education, training, technology, and data initiatives. 

This project was developed through a Cooperative Agreement (Developing Materials on the 

Long-Term Health Effects of Occupational Respiratory Exposures on Fire Fighters' Respiratory 

Health and the Ability of Exposure Reduction and Post-Exposure Mitigation Strategies to Improve 

Outcomes - EME-2003-CA-0342) between the Department of Homeland Security, United States 

Fire Administration and the International Association of Fire Fighters. 

Copyright © 2010 by the International Association of Fire Fighters. This publication is protected by 

copyright. The IAFF authorizes the reproduction of this document exactly and completely for the 

purpose of increasing distribution of the materials. None of the materials may be sold for a profit 

under the provisions of public domain. These materials have been copyrighted under the copyright 

laws of the United States. Permission to duplicate these materials is conditional upon meeting the 

above criteria and may be rescinded by the IAFF for failure to comply 

International Standard Book Number: 0-942920-51-1

PREFACE 

The United States Fire Administration (USFA) is committed to using all 

means possible for reducing the incidence of occupational diseases, injuries 

and deaths to fire fighters. One of these means is to partner with fire service 

organizations who share this same admirable goal. One such organization 

is the International Association of Fire Fighters (IAFF). As a labor union, the 

IAFF has been deeply committed to improving the safety of their members 

and all fire fighters as a whole. This is why the USFA was pleased to work with 

the IAFF through a cooperative agreement to research and develop materials 

addressing the long-term effects from occupational respiratory exposures on 

fire fighter’s health and the ability of exposure reduction and post-exposure 

mitigation strategies to improve health outcomes. The USFA gratefully 

acknowledges the following leaders of the IAFF for their willingness to partner 

on this project. 

General President General Secretary-Treasurer 

Harold A. Schaitberger Thomas H. Miller 

Assistant to the General President 

Occupational Health, Safety & Medicine 

Richard M. Duffy 

Director of Occupational Health and Safety 

James E. Brinkley 

International Association of Fire Fighters, AFL-CIO, CLC 

Division of Occupational Health, Safety and Medicine 

1750 New York Avenue, NW 

Washington, DC 20006 

(202) 737-8484 

(202) 737-8418 (FAX) 

www.iaff.org 

Respiratory Diseases and the Fire Service i

ii 

EDITORS: 

Respiratory Diseases and the Fire Service 

The IAFF would also like to thank the following editors and authors for their 

contributions in addressing fire fighter respiratory diseases and the editors for 

their tireless efforts in developing and editing this manual so it is consistent, 

readable and understandable to this Nation’s fire service. 

Richard Duffy, MSc 


Occupational Health, Safety and Medicine 

International Association of Fire Fighters 

Washington, DC 

Andrew Berman, MD 

Program Director, Combined Training Program 

in Pulmonary and Critical Care Medicine 

Associate Professor of Clinical Medicine 

Albert Einstein College of Medicine 

Pulmonary Division 

Montefiore Medical Center 

Bronx, NY 

David Prezant, MD 

Professor of Medicine 




Bronx, NY 

and 

Chief Medical Officer, Office of Medical Affairs 

Co-Director of WTC Medical Programs 

Fire Department City of New York 

Brooklyn, NY 

CONTRIBUTING AUTHORS: 

Amgad Abdu, MD 

Pulmonary Fellow 



Bronx, NY 

Thomas K. Aldrich, MD 





Bronx, NY 

David W. Appel, MD 

Associate Professor of Medicine 


Director of the Pulmonary Sleep Laboratory 



Bronx, NY 

Matthew P. Bars, MS, CTTS 

Director- FDNY Tobacco Cessation Program 

Director, IQuit Smoking Centers of Excellence 

Program Director-Palisades Medical Center 

Montvale, NJ 

Andrew Berman, MD 

Program Director, Combined Training Program 

in Pulmonary and Critical Care Medicine 





Bronx, NY 

Alpana Chandra, MD 



Jacobi Medical Center 

Bronx, NY 

Naricha Chirakalwasan, MD 




Bronx, NY 

Asha Devereaux, MD, MPH 

President-California Thoracic Society 

Pulmonary and Critical Care Medicine 

Coronado, CA

Peter V. Dicpinigaitis, MD 

Professor of Clinical Medicine 



Director Cough Center 



Bronx, NY 

Carrie D. Dorsey, MD, MPH 

Assistant Professor 

University of Maryland School of Medicine 

Occupational Health Program 

Baltimore, MD 

Richard Duffy, MSc 


Occupational Health, Safety and Medicine 



Felicia F. Dworkin, MD 

Deputy Director Medical Affairs 

Bureau of Tuberculosis Control 

New York City Department of Health and 

Mental Hygiene 

New York, NY 

Adrienne Flowers, MD 

University of Maryland School of Medicine 

Occupational Health Program 

Baltimore, MD 

James Geiling, MD 


Dartmouth Medical School 

Hanover, NH 


Chief, Medical Service 

VA Medical Center 

White River Junction, VT 

Subha Ghosh, MD 

Assistant Professor of Radiology 

Ohio State University Medical Center 

Department of Radiology 

Columbus, OH 

Linda B. Haramati, MD, MS 

Professor of Clinical Radiology 


Director of Cardiothoracic Imaging 

Department of Radiology 


Bronx, NY 

Chrispin Kambili, MD 

Assistant Commissioner and Director, Bureau 

of Tuberculosis Control 



New York, NY 

Robert Kaner, MD 


Associate Professor of Genetic Medicine 

Weill Cornell Medical College 


New York Hospital 

New York, NY 

Kerry J. Kelly, MD 

Chief Medical Officer, Bureau of Health 

Services 


Co-Director of World Trade Center Medical 

Programs 


Brooklyn, NY 

Angeline A. Lazarus, MD 


Uniformed Services University 

Bethesda, MD 

Stephen M. Levin, MD 


Department of Community and Preventive 

Medicine 

Mount Sinai School of Medicine 

New York, NY 

Michelle Macaraig, MPH 

Assistant Director for Policy and Planning 

Coordination 




New York, NY 

Melissa A. McDiarmid, MD, MPH 

Professor of Medicine and Director, 

University of Maryland Occupational Health 

Program 

Baltimore, MD 

Lawrence C. Mohr, MD 

Professor of Medicine, Biometry and 

Epidemiology 

Director, Environmental Biosciences Program 

Medical University of South Carolina 

Charleston, South Carolina 

Diana Nilsen, MD, RN 

Director, Medical Affairs 




New York, NY 

David Ost, MD, MPH 


New York University School of Medicine 

New York, NY 

Respiratory Diseases and the Fire Service iii

iv 


David Prezant, MD 





Bronx, NY 


Chief Medical Officer, Office of Medical Affairs 

Co-Director of World Trade Center Medical 

Programs 


Brooklyn, NY 

Jaswinderpal Sandhu, MD 




Bronx, NY 

Michael R. Shohet, MD 

Associate Clinical Professor 

Otolaryngology- Head and Neck Surgery 

Mount Sinai School of Medicine 

New York, NY 

Dorsett D Smith, MD 

Clinical Professor of Medicine 

Division of Pulmonary Diseases and Critical 

Care Medicine 

Department of Medicine 

University of Washington Medical School 

Seattle, Washington 

Leah Spinner, MD 




Bronx, NY 

Michael Weiden, MD 


NYU School of Medicine 

Division of Pulmonary Medicine 

New York, NY 


Medical Officer, Bureau of Health Services 

World Trade Center Medical Program 


Brooklyn, NY 

In concert with the United States Fire Administration, the IAFF sought independent 

review of this effort to provide us with technical and critical comments so as 

to ensure a complete and sound final product. The IAFF thanks the following 

organizations and individuals for their review of this manual. 

William Troup 

Fire Program Specialist, Project Manager 

United States Fire Administration 

Emmitsburg, MD 

James Melius, MD, DrPH 

Chair, Medical Advisory Board 


Administrator, New York State Laborers’ Health 

and Safety Trust Fund 

Albany, NY 

Sandy Bogucki, MD, PhD, FACEP 

Associate Professor, Emergency Medicine, Yale 

University 

Associate EMS Medical Director and Fire 

Surgeon, Branford Fire Department 

New Haven, CT 

Sara A. Pyle, PhD 

Assistant Professor 

Preventive Medicine & Family Medicine 

Kansas City University of Medicine & 

Biosciences 

Kansas City, MO 

Ed Nied 

Deputy Chief 

Tucson Fire Department 

Director, IAFC Health, Safety and Survival 

Section 

Tucson, AZ 

Lu-Ann Beeckman-Wagner, PhD 

Health Scientist 

Division of Respiratory Disease Studies 

NIOSH 

Morgantown, WV 

Robert Castellan, MD, MPH 

Expert 


NIOSH 


Christopher Coffey, PhD 

Chief 

Laboratory Research Branch 


NIOSH 


Paul Enright, MD 

Expert Consultant to NIOSH 

Professor 

University of Arizona 

Tucson, Arizona 

Thomas Hales, MD, MPH 

Senior Medical Epidemiologist 

Team Co-Leader, NIOSH Fire Fighter Fatality 

Investigation and Prevention Program 

NIOSH 

Cincinnati, OH

Paul Henneberger, ScD, MPH 

Research Epidemiologist 


NIOSH 


Mark Hoover, PhD, CHP, CIH, 

Research Physical Scientist 


NIOSH 


Rick Hull, PhD 

Technical Editor 

National Center for Chronic Disease Prevention 

and. Health Promotion 

NIOSH 

Atlanta, GA 

Eva Hnizdo, PhD 

Senior Service Fellow 


NIOSH 


Kay Kreiss, MD 

Chief 

Field Studies Branch 

Division of Respiratory Disease Surveillance 

NIOSH 


Travis Kubale, PhD 

Epidemiologist 

Division of Surveillance, Hazard Evaluations, 

and Field Studies 

NIOSH 

Cincinnati, OH 

Dori Reissman, MD, MPH 

Senior Medical Advisor 

Medical and Clinical Science Director 

WTC Responder Health Program 

NIOSH 


Roger R. Rosa, PhD 

Senior Scientist 

Office of the Director 

NIOSH 


Philip LoBue, MD 

Medical Officer 

National Center for HIV/AIDS, Viral Hepatitis, 

STD, and TB Prevention 

Centers for Disease Control and Prevention 

Atlanta, GA 

Respiratory Diseases and the Fire Service v

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TABLE OF CONTENTS 

Introduction ....................................................................................................... 1 

Fire Fighter Studies ..................................................................................... 2 

Worker Compensation and Benefits .......................................................... 3 

Implementing Respiratory Disease Programs .......................................... 6 

Summary........................................................................................................8 

The Normal Lung and Risks for Developing Lung Disease 

Chapter 1-1 • Anatomy .................................................................................... 11 

Lung Components .................................................................................... 11 

Bronchial Tree ..................................................................................... 11 

Alveoli .................................................................................................. 11 

Parenchyma ......................................................................................... 12 

Cell Morphology and Function ................................................................ 12 

Normal Physiology .................................................................................... 13 

References.................................................................................................. 15 

Chapter 1-2 • Occupational Risks of Chest Disease in Fire Fighters ........... 17 

Inhalation of Combustion Products ........................................................ 17 

Acute Effects ........................................................................................ 17 

Chronic Effects .................................................................................... 18 

Summary of Studies of Pulmonary Function in Fire Fighters................ 18 

Fire Fighters and Diseases of the Respiratory System ............................ 22 

Summary of Studies of Respiratory Disease and Mortality 

in Fire Fighters ........................................................................................... 23 

References.................................................................................................. 24 

Lung Disease 

Chapter 2-1 • Disorders of The Upper Aerodigestive Tract .......................... 27 

Introduction ..................................................................................................... 27 

Anatomy ..................................................................................................... 27 

Nose and Sinuses ................................................................................ 27 

Oral Cavity, Pharynx, and Larynx ...................................................... 28 

Disease ....................................................................................................... 28 

Rhinitis, Sinusitis, and Rhinosinusitis ............................................... 28 

Pharyngitis, Laryngitis, and Laryngopharyngitis.............................. 31 

Chapter 2-2 • Respiratory Infections – Bronchitis and Pneumonia ............ 35 

Introduction .............................................................................................. 35 

Airway Infections ...................................................................................... 35 

Acute Bronchitis .................................................................................. 35 

Chronic Bronchitis .............................................................................. 37 

Bronchiolitis ........................................................................................ 39 

Bronchiolitis Obliterans With Organizing Pneumonia (BOOP) ...... 39 

Bronchiectasis ..................................................................................... 39 

Respiratory Diseases and the Fire Service vii

viii 


Pneumonias ............................................................................................... 42 

Pneumonia .......................................................................................... 43 

Mortality and Severity Assessment .................................................... 44 

Common Organisms Responsible For 

Community-Acquired Pneumonias .................................................. 39 

Hospital-Acquired Pneumonia .......................................................... 49 

Other Lung Infections ............................................................................... 49 

Lung Abscess ....................................................................................... 49 

Pleural Effusions and Empyema ........................................................ 50 

References.................................................................................................. 50 

Chapter 2-3 • Tuberculosis: A Primer For First Responders ........................ 53 

Introduction .............................................................................................. 53 

Epidemiology of TB ................................................................................... 54 

Pathogenesis, Transmission, Infection & Proliferation .......................... 56 

Host Immune Response ..................................................................... 57 

Progression From Infection to Active Disease .................................. 57 

Clinical Aspects of TB Disease ........................................................... 58 

Evaluation of Persons With Suspected Active TB Disease ............... 58 

Diagnostic Microbiology .................................................................... 59 

Treatment of Patients With Active TB Disease.................................. 59 

Drug-Resistant TB ............................................................................... 60 

Latent TB Infection ............................................................................. 60 

Diagnostic Tests For TB Infection ............................................................ 61 

Tuberculin Skin Test (TST) ................................................................. 61 

Blood Tests (e.g. Quantiferon® - TB Gold) ......................................... 62 

Populations Who Should Be Tested For LTBI ................................... 63 

Interpretation of LTBIs: Causes of False Positive and 

False Negative TST Reactions ............................................................. 66 

BCG Vaccinated Individuals ............................................................... 66 

Vaccination With Live Attenuated Vaccines ..................................... 66 

Anergy ................................................................................................. 67 

Two-Step Tuberculin Skin Testing ........................................................... 68 

Clinical Evaluation For Latent TB Infection ............................................ 68 

Medical History and Physical Examination ...................................... 68 

Chest X-Ray.......................................................................................... 69 

Sputum Examinations ........................................................................ 69 

Considerations of Pregnant Women ................................................. 70 

LTBI Treatment Regimens ........................................................................ 70 

Isoniazid............................................................................................... 70 

Rifampin .............................................................................................. 74 

Rifampin & PZA Combination ........................................................... 74 

Contacts to Multidrug Resistant TB (MDRTB) Cases ............................. 75 

Treatment of Close Contacts With A Prior Positive 

Test For TB Infection ........................................................................... 75 

Monitoring Patients During Treatment ............................................. 75

Summary.................................................................................................... 76 

References.................................................................................................. 76 

Chapter 2-4 • Asthma ...................................................................................... 79 

Epidemiology ............................................................................................ 79 

Risk Factors ................................................................................................ 79 

Pathophysiology ........................................................................................ 81 

Clinical Manifestation............................................................................... 82 

Diagnosis ................................................................................................... 82 

Differential Diagnosis ............................................................................... 83 

Classification of Asthma Severity ............................................................. 83 

Management of Asthma ........................................................................... 84 

Medications ............................................................................................... 85 

Quick-Relief Medications ................................................................... 85 

Short-Acting Beta-Agonists (SABA) .................................................. 85 

Anticholinergics .................................................................................. 85 

Long-Term Control Medications ....................................................... 85 

Inhaled Corticosteroids (ICS) ............................................................ 85 

Long Acting Beta-Agonists (LABA) .................................................... 86 

Leukotriene Receptor Antagonists (LTRA) ....................................... 86 

Mast Cell Stabilizers ............................................................................ 86 

Methyxanthines ................................................................................... 87 

Anti IgE Antibody ................................................................................ 87 

Immunotherapy .................................................................................. 87 

Stepwise Approach to Therapy ................................................................. 87 

The Asthma Control Test .......................................................................... 87 

Non-Pharmacologic Therapy ............................................................. 88 

Asthma Exacerbation ................................................................................ 88 

References.................................................................................................. 90 

Chapter 2-5 • Chronic Obstructive Lung Disease (COPD)........................... 93 

Introduction .............................................................................................. 93 

Definition ................................................................................................... 93 

Pathology ................................................................................................... 94 

Natural History ......................................................................................... 94 

Clinical Manifestations ............................................................................. 95 

Classification and Diagnosis of COPD .................................................... 95 

Burden of COPD ........................................................................................ 97 

Risk Factors ................................................................................................ 98 

Management.............................................................................................. 99 

Summary.................................................................................................. 104 

References................................................................................................ 104 

Chapter 2-6 • Sarcoidosis .............................................................................. 107 

References................................................................................................ 117 

Respiratory Diseases and the Fire Service ix

x 


Chapter 2-7 • Pulmonary Fibrosis and Interstitial Lung Disease .............. 119 

Pulmonary Fibrosis ................................................................................. 119 

Major Categories of Interstitial Lung Disease 

and Pulmonary Fibrosis ................................................................... 119 

Symptoms of Pulmonary Fibrosis ................................................... 121 

Physiologic Consequences of Interstitial Lung 

Disease and Pulmonary Fibrosis ..................................................... 122 

Diagnosis of Pulmonary Fibrosis Made........................................... 123 

Prognosis ........................................................................................... 125 

Available Treatment ......................................................................... 126 

Prevention of Pulmonary Fibrosis ......................................................... 127 

Increased Risk to Fire Fighters ............................................................... 127 

Relationship to World Trade Center Exposure ..................................... 128 

References................................................................................................ 128 

Chapter 2-8 • Pulmonary Vascular Diseases ............................................... 129 

Pulmonary Hypertension (PH) .............................................................. 129 

Pathology ........................................................................................... 129 

Epidemiology .................................................................................... 130 

Etiology .............................................................................................. 130 

Signs and Symptoms ......................................................................... 132 

Classification ..................................................................................... 132 

Diagnostic Testing ............................................................................. 132 

Medical Management ............................................................................. 134 

General Measures ............................................................................. 134 

Specific Measures .............................................................................. 134 

Pulmonary Embolism ............................................................................. 135 

Epidemiology .................................................................................... 135 

Risk Factors ........................................................................................ 135 

Clinical Presentation ......................................................................... 136 

Diagnostic Tests................................................................................. 136 

Evaluation for DVT ............................................................................ 137 

D-Dimer Concentration ................................................................... 137 

Ventilation-Perfusion (V/Q) Scan .................................................... 137 

Spiral CT or CT Angiogram .............................................................. 137 

Pulmonary Angiogram ..................................................................... 137 

Management............................................................................................ 138 

General Measures ............................................................................. 138 

Specific Measures .............................................................................. 138 

Prognosis ........................................................................................... 138 

Pulmonary Edema .................................................................................. 138 

Pulmonary Edema Associated with Inhalation 

of Foreign Material ............................................................................ 139 

References................................................................................................ 140 

Chapter 2-9 • Fire Fighter Lung Cancer ....................................................... 141 

The Fire Fighting Environment .............................................................. 141

Lung Cancer Epidemiology .................................................................... 142 

Lung Cancer ............................................................................................ 143 

Non Small Cell Lung Cancer (NSCLC) ............................................ 143 

Clinical Presentation and Symptoms of NSCLC ....................... 145 

Diagnosis .................................................................................... 146 

Tissue Biopsy ............................................................................... 147 

Staging of NSCLC ........................................................................ 148 

Prognosis ..................................................................................... 151 

Treatment of NSCLC .................................................................. 153 

Small Cell Lung Cancer .................................................................... 154 

Clinical Presentation and Symptoms ........................................ 154 

Diagnosis ..................................................................................... 155 

Staging .......................................................................................... 155 

Prognosis ..................................................................................... 155 

Treatment ................................................................................... 156 

Screening For Lung Cancer .................................................................... 156 

Prevention................................................................................................ 157 

References................................................................................................ 157 

Chapter 2-10 • Asbestos Related Lung Diseases ......................................... 161 

Introduction ............................................................................................ 161 

What Is Asbestos? .................................................................................... 162 

The Diseases Caused By Asbestos .................................................... 162 

How Asbestos Causes Disease ......................................................... 163 

Health Effects of Exposure to Asbestos ................................................. 164 

Non-Malignant Asbestos Related Diseases .................................. 164 

Pulmonary Asbestosis ................................................................. 164 

Pleural Thickening or Asbestos-Related Pleural Fibrosis ........ 166 

Benign Asbestotic Pleural Effusions .......................................... 167 

Treatment of Non-Cancerous Asbestos-Related Disease .................... 168 

Asbestos-Related Cancers ...................................................................... 168 

Lung Cancer ...................................................................................... 168 

Cigarette Smoking and Exposure to Asbestos ................................. 169 

Treatment of Lung Cancer ................................................................ 170 

Malignant Mesothelioma ................................................................. 170 

Treatment of Malignant Mesothelioma ................................................ 171 

Preventing Asbestos-Related Disease Among Fire Fighters .... 171 

References................................................................................................ 172 

Chapter 2-11 • Sleep Apnea Syndrome ........................................................ 173 

Sleep ......................................................................................................... 173 

Sleep Stages ....................................................................................... 173 

Obstructive Sleep Apnea .................................................................. 174 

Historical Perspective ....................................................................... 174 

Epidemiology .................................................................................... 174 

Risk Factors ........................................................................................ 175 

Pathophysiology ................................................................................ 175 

Respiratory Diseases and the Fire Service xi

xii 


Clinical Manifestations ..................................................................... 176 

Diagnosis ........................................................................................... 177 

Treatment of OSA .............................................................................. 179 

Central Sleep Apnea ................................................................................ 182 

Mixed Apnea ............................................................................................ 182 

Upper Airway Resistance Syndrome ..................................................... 183 

Narcolepsy ............................................................................................... 183 

References................................................................................................ 184 

Chapter 2-12 • Cough .................................................................................... 187 

Mechanism of Cough .............................................................................. 187 

Acute Cough ............................................................................................ 188 

Acute Cough and OTC Cough and Cold Products.......................... 188 

Subacute Cough ...................................................................................... 189 

Chronic Cough ........................................................................................ 190 

Causes of Chronic Cough ................................................................. 190 

Postnasal Drip Syndrome (PNDS) ............................................. 190 

Asthma ......................................................................................... 191 

Non-Asthmatic Eosinophilic Bronchitis (EB) ........................... 191 

Gastroesophageal Reflux Disease (GERD) ................................ 191 

Other Specific Issues Relevant to Chronic Cough ................................ 193 

Cigarette Smoking ............................................................................. 193 

Gender ............................................................................................... 193 

Medications Taken for Other Reasons ............................................. 193 

World Trade Center Cough .................................................................... 194 

References................................................................................................ 194 

Inhalation Injuries 

Chapter 3-1 • Inhalation Lung Injury from Smoke 

Particulates, Gases and Chemicals .............................................................. 197 

Inhalation Respiratory Illnesses from Aerosolized Particulates .......... 197 

Inhalation Respiratory Illnesses from Gases and Vapors .................... 203 

Hydrogen Cyanide ............................................................................ 203 

Carbon Monoxide ............................................................................. 204 

Exposure to Irritant Vapors and Gases .................................................. 206 

Chlorine ............................................................................................. 206 

Phosgene ............................................................................................ 206 

Diagnosis and Treatment ....................................................................... 207 

History and Physical Examination ................................................... 207 

Diagnostic Testing ............................................................................. 208 

Other Pulmonary Functions ............................................................. 208 

Chest Imaging.................................................................................... 209 

Invasive Diagnostic Methods ........................................................... 209 

Treatment .......................................................................................... 209 

References................................................................................................ 211

Chapter 3-2 • Inhalation Lung Injury and Radiation Illness ...................... 217 

Radiation Doses ...................................................................................... 218 

Acute Radiation Illness ........................................................................... 219 

Decontamination of Radiological Casualties ....................................... 222 

Internal Radiation Contamination ........................................................ 223 

Reference ................................................................................................. 224 

Chapter 3-3 • Inhalation Lung Injury – Nerve Agents ................................ 225 

References................................................................................................ 227 

Chapter 3-4 • Disaster Related Infections: 

Pandemics and Bioterrorism ........................................................................ 231 

Pandemic ................................................................................................. 231 

Epidemics Post-Disaster ......................................................................... 232 

Biological Terrorism Agents ................................................................... 235 

Smallpox ............................................................................................ 236 

Pathogenesis and Clinical Presentation .................................... 236 

Laboratory Diagnosis .................................................................. 237 

Treatment .................................................................................... 238 

Infection Control ......................................................................... 238 

Inhalational Anthrax ......................................................................... 238 



Treatment .................................................................................... 239 


Tularemia ........................................................................................... 240 



Treatment .................................................................................... 242 


Plague ................................................................................................. 243 



Treatment .................................................................................... 245 


Botulinum .......................................................................................... 245 

Pathogenesis and Clinical Manifestations ................................ 246 

Treatment .................................................................................... 246 


References................................................................................................ 246 

Chapter 3-5 • World Trade Center Respiratory Diseases ........................... 253 

Introduction ............................................................................................ 253 

Upper Respiratory Disease ..................................................................... 256 

Reactive Upper Airways Dysfunction Syndrome (RUDS) 

and Chronic Rhinosinusitis ............................................................. 256 

Lower Respiratory Disease ..................................................................... 256 

Respiratory Diseases and the Fire Service xiii

xiv 


Reactive (Lower) Airways Dysfunction Syndrome (RADS) 

and Asthma ........................................................................................ 258 

Gastroesophageal Reflux Disease (GERD) ...................................... 260 

Parenchymal Lung Diseases .................................................................. 261 

Pulmonary Malignancies........................................................................ 262 

The Impact of Exposure Time On Respiratory Disease .................. 262 

Treatment of WTC Upper and Lower Airways Disease ........................ 263 

Conclusion ............................................................................................... 265 

References................................................................................................ 266 

Diagnosis and Treatment 

Chapter 4-1 • Pulmonary Function Tests for Diagnostic and Disability 

Evaluations ..................................................................................................... 271 

Introduction ............................................................................................ 271 

Peak Flow/Spirometry/Bronchodilator Responsiveness ..................... 272 

Peak Flow Meter ................................................................................ 272 

Spirometry ......................................................................................... 272 

Flow Volume Loop ............................................................................ 274 

Bronchodilator Responsiveness or Reversibility ............................ 274 

Test of Lung Volume And Diffusion Capacity ....................................... 275 

Lung Volume Measurements ........................................................... 275 

Body Plethysmography ..................................................................... 278 

Diffusing Capacity ............................................................................. 278 

Provocative Challenge Testing (Methacholine, Cold Air 

and Exercise) ........................................................................................... 280 

Exercise Testing ....................................................................................... 281 

Cardiopulmonary Exercise Testing .................................................. 281 

Six-Minute Walk Test ........................................................................ 282 

Disability Evaluation ............................................................................... 282 

References................................................................................................ 283 

Chapter 4-2 • Imaging Modalities in Respiratory Diseases ........................ 285 

Commonly Used Modalities ................................................................... 285 

Chest X-Ray (CXR) ............................................................................ 285 

Science Behind X-Rays ............................................................... 285 

Equipment and Procedure ........................................................ 285 

Common Uses ............................................................................. 286 

Benefits of Procedure .................................................................. 286 

Risks of Procedure ....................................................................... 286 

Limitations ................................................................................... 287 

Abnormal Patterns on CXR ........................................................ 287 

Pleural Abnormalities ................................................................. 288 

Shadows and Other Markings .................................................... 288 

Computerized Tomography (CT) Scan ........................................... 289 

Equipment and Procedure ....................................................... 289 

Common Uses ............................................................................. 290 

Role of Chest CT in the Diagnosis of Respiratory Diseases..... 290

Benefits ........................................................................................ 294 

Risks ............................................................................................. 294 

Limitations ................................................................................... 295 

Future Advances .......................................................................... 295 

Role of Special Imaging Modalities: PET & MRI Scans ........................ 295 

PET Scan ............................................................................................ 295 

MRI Scan ............................................................................................ 296 

Image Guided Tissue Sampling ............................................................. 297 

Preparatory Instructions................................................................... 297 

Nature of the Procedure.................................................................... 297 

Needles ........................................................................................ 297 

Image Guidance .......................................................................... 297 

Procedure..................................................................................... 298 

Benefits ........................................................................................ 299 

Risks ............................................................................................. 299 

Limitations ................................................................................... 299 

Imaging of Pulmonary Arteries And Veins ............................................ 299 

Pulmonary Angiography .................................................................. 300 

Conventional (Catheter) Pulmonary Angiography ........................ 300 

CT Pulmonary Angiography (CTPA) ............................................... 300 

Benefits ........................................................................................ 300 

Limitations ................................................................................... 300 

Risks ............................................................................................. 301 

Ventilation Perfusion Scintigraphy (VQ Scanning) ........................ 301 

Benefits ........................................................................................ 301 

Limitations ................................................................................... 301 

Risks ............................................................................................. 302 

Role of Ultrasonography in Imaging of Pulmonary Embolism ........... 302 

Chapter 4-3 • The Solitary Pulmonary Nodule ............................................ 303 

Definition ................................................................................................. 303 

Incidence and Prevalence ...................................................................... 304 

Malignant Solitary Pulmonary Nodules ................................................ 304 

Benign Solitary Pulmonary Nodules ..................................................... 305 

Imaging Techniques................................................................................ 306 

Plain Chest Radiography ................................................................. 307 

Computed Tomography ................................................................... 307 

Positron Emission Tomography (PET) ............................................ 308 

Distinguishing Between Benign And Malignant Nodules ................... 308 

Nodule Shape and Calcification Patterns ........................................ 309 

Assessment of Nodule Growth Rate and 

Frequency of Follow-up Imaging ..................................................... 309 

Estimating Probability of Malignancy ............................................. 311 

Biopsy Techniques .................................................................................. 312 

Bronchoscopy .................................................................................... 312 

Percutaneous Needle Aspiration ..................................................... 313 

Thoracotomy and Thoracoscopy...................................................... 313 

Respiratory Diseases and the Fire Service xv

xvi 


Diagnostic Approach .............................................................................. 315 

Fire Fighters and Lung Nodules ....................................................... 316 

References................................................................................................ 317 

Chapter 4-4 • Where There’s Smoke…There’s Help! Self-Help for Tobacco 

Dependent Fire Fighters and other First-Responders ................................ 319 

Tobacco Addiction .................................................................................. 320 

Measuring Your Tobacco Addiction ................................................ 321 

Let’s Get Ready! ....................................................................................... 321 

Reduction to Cessation Treatments (Reduce then Quit) ............... 323 

Keep a Cigarette Log ......................................................................... 324 

No Ashtrays Instead Use a Cigarette “Coughee” Jar ....................... 325 

Increase the Inconvenience of Smoking ......................................... 325 

Take Inventory and Do a Balance Sheet .......................................... 325 

Avoid People, Places, Things You Associate with Smoking ............ 326 

Alcohol and Tobacco Use ................................................................. 326 

Sadness, Depression and Post Traumatic Stress ............................ 327 

The Money You Save ........................................................................ 328 

Exercise – Start Slow, Start with Your Doctor’s Input, 

but Start! ............................................................................................. 328 

Keep Oral Low-Calorie Substitutes Handy ..................................... 328 

Associate Only with Non-Smokers for a While ............................... 328 

Medications Are Essential To Increase Your Chances of Success ....... 329 

Chantix® (Varenicline) or Champix® (Outside the USA) ................. 330 

Bupropion (Wellbutrin, Zyban) ...................................................... 330 

Nicotine Replacement Medications ................................................ 331 

Nicotine Nasal Spray ................................................................... 331 

Nicotine Inhaler .......................................................................... 332 

Nicotine Polacrilex Gum ............................................................ 332 

Nicotine Polacrilex Lozenges ..................................................... 333 

Nicotine Patches ........................................................................ 333 

Combination Medications.......................................................... 334 

Tobacco Treatment Decision Guidelines ........................................ 334 

U.S. Federal and State Programs ............................................................ 345 

IAFF: A Tobacco Free Union .................................................................. 345 

A Final Word ............................................................................................ 346 

References................................................................................................ 346 

Chapter 4-5 • Respiratory Failure, Assisted Ventilation, 

Mechanical Ventilation and Weaning .......................................................... 337 

Types of Respiratory Failure ................................................................... 337 

Hypoxic Respiratory Failure ............................................................. 338 

Hypercapnic Respiratory Failure ..................................................... 338 

Clinical Assessment of Respiratory Failure ........................................... 340 

Laboratory Findings ......................................................................... 341 

Treatment of Respiratory Failure ........................................................... 342

Mechanical Ventilation ..................................................................... 343 

Noninvasive vs. Invasive Mechanical Ventilatory Support ...... 343 

Types or Modes of Mechanical Ventilation ..................................... 344 

Assist/Control .............................................................................. 344 

Pressure Support and CPAP (PS/CPAP) .................................... 344 

Synchronous Intermittent Mandatory Ventilation (SIMV) ...... 345 

Specialized Modes ...................................................................... 345 

Weaning or Removing a Patient from Mechanical Ventilation............ 345 

The Decision to Use Invasive Ventilatory Support and the 

Importance of Advance Directives in Patients with Chronic 

Disease ..................................................................................................... 346 

Conclusions ............................................................................................. 347 

References................................................................................................ 347 

Respiratory Diseases and the Fire Service xvii


Introduction 

By Richard M. Duffy, MSc 


Respiratory diseases remain a significant health issue for fire fighters and 

emergency responders, as well as civilians. Respiratory disease is the number 

three killer in North America, exceeded only by heart disease and cancer, and 

is responsible for one in six deaths. The American Respiratory Association 

estimates that more than 35 million Americans are living with chronic respiratory 

diseases such as asthma or chronic obstructive pulmonary diseases (COPD) 

including emphysema and chronic bronchitis. 

Fire fighters work hard each and every day, proudly protecting and serving 

our citizens by answering the call for help -- a call to save lives. That call 

may be to suppress fire and save lives jeopardized by smoke and flame. It 

may be a response to a hazardous materials incident, a structural collapse or 

other special operations event. The response may be for emergency medical 

assistance and transport to the hospital, with potential exposures to a host of 

infectious disease. Fire fighters have little idea about the identity of many of 

the materials they are exposed to or the health hazards of such exposures -- 

whether they are chemical, biological or particulates. Nevertheless, fire fighters 

and emergency medical responders continue to respond to the scene and work 

immediately to save lives and reduce property damage without regard to the 

potential health hazards that may exist. A fire emergency has no engineering 

controls or occupational safety and health standards to reduce the effect of 

irritating, asphyxiating or toxic gases, aerosols, chemicals or particulates. It 

is an uncontrollable environment that is fought by fire fighters using heavy, 

bulky and often times inadequate personal protective equipment and clothing. 

An occupational disease takes years to develop. It is the result of a career 

of responding to fires and hazardous materials incidents; it is caused by 

breathing toxic smoke, fumes, biological agents, and particulate matter on the 

job; and it is the response to continuous medical runs or extricating victims 

at accidents. Some health effects are immediate while others may take years 

and even decades to develop and because some respiratory diseases develop 

over time, it’s impossible to say, “This specific emergency response caused 

my disease,” yet fire fighters continue to get sick and die from occupationallycaused 

respiratory diseases. 

Variability in exposures among fire fighters can be great; however, a number 

of exposures are commonly found in many fire scenarios. The common 

combustion products encountered by fire fighters that present respiratory 

disease hazards include but are not limited to: acrylonitrile, asbestos, arsenic, 

benzene, benzo(a)pyrene and other polycyclic hydrocarbons (PAHs), cadmium, 

chlorophenols, chromium, diesel fumes, carbon monoxide, dioxins, ethylene 

oxide, formaldehyde, orthotoluide, polychlorinated biphenyls and vinyl 

chloride. Also, findings from fire fighters monitored during the overhaul 

Introduction 

1

2 

Introduction 

phase (fire is extinguished, clean-up begins and where respiratory protection 

is not usually available) of structural fires indicates that short-term exposure 

levels are exceeded for acrolein, benzene, carbon monoxide, formaldehyde, 

glutaraldehyde, nitrogen dioxide and sulfur dioxide as well as soots and 

particulates. They are often exposed in their fire stations to significant levels 

of diesel particulate from the operation of the diesel fueled fire apparatus. 

Fire fighters are routinely exposed to respirable particulate matter consisting 

of liquids, hydrocarbons, soots, diesel fumes, dusts, acids from aerosols, and 

smoke. Health effects are known to be produced not just by the particulates 

themselves, but also by certain chemicals adsorbed onto the particulates. 

Further, the mixture of hazardous chemicals is different at every fire and the 

synergistic effects of these substances are largely unknown. 

FIRE FIGHTER STUDIES 

Although fire fighters have been shown in some studies to suffer chronic 

respiratory morbidity from their occupational exposures, fire fighters are 

probably at increased risk for dying from non-malignant respiratory diseases. 

Such studies that address and link fire fighting with respiratory diseases fall 

into three main groups—laboratory studies, field studies and epidemiological 

studies. The first, involving animal laboratory experiments, have identified 

exposure to certain chemicals, biological agents and particulate substances 

and their contribution to the respiratory disease process. Such studies are 

invaluable to the understanding of the effect such substances can have on 

humans and they play a significant role in hazard identification for further 

risk assessment. 

The second group, field studies, documents the exposure of fire fighters 

to these agents through industrial hygiene or biological and physiological 

monitoring. Industrial hygiene data indicates that the fire environment contains 

a number of potentially dangerous toxins. Due to the highly unpredictable 

nature of the fire fighters’ environment, it is almost impossible to predict with 

any certainty all of the exposures that could be encountered at any given fire. 

However, these studies are important since they identify and characterize 

fire fighter exposures during suppression and overhaul at fires as well as at 

hazardous materials incidents or other special operations responses. 

The third group, epidemiologic studies of fire fighters and other occupational 

groups, is performed to determine if exposures actually result in elevated rates 

of disease. For example, epidemiological studies have consistently shown 

excesses of nonmalignant respiratory disease in fire fighters; acute and chronic 

respiratory function impairment, acute increase in airway reactivity and 

inflammatory changes in the lower airways of fire fighters. However, there 

have also been a number of other epidemiologic studies that have not found 

an increased morbidity or mortality or they provided conflicting information 

on the health effects of fire fighting on the respiratory system. This is due to 

a number of factors: 

• Statistical constraints — the number of individuals studied may not be 

sufficient to detect a difference. 

• The studies rely on mortality, measuring only deaths from respiratory 

disease. Differences in survivorship between an occupational group

and the general population resulting from disparities in the quality and 

accessibility of medical care or other factors may result in misleading 

conclusions about disease prevalence. 

• Mortality studies rely on death certificates that are frequently inaccurate 

and may erode the ability of the study to detect real differences. 

• Due to the physical and medical requirements, fire fighters tend to be 

healthier than the general population with disease incidence significantly 

less than the general population. An increase in the prevalence of a 

medical condition arising from workplace exposures may therefore be 

missed with comparison to the general population. This “healthy worker 

effect” is accentuated with fire fighters who are extremely healthy, and 

has been termed the “super healthy worker effect.” 

• When studying an occupational group, certain sub-populations may be at 

greater risk for a disease due to differences in exposures, administrative 

policies, or other reasons. The ability of a study to identify and establish 

the increased rates in these sub-groups may be limited due to statistical 

and study design constraints. 

• Anyofthesefactorscouldresultinanotherwisewell-designedepidemiologic 

study failing to find an increase in the prevalence of an illness even if 

one existed (i.e. a “false negative” result). 

WORKER COMPENSATION AND BENEFITS 

For more than fifty years, the International Association of Fire Fighters has 

been addressing the issues of fire fighters and respiratory diseases. The 

IAFF has protected its members by pursuing enactment of legislation that 

provides protection and compensation for those fire fighters whose health has 

deteriorated through the performance of their fire fighting occupation. Such 

IAFF-sponsored benefit laws have ranged from federal legislation to provide 

compensation for the families of those fire fighters who die or are severely 

disabled in the line of duty to federal, state and provincial legislation extending 

retirement and/or worker compensation benefits to those who become disabled 

from occupationally-contracted diseases. 

Some are confused on the issue of paying for treatment of a fire fighter injured 

at work, in this case through an exposure to a toxic material, carcinogen or an 

infectious disease. Some also state that fire fighters are entitled to worker’s 

compensation for injuries and illnesses and that their bills are routinely paid 

for and the fire fighter is compensated for lost productivity. Well, that is exactly 

what fire fighter "presumptive" legislation does. It provides for a rebuttable 

presumption -- that is, the employer may tangibly demonstrate that the exposure 

did not occur in the line of duty -- to compensate a fire fighter if an exposure 

leads to a disease. Just as a fire fighter would be compensated for injuries that 

occurred after falling through the roof of a burning structure, a fire fighter 

who develops a respiratory disease from job exposure would and should be 

compensated. The worker’s compensation system was designed decades ago 

to handle injuries easily linked to the workplace, such as a broken leg or a cut 

hand. As medical science has improved, we’ve learned that respiratory diseases 

as well as heart diseases, infectious diseases and cancer are directly related 

to the work environment, including toxic chemicals in smoke or particulates. 

Introduction 

3

4 

Introduction 

In recognition of the causal relationship of the fire fighting occupation 

and respiratory disease, 41 states and 7 provinces have adopted some type of 

presumptive disease law to afford protection to fire fighters with these conditions. 

The states and provinces that have occupational disease presumptive laws are 

identified in Table 1. Similar legislation is currently being addressed in the US 

Congress to provide the same protection for federal fire fighters. 

Table 1: State and Provincial Presumptive Disability Laws 

All of these laws presume, in the case of fire fighters, that heart, respiratory, 

and infectious diseases, as well as cancer are occupationally related. 

Consequently, their provisions rightfully place the burden of proof to deny 

worker compensation and/or retirement benefits on the fire fighter’s employer. 

Additionally, many pension and workers’ compensation boards in the 

United States and Canada have established a history of identifying heart, 

respiratory and infectious diseases and cancer in fire fighters as employment-

elated. While all these state and provincial laws recognize these diseases as 

occupationally related, some have exclusions and prerequisites for obtaining 

benefits (see Table 2). 

Table 2: Presumptive Disability Laws Inclusions and Prerequisites 

In a recent study, Dr. Tee Guidotti, from the George Washington University 

Medical Center, addressed the fire fighter occupational disease issues relevant 

to worker compensation issues and reasonableness of adopting a policy 

of presumption for those diseases associated with the occupation of fire 

fighting. Guidotti states that these “presumptions” are based on the weight of 

evidence, as required by adjudication, not on scientific certainty, but reflect a 

legitimate and necessary interpretation of the data for the intended purpose 

of compensating a worker for an injury (in this case an exposure that led to a 

disease outcome). Guidotti made it clear that the assessments are for medicolegal 

Introduction 

5

6 

Introduction 

and adjudicatory purposes and are not intended to replace the standards of 

scientific certainty that are the foundation of etiologic investigation for the 

causation of disease. They are social constructs required to resolve disputes in 

the absence of scientific certainty. Understanding this is why most states and 

provinces have adopted legislation or revised compensation regulations that 

provide a rebuttable presumption when a fire fighter develops occupational 

diseases. Further, based on actual experience in those states and provinces, the 

cost per claim is substantially less than the unsubstantiated figures asserted 

by others. The reason for this, unlike benefits for other occupations, is the 

higher mortality rate and significantly shorter life expectancy associated 

with fire fighting and emergency response occupations. These individuals 

are dying too quickly from occupational diseases, unfortunately producing a 

significant savings in worker compensation costs and pension annuities for 

states, provinces and municipalities. 

The IAFF maintains full copies of all state laws or regulations and a number 

of worker compensation awards from the United States and Canada that address 

these diseases. The IAFF also maintains an up-to-date website that contains 

an information database of the current presumptive disability provisions 

in the United States and Canada. This website provides the full legislation 

from each state and province where a presumptive disease law was enacted. 

Additionally, the site provides information on how presumptive laws benefit 

fire fighters and EMS personnel; the limitations of presumptive disability laws; 

how to bring or maintain such federal, state or provincial legislation; a history 

of fire fighter disability laws; and presumptive legislation updates and stories. 

The IAFF is committed to maintain this as a dynamic site which is accessible 

at: http://www.iaff.org/hs/phi/. The IAFF also continues to provide direct 

assistance and information to its affiliates to obtain or maintain presumptive 

legislation and regulations. 

IMPLEMENTING RESPIRATORY DISEASE PROGRAMS 

The IAFF and the International Association of Fire Chiefs (IAFC) created the 

Fire Service Joint Labor Management Wellness-Fitness Initiative (WFI) in 

1996 to improve the health and fitness of fire fighters and paramedics across 

North America. Medical, wellness and fitness programs that are developed 

and implemented in accordance with the WFI will help secure the highest 

possible level of health to fire response personnel. These programs have also 

been shown to provide the additional benefit of being cost effective, typically 

by reducing the number of work-related injuries and lost workdays due to 

injury or illness. 

This was an unprecedented endeavor to join together labor and management 

to evaluate and improve the health, wellness and fitness of fire fighters and 

EMS providers. It has been supported by the IAFF, as well as by the IAFC, the 

individual fire departments participating in the initiative and with additional 

funding provided by the Federal Emergency Management Agency’s Fire 

Prevention and Safety grant program. The following are the fire departments 

and IAFF locals participating in this project (See Table 3).

WFI Task Force Jurisdictions 

• Austin, Texas Fire Department / IAFF Local 975 

• Calgary, Alberta Fire Department / IAFF Local 255 

• Charlotte, North Carolina Fire Department /IAFF Local 660 

• Fairfax County, Virginia Fire and Rescue Department / IAFF Local 

2068 

• Indianapolis, Indiana Fire Department / IAFF Local 416 

• Los Angeles County, California Fire Department / IAFF Local 1014 

• Miami Dade County, Florida Fire Rescue Department / IAFF Local 1403 

• Fire Department, City of New York / IAFF Locals 94 and 854 

• Phoenix, Arizona Fire Department / IAFF Local 493 

• Seattle, Washington Fire Department / IAFF Local 27 and 2898 

Table 3: WFI Task Force Jurisdictions 

Each of these departments formally agreed to assist in the development of 

the program and to adopt it for their members. Further the IAFF has provided 

the program to thousands of fire departments in the United States and Canada. 

Specifically, fire departments must offer medical exams, fitness evaluations 

and individual program design, rehabilitation following injuries and illnesses, 

and behavioral health services. The program also specifies protocols for physical 

exams, laboratory testing, and other objective tests (pulmonary function 

testing, electrocardiograms, audiometry, chest x-rays). All must assess aerobic 

capacity, strength, endurance, and flexibility using the specified protocols. 

The WFI also provides tools to collect data from these evaluations as well as 

the methods to transfer the data to the IAFF. 

The medical component was specifically designed to provide a cost-effective 

investment in early detection, disease prevention, and health promotion for 

fire fighters. It provides for the initial creation of a baseline from which to 

monitor future effects of exposure to specific biological, physical, or chemical 

agents. The baseline and then subsequent annual evaluations provide the 

ability to detect changes in an individual’s health that may be related to their 

work environment. It allows for the physician to provide the fire fighter with 

information about their occupational hazards and current health status. 

Clearly, it provides the jurisdiction the ability to limit out-of-service time 

through prevention and early intervention of health problems. 

The largest success of the WFI was demonstrated immediately after 

September 11, 2001. The fall of the twin towers and the collapse and destruction 

of other buildings at the World Trade Center (WTC) site created a dust cloud 

composed of large and small particulate matter coated with combustion byproducts. 

For three days, Ground Zero was enveloped in that dust cloud. The 

fires that continued to burn at the site until mid-December created additional 

exposures and resulted in repeated dust aerosolization. Nearly 2,000 FDNY 

Introduction 

7

8 

Introduction 

rescue workers responded on the morning of 9/11, as did nearly 10,000 during 

the next 36 hours. And in the weeks and months following 9/11, virtually all 

of FDNY first responders worked at the WTC site – amid the debris and dust. 

As a group, FDNY fire fighters experienced more exposure to the physical 

and emotional hazards at the disaster site than any other group of workers. 

FDNY, as a participant in the WFI, had implemented the baseline and annual 

medical component four years prior to 9/11. The adoption of the WFI provided 

the vehicle to intervene with early diagnosis and aggressive treatment of all 

affected fire fighters, which clearly improved medical outcomes. FDNY’s WFI 

program had over a 95 percent participation rate, which enabled its Medical 

Division to analyze and publish data providing critical and unique insights 

about WTC health effects. While the tragedy of 9/11 brought the medical issues 

of fire fighters and respiratory diseases to the frontline, the medical successes 

through the FDNY-IAFF WFI and medical evaluation program must be used 

as the driving force for all fire departments for adopting this program. There 

are no longer any excuses. 

The IAFF also worked directly with the National Fire Protection Association 

(NFPA) and their Technical Committee responsible for NFPA 1582, Standard on 

Comprehensive Occupational Medical Program for Fire Departments to ensure 

that IAFF and NFPA documents were consistent with each other. We provided 

our copyrighted materials to NFPA, with the provision that the incumbent 

evaluations mirror the WFI. 

The current 2007 edition of NFPA 1582, includes a stringent standard 

for candidate fire fighters, as well as a more flexible guidance for medical 

determinations for incumbent fire fighters based upon the specific nature 

of their condition and the duties and functions of their job. The standard 

addresses job tasks, where it is explained that those medical conditions that 

potentially interfere with a member's ability to safely perform essential job 

tasks are listed by organ system. Most importantly, possession of one or more 

of the conditions listed within the standard for incumbent fire fighters does 

not indicate a blanket prohibition from continuing to perform the essential 

job tasks, nor does it require automatic retirement or separation from the fire 

department. 

The standard gives the fire department physicians guidance for determining 

a member’s ability to medically and physically function using the individual 

medical assessment. 

Foremost, this standard was fundamentally developed for, and primarily 

intended, as guidance for physicians, to provide them with advice for an 

association or relationship between essential job functions of a fire fighter as 

an individual and the fire fighter’s medical condition(s). 

The federal government, through the National Institute for Occupational 

Safety and Health (NIOSH) also recognized that hiring and maintaining 

medically and physically-fit fire fighters is an important step in reducing fire 

fighter’s occupational disease. They are now in full support of the WFI and 

NIOSH further recommends that all jurisdictions adopt this program for their 

fire departments.

Fire department wellness programs do make economic sense. Adopting 

and implementing an occupational wellness program, such as the WFI, can 

reduce occupational claims and costs while simultaneously improving the 

quality and longevity of a fire fighter’s life. 

SUMMARY 

This manual is written for fire fighters and emergency medical responders, a 

group of individuals who face special occupational risks of respiratory diseases 

due to fire ground exposures and their direct interaction and contact with the 

public. Respiratory diseases in fire fighters have been an area of concern and 

focus for the International Association of Fire Fighters and others for several 

decades. 

Although medical progress has led to improvements in the diagnosis and 

treatment of respiratory diseases, prevention remains the best method of 

decreasing the number of such diseases and related deaths. Understanding 

diseases of the respiratory system, identifying respiratory disease-causing 

agents, and avoiding exposure to these agents are key in preventing respiratory 

diseases. 

The IAFF knows that you will find this manual both informative and useful. 

Introduction 

9


Chapter 1-1 

Anatomy 

By Dr. Carrie Dorsey, MD, MPH 

The main function of the lungs is to provide oxygen to the body and remove 

the carbon dioxide that is formed during metabolism. It is important to have 

an understanding of the normal structure and function of the lungs prior to 

discussing the diseases and injuries that can occur in the lungs. 

LUNG COMPONENTS 

The lungs are made up from a series of components all working together to 

support the respiratory effort. 

Bronchial Tree 

The lungs can be thought of as branching trees. The main airways into the 

lungs are the right and left main stem bronchi which branch off of the trachea. 

Each of these branch to form the bronchi which lead into the main lobes of the 

lungs. The right lung has three lobes and the left has two lobes. The airways 

continue to divide separating the lung into smaller and smaller units. The 

airways terminate at the air sacks known as alveoli. This is the primary site 

of gas exchange with the blood. As the airways divide they can be grouped 

into several distinct categories based on structure. The bronchi are the 

larger airways and are distinguished by the presence of cartilage in the wall 

and glands just below the mucosal surface. As the branches become smaller 

they no longer contain cartilage or glands. These are the bronchioles. The 

bronchioles continue to branch at last forming the terminal bronchioles. Distal 

to the terminal bronchiole is the respiratory unit of the lung or acinus, the site 

of gas exchange. It is composed of alveoli and the respiratory bronchioles. 

The airway walls of the respiratory unit are very thin, the width of a single 

cell, to facilitate the transfer of gases. The airways to the level of the terminal 

bronchiole are surrounded by a layer of smooth muscle that is able to control 

the diameter of the airways by contracting and relaxing. The smooth muscle 

cells are controlled by the autonomic nervous system and also by chemical 

signals released from near by cells. 

Alveoli 

The alveoli and respiratory bronchioles warrant further discussion given the 

essential role they play in supplying the body with oxygen. As discussed above 

the walls of the alveoli are thin and designed to allow for efficient transfer of 

gas with the blood. In addition they are an important site of defense against 

infection. 

Chapter 1-1 • Anatomy 

11

12 Chapter 1-1 • Anatomy 

The wall of the alveoli is primarily made up of two types of cells, the type I 

pneumocytes and type II pneumocytes. There are also alveolar macrophages 

(involved with defense) found in the alveoli or attached to the wall. The cells 

are described in detail below. Because the alveoli are designed to easily expand 

when we breathe in and collapse when breathing out there is a risk that 

the thin walls would stick together. To prevent this there is a layer of a protein 

called surfactant coating the alveolar membranes. Surrounding the alveoli 

is a complex network of capillaries that carry the blood and red blood cells 

through the lungs to pick up oxygen and discard the carbon dioxide. Between 

the capillaries and the alveoli cells is a layer of protein called the basement 

membrane and the pulmonary interstitium. The latter contains a variety of 

cells, collagen and elastic fibers that facilitate the expanse of the lungs. 

Parenchyma 

The definition of parenchyma is: The tissue characteristic of an organ, as 

distinguished from associated connective or supporting tissues. The majority 

of the lung tissue consists of the airways and gas exchange membranes as 

discussed above. There is some interstitial tissue between the alveolar cells 

and the capillary wall. 

Cell Morphology and Function 

There are many different types of cells found in the airways of the lung. A 

variety of functions are performed by these different cells. For example some 

cells are present for physical support, some produce secretions and others 

defend the body against infection. Approximately 50 distinct cells have been 

identified in the airways. 1 Below you will find a brief description of some of 

the important cell types. 

Type I pneumocyte: These are the flat epithelial cells of the alveolar wall 

that have the appearance of a fried egg with long processes extending out 

when seen under a microscope. They account for 95% of the alveolar surface . 2 

Type II pneumocyte: These are the cells responsible for the production of 

surfactant; the protein material that keeps the alveoli from closing off during 

exhalation. They are rounded in appearance. The surfactant is stored in 

small sacks called lamellar bodies. They are also involved with the regulation 

of fluid in the lungs. 1 

Alveolar macrophages: These are cells that clear the lung of particles such 

as bacteria and dust. They enter the alveoli from the blood through small 

holes in the wall called the pores of Kohn. 

Smooth muscle cells: As discussed above the airways down through the level 

of the terminal bronchioles contain bands of smooth muscle. The muscle 

cells are controlled by the autonomic nervous system and chemical or hormones 

released from other cells such as mast or neuroendocrine cells. 1 The 

contraction of the muscle cells leads to a narrowing of the airways. 

Ciliated epithelia cells: The lining of the majority of the airways is composed 

of pseudostratified, tall, columnar, ciliated epithelial cells. The cilia 

are hair-like projections on the surface of these cells that beat in rhythmic 

waves, allowing the movement of mucus and particles out of the lungs. This 

mechanism is also a defense mechanism against infection.

Low cuboidal epithelial cells: The terminal airways are lined by this type 

of epithelia cell. They are only partially ciliated. 

Goblet cells: This cell type is found interspersed with the ciliated epithelial 

cells. There are no goblet cells below the level of the terminal bronchioles. 

These cells produce mucus, the main component of the respiratory secretions. 

Basal cells: These are small epithelia cells that are found along the basement 

membrane of the epithelium. They give rise to the epithelial cells discussed 

above. 

Lymphocytes and mast cells: These cells are part of the immune defense 

of the body. They can be found dispersed within the epithelia lining of the 

airways. 

Clara cells: These domed cells are interspersed with the epithelial cells. 

They make, store and secrete a variety of substances including lipids and 

proteins. They can also develop into other cell types as needed to replace 

the loss of cells. 

NORMAL PHYSIOLOGY 

As discussed above the primary function of the lungs is to provide oxygen to 

the body and remove carbon dioxide. This is accomplished by the exchange 

of air in the lungs with the ambient air through the process of pulmonary 

ventilation. The first phase of ventilation is inspiration. This is initiated when 

the diaphragm contracts causing it to descend into the abdomen. When this 

occurs the volume of the lungs increases and by the laws of physics the pressure 

within the lungs decreases leading to a rush of air into the lungs. The 

opposite occurs during expiration. When the diaphragm relaxes and the lung 

tissues naturally recoil, the pressure in the lungs increases pushing air out 

of the lungs. Respiration is controlled by a number of factors including the 

autonomic nervous system, the voluntary muscles of respiration, the levels 

of carbon dioxide and oxygen in the blood, and the level of acid in the blood. 

During normal respiration between 400 and 1000 ml of air is moved into and 

out of the lungs; however, all of this volume is not available for gas exchange. 

Gases are exchanged across the respiratory bronchioles and the alveoli. The 

airways proximal to these are referred to as the conducting airways or anatomic 

dead space. This volume on average is between 130 and 180 ml. Ventilatory 

function is often expressed as minute ventilation. This is the amount or 

volume of air breathed each minute and is a function of the tidal volume (see 

table of lung volume definitions) and the breathing rate. Under normal resting 

conditions the minute ventilation is approximately 6 L. During exercise this 

can increased as a result of increasing the rate breathing and volume of each 

breath to as much as 150 L. 3 There are a variety of different lung volumes that 

have been defined. These are useful for the diagnosis and discussion of disease 

processes affecting the lungs. A brief description of the lung volumes which 

can be measured or calculated using pulmonary function tests is presented 

in Figure 1-1.1. A more detailed review is discussed in a later chapter. 


13

14 Chapter 1-1 • Anatomy 

Where: 

Figure 1.1.1 

Figure 1-1.1 Lung Volumes Measured in a Pulmonary Function Test 

VT = Tidal Volume: volume of air normally inhaled or exhaled (0.4-1.0 L). 

IRV = Inspiratory Reserve Volume: the additional volume of air inhaled 

(after the tidal volume) by taking a full deep breath (2.5-3.5 L). 

ERV = Expiratory Reserve Volume: the additional volume of air exhaled 

(after the tidal volume) by forcing out a full deep breath (2.5-3.5 L). 

RV = Residual Volume: the volume of air that remains in the lungs following 

a maximal exhalation (0.9-1.4 L for men; 0.8-1.2 L for woman). 

VC = Vital Capacity: maximal volume of air that can be forced out after 

a maximal inspiration, down to the residual volume (4-5 L in men, 3-4 

L in woman). This equals IRV + TV + ERV. 

TLC = Total Lung Capacity: the amount of gas contained in the lungs 

at maximal inspiration (4-6 L). This equals VC + RV. 

FRC = Functional Residual Capacity: the amount of air in the lungs at 

the end of a normal breath; i.e., after the tidal volume is exhaled. This 

equals ERV + RV. 

Ventilation is also dependent on airflow. Through the upper airways and 

to the level of the terminal bronchioles, airflow occurs by bulk movement or 

convection. Because of the vast increase in cross-sectional area after the terminal 

bronchioles airflow slows and the gas molecules move by diffusion. The 

velocity of airflow is dependent on both airway resistance related to the size of 

the airway and lung compliance (stiffness) that results from the mechanical 

constraints of the chest wall. 

All areas of the lungs do not receive equal ventilation. The base of the lung 

receives more ventilation per volume of lung than does the top or apex. This 

distribution varies with position of the body. For example when lying on the

ack the portions of the lungs closest to the ground (dependent portion) receive 

the bulk of the ventilation. 1 In order to ensure adequate and efficient gas 

exchange the body adjusts blood flow through the lungs so that the majority of 

blood flows through capillaries in the areas of the lung with the most ventilation. 

In other words ventilation and perfusion are matched. 

An understanding of normal lung function and physiology provides important 

clues to the mechanisms underlying diseases of the lung. For example, the 

abrupt change in flow from convective to diffusion at the level of the terminal 

bronchioles causes some inhaled particulates to get deposited here, making 

this area susceptible to damage. 1 Another example relates to the differential 

ventilation of lung tissue. Diseases which primarily affect the apex of the lung 

will impact breathing differently than those diseases that affect the base. In 

the following chapters, specific diseases of the pulmonary system will be 

discussed; a basic understanding of the normal structure and function of the 

lungs will allow for a more complete understanding. 

REFERENCES 

1. Mason editor. Murray and Nadel’s Textbook of Respiratory Medicine, 4th 

edition 2005. Saunders, An Imprint of Elsevier. 

2. Cotran, Kumar, and Robbins editors. Robbins: Pathologic Basis of Disease, 

5th edition 1994. W.B. Saunders Company 

3. McArdle WD, Katch FI, Katch VL editors. Exercise Physiology: Energy, 

Nutrition, and Human Performance, 5th edition. Lippincott, Williams 

and Wilkens 2001. 


15


Chapter 1-2 

Occupational Risks of 

Chest Disease in 

Fire Fighters 

By Dr. Carrie Dorsey, MD, MPH 

INHALATION OF COMBUSTION 

PRODUCTS 

Fire smoke is a complex mixture of chemicals that result from the combustion 

(complete burning) and pyrolysis (incomplete burning) of materials. The 

products of combustion formed during any given fire are dependent on the 

materials consumed within the fire, the amount of oxygen present and the 

temperature at which the fire burns. 1 Because of the various factors that 

influence combustion it is difficult to predict what a fire fighter is exposed to 

at a specific fire. There are however a number of chemicals that are routinely 

found in fire smoke. For example, carbon monoxide is produced during all 

combustion reactions and carbon dioxide, nitrogen dioxide, hydrogen chloride, 

cyanide, and sulfur dioxide are also commonly detected. 

When considering the risk of chest disease in fire fighters exposed to the 

products of combustion it is helpful to break these down into acute effects 

(those happening at or shortly following exposure and which tend to resolve), 

and chronic effects (those changes in health that occur following multiple 

or long-term exposures). The following is a discussion of each of these with 

respect to the respiratory system. 

Acute Effects 

Within fire smoke there are gases and particles that can be irritating and 

or toxic to the respiratory system. Injury can result from thermal exposure, 

asphyxiation, and response to irritants and toxicants. Symptoms and signs of 

inhalation that indicate damage to the respiratory system include tachypnea 

(rapid breathing), cough, hoarseness, stridor (loud breathing on inhalation 

and exhalation), shortness of breath, retractions (contraction of the abdominal 

and neck muscles), wheezing, sooty sputum, chest pain and rales/rhonchi 

(abnormal breath sounds heard with a stethoscope) . 2 

Because of the respiratory system’s ability to rapidly cool inhaled air, 

thermal injury is isolated to the upper airways (nose, mouth and pharynx). 

Asphyxiation (lack of oxygen) can result from the replacement of oxygen by 

another chemical in the environment known as a simple asphyxiant or by the 

interference of the body’s ability to transport and deliver oxygen to the tissues 

(chemical asphyxiant). Simple asphixiants include carbon dioxide, methane, 

Chapter 1-2 • Occupational Risks of Chest Disease in Fire Fighters 

17

18 Chapter 1-2 • Occupational Risks of Chest Disease in Fire Fighters 

helium, nitrogen and nitrogen oxide. Examples of chemical asphyxiants are 

carbon monoxide, cyanide, hydrogen sulfide and arsine gas. 3 The symptoms 

and signs of hypoxemia and anoxia (low oxygen in the blood) can include 

lightheadedness, shortness of breath, chest pain, coma or death. 

The effects of exposure to irritants such as hydrogen chloride, sulfur 

dioxide, phosgene, acrolein, ammonia and particulates are dependent on 

the size of the particle and how readily the chemical dissolves in water. These 

properties determine where in the respiratory tract the chemical or particle 

is deposited and absorbed. Hydrogen chloride is very soluble therefore injury 

occurs in the upper airway as opposed to phosgene which effects mainly in the 

lower respiratory tract (the lungs). 3 At high dose exposure, particle size and 

solubility are less predictive of the site of injury and there may be a pan-airway 

inflammatory response involving upper and lower airways and even alveoli. 

The irritants cause injury to the epithelial lining of the respiratory tract and 

inflammation. As discussed above this causes a variety of symptoms such 

as cough, shortness of breath, chest pain and increased mucous production. 

A number of studies of smoke inhalation in fire fighters have demonstrated 

increased symptoms, transient hypoxemia, hyperreactive (spasmodic or 

twitchy) airways and changes in pulmonary function test measurements. 

However, other studies have showed little effect and this is thought to be 

due to the increased use of respiratory protective equipment in more recent 

times. 4 A brief description of the studies of pulmonary function in fire fighters 

is found below. 

Chronic Effects on Pulmonary Function, Respiratory Illnesses 

and Mortality 

Studies of the long term effects of repeated exposure to smoke have not been 

conclusive. Many of the studies summarized below do not indicate that fire 

fighters have a significant decline in lung function over time. The findings of 

these studies may be influenced by factors such as fire fighters with respiratory 

disease transferring to non-firefighting duties or retiring or an underestimate 

of the effect because of the healthy worker effect. Improvement in respiratory 

protective equipment and its use is also likely preventing the development of 

chronic lung disease. 4 

SUMMARY OF STUDIES OF PULMONARY 

FUNCTION IN FIRE FIGHTERS 

The Forced Vital Capacity (FVC) is the total amount a person can breathe in 

or out with a single breath. The Forced Expiratory Volume in the first second 

of exhalation (FEV1) and Force Expiratory Flow measured in the mid-portion 

of exhalation (FEF25-75) can be used as measures of airway resistance. More 

can be found about these and other pulmonary function tests in the separate 

chapter on pulmonary function testing in this book. What follows here is a brief 

description of the relevant literature on pulmonary functions in fire fighters. 

Peters et al 1974: Measured pulmonary function at the start of the study 

and then one year later in 1,430 Boston fire fighters. The FVC and FEV1 both 

decreased more than expected over a one year time period. The rate of loss for

oth was significantly related to the number of fires fought, with increased 

rate of loss as the number of fires increased. 5 

Musk et al 1977a: Followed 1,146 Boston fire fighters from the same cohort 

as Peters et al for 3 years. The annual decline in FVC and FEV1 over the study 

period was less than observed in the initial year of the study. Fire fighters who 

fought no fires had a higher rate of decline. This was thought to be related to 

fire fighters with lung disease being selected for duties not involving active 

fire fighting. 6 

Musk et al 1977b: The authors also followed a group of retirees from the 

Boston cohort for five years. They observed that if the fire fighter retired with 

a shorter length of service, the individual had a non-significant increased 

rate of lung function loss and was more likely to have chronic bronchitis. The 

values of the pulmonary function tests were slightly lower than the expected 

values predicted for the study population. 7 

Musk et al 1979: In a group of 39 fire fighters the average decrease in FEV1 

following smoke exposure was 50 ml. The decline was related to severity of 

smoke exposure. 8 

Loke 1980: Fire fighters completed a self-administered respiratory and 

occupational history questionnaire and completed pulmonary function tests. 

Four of the 22 tested had evidence of airway obstruction on testing without 

symptoms. Seven of the fire fighters were tested again after exposure to 

heavy smoke. No difference in pulmonary function was detected comparing 

pre- and post-exposure tests. 9 

Musk et al 1982: 951 fire fighters from the Boston cohort were followed for 

six years. The declines in FEV1 and FVC over the six years were similar to 

those expected for healthy, non-smoking adults and were not correlated to 

firefighting exposure. The authors concluded that increased use of protective 

equipment in the cohort was protecting against the long-term effects of 

exposure to fire smoke. 10 

Sheppard et al 1986: FEV1 and FVC were measured before and after each 

shift and fire for 29 fire fighters over an 8-week period. Approximately one 

quarter of those measurements obtained within two hours of fighting a 

fire decreased by greater than two standard deviations. In some cases this 

decrement persisted up to 18.5 hours. 11 

Horsfield et al 1988: The pulmonary function tests of the controls which 

consisted of non-smoking men employed in occupations other than fire 

fighting declined at a faster rate over four years than in the fire fighters. 

This shows that fire fighters are healthier than the general population (“the 

healthy worker effect”) and is discussed further at the end of this chapter. 

In this study, the healthy worker effect is greater than any potential negative 

affect from fire exposures. 12 

Brandt-Rauf et al 1989: For individuals not wearing respiratory protective 

equipment there was a significant post-fire decline in FEV1 and FVC. The 

individuals in this study were participating in an environmental monitoring 

and medical surveillance program. 13 

Markowitz 1989: Followed a cohort of New Jersey fire fighters exposed to 

large quantities of hydrochloric acid in a PVC fire over approximately two 


19


years. At the initial evaluation there was a significant increase in pulmonary 

symptoms including cough, wheeze, shortness of breath and chest pain. 

These symptoms with the exception of wheezing remained significantly 

increased at the second evaluation. Of the cohort nine percent were told that 

they had asthma and 14% bronchitis following the time of the exposure. This 

was nearly significant when compared to unexposed fire fighters. 14 

Sherman et al 1989: Pulmonary function and methacholine challenge 

testing was completed pre- and post-shift on 18 fire fighters in Seattle. The 

mean FEV1 and FEF25-75 significantly decreased. 15 

Chia et al 1990: Twenty fire fighters were exposed to smoke in a smoke 

chamber. Airway reactivity to inhaled histamine was measured before and 

after exposure. Prior to exposure none had increased reactivity; however, 

following exposure 80% of the fire fighters had increased airway reactivity. 

Length of time as a fire fighter contributed to the relationship. 16 

Large et al 1990: Significant declines in FEV1 and FEF25-75 were measured 

in fire fighters following exposure. The other measures such as FVC also 

declined however not statistically significantly. 17 

Rothman et al 1991: Cross-seasonal changes in pulmonary function and 

symptoms were studied in 52 wildland fire fighters. Respiratory symptoms 

significantly increased from the beginning to the end of the season. Declines 

in FVC and FEV1 were noted; however, they were not significant. 18 

Liu et al 1992: 63 wildland fire fighters both fulltime and seasonal were 

evaluated with questionnaires, spirometry and methacholine challenge 

testing before and after the fire season. The individual mean FVC, FEV1 and 

FEF25-75 declined significantly across the season. Airway responsiveness as 

measured by the methacholine challenge test increased significantly by the 

end of the fire fighting season. 19 

Betchley et al 1997: Investigated the cross-shift pulmonary effects in forest 

fire fighters. There was significant mean individual decline in FVC, FEV1 

andFEF25-75 from pre-shift to post-shift. Declines were also seen when 

comparing pre-season to post-season measurements. 20 

Burgess et al 2001: The authors demonstrated acute changes in spirometry 

and lung permeability following fire overhaul despite the use of full-face 

cartridge respirators. 21 

Mustaijbegovic et al 2001: Active fire fighters had significantly more 

respiratory symptoms as compared to unexposed controls. The higher 

prevalence of symptoms was related to duration of employment and smoking 

status of the individual. As length of employment increased the decline 

in FVC increased. Early signs of airway obstruction were observed on the 

pulmonary function tests. 22 

Banauch et al 2003: New York City Fire Department rescue workers 

experienced massive exposure to airborne particulates at the World Trade 

Center site. Aims of this longitudinal study were to (1) determine if bronchial 

hyperreactivity was present, persistent, and independently associated with 

exposure intensity, (2) identify objective measures shortly after the collapse 

that would predict persistent hyperreactivity and a diagnosis of reactive 

airways dysfunction 6 months post-collapse. A representative sample of 179

NYC Fire Department rescue workers (fire fighters and EMS) stratified by 

exposure intensity to World Trade Center Dust (high, moderate, and control) 

without current smoking or prior respiratory disease were enrolled. Highly 

exposed workers arrived within two hours of collapse, moderately exposed 

workers arrived later on days one to two; control subjects were not exposed. 

Hyperreactivity (positive methacholine challenge tests) at one, three, and six 

months post-collapse was associated with exposure intensity, independent of 

ex-smoking and airflow obstruction. Six months post-collapse, highly exposed 

workers were 6.8 times more likely than moderately exposed workers and 

control subjects to be hyperreactive and hyperreactivity persisted in 55% of 

those hyperreactive at one and/or three months. In highly exposed subjects, 

hyperreactivity one or three months post-collapse was the sole predictor for 

reactive airways dysfunction or new onset asthma. 23 

Banauch et al 2006: New York City fire fighters’ pulmonary function (FVC 

and FEV-1) were studied for six years. In the five years pre-World Trade Center 

exposure, the mean annual decline in FVC and FEV-1 was not significantly 

different from the general population – averaging a 31 ml annual decrease in 

FEV-1. In the first year post-World Trade Center exposure, the mean decline 

in FEV-1 was 372 ml and there was an exposure intensity effect. This study 

demonstrates that annual declines in pulmonary function does not occur 

at an accelerated rate in fire fighters wearing modern respiratory protective 

equipment but when exposed to overwhelming irritants without respiratory 

protection, accelerated decline in pulmonary function can occur. Future 

studies are ongoing to determine if this effect is permanent. 24 

Gaughan et al 2008: Wildland fire fighters were studied with respiratory 

questionnaires, spirometry (FVC and FEV1) and chemical measurements of 

inflammation (albumin, eosinophilic cationic protein, and myeloperoxidase) 

in sputum and nasal lavage fluid. Assessments were made pre-season, postfire, 

and post-season. Fifty-eight fire fighters had at least two assessments. 

Mean upper and lower respiratory symptom scores were significantly higher 

post-fire compared to pre-season. Lung function declined with mean FEV1 

significantly lower post-fire as compared to pre-season and then recovered 

in the post-season. Individual increases in sputum and nasal measures of 

inflammation increased post-fire and were significantly associated with 

post-fire respiratory symptom scores. 25 

Miedinger D et al 2007: The authors prospectively determined the diagnostic 

value of respiratory symptoms and various tests used for asthma assessments. 

A questionnaire, spirometry, direct and indirect airway challenge tests, 

exhaled nitric oxide, and skin-prick tests were administered prospectively to 

101 of 107 fire fighters employed in Basel, Switzerland. Asthma was defined as 

the combination of respiratory symptoms with airway hyperresponsiveness. 

Asthma was diagnosed in 14% (14 of 101 fire fighters). Wheezing was the most 

sensitive symptom for the diagnosis of asthma (sensitivity, 78%; specificity, 

93%). Other respiratory symptoms showed a higher specificity than wheezing 

but a markedly lower sensitivity. Bronchial airway challenge with mannitol 

was the most sensitive (92%) and specific (97%) diagnostic test for asthma. 

Using a cutoff point of 47 parts per billion, nitric oxide had a similar specificity 

(96%) but lower sensitivity (42%) compared to the direct (methacholine) 


21


and indirect (mannitol) airway challenge tests. Asthma was considerably 

under-diagnosed in fire fighters. The combination of a structured symptom 

questionnaire with a bronchial challenge test identified fire fighters with 

asthma. The authors conclude that these tests should routinely be used in 

the assessment of active fire fighters and may be of help when evaluating 

candidates for this profession. 26 

FIRE FIGHTERS AND DISEASES OF THE 

RESPIRATORY SYSTEM 

Attempts to establish associations between fire fighters and occupational 

diseases have yielded conflicting results, reflecting the challenges encountered 

in studying this population. Because fire fighters are selected for their abilities 

to perform strenuous tasks they should demonstrate a “healthy worker effect.” 

The term “healthy worker effect” is used when a population has lower rates of 

disease and death than the general population thereby, accidentally masking 

exposure-response associations. To control for this, some studies rely on 

comparisons of fire fighters to police officers, a group presumed to be similar 

in physical abilities and socioeconomic status. Longitudinal dropout (due to 

job change or early retirement) may also reduce morbidity and mortality rates. 

Fire fighters who experience health problems related to their work may choose 

to leave their position, creating a survivor effect of individuals more resistant to 

the effects of firefighter exposures. Other issues that may influence morbidity 

and mortality rates in fire fighters are differences in exposures, both makeup 

and duration, between individuals and between different fire departments. 

In fact, the occupational exposures experienced by fire fighters varies greatly, 

influenced by the types of fires encountered, job responsibilities, and use of 

personal protective equipment. A further complication is that studies rarely 

account for non-occupational risk factors such as cigarette smoking due to lack 

of data. Finally, mortality studies frequently rely solely on death certificates 

even though it is well known that the occupation and cause of death may be 

inaccurate. Despite these difficulties, many important observations about the 

health of fire fighters have been made. 

Overall, fire fighters have repeatedly been shown to have all-cause mortality 

rates less than or equal to reference populations. Increased death rates 

from non-cancer respiratory disease have not been found when the general 

population was used for comparison. To reduce the presumed impact of the 

“healthy worker effect”, two studies used police officers for comparison. In 

both of these studies, fire fighters had increased mortality from non-cancer 

27, 28 

respiratory disease. 

By definition, mortality studies do not identify the human cost of chronic 

debilitating lung disease. Very large exposures to pulmonary toxicants can lead 

to permanent lung damage and disability. At 22 months, 9.4% of fire fighters 

exposed to hydrochloric acid during a large PVC fire were diagnosed with 

asthma and 14.3% were told that they had bronchitis. 14 Asthma or reactive 

airways dysfunction has also been shown to occur in fire fighters exposed to 

WTC dust. 23, 29 Fire fighters have not been shown to be at an increased risk of 

death from lung cancer, but again these studies are also confounded by the 

"healthy worker effect" and longitudinal dropout.

More studies are needed but epidemiologic evidence increasingly suggests 

that fire fighters are at increased risk for the development of sarcoidosis. 

Sarcoidosis is discussed in detail in a later chapter in this book. A cluster of 

three cases in a group of 10 fire fighters who began training together in 1979 

prompted an investigation involving active and retired fire fighters, police 

officers and controls. Fire fighting was significantly associated with one marker 

of immune system activation suggesting that fire fighters may be at increased 

risk for the development of sarcoidosis . 30 In addition, the annual incidence 

rate for sarcoidosis was increased in New York City fire fighters as compared to 

a concurrent New York City EMS pre-hospital healthcare worker control group 

and historic controls. 31 Nearly all of these fire fighters were asymptomatic 

with normal pulmonary and exercise function. After exposures at the WTC, 

a dramatic increase in the annual incidence of sarcoidosis in New York City 

fire fighters and EMS healthcare workers was demonstrated. 32 Furthermore, 

this group was symptomatic with evidence for obstructive airways disease, 

hyperreactivity and rarely arthritis. 

Summary of Studies of Respiratory Morbidity and Mortality in 


Musk et al 1978: Boston fire fighters were found to have a standardized 

mortality rate (SMR) for non-cancer respiratory disease of 0.93 as compared 

to the general male population of Massachusetts. A value of < 1 implies a 

decreased risk. 33 

Feuer et al 1986: When New Jersey fire fighters were compared to police 

officers a significant increase in the risk of death from non-cancer respiratory 

disease was observed (proportionate mortality ratio [PMR] 1.98) . 27 

Vena et al 1987: Again using the general population as a comparison group 

fire fighters from Buffalo, New York were found to be at less risk for non-cancer 

respiratory disease (SMR 0.48). In addition risk of death from respiratory 

cancers was less than the general population (SMR 0.94) . 34 

Rosenstock et al 1990: Fire fighters in three northwestern cities had significantly 

increased mortality due to non-cancer respiratory disease (SMR 1.41) . 28 

Sama et al 1990: A non-significant elevation in mortality due to lung cancer 

was found in fire fighters as compared to the general population (SMR 1.22) 

and to police officers (SMR 1.33). 35 

Beaumont et al 1991: Significantly less respiratory disease deaths were 

observed in San Francisco fire fighters as compared to the general population. 

The SMR was 0.63 for non-cancer and 0.84 for respiratory cancer deaths. 36 

Grimes et al 1991: Observed less death related to respiratory disease as 

compared to the general population. 37 

Guidotti 1993: A slight but non-significant increase in the risk of obstructive 

pulmonary disease was observed (SMR 1.57) . 38 

Aronson et al 1994: Observed less death related to respiratory disease as 


Burnett et al 1994: A large survey of fire fighters in 27 states showed decreased 

risk of death from non-cancer and cancer respiratory disease. 40 


23


Tornling et al 1994: Observed less death related to respiratory disease as 


Prezant et al 2002: The first reported series of 332 fire fighters who developed 

severe and persistent cough, shortness of breath, gastroesophageal reflux, 

sinus congestion/drip and other upper/lower respiratory symptoms after 

exposure to WTC dust. Evaluation demonstrated that 63% had a bronchodilator 

response and 24% had bronchial hyperreactivity, both findings consistent 

with asthma and obstructive airways disease. The clinical and physiological 

severity was related to the intensity of exposure. 29 

Ma et al 2005: In the most recent study to evaluate mortality in fire fighters 

there was a slight but non-significant increase in the risk of death from 

respiratory disease in female fire fighters as compared to the general 

population. Decreased risk was seen for the male fire fighters. 42 

REFERENCES 

1. Lees PSJ. Combustion products and other firefighter exposures. Occupational 

Medicine: State of the Art Reviews. 1995;10:691-706. 

2. Cohen MA, Guzzardi LJ. Inhalation of products of combustion. Ann Emerg 

Med. 1983;12:628-632. 

3. Bizovi KE, Leilin JD. Smoke inhalation among firefighters. Occupational 


4. Scannell CH, Balmes JR. Pulmonary effects of firefighting. Occupational 


5. Peters JM, Theriault GP, Fine LJ, Wegman DH. Chronic effect of fire fighting 

on pulmonary function. N Eng J Med. 1974;291:1320-1322. 

6. Musk AW, Peters JM, Wegman DH. Lung function in fire fighters, I: a three 

year follow-up of active subjects. Am J Public Health. 1977a;67:626-629. 

7. Musk AW, Peters JM, Wegman DH. Lung function in fire fighters II: a five 

year follow-up of retirees. Am J Public Health. 1977b;67:630-633. 

8. Musk AW, Smith TJ, Peters JM, McLaughlin E. Pulmonary function in 

firefighters: acute changes in ventilatory capacity and their correlates. 

Br J Ind Med. 1979;36:29-34. 

9. Loke J, Matthay RA, Putman CE, Smith GJW. Acute and chronic effects of 

fire fighting on pulmonary function. Chest. 1980;77:369-373. 

10. Musk Aw, Peters JM, Bernstein L, Rubin C, Monroe CB. Pulmonary function 

in firefighters: a six-year follow-up in the Boston Fire Department. Am J 

Ind Med. 1982;3:3-9. 

11. Sheppard D, Distefano S, Morse L, Becker C. Acute effects of routine 

firefighting on lung function. Am J Ind Med. 1986;9:333-340. 

12. Horsefield K, Guyatt AR, Cooper FM, Buckman MP, Cumming G. Lung 

function in West Sussex firemen: a four year study. Br J Ind Med. 1988;45:116- 

121.

13. Brandt-Rauf PW, Cosman B, Fallon LF, Tarantini T, Idema C. Health hazards 

of firefighters: acute pulmonary effects after toxic exposures. Br J Ind Med. 

1989;46:209-211. 

14. Markowitz JS. Self-reported short- and long-term respiratory effects among 

PVC-exposed firefighters. Arch Environ Health. 1989;44:30-33. 

15. Sherman CB, Barnhart S, Miller MF, Segal MR, Aitken M, Schoene R. Daniell 

W, Rosenstock L. Firefighting acutely increases airway responsiveness. 

Am Rev Respir Dis. 1989;140:185-190. 

16. Chia KS, Jeyaratnam J, Chan TB, Lim TK. Airway responsiveness of 

firefighters after smoke exposure. Br J Ind Med. 1990;47:524-527, 

17. Large AA, Owens GR, Hoffman LA. The short-term effects of smoke exposure 

on the pulmonary function of firefighters. Chest. 1990;97:806-809. 

18. Rothman N, Ford DP, Baser ME, Hansen JA, O’Toole T, Tockman MS, 

Strickland PT. Pulmonary function and respiratory symptoms in wildland 

firefighters. J Occup Med. 1991;33:1163-1167. 

19. Liu D, Tager IB, Balmes JR, Harrison RJ. The effect of smoke inhalation on 

lung function and airway responsiveness in wildland fire fighters. Am Rev 

Respir Dis. 1992;146:1469-1473. 

20. Betchley C, Koenig JQ, van Belle G, Checkoway H, Reinhardt T. Pulmonary 

function and respiratory symptoms in forest firefighters. Am J Ind Med. 

1997;31:503-509. 

21. Burgess JL, Nanson CJ, Bolstad-Johson DM, Gerkin R, Hysong TA, Lantz 

RC, Sherril DL, Crutchfield CD, Quan SF, Bernard AM, Witten ML. Adverse 

respiratory effects following overhaul in firefighters. J Occup Environ Med. 

2001;43:467-473. 

22. Mustaijbegovic J, Zuskin e, Schachter EN, Kern J, Vrcic-Keglevic M, Heimer 

S, Vitale K, Nada T. respiratory function in active firefighters. Am J Ind 

med. 2001;40:55-62. 

23. Banauch GI, Alleyne D, Sanchez R, Olender K, Weiden M, Kelly KJ, and 

Prezant DJ. Persistent bronchial hyperreactivity in New York City firefighters 

and rescue workers following collapse of World Trade Center. Am. J. Resp. 

Crit. Care Med. 2003; 168:54-62. 

24. Banauch GI, Hall C, Weiden M, Cohen HW, Aldrich TK, Christodoulou 

V, Arcentales N, Kelly KJ, and Prezant DJ. Pulmonary function loss after 

World Trade Center exposure in the New York City Fire Department. Am. 

J. Respir. Crit. Care Med. 2006; 174:312-319. 

25. Miedinger D, Chhajed PN, Tamm M, Stolz D, Surber C, Leuppi JD. Diagnostic 

tests for asthma in firefighters. Chest 2007;131:1760-1767. 

26. Gaughan DM, Cox-Ganser JM, Enright PL, Castellan RM, Wagner GR, 

Hobbs GR, Bledsoe TA, Siegel PD, Kreiss K, Weissman DN. Acute upper 

and lower respiratory effects in wildland firefighters. J Occup Environ 

Med. 2008;50:1019-1028. 


25


27. Feuer E, Rosenman K. Mortality in police and firefighters in New Jersey. 

Am J Ind Med. 1986;9:517-527. 

28. Rosenstock L, Demers P, Heyer NJ, Barnhart S. Respiratory mortality 

among firefighters. Br J Ind Med. 1990;47:462-465. 

29. Prezant DJ, Weiden M, Banauch GI, McGuinness G, Rom WN, Aldrich TK 

and Kelly KJ. Cough and bronchial responsiveness in firefighters at the 

World Trade Center site. N Eng J Med 2002;347:806-15. 

30. Kern DG, Neill MA, Wrenn DS, Varone JC. Investigation of a unique timespace 

cluster of sarcoidosis in firefighters. Am Rev Respir Dis. 1993;148:974- 

980. 

31. Prezant DJ, Dhala A, Goldstein A, Janus D, Ortiz F, Aldrich TK, Kelly KJ. 

The incidence, prevalence, and severity of sarcoidosis in New York City 

firefighters. Chest. 1999;116:1183-1193. 

32. Izbicki G, Chavko R, Banauch GI, Weiden M, Berger K, Kelly KJ, Aldrich 

TK and Prezant DJ. World Trade Center Sarcoid-like Granulomatous 

Pulmonary Disease in New York City Fire Department Rescue Workers. 

Chest, 2007;131:1414-1423. 

33. Musk Aw, Monson RR, Peters JM, Peters RK. Mortality among Boston 

firefighters, 1915-1975. Br J Ind Med. 1978;35:104-108. 

34. Vena JE, Fiedler RC. Mortality of a municipal-worker cohort: IV. Firefighters. 

Am J Ind Med. 1987;11:671-684. 

35. Sama SR, Martin TR, Davis LK, Kriebel D. Cancer incidence among 

Massachusetts firefighters, 1982-1986. Am J Ind Med. 1990;18:47-54. 

36. Beaumont JJ, Chu GST, Jones JR , et al. An epidemiologic study of cancer 

and other causes of mortality in San Francisco firefighters. Am J Ind Med. 

1991;19:357-372. 

37. Grimes G, Hirsch D, Borgeson D. Risk of death among Honolulu firefighters. 

Hawaii Medical J. 1991;50:82-85. 

38. Guidotti TL. Mortality of urban firefighters in Alberta, 1927-1987. Am J Ind 

Med. 1993;23:921-940. 

39. Aronson KJ, Tomlinson GA, Smith L. Mortality among firefighters in 

metropolitan Toronto. Am J Ind Med. 1994;26:89-101. 

40. Burnett CA, Halperin WE, Lalich NR, Sestito JP. Mortality among fire 

fighters: a 27 state survey. Am J Ind Med. 1994;26:831-833. 

41. Tornling G, Gustavsson P, Hogstedt C. Mortality and cancer incidence in 

Stockholm firefighters. Am J Ind Med. 1994;25:219-228. 

42. Ma F, Fleming LE, Lee DJ, Trapido e, Gerace TA, Lai H, Lai S. Mortality in 

Florida professional firefighters, 1972 to 1999. Am J Ind Med. 2005;47:509- 

517.

Chapter 2-1 

Disorders of the Upper 

Aerodigestive Tract 

By Dr. Michael Shohet, MD 

INTRODUCTION 

The upper aerodigestive tract, typically defined as the mucous membranelined 

structures from the nostrils and lips to the vocal cords and uppermost 

portion of the esophagus, is the portal for virtually everything that we inhale or 

ingest. Consequently, it is also the chief portal to workplace-related potential 

irritants. These irritants come in many forms, and the type of injury they 

produce is equally variable. Though certain exposures, especially those that 

cause allergies, are not considered serious or life threatening, increased 

research and experience has shown a much more prominent relationship 

between the upper airways and lung diseases. Additionally, the amount of 

disability related to chronic irritation of the upper airway such as the nose 

and sinuses, cannot be underestimated. If one just considers the economic 

impact of these disorders, it is clear that these diseases cannot be overlooked. 

ANATOMY 

Nose and Sinuses 

The nasal passages are paired cavities separated by a midline partition called 

the nasal septum. The chief functions of the nose are for smell, breathing, 

defense, and humidification. Specialized types of mucous membrane achieve 

these functions. In order to optimize efficiency, there are bony projections 

within the nasal cavities called turbinates that are also lined by this specialized 

mucous membrane. These turbinates are also comprised of many blood vessels 

that allow them to swell and shrink as necessary in order to better humidify, 

warm, and filter the air we breathe. Though it is normal for the turbinates to 

swell and shrink as part of our normal nasal function, the phenomenon of these 

mucous membranes swelling to excessively large levels is what we perceive as 

nasal congestion. Congestion has many causes including response to allergens 

and irritants, and is a chief symptom of rhinosinusitis. 

There are several air-filled hollows of the skull that are also lined by mucous 

membrane. These are found adjacent to the nasal cavities and are termed 

paranasal sinuses. The sinuses really serve no definitive function beside perhaps 

lightening the skull or protecting the brain from some forms of high-impact 

trauma. There are many ways that the sinuses can become a problem, however. 

Chapter 2-1 • Disorders of the Upper Aerodigestive Tract 

27

28 Chapter 2-1 • Disorders of the Upper Aerodigestive Tract 

Oral Cavity, Pharynx, and Larynx 

Fortunately, an explanation of the function of the mouth and tongue is likely 

not necessary. It should be noted that though we generally consider the tongue 

to be responsible for our sense of taste, the tongue really only gives us the 

sensations of sweetness, saltiness, bitterness, and sourness. The fine essences 

of food taste are accomplished by our sense of smell. 

The oral cavity structures are also lined by specialized mucous membranes. 

They are separated from the nasal cavity by the hard and soft palate. The palate 

may vary in size and shape in each individual, and along with the back of the 

tongue and nose, have specialized lymphoid tissue attached to them termed 

tonsils and adenoids. These structures may become enlarged or swollen as 

a manifestation of upper airway irritation as well, and are components that 

may need to be addressed in the management of various types of upper airway 

obstruction including obstructive sleep apnea. 

The rest of the throat is called the pharynx and larynx. Also lined by 

mucous membrane, the primary functions of the larynx are maintenance of a 

breathing passage, protection of the airway, and phonation. The cough reflex 

is important for protecting the airway during swallowing, but also in response 

to potentially noxious irritants that may be inhaled. The larynx is composed 

of cartilage, muscles, and nerves along with the vocal cords. The functions of 

speech, breathing, coughing, and swallowing are quite complex, with many 

ways for things to go wrong or become discoordinated. Given the larynx’s role 

as a primary defense of the lower respiratory tract, its function and hygiene 

must not be taken for granted. 

DISEASE 

Rhinitis, Sinusitis, and Rhinosinusitis 

Rhinitis means inflammation of the nasal cavities. Sinusitis means inflammation 

of the sinuses. Since the nasal cavities and sinuses are lined by the same type 

of specialized mucous membrane and the irritation and symptoms are often 

continuous and closely related to one another, the term rhinosinusitis has 

become popularized and preferred amongst specialists. 

The extent of inflammation can be quite variable. Similarly, the symptoms 

can be quite diverse even within the same individual. This may range from 

simple congestion or runny nose to intense pain or pressure in the cheeks, 

around the eyes, or headache. Loss of smell, weakness, tiredness, cough (often 

more severe at night,) and drainage down the back of the throat (postnasal 

drip) are other common manifestations of rhinosinusitis (Table 2-1.1). 

We typically classify rhinosinusitis as being one of two broad categories with 

different causes and courses: acute or chronic. Acute rhinosinusitis simply refers 

to an inflammatory episode lasting less than two weeks. Complete resolution of 

symptoms is typical in acute infections, as these are usually preceded or caused 

by viral infections of the nose and sinuses often called “colds.” The typical 

scenario would be that someone catches a cold that results in inflammation 

of the nasal passages. If this inflammation is enough to impair the effective 

circulation and clearance of the sinuses, a bacterial infection of the sinuses 

(acute rhinosinusitis) may result. The symptoms of acute rhinosinusitis often

differ from those of chronic rhinosinusitis in that the pain is often more sharp 

and severe, often with tenderness when the sinus is touched. Fever, blood and 

foul nasal discharge are all more common in acute cases. Acute rhinosinusitis 

can frequently be avoided if the cold is treated effectively with decongestants 

and anti-inflammatory medications. If acute infections recur very regularly 

(greater than four episodes yearly,) the possibilities of anatomic predispositions 

or issues with the immune system should be considered. Similarly, if one 

develops a complication of acute rhinosinusitis such as a brain or eye infection, 

further investigations are warranted and may include specialized imaging 

such as a CT scan, blood work to evaluate the immune system and to check 

for diabetes, as well as examination by a specialist. 

Signs and Symptoms of Chronic Rhinosinusitis 

• Facial pain and pressure including the cheeks, between the eyes, 

and forehead 

• Nasal congestion or obstruction 

• Drainage of discolored mucous from the nose or down the back of 

the throat (postnasal drainage) 

• Alteration in the sense of smell or taste 

• Aching of the upper teeth 

• Headache 

• Bad breath 

• Fatigue 

• Cough 

Table 2-1.1 Signs and Symptoms of Chronic Rhinosinusitis 

In cases of rhinosinusitis where the symptoms persist for over 12 weeks 

(chronic rhinosinusitis) there is usually some form of more persistent irritation 

of the nasal passages such as allergens, irritants, temperature extremes, wood 

dust, metal dust and chemicals. It should be noted that a clear demarcation 

between allergies and other causes of chronic inflammation of the mucous 

membranes of the nose and sinuses could be difficult. Not only can both types 

of inflammation be present in the same individual, but also often one's allergic 

disease could become substantially worsened by occupational exposures. 

For this reason protection from environmental and occupational irritants 

can be helpful in both allergic and non-allergic individuals. The relationship 

between asthma and chronic rhinosinusitis has been well described, and can 

best be understood by the fact that the entire upper respiratory tract is lined 

by the same type of mucous membrane, and therefore may react to similar 

irritants or allergens. 

The evaluation and management of chronic rhinosinusitis can be quite variable 

and complex. As the underlying cause is often exposure to some type of irritant 

whether it is a classical allergy or not, the detection of and protection from these 

irritants is quite helpful if possible. This evaluation may include formal allergy 

testing either by means of a blood test or evaluation by an allergist, and taking 

a careful history to determine if there is some preceding exposure or seasonal 

variation to the symptoms that may give some clue as to the irritant. In cases 


29

30 


where the offending agents can be determined, avoidance is recommended. 

If this cannot be practically achieved other options are considered and can be 

described as those that either decrease the body’s exposure to the irritants, 

or those that attenuate the bodies response to the irritants. Practical ways of 

decreasing the body’s exposure to airway irritants would include a mask or 

respirator designed to filter out the offending particles, or a nasal and sinus 

saline rinse applied immediately after a large exposure or on a regular basis 

in situations where the exposures are more persistent. (Table 2-1.2) 

Steps for Minimizing Symptoms of Chronic Rhinosinusitis 

• Avoidance of airway irritants such as smoke, dust, and toxic fumessometimes 

by use of a mask or respirator 

• Use of a saline nasal rinse to cleanse the nasal passages 

• Room humidification (with a humidifier that is cleaned regularly) 

• Allergy testing to learn of other possible triggers to avoid 

• Ensure you are drinking plenty of fluids 

• Avoid upper respiratory infections by washing your hands regularly 

and after any contact with people you suspect of being sick 

• Consultation with a physician to discuss medications which may 

decrease your body’s sensitivity to nasal irritants 

Table 2-1.2 Self-Care Steps for Minimizing Symptoms of Chronic Rhinosinusitis 

There are a number of ways to alleviate the nasal response to airway irritants 

both allergic and non-allergic. This would include topical and systemic 

(usually taken by mouth) medications designed to minimize the inflammatory 

response. A good example would be the use of an antihistamine pill for seasonal 

allergies. Some medications and nose sprays are intended for symptomatic 

relief, and some are intended to minimize the development of symptoms. This 

distinction is very important, and should be clarified with your physician in 

order to ensure proper use. 

In situations where symptoms persist even with carefully considered 

medical therapy, one must be evaluated for other factors. Certain defects of the 

immune system, either innate or acquired, may be considered. There are also 

anatomic factors that may warrant evaluation and possible treatment such as 

obstructing polyps, major deformities of the nasal septum, or narrowing or 

obstruction of the natural sinus openings. Benign and malignant tumors of 

the nasal cavities, though rare, have many of the same signs and symptoms as 

chronic rhinosinusitis, so evaluation is important if symptoms persist despite 

what would otherwise be considered adequate treatment. Sometimes a surgical 

procedure is helpful in addressing nasal obstructions or clearing the sinuses 

in order for them to clear more effectively. It should be noted that surgery is 

rarely if ever to be considered a cure for chronic sinusitis. It is simply one more 

tool that specialists have available in their armament in order to relieve most 

symptoms, and improve the body’s ability to be more resilient when exposed 

to environmental allergens or irritants. 

In cases where people tend to be much more symptomatic on one side, or 

if these symptoms persist despite aggressive treatment, the possibility of a

sinus tumor or cancer should be entertained and appropriate test ordered 

including sinus CT scans and endoscopy. As there are many occupational 

exposures that have been associated with higher incidences of certain types 

of sinus cancers, and the latency, or time between the actual exposure and 

the development of the resulting disease can be more than a decade, careful 

acquisition of all known exposures is important. 

Pharyngitis, Laryngitis, and Laryngopharyngitis 

Irritation of the throat has many names depending on where the irritation 

occurs. As the irritation is often not isolated to one specific area the term 

laryngopharyngitis, irritation of the throat and voice box, has become more 

favored. The main symptoms of laryngopharyngitis are throat soreness or 

change in voice. Throat dryness, cough, and trouble swallowing are other 

potential symptoms. Often one feels a tickling sensation, rawness, or lump in 

the throat. In some circumstances, the irritation can cause abnormal coordination 

of the vocal cords during normal breathing, resulting in a choking 

sensation, throat tightness, or even shortness of breath (Table 2-1.3). If the 

symptoms are severe, persistent, or progressive, prompt evaluation is necessary. 

Some forms of acute inflammation of the throat can progress to airway 

obstruction, and should be taken seriously. Persistent hoarseness can be a 

sign of something more serious, and should be evaluated if present for more 

than four to six weeks. 

Signs and Symptoms of Chronic Laryngopharyngitis 

• Hoarseness or loss of voice 

• Raw or sore throat 

• Cough (typically dry) 

• Difficulty breathing 

• Sensation of a lump in the throat 

• Trouble swallowing 

Table 2-1.3 Signs and Symptoms of Chronic Laryngopharyngitis 

As the throat is a mucous membrane lined passage, the same potential 

irritants as those of the nose and sinuses exist. These include viral infections, 

airway irritants, and smoke. Additionally, overuse or abuse of the voice may 

increase the risk of laryngitis. 

There are acute and chronic forms of laryngopharyngitis. A viral laryngitis, 

for instance, is typically acute (short-lived), while symptoms that are more long 

lasting usually point to a persistent irritating source such as severe allergies, 

smoking or chemical irritant exposure, habitual vocal strain, or acid reflux 

continually irritating the larynx. 

While most cases of acute laryngitis are managed with self-care, chronic 

laryngitis, cases lasting for more than two weeks, should usually be managed 

only after discussing one’s symptoms with a physician. Voice rest, adequate 

fluid intake, lubricants such as throat lozenges, and ensuring that the ambient 

air is humid without being contaminated with mold or fungus are excellent 

first steps to ensuring prompt recovery in cases of acute laryngopharyngitis. 


31

32 Chapter 2-1 • Disorders of the Upper Aerodigestive Tract 

The typical evaluation of chronic laryngopharyngitis or hoarseness is a 

thorough evaluation of one’s exposures and risk factors. Cigarette smoking, 

allergies, repeated exposure to environmental irritants, and voice overuse are 

often substantial risk factors. In some situations, evaluation of the voice and the 

throat and vocal cords by a specialist is necessary. This exam is often aided by 

performing a laryngoscopy procedure in which a very small fiberoptic scope 

is placed in the throat in order to view the mucous membrane surfaces and 

architecture with excellent resolution. The coordination of the muscles of the 

larynx can be examined as well as the vibrations of the vocal cords when using 

specialized instruments. Biopsies can be taken if anything suspicious is seen. 

As the treatment of chronic laryngopharyngitis largely depends on what 

is the underlying cause, a specialist evaluation is sometimes necessary in 

order to determine what that cause is. One common cause that warrants 

further discussion is chronic laryngopharyngitis due to reflux disease. This 

disorder refers to the backflow of stomach contents through the esophagus 

and potentially into the larynx and pharynx. When the reflux is limited to 

the esophagus, it may cause erosions that are experienced as heartburn (a 

burning sensation in the middle of the chest.) However, only half of patients 

diagnosed with reflux experience heartburn. This is due not only to the fact 

that the esophagus has more protective properties, but that the reflux is not 

spending enough time in the esophagus. As the esophagus is better suited to 

withstand the irritation of stomach contents such as acid, often a patient will 

have throat symptoms suggestive of laryngopharyngitis prior to experiencing 

traditional heartburn. Reflux can occur day and night, and often takes place 

even hours after a meal (Table 2-1.4). 

Tips for Reducing Reflux 

• Quit smoking or using any tobacco 

• Avoid caffeine (found in most coffee, tea, soda (especially cola), 

and mints) 

• Avoid alcohol 

• Avoid lying down two to three hours after eating 

• Avoid eating excessively large meals 

• Avoid eating foods that may trigger reflux including fatty or spicy 

foods, chocolate, onions, and tomato sauce 

• Control your weight 

• Loosen your belt and avoid tight-fitting clothes 

• Raise the head of your bed by placing blocks under the head of 

the bed or placing a wedge under the mattress 

Table 2-1.4 Tips for Reducing Reflux 

In addition to laryngoscopy, other testing may be necessary in order 

to definitively determine the underlying cause(s) of an individual’s 

laryngopharyngitis. If allergies are suspected, they may be further evaluated 

with allergy testing. In cases where reflux is suspected, there are other tests 

that may confirm the presence of acid in the throat and the esophagus. PH 

monitoring incorporates a probe, with the ability to measure acidity of fluids,

placed into the throat for several hours. The data acquired is subsequently 

uploaded into a computer and provides an excellent picture of the amount and 

timing acid reflux. Another test uses an endoscope consisting of a light and 

camera that is inserted down the throat and into the esophagus. It can detect 

erosions or abnormal changes in the lining of the esophagus and stomach. If 

anything appears to be suspicious, a biopsy can be taken. 

Less specific, yet often-helpful treatments for chronic laryngopharyngitis 

include voice rest, adequate hydration with non-alcoholic beverages, smoking 

avoidance, and avoidance of known upper airway irritants (Table 2-1.5). 

Steps for Minimizing Symptoms of Chronic Laryngopharyngitis 

• Avoidance of airway irritants such as smoke, dust, and toxic 

fumessometimes by use of a mask or respirator 

•. Avoid talking too loudly or for too long 

• Avoid whispering which causes increased strain on the throat 

• Avoid clearing your throat 

• Keep your throat moistened and your body hydrated by drinking 

plenty of non-alcoholic fluids 

• Avoid upper respiratory infections by washing your hands regularly 

and after any contact with people you suspect of being sick 

• Treat potential underlying causes of laryngopharyngitis including 

reflux, smoking, or alcoholism 

Table 2-1.5 Steps for Minimizing Symptoms of Chronic Laryngopharyngitis 

The use of antibiotics for management of chronic laryngitis is quite limited 

as most infectious cases are caused by a viral rather than bacterial infection. 

Potent anti-inflammatory medications including corticosteroids are sometimes 

helpful, and in circumstances when reflux is a major factor and conventional 

reflux lifestyle precautions fail to improve symptoms, antireflux medications 

or potent antacids may be prescribed. 


33


Chapter 2-2 

Respiratory Infections – 

Bronchitis and 

Pneumonia 

By Dr. Andrew Berman, MD and Dr. David Prezant, MD 

INTRODUCTION 

Respiratory tract infections are divided into two types: those of the upper 

respiratory tract and those of the lower respiratory tract. The upper respiratory 

tract consists of the nose, throat (pharynx), voice box (larynx) and the upper 

windpipe (trachea). Infections of the upper respiratory tract include the 

common cold, tonsillitis, sore throat (pharngitis), sinusitis, and laryngitis. 

These infections are commonly caused by viruses and are often self-limiting. 

In contrast, infections of the lower respiratory tract are more serious, often 

require antibiotics, and sometimes hospitalization. The lower respiratory 

tract includes the bronchi (the first main branches off the wind pipe into the 

lungs), bronchioles (smaller airtubes that branch off the bronchi), and alveoli (the 

air sacs at the end of the bronchioles). Infections in these areas include bronchitis, 

bronchiolitis and pneumonia. This chapter reviews upper and lower respiratory 

tract infections and their treatment. Details on sinusitis are discussed in a 

separate chapter on upper airways disease. 

AIRWAY INFECTIONS 

Acute Bronchitis 

Acute Bronchitis is defined as inflammation of the trachea, bronchi, and/or 

the bronchioles of the lung in response to an infection. Inflammation of these 

large airways leads to airway narrowing and mucus production, and results in 

a cough which is self-limited. Among out-patients, acute bronchitis is one of 

the most common illnesses in the United States, especially during the winter 

and fall seasons. 1 Chronic bronchitis is a clinically-distinct disease and will 

be discussed separately. 

Acute bronchitis is almost always caused by viruses, though these organisms 

are infrequently isolated. 2 The same viruses that cause a common cold can 

cause acute bronchitis, and are usually obtained in a similar manner including 

hand-to-hand contact and inhalation of aerosolized particles from coughing 

or sneezing. These viruses include adenovirus, influenza A and B virus, 

coronavirus, rhinovirus, herpes simplex, respiratory syncytial virus, and 

parainfluenza virus. For the influenza virus, the incubation period (the time 

between contact and infection) is two to four days and epidemics occur between 

Chapter 2-2 • Respiratory Infections — Bronchitis and Pneumonia 

35

36 Chapter 2-2 • Respiratory Infections — Bronchitis and Pneumonia 

fall and early spring. Bacteria are much less likely to cause acute bronchitis and 

are not commonly isolated. Bacteria that may cause acute bronchitis include 

Hemophilus influenzae, Pneumococcus, Moraxella catarrhalis and certain 

atypical bacteria, such as Mycoplasma pneumoniae and Chlamydophila 

pneumonia. Acute bronchitis can also be caused by the bacteria that cause 

whooping cough (Bordetella pertussis). 

Acute bronchitis is diagnosed based on clinical features. Most commonly, 

the patient complains of a cough, usually with discolored sputum. If the cough 

is severe, patients may cough up small amounts of blood (hemoptysis). Despite 

what many believe, thick discolored sputum does not mean there is a bacterial 

infection. The cough lasts at least five days and may persist for weeks. 3 Sore 

throat and mild shortness of breath may be reported. Patients often recall 

contact with an individual with similar symptoms. Fever is uncommon and 

if present, may suggest the diagnosis of pneumonia. Some patients develop 

wheezing due to bronchospasm and lung function studies may show reduced 

flow rates consistent with an obstructive pattern (ex. FEV1 and FEV1/FVC ratio). 

Bronchodilator response and airway hyperreactivity may also be demonstrated. 

Although wheezing is usually self-limiting and resolves in five to six weeks4 , 

viral bronchitis has been implicated as one cause of prolonged or even lifelong 

asthma in children and adults. 

Additional testing is often not necessary in diagnosing acute bronchitis, 

especially when vital signs and chest examination are normal. When temperature, 

respiratory rate or pulse rate is elevated, a chest x-ray may be performed to 

rule out pneumonia. The chest x-ray in patients with acute bronchitis does 

not show abnormalities, while “infiltrates” are commonly seen in patients 

with pneumonia (see below and the chapter on radiology). In the elderly, 

however, pneumonia may be present without altered vital signs, making these 

two conditions difficult to differentiate in this population without a chest 

x-ray. Sputum gram stain shows inflammatory cells and may show bacterial 

organisms, though since bacteria do not usually cause acute bronchitis, sputum 

studies are not recommended unless the chest x-ray is abnormal. If pertussis 

is suspected, nasopharyngeal cultures may be obtained. 

Generally, acute bronchitis is self-limiting. Treatment centers on lessening 

symptoms (fever and body aches) and often includes agents such as nonsteroidal 

anti-inflammatory drugs (such as ibuprofen or Motrin), aspirin, or acetaminophen 

(Tylenol). Cough suppressants are usually not effective but can be used if the 

cough is severe or interfering with sleep. There is limited and inconsistent 

data for the role of beta-agonists as bronchodilators. 5 Inhaled anticholinergic 

agents are not recommended. Though inhaled corticosteroids are sometimes 

prescribed, there is no data supporting their use. 

Antibiotics are commonly prescribed though are not indicated in the vast 

majority of bronchitis cases. In a published systematic review 5 where a series of 

studies were analyzed together, patients receiving antibiotics had a clinically 

insignificant shorter duration of cough (about one-half day less). However, 

there was also a trend towards an increase in adverse effects in the antibiotic 

group, leading the authors to conclude that any modest benefit was matched 

by the detriment from potential adverse effects. In another study, in patients 

with acute bronchitis without underlying lung disease, investigators found 

that antibiotic treatment did not differ from prescribing vitamin C. 6

Despite this evidence, however, physicians continue to frequently prescribe 

antibiotics for acute bronchitis, with a trend towards the use of newer, more 

broad-spectrum agents. Inappropriate use of antibiotics leads to increased 

bacterial resistance and adverse effects including infectious diarrhea caused 

by alterations of the normal gut flora. 

Published guidelines recommend antibiotic treatment only in certain 

cases. 7 Treatment of pertussis is recommended mainly to reduce transmission. 

Pertussis may be suspected as the causative agent when the patient reports 

coughing fits, with or without a whooping (or gasping) sound or post-cough 

vomiting. Treatment of pertussis is with an antibiotic from the macrolide 

class, such as azithromycin (Zithromax) or clarithromycin (Biaxin), though 

benefit is only observed if treatment is begun within the first week. If there 

is an influenza outbreak in the community, and infection with influenza A 

is suspected, therapy with the anti-influenza drugs, oseltamivir (Tamiflu) 

or zanamivir (Relenza), can be considered as the morbidity associated with 

this virus is great. Clinical benefit from treatment occurs when these drugs 

are initiated within two days of the onset of symptoms, and is defined as a 

patient having about one day less of symptoms. During an epidemic, these 

medications may also be used to prevent illness in high-risk individuals until 

vaccination can be administered. However, with increasing use of antiviral 

medications, resistance appears to be occurring. All high-risk patients (the 

elderly and those with chronic disease) should receive annual vaccination 

against the influenza strains most likely to be epidemic. Only if a bacterial 

etiology is suspected are antibiotics indicated. 

Because influenza interferes with the immune system, patients with acute 

influenza bronchitis may rarely go on to develop secondary viral or bacterial 

pneumonia. Post-influenza pneumonia caused by a virus should be suspected 

when cough, shortness of breath and fever persist for weeks. Post-influenza 

pneumonia caused by bacterial should be suspected when there was improvement 

followed by reoccurrence of symptoms one to two weeks later. The most common 

bacterial causes include Pneumococcus pneumonia, Staphylococcus aureus, 

Haemophilus influenzae, and Gram-negative organisms from the gut. 

Chronic Bronchitis 

Chronic Bronchitis is a subcategory of Chronic Obstructive Pulmonary Disease 

(COPD). It is characterized by persistent inflammation of the airways and is 

defined as the presence of a daily cough with sputum production for 3 months, 

two years in a row, in a patient in who other causes of chronic cough have 

been excluded. 8 Common to this condition are periodic acute exacerbations, 

usually due to respiratory infections. As the disease progresses, the time 

between acute exacerbations shortens. This topic is covered in greater detail 

in a separate chapter. 

Cigarette smoking is the main cause of chronic bronchitis. Other far 

less common causes include inhalational injury from occupational and 

environmental exposures. The airways of patients with chronic bronchitis are 

inflamed and produce extra mucus. In addition, mucus clearance is decreased. 

Both airway inflammation and extra mucus lead to narrowing of the airways 

which is why patients feel that it is hard for air to move out of the lungs and 

that they have mucus which is hard to get out. Overtime, inflammation and 


37

38 

mucus plugging can lead to progressive loss of lung function and patients 

may complain of breathlessness. Infections can cause acute exacerbations of 

chronic bronchitis and may worsen this condition, leading to further declines 

in pulmonary function. 

Chronic bronchitis should be considered in any patient with a history of 

tobacco use with a chronic cough and sputum production. Patients may have 

shortness of breath, usually when walking up inclined surfaces or steps or when 

carrying bags. Lung exam may reveal decreased breath sounds or wheezing, 

especially during exertion. Also, the time spent in expiration is often more 

than the amount of time spent for inspiration. In such patients, spirometry 

should be performed to confirm the diagnosis and grade the severity. A reduced 

FEV/FVC ratio (usually less than 70%), bronchodilator response and/or airway 

hyperreactivity are all indicators of significant airway obstruction, although 

the latter two are more common in asthma than in COPD. 

Patients with chronic bronchitis may have recurrent episodes of acute 

bronchitis, occurring one to two times per year, but the clinical picture and 

bacteriology differ from that seen in normal adults. Such episodes are termed 

acute exacerbations and are defined as an acute increase in symptoms beyond 

normal day-to-day variation. This generally includes one or more of the 

following: increased frequency and severity of cough, increases in volume and/ 

or changes in the character of sputum production, and/or worsening shortness 

of breath. 8 Most exacerbations of COPD are due to viral or bacterial respiratory 

infections. As opposed to acute bronchitis, bacterial infection is implicated 

in approximately one-half of acute exacerbations of chronic bronchitis. It is 

often difficult to determine if the cause is viral or bacterial because patients 

with chronic bronchitis have bacterial colonization of their airways even 

in the absence of acute infection. Common viral causes are adenovirus, 

influenza, rhinovirus, coronavirus, herpes simplex, and respiratory syncytial 

virus. Common bacterial causes are Haemophilus influenzae, Streptococcus 

pneumoniae, Moraxella catarrhalis, Chlamydia and Mycoplasma pneumoniae. 

Management and treatment of stable chronic bronchitis/COPD is discussed 

elsewhere in another chapter in this book. Antibiotics are generally reserved for 

use in acute exacerbations. As COPD progresses and lung function declines, the 

bacteria implicated in exacerbations change, and often require more broader 

spectrum antibiotics. Therefore, it is important to consider the patient’s lung 

function when selecting an antibiotic regimen. Currently, effective antibiotics 

include amoxicillin combined with the B-lactamase inhibitor clavulanate 

(Augmentin), macrolides such as azithromycin (Zithromax) and clarithromycin 

(Biaxin), fluoroquinolones (such as Levaquin and Avelox), and doxycycline. 

Antibiotics have been shown to have a significant benefit in patients with 

acute exacerbations. In an analysis of results of several studies looked at 

together, antibiotics increased the likelihood of clinical improvement, especially 

in patients with a severe exacerbation. 9,10 The Global Initiative for Chronic 

Obstructive Lung Disease (also known as GOLD) treatment guidelines, based 

on results from a randomized controlled trial showing significant benefit when 

antibiotics were given to patients who presented with shortness of breath 

and an increase in sputum volume and purulence, recommend antibiotic 

treatment in patients with these cardinal symptoms. 8 In addition, treatment 

Chapter 2-2 • Respiratory Infections — Bronchitis and Pneumonia

directed to airflow obstruction with bronchodilators and corticosteroids are 

frequently prescribed in an effort to break the cycle of chronic inflammation 

and recurrent airway injury. 

Bronchiolitis 

Bronchiolitis, an infection of the small peripheral airways, is primarily a viral 

infection occurring in infants. The most common causes include respiratory 

syncytial virus, parainfluenza virus type 3, influenza virus, adenovirus, 

and rhinovirus. Clinical presentation is cough, fever, and fatigue. The chest 

radiograph is typically normal but a high resolution chest CT scan shows 

small airway inflammation without infiltrates, often referred to as a “tree-inbud 

pattern.” Treatment is supportive with hydration, oxygen, and possibly 

bronchodilators. Recently, aerosolized ribavirin has been advocated to treat 

respiratory syncytial virus, a common cause of bronchiolitis in the midwinter 

and spring. Mycoplasma pneumoniae and Legionella pneumoniae are other 

infectious organisms that can cause bronchiolitis. When suspected, currently 

effective antibiotics include macrolides and fluoroquinolones. 

Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) 

Bronchiolitis obliterans with organizing pneumonia (BOOP) and now also called 

crytogenic organizing pneumonia is a specific form of bronchiolitis. It can result 

from a viral infection, though may also be the result of inhalational injury, drug 

effects, or inflammation from a noninfectious systemic illness such as rheumatoid 

arthritis. Patients present with chronic symptoms which commonly include 

a persistent dry cough and shortness of breath. Lung exam reveals crackles 

or a “velcro” sound. Unlike bronchitis where the chest radiograph should be 

normal, in BOOP the chest radiograph may show segmental infiltrates. A chest 

CT scan shows a classic picture of inflamed peripheral airways and segmental 

infiltrates. Pulmonary function tests show a restrictive pattern. BOOP is not 

responsive to antibiotics; instead treatment centers on oral corticosteroids. If 

initiated early, there is often a dramatic response in the first few days of steroid 

treatment. Treatment duration can vary though it is usually at least six months. 

Relapse can occur if steroids are discontinued too soon. 

Bronchiectasis 

Bronchiectasis is defined as destruction and permanent dilatation (widening) 

of the large airways. Dilated airways make it difficult to clear secretions, and 

can collapse causing airflow obstruction and recurrent infections. A person 

may be born with it or may develop it later in life as a result of airway infection 

or inhalation injury. Bronchiectasis may be isolated to a small area of the 

lung or may be extensive. While relatively uncommon in the United States, 

it's prevalence increases with age. 11 Once established, recurrent respiratory 

infections are common. 

Bronchiectasis can result from recurrent infection of the airways. Many 

patients demonstrate abnormal defenses against infection due to problems 

with their immune system. Immunodeficiency states may be present at birth 

(congenital) such as hypogammaglobulinemia, or are acquired, such as AIDS. 

Bronchiectasis can also result from an infection that does not clear due to a 

blocked airway, which can occur as a result of a foreign body aspiration. 


39


In adults, this is often aspirated food or a tooth. Certain lung infections 

(for example, tuberculosis or fungal infections) can lead to bronchiectasis. 

About half the cases of bronchiectasis in the United States today are caused by 

Cystic Fibrosis. This is an inherited multisystem disease that results in thick 

mucus which is difficult to clear. While most patients are children, up to seven 

percent are diagnosed at age 18 years or older. 12 Other systemic diseases that 

can cause bronchiectasis include rheumatoid arthritis, influenza, immotile 

cilia syndrome, or allergic bronchopulmonary aspergillosis. 

Patients often report frequent bouts of “bronchitis” before they are diagnosed. 

When the patient reports cough and daily production of thick sputum for months 

or even years, the diagnosis of bronchiectasis should be explored. About one 

quarter of patients report coughing up blood, usually described as streaks. 13 

Lung exam may reveal crackles and wheezing. The chest x-ray is abnormal 

in most patients with bronchiectasis, though findings can be nonspecific. A 

high resolution CT scan of the chest usually is needed to make the diagnosis 

and shows airway dilatation, bronchial thickening (Figure 2-2.1), and cysts 

(Figure 2-2.2). Once the diagnosis is made, an etiology is explored. A history 

of recurrent sinus infections may suggest an abnormality in host defense 

prompting specific studies of the immune system. A sweat test can be pursued 

to evaluate for cystic fibrosis. 

Figure 2-2.1: Bronchiectasis demonstrated by dilated, enlarged thickened airways (arrows) 

During acute exacerbations of bronchiectasis, patients report an increase 

in sputum production over their usual amount, shortness of breath and/or 

wheezing. Since these clinical features are shared with COPD, patients who 

present during an acute exacerbation may be misdiagnosed. Further, some 

patients only report fatigue and lack of energy, with decreased appetite and

Figure 2-2.2: Cystic Bronchiectasis 

weight loss, which may also lead to pursuit of an alternative diagnosis. Fever 

may or may not be present. During acute exacerbations, chest x-rays are often 

unchanged from prior evaluations. CT scans however may detect changes not 

appreciated on chest x-rays. 

Treatment of bronchiectasis should focus on treating the underlying cause, 

controlling respiratory infections, managing secretions, and addressing 

complications. While the condition is irreversible, treatment can lessen 

symptoms and may be able to prevent additional damage. As noted above, 

patients can acquire bronchiectasis from several different pathways. When 

the cause is infection with airway obstruction due to an aspirated foreign 

body, a pulmonologist can try to retrieve the object by placing a flexible rubber 

tube into the airways called a bronchoscope. In those patients with recurrent 

infections due to low or missing immune system factors, replacement of the 

missing factor, when possible, leads to a significant reduction in the frequency 

of future infections. HIV disease (AIDS) can also lead to recurrent infections, 

and should be treated with appropriate anti-retroviral medications to improve 

the immune response. While the gene that causes cystic fibrosis has been 

isolated, there remains no available treatment for the primary defect. 

Treating acute respiratory infections is paramount when treating bronchiectasis, 

since infections are not only the cause of the disease but also are the cause of 

disease progression. All patients should be asked to submit a sputum culture in 

an attempt to isolate bacteria and to determine which antibiotics would work 

best (reported as the sensitivity of the bacteria). Over time, resistance to some 

of the more common antibiotics is often demonstrated due to prior antibiotic 

treatments. After the most appropriate antibiotic is selected, treatment for 

acute exacerbations generally continues for 7 to 10 days. 14 Occasionally, an 

additional or longer course of antibiotics may be necessary in patients who 

do not adequately respond. 


41


Antibiotic treatment is sometimes given before an acute infection arises. 

This approach of preventive antibiotic treatment is considered when a patient 

has frequent exacerbations. Treatment is usually with a regimen of oral 

antibiotics, though aerosolized antibiotics are also sometimes used. Side effects 

of aerosolized antibiotics include coughing, wheezing or shortness of breath. 

Despite treatment, sputum from the airways of patients with bronchiectasis 

can continue to grow organisms. When this occurs, the patient is said to be 

colonized. Patients colonized with the bacteria, Pseudomonas aeruginosa, have 

been shown to have impaired health-related quality of life. 15 Mycobacterium 

avium complex and the fungus, Aspergillus, are other colonizers that can be 

isolated in patients with bronchiectasis. 

Managing secretions (known as bronchial hygiene) in patients with 

bronchiectasis is difficult, though central to management, since retained 

secretions can worsen this disease. Several techniques are available, such as 

maintaining adequate hydration and nebulizing saline. Chest physiotherapy 

by clapping ones hands on the patient’s back and chest along with postural 

drainage are other techniques. Mechanical devices are also available including 

vests that shake your chest and handheld devices that you blow into and cause 

a vibration that travels back into the lungs. Each technique has the same 

goal: to loosen thick secretions. Bronchodilator therapy is often prescribed 

to manage secretions and to address airflow obstruction. 

When treatment of the underlying cause plus antibiotics and bronchial 

hygiene does not lead to improvement, surgery can be considered if the 

bronchiectatic airways are mostly limited to one part of the lung. Surgery is 

also considered when persistent infections lead to destruction and bleeding 

that cannot be controlled by other measures. There are however no controlled 

studies to determine if surgery is more beneficial than non-surgical treatment. 16 

PNEUMONIAS 

In the United States annually, community acquired pneumonia is responsible 

for over 50 million days of medical leave from work, over 1 million cases 

are hospitalized, and it is the sixth leading cause of death. 17, 18 Communityacquired 

infections may be viral, bacterial or rarely fungal and parasitic. 

Hospital-acquired or nosocomial pneumonia which have a far higher 

mortality rate, are usually bacterial in origin, although viral infections can 

also occur, particularly if hospital personnel with acute viral infections come 

to work and then spread their infection to patients. The risk for pneumonia is 

increased in patient populations due to immune suppression or underlying 

cardiopulmonary functional impairment. Among the elderly, the annual 

incidence of pneumonia is estimated to be between 180/10,000 and 440/10,000 

as compared to 50/10,000 and 120/10,000 in the general population. 19, 20 In the 

elderly, pneumonia is the fourth leading cause of death. 21 In critically ill patients 

treated with mechanical ventilation, hospital acquired pneumonia develops in 

10 to 70% of all patients, depending on the type of illness that led to intubation 

and mechanical ventilation. 22 Of even greater consequence is the fact that 

mortality rates are also dependent on the underlying disease. If the underlying 

disease responsible for respiratory failure was the adult respiratory distress 

syndrome (ARDS) and hospital acquired pneumonia occurs, then survival 

rates are less than 15% as compared to survival rates greater than 50% in ARDS

patients without hospital acquired pneumonia. 23 Other groups at increased 

risk for pneumonia include patients with cardiac disease, chronic obstructive 

lung disease, cystic fibrosis, bronchiectasis, splenic dysfunction or absence, 

cancer, cirrhosis (liver failure), renal failure, diabetes, sickle cell disease, any 

immunosuppressive therapy or disease state, alcoholism and malnutrition. 24, 

25 Because these patient groups are at increased risk of infection, available 

vaccines to prevent respiratory infection are recommended (e.g. Influenza 

and Pneumococcal vaccines). 

Pneumonia 

Pneumonia is an infection of lung tissue involving the alveoli where gas 

exchange takes place. Infections that produce pneumonia often do so by 

causing the alveoli to fill with inflammatory cells and fluid. Everyday, bacteria 

are inhaled into the lower airways without causing bronchitis or pneumonia. 

When pulmonary infections occur, it is the result of a virulent organism, a 

large dose or an impaired immune system. Bacteria can reach the lung by any 

one of four routes: inhaling organisms in the air, aspiration from a previously 

colonized upper airway, spread from a bloodborne source, or spread from 

an adjacent, contiguous area of infection. Aspiration is the major cause for 

most forms of pneumonia. All of us aspirate small amounts of upper airway 

secretions every night, but as a percent of the population very few individuals 

actually develop pneumonia. This form of aspiration is distinguished from 

severe aspiration of large amounts of oral and gastric contents resulting 

from impaired consciousness (due to alcohol, drugs, seizures, shock, or 

neuromuscular disease) or altered respiratory tract anatomy. When aspiration 

involves primarily bacteria, pneumonia may occur. 

When pneumonia involves an entire lobe of the lung, it is termed “lobar 

pneumonia,” (Figure 2-2.3) and when severe, more than one lobe is involved. 

Figure 2-2.3: Chest radiograph showing community acquired pneumonia involving the 

right upper lobe. 


43


Pneumonia can also occur as patchy infiltrates adjacent to bronchial airways 

and is then termed “bronchopneumonia.” Pneumonias can be classified 

according to their clinical presentation as either “typical” or “atypical.” Typical 

pneumonias are characterized by sudden onset of fever, chills, productive cough 

and pleuritic stabbing-like chest pain. Bacterial infections are the usual cause 

of typical pneumonias and common ones include: Streptococcus pneumoniae, 

Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, 

aerobic Gram-negative bacteria, and anaerobes. 24, 25 Atypical pneumonia 

is characterized by fever without chills, nonproductive cough, headache, 

and body aches. Atypical pneumonias are most commonly due to viruses, 

Mycoplasma pneumoniae and Legionella pneumoniae . 24, 25 Despite this 

classification into typical and atypical pneumonia being useful clinically, 

it is often difficult to predict the specific infection that is actually causing 

the pneumonia and most guidelines do not rely solely on this classification 

for antibiotic recommendations. 26, 27 Organisms that cause pneumonia may 

produce clinical presentations that overlap both typical and atypical syndromes. 

Pneumonia also commonly occurs in patients who have coexisting illnesses 

which alter the clinical presentation. For example, if a patient has an impaired 

immune response (such as the elderly, alcoholics, diabetics, or patients with 

AIDS), typical pneumonia symptoms may be absent. 

Mortality and Severity Assessment 

Mortality rates from pneumonia, regardless of the organism responsible, 

are always highest in patients with coexisting serious illnesses such as 

cardiopulmonary diseases, cirrhosis (liver failure), renal failure, malignancy, 

diabetes, and in patients with immune deficiencies (regardless of cause). 

The mortality rate for severe pneumonia exceeds 25%. 28 Criteria for severe 

pneumonia include a respiratory rate above 30 breaths per minute; severe 

hypoxemia (low oxygenation), multilobar involvement, respiratory failure 

requiring mechanical ventilation, shock, acute renal failure, bacteremia 

(organisms in the blood) and/or extra-pulmonary spread of infection. Severity 

assessment scores have been developed to improve early identification and 

hopefully decrease mortality rates in these patients. The Pneumonia Severity 

Index (PSI) assesses points for each of several factors including: 28 age; coexisting 

illness (cancer, liver disease, cerebrovascular disease and kidney disease); 

physical exam findings (altered mental status, respiratory rate >30 breaths/ 

min, heart rate >125 beats/min, systolic hypotension, high or low temperature); 

and laboratory findings (acidosis, renal failure, hyponatremia, hyperglycemia, 

anemia, hypoxia, pleural fluid). The more points, the greater risk of death 

within the first 30 days. 

The organism responsible for causing a patient’s pneumonia can be predicted 

by the status of the patient’s underlying immune system and other coexisting 

diseases, as well as their place of residence - the community or a hospital/chronic 

care facility. 26, 27 In the community, viruses may account for up to one-third of all 

pneumonias. The most common bacterial organism responsible for communityacquired 

infection in all types of patients is Streptococcus or Pneumococcal 

pneumoniae. Other common organisms include Mycoplasma pneumoniae, 

Chlamydia pneumoniae, Hemophilus Influenzae, Legionella pneumonia and 

in certain patients with specific coexisting diseases Staphylococcus Aureus, 

Gram negative bacteria (Klebsiella pneumonia and Pseudomonas pneumonia),

and Pneumocystis carinii. Unusual organisms should be suspected if the 

patient has a recent travel or exposure history – tularemia (in hunters), plague 

(from exposure to small animals in the mid-western US), anthrax (in wool 

sorters and tanners), Cryptococcus (from pigeon droppings), Histoplasmosis 

(from river valleys or bat droppings), Coccidioidomycosis (in the southwestern 

United States), psittacosis (from infected birds), or parasitic infestation (from 

travel to the tropics). 

Common Organisms Responsible for Community-Acquired 

Pneumonias 

Streptococcus or Pneumococcal pneumonia is a Gram-positive, lancet-shaped 

diplococcus and is the most common cause of community acquired pneumonia 

in all populations, regardless of age or coexisting disease. Eight-five percent 

of all pneumococcal pneumonias are caused by any one of 23 serotypes. The 

pneumococcal vaccine (Pneumovax) provides protection against all 23 serotypes. 

Infection is the most common in the winter and early spring, and therefore 

it is not surprising that many patients report have a preceding viral illness. 

Spread is from person-to-person and pneumonia develops when colonizing 

organisms are aspirated at a high enough dose to cause infection. Patients with 

an intact immune response present with the “typical” pneumonia syndrome of 

abrupt onset of a febrile illness, appearing ill or “toxic” with a cough productive 

of rusty colored sputum and complaining of pleuritic stabbing chest pain. 

Chest radiographs can show a lobar or bronchopneumonia pattern. Physical 

examination of the chest may show evidence for consolidation with absent 

breath sounds. Bacteremia (organisms in the blood) can occur in 15 to 25% of 

all patients and mortality rates are substantially higher in such cases. While 

penicillin or erythromycin can be prescribed, current treatment for outpatients 

with community-acquired pneumonia usually includes macrolides such as 

azithromycin (Zithromax) and clarithromycin (Biaxin), based on an easier 

to comply with dosing interval and less gastrointestinal side effects. Also 

used are oral beta-lactams such as cefuroxime, amoxicillin, or amoxicillinclavulanate. 

Fluoroquinolones with activity against Streptococcus pneumonia 

(such as Levaquin and Avelox) can be substituted when needed though some 

recommend against the use of this class of antibiotics as first-line therapy due 

to risk of developing resistance. 

Unfortunately, the incidence of penicillin resistant pneumococci is rising. 

Ten percent of strains in the United States are intermediately resistant to 

penicillin but can still be treated with high dose penicillin, while one percent 

are highly resistant and require treatment with Vancomycin. With effective 

therapy, clinical improvement occurs in 24 to 48 hours. As is often the case in 

any type of pneumonia, radiographic improvement lags behind the clinical 

response and may take months to clear and become normal. 

Legionella pneumonia is a Gram-negative bacillus first characterized 

after it led to a pneumonia epidemic in Philadelphia in 1976. Retrospective 

analysis of stored specimens has shown that Legionella pneumonia has caused 

human disease since at least 1965. At least 12 different serogroups have been 

described, with serogroup 1 causing most cases. The organism is water borne 

and can emanate from air conditioning equipment, drinking water, lakes and 

river banks, water faucets, hot tubs and shower heads. Infection is caused by 


45

46 

inhalation of an infected aerosol generated by a contaminated water source. 

When a water system becomes infected in an institution, endemic outbreaks 

may occur, as has been the case in some hospitals. Legionella infection can 

also cause sporadic cases. Person-to-person spread has not been documented, 

nor has infection via aspiration from a colonized oropharynx, although it 

may be possible that the infection can develop after subclinical aspiration 

of contaminated water. The incubation period is 2 to 10 days. Patients with 

Legionella pneumonia commonly present with high fever, chills, headache, 

body aches and elevated white blood cell counts. Features that can suggest 

the diagnosis specifically are the presence of pneumonia with preceding 

diarrhea, along with mental confusion, relatively slow heart rates, low blood 

sodium levels, and liver function abnormalities. The patient may have a dry or 

productive cough, pleuritic stabbing chest pain, and shortness of breath. The 

chest radiograph is not specific and may show bronchopneumonia, unilateral 

or bilateral disease, lobar consolidation, or rounded densities with cavitation. 

Symptoms are rapidly progressive, and the patient may appear to be quite ill or 

“toxic”. Legionella pneumonia is a major cause of severe community acquired 

pneumonia. Some patients may develop renal failure and this combination 

of respiratory failure and renal failure has a high mortality rate. Currently, 

effective therapy is with macrolides and flouroquinolones. 

Haemophilus influenza is a Gram-negative coccobacillary rod that occurs 

in either a typable, encapsulated form or a nontypable, unencapsulated form. 

Because pneumonia from Haemophilus influenzae occurs commonly in 

patients with impaired immune defenses, most patients will have an underlying 

illness, such as COPD, an immune deficiency, or alcoholism. Patients present 

with a sudden onset of fever, sore throat, cough and pleuritic stabbing chest 

pain. Children frequently have earaches. Complications include empyema 

(infected pleural space between the lungs and chest wall), lung abscess, 

meningitis, arthritis, and pericarditis. Adult mortality rates are high and 

mostly reflect the impact of the coexisting illness. Currently, effective therapy 

for H. influenzae infection, due to rising resistance, is either a combination of 

amoxicillin and clavulanic acid, third-generation cephalosporins, trimethoprim/ 

sulfamethoxazole, macrolides or the fluoroquinolones. Many isolates are also 

resistant to ampicillin and erythromycin, therefore these antibiotics should 

not be used. 

Mycoplasma pneumoniae commonly causes minor upper respiratory 

tract illnesses or bronchitis. Although pneumonia occurs in 10% or less of all 

Mycoplasma infections, this organism is still a common cause of pneumonia. 

In the general population, it may account for 20% of all pneumonia cases, and 

up to 50% in certain populations, such as college students. The disease occurs 

year-round, with slight increase in the fall and winter. All age groups are affected, 

but disease is more common in those under 20 years of age. The incubation 

period is anywhere from two to three weeks and when pneumonia occurs, the 

usual presentation is in the form of an atypical pneumonia. Patients commonly 

have a dry cough, fever, chills, headache, and fatigue. Up to half will have upper 

respiratory tract symptoms including sore throat and earache. Chest radiographs 

show interstitial infiltrates, which are usually unilateral and in the lower lobe, 

but can be bilateral and multilobar. The patient usually does not appear as ill 

as suggested by the radiographic picture. Most cases resolve in 7 to 10 days, 


ut rarely patients will have a severe illness with respiratory failure. When 

severe, infection is often characterized by its extrapulmonary manifestations 

including meningoencephalitis, meningitis, autoimmune hemolytic anemia, 

myocarditis, pericarditis, hepatitis, gastroenteritis, arthralgias, pancreatitis, 

and renal insufficiency. Currently, effective antibiotics include macrolides, 

doxycyline, and the fluoroquinolones. 

Chlamydia pneumonia is a relatively common cause of pneumonia in 

teenagers and adults. Patients present with fever, chills, sore throats, hoarse 

voices, pleuritic chest pain, headache, and cough and only rarely progress to 

respiratory failure. Currently, effective treatment is doxycycline, macrolides 

and the fluoroquinolones. Duration of treatment is usually two to three weeks. 

Staphylococcus aureus can cause community acquired pneumonia in normal 

patients recovering from influenza, in patients addicted to intravenous drug 

use, and in the elderly. Patients present with sudden onset of fever, shortness 

of breath, and cough productive of purulent sputum. The radiograph may 

show infiltrates, cavities, and/or lung abscess. An infected pleural effusion 

(fluid in the space between the lung and chest wall), called an empyema may 

also occur. Currently, effective treatment is with an anti-staphylococcal 

penicillin (methicillin) or if methicillin resistant (referred to as MRSA), then 

vancomycin. Strains resistant to methicillin have become increasingly common. 

Extrapulmonary complications include endocarditis (heart infection) and 

meningitis (brain infection). 

Viruses may account for at least 20% of all community-acquired pneumonias. 

Viruses are spread by aerosol or by person-to-person contact through 

infected secretions. The common agents causing lower respiratory infection 

include adenovirus, influenza virus, herpes group viruses (which include 

cytomegalovirus), parainfluenza virus, and respiratory syncytial virus. Many 

patients with viral pneumonia have a mild “atypical” pneumonia with dry 

cough, fever, and a radiograph "looks worse than the patient." When bacterial 

superinfection is present, the illness is biphasic, with initial improvement from 

the primary viral infection followed by sudden increase in fever along with 

purulent sputum and lobar consolidation. Rash occurs with varicella-zoster, 

measles, cytomegalovirus, and enterovirus infections. Sore throat accompanies 

infection by adenovirus, influenza and enterovirus. Liver inflammation 

(hepatitis) is often present with infectious mononucleosis (Epstein-Barr virus) 

and cytomegalovirus. Viral pneumonia is an entirely different entity if the 

patient is immunocompromised. Patients with AIDS, malignancy, or major 

organ transplantation can develop severe viral pneumonia that progresses 

to respiratory failure requiring mechanical ventilation. Viruses that cause 

severe pneumonia in the immunosuppressed patient include cytomegalovirus, 

varicella-zoster, and herpes simplex virus. Patients with cytomegalovirus 

infection have been successfully treated with gancyclovir. Pneumonia from 

herpes simplex and varicella-zoster can be treated with acyclovir. 

Klebsiella pneumoniae is a Gram-negative rod from the gut. Mortality rates may 

be as high as 50% because it generally affects patients with impaired immune 

systems, debilitated individuals with coexisting conditions such as patients 

with alcoholism, diabetes, cardiopulmonary diseases, renal failure, or cancer, 

or the elderly living in nursing homes. The onset is sudden with productive 

cough, pleuritic stabbing chest pain, shaking chills and fevers. Patients look 


47

48 

ill or “toxic". The chest radiograph shows dense consolidated infiltrates in the 

upper lobe with a fissure bulging downward. Lung abscess may result. Other 

complications include pericarditis, meningitis, and empyema. Diagnosis is 

suspected by finding Gram-negative rods in the sputum in a patient with a 

compatible illness and risk factors. Currently, effective antibiotics include thirdgeneration 

cephalosporins, aminoglycosides, antipseudomonal penicillin, 

aztreonam, imipenem, or fluoroquinolones. 

Pneumocystis carinii pneumonia (PCP) is common in immunosuppressed 

patients with AIDS HIV infection. The organism can easily be recognized by 

microscopic examination of induced sputum, bronchoalveolar lavage fluid 

from the lung, or lung biopsy. Most patients probably acquired Pneumocystis 

carinii from natural sources prior to the onset of AIDS and contained it 

within the lung. Once AIDS develops, the patient’s immune system no longer 

functions optimally and latent infection with Pneumocystis carinii may become 

reactivated. Alternatively, a new infection or even re-infection may occur. Like 

most patients with pneumonia, the clinical presentation includes fever, cough, 

shortness of breath and fatigue. However, with PCP the fevers are prolonged; 

the cough is dry; night sweats may occur; and weight loss can be severe. The 

chest radiograph usually shows bilateral diffuse infiltrates that are mostly in 

the lower lobes (Figure 2-2.4), although asymmetric focal infiltrates, nodules 

or even cysts (mini-cavities) may occasionally be seen. 

Figure 2-2.4: Chest radiograph showing Pneumocystis carinii pneumonia in an AIDS patient. 

. 

Note that the bilateral lower lobe involvement 

For many patients with Pneumocystis carinii, it is there first sign of AIDS. 

Therefore, all patients with this clinical presentation should be questioned for 

AIDS risk factors and Pneumocystis carinii should be considered. Findings that 

suggest the diagnosis are a compatible chest radiograph, low rather than elevated 

white blood cell counts, elevated lactate dehydrogenase (LDH) levels in the 

blood, fungal infection in the rear of the throat (oral candidiasis or thrush), and 

hypoxemia (low oxygenation) occurring with exertion that is out of proportion 

to that suggested by the chest radiograph. Pneumocystis carinii can also occur 

in immunocompromised patients without AIDS, such as lymphoma or after 

long-term oral corticosteroid treatment. With appropriate therapy over 90% 

survival rates are expected, especially if the clinical manifestations are not 

severe and it is the first episode of Pneumocystis carinii pneumonia. Treatment 


is with trimethoprim-sulfamethoxazole (Bactrim) but for those who cannot 

tolerate this antibiotic, pentamidine or trimethoprim/dapsone may be used. 

The addition of oral corticosteroids to the therapeutic regimen has been shown 

to be highly effective in improving survival rates for those with hypoxemia. 

After recovery from pneumonia, patients should receive chemoprophylaxis 

against recurrent infection and antiviral therapy if HIV positive. 

Hospital-Acquired Pneumonia 

Hospital-Acquired Pneumonia or nosocomial pneumonia is different from 

community acquired pneumonias not only because the organisms responsible 

differ but more importantly because the patients differ, suffering from coexistent 

diseases and immunosuppression far worse than that encountered in the 

community. 24, 25, 26, 27, 28 Gram-negative organisms (particularly Pseudomonas 

aeruginosa) are the predominant cause of hospital acquired pneumonia. 

However, organisms responsible for community acquired pneumonia still occur 

in the hospitalized environment. Four major risk factors for hospital acquired 

pneumonia exist – (1) acute illness (such as ARDS, sepsis, shock, abdominal 

surgery/infection); (2) coexisting chronic illnesses such as cardiopulmonary 

diseases, diabetes, cancer, renal failure, liver failure, immunosuppression 

and other systemic illnesses; (3) therapeutic interventions; and (4) impaired 

nutritional status. All are associated with increased mortality rates. 

OTHER LUNG INFECTIONS 

Lung Abscess 

Lung abscess is a necrotizing infection generally caused by aspiration of anaerobic 

bacteria occurring either in the community or the hospital. The radiograph 

will show single or multiple cavities each at least 2 cm in diameter. 24, 25 The 

cavity may contain an air-fluid level (Figure 2-2.5) and may be associated with 

or preceded by pneumonia. Patients present with low-grade fever, weight loss, 

and cough with foul-smelling sputum. The risk factors and microbiology of 

lung abscess are similar to those of community acquired pneumonia; lung 

abscess is usually a complication of aspiration. 

Figure 2-2.5: Chest radiograph showing right lower lobe lung abcess – a large cavity with 

air-fluid level. 


49


Currently, effective treatment is with penicillin or clindamycin. 29 Patients 

may improve within a week of antibiotics but it may take several months for 

the cavity to close and the chest radiograph to clear. Antibiotic therapy should 

be continued until the chest radiograph clears. When lung abscess arise unrelated 

to aspiration, poor dentition or airway obstruction (lung cancer or a 

foreign body) should be suspected. Additionally, certain organisms should 

be considered such as tuberculosis, fungi, Staphylococcus aureus, Klebsiella 

pneumoniae, Pseudomonas aeruginosa, and Streptococci pneumonia. Complications 

of lung abscess include empyema (infection in the pleural space 

between the lung and chest wall), broncho-pleural fistula, and brain abscess. 

Pleural Effusions and Empyema 

Approximately 40% to 60% of bacterial pneumonias will have evidence on chest 

radiograph of pleural effusion (fluid between the lung and chest wall). Most 

commonly, this is an inflammatory reaction consisting of fluid but no bacteria 

or organisms within the pleural space/fluid. Characteristics of this fluid have 

been shown to be excellent predictors of clinical outcomes. 30, 31 If the fluid is 

high in protein content, acidotic or low in glucose content, then drainage is 

recommended. If not, then merely treating the associated pneumonia with 

antibiotics is usually sufficient. Empyema is a term reserved for fluid in the 

pleural space that is not just an inflammatory reaction to the pneumonia 

but is an actual infection with organisms in the space/fluid (Figure 2-2.6). 

Empyema is rare occurring in only one to two percent of hospitalized patients 

with community-acquired pneumonia. 30, 31, 32, 33 It is most often caused by 

32, 33 

Streptococci pneumonia, Staphylococcus aureus, and anaerobic infections. 

Empyema requires extensive drainage of the fluid and antibiotics. Antibiotics 

should be based on culture results from the pleural fluid. 

Figure 2-2.6: Chest radiograph showing left-sided pneumonia and pleural effusion which 

upon sampling was filled with bacteria indicating an empyema. 

REFERENCES 

1. DeLozier JE, Gagnon RO. National Ambulatory Care Survey: 1989 summary. 

Advanced data from vital and health statistics. No. 203. Hyattsville, MD: 

National Center for Health Statistics, 1991:1-11. Gonzales, R, Sande, M. 

What will it take to stop physicians from prescribing antibiotics in acute 

bronchitis? Lancet 1995; 345:665. 

2. Macfarlane J, Holmes W, Gard P, et al. Prospective study of the incidence, 

etiology and outcome of adult lower respiratory tract illness in the 

community. Thorax 2001;56:109-14.

3. Wenzel, RP, Fowler AA, 3rd. Clinical practice. Acute bronchitis. N Engl J 

Med 2006; 355:2125. 

4. Boldy DAR, Skidmore SJ, Ayres JG. Acute bronchitis in the community: 

clinical features, infective factors, changes in pulmonary function and 

bronchial reactivity to histamine. Respir Med 1990;84:377- 85. 

5. Smucny, J, Fahey, T, Becker, L, Glazier, R. Antibiotics for acute bronchitis. 

Cochrane Database Syst Rev 2004; CD00024 

6. Evans, AT, Husain, S, Durairaj, L, et al. Azithromycin for acute bronchitis: 

a randomized, double-blind, controlled trial. Lancet 2002; 359:1648 

7. Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based 

clinical practice guidelines. Chest 2006;129:Suppl: 95S-103S. 

8. Global strategy for the diagnosis, management and prevention of COPD, 

Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007. http:// 

www.goldcopd.org. (Accessed July 7, 2008). 

9. Anthonisen NR; Manfreda J; Warren CP; Hershfield ES; Harding GK; Nelson 

NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary 

disease. Ann Intern Med 1987 Feb;106(2):196-204. 

10. Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive 

pulmonary disease exacerbations. A meta-analysis. JAMA 1995;273:957-60 

11. Weycker, D, Edelsberg, J, Oster, G, Tino, G. Prevalence and economic 

burden of bronchiectasis. Clin Pulm Med 2005; 12:205. 

12. Gilljam, M, Ellis, L, Corey, M, et al. Clinical manifestations of cystic fibrosis 

among patients with diagnosis in adulthood. Chest 2004; 126:1215 

13. King, PT, Holdsworth, SR, Freezer, NJ, et al. Characterisation of the onset 

and presenting clinical features of adult bronchiectasis. Respir Med 2006; 

100:2183. 

14. Barker, A. Medical Progress. Bronchiectasis. N Engl J Med 2002; 346:1383- 

93 

15. Wilson, CB, Jones, PW, O’Leary CJ, et al. Effect of sputum bacteriology on 

the quality of life of patients with bronchiectasis. Eur Respir J 1997; 10:1754. 

16. Corless JA, Warburton CJ. Surgery versus non-surgical treatment for 

bronchiectasis. Cochrane Database of Systematic Reviews 2000, Issue 4. 

Art. No.: CD002180. DOI: 10.1002/14651858.CD002180. 

17. Garibaldi RA. Epidemiology of community acquired respiratory tract 

infections in adults: incidence, etiology and impact. Am J Med 1985; 

78:32S-37S. 

18. Lung Disease Data 1994, American Lung Associaton. 1994, 37-42. 

19. Marie TJ. Community acquired pneumonia in the elderly. Clin Infec Dis. 

2000; 31:347-382. 


51


20. Kaplan V, Angus DC, Griffin MF, et al. A prospective study of age and 

lifestyle factors in relation to community acquired pneumonia in US men 

and women. Arch Intern Med. 2000; 160:3082-2088. 

21. Schneider EL. Infectious diseases in the elderly. Ann Intern Med. 1983; 

98:395-400 

22. Ashbaugh DG, Petty TL. Sepsis complicating the acute respiratory distresss 

syndrome. Surg Gynecol Obstet. 1972; 135:865-869 

23. Seidenfeld JJ, Pohl DF, Bell RD, et al. Nosocomial pneumonia in ventilated 

patients: a cohort study evaluating attributable mortality and hospital 

stay. Am J Med 1986; 94:281-288 

24. Niederman MS and Sarosi GA. Respiratory tract infections. Chapter 16, 

pgs 423-478. In Chest Medicine – Essentials of pulmonary and critical 

care medicine. Editors: George RB, Light RW, Matthay MA and Matthay 

RA, 3rd ed. Williams and Wilkins, Baltimore Maryland 1995. 

25. Goetz MB, Rhew DC, and Torres A. Pyogenic bacterial pneumonia, lung 

abcess and empyema. Chapter 32, pgs 920-978. In Textbook of respiratory 

medicine. Editors: Mason RJ, Broaddius C, Murray JF and Nadel JA. 4th 

ed. Elsevier Saunders Inc., Philadelphia PA, 2005 

26. Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the 

management of community acquired pneumonia in adults. Infectious 

Diseases Society of America. Clin Infect Dis. 2000; 31:347-382 

27. Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for the management 

of adults with community acquired pneumonia: diagnosis assessment of 

severity, antimicrobial therapy and prevention. Am J Respir Crit Care Med 

2001; 163:1730-1754 

28. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule for identifying low 

risk patients with community acquired pneumonia. New England Journal 

of Medicine. 1997; 336:243-250 

29. Levison ME, Mangura CT, Lorber B, et al. Clindamycin compared with 

penicillin for the treatment of anaerobic lung abscess. Ann Intern Med. 

1983; 99:444-450 

30. Light RW. Clinical practice: pleural effusion. New England Journal of 

Medicine. 2002; 346:1971-1977 

31. Colice GL, Curtis A, Deslauriers J et al. Medical and surgical treatment of 

parapneumonic effusions: An evidence based guideline. Chest. 2000;118:1158- 

1171. 

32. Bartlett JG, Gorbach SI, Thadepalli H et al. Bacteriology of empyema. 

Lancet 1974; 1:338-340 

33. Varkey B, Rose HD, Kutty CP et al. Empyema thoracis during a ten-year 

period: Analysis of 72 cases and comparison to a previous study (1952- 

1967). Arch Intern Med. 1981; 141:1771-1776

Chapter 2-3 

Tuberculosis: A Primer 

for First Responders 

By Dr. Felicia F. Dworkin, MD, FCCP 

Dr. Michelle Macaraig, MPH 

Dr. Diana Nilsen, MD, RN 

Dr. Chrispin Kambili, MD 

New York City Department of Health and Mental Hygiene 

Bureau of TB Control 

INTRODUCTION 

Tuberculosis (TB) is an airborne and potentially life-threatening infectious 

disease caused by bacteria of the Mycobacterium tuberculosis complex, a 

grouping of closely related species of mycobacteria (including M. tuberculosis 

(M. tb), M. bovis, and M. africanum). These mycobacteria are sometimes 

referred to as tuberculous mycobacteria. Other mycobacteria are called 

nontuberculous mycobacteria because they do not cause TB, one common type 

being Mycobacterium avium complex. While nontuberculous mycobacteria 

can also cause disease, it is not transmitted by person to person contact. 

TB disease is contracted when a person inhales air that contains the TB 

bacteria produced from a person who has the disease, either by coughing, 

talking, sneezing or singing. The disease mainly affects the lungs, but it can 

also affect other parts of the body such as the brain, kidneys, or the spine. 

A person with the pulmonary type of TB disease may manifest signs and 

symptoms such as prolonged cough, chest pains, weight loss or fatigue and is 

capable of transmitting the bacteria to other people. TB disease that affects 

other parts of the body can have various signs and symptoms depending on 

the site and is rarely infectious unless it also affects the lungs. An untreated 

person with TB can die from the disease; however, it is nearly 100% curable 

with an appropriate medical regimen. 

In contrast, latent TB infection (LTBI) is the presence of M. tb organisms 

in the body, but the body’s immune system is keeping the bacteria from 

reproducing. Most people with LTBI have a positive test for TB infection 

(TTBI), either a tuberculin skin test or blood test. However, those who have 

LTBI cannot transmit the disease to others. These people are asymptomatic 

and usually have a normal chest x-ray. See Table 2-3.1 for a comparison of the 

two conditions. 

This chapter discusses TB disease and LTBI including epidemiology, 

pathogenesis, diagnosis and treatment of these two conditions. 

Chapter 2-3 • Tuberculosis: A Primer for First Responders 

53

54 Chapter 2-3 • Tuberculosis: A Primer for First Responders 

A Person with Active TB Disease A Person with LTBI 

Has active TB bacteria in his/her body 

Usually has a skin test or blood test 

result indicating TB infection 

Usually has an abnormal chest x-ray, 

and positive sputum smear or culture 

Usually feels sick and may have symptoms 

such as coughing, fever, and 

weight loss 

Has TB bacteria in his/her body that 

are alive, but inactive 

Usually has a skin test or blood test 

result indicating TB infection 

Usually has a normal chest x-ray and 

has negative sputum tests 

Does not feel sick 

May spread TB bacteria to others Cannot spread TB bacteria to others 

Needs treatment with appropriate 

antibiotics against active TB disease 

Needs treatment with appropriate 

antibiotics for latent TB infection to 

prevent TB disease 

Table 2-3.1. The Difference Between Latent TB Infection and Active TB Disease (Adapted 

from CDC (2007) TB Elimination: The difference between latent TB infection and active 

TB disease. Retrieved from http://www.cdc.gov/tb/pubs/tbfactsheets/LTBIandActiveTB.htm 

EPIDEMIOLOGY OF TB 

TB disease is one of the leading infectious causes of death worldwide, yet it is 

preventable and, in most cases, curable. Each year, about nine million people 

develop TB disease and two million people die worldwide. In fact, among those 

older than five years of age, TB disease is one of the leading causes of death 

due to infectious disease in the world. 

Within the United States (US), physicians and other health care providers 

are required by law to report TB cases to their state or local health department. 

Each year the 50 states, the District of Columbia, New York City, Puerto Rico, 

and seven other jurisdictions in the Pacific and Caribbean report TB cases to 

the Centers for Disease Control and Prevention, who in turn compiles the data 

and provides an annual summary of TB cases in the United States. 

In 1953, when nationwide TB reporting first began, there were more than 

84,000 TB cases in the US (the 50 states and District of Columbia). From 1953 

through 1984, the number of TB cases decreased by an average of 6% each 

year. In 1985, the number of cases reached a low of 22,201. Between 1985 and 

1992 there was a resurgence of TB, with the number of new cases increasing 

from 22,201 in 1985 to 26,673 in 1992, an increase of about 20% (Figure 2-3.1). 

The resurgence in TB cases between 1985 and 1992 was attributed to at least 

these five factors: 

• Inadequate funding for TB control and other public health efforts. 

• The HIV epidemic. 

• Increased immigration from countries where TB is common. 

• The spread of TB in congregate settings. 

• Development and transmission of multidrug-resistant TB (MDRTB) 

strains which are more difficult to treat.

In 1993, the upward trend of new TB cases reversed. From 1993 through 

2006, the number of TB cases reported annually in the US steadily declined. 

(Figure 2-3.1) In 2006, there were a total of 13,779 new TB cases resulting in 

the lowest number of reported cases since national reporting began in 1953. 

28,000 

26,000 

24,000 

22,000 

20,000 

18,000 

16,000 

14,000 

12,000 

10,000 

1982 1986 1990 1994 1998 2002 2006 

Figure 2-3.1 TB Cases Reported in US (Reported TB in the United States, 2006. Atlanta, 

GA: U.S. Department of Health and Human Services, CDC, September 2007) 

The continued decline in reported TB cases since 1993 may be attributed to 

the increase in resources used to strengthen TB control efforts. The increase in 

federal, state, and other funds and resources allowed TB programs to improve 

efforts in TB control by promptly identifying persons with TB, initiating 

appropriate treatment for TB cases and ensuring completion of treatment. 

Despite this national trend reflecting a steady decline in the number of 

TB cases reported annually, there are still several areas of ongoing concern: 

• TB cases continue to be reported in every state and have actually 

increased in some areas. 

• More than half of all TB cases in the US are among non-US born residents. 

• Due to socioeconomic reasons, TB continues to affect minorities 

disproportionately (Hispanics, non-Hispanic blacks or African Americans, 

and Asians have higher TB rates than non-Hispanic whites). 

• Multidrug resistant TB (MDRTB) and extensively drug resistant TB 

(XDR TB) remain a serious public health concern. Patients who do not 

complete therapy or take their therapy inappropriately can develop 

and spread strains of TB that are resistant to available drugs. 

PATHOGENESIS, TRANSMISSION, INFECTION 

AND PROLIFERATION 

TB primarily affects the lungs, although it can also affect other parts of the 

body such as the brain, the kidneys, or the spine. Transmission of TB occurs 

when an infectious patient expels small droplets containing TB bacteria into 

the air when he/she coughs, sings or speaks and a susceptible person inhales 

the bacteria and becomes infected. (Figure 2-3.2) These tiny droplets float 

in air, the fluid evaporates and the living bacteria may remain airborne for 

several hours until inhaled. 


55


Figure 2-3.2: TB is spread from person to person through the air. The dots in the air represent 

droplets containing TB bacteria. (Source: CDC. Core Curriculum on Tuberculosis. By CDC. 

2000. 18 August 2008. http://www.cdc.gov/nchstp/tb/pubs/corecurr/default.htm 

The factors that determine the likelihood of transmission of M. tb are: 

• The number of bacteria being expelled into the air. 

• The concentration of bacteria in the air determined by the volume of 

the space and its ventilation. 

• The length of time an exposed person breathes the contaminated air. 

Approximately 10% of individuals latently infected with TB who are not given 

therapy will develop active TB. The risk in developing TB disease is highest 

in the first two years after infection. Patients with certain medical conditions 

have an increased risk of developing TB disease. When the immune system is 

weakened, the body may not be able to control the multiplication and spread 

of TB bacteria. Patients who are HIV infected are thought to be more likely 

to become infected with M. tb after exposure than persons without HIV. Also 

people infected with M. tb and HIV are more likely to develop TB disease than 

people who are infected with M. tb alone. However, they are no more likely to 

transmit M. tb to other persons. The risk of developing TB disease is 7% to 10% 

each year for people who are infected with both M. tb and HIV, particularly for 

those who are not taking antiretroviral therapy, whereas it is 10% over a lifetime 

for people infected only with M. tb. For people with LTBI and diabetes, the risk 

is three times as high, or about 30% over a lifetime. Figure 2-3.3 illustrates the 

risks to disease progression. 

Host Immune Response 

Within 2-12 weeks after exposure and subsequent infection with M. tb, the body 

mounts an immune response to limit further replication of the TB bacteria. 

This cellular immune response is the basis for the tests for TB infection 

currently used for testing: the tuberculin skin test (TST) and the blood test 

(QuantiFERON ® -Gold). Some bacteria remain quiescent in the body and are 

viable for many years.

TB exposed 

Not TB 

exposed 

Risk of Exposure 

Not TB 

Infected 

TB Infected 

Risk of Infection 

Primary TB 

Disease 

Latent TB 

Infection 

Risk of Primary 

Disease 

Reactivation 

TB Disease 

Persistent 

latent TB 

Infection 

Risk of Reactivation 

Disease 

Figure 2-3.3: Time course of events from exposure to disease and definition of transition risks 

(Adapted from Horsburgh CR, Moore M, Castro K. (2005). Epidemiology of TB in the United 

States; TB (second edition). Edited by William N. Rom and Stuart M. Gray. Philadelphia: 

Lippincott, Williams & Wilkins.) 

In the body, a characteristic pathologic lesion typical of TB infection called 

a granuloma is formed, which is a spherical collection of inflammatory cells 

with a small area of central cheeselike (caseous) necrosis. In up to 90% of the 

individuals who become infected with the TB bacteria, these small granulomas 

remain localized and quiescent, and may become calcified. The primary 

immunologic response that follows infection is generally inapparent both 

clinically and radiographically. 

Progression From Infection To Active Disease 

Not everyone who is infected with TB develops TB disease. The risk of progression 

to active TB is determined by certain risk factors which will be discussed later 

in the chapter. There are two terms to describe a patient who progresses from 

TB infection to active TB disease: primary TB and reactivation TB. Primary 

TB is rapidly progressive without a period of latency in the weeks to months 

following initial infection. It occurs most commonly in infants with immature 

immune systems, elderly people with waning immunity and HIV-infected 

persons. The site of disease reflects the path of infection, appearing as enlarged 

hilar or mediastinal lymph nodes and lower or middle lung field infiltrates on 

chest x-ray. Reactivation TB occurs after a period of latency (usually within two 

years), but sometimes decades after primary infection. When this occurs, the 

site of disease is most commonly the apices of the lungs, but may also include 

other sites seeded during the primary infection. 

If the infection is not kept contained, the bacteria will multiply, provoking 

the release of inflammatory agents which lead to more inflammation, tissue 

destruction and disease progression. Ultimately, this inflammation may cause 

the formation of a tuberculous cavity in the lung. From this cavity, the disease 

may progress to other parts of the lung. 


57


Clinical Aspects of TB Disease 

Progressive primary or reactivation pulmonary TB often presents with a 

gradual onset of non-specific symptoms that may be tolerated by the patient. 

The duration of symptoms before presentation may vary widely, from days to 

months. Presenting features may initially be related to the respiratory system 

and/or present as constitutional symptoms of cough, chest pain and dyspnea. 

Cough typically lasts at least two to three weeks, but can persist longer (months) 

and is usually productive of mucoid, muco-purulent or blood tinged sputum. 

Massive hemoptysis (coughing of blood) can also be a presenting feature. 

Fever with sweats (mostly at night) and chills are common. Other nonspecific 

symptoms include weakness, anorexia (loss of appetite), and unintended weight 

loss. TB disease involving other organs of the body is termed extrapulmonary 

TB, and the related symptoms depend on the affected organ. 

Evaluation of Persons with Suspected Active TB Disease 

When a person is suspected of having TB, he/she should have a medical 

evaluation including a history, physical examination, a TTBI (either a TST or 

a blood test), chest x-ray or other diagnostic imaging, and specimens for acid 

fast bacilli (AFB) smear microscopy and cultures depending on site of disease. 

When evaluating a patient’s medical history, clinicians should ask about 

the patient’s history of TB exposure, infection, or prior TB disease. It is also 

important to consider demographic factors that may increase the patient’s 

risk for exposure to TB (e.g., immigration from countries with high rates of 

TB, homelessness, incarceration or health care work). Also, clinicians should 

determine whether the patient has other medical conditions, especially HIV 

infection, that can increase the risk of LTBI progressing to TB disease. 

Chest radiographic features of pulmonary TB are not characteristic and can 

simulate other diseases. These include upper lobe infiltrates or consolidation, 

cavitations (which may occur in approximately 40% cases), bilateral infiltrates or 

infiltrates with pleural effusions, and scarring, fibronodular or calcific changes. 

A normal chest x-ray does not exclude pulmonary TB and has been reported in 

approximately 10% of immunocompetent and 20% of immunocompromised 

patients. 

Computed tomography (CT) of the chest can be used as an adjunct to identify 

lesions suggestive of TB such as cavitation, mediastinal and paratracheal 

lymphadenopathy, endobronchial TB, and dissemination to the lung parenchyma 

(miliary TB). 

Diagnostic Microbiology 

The gold standard for diagnosing TB is by culturing a specimen from an 

appropriate disease site. For pulmonary TB, a respiratory specimen such 

as sputum is generally collected. There are two advantages in collecting 

samples for culture: 1) It is more sensitive because it allows differentiation 

of mycobacteria that are part of the M. tb complex from those that are 

nontuberculosis mycobacteria and 2) it allows for drug susceptibility testing 

to determine if the bacteria is resistant to any of the anti-TB drugs. However, 

since TB is a slow growing bacterium, results with this method can take up to 

eight weeks to obtain.

In general, the AFB smear test is the first test to diagnose TB in the specimen. 

This test evaluates the number of bacteria in the specimen by looking under 

the microscope. The number of bacteria seen under the microscope generally 

correlates with the infectiousness of the patient. However, absence of the 

bacteria from any specimen does not rule out disease. Although the AFB smear 

suggests presence of the TB bacteria, a culture is still needed to confirm that 

the AFB are M. tb. Culture examinations should be completed on all specimens 

regardless of AFB smear results. 

Another detection method is the use of nucleic acid amplification (NAA) 

techniques. NAA tests identify genetic material unique to M. tb complex directly 

in pre-processed clinical samples. The test is used to detect M. tb in respiratory 

specimens from previously untreated patients with a high clinical suspicion for 

TB, and since the test does not require growth of the TB bacteria, results can 

be available in a few days. A positive NAA in an AFB smear positive respiratory 

specimen is highly suggestive of TB disease, but the diagnosis should still 

be confirmed by culture so drug-susceptibility testing can be performed. A 

negative NAA result is suggestive of nontuberculous mycobacteria, but it does 

not rule out the diagnosis of TB in a smear negative or positive respiratory 

specimen. The diagnosis would also depend on the overall clinical picture, 

clinical judgment and the culture results. Since NAA tests can detect nucleic 

acid from dead as well as live organisms, a positive result from dead bacteria can 

remain for long periods of time even after the patient has been on appropriate 

treatment or after completing treatment. Therefore, this method is used only 

for initial diagnosis of untreated TB patients. 

Treatment of Patients with Active TB Disease 

All individuals with highly suspected TB should begin treatment as soon as 

appropriate specimens are collected. Treatment should not be delayed while 

waiting for confirmation by culture or susceptibility results. Most patients with 

drug susceptible TB (TB that can be treated with the first-line TB treatment 

drugs) can be treated with a standard six-month drug regimen. Treatment is 

divided into two phases: the intensive phase and the continuation phase. Since 

susceptibility results are not available at the beginning of therapy, patients 

are started on a standard four-drug regimen of isoniazid (INH), rifampin, 

pyrazinamide and ethambutol. Regimens should be adjusted as soon as 

susceptibility results become available. The length of the continuation phase 

depends on the therapy prescribed and the susceptibility results. Treatment of 

TB resistant to one or more drugs is more complex, and should be managed by a 

physician that is experienced in the treatment of TB. Current recommendations 

for treatment of TB in adults who are HIV infected are, with few exceptions, 

the same as for the rest of the population. 

Directly observed therapy (DOT), the standard of care in TB treatment, is the 

best way to ensure that patients complete an adequate course of treatment for 

TB. DOT means that a health care worker, or another responsible individual, 

directly observes and supervises every dose of anti-TB medication taken by 

the patient. DOT regimens may be daily, or prescribed in higher doses to 

be taken two or three times a week. When TB treatment is complicated by 

interactions between drugs used for TB and those used for HIV infection, there 

is a paramount need for close medical evaluation and supervision to assure 

the continuity of TB therapy. 


59


Drug-Resistant TB 

Drug-resistant TB is caused by M. tb organisms that are resistant to at least 

one of the first-line TB treatment drugs (INH, rifampin, pyrazinamide, and 

ethambutol). Drug-resistant TB can be transmitted in the same way as drugsusceptible 

TB. However, drug-resistant TB can be more difficult to treat 

because it can survive in a patient’s body even after treatment with the firstline 

drugs is started. Furthermore, if patients are not properly diagnosed with 

drug-resistant TB and are given an inadequate treatment regimen, they may be 

infectious for a longer period of time and develop additional drug resistance. 

A patient is diagnosed with multidrug-resistant TB (MDRTB) if the TB 

bacteria are resistant to at least INH and rifampin. A patient is diagnosed with 

extensively drug-resistant TB (XDRTB) if the TB bacteria are resistant to INH 

and rifampin, plus any fluoroquinolone and at least one of three injectable 

second-line drugs (such as amikacin, kanamycin, or capreomycin). 

Drug-resistant TB can manifest in two different ways: primary and secondary 

(acquired). Primary resistance is caused by person-to-person transmission of 

drug-resistant organisms. Secondary resistance develops during TB treatment, 

either because the patient was not treated with the appropriate treatment regimen 

or because the patient did not follow the treatment regimen as prescribed. 

Treatment of drug resistant TB can be more complicated and may take longer 

to treat, and can involve second line medications which may be more difficult 

for the patient to tolerate. Patients should be managed by a physician, expert 

in treating drug resistant TB. Drug-resistant TB patients should also be closely 

monitored to see if they are responding to treatment and should be on daily 

or twice daily DOT, to monitor medications given twice a day. 

Latent TB Infection 

A person with latent TB infection (LTBI) may develop reactivation of TB disease, 

usually when his or her immunity has diminished or he or she develops a 

clinical condition that increases the likelihood of progression from LTBI to 

active TB disease. The most efficient way to decrease the incidence of TB 

disease is to prevent this reactivation from occurring. Identifying and treating 

those individuals with LTBI, especially those who are at the highest risk for 

developing disease, benefits both the infected persons and other susceptible 

persons in their communities. 

In April 2000, the American Thoracic Society (ATS) and Centers for Disease 

Control and Prevention (CDC) revised their guidelines for the treatment of 

LTBI, which were subsequently endorsed by the Infectious Disease Society 

of America and the American College of Physicians. These recommendations 

described the intended intervention more accurately as the “treatment of 

LTBI” rather than “preventive therapy” or chemoprophylaxis”, to promote a 

greater understanding that one is treating an infection, rather than just trying 

to prevent a disease.

DIAGNOSTIC TESTS FOR TB INFECTION 

Tuberculin Skin Test (TST) 

Currently, there are two tests for TB infection (TTBI): TST and a blood-based 

test. The TST is the most commonly used test. It requires the injection of a 

purified protein derivative (PPD) of the TB bacteria under the skin. The test 

is read between 48-72 hours by a trained health care worker who will look 

for swelling and hardness (induration) at the site of the injection and must 

record the result in millimeters and not simply as “positive” or “negative”. The 

three cut-off points for defining a positive TST result are >5mm, >10mm, and 

>15mm of induration which is determined according to patients’ medical and 

epidemiologic risk factors (Table 2-3.2). A TST is not necessary for individuals 

with a reliable history of, or a previously documented positive TST result. 

Determination of a Positive Skin Test 

≥ 5 mm for Persons with HIV-infection 

Recent contacts of persons with active TB 

Persons with evidence of old, healed TB lesions on chest x-rays 

Persons with organ transplants and other immunosuppressed 

persons, such as patients receiving prolonged corticosteroid 

therapy [the equivalent of >15 mg/d of prednisone for one month or 

more],TNF-alpha blockers and chemotherapy 

≥ 10 mm for Persons who have immigrated within the past 5 years from areas with 

high TB rates 

Injection drug users 

Persons who live or work in institutional settings where exposure to 

TB may be likely (e.g., hospitals, prisons, homeless shelters, single 

room occupancy units (SROs), nursing homes) 

Mycobacteriology laboratory personnel 

Persons with clinical conditions associated with increased risk of 

progression to active TB, including: 

Silicosis 

Chronic renal failure 

Diabetes mellitus 

Gastrectomy/jejunoileal bypass 

Some hematologic disorders, such as leukemias or lymphomas 

Specific malignancies such as carcinoma of the head, neck or lung 

Body weight ≥ 10% below ideal or BMI

62 


Patients who have a positive TST reaction should undergo clinical evaluation, 

including a chest x-ray (CXR) to rule out TB disease (See evaluation of TB 

disease). If the initial CXR is normal, repeated chest x-rays for screening 

purposes are not indicated unless the individual develops signs or symptoms 

of TB. The decision to begin treatment for LTBI in someone who is found to be 

TST-positive is based on CDC/ATS guidelines. 

Blood tests (eg. QuantiFERON ® -TB Gold) 

The blood test, QuantiFERON®-TB Gold (QFT-G), is a blood test approved 

by the US Food and Drug Administration (FDA) in 2005 for detection of TB 

infection. As an alternative to the TST, QFT-G may offer clinicians a simpler, 

more accurate, reliable and convenient TB diagnostic tool. QFT-G is highly 

specific, and a positive test result is strongly predictive of true infection with 

M. tb. The test is approved for use in diagnosing M. tb infection in persons with 

active TB disease or with LTBI; however, it cannot differentiate between the two. 

QFT-G specifically detects immune responses to two proteins made by M. 

tb. These proteins are absent from all BCG vaccine preparations and from 

all nontuberculous mycobacteria (NTM), with the exception of M.kansasii, 

M.marinum and M.szulgai. As a result, the QFT-G test is not affected by the 

individual’s BCG vaccination status nor by the individual’s sensitization to 

most NTMs, thus providing a more accurate test of TB infection compared to 

the TST. At present, the major drawback to this test is that blood samples must 

be processed within 12 hours of the blood draw. In addition, the test has not 

been fully studied in many groups, including children, those with impaired 

immune function and in contacts to active TB cases. The ability of QFT-G to 

predict risk of LTBI progressing to active TB disease has not yet been determined. 

The QFT-G can be used to assess any patient for LTBI who would otherwise 

be a candidate for a TST. It can also be used to aid in the initial diagnosis of 

active TB. However, it should not be used for patients currently receiving anti-TB 

drugs for active TB, or for patients receiving treatment for LTBI (while there is 

no specific FDA recommendation against using QFT-G in patients receiving 

treatment, there is evidence that such treatment will effect results). The test 

is reported as positive, negative or indeterminate: 

• A negative QFT-G result should be interpreted as a negative TST 

result, suggesting TB infection is unlikely, and in general no further 

evaluation is needed. A patient who has symptoms of TB despite a 

negative QFT-G result should be evaluated appropriately. 

• A positive QFT-G result should be interpreted as a positive TST result, 

and suggests TB infection is likely. TB disease will still need to be 

excluded by a medical evaluation, chest x-ray and if indicated sputum 

or other specimen studies. (See Clinical Evaluation for LTBI section 

below). 

• An indeterminate QFT-G result cannot be interpreted due to a lack 

of response by the test control groups. In this situation a repeat 

QFT-G or administering the TST could be done. QFT-G results may 

be indeterminate due to laboratory errors, a result being very near 

the cut-off point between positive and negative readings or patient 

anergy (See Anergy below). If two different specimens from a patient

yield indeterminate results, the QFT-G for that person should not be 

repeated, since a third test is not likely to give a non-indeterminate 

result. 

QFT-G can be cost effective by eliminating the need for a second patient 

visit for test interpretation and by the elimination of common false-positive 

results, which typically involve both unnecessary clinical evaluation to rule 

out active TB and treatment for LTBI. In addition, QFT-G can eliminate the 

need for the repeat TST when two-step testing is required for health care 

worker screening (see Two-Step Tuberculin Skin Testing). That, in turn, may 

lower administrative costs of maintaining testing compliance in health-care 

facilities, which may offset the slightly higher cost of QFT-G, compared to TST. 

Newer versions of blood tests, which may address some of the limitations 

of the QFT-G, have recently been approved by the FDA, including QFT-G "In- 

Tube" and T-SPOT.TB. TB diagnostics is a rapidly evolving field, and these 

guidelines may change as more data becomes available. Blood testing (QFT-G) 

is increasingly becoming an alternative to the TST for identifying TB infection. 

Table 2-3.3 outlines the differences between QFT-G and TST. 

QuantiFERON®-TB Gold Test Tuberculin Skin Test 

• In vitro, controlled laboratory test with 

minimal inter-reader variability 

• M.tb specific antigens used 

• No boosting; two-step testing not 

needed 

• One patient visit possible 

• Unaffected by BCG or most 

environmental mycobacteria 

• Simple positive / indeterminate / 

negative result independent of risk of 

disease 

• Ability to predict the risk of latent TB 

infection progression to TB disease 

has not yet been determined 

• In vivo, subject to errors during 

implantation and interpretation 

• Less specific purified protein 

derivative used 

• Boosting, with repeated testing 

• Two patient visits minimum 

• False-positive tests can occur after 

BCG and environmental mycobacteria 

exposure 

• Interpretation based on patient’s risk 

of TB or development of disease 

• Risk of progression to active disease is 

known for many high risk patients 

Table 2-3.3: Differences between QFT-G and TST (Adapted from the New York City Department 

of Health and Mental Hygiene (2008). Treatment of Pulmonary TB; In Clinical Policies and 

Protocols (4th ed., pg 184). New York) 

POPULATIONS WHO SHOULD BE TESTED FOR LTBI 

Targeted testing, or screening for LTBI should be focused on populations who 

would benefit by treatment. Persons at high risk for developing TB disease have 

either been recently infected with M. tb or, if already infected, are at increased 

risk for developing TB disease due to clinical conditions that are associated with 

an increased risk of progression of LTBI to active TB. In general, populations at 

low risk for LTBI (no medical risk factors and low risk of exposure to TB) should 

not be tested since false positive reactions are common. Table 2-3.4 lists the 

characteristics of individuals who should be tested for LTBI. 

Close contacts of persons with active TB disease should receive a baseline 

TTBI immediately after exposure. Since it can take up to eight weeks (window 

period) after M. tb infection for the immune system to respond to a TTBI, a 

negative TTBI result during this period may not be accurate. It is therefore 


63


recommended that close contacts with negative TTBI results during the window 

period should be retested eight weeks from the contact’s most recent exposure 

to the active TB case. If the second test is negative, the contact would then be 

considered “not infected” (unless in severely immunosuppressed patients) 

due to the exposure. If the test is positive anytime after exposure, regardless of 

the eight week period, the person should be evaluated to rule out TB disease. 

Individuals Who May Have Been 

Recently Infected 

Persons who have had close contact with 

individuals with active TB. Retesting may 

be necessary eight weeks after original 

test 

Persons who have immigrated to the US 

within the past five years from areas with 

high TB rates* should be tested the first 

time they enter the health care system in 

the US 

Persons with prolonged stay (>one 

month) in areas with high TB rates 

Persons who live or work in clinical or 

institutional settings where TB exposure 

may be likely (CDC and local guidelines 

recommend testing annually): 

• hospitals 

• prisons 

• homeless shelters 

• nursing homes 

• mycobacteriology labs 

Persons who provide emergency medical 

response, including EMS personnel and 

fire fighters 

Children/adolescents exposed to adults in 

high-risk categories 

Table 2-3.4: Individuals who should be tested for LTBI 

Individuals With Clinical Conditions 

Associated with Progression from 

LTBI to Active TB 

Persons with HIV infection should be 

tested as soon as possible after diagnosis 

of HIV infection, and at least once a year 

afterward 

Injection drug users 

Persons with evidence of old, healed TB 

lesions on chest x-ray 

Underweight persons (≥ 10% under ideal 

body weight) 

Persons with any of the following medical 

conditions or risk factors for TB disease: 

• Diabetes mellitus 

• Silicosis 

• Cancer of the head, neck or lung 

• Hematologic and 

reticuloendothelial disease (e.g., 

leukemia and Hodgkin’s disease) 

• End-stage renal disease 

• Gastrectomy or jejunoileal bypass 

• Chronic malabsorption syndromes 

• Organ transplants or on transplant 

lists 

• Receiving prolonged 

corticosteroid therapy or other 

immunosuppressive therapy 

(e.g., receiving the equivalent of 

≥ 15mg of prednisone for ≥ one 

month, TNF-alpha blockers or 

chemotherapy) 

All individuals who are HIV-positive should receive a TTBI as soon as 

HIV infection is diagnosed. The test should be considered for such patients, 

especially those at high-risk for TB exposure, on an annual basis or as soon 

after an exposure to active TB occurs. 

Recent immigrants (i.e., those who have been in the United States for less 

than five years), who have come from countries with high rates of TB, such as 

those listed in Table 2-3.5, should be tested for TB infection when they enter 

the medical care system in the U.S. They should also be tested any time after 

they return to their native country or after a prolonged (more than one month) 

stay abroad. Additionally, individuals who have had a prolonged stay (more

than one month) abroad in areas where TB rates are high should be evaluated 

immediately after return or at their next medical examination. 

Africa 

All countries except 

Seychelles 

Eastern Mediterranean 

Afghanistan 

Bahrain 

Djibouti 

Egypt 

Iraq 

Morocco 

Pakistan 

Qatar 

Somalia 

Sudan 

Yemen 

Europe 

Armenia 

Azerbaijan 

Belarus 

Bosnia and Herzegovina 

Estonia 

Georgia 

Kazakhstan 

Kyrgyzstan 

Latvia 

Lithuania 

Moldova (Rep. of ) 

Romania 

Russian Federation 

Tajikistan 

Turkmenistan 

Ukraine 

Uzbekistan 

Countries with High TB Rates 

North, Central and 

South America 

Belize 

Bolivia 

Brazil 

Columbia 

Dominican Republic 

Ecuador 

El Salvador 

Guatemala 

Guyana 

Haiti 

Honduras 

Mexico2 

Nicaragua 

Panama 

Paraguay 

Peru 

Suriname 

Southeast Asia 

Bangladesh 

Bhutan 

India 

Indonesia 

North Korea (DPRK) 

Maldives 

Myanmar 

Nepal 

Sri Lanka 

Thailand 

Timor-Leste 

Western Pacific 

Brunei Darussalam 

Cambodia 

China 

China (Hong Kong SAR) 

Guam 

Kiribati 

Lao PDR 

Macao (China) 

Malaysia 

Marshall Islands 

Micronesia 

Mongolia 

New Caledonia 

Northern Mariana Islands 

Palau 

Papua New Guinea 

Philippines 

Solomon Islands 

South Korea (ROK) 

Vanuatu 

Viet Nam 

Notes: 

1. Source: World Health Organization. Global TB Control-- Surveillance, Planning, 

Financing: WHO Report 2007. Geneva, World Health Organization (WHO/ 

HTM/TB/2007.376). http://www.who.int/tb/publications/global_report/2007/ 

pdf/full.pdf “High-incidence areas” are defined by the New York City TB Control 

Program as areas with reported or estimated ≥20 new smear-positive cases per 

100,000 persons. 

2. Has an estimated incidence of < 20 smear-positive cases per 100,000 persons; 

however, the Mexican community in NYC has a high burden of disease. 

Table 2-3.5: Countries/Areas with an Estimated or Reported High Incidence of TB, 2005 

Individuals who live or work in institutional settings (e.g., prisons, hospitals, 

nursing homes, shelters) and emergency medical responders come under 

testing recommendations that vary according to the risk of transmission based 

on local and CDC guidelines. Most guidelines recommend annual testing of 

these employees. 


65


Individuals with immunosuppressive conditions or who are being treated 

with immunosuppressive agents should be evaluated and treated for LTBI, either 

at the time that the condition is diagnosed or before starting treatment with 

immunosuppressive therapies such as prolonged corticosteroids (equivalent 

of prednisone >15mg/kg/d for at least one month) and TNF-alpha blockers 

(infliximab, etanercept and adalimumab). Patients awaiting transplant should 

be evaluated for LTBI. TST results in immunosuppressed individuals may be 

falsely negative, either due to the drug therapy or to an underlying medical 

condition causing anergy (discussed below). 

Interpretations: Causes of False Positive and False Negative 

TST Reactions 

TST results must be interpreted with caution if an individual experiences one 

of the following factors listed in Table 2-3.6. In medicine, a false positive test 

is when the patient has a positive test result for a medical condition, but in 

reality does not have the condition. A false negative test is when the patient 

has a medical condition but the test for the condition is negative. TST may 

show false positive or false negative results due to co-morbidity with various 

infections, inappropriate timing in the administration of both the TST and 

other live virus vaccines, concomitant medical conditions, reactions with 

drugs that suppress the immune response and fluctuation of induration size 

from repeated TSTs. 

BCG Vaccinated Individuals 

TTBIs are not contraindicated for persons who have been vaccinated with 

Bacille Calmette Guérin (BCG). A history of BCG vaccination should not be 

considered, either when deciding to test and/or when determining if the test 

result is positive in high-risk individuals. Although BCG vaccination can cause a 

false positive cross-reaction to the TST, BCG-related sensitivity to tuberculin is 

highly variable and tends to decrease over time. There is no way to distinguish 

between a positive reaction due to BCG-induced sensitivity and a positive 

reaction due to true TB infection. Therefore, a positive reaction to the TST in 

BCG-vaccinated persons should be interpreted as indicating infection with M. 

tb when the person tested is at increased risk of recent infection or when the 

person has a medical condition that increases the risk of progression to active 

TB disease. Prior BCG vaccination is not a concern when using the QFT-G test, 

as the test will distinguish between TB infection and the BCG vaccination.

Infections 

Factors 

Live virus vaccines 

Concomitant medical 

conditions 

Drugs and technical 

factors 

False-Negative 

Reactions 

Viral illnesses (HIV, 

measles, varicella) 

Bacterial illnesses (typhoid 

fever, pertussis, brucellosis 

typhus, leprosy 

Early TB infection (< 12 

wks.) 

Severe TB disease 

(meningitis, miliary) 

Fungal disease 

(Blastomycosis) 

Measles 

Polio 

Varicella 

Smallpox 

Metabolic abnormalities 

Chronic renal failure 

Primary 

immunodeficiencies 

Malignancies (e.g. 

Hodgkin’s disease, 

lymphoma, leukemia) 

Sarcoidosis 

Poor nutrition 

Newborns and children 

< two years of age 

Low protein states 

Corticosteroids or other 

immunosuppressive 

medications 

Chemotherapy 

Material: poor quality; 

inadequate dose (one 

TU); improper storage 

(exposure to heat/light)); 

expired 

Administration: not 

injected intradermally; too 

long in syringe 

Reading: inexperienced or 

biased reader; recording 

error, read too early/late 

False-Positive 

Reactions 

Exposure to 

nontuberculous 

mycobacteria 

Bacille Calmetter-Guerin 

vaccine (BCG) 

Transfusion with whole 

blood from donors with 

known positive TST 

Inexperienced or biased 

reader 

Interpretative Decreasing mm induration Increasing mm induration 

Table 2-3.6: Factors Associated with False Negative or False Positive TST Reactions 


67


Vaccination with Live Attenuated Vaccines 

Vaccination with live attenuated viral vaccines such as measles, mumps and/ 

or rubella (MMR), oral polio, varicella and others can cause a false-negative 

reaction to the TST. The Advisory Committee on Immunization Practices 

recommends that the TST can be administered on the same day as the live 

vaccine because immunosuppression does not appear until after the first 48 

hours post-vaccination. If a skin test is needed, and was not given at the same 

time of the vaccination, it is recommended to wait four to six weeks before 

administering it. The effects of live attenuated vaccines have not been studied 

in relation to using the QFT-G test. The current recommendation is to perform 

the QFT-G test on the same day as the vaccination, as with the TST. 

Anergy 

Anergy is the inability to respond to a skin test antigen such as the TST, to which 

a person should normally react. An impaired immune response is directly 

related to medical conditions that affect the cellular immunity. Individuals 

who mount a response to any antigen are considered to have relatively intact 

cellular immunity, whereas those who cannot mount any response are considered 

“anergic”. Anergy may be caused by many factors, such as HIV infection with 

low CD4 cell count, severe or febrile illness, measles or other viral infections, 

Hodgkin’s disease, sarcoidosis, live-virus vaccination, or the administration 

of corticosteroids or immunosuppressive drugs. Overwhelming TB disease 

can also lead to false-negative reactions. 

In the United States, anergy testing is no longer recommended as part of 

routine screening for TB infection among individuals infected with HIV due 

to the lack of standardization and outcome data that limit evaluation of its 

effectiveness. It also has no role in the evaluation of contacts. In general, HIVinfected 

close contacts of a person with pulmonary or laryngeal TB should 

receive an evaluation and treatment for LTBI, regardless of the TST result. HIV 

infected individuals who are not known to be contacts should be evaluated for 

treatment for LTBI according to their risk for TB exposure and infection. On 

average, 10 to 25% of patients with TB disease have negative reactions when 

tested with a TST at diagnosis before treatment. 

TWO-STEP TUBERCULIN SKIN TESTING 

In most individuals, TST testing sensitivity persists throughout life. However, 

in some TB-infected individuals, the ability to react to a TST diminishes over 

time, so the size of the skin test may decrease or disappear altogether. Thus, 

infected individuals who are skin tested many years after infection may have 

a negative TST reaction. However, if they are retested within the next year, 

they may have a positive reaction. This phenomenon, called the “booster 

phenomenon,” occurs because the first TST “boosted” the immune response 

that had diminished over the years. Boosting is most common in persons 

age 55 and older and can also occur in BCG vaccinated persons. The booster 

phenomenon can complicate the interpretation of TST results in settings where 

testing is done repeatedly since a boosted reaction to a second TST may be 

mistaken for a recent conversion. Consequently, an infection acquired years 

ago may be interpreted as a recent infection.

Two-step testing is used to reduce the likelihood that a boosted reaction will 

be misinterpreted as a recent infection. Individuals who will be tuberculin 

skin tested repeatedly as part of routine periodic evaluations should undergo 

two-step testing the first time they are tested. This would include health care 

workers and employees or residents of congregate settings. With this type of 

testing, an initial TST is done. If the result is negative, a second TST is given one 

to three weeks later. The result of the second test is then used as the baseline. A 

positive reaction to the second test probably represents a boosted reaction (past 

infection or prior BCG vaccination), and the patient is considered previously 

infected. Some experts recommend two-step testing in immunosuppressed 

individuals. This would not be considered a positive test from a recent infection. 

If the second test is negative, the patient is considered uninfected. In these 

persons, a positive reaction to any subsequent test is likely to represent new 

infection with M. tb (skin test conversion). The QFT-G test eliminates the need 

for two-step testing, for those who are recommended to have it. 

CLINICAL EVALUATION FOR LATENT TB INFECTION 

When a patient has been has been diagnosed to have LTBI based on his/her 

risk and the TST or QFT-G results, further evaluation is deemed necessary in 

order for the physician to make a treatment decision. Not everyone with latent 

infection is a candidate for treatment. However, all high-risk individuals who 

test positive for TB infection should receive treatment for LTBI as soon as active 

TB has been ruled out. 

Medical History and Physical Examination 

Every patient who tests positive for TB infection should be examined by a 

physician, both to rule out TB disease and to be evaluated for treatment of LTBI. 

The clinical evaluation should include a medical history, physical examination, 

chest x-ray, and sputum smear and culture if indicated. 

All patients should be asked about risk factors which may put them in a 

high risk category for the development of TB disease, including recent close 

contact with a person who has TB. However, some patients are not aware that 

they are contacts. 

All patients should be asked about previous treatment for LTBI. Additionally, 

those who have completed a course of treatment for LTBI in the past should 

be asked about recent close contact with a person who has TB. If the patient 

is a contact and meets the criteria for any of the following, the patient should 

be considered for a repeat course of treatment for LTBI: 

• Less than five years of age. 

• Between the ages of 5-15 years at the physician discretion. 

• HIV infected or otherwise immunosuppressed. 

• A behavioral risk for HIV infection who has declined HIV testing. 

All patients 13 years of age or older, especially those who have a positive 

TTBI or have risk factors for HIV, should be offered counseling and testing for 

HIV unless they have documentation of (1) a positive HIV antibody test or (2) a 

negative HIV antibody test obtained within the last six months. Those younger 


69

70 


than 18 years should be counseled and offered testing if they have behavioral 

risk factors for HIV and have no documented history of a positive HIV test. 

All patients should be evaluated for and asked about their history of alcohol 

ingestion, liver disease and hepatitis, and if indicated perform a blood count 

and baseline liver function tests (LFT), as well as a viral hepatitis screening 

profile. All patients should be assessed for contraindications to treatment 

for LTBI. 

Chest X-Ray 

Everyone considered for LTBI treatment should have a posteroanterior-lateral 

(PA-Lat) chest x-ray to rule out pulmonary TB disease. If the chest x-ray is 

normal and there are no symptoms consistent with active TB present, TTBIpositive 

persons may be candidates for treatment of LTBI. If radiographic or 

clinical findings are consistent with pulmonary or extrapulmonary TB, further 

examination (e.g., medical evaluation, bacteriologic test, and a comparison of 

the current and old chest radiographs) should be done to determine if treatment 

for active TB is indicated. 

Due to the risk for progressive and/or congenital TB, pregnant women who 

have a positive TST or who have negative skin-test results, but who are recent 

contacts of persons with infectious TB disease should have a chest x-ray (with 

appropriate lead shielding) as soon as feasible, even during the first trimester 

of pregnancy. 

Sputum Examinations 

Most persons with LTBI will have a normal chest x-ray, or have calcified 

pulmonary nodules and therefore do not require bacteriologic examination of 

the sputum. However, persons with chest radiographic findings suggestive of 

prior healed TB should have three consecutive sputum samples, obtained on 

different days, submitted for AFB smear and culture. If the results of sputum 

smears and cultures are negative and any respiratory symptoms (if present) 

can be explained by another etiology, the person would then be a candidate 

for treatment of LTBI. If sputum bacteriologic results are negative, but the 

activity or etiology of a radiographic abnormality remains questionable, further 

diagnostic evaluation (i.e. bronchoscopy, needle aspiration biopsy) should be 

undertaken to further evaluate for TB disease. 

Consideration of Pregnant Women as Candidates for 

Latent TB Infection Treatment 

Pregnant women should receive a TTBI only if there is either a risk factor for 

LTBI or for increased risk for progression of LTBI to TB disease. Although the 

need to treat active TB during pregnancy is unquestioned, treatment of LTBI in 

pregnant women is more controversial, since the possible risk of hepatotoxicity 

must be weighed against the risk of developing active TB. However, for women 

who are HIV-positive or who have been recently infected with TB (such as 

contacts of active TB cases or known recent conversions), the start of therapy 

should not be delayed on the basis of pregnancy alone, even during the first 

trimester. Pregnant patients treated for LTBI should have careful clinical and 

laboratory monitoring for hepatitis.

Treatment should be started during the first trimester of pregnancy if the 

TST is >5mm for: 

• Pregnant women who are HIV-positive or who have behavioral risk 

factors for HIV infection, but decline HIV testing. 

• Pregnant women who have been in close contact with a smear positive 

pulmonary TB patient. At the physician’s discretion, start of treatment 

can be delayed until after the second trimester but the patient should 

be under close observation for development of TB symptoms. 

If the pregnant patient has a documented TST conversion in the past two 

years, treatment should be started promptly after the first trimester. For all 

other pregnant women with other risk factors, including those with radiographic 

evidence of old healed TB, treatment for LTBI should be started two to three 

months after delivery. In pregnant women known or suspected to be infected 

with a TB strain resistant to at least INH and rifampin (MDRTB), treatment for 

LTBI should be delayed until after delivery. This will avoid possible adverse 

effects of the medications on the developing fetus. A CXR should be obtained 

initially and again if the woman develops symptoms suggestive of TB disease. 

A lead shield should be used when performing CXRs on pregnant women. 

LTBI TREATMENT REGIMENS 

Isoniazid 

Single drug treatment of LTBI should not be started until active TB has been 

excluded. The optimal regimen for treatment for LTBI in individuals with no 

known exposure to a drug resistant case of TB is isoniazid (INH), given daily 

or twice weekly for nine months (Table 2-3.7). For adults who are HIV negative, 

six months of INH is an acceptable alternative if the nine-month regimen 

cannot be given. However, six months of INH is not recommended for HIVpositive 

persons, children younger than 18 years of age and individuals with 

fibrotic lesions consistent with TB on CXR. The nine-month regimen may be 

administered concurrently with any antiretroviral regimen used to treat HIV 

infection. 

Contraindications to treatment of LTBI with INH are: 

• A history of an INH-induced reaction, including hepatic, skin or allergic 

reactions, or neuropathy. 

• Close contact with a person who has INH resistant TB. 

• Severe chronic liver disease. 

• Pregnancy, unless the woman is HIV infected, a recent TST converter 

or a close contact. 

The risk of INH toxicity has been shown to increase with age, particularly in 

older adults. Those who are contacts, or who have clinical conditions associated 

with increased risk of progression to active TB, should be treated regardless 

of age. However, the risk-benefit ratio from INH may not favor treatment of 

older adults whose only risk factor is recent immigration. This group should 

be closely monitored for INH toxicity and should even possibly be excluded 

from treatment. 


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72 

Drug and Duration 

Isoniazid 

(INH) 

Children: 9 months 

Adults: 9 months 

Rifampin 

(RIF) 




Treatment for Latent TB Infection 

Dosage 

Daily Twice Weekly 

Children: 5-10 mg/kg 

(max 300 mg) 

Adults: 5 mg/kg 

(max 300 mg) 

Completion Criteria 

270 doses within 12 

months 

Children: 10-20 mg/kg 

(max 600 mg) 


182 doses within nine 

months 

Adults: 600 mg [range 

8-12 mg/kg] (max 600 

mg) 


120 doses within six 

months 

Children: 20-30mg/kg 

(max 900 mg) 


(max 900 mg) 


76 doses within 12 

months 

Children: Not 

recommended 

Adults: 600 mg3 [range 

8-12 mg/kg] (max 600 

mg) 



months 

Table 2-3.7: Treatment for Latent TB Infection 

Major Adverse 

Reactions 

Recommended 

Monthly Monitoring1 

Symptoms include: 

Unexplained anorexia, 

nausea, vomiting, 

dark urine, jaundice, 

persistent fatigue, 

weakness, abdominal 

tenderness (especially 

right upper quadrant 

discomfort), easy 

bruising or bleeding, 

rash, persistent 

paresthesias of the 

hands and feet, and 

arthalgia. 

Signs include: 

Elevated LFTs, hepatitis, 

icterus, rash, peripheral 

neuropathy, increased 

phenytoin levels, 

possible interaction with 

disulfiram (Antabuse®) 

Clinical evaluation: 

LFTs (if baseline is 

abnormal or patient has 

risk factors for toxicity) 2 


Nausea, vomiting, loss 

of appetite, rash, fever or 

flu-like symptoms, easy 

bruising 


Elevated LFTs, hepatitis, 

rash, thrombocytopenia. 

Reduces levels 

of many drugs, 

including methadone, 

warfarin, hormonal 

contraception, oral 

hypoglycemic agents, 

theophylline, dapsone, 

ketoconazole, PIs, and 

NNRTIs. 





CBC, including platelets 

as needed 

Comments 

Preferred regimen for all 

individuals. 

- Vitamin B6 (25 mg/ 

day) or pyridoxine may 

decrease peripheral and 

CNS effects and should 

be used in patients 

who are: 

• Abusing alcohol 

• Pregnant 

• Breastfeeding infants 

on INH 

• Malnourished 

Or have: 

• HIV 

• Cancer 

• Chronic renal or liver 

disease 

• Diabetes 

• Pre-existing peripheral 

neuropathy 

Note: Aluminumcontaining 

antacids 

reduce absorption. 

May be used to treat 

persons who have 

been exposed to INHresistant,rifampinsusceptible 

TB or who 

have severe toxicity to 

INH, or are unlikely to 

be available for more 

than 4-6 months 

Be aware that: 

-There will be orange 

discoloration of 

secretions, urine, tears, 

and contact lenses 

- Patients receiving 

methadone will need 

their methadone dosage 

increased by an average 

of 50% to avoid opioid 

withdrawal. 

- Interactions with 

many drugs can lead 

to decreased levels of 

either or both. 

- Rifampin may make 

glucose control more 

difficult in diabetics. 

- Rifampin is 

contraindicated for 

patients taking most PIs 

and NNRTIs4 

- Patients should be 

advised to use barrier 

contraceptives while on 

rifampin.

Rifabutin 

(RBT) 



Children: 5 mg/kg 

(max 300 mg) 

(Little data) 


182 doses within nine 

months 


(max 300 mg) 



months 

Children: Not 

recommended 


(max 300 mg) 



months 


Stomach upset, chest 

pain, nausea, vomiting, 

headache, rash, muscle 

aches, redness and pain 

of the eye. 


Elevated LFTs, 

hepatitis, neutropenia, 

thrombocytopenia. 

Reduced levels of 

many drugs including 

PIs, NNRTIs, dapsone, 

ketoconazole, 

and hormonal 

contraception. However 

some drugs, including 

PIs and some NNRTIs 

do increase levels of 

rifabutin. 





CBC, including platelets 

as needed 

May be used to treat 

LTBI in HIV-infected 

persons who fit the 

criteria for rifampin 

treatment but for 

whom rifampin is 

contraindicated, or 

for others who need 

a rifamycin but are 

intolerant to rifampin. 

Be aware that: 

-There will be orange 

discoloration of 

secretions, urine, tears, 

and contact lenses 

- Interaction occurs with 

many drugs. 

- For HIV-infected 

persons, it is necessary 

to adjust the daily 

or intermittent dose 

of rifabutin and 

monitor for decreased 

antiretroviral activity 

and for rifabutin toxicity, 

if taken concurrently 

with PIs and NNRTIs.4 

- Methadone dosage 

generally does not need 

to be increased. 

- Patients should be 

advised to use barrier 

contraceptives. 

Abbreviations: CBC=complete blood count, CNS=central nervous system, LFTs=liver function tests, NNRTI=non-nucleoside reverse 

transcriptase inhibitors, PI=protease inhibitor 

1. Baseline LFTs should be done for everyone over the age of 35, all HIV-infected persons, pregnant and postpartum women (up totwo 

to three months postpartum), those with history of hepatitis, liver disease or alcohol abuse, injection drug users, and those on treatment 

with other potential hepatotoxic agents. A baseline CBC with platelets should be done on anyone prescribed a rifamycin-containing 

regimen. 

2. Monthly LFTs should be conducted for all HIV-infected persons, pregnant and postpartum women (up to 2-3 months postpartum), 

those with history of hepatitis, liver disease or alcohol abuse, injection drug users, and those on treatment with other potential 

hepatotoxic agents. Those whose baseline LFTs were abnormal should be monitored monthly regardless of other conditions. 

3. There is very little data or clinical experience on the use of intermittent treatment of latent TB infection with rifampin or rifabutin. These 

regimens should be used with caution. 

4. Please see the NYC Bureau of TB Control’s HIV/TB treatment guidelines (www.nyc.gov/html/doh/downloads/pdf/tb/tbanti.pdf). 

Table 2-3.7 (continued): Treatment for Latent TB Infection 

Patients should be identified for possible risk factors for hepatotoxicity 

prior to starting therapy for LTBI. Baseline blood tests including a blood cell 

count, LFTs, as well as a viral hepatitis screening profile should be obtained 

in patients who: 

• Are HIV-positive. 

• Have a history of heavy alcohol ingestion, liver disease or chronic 

hepatitis. 

• Are pregnant or postpartum (up to two to three months after delivery). 

• Have a history of drug injection. 

• Are older than 35 years. 

• Are starting treatment for LTBI with two or more anti-TB drugs. 

• Are already taking hepatotoxic drugs for other medical conditions. 

If the LFTs are three to five times above the normal limit at baseline, 

consideration for delaying LTBI therapy should be made while further 

evaluation is done for cause of the hepatic condition. Otherwise, the regimen 

for LTBI should be selected based on the indication for therapy and the risk of 

drug induced liver injury (i.e., rifampin may be considered in INH-resistance 

contacts or a need to complete treatment in a shorter time). 


73

74 


Directly Observed Therapy (DOT) for LTBI is an effective method for 

promoting adherence to treatment. Due to limited resources, however, most 

public health programs cannot provide DOT to all patients receiving LTBI 

therapy. However, if DOT is being provided to an active case, the household 

contacts receiving LTBI therapy can also receive home-based DOT. Patients 

receiving DOT treatment for LTBI may be considered candidates for twiceweekly 

therapy. 

Rifampin 

An alternative regimen to INH is to give adult patients (with or without HIV 

infection) four months of rifampin for treatment of LTBI. This course is 

especially recommended if there are adverse reactions or resistance to INH, 

but not to rifampin; or if the individual will not be available for more than four 

to six months and is thus unlikely to complete a nine-month INH regimen. 

If a rifampin- containing regimen is chosen for HIV-infected patients with 

LTBI, the drug to drug interactions and dose adjustments for antiretroviral 

drugs and rifamycin need to be taken into consideration, and rifabutin given 

where appropriate. 

Children (with or without HIV infection) who have been exposed to INHresistant, 

rifampin-susceptible TB should be treated with at least six months 

of rifampin. Although INH is the only drug that has been studied on a large 

scale for treatment for LTBI, rifampin is probably equally effective. If needed, 

rifabutin can be substituted for rifampin. 

Rifabutin may be used with regimens containing the non-nucleoside reverse 

transcriptase inhibitors (NNRTIs) efavirenz and nevirapine, or many protease 

inhibitors (PIs) used in the management of HIV. There is insufficient data on the 

use of rifabutin in antiretroviral regimens containing combinations of NNRTIs 

and PIs, or other multiple PI combinations. The websites: www.nyc.gov/html/ 

doh/downloads/pdf/tb/tbanti.pdf or www.cdc.gov/tb/TB_HIV_Drugs/default. 

htm or www.AIDSinfo.nih.gov are continuing sources of information on this 

subject, as recommendations are consistently changing. Contraindications 

to the use of rifampin in treating LTBI are: 

• A history of rifampin-induced reactions, including skin and other 

allergic reactions, hepatitis or thrombocytopenia. 

• Severe chronic liver disease. 

• Pregnancy, unless the woman is HIV-infected, a recent TST converter, a 

close contact of an INH-resistant case or is intolerant to INH and needs 

to be treated (see above). 

• Current treatment with certain PIs or NNRTIs (an alternative is to use 

selected antiretroviral drugs with rifabutin, see above). 

Rifampin & PZA Combination 

The two-month regimen containing rifampin and pyrazinamide as an option for 

LTBI treatment is no longer recommended due to high rates of hospitalization 

and death from liver injury associated with the use of a daily or twice-weekly 

two-month regimen of rifampin plus pyrazinamide. As a result, this regimen 

should generally not be offered to HIV-negative or HIV-positive persons with 

LTBI.

CONTACTS TO MULTIDRUG RESISTANT 

TB (MDRTB) CASES 

There have been no controlled trials of treatment for LTBI with drugs other 

than INH and rifampin. Therefore, treatment protocols for contacts of patients 

with INH- and rifampin-resistant TB are largely empirical, and all regimens 

must be individualized. Therapy should be initiated by a physician expert in 

treatment of this condition. TB disease must be excluded before any therapy 

regimens for LTBI are initiated. Regimens given for LTBI are comprised of 

two medications to which the organism of the index case is susceptible for 

6-12 months. If the contact chooses not to take LTBI therapy, he/she should 

be followed for the next two years with a symptom review and chest x-ray. 

Treatment of Close Contacts with a Prior Positive Test for TB 

Infection 

Close contacts to a TB case with a documented previous positive TTBI should 

be treated again for LTBI after active TB is ruled out if they are HIV positive, 

or at risk for HIV disease but have declined testing. Treatment should also be 

considered for the following individuals who have a previous positive TTBI, but 

who have subsequently been in close contact with a person who has infectious 

pulmonary TB: 

• Persons with immunosuppressive conditions and other medical risk 

factors for TB, other than HIV infection. 

• Children younger than 18 years of age. 

• Asymptomatic, HIV-negative persons who have had heavy exposure 

to a person with highly infectious pulmonary or laryngeal TB (i.e., the 

presence of secondary cases or documented conversions in the close 

contacts). 

• The regimen for LTBI again should depend on the susceptibility of the 

index case isolate. 

Monitoring Patients During Treatment 

All patients receiving treatment for LTBI should be monitored on a monthly 

basis, with directed clinical examinations and blood tests as needed. Patients 

also need to be educated about the signs and symptoms of adverse drug reactions 

and the need for prompt cessation of treatment and clinical evaluation should 

symptoms occur. 

Adverse effects with INH or rifampin may include unexplained anorexia, 

nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the 

hands and/or feet, persistent fatigue, weakness or fever lasting three days or 

more, abdominal tenderness (especially right upper quadrant discomfort), 

easy bruising or bleeding and arthralgia. Appropriate educational materials 

in the patient’s language should be provided. 


75


Monthly liver function tests (LFTs) should be done in patients who: 

• Are HIV-positive. 

• Have a history of alcohol abuse, liver disease, chronic hepatitis. 

• Are pregnant or postpartum women (two to three months after delivery). 

• Are currently injecting drugs. 

• Are on potentially hepatotoxic agents. 

• Have baseline abnormal LFTs not due to the conditions above. 

In addition, laboratory testing should be used to evaluate specific adverse 

events that may occur during treatment. If the patient develops hepatotoxicity, 

medication should be stopped, and the patient’s LFTs should be monitored 

closely. If indicated, other possible risk factors for hepatotoxicity should be 

identified. 

SUMMARY 

Despite the fact that TB is preventable and curable, it remains a public health 

threat in the US and around the world. There have been great strides in reducing 

the number of cases of active TB over the years due to increased resources 

allotted to TB control programs and aggressive initiation of DOT in the treatment 

of TB. However we still face many challenges in TB control programs today 

including the prompt identification of cases and contacts and placing them 

on appropriate treatment and also the increasing emergence of MDRTB and 

XDRTB. There is a large group of individuals who have LTBI globally and 

finding new modalities to reduce the percentage of this group who remain at 

substantial risk for subsequent active TB has and will continue to be difficult. 

DOT remains one of the most effective methods to ensure patients complete 

treatment for TB disease, yet many TB programs do not have enough resources 

to apply the use of DOT when treating LTBI patients, and therefore completion 

of treatment among these patients remains low. The future of reducing TB 

disease and latent infection will depend on the continued vigilance of case 

finding, contact identification and treatment of contacts. Despite the advances 

made over the years, there is a continued need to develop new diagnostic tools 

and therapies to combat this complex disease. 

REFERENCES 

1. American Thoracic Society. Diagnostic Standards and Classification of TB 

in Adults and Children. Am J Respir Crit Care Med 2000; 161: 1376-1395. 

2. American Thoracic Society and Centers for Disease Control and Prevention. 

Targeted tuberculin testing and treatment of latent TB infection. Am J 

Respir Crit Care Med. 2000; 161: S221-S247. 

3. Brudney K, Dobkin J. Resurgent TB in New York City: HIV, homelessness 

and the decline of TB control programs. Am Rev Respir Dis 1991; 144:745- 

749.

4. CDC. Update: Adverse event data and revised American Thoracic Society/ 

CDC recommendations against the use of rifampin and pyrazinamide 

for treatment of latent TB infection – United States, 2003. MMWR Morbid 

Mortal Wkly Rep 2003; 52(31):735-739. 

5. CDC. TB Elimination: Diagnosis of TB disease. By CDC. 2006. 18 August 

18, 2008 

6. CDC. Guidelines for Preventing the Transmission of Mycobacterium TB 

in Health-Care Settings, 2005. MMWR 2005;54(No. RR-17): pg 1-8. 

7. CDC. General recommendations on immunization: recommendations 

of the Advisory Committee on Immunization Practices (ACIP). MMWR 

1994; 43 (RR-1): 25. 

8. CDC. Guidelines for investigation of contacts of persons with infectious 

tuberculosis. MMWR 2005;54(RR-15):1-47. 

9. CDC. Guidelines for using the QuantiFERON-TB Gold test for detecting 

Mycobacterium tuberculosis infection. MMWR 2005;54:49-55. 

10. CDC. Management of person exposed to multidrug resistant TB. MMWR 

1992;41:61-71. 

11. Daley, C. L., P. M. Small, G. F. Schecter, G. K. Schoolnik, R. A. McAdam, W. 

R. Jacobs, Jr., and P. C. Hopewell. 1992. An outbreak of TB with accelerated 

progression among persons infected with the human immunodeficiency 

virus. An analysis using restriction-fragment-length polymorphisms. N. 

Engl. J. Med. 326:231-235. 

12. Holden M, Dubin MR, Diamond PH. Frequency of negative intermediatestrength 

tuberculin sensitivity in patients with active TB. New Engl J Med 

1971;285:1506-09. 

13. Horsburgh, J 1996. TB without tubercules. Tuber. Lung Dis. 77: 197-198. 

14. Kopanoff DE, Snider DE, Cars GJ. Isoniazid-related hepatitis: a United 

States Public Health Service Cooperative Surveillance Study. Am Rev 

Respir Dis 1978; 117:991–1001. 

15. Monir M, Abusabaah Y, Mousa AB, Masoud AA. (2004). Post-primary 

pulmonary TB. In TB (pg 313). Berlin Heidelberg: Springer-Verlag. 

16. Munsiff S, Nilsen D, King L, Dworkin F. Testing and treatment for latent 

TB infection. City Health Information. 2006:25(4)21-32. 

17. Nash DR, Douglass JE. Anergy in active pulmonary TB. A comparison 

between positive and negative reactors and an evaluation of 5 TU and 250 

TU skin test doses. Chest 1980;77:32-7. 

18. New York City Department of Health and Mental Hygiene (2008). Treatment 

of Pulmonary TB. In Clinical Policies and Protocols (4th ed., pg 184). New 

York: Author. 


77


19. Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid 

preventive therapy: a 7-year survey from a public health TB clinic. JAMA 

1999; 281:1014–8. 

20. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, et al. An official 

ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir 

Crit Care Med. 2006;174(8):935-52. 

21. van Hest R, Baars H, Kik S, van Gerven P, Trompenaars MCh, Kalisvaart N 

et al. Hepatotoxicity of Rifampin-Pyrazinamide and Isoniazid Preventive 

Therapy and TB Treatment. Clin Infect Dis 2004 August 15;39(4):488-496.

Chapter 2-4 

Asthma 

By Dr. Naricha Chirakalwasan, M.D. 

Dr. Andrew Berman, M.D. 

Asthma is a chronic inflammatory disease of the airways. 1 This inflammation 

can lead to airway hyperreactivity when exposed to triggers (such as irritants, 

allergens, temperature/humidity change, stress and exertion) and acute airflow 

limitation producing symptoms, such as cough, wheeze, chest tightness and 

shortness of breath. These symptoms are at least partially reversible with 

bronchodilator medications. Airway inflammation is present even in mild 

disease. 

EPIDEMIOLOGY 

An estimated 23.4 million Americans have asthma and the prevalence has 

been steadily increasing. 2,3 The incidence of asthma is greater in childhood 

compared to adulthood. Each year, there are nearly 500,000 hospitalizations 

and close to two million visits to the Emergency Department. Nearly one 

quarter of adults with asthma missed work during the prior year due to asthma 

and over one third of parents of asthmatics missed work in the prior year. The 

annual direct and indirect health cost is estimated at over 16 billion dollars. 

Fortunately the overall mortality of asthma in the United States appears to be 

decreasing. Of concern, the mortality rate appears to be higher among African 

Americans and Puerto Rican Americans, perhaps due to factors such as health 

care access, environmental factors, and/or genetic influences. 

RISK FACTORS 

Both genetic and environmental risk factors have been sited for the development 

of asthma. Some studies have shown a more than 25% chance of having a 

child with asthma if one of the parents has asthma. Numerous studies have 

also linked asthma to allergic diseases which occur in families with a genetic 

predisposition towards the development of a hypersensitivity reaction to 

environmental allergens. There have been many reports describing the 

identification of potential asthma-susceptibility genes, and such research 

and genetic findings will lead to better disease classification and treatment. 

Environmental risk factors include exposure to maternal smoking during 

pregnancy, chemical sensitizers, air pollutants, allergens and infections of 

the respiratory tract. Studies have shown a two-fold risk of a child developing 

asthma if the mother smokes while pregnant. Environmental tobacco smoke 

may also be linked to adverse asthma-related outcomes. 4,5 Vigorous outdoor 

exercise in regions with high levels of ozone also has been shown to predispose 

to the development of asthma, and particulate air pollution from motor 

vehicles has been suspected of contributing to the increased prevalence. 5 The 

indoor environment is just as important, perhaps more-so, where exposure 

Chapter 2-4 • Asthma 

79

80 Chapter 2-4 • Asthma 

to such allergens as house dust mites, cats, dogs, cockroaches, and molds 

may be associated with allergic asthma. Interestingly, it has also been shown 

that exposure to cat or dog allergen early in life may actually be protective 

against later development of asthma. Certain bacterial infections including 

Chlamydia pneumoniae and Mycoplasma pneumoniae, as well as a number 

of viral infections, can stimulate local inflammatory reactions, and may be 

associated with asthma. Low or high birth weight, prematurity, and obesity 

have been shown to increase the risk of asthma. Just as with coronary artery 

disease, consumption of oily fish (salmon, tuna, shark) rich in omega-3 fats 

may be protective. 

Work related asthma includes occupational asthma and work-aggravated 

asthma. Occupational asthma is airflow limitation and/or airway 

hyperresponsiveness caused by exposure to a specific agent or conditions 

in a particular work environment. 6 Recent data from the Sentinel Health 

Notification System for Occupational Risk (SENSOR) program indicates that 

exposure to irritants are frequently reported as causes of new-onset asthma. 7 

The intensity of the exposure is likely to be a risk factor for irritant-induced 

asthma. Several cohort studies have suggested that work-related exposure 

to machining fluid, chemicals, laboratory animals, flour and latex may be 

associated with new-onset asthma. In contrast to work-related asthma, workaggravated 

asthma is defined by preexisting asthma that is made worse or 

exacerbated by the work environment. 

Reactive Airways Dysfunction Syndrome (RADS) is defined as persistent 

respiratory symptoms and airway hyperreactivity in patients with a history of 

acute exposure to an inhaled agent (gas or aerosol) and without a prior history 

of allergies, smoking or asthma. 8 However, for practical purposes, RADS can 

be assumed to be present when there are new episodic respiratory symptoms 

with spirometric evidence of lower airways obstruction, especially when the 

obstruction can be reversed by administration of bronchodilating drugs. 

Although RADS was initially reserved for only acute exposures to chemical 

gases and fumes, 8 it’s use has been extended by some to include chronic 

exposures to gases and fumes and recently even to acute/chronic exposures 

to particulates. Others argue that extending the definition of RADS clouds 

any distinction between RADS and irritant-induced asthma. Regardless of 

this controversy in terminology, RADS or irritant induced asthma has been 

reported after smoke inhalation in both civilians and fire fighters. 9,10,11 

Currently, not enough is known about bronchospastic inflammatory airways 

diseases to know if there are important distinctions, such as mechanism of 

occurrence, degree of severity, response to treatment, or prognosis, between 

RADS, irritant-induced asthma, occupational asthma, allergic asthma or 

non-specific asthma. What we do know is that clinically these distinctions are 

currently meaningless. All of these illnesses have in common provocability 

(reaction to airborne irritants, allergens, temperature/humidity and exercise), at 

least partially reversible airways obstruction in response to asthma medications 

(see below) and may rarely progress to irreversible lower airways obstructive 

disease (airway remodeling). 

The risk of lung diseases including asthma following the collapse of the 

World Trade Center (WTC) towers is discussed in greater detail in a separate 

chapter. WTC studies have allowed us to describe the incidence of bronchial

hyperreactivity, RADS or irritant-induced asthma after a major disaster 

and to evaluate its persistence longitudinally in large cohorts. In a sample 

of rescue workers from the Fire Department of the City of New York (FDNY) 

whose bronchial hyperreactivity was measured six months after 9/11/01, those 

who arrived at the WTC site on 9/11 were 7.8 times more likely to experience 

bronchial hyper-reactivity than were those fire fighters who arrived to the 

site at a later date and/or had lower exposure levels. 12,13 A dose response was 

evident in this FDNY study: RADS emerged in 20% of highly exposed (present 

during the morning of collapse) and 8% of moderately exposed rescue workers 

(present after the morning of 9/11 but within the first 48 hours). 13 In the 

NY/NJ Consortium Program for non-FDNY WTC workers/volunteers, 45% 

reported symptoms consistent with lower airway disorders, including asthma 

and asthma variants. 14 The WTC Registry has published its findings on selfreported 

“newly diagnosed asthma (post-9/11/01) by a doctor or other health 

professional” in 25,748 WTC workers from a diverse range of occupations/ 

organizations but all without a prior history of asthma. 15 Newly-diagnosed 

asthma was reported by 926 workers, for a three-year incidence rate of 3.6%, or 

12-fold higher than the expected risk in the general population. Earlier arrival, 

total duration of work, exposure to the dust cloud, and working on the pile at 

the WTC site increased the risk asthma. 

PATHOPHYSIOLOGY 

Asthma is characterized by chronic inflammation of the airway wall which is 

present even in the asymptomatic patient. Microscopically, there is a patchy 

loss of the epithelium or cellular layer covering the airway, leaving airway 

nerves exposed. There is accumulation of inflammatory cells, including 

eosinophils, which can release their contents and cause further inflammation. 

Enlargement of airway smooth muscle, increased number and size of bronchial 

blood vessels, and an accumulation of abnormal mucus in the airways all 

contribute to worsening airflow obstruction. Persistent inflammation may 

lead to a change in the structure of the airway due to the development of 

fibrosis (scar-like tissue) beneath the cellular layer covering of the bronchus. 

This process is referred to as airway remodeling (Figure 2-4.1). 

Figure 2-4.1: Airway pathology in asthma is detected in this photomicrograph of a section 

from an endobronchial biopsy taken during bronchoscopy from a subject with mild chronic 

asthma. Goblet (mucus) cell metaplasia, subepithelial fibrosis, and eosinophilic infiltration 

of the submucosa are shown. (Hematoxylin and eosin stain; ×1200.) Courtesy of Murray 

and Nadel’s Textbook of Respiratory Medicine, 4th edition. 


81


CLINICAL MANIFESTATION 

Patients usually present with difficulty breathing (dyspnea), audible wheezing, 

and tightness in the chest. Cough can occur in association with these symptoms 

or be the only symptom, a condition called cough-variant asthma. Patients 

may report coughing mainly at night, which can awaken them from sleep. 

Breathing problems (cough, wheeze and/or shortness of breath) can be 

triggered by physical activity, during particular seasons, or after exposure to 

allergens, irritants, or changes in temperature/humidity. A history of persistent 

respiratory tract infections is sometimes found. 

Physical findings on examination include tachypnea (increased respiratory 

rate), wheezing, and a prolonged time-phase for expiration. When the presentation 

is more severe, decreased breath sounds, excessive use of respiratory muscles 

and rarely even cyanosis (low oxygen levels causing bluish discoloration of 

skin and mucous membranes) can be found. 

DIAGNOSIS 

A definitive diagnostic test for asthma does not yet exist. Family history, 

symptoms, and physical examination may suggest the diagnosis of asthma. 16 

Provocable or triggerable symptoms with reversibility following either removal 

of the trigger or administration of a bronchodilator medication are the hallmark 

of asthma. Lung function testing may confirm the diagnosis and exclude 

other causes of these symptoms. Spirometry is a test most commonly used to 

evaluate the two main characteristic features of asthma: airflow obstruction, 

which is at least partially reversible, and airway hyperresponsiveness. During 

spirometry, patients are asked to forcibly exhale after taking a full breath in. 

After consistent measurements are obtained, a bronchodilator is administered 

and the testing is repeated to assess change. Airway obstruction is present when 

the ratio of the amount exhaled in one second (referred to as the FEV1 or forced 

expiratory volume at one second) to the total amount exhaled (referred to as the 

FVC or forced vital capacity) is less than 0.7 or when ratio is within the lower 

limit of normal (LLN) distribution. NIOSH provides an excellent spirometry 

reference value calculator (based on NHANES III reference equations) which 

allows determination of the LLN for a specific age, gender, race and height 

(see: http://www.cdc.gov/niosh/topics/spirometry/RefCalculator.html). 

Reversibility is documented when the FEV1 or FVC increases by 12% and 200cc 

of volume after the bronchodilator is given. Peak expiratory flow rate (PEFR) 

measured with a hand-held peak flow meter can be used to assess changes in 

lung function at the work place to help diagnose work-related asthma and to 

document the relationship of lung function to suspected triggers. This method 

however is more effort dependent and less reproducible than spirometry. Tests 

of pulmonary function are described in another chapter in greater detail. 

Bronchoprovocative tests measuring airway hyperresponsiveness can 

be done if baseline spirometry is normal or near-normal but the patient has 

symptoms suggestive of asthma. In this test, a substance that induces or 

provokes asthma is inhaled in increasing doses and spirometry is repeated 

until the FEV1 falls 20% or the highest dose is delivered without a significant 

FEV1 change. Methacholine challenge testing is the most commonly used 

bronchoprovocative test in the United States and Canada, though some centers

use cold-air or exercise, histamine or mannitol challenge testing. A negative 

methacholine challenge test virtually excludes asthma due to its high sensitivity. 

Several other tests are often done to evaluate a patient with suspected 

asthma, but are not diagnostic. Skin testing is often performed on patients with 

allergies and asthma. The presence of positive skin tests may help the patient 

avoid specific allergens that can trigger or worsen asthma. Sputum analysis 

and chest x-rays are generally non-specific in asthma, but are more useful in 

excluding other disease processes. Chest CT scans may show bronchial wall 

thickening and/or air-trapping in asthma and other obstructive airways diseases 

(ex. emphysema, chronic bronchitis, bronchiolitis obliterans, etc.) but are 

most useful in excluding other disease processes. Oxygenation is usually not 

a problem during most asthma attacks but measurement of oxygen saturation 

is helpful in severe exacerbations. A new measure of asthma severity is the 

amount of exhaled nitric oxide, a marker of inflammation. 

DIFFERENTIAL DIAGNOSIS 

Several diseases can mimic asthma by producing similar symptoms, and has 

lead to the saying, “all that wheezes is not asthma.” 17 Other diseases that can 

be misdiagnosed as asthma include: 

• Upper airway obstruction, due to multiple causes including inhaled or 

aspirated foreign body, tumor, abscess, or epiglottitis (medical emergency 

in children secondary to infection/inflammation of the epiglottis, the 

lid-like structure overhanging the entrance to the larynx at the back 

of the throat). 

• Vocal cord paralysis/dysfunction, characterized by an inappropriate 

closing of the vocal cords during respiration causing upper airway 

obstruction. 

• Upper-airway and/or lower-airway respiratory infections. 

• Chronic bronchitis, which is often due to smoking and is defined as the 

presence of a chronic productive cough for three months during each 

of two successive years, and is part of the condition known as chronic 

obstructive airways disease (COPD), described in another chapter. 

• Endobronchial lesions (mass-lesions inside the lower airways due to 

inhalation or aspiration of foreign bodies, scarring or tumors), which 

can cause localized wheezing. 

• Congestive heart failure causing wheezing due to pulmonary edema 

or fluid filling air sacs. 

• Gastro-esophageal reflux disease (GERD), the disease with reflux of 

the stomach and duodenal contents into the esophagus. 

• Pulmonary embolism (a blood clot that travels to the lungs). 

CLASSIFICATION OF ASTHMA SEVERITY 

In 2005, the National Heart, Lung, and Blood Institute of the National Institutes 

of Health (NIH/NHLBI) published a guideline for evaluation of asthma severity 

based on the symptoms and pulmonary function (FEV1 and PEFR). The 

primary goal of this classification is to determine who has intermittent and 


83


who has persistent asthma. Patients with intermittent asthma are treated with 

short-acting bronchodilators, used when needed. All other patients should be 

treated with daily inhaled corticosteroids. Additional asthma medications are 

prescribed as asthma severity worsens. 

In 2007, the NIH/NHLBI guidelines were modified to effectively classify 

patients as either under control or poorly controlled, based on impairment 

and risk. 18 Impairment is based on the frequency of symptoms, night-time 

awakenings, frequency of need for rescue (short-acting) bronchodilator 

therapy, and functional limitations. Risk is the likelihood that the patient will 

experience an asthma exacerbation. Based on impairment and risk criteria 

(as seen in Table 2-4.1), treatment can be stepped up or stepped down. The 

stepwise approach to asthma treatment is discussed later in this chapter. 

Risk Impairment 

Exscerbations 

Requiring OCS 

Symptons 

Night-time 

Awakenings 

Use of SABA 

for Symptom 

Relief 

Interference 

with Normal 

Acitivity 

0-1/year ≤2 days/wk ≤2x/month ≤2 days/wk None 

≤2/year 

>2 days/wk, 

not daily 

Daily 

Throughout 

the day 

3-4 x/month 

>1 x/wk, not 

nightly 

Often 

7x/wk 

> 2 days/wk, 

not daily or 

>1 x/day 

Daily 

Several x/day 

Minor 

limitation 

Some 

limitation 

Extremely 

limited 

Lung 

Function 

FEV1 normal 

between 

exacerbations 

(>80%); 

FEV1/FVC 

normal 

FEV1 >80%; 

FEV1/FVC 

normal 

FEV1 >60% 

but

management plans, developed by the physician and patient for co-management 

of asthma attacks, should be understood by the patient. 

MEDICATIONS 

Asthma medications are classified as quick-relief (rescue) and long-term 

control (maintenance) medications. Quick-relief medications are taken to 

promptly reverse airflow obstruction and relieve symptoms. Long-term control 

medications are taken daily to maintain control of persistent asthma with 

the goal of reducing the number of attacks and their severity. Generally, the 

treatment is based on the severity of asthma (refer back to Table 2-4.1). 

Quick-Relief Medications 

Short-Acting Beta-Agonists (SABA) 

Short-acting beta-agonists act primarily on beta-adrenergic receptors to relax 

bronchial smooth muscle contraction. They do not reduce airway inflammation 

and therefore are not control medications. The beta-agonists are usually 

delivered by an inhaler or nebulizer. The most commonly used beta-agonist 

in the United States is albuterol. The action begins within five minutes of use 

and lasts as long as four hours, and may require re-dosing. They are used as 

needed only. Common side effects are tremor, nervousness and tachycardia. 

Recent regulations from the Environmental Protection Agency (EPA) have 

led to a ban of the substance that was previously used to propel albuterol 

from the inhaler. 19 This is not because the propellant was dangerous to the 

patient but rather because it was harmful to the earth’s ozone layer. Currently, 

albuterol is available as albuterol HFA which does not have these propellants. 

Other agents in this class are marketed in the United States under the trade 

names Ventolin®, Proventil®, Proair® and Maxair®. Studies have shown that the 

old and new preparations of albuterol are equally as effective, although you 

may notice that HFA inhalers do not seem to be hitting your throat with the 

same force. Long-acting preparations of beta-agonists are also available but 

should never be used as quick-relief medications and should never be used 

without an inhaled corticosteroid. This class will be discussed in the control 

medication section. 

Anticholinergics 

Anticholinergics, such as ipratropium bromide (marketed as Atrovent®), also 

promote smooth muscle relaxation, though beta-agonists are more effective 

bronchodilators in the asthmatic population. These agents have a slower 

onset of action but may last longer. Common side effects of anticholinergics 

are nausea and dry mouth. In general, these agents are used when there 

is intolerance to beta-agonists, but in certain cases they may be used in 

combination (albuterol plus ipratropium bromide, marketed as Combivent®). 

A long-acting anticholinergic medication, tiotropium (marketed as Spiriva®), 

is currently available but not indicated for asthma at this time. 


85

86 


Long-Term Control Medications 

Inhaled Corticosteroids (ICS) 

Inhaled corticosteroids are currently the mainstay of asthma treatment for 

all patients except those with mild intermittent asthma (refer to Table 2-4.1). 

Inhaled steroids are potent anti-inflammatory agents that require daily use. 

Numerous studies have shown that inhaled steroids reduce daily asthma 

symptoms, reduce the severity and frequency of asthma exacerbations, 

reduce the need for bronchodilator therapy, and improve lung function. Most 

importantly, regular use of inhaled steroids is associated with reduced asthma 

mortality. They can be delivered by a metered dose inhaler, dry powder inhaler 

or nebulizer. Common side-effects are oral thrush (fungal infection), change of 

voice, and cough. It is extremely unusual for inhaled corticosteroids to cause 

the side-effects associated with oral corticosteroids (see below). Currently 

there are multiple inhaled corticosteroids available in the United States and 

marketed under the names Pulmicort®, Flovent®, Asmanex®, Asmacort®, QVar®, 

etc. They are also available in combination with long acting beta-agonists and 

marketed under the trade names Advair® and Symbicort®. 

Long Acting Beta-Agonists (LABA) 

Long acting beta-agonists are available in the form of salmeterol (marketed 

as Serevent®) and formoterol (marketed as Foradil®). Both have significantly 

longer half lives than albuterol, thereby requiring dosing only every 12 hours. 

Onset varies, with formoterol working quicker. One large study raised concern 

regarding asthma mortality and use of long-acting beta-agonists as monotherapy. 

It remains unclear if this was a reflection of a drug side-effect or underlying 

asthma disease severity. Until this is known, these agents should always be 

used in combination with inhaled steroids This combination is indicated in 

those patients who have moderate or severe persistent asthma. Single inhalers 

containing both a long acting beta-agonist and an inhaled corticosteroid 

(marketed as Advair® and Symbicort®) are available to promote compliance 

and to help prevent the use of these agents as monotherapy. 

Leukotriene receptor antagonists (LTRA) 

Leukotriene antagonists are generally an add-on therapy in the patients who are 

on inhaled corticosteroids, who cannot tolerate inhaled corticosteroids or who 

have a very strong allergy history with co-existent allergic rhinitis (nose drip/ 

congestion). Leukotriene antagonists block leukotrienes which are substances 

released from inflammatory cells and that cause bronchoconstriction. This class 

of medication, of which the most commonly used is montelukast (marketed as 

Singulair®) is available in pill form, and is usually taken at nighttime. They may 

play a role in treating patients with environmental allergies as well as aspirinsensitive 

asthma. Side-effects may include headache and flu-like symptoms. 

Mast Cell Stabilizers 

Mast cell stabilizers include cromolyn (marketed as Intal®) and nedocromil. 

They are another possible add-on therapy in patients who are on inhaled 

corticosteroids and who cannot tolerate inhaled corticosteroids, or who have 

a very strong allergy history with co-existent allergic rhinitis (nose drip/

congestion). They are delivered by metered dose inhalers. Dosing intervals 

tend to make compliance difficult. They are not commonly prescribed in the 

adult population. Side-effects are rare, but can include cough and dry throat. 

Overall, the role of this class of medication in the treatment of adult asthmatics 

is considered limited. 

Methyxanthines 

Methylxanthines, such as theophyline (marketed as Theodur® or Unidur®), are 

one of the oldest classes of asthma medication. They are taken in pill form. It is 

not currently recommended as a first line medication, but can be considered 

as an add-on therapy to inhaled steroids. Many common medications interfere 

with the metabolism of this class of medications that can result in high blood 

levels and side-effects that can range from nausea and vomiting to seizures 

and cardiac arrhythmias. 

Anti IgE Antibody 

Omalizumab (marketed as Xolair®), an anti-IgE antibody, is a fairly new 

treatment for patients with allergic asthma who are poorly controlled on 

inhaled steroids and have high circulating IgE blood levels. 20 Treatment is 

usually, but not always, reserved for patients with high circulating IgE blood 

levels. Anti IgE antibody prevents the release of inflammatory mediators from 

inflammatory cells. This medication is given through subcutaneous injection 

every two to four weeks. It has been shown to reduce asthma exacerbations, 

lessen asthma severity and reduce the need for high dose steroids. Common 

side-effects are injection-site reaction and viral infection. Cases of anaphylaxis 

(a severe life-threatening allergic reaction) have been reported. 

Immunotherapy 

Immunotherapy, or “allergy shots,” can be considered as a treatment option, 

in addition to optimal asthma treatment, in patients with fair control and a 

significant allergic component. Their usefulness in the control of asthma is 

controversial but studies do show some level of improvement in asthma patients 

with allergic rhinitis. They should not be used in asymptomatic patients who 

have positive skin or blood tests for an allergen. The purpose is to give low 

doses of allergen to reduce the immediate hypersensitivity reaction, a process 

known as desensitization. The common side-effects are injection-site reaction 

and viral infection. The potential serious complication is anaphylaxis. 

STEPWISE APPROACH TO THERAPY 

The NIH/NHLBI recommended treatment for asthma is based on the patient’s 

severity and control and is presented in Table 2-4.2. Step 1 is the treatment 

for intermittent asthma. Steps 2-5 are treatment regimens for patients with 

persistent asthma. Mild asthma is treated according to Step 2, moderate; Step 

3, and severe, Step 4 or 5. If the patient’s asthma is not controlled, therapy 

can be stepped up one or two steps. A short-course of oral corticosteroids is 

sometimes necessary (Step 6). For patients with asthma that is well controlled 

for several months, therapy can be stepped down. Monitoring to ensure 

maintained control is necessary. It is not uncommon for patients to step up 

or down depending on season, stress, infection etc. 


87


Table 2-4.2: Stepwise approach to therapy. From the Expert Panel report 3: Guidelines for 

the Diagnosis and Management of Asthma (EPR-3 2007). NIH Item No. 08-4051. Available 

at http//www.nhlbi.nih.gov/guidelines/asthgdln.htm 

THE ASTHMA CONTROL TEST 

One useful and easy-to-use tool to measure control is the Asthma Control Test 

(see Table 2-4.3). 21 This test is a validated questionnaire that is aligned with 

the above NIH goals of asthma step-therapy. It is a simple five-question quiz 

that patients can fill out with their physician. A score of ≤19 suggests asthma 

may not be controlled as well as it could be. 

Table 2-4.3: The Asthma Control Test

Non-Pharmacologic Therapy 

Reduction in trigger exposure can improve asthma symptoms. In a large homebased 

study looking into environmental interventions among urban children 

with asthma, encasing pillows, mattresses and box springs with impermeable 

covers and using HEPA filters in heating/cooling systems reduced the number 

of days with asthma symptoms. A list of preventive actions to reduce exposure 

to environmental allergens is presented in Table 2-4.4. 

RISK FACTOR ACTIONS 

Domestic dust mite allergens (so 

small they are not visible to the naked 

eye) 

Tobacco smoke (whether the patient 

smokes or breathes in the smoke from 

others) 

Allergens from animals with fur 

Cockroach allergen 

Outdoor pollens and mold 

Indoor mold 

Physical activity 

Drugs 

Wash bed linens and blankets weekly in 

hot water and dryer or the sun. Encase 

pillows and mattresses in air-tight 

covers. Replace carpets with linoleum 

or wood flooring, especially in sleeping 

rooms. Use vinyl, leather, or plain 

wooden furniture instead of fabricupholstered 

furniture. If possible, use 

vacuum cleaner with filers. 

Stay away from tobacco smoke. 

Patients and parents should not smoke. 

Remove animals from the home, or at 

least from the sleeping area. 

Clean the home thoroughly and often. 

Use pesticide spray -- but make sure the 

patient is not at home when spraying 

occurs. 

Close windows and doors and remain 

indoors when pollen and mold counts 

are highest. 

Reduce dampness in the home; clean 

any damp areas frequently. 

Do not avoid physical activity. 

Symptoms can be prevented by taking 

a rapid-acting inhaled beta2 agonist, 

a cromone, or a leukotriene modifier 

before strenuous exercise. 

Do not take beta blockers or aspirin 

or NSAIDs if these medicines cause 

asthma symptoms. 

Table 2-4.4: Common asthma risk factors and actions to reduce exposure From Global 

Initiative for Asthma (GINA), NHLBI. Global strategy for asthma management and prevention; 

Bethesda (MD); 2005 

ASTHMA EXACERBATION 

An acute asthma attack is the most common respiratory emergency. The most 

common precipitating factor is an acute viral infection, though other common 

triggers include noxious odors, weather extremes, irritant exposure, allergen 

exposure, and emotional crises. Lack of adherence to the asthma medication 

plan is often a contributing factor. 


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Treatment should be started as soon as possible. Clues for a severe attack 

include shortness of breath precluding sleep, need to sleep upright to reduce 

shortness of breath, unable to speak in full-sentences, use of accessory respiratory 

muscles in the neck to help move air in and out, cyanosis, fatigue, and mental 

status changes. Beta-agonists are the main treatment in an acute asthma attack, 

and can be given via a nebulizer or by metered dose inhaler with a spacer, 

every 20 minutes for the first hour. When the attack is severe, beta-agonists 

can be given by direct injection into the skin or muscle. Anticholinergics can 

be used concomitantly. Increasing the dose of inhaled corticosteroids during 

an asthma exacerbation is not effective and is not recommended. 22 Systemic 

corticosteroids should be prescribed for all patients with asthma attacks who do 

not favorably respond to beta-agonist therapy. A typical regimen is prednisone 

40-60 mg/day for 7 to 10 days, with or without a taper over days to weeks. The 

need to treat a life-threatening severe, persistent asthma attack overrides any 

potential concern about oral corticosteroid side-effects, such as acne, weight 

gain, hypertension, elevated blood glucose levels, or osteoporosis. 

Hospitalization may be required for patients that did not respond to the initial 

treatment. In addition, hospitalization should be considered for those patients 

who have previously had respiratory failure associated with an exacerbation, 

and for those with psychosocial issues such as inadequacy of home support 

and lack of access to medical care and medications, as these all have been 

associated with fatal asthma attacks. 

Asthma cannot be cured but it can be controlled. The earlier the treatment 

is started, the better the outcome is. This applies to both maintenance and 

rescue therapy. Following the above NIH/NHLBI stepwise guidelines, asthma 

management plans should be co-developed by the physician and patient. This 

joint effort allows the plan to be tailored to meet the patient’s individual needs 

and will inevitably improve patient adherence. Following this plan, patients 

should self adjust their asthma treatment at home based on symptoms and 

peak flow measurement, and communicate changes with their health care 

provider. 

REFERENCES 

1. Boushey Jr HA, Corry DB, Fahy JV, et. Asthma In: Murray JF, Nadel JA. 

Murray and Nadel’s Textbook of Respiratory Medicine, 4th ed. Philadelphia, 

PA: W.B.Saunders, 2005: 1168-121 

2. Pleis JR, Lucas JW, Ward BW. Summary health statistics for U.S. adults: 

National Health Interview Survey, 2008. National Center for Health 

Statistics. Vital Health Stat 10 (242). 2009. 

3. Bloom B, Cohen RA, Freeman G. Summary health statistics for U.S. 

children: National Health Interview Survey, 2008. National Center for 

Health Statistics. Vital Health Stat 10 (244). 2009. 

4. Dhala A, Pinsker K, Prezant DJ. Respiratory health consequences of 

environmental tobacco smoke. Clin Occup Environ Med. 2006;5(1):139-56 

5. Tatum AJ, Shapiro GG. The effects of outdoor air pollution and tobacco 

smoke on asthma. Immunol Allergy Clin North Am. 2005 Feb;25(1):15-30

6. Balmes JR. Occupational airways diseases from chronic low-level exposure 

to irritants. Clin Chest Med. 2002 Dec;23(4):727-735 

7. Arnaiz NO, Kaufman JD. New Developments in work-related asthma. 

Clinics in Chest Medicine 23 (2002): 737-747. 

8. Tarlo SM, Balmes J, Balkissoon R, Beach J, Beckett W, Bernstein D, Blanc 

PD, Brooks SM, Cowl CT, Daroowalla F, Harber P, Lemiere C, Liss GM, 

Pacheco KA, Redlich CA, Rowe B and Heitzer J. Diagnosis and management 

of work-related asthma: American College of Chest Physicians Consensus 

Statement. Chest 2008;134;1-41. 

9. Sherman CB, Barnhart S, Miller MF, Segal MR, Aitken M, Schoene R, Daniell 

W, Rosenstock L. Firefighting acutely increases airway responsiveness. 

Am Rev Respir Dis 1989; 140,185-90. 


firefighters after smoke exposure. Br J Industr Med 1990; 47:524-27. 

11. Kinsella J, Carter R, Reid W, Campbell D, Clark C. Increased airways 

reactivity after smoke inhalation. Lancet 1991; 337:595-7. 

12. Prezant DJ, Weiden M, Banauch GI, et al. Cough & bronchial responsiveness 

in firefighters at the World Trade Center site. N Eng J Med 2002; 347:806-15. 

13. Banauch GI, Alleyne D, Sanchez R, et al. Persistent bronchial hyperreactivity 

in New York City firefighters & rescue workers following collapse of World 

Trade Center. Am. J. Resp. Crit. Care Med. 2003; 168:54-62. 

14. Herbert, R, Moline, J, Skloot G, et al. “The World Trade Center Disaster and 

Health of Workers; Five Year Assessment of a Unique Medical Screening 

Program” Environmental Health Perspectives. 2006; 114:1853-8. 

15. Wheeler K, McKelvey W, Thorpe L, et al. Asthma diagnosed after 11 

September 2001 among rescue and recovery workers: findings from the 

World Trade Center Health Registry. Environ Health Perspect. 2007;115(11): 

1584-1590. 

16. Mathur SK, Busse WW. Asthma: diagnosis and management. Med Clin 

North Am 2006. Jan;90(1):39-60. 

17. Teirstein AS. The differential diagnosis of asthma. The Mount Sinai Journal 

of Medicine 1991;58(6): 466-471 

18. The National Heart, Lung, and Blood Institute. National Asthma Education 

and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis 

and Management of Asthma, Summary Report, October 2007. NIH Pub 

No. 08-5846. 

19. FDA advises patients to switch to HFA-propelled albuterol inhalers now. 

Bethesda, MD: U.S. Food and Drug Administration; May 30, 2008. 

20. Walker S., Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults 

and children. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003559 


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21. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma 

control test: a survey for assessing asthma control. J Allergy Clin Immunol. 

2004;113(1):59-65. 

22. Rice-McDonald G, Bowler S, Staines G, Mitchell C. Doubling daily inhaled 

corticosteroid dose is ineffective in mild to moderately severe attacks of 

asthma in adults. Intern Med J. 2005;35(12):693-698.

Chapter 2-5 

Chronic Obstructive 

Pulmonary Disease 

By Dr. Kenneth Pinsker, MD and Dr. Leah Spinner, MD 

INTRODUCTION 

Chronic Obstructive Pulmonary Disease (COPD) is a disease marked by cough 

and shortness of breath, and characterized by limitation of airflow, making 

it difficult to empty the lungs. It is a major cause of sickness and mortality 

(death) in the United States and throughout the world. Many people remain 

undiagnosed and suffer for years, or die prematurely due to its complications. 

COPD is currently the fourth leading cause of death in the world, and further 

increases in its prevalence are predicted in the coming years, as the general 

population is living longer with continued exposure to risk factors. There 

are about 14 million people known to have COPD in the United States. Some 

of the current goals in the management of COPD are to improve awareness, 

recognition, and prevention of this disease among both healthcare providers 

and patients, as well as to impress upon healthcare policymakers the burden 

of this disease. 

Definition 

COPD is defined by chronic airflow limitation in the lungs which is treatable 

and preventable, with some effects outside the lung that contribute to its 

severity in individual patients. The airflow limitation is not completely 

reversible, and is usually progressive over the course of the disease. One of 

the major differences between COPD and asthma is that the airflow limitation 

of bronchospasm in COPD is not nearly as reversible as it is in asthma. COPD 

is associated with an abnormal inflammatory response in the lungs. Overall, 

cigarette smoking is the greatest risk factor for the development of COPD. 

However, inhalation exposures, occupational or environmental are important 

additional sources of risk. For fire fighters, these exposures occur not only 

during fire suppression but also during overhaul when SCBA is far less likely 

to be used. Air pollution and in other countries air pollution from burning of 

biomass fuels also contributes to the risk of COPD. 

Some of the non-pulmonary effects of COPD include muscle wasting, weight 

loss, nutritional abnormalities and congestive heart failure. Because of the 

relationship between COPD and smoking, patients also have other diseases 

that are related to or worsened by smoking such as lung cancer, coronary 

artery disease, stroke, peripheral vascular disease and diabetes. Therefore, 

a comprehensive approach is required when treating COPD patients in order 

to identify and treat all the conditions associated with it and to improve the 

patients’ overall quality of life. 

Chapter 2-5 • Chronic Obstructive Pulmonary Disease (COPD) 

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94 Chapter 2-5 • Chronic Obstructive Pulmonary Disease (COPD) 

Pathology 

COPD affects the three major components of the lungs: the airways which 

consist of multiple generations of branching bronchial tubes, the tissue that 

supports these tubes and contributes to the exchange of gases such as oxygen 

and carbon dioxide, and the blood vessels that surround them. The chronic 

inflammation which underlies the pathologic changes in COPD causes 

structural distortions in the airways and destruction of lung tissue. This leads 

to a decreased number of these gas exchange elements (called alveoli) from the 

rest of the airways and a decrease in the elastic property of the lungs. There is 

also enlargement of the mucus-producing glands, which produce excessive 

mucus and sputum. Another contributing factor to the pathologic changes in 

COPD is an imbalance between the proteins that break down the supporting 

tissue in the lungs and those that protect against it, favoring the destructive 

ones. The end result of all these changes is a decreased ability of the airway to 

remain open during expiration, resulting in airflow limitation, or obstruction. 

In the past, COPD was defined by the terms “emphysema” and “chronic 

bronchitis”. Emphysema is defined by permanent enlargement of the air 

sacs at the end of the branching airways accompanied by destruction of their 

walls, and is really a pathological definition of COPD. This represents one of 

many other changes that occur in patients with COPD. Normally the lungs are 

elastic and have inherent stretchiness and springiness. In emphysema, they 

loose their elasticity and it takes a lot of effort to empty the air out of them. 

Because the lungs do not empty efficiently, they contain more air than normal 

and this produces the air trapping or hyperinflation. Obstruction of airflow 

occurs because the walls of the bronchial tubes are unable to stay open during 

exhalation but rather collapse, preventing the lungs from expelling the air. 

Chronic bronchitis is defined as the presence of cough and sputum production 

for at least three months in each of two consecutive years and which is not due 

to another cause. It is a clinical diagnosis which does not reflect the severity of 

airflow limitation. It develops secondary to constant swelling and irritability 

of the airway tubes with excessive mucus production. Airway obstruction 

occurs in chronic bronchitis because the swelling and excessive mucus cause 

narrowing of the breathing tubes and prevent air from reaching the air alveoli 

and the lungs from emptying fully. Cough and sputum production may precede 

the development of airflow limitation in chronic bronchitis; on the other hand, 

patients with emphysema may have significant airflow limitation without 

chronic cough and sputum. Chronic bronchitis and emphysema are useful 

to define a spectrum of clinical and pathological changes in COPD without 

necessarily placing patients strictly into one or the other category as most 

patients have components of each disease process. 

Natural History 

The natural history of COPD is variable. It usually begins insidiously, without 

the patient being aware of its presence until symptoms become noticeable. 

COPD is generally a progressive disease, especially with continued exposure 

to risk factors such as cigarette smoke or environmental pollutants. Stopping 

exposure can result in some improvement in lung function and can even stop

the progressive decline in lung function, but once it develops, COPD cannot 

generally be cured and must be treated continuously. Treatment can reduce 

symptoms, improve quality of life, reduce exacerbations and may improve 

mortality, but cannot cure the disease. For fire fighters this highlights the 

importance of preventing inhalation exposures whenever possible through 

proper use of SCBA and through longitudinal monitoring of pulmonary 

function at the annual medical or whenever symptoms occur in order to 

identify reductions in lung function in excess of normal aging. 

Clinical Manifestations 

The most common clinical features of COPD are cough, sputum production 

and shortness of breath. Cough is the most frequent symptom reported by 

patients but it is often the breathlessness and decreased exercise tolerance 

that causes them to seek medical attention. Sputum production initially goes 

unnoticed or is described as scant. Later in the course it may become thicker 

and more of a daily problem, being difficult to expectorate, especially in the 

morning hours. Sputum production is also related to smoking status, with 

smokers having much more sputum than nonsmokers. Shortness of breath 

occurs initially with exertion, and as the disease progresses it occurs with less 

and less effort, to such an extent that many patients avoid exertion in order 

to prevent breathlessness and become quite inactive. Eventually activities of 

daily living such as working or even eating may cause symptoms. In addition 

to coughing up infected and discolored sputum, some patients with COPD may 

cough up blood. This typically occurs in patients who have chronic bronchitis 

and in association with an episode of infection. It can also be a manifestation 

of lung cancer, to which this population is susceptible. 

As previously mentioned, patients with COPD also have extrapulmonary 

manifestations of the disease, such as muscle wasting and congestive heart 

failure. Therefore they may appear extremely thin and emaciated, or they 

may have swelling of their extremities (edema) from congestive heart failure. 

Many patients will also have hypoxia, which refers to low oxygen levels, and 

may have a cyanotic or bluish discoloration to their skin, especially their lips 

and nails. Physical examination of the lungs can be normal in some patients. 

In others it may reveal decreased breath sounds or high pitched noises such 

as wheezing or rhonchi (lower raspy noises). The most consistent finding is a 

prolonged expiratory time during which inspired air is being exhaled, and is 

indicative of significant airway obstruction. As patients become breathless 

on minimal exertion or even at rest they will be observed to have purse-lipped 

breathing and sitting forward and leaning on their elbows or supporting their 

upper body with extended arms. 

The natural course of COPD is characterized by periods of stability 

interrupted by an acute worsening of symptoms termed exacerbations, which 

are characterized by cough, shortness of breath and sputum production. These 

episodes are often associated with viral or bacterial respiratory tract infections. 

Overall the progressive nature of the disease and the frequent exacerbations 

result in patients having poor quality of life, and depression is often present. 


95


CLASSIFICATION AND DIAGNOSIS OF COPD 

COPD is classified according to severity by using spirometry to measure lung 

function. The two most useful measures are the forced vital capacity (FVC) and 

the forced expiratory volume in one second (FEV1). These are measurements 

of volume and are obtained by having the patient blow into a flow meter that 

records the volume of air exhaled as well as the rate of flow. For the FVC the 

patient takes a maximal deep breath and then exhales as forcefully and rapidly 

as possible until the lungs cannot empty any further. The FEV1 is the volume of 

air exhaled in the first second of the FVC test, and it is the most reproducible of 

all the lung volumes obtained by spirometry. The reduction in these volumes is 

reflective of the pathological changes in COPD. In emphysema, lung tissue is 

destroyed and lost, and lung elasticity is decreased. The airways are narrowed 

and there is increased resistance to flow. These lead to a decrease in maximal 

flow as reflected by a decrease in FEV1 and to a lesser degree FVC. In chronic 

bronchitis the thick secretions in the airways and the structural distortion 

lead to narrowing of the airway, increased resistance to flow, and decreased 

maximal flow. 

In order to be considered an obstructive pattern as in COPD, the FEV1 to 

FVC ratio should be below 70%, and the FEV1 should be less than 80% of the 

predicted normal value. Even more accurate than expressing lung function as 

percent predicted is identifying whether that lung function is below the lower 

limits of normal (LLN). Use of the LLN to avoid false-diagnosis is especially 

important in older or taller individuals. Spirometry if abnormal should 

then be performed before and after the patient is administered an inhaled 

bronchodilator, with the post-bronchodilator FEV1 and FVC used to classify 

the disease into four stages. 

• Stage I: Mild COPD – characterized by mild airflow limitation (FEV1/FVC 

< .70 or preferably LLN

Spirometric Classification of COPD 

Severity Based on Post-Bronchodilator FEV1 

Stage I: FEV1/FVC < 0.70 or preferably LLN

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different survey methods and variable reporting rates across countries. This is 

generally due to a major under-recognition and under-diagnosis worldwide. As 

such, the prevalence data that exist actually underestimate the total burden of 

COPD because many patients are diagnosed late in the course of the disease. 

This explains why improving awareness of COPD has become such a major 

theme in the field of pulmonary medicine in the last few years. 

In general, the prevalence of COPD is higher in smokers and ex-smokers 

than non-smokers, in men than in women, and in those over forty. The World 

Health Organization estimated that the worldwide prevalence of COPD in 

1990 was 9.34 for every 1,000 men and 7.33 for every 1,000 women. In terms of 

mortality, COPD is currently the fourth leading cause of death in the world, 

and even mortality data underestimate COPD as a cause of death because it 

is more likely to be cited as a contributing factor rather than a cause, or not 

listed at all on the death certificate. Large studies have projected that by the 

year 2020 COPD will be the third leading cause of death worldwide. This is due 

to increased trends in smoking and to more of the population living longer. 

This trend in COPD mortality is in contrast to that seen in three other leading 

causes of death, namely cancer, stroke and heart disease where the death rates 

are on the decline. Mortality rates for women are also rising as women smoke 

more than in the past. Therefore the importance of smoking cessation in the 

management of COPD cannot be overemphasized. 

COPD is a very costly disease with both direct costs (value of healthcare 

resources allocated to diagnosis and medical treatment) and indirect costs 

(financial consequences of disability, missed work, premature death, and 

caregiver costs). In the United States in 2002 direct costs were estimated at 

$18 billion and the indirect costs totaled $14.1 billion. In developing countries 

where financial gain is directly related to human productivity, indirect costs 

have a greater impact on the economic burden of COPD than do direct costs. 

There is a direct relationship between the severity of COPD and costs – the 

sicker the patient, the greater the costs. 

Risk Factors 

Risk factors are identifiable causes that place people at risk for developing a 

disease. Identification of risk factors is important in the design of prevention 

and treatment plans for COPD. COPD risk factors can be classified as genetic 

or environmental, and there is a complex relationship between these factors. 

For example, for two individuals with similar smoking histories, one may 

develop COPD because of different genetic predisposition or longer life span. 

COPD is a disease that is related to multiple genetic abnormalities, but not 

all are required to produce the disease. The best documented genetic defect is 

called alpha-1 antitrypsin deficiency, which is a hereditary defect of a protein 

in the lungs. This protein is involved in repairing the lungs from injury due 

to other destructive proteins. When there is an imbalance between injury 

and repair, as in alpha-1 antitrypsin deficiency, premature and accelerated 

development of emphysema may occur. There is considerable variability 

among individuals with this risk factor in the severity of COPD and decline in 

lung function, and smokers are at even greater risk. This is a good example of 

how genetic and environmental factors interact to produce the final outcome 

of disease in individuals.

Another risk factor in the development of COPD is inhalational exposure 

of noxious particles. Cigarette smoke is by far the most common risk factor. 

It is estimated that 15-20% of smokers develop clinically significant COPD, 

but this is likely an underestimation as many more will develop abnormal 

lung function if they continue to smoke. Cigar and pipe smokers are also at 

risk, but not as great as cigarette smokers. The risk for cigarette smokers is 

related to total number of packs smoked, age at starting to smoke and current 

smoking status, however some smokers may never develop COPD, suggesting 

that genetic factors play a role in modifying the risk. Exposure to secondhand 

smoke should also be considered in the evaluation of patients with COPD. In 

the surgeon general’s latest report in 2006 on the effects of secondhand smoke 

in relation to COPD, it stated that “the evidence is suggestive but not sufficient 

to infer a causal relationship between secondhand smoke exposure and risk 

for chronic obstructive pulmonary disease.” It went on to state that “the 

evidence is inadequate to infer the presence or absence of a causal relationship 

between secondhand smoke exposure and morbidity in persons with chronic 

obstructive pulmonary disease.” In other words, secondhand smoke may 

be a risk factor for COPD, but in those who already have COPD it is unclear 

whether secondhand smoke can cause any further lung damage. Despite the 

progress that has been made in reducing exposure to secondhand smoke, 60% 

of American nonsmokers still have evidence of secondhand smoke exposure. 

Other inhalational exposures include occupational dusts and chemical 

fumes, which are linked to the development of disease in fewer than 10 - 20% of 

patients with COPD. This is especially true for fire fighters. In other countries, 

there is increasing evidence that indoor air pollution from burning biomass 

fuels in poorly ventilated areas may also be a risk factor for COPD. The role 

of outdoor air pollution in causing COPD is also important, but appears to be 

small when compared to cigarette smoking (Figure 2-5.1). 

COPD Risk is Related to the Total Burden of 

Inhaled Particles 

Cigarette Smoke 

Occupational Dust and Chemicals 

Environmental Tobacco Smoke (ETS) 

Indoor and Outdoor Air Pollution 

Figure 2-5.1: Inhaled Particles and COPD Risk 3 


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A few other risk factors deserve mention, such as lung growth during gestation 

and in childhood. Any process that affects lung maturation during this time 

can increase one’s risk for COPD. A history of repeated childhood respiratory 

infections plays a role in the development of reduced lung function, and may 

possibly be a risk factor for COPD. The role of gender in COPD risk is unclear. 

Previous studies have shown that COPD prevalence and mortality were 

greater in men. However, now that women are smoking more the prevalence 

is almost equal. Women are also more susceptible to the effects of cigarette 

smoking, which will likely have a further effect on prevalence and mortality 

rates. Poor socioeconomic status is related to the development of COPD, but 

it is unknown whether this is due to the effects of pollution and malnutrition 

(which is an independent risk factor for COPD). Finally, asthma may be a risk 

factor although the evidence is inconclusive. Many patients with asthma 

may develop inflammation similar to that in COPD, especially in asthmatics 

who smoke. One report on the course of patients with obstructive airways 

disease found that asthmatics had a 12-fold higher risk of acquiring COPD 

than those without asthma, after adjusting for smoking status. Therefore, it 

can sometimes be difficult to distinguish between the two diseases, referring 

to patients simply as having asthma/COPD. 

MANAGEMENT 

Effective COPD treatment includes four components: assess and monitor 

disease; reduce risk factors; manage stable COPD; manage exacerbations. 

The goals of COPD management are to: prevent disease progression, relieve 

symptoms, improve exercise tolerance, improve health status, prevent and 

treat complications, prevent and treat exacerbations, and reduce mortality. 

A diagnosis of COPD should be assessed in anyone who has cough, sputum 

production, shortness of breath or exposure to risk factors for the disease. A 

key component in disease assessment is educating patients, physicians and 

the public that these symptoms should be evaluated seriously. Patients should 

be identified as early as possible in the course of the disease and spirometry 

should be available to healthcare providers to confirm the diagnosis. In addition 

to spirometry, patients should have a complete physical examination, chest 

x-ray, and measurements of oxygen levels. Follow-up visits should include a 

discussion of new or worsening symptoms, inquiries about exposure to risk 

factors, monitoring for complications, and assessment of lung function (Figure 

2-5.2).

Key Indicators for Considering a Diagnosis of COPD 

Consider COPD, and perform spirometry, if any of these indicators are present in an individual over 

age 40. These indicators are not diagnostic themselves, but the presence of multiple key indicators increases 

the probability of a diagnosis of COPD. Spirometry is needed to establish a diagnosis of COPD. 

Dyspnea that is: 

Progressive (worsens over time) 

Usually worse with exercise 

Persistent (present every day) 

Described by the patient as an "increased effort to 

breath", "heaviness", "air hunger" or "gasping" 

Chronic Cough: May be intermittent and may be unproductive 

Chronic Sputum Production: 

History of Exposure to Risk 

Factors, especially: 

Figure 2-5.2: COPD and Key Indicators 3 

Any pattern of chronic sputum production may 

indicate COPD 

Tobacco smoke 

Occupational dusts and chemicals 

Smoke from home cooking and heating fuels. 

COPD is a progressive disease and the patterns of symptom development are 

well established. In mild COPD, cough and sputum production can be present 

for many years before the development of airflow limitation, and symptoms are 

often ignored by patients. In moderate COPD, patients experience breathlessness 

which may interfere with their daily activities. This is the stage at which they 

seek medical attention and may be diagnosed with COPD. Some patients do 

not have any of these symptoms and only come to attention when airflow 

limitation becomes so severe that they cannot breathe, often at times of an 

acute pulmonary infection or a cardiac event. This is the stage where patients 

are at risk for developing chronic respiratory failure, congestive heart failure, 

muscle wasting, and where oxygen levels become limiting (Figure 2-5.3). 


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Suggested Questions for Follow-Up Visits 

Monitor exposure to risk factors: 

Has your exposure to risk factors changed since your last visit? 

• Since your last visit, have you quit smoking, or are you still smoking? 

• If you are still smoking, how many cigarettes/how much tobacco per day? 

• Would you like to quit smoking? 

• Has there been any change in your working environment? 

Monitor disease progression and development of complications: 

• How much can you do before you get short of breath? 

• (Use an everyday example, such as walking up flights of stairs, up a hill, or on flat 

ground.) 

• Has your breathlessness worsened, improved, or stayed the same since your last 

visit? 

• Have you had to reduce your activities because of your breathing or any other symptom? 

• Have any of your symptoms worsened since your last visit? 

• Have you experienced any new symptoms since your last visit? 

• Has your sleep been disrupted by breathlessness or other chest symptoms? 

• Since your last visit, have you missed any work/had to see a doctor because of your 

symptoms? 

Monitor pharmacotherapy and other medical treatment: 

What medicine are you taking? 

How often do you take each medicine? 

• How much do you take each time? 

• Have you missed or stopped taking any regular doses of your medicine for any 

reason? 

• Have you had trouble filling your prescriptions (e.g., for financial reasons, not on 

formulary)? 

• Please show me how you use your inhaler. 

• Have you tried any other medicines or remedies? 

• Has your treatment been effective in controlling your symptoms? 

• Has your treatment caused you any problems? 

Monitor exacerbation history: 

• Since your last visit, have you had any episodes/times when your symptoms were a 

lot worse than usual? 

• If so, how long did the episode(s) last? What do you think caused the symptoms to 

get worse? What did you do to control the symptoms? 

Figure 2-5.3: COPD and Follow-Up Visits3 The second component in the management of COPD is the identification, 

reduction and control of risk factors (Figure 2-5.4 and Figure 2-5.5). For 

fire fighters, prevention is the focus through a mandatory SCBA program 

and longitudinal monitoring of pulmonary function at the annual medical 

examination or whenever symptoms occur in order to identify reductions 

in lung function in excess of normal aging. In those that are tobacco users, 

smoking prevention and cessation programs are of equal importance. Smoking 

cessation is the single most effective and cost-effective way to reduce the risk 

of developing COPD and to stop its progression. Tobacco is addictive and leads 

to dependence, in most cases requiring pharmacologic therapy to overcome 

it. This comes in the form of nicotine replacement (gum, patch, inhaler, nasal 

spray, sublingual tablet, or lozenge) or the antidepressant bupropion. Another 

medication which was recently introduced is varenicline, functioning as a

nicotine replacement. Tobacco cessation programs and medications are 

discussed in a separate chapter in this book. 

ASK: 

ADVISE: 

ASSESS: 

ASSIST: 

ARRANGE: 

Brief Strategies to Help the Patient Willing to Quit 

Systematically identify all tobacco users at every visit. 

Implement an office-wide system that ensures that, for EVERY patient at 

EVERY clinic visit, tobacco-use status is queried and documented. 

Strongly urge all tobacco users to quit. 

In a clear, strong, and personalized manner, urge every tobacco user to 

quit. 

Determine willingness to make a quit attempt. 

Ask every tobacco user if he or she is willing to make a quit attempt at 

this time (e.g., within the next 30 days). 

Aid the patient in quitting. 

Help the patient with a quit plan; provide practical counseling; provide 

intra-treatment social support; help the patient obtain extra-treatment 

social support; recommend use of approved pharmacotherapy except in 

special circumstances; provide supplementary materials. 

Schedule follow-up contact. 

Schedule follow-up contact, either in person or via telephone. 

Figure 2-5.4 Tobacco Quit Strategies 3 ) 

US Public Health Service Report: 

Treating Tobacco Use and Dependence; A Clinical Practice Guideline -- Major Findings and 

Recommendations 

1. Tobacco dependence is a chronic condition that warrants repeated treatment until long-term 

or permanent abstinence is achieved. 

2. Effective treatments for tobacco dependence exist and all tobacco users should be offered 

these treatments. 

3. Clinicians and health care delivery systems must institutionalize the consistent identification, 

documentation, and treatment of every tobacco user at every visit. 

4. Brief smoking cessation counseling is effective and every tobacco user should be offered such 

advice at every contact with health care providers. 

5. There is a strong dose-response relation between the intensity of tobacco dependence 

counseling and its effectiveness. 

6. Three types of counseling were found to be especially effective: practical counseling, social 

support as part of treatment, and social support arranged outside of treatment. 

7. Five first-line pharmacotherapies for tobacco dependence – bupropion SR, nicotine gum, 

nicotine inhaler, nicotine nasal spray, and nicotine patch – are effective and at least one of 

these medications should be prescribed in the absence of contraindications. 

8. Tobacco dependence treatments are cost effective relative to other medical and disease 

prevention interventions. 

Figure 2-5.5: Treating Tobacco Use and Dependence3 Counseling is especially effective in smoking cessation and includes the 

following strategies: strongly advise all smokers to quit; determine willingness 

to attempt quitting; assist the patient in quitting by providing practical 

Chapter 2-5 • Chronic Obstructive Pulmonary Disease (COPD) 103


counseling, social support and medications. There is a strong positive relationship 

between the intensity of counseling and cessation success. Even short periods 

of counseling can achieve cessation rates of 5-10%. Occupational exposures 

can be reduced by efforts to control and monitor exposure in the workplace. 

Reducing the risk of indoor and outdoor pollution requires protective steps 

taken by individual patients and initiatives by public policy-makers. Regulation 

of air quality is an important aspect of this initiative. 

The third component in the management of COPD is the treatment of 

stable disease which requires a multidisciplinary approach including 

patient education, medication, oxygen therapy, rehabilitation and exercise, 

vaccination, and surgery. Patient education is important in improving coping 

skills, medication compliance, smoking cessation, and patient responses to 

exacerbations. Because most medical regimens include inhaled pumps which 

can be difficult to use, proper education on inhaler technique is essential to 

achieve medication effectiveness. Education about the progressive nature 

of COPD is necessary in order to have discussions on end-of-life issues with 

patients who have severe disease and do not wish for aggressive care at the 

end of their life. 

Medical treatment of stable COPD is used to prevent and control symptoms, 

reduce the frequency and severity of exacerbations, improve health status, 

and improve exercise tolerance. Most of the medications do not modify the 

long-term decline in lung function, however this should not deter patients 

from using them. The two main classes of medications are bronchodilators 

and inhaled steroids. Bronchodilators are inhaled medications that widen the 

airways by targeting protein receptors in the airways. They relax the muscles 

surrounding the airways that tend to maintain them in a narrower position. 

Consequently these drugs dilate the airway, improve emptying of the lungs, 

reduce air trapping at rest and during exercise and allow people with COPD to 

breathe better. The actual changes in FEV1 are smaller than the clinical effects. 

The two principal bronchodilators are the beta-agonists and the anticholinergics. 

They differ in their protein receptor targets but both achieve the same airway 

widening. Some of the inhalers work for a short period of time while others last 

for many hours. For patients with mild and intermittent symptoms, inhalers 

are prescribed for as-needed usage, but as symptoms progress patients are 

instructed to take them on a regular basis. Regular use of the long-acting 

bronchodilators is more effective and convenient than treatment with shortacting 

bronchodilators. Long-acting bronchodilators should be taken with 

inhaled steroids. A combination inhaler containing both a beta-agonist and an 

anticholinergic may produce additional improvements in lung function than 

taking either alone. A combination also leads to fewer exacerbations than either 

drug alone. In the last few years a new long acting, once daily anticholinergic 

appeared on the market called Tiotropium. This drug was a welcome addition 

to the bronchodilators because of its convenient dosing and relatively easy use. 

Compared to other anticholinergics, studies have shown that Tiotropium is more 

effective in improving breathlessness, reducing frequency of exacerbations, 

slowing the decline in lung function over one year as measured by FEV1, and 

improving quality of life. Studies have further demonstrated that compared to 

long acting beta-agonists, Tiotropium was better at improving lung function 

as measured by FEV1. Patients should be aware that these medications do

have occasional side effects. The main side effects with beta-agonists include 

increased heart rate, possible heart rhythm disturbances and a hand tremor. 

The main side effects reported for anticholinergics are mouth dryness and a 

bitter, metallic taste in the mouth. 

Inhaled steroids are another mainstay in the treatment of stable COPD. 

They do not modify the decline in lung function over time, however regular 

treatment is appropriate for patients with severe and very severe COPD (stage 

III and IV) to reduce inflammation in the bronchial tubes, exacerbations and 

therefore improve quality of life. Combination inhalers containing steroids 

and long-acting beta-agonists are more effective than using both components 

individually. It is not recommended to use steroid pills to treat COPD on a 

continuous basis, as effectiveness has not been definitively proven in clinical 

trials and there are too many side effects, especially in the elderly patients. 

The use of oral or intravenous steroids for exacerbations however is usually 

necessary. 

Patients with COPD have frequent exacerbations which can be associated 

with viral and bacterial respiratory tract infections. Therefore an extremely 

critical part of maintenance therapy is vaccination for influenza and pneumonia. 

Pulmonary rehabilitation is another aspect of COPD management. This 

consists of exercise training, nutrition counseling, and education. Some of the 

benefits of pulmonary rehabilitation include: improving exercise tolerance and 

quality of life, reducing breathlessness and the frequency of exacerbations, and 

diminishing the occurrence of anxiety and depression associated with COPD. 

There may be some benefit on survival, but the studies are somewhat lacking. 

The only treatment which has been proven unequivocally to improve survival 

is oxygen therapy when given on a long-term and continuous basis. Oxygen is 

generally indicated when the blood oxygen level drops below a certain level 

at rest or during exercise, or if congestive heart failure is present. 

Surgery is a controversial issue in the treatment of COPD. Some studies 

have reported success in removing damaged parts of the lungs but it was 

limited to select patients. Much more information is required before surgery 

is incorporated as a mainstay of COPD management. In patients with very 

severe emphysema, lung transplantation can improve quality of life and 

general ability to function, but survival benefit may disappear after two years. 

Exacerbations are important events in the course of COPD. The most common 

cause of an exacerbation is infection, bacterial or viral, and therefore antibiotics 

are part of the treatment plan. Intravenous steroids are also beneficial because 

they shorten recovery time and help to restore lung function more quickly. Sicker 

patients often require oxygen during this time and for a few weeks to months 

following the episode. Of course patients continue to take bronchodilators, 

although they are usually administered in a humidified form. Finally, when 

patients are in respiratory failure they may require placement on a mechanical 

ventilator (discussed further in another chapter). 

Chapter 2-5 • Chronic Obstructive Pulmonary Disease (COPD) 105

106 Chapter 2-5 • Chronic Obstructive Lung Disease (COPD) 

SUMMARY 

In summary, COPD is a progressive disease of airflow obstruction characterized 

by the symptoms of cough, shortness of breath especially on exertion, and 

excessive sputum production. It is the fourth leading cause of death in the 

world today with projections for increased mortality over coming years. COPD 

is preventable and therefore strategies aimed at prevention must focus on 

minimizing occupational and environmental exposures, smoking cessation, 

and a pulmonary function monitoring program performed at annual medical 

examinations in order to identify early but significant changes in lung function. 

Treatment plans are multifaceted, focusing on amelioration of symptoms and 

slowing the unavoidable decline in lung function, with the ultimate goal being 

to maintain quality of life. 

REFERENCES 

1. Pauwels RA, Buist AS, Calverley PMA, Jenkins C, Hurd SS, the GOLD 

Scientific Committee. Global strategy for the diagnosis, management, 

and prevention of chronic obstructive pulmonary disease. NHLBI/WHO 

Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop 

summary. Am J Respir Crit Care Med 2001;163:1256-1276. 

2. Celli BR, MacNee W, committee members. Standards for the diagnosis 

and treatment of patients with COPD: a summary of the ATS/ERS position 

paper. Eur Respir J 2004;23:932-946. 

3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy 

for the diagnosis, management, and prevention of Chronic Obstructive 

Lung Disease. 2006. Available from: www.goldcopd.org. 

4. The health consequences of involuntary exposure to tobacco smoke. A report 

of the surgeon general. 2006. Available from: URL: www.surgeongeneral. 

gov. 

5. Casaburi R, Conoscenti CS. Lung function improvements with oncedaily 

tiotropium in chronic obstructive pulmonary disease. Am J Med 

2004;117:33S-40S. 

6. Vincken W and van Noord JA et al. Improved health outcomes in patients 

with COPD during 1 year’s treatment with tiotropium. Eur Respir J 

2002;19:209-216. 

7. Shapiro SD, Snider GL, Rennard SI. Chronic bronchitis and emphysema. 

In: RM Mason, JF Murray, VC Broaddus, JA Nadel, editors. Textbook of 

Respiratory M, Medicine, 4th ed. Elsevier Saunders; 2005. p. 1115-1167. 

8. GSK Press Release “GSK announces positive results of Seretide study in 

patients with chronic obstructive pulmonary disease” March 28th 2006. 

Available from: URL: www.gsk.com/media/pressreleases.htm.

Chapter 2-6 

Sarcoidosis 

By Dr. David Prezant, MD 

Sarcoidosis is a multiorgan system inflammatory disorder that typically occurs 

in early adulthood. 1,2 It can affect almost any organ, with over 90% of cases 

having involvement of the lungs and intra-thoracic lymph nodes. These lymph 

nodes are located in 3 areas of the chest – hilar, mediastinal and paratracheal, 

which when involved are engorged with inflammatory cells leading to their 

enlargement. This is referred to as adenopathy or lymphadenopathy. Extrathoracic 

involvement may be evident in as many as 52% of cases. 1,3 Other 

organs frequently involved are the skin and eyes. Less than 10% of the cases 

involve other organs (heart, liver, brain, nerves, endocrine glands, bones, 

joints, etc.). Figure 2-6.1 is a photomicrograph of biopsy material from an 

involved organ and shows a non-caseating or non-necrotizing granuloma 

(an epitheloid cell surrounded by a rim of lymphocytic inflammatory cells 

and fibroblasts). Non-caseating granulomas are formed by an unfettered 

immune response involving inflammatory cells – specifically T-lymphocyte 

helper cells (TH1) producing cytokines (ex. interferon-y, interleukin-2, and 

tumor necrosis factor) that attract greater numbers of inflammatory cells. 1 

Figure 2-6.1: Microscopic image of a Granuloma – The Classic Pathologic Biopsy Finding 

in Sarcoidosis 

Criteria needed for the diagnosis of sarcoidosis include (1) a clinical and 

radiographic picture compatible with the diagnosis; (2) biopsy proven evidence 

of non-caseating granulomas; and (3) exclusion of other conditions that can 

produce similar pathology, including lymphoma, infections (tuberculosis 

Chapter 2-6 • Sarcoidosis 

107

108 Chapter 2-6 • Sarcoidosis 

or fungal), autoimmune diseases or rheumatologic diseases (Wegeners, 

Lupus, Sjogren’s syndrome, etc.) and inhalational diseases (hypersensitivity 

pneumonitis or foreign body reactions). 1-3 

In this chapter, we will review the basic epidemiology of sarcoidosis (prevalence 

rates in different populations), symptoms, organs involved, prognosis and 

treatment. We then conclude by discussing existing evidence for an increased 

rate of disease in certain occupations such as firefighting. 

Sarcoidosis occurs worldwide. The exact cause is unknown but it is unlikely 

that sarcoidosis is caused by a single agent or antigen. The current hypothesis 

is that sarcoidosis is an autoimmune disease that results from a variety of 

genetic-environmental interactions that have yet to be characterized. Genetic 

influences appear to play a role because sarcoidosis is more common in African- 

Americans and Hispanics of Puerto Rican descent than among Caucasians or 

Asians. 4- 10 Tobacco smoke is not associated with an increased prevalence rate 

of sarcoidosis. 1,4 Infections (Atypical Mycobacterium, Chlamydia, viruses and 

others) were thought to be potential causative agents. However, tissue analysis, 

culture, and molecular identification methods have not supported infection 

as a likely mechanism. Environmental agents that do appear to be associated 

with increased prevalence rates include microbial bioaerosols, pesticides, wood 

burning stoves (wood dust or smoke), 11 chemical dust, 12 man-made fibers, 13 

silica, 14 and metals. 15 One particular metal deserves special mention. Chronic 

beryllium exposure produces a disease that is clinically, radiographically and 

pathologically indistinguishable from sarcoidosis. 16 Most cases of sarcoidosis 

have no evidence for beryllium exposure by either history or laboratory testing 

(beryllium lymphocyte proliferation blood test). When evidence for beryllium 

sensitivity is present then the disease is no longer called sarcoidosis and is 

instead called berylliosis. 

Diagnosis typically occurs in adults between age 20 and 50, but rarely can 

occur in children or the elderly. 1-4 It affects males and females, with a slightly 

greater prevalence rate in females. Although sarcoidosis has been reported 

in identical twins, it is not felt to be hereditary. In the US, prevalence rates 

vary from 1 to 40 per 100,000. 4, 9-10 Race and ethnicity have strong affects on 

prevalence rates. 9 Worldwide, in Caucasians prevalence rates average 10 per 

100,000 with the highest rates in Northern Europe but none as high as found in 

African-Americans ranging from 35 to 64 cases per 100,000. 4-10 In the United 

States, prevalence rates range from 2.5 to 7.6 per 100,000 for Caucasian males 

and from 13.2 to 81.8 per 100,000 for African-American males. 4, 9-10 In New York 

City (NYC), prevalence rates may be as high as 17 per 100,000 for Caucasians 

and 64 per 100,000 for African Americans. 10 Without doubt, these published 

rates underestimate the true prevalence as most individuals are asymptomatic 

and remain undiagnosed unless chest radiography was performed. In fact, the 

highest prevalence rates are found in populations receiving mandatory chest 

radiographs as part of an occupational or tuberculosis screening program. 

Because over 90% of sarcoidosis patients have lung involvement and most 

are asymptomatic, the typical clinical presentation is patients referred for 

evaluation of an abnormal chest radiograph that suggests sarcoidosis, but may 

less commonly be due to lymphoma or rarely tuberculosis. Patients may also 

present with symptoms related to the specific organ(s) involved17,18 , which for

the lung would be shortness of breath with or without cough. Sometimes these 

symptoms are not related to a specific organ and are termed “constitutional 

symptoms” such as fatigue, fever, and weight loss (with or without loss of 

appetite). When symptomatic, the clinical presentation is usually that of 

insidious onset over months to years but may also be acute in onset. When 

acute, patients may present with a classic constellation of symptoms called 

Lofgren’s syndrome which includes: fever, swollen lymph nodes within the 

chest (bilateral hilar and mediastinal adenopathy), erythema nodosum (painful 

red bumps on the lower anterior legs) and arthritis (multiple joints but most 

commonly both ankles). Generally, acute disease has a good prognosis with 

spontaneous resolution being a frequent outcome. Chronic disease is found 

more often in symptomatic patients with insidious onset and multiorgan 

involvement. Exacerbations and relapses are more common in patients with 

chronic sarcoidosis and are typically treated with oral corticosteroids (see 

treatment section below). 

How is the diagnosis of sarcoidosis confirmed? Laboratory test results can 

support the diagnostic impression but cannot confirm it. Such data includes: 

elevated lymphocytes in lung lavage fluid, elevated angiotensin converting 

enzyme (ACE) levels in the blood, positive gallium scan, or anergy (absence 

of skin sensitization to common allergens). It is generally recommended 

that patients with sarcoidosis have biopsy confirmation of their diagnosis. 

Transbronchial lung biopsy is usually the procedure of choice and yields a 

diagnosis in the majority of cases. Other options for obtaining tissue: biopsy 

of the mediastinal lymph nodes by mediastinoscopy, bronchoscopy or 

gastroesophageal endoscopy, video-assisted thoracoscopic lung biopsy, and 

rarely surgical open-lung biopsy. In some patients who have typical clinical 

and radiographic features and who have other organ involvement (ex. skin 

nodules, or eye, sinus or salivary gland symptoms), biopsies can be obtained 

less invasively from these extra-thoracic organs. 

Chest radiographs in sarcoidosis are classified as Stage 0 through Stage IV. 19 

It is important to realize that chest radiographic staging does not correspond 

to the chronologic progression of disease. Patients may present at any stage 

of radiographic disease. The term Stage 0 is reserved for the rare group who 

present with only extra-thoracic organ involvement and have a normal chest 

radiograph. This group has a low likelihood of disease progression. Stage I chest 

radiographs are the most common and show bilateral hilar and mediastinal 

adenopathy without obvious lung involvement (Figure 2-6.2). However, the 

majority of these patients do have microscopic lung involvement with positive 

diagnostic findings on transbronchial lung biopsies. Also the majority of 

these patients will demonstrate spontaneous resolution of their disease 

without relapse. Stage II radiographs show bilateral hilar and mediastinal 

adenopathy along with lung infiltrates and/or nodules (Figure 2-6.3). 

Stage III radiographs show lung infiltrates and/or nodules without hilar or 

mediastinal adenopathy (Figure 2-6.4). Although less likely than in Stage I, 

spontaneous remission may still be possible in Stage II and III disease. Stage 

IV radiographs show bilateral lung fibrosis (scarring) mostly in the upper and 

middle lobes of the lung (Figure 2-6.5). Once fibrosis is present, spontaneous 

remission can no longer occur and these patients have the worse prognosis. 


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110 


Figure 2-6.2: Chest radiograph of Stage I Sarcoidosis – enlarged lymph nodes (arrows) 

Figure 2-6.3: Chest radiograph of Stage II Sarcoidosis – enlarged lymph nodes (arrow 

pointing up) and involvement of lung tissue (arrow pointing down) 

Figure 2-6.4: Chest radiograph of Stage III Sarcoidosis – involvement of lung tissue (arrows) 

without swollen lymph nodes

Figure 2-6.5: Chest radiograph showing Stage IV Sarcoidosis with fibrosis and cavities 

The most common manifestation of pulmonary sarcoidosis is granulomatous 

involvement of lung tissue at the alveolar level. 1,17,18 This is where gas exchange 

occurs and once considerable involvement occurs, there are reductions in lung 

volumes, and oxygen diffusion from the alveolar membrane to the red blood 

cells becomes impaired leading to low oxygen levels in the blood (hypoxemia). 

Endobronchial involvement (granulomas in the airways) may also occur. 

Patients with endobronchial involvement have intractable cough and may 

have asthma-like disease with airflow limitation and wheezing. In contrast, 

necrotizing sarcoidosis is a rare form of the disease and refers to the presence of 

cavitation on radiographic imaging and necrosis with granulomatous vasculitis 

on pathology. Patients may be asymptomatic or may have nonspecific symptoms 

(fever, fatigue, and weight loss) and pulmonary symptoms (shortness of breath, 

cough and chest pain). Most patients respond to steroids. Other pulmonary 

manifestations include various forms of pleural disease, including pleural 

effusion (fluid between the lung and chest wall), pleural thickening, pleural 

nodules, and pneumothorax (rupture of the lung). High-resolution CT has 

improved the detection of pleural disease, especially pleural thickening and 

pleural nodules, which may be found in anywhere from 20 - 75% of patients. 

Effusions are less common and resolve spontaneously or with steroid therapy. 

Pneumothorax is an extremely rare complication. 

Pulmonary function may be normal, even with stage I, II or III radiographic 

abnormalities, or may demonstrate restriction or obstruction, with or without 

abnormal gas exchange (reduction in oxygenation). The most frequent pulmonary 

function finding is normal function, but when abnormalities occur, they 

typically show a restrictive physiology with reduced lung volumes (the vital 

capacity and total lung capacity) and reduced gas exchange (diffusing capacity 

and oxygen saturation). In general, gas exchange abnormalities provide the 

best indication for the need for treatment (see below). 

Although the lung is the most common site of involvement, it is not uncommon 

for other organs to be involved and in fact confidence in the diagnosis of 

sarcoidosis increases when extra-pulmonary involvement is found. 17,18 Skin 

involvement, occurs in about a quarter of patients, with the most common 

lesion being erythema nodosum on the anterior surface of the lower legs. 


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112 


Other skin findings may occur and when necessary skin involvement can 

be proven by a skin punch biopsy done by a dermatologist. Eye involvement 

occurs in 10 - 80% of sarcoidosis patients. The most common presentation is 

uveitis and typical symptoms include pain, redness, photophobia (avoidance 

of light), and lacrimation (increased tears). Other eye problems include 

conjunctivitis, hemorrhage, cataracts, glaucoma, and retinal ischemia. Eye 

findings may be confused with another autoimmune disease – Sjogren’s 

syndrome. Annual ophthalmologic evaluation is recommended as blindness 

is a rare but preventable complication. 

Clinically significant cardiac involvement is rare but is difficult to diagnose. 

Unfortunately, the diagnosis is commonly made when a patient presents with 

sudden death from ventricular arrhythmias or complete heart block and this 

appears to have been the case in a recent National Institute for Occupational 

Safety and Health (NIOSH) fire fatality investigation. 20 For this reason, we 

recommend a cardiac evaluation in every patient, especially fire fighters, after 

sarcoidosis is first diagnosed. For fire fighters, we believe this should include 

an electrocardiogram and imaging at rest and stress. Electrocardiograms 

may show evidence of electrical conduction abnormalities and arrhythmias. 

Echocardiogram imaging may show evidence for cardiomyopathy (enlarged 

heart with abnormal function), dilation, decreased ejection fraction, or wall 

motion abnormalities. Radionuclide imaging studies (thallium, gallium, 

or technetium) and cardiac MRI may be even more accurate at revealing 

abnormalities. 

Other organs are even less commonly involved but when inflamed may 

present with salivary and parotid gland enlargement, chronic rhinosinusitis, 

extra-thoracic adenopathy (cervical, axillary, epitrochlear, and inguinal 

areas), liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), 

anemia, or arthritis. Neurologic involvement (central or peripheral) occurs 

in less than 10% of patients and if symptomatic may present with headaches, 

fatigue, unilateral facial nerve paralysis or muscle weakness. Endocrine 

or hormonal abnormalities are rare and may involve any endocrine gland, 

especially the pituitary gland. Abnormal calcium metabolism may result from 

increased vitamin D activation producing elevated calcium levels in the blood 

(hypercalcemia) and urine (hypercalcuria). Untreated, elevated calcium levels 

may lead to renal stones and eventually renal failure. 

The clinical impact of sarcoidosis depends on which organs are involved 

and the extent of the granulomatous inflammation. Once the diagnosis is 

confirmed the patient should be evaluated as to the extent and severity of disease 

and then followed at regular intervals. Symptoms should prompt evaluation 

of the relevant organ(s) and treatment would be based on the severity of that 

involvement. Even if asymptomatic, all sarcoid patients should have their lungs, 

eyes, heart and calcium levels evaluated at the time of initial diagnosis and 

probably annually thereafter. This evaluation should include chest imaging 

(radiographs or CT), pulmonary function tests (flow rates, volumes, diffusion 

and oxygen levels), eye exam by an ophthalmologist, electrocardiogram (with 

cardiac imaging initially and when clinically indicated), and calcium levels 

(blood and urine). 

Treatment of sarcoidosis is indicated when organ dysfunction is clinically 

significant. 1 Oral corticosteroids are first-line therapy. Inhaled corticosteroids

have little effect unless there are asthma-like symptoms. In sarcoidosis, oral 

corticosteroids are used to improve function of the involved organ (assessed 

by pulmonary function tests and oxygen levels) thereby, providing symptom 

relief and an improved quality of life while possibly preventing disease 

progression. However, these goals must be balanced by the potential for 

serious side effects from the long-term use of corticosteroids and the lack of 

certainty that disease progression can be influenced over the long-term. For 

this reason, it is not recommended to treat asymptomatic patients with minimal 

organ involvement (ex. patients with Stage 1 or Stage II radiographic sarcoid 

and normal pulmonary function tests). Indications for treatment with oral 

corticosteroids would include lung involvement with impaired gas exchange 

(reduced diffusion and hypoxemia), eye disease that has failed to improve 

with topical treatment, cardiac involvement (e.g., cardiomyopathy or serious 

arrhythmias), elevated calcium levels (blood or urine) with recurrent kidney 

stones or renal insufficiency; disfiguring skin lesions, severe platelet deficiency 

with bleeding, severe liver insufficiency, and/or incapacitating bone, muscle 

or neurologic involvement. A typical starting dose is 40 mg of prednisone, 

or its equivalent, daily or on alternate days. Patients are followed carefully 

and those with objective improvement begin to gradually and slowly taper or 

reduce their corticosteroid dose over the next 6 to 12 months to as low a level 

as tolerated without return of symptoms or organ dysfunction. Many patients 

will have a good clinical response and objective measures of improved organ 

function, allowing corticosteroids to be discontinued. Unfortunately, some 

have relapses requiring repeat corticosteroid treatment. In some patients, 

either during initial treatment or re-treatment with corticosteroids, side effects 

are intolerable or treatment response is inadequate. These patients qualify for 

second-line immunosuppressive drugs. Hydroxychloroquine is a first-line 

or second-line drug used when sarcoidosis is the cause of isolated skin, bone 

or calcium problems. Methotrexate is a second-line drug used alone or as a 

steroid-sparing agent. It may take up to six months to demonstrate a treatment 

effect. Recently, a new class of medication (TNF antagonists) has been used in 

patients unresponsive to steroids and methotrexate. Rarely, (approximately 1% of 

patients) develop severe life-threatening pulmonary disease (severe hypoxemia 

and pulmonary hypertension) despite aggressive use of immunosuppressive 

medications and may be candidates for lung transplantation. 

Is the prevalence of sarcoidosis increased in fire fighters? Occupational 

clusters of sarcoidosis are not unknown and have been reported in nurses, 21 

United States Navy enlisted men serving on aircraft carriers, 22,23,24 teachers, 25 

automobile manufacturers, 25 retail industry workers, 25 and as previously 

mentioned beryllium workers. 16 In 1993, Kern was the first to report a cluster 

of three cases in fire fighters from Rhode Island. 26 In 1996, Prezant and coworkers 

reported an increased rate of sarcoidosis in fire fighters from the Fire 

Department City of New York (FDNY), the largest fire department in the world 

employing nearly 11,500 fire fighters and fire officers. 27 In 2006, using this 

previously published prevalence rate as a baseline, Prezant and coworkers 

reported an even higher rate of sarcoidosis in FDNY fire fighters exposed to 

World Trade Center Dust. 28 

Case ascertainment for the identification of FDNY fire fighters with sarcoidosis 

involved five pathways. 27,28 First, a chart review of all currently employed 

FDNY fire fighters was completed to identify fire fighters with sarcoidosis 


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114 


prior to the start of our prospective study in 1985. Second, beginning in 1985, 

all FDNY fire fighters with signs or symptoms of pulmonary disease were 

referred to a pulmonary specialist at the FDNY Bureau of Health Services for 

prospective evaluation, database collection and when indicated, treatment. 

Third, all chest radiographs taken at FDNY were prospectively reviewed. This 

review was accomplished as follows: (a) all films were routinely interpreted by a 

board-certified radiologist without knowledge that a study was underway; and 

(b) if the radiographic findings as evaluated by the radiologist were abnormal, 

the chest radiograph was reviewed by our board-certified pulmonologist, 

who was aware that a pulmonary surveillance study (for all lung disease, not 

just sarcoidosis) was underway. FDNY fire fighters have a chest radiograph as 

part of their FDNY pre-employment evaluation and then on an average threeyear 

cycle as part of their FDNY IAFF wellness medical evaluation. Fourth, 

all disability leave and retirement applications were reviewed for sarcoidosis 

cases. Finally, health and safety representatives of the unions representing 

FDNY fire fighters were told of this initiative and of our interest in evaluating 

fire fighters with sarcoidosis. In 1995 an additional group of FDNY Emergency 

Medical Services (EMS) healthcare workers (emergency medical technicians 

and paramedics) were included in the study. In 2001, disease surveillance for 

sarcoidosis continued under the auspices of the FDNY World Trade Center 

(WTC) Monitoring and Treatment Program. 

Inclusion in this study required biopsy proven pathologic evidence of sterile 

non-caseating granulomas compatible with the diagnosis of sarcoidosis and no 

clinical or radiographic evidence of sarcoidosis prior to FDNY employment. To 

ensure the latter, an independent radiologist, without knowledge of the study 

or diagnosis in question, reviewed the pre-employment chest radiographs in 

suspected cases. Prior to 9/11/01, one fire fighter and one EMS HCW refused a 

biopsy and were excluded from the study. After 9/11/01, none refused biopsy. 

Pre- and post-9/11/01, the majority of biopsies were obtained by mediastinoscopy 

of intra-thoracic lymph nodes. Three cases suspected of occurring prior to 

FDNY employment were excluded from study. 

Between 9/11/1985 and 9/10/2001, 22 FDNY fire fighters were diagnosed with 

granulomatous disease consistent with the diagnosis of sarcoidosis (Figure 

2-6.6). 27,28 All 22 were male, one was African-American, one was an ex-smoker 

and none were EMS workers. The average number of new cases was two per year 

with a range of zero to five per year and the average annual incidence rate for 

FDNY rescue workers (fire fighters and EMS) was 14 cases per 100,000. 76% of 

the cases had Stage 0 or Stage 1 radiographic imaging. Although, shortness of 

breath on exertion was the most common symptom, (nearly 50% of the cases) 

it was mild and most had normal pulmonary functions. None had evidence 

for asthma or airway hyperreactivity on bronchodilator testing and cold air 

challenge testing, and only one had abnormal gas exchange with a reduced 

diffusion of oxygen. Three patients (14%) were treated with oral corticosteroids; 

two cases with shortness of breath and abnormal pulmonary function, and one 

case with joint aches and normal pulmonary function. After 12 to 18 months, 

all three fire fighters were off medication, asymptomatic, and returned to full 

fire fighter duties without further exacerbations. 

After the WTC (between 09/11/01 and 09/11/06), 26 WTC-exposed FDNY 

rescue workers were diagnosed with granulomatous disease consistent with

the diagnosis of sarcoidosis (see Figure 2-6.6). One was female, two were 

African-American, two were ex-smokers and three were EMS workers. All 26 

arrived at the WTC site within the first three days of the collapse. Thirteen 

patients presented in the first year post-WTC (9/11/01 to 9/10/02), one in the 

second year (2003), four in the third year (2004), four in the fourth year (2005) 

and four in the fifth year. Incidence rates were 86/100,000 exposed workers 

during the first 12 months post-WTC and then averaged 22/100,000 in the years 

thereafter as compared to 14/100,000 during the 15 years pre-WTC. 27,28 The 

annual incidence rate of sarcoidosis among FDNY rescue workers significantly 

increased in the five years post-WTC. Nearly identical increases in incidence 

rates were seen in patients whose diagnostic evaluation was initiated due to an 

abnormal chest radiograph as compared to those initiated due to symptoms. 

Although chest radiograph screening increased in the years immediately 

post-WTC, statistical analysis demonstrates that the increased incidence of 

sarcoidosis post-WTC did not result from the relative increase in the number 

of screening chest radiographs. 

Figure 2-6.6: The number of cases of biopsy proven World Trade Center Sarcoid-like 

Granulomatous Pulmonary Disease (WTC-SLGPD) in the 5 years since 9/11/01 as compared 

to pre-WTC cases of sarcoidosis or SLGPD starting from 1985 in rescue workers from the 

Fire Department of the City of New York (FDNY). 

After the WTC, the presentation shifted towards greater radiographic and 

clinical findings. Only 35% presented with Stage 0 or Stage I sarcoidosis on chest 

radiographic imaging. Asthma-like symptoms were now common, with nearly 

70% reporting cough, shortness of breath, chest tightness and/or wheezing 

exacerbated by exercise/irritant exposure or improved by bronchodilators. 

Pulmonary functions confirmed reversible airways obstruction in at least a 

third of these cases. New-onset airway obstruction was evident on spirometry 

in four (15%) patients, two of whom had a bronchodilator response. Airway 

hyperreactivity was assessed in 21 of 26 patients by either methacholine or 

cold air challenge and positive results were found in eight (38%). Although the 

incidence rate for sarcoidosis returned to almost pre-9/11 levels after the first 

year, asthma rates remained similarly high in both those diagnosed within 

the first year post-WTC and those diagnosed in years two through five. What 

remained similar to pre-9/11 was that gas exchange abnormalities remained 

rare with abnormal diffusion of oxygen evident in only two patients (8%). 

After the WTC, eight patients (31%) were treated with oral corticosteroids. 

During this study, 22 patients were diagnosed within the first four years post- 


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WTC and therefore had follow-up for at least one year. Pulmonary function 

improved in the two patients with abnormally low diffusion of oxygen (both 

treated with oral corticosteroids) and remained stable in the other 24 patients. 

Chest imaging abnormalities remained unchanged in 12 (two received oral 

corticosteroids), improved in four (two received oral corticosteroids), and 

resolved in six patients (two received oral corticosteroids). All 18 patients with 

asthma by any criteria were treated with inhaled steroids and bronchodilators, 

with subjective improvements in symptoms. 

Increased incidence of sarcoidosis or of a sarcoid-like granulomatous 

pulmonary granulomatous disorder (SLGPD) within a large population 

shortly after experiencing an intense environmental inhalation exposure of 

any type has, to our knowledge, never been described. All 26 patients were 

present during the first 72 hours post-WTC collapse when respirable dust 

concentrations were at their highest. During this time period, most patients 

reported no mask use or “minimal” use of a “dust” or N95 mask and no patient 

reported wearing a P-100 respirator. That such an intense exposure post-WTC 

could shortly thereafter induce a pulmonary granulomatous reaction has 

previously been reported for a single case only. 29 Several additional cases of 

sarcoidosis or SLGPD have been observed in the WTC workers and volunteers 

cohort (non-FDNY) followed by the Mt. Sinai Medical Center – World Trade 

Center Clinical Consortium (personal communication, R. Herbert, MD) as 

well as in the NYC Department of Health’s WTC Registry. 

Should these post-9/11/01 cases be classified as sarcoidosis, inhalation induced 

SLGPD or hypersensitivity pneumonitis? None of our cases reported acute 

systemic symptoms (weight loss, fever, etc.) or exposures (ex. birds) typical of 

hypersensitivity pneumonitis. Nor were chest CT and biopsy findings typical 

of hypersensitivity pneumonitis. Bilateral hilar adenopathy is a rare finding 

in hypersensitivity pneumonitis. Over 400 substances have been identified in 

airborne and settled samples of WTC dust, many of which have been previously 

reported to be associated with sarcoidosis. 11-16 Future tests are planned to 

determine if beryllium sensitivity was present but it may be too late to determine 

the exact chemical, element or mixture responsible. Regardless, we believe that 

there is clear epidemiologic evidence for an association between sarcoidosis or 

SLGPD and firefighting and WTC dust exposure. These results will hopefully 

add new insight into the etiology of sarcoidosis as well as providing increased 

attention to the need for improved respiratory protection and surveillance 

following environmental/occupational exposures. 

REFERENCES 

1. Wasfi YS and Newman LS. Sarcoidosis in Murray and Nadel’s Textbook of 

Respiratory Medicine, 4th ed. Pg 1634-1655. Elsevier Saunders, Philadelphia 

Pa. 2005. 

2. American Thoracic Society/European Respiratory Society. Statement on 

sarcoidosis. Joint statement of the American Thoracic Society (ATS), the 

European Respiratory Society (ERS) and the World Association of Sarcoidosis 

and Other Granulomatous Disorders (WASOG) adopted by the ATS board 

of Directors and by the ERS Executive Committee, February 1999. Am J 

Respir Crit Care Med 1999; 160:736-755.

3. Newman LS, Rose CS, Bresnitz EA, et al.; ACCESS Research Group. A case 

control etiologic study of sarcoidosis: environmental and occupational 

risk factors. Am J Respir Crit Care Med. 2004;170:1324-30. 

4. Tierstein AS, Lesser M. Worldwide distribution and epidemiology of 

sarcoidosis. In: Fanburg BL, ed. Sarcoidosis and other granulomatous 

diseases of the lung. New York, NY: Marcel Dekker, 1983; 101–134. 

5. Parkes SA, Baker SB, Bourdillon RE, et al. Epidemiology of sarcoidosis in 

the Isle of Man: 1. A case controlled study. Thorax 1987; 42:420–426. 

6. Hosoda Y, Yamaguchi M, Hiraga Y. Global epidemiology of sarcoidosis: 

what story do prevalence and incidence tell us? Clin Chest Med 1997; 

18:681–694 

7. Bauer HJ, Lofgren S. International study of pulmonary sarcoidosis in mass 

chest radiography. Acta Med Scand 1964;176(suppl425):103–105 

8. Logan J. Prevalence of sarcoidosis in Ireland: proceedings of the Third 

International Conference on Sarcoidosis. Acta Med Scand 1964; (Suppl425); 

176:126 

9. Rybicki BA, Major M, Popovich J, et al. Racial differences in sarcoidosis 

incidence: a 5 year study in a health maintenance organization. Am J 

Epidemiol 1997; 145:234–241 

10. Robins AB, Abeles H, Chaves AD. Prevalence and demographic characteristics 

of sarcoidosis. Bureau of Tuberculosis, New York, NY: Department of Health, 

NY, 1962; 149–151. 

11. Kajdasz DK, Lackland DT, Mohr LC, et al. A current assessment of rurally 

linked exposures as potential risk factors for sarcoidosis. Ann Epidemiol 

2001;11:111-117 

12. Armbruster C, Dekan G, Hovorka A. Granulomatous pneumonitis and 

mediastinal lymphadenopathy due to photocopier toner dust [letter]. 

Lancet 1996;34:690 

13. Drent M, Bomans PH, Van Suylen RJ, et al. Association of manmade 

mineral fiber exposure and sarcoid like granulomas. 

Respir Med. 2000;94:815-820. 

14. Rafnsson V, Ingimarsson O, Hjalmarsson I, et al. Association 

between exposure to crystalline silica and risk of sarcoidosis. 

Occup Environ Med. 1998;55:657-660. 

15. Newman LS. Metals that cause sarcoidosis. Semin Respir Infect 1998; 

13:212-220. 

16. Richeldi L, Kreiss K, Mroz MM, et al. Interaction of genetic and exposure 

factors in the prevalence of berylliosis. Am J Ind Med 1997; 32:337–340 

17. Judson MA, Baughman RP, Teirstein AS, et al. Defining organ involvement 

in sarcoidosis: the ACCESS proposed instrument. ACCESS Research Group. 

A Case Control Etiologic Study of Sarcoidosis. Sarcoidosis Vasc Diffuse 

Lung Dis. 1999;16:75-86. 


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18. Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of 

patients in a case control study of sarcoidosis. Am J Resp Crit Care Med 

2001; 164:1885-1889. 

19. Scadding JG. Prognosis of intra-thoracic sarcoidosis in England. Br. Med. 

J. 1961; 4:1165-1172. 

20. Firefighter fatality Investigation Report F2003-2008 CDC/NIOSH. www. 

cdc.gov/niosh/fire/reports/face200308.htm 

21. Edmonstone WM. Sarcoidosis in nurses: is there an association? Thorax 

1998;43:342-343. 

22. Sartwell PE, Edwards LB. Epidemiology of sarcoidosis in the U.S. Navy. 

Am J Epidemiol 1974; 99:250–257 

23. National Institute for Occupational Safety, Centers for Disease Control: 

sarcoidosis among US Navy enlisted men; 1965-1993. MMWR 1997;46:539- 

543. 

24. Gorham ED, Garland CF, Garland RC, et al. Trends and occupational 

associations in incidence of hospitalized pulmonary sarcoidosis and other 

lung diseases in Navy personnel; a 27-year historical prospective study, 

1975-2001. Chest 2004;126:1431-1438. 

25. Barnard J, Rose C, Newman L, Canner M, et al. Job and industry classifications 

associated with sarcoidosis in a case-control etiologic study of sarcoidosis 

(ACCESS). J Occup Environ Med 2005; 47:226-234. 

26. Kern DG, Neill MA, Wrenn DS, et al. Investigation of a unique time-space 

cluster of sarcoidosis in firefighters. Am Rev Respir Dis 1993; 148:974–980 

27. Prezant D, Dhala A, Goldstein A, et al. The incidence, prevalence and 

severity of sarcoidosis in New-York City firefighters. Chest 1999;116:1183- 

1193. 

28. Izbicki G, Chavko R, Banauch GI, Weiden M, Berger K, Kelly KJ, Hall C, 

Aldrich TK and Prezant DJ. World Trade Center Sarcoid-like Granulomatous 


Chest, 2007;131:1414-1423. 

29. Safirstein BH, Klukowitcz A, Miller R, et al. Granulomatous pneumonitis 

following exposure to the World Trade center collapse. Chest 2003;123:301- 

304.

Chapter 2-7 

Pulmonary Fibrosis and 

Interstitial Lung 

Disease 

By Dr. Robert Kaner, MD 

PULMONARY FIBROSIS 

Pulmonary fibrosis refers to a variety of conditions that result in scarring in 

the gas exchanging regions in the lungs. 1,2 There are a number of inhaled 

environmental agents that can cause pulmonary fibrosis; which is the end 

result of chronic lung inflammation. In addition, there are lung diseases of 

unknown cause that result in pulmonary fibrosis. While epidemiologic studies 

have not shown an increased incidence of pulmonary fibrosis in fire fighters, 

this topic is of interest to fire fighters because of their potential to inhale smoke 

as well as industrial substances such as insulation particles and chemicals 

that may become airborne during fires and explosions. The key concept is that 

environmental exposure to potentially-fibrogenic substances can largely be 

prevented through the appropriate use of properly fitting respirators. 

In order to understand how and where pulmonary fibrosis occurs, it is 

necessary to describe some basic facts about the organization of the lung. 

The lung is composed of a number of different types of structures that serve 

different functions. Inhaled substances pass through the upper airway, vocal 

cords and larynx prior to traveling through the branching tubes that make up 

the bronchial tree. The airways terminate in the tiniest passages that lead into 

the alveoli, the gas exchanging units of the lung. In the alveoli, the pulmonary 

capillaries (the smallest caliber blood vessels) run directly adjacent to the 

alveolar air sacs, allowing for the efficient exchange of oxygen and carbon 

dioxide between blood and air. Scar tissue can form in the walls of the alveoli 

or in the airspaces of the alveoli or both. The extremely thin space in between 

the alveolar wall and the capillary is called the interstitium. This interstitial 

space becomes dramatically widened by inflammatory cells and the deposition 

of scar tissue, hence the broad category of this class of lung problems is termed 

‘interstitial lung disease’. 

Major Categories of Interstitial Lung Disease and Pulmonary 

Fibrosis 

The major environmental agents that are implicated in occupational pulmonary 

fibrosis include inhalation of industrial dusts such as asbestos fibers, silica 

(from sandblasting) and coal dust from mining. Many other substances have 

been linked to the development of pulmonary fibrosis in humans and animal 

models including fiberglass, mica and industrial dusts from refining of organic 

Chapter 2-7 • Pulmonary Fibrosis and Interstitial Lung Disease 

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120 Chapter 2-7 • Pulmonary Fibrosis and Interstitial Lung Disease 

products like cotton. The key characteristic shared by all particles that can 

cause pulmonary fibrosis is the size of the particles. If the particles are larger 

than three microns in length they tend to deposit in the nose, throat and large 

airways of the lung. Smaller particles are increasingly likely to be deposited 

in the terminal airways or alveoli, where they can cause inflammation and 

subsequent scarring, leading to interstitial lung disease and fibrosis. In general, 

single short exposures are much less likely to cause fibrosis than repeated daily 

exposures over years. Of asbestos workers developing asbestosis (interstitial 

lung disease due to asbestos) half have had >20 years of exposure. However, 

many cases have occurred in workers with 20% 

depending upon if they were engaged in the manufacture of cement products 

containing asbestos, mining and milling of asbestos (highest prevalence) 

or manufacture of asbestos fiber or rope. In the US, common occupational 

exposures occurred in shipyard workers who sprayed asbestos insulation on 

the surfaces of the holds of ships in naval shipyards, as well as those working in 

the same work environment. Other occupational exposures included grinding 

brake linings, which formerly contained asbestos and may still be present in old 

and replacement brake pads and clutch plates. The particles must be airborne 

in order to cause disease, so intact insulation that is not degraded in some way 

does not represent a true risk of asbestos exposure until the integrity of the 

sealed substance is compromised during maintenance or removal activities that 

lead to the airborne release of asbestos fibers. Of note, fibers that are brought 

home on the surface of clothing can become airborne again when the clothing 

is handled, leading to exposure of family members. Asbestosis is of particular 

concern to fire fighters due to their potential exposure to insulation containing 

asbestos that was used in residential homes. Asbestos can still be found in floor 

and ceiling tiles, shingles, flashing and siding, pipe cement, plasters and joint 

compounds, all of which could become damaged and airborne during a fire. 

For further information on the health consequences of asbestos exposure, see 

the Chapter on Asbestos-Related Lung Disease. 

Another common type of interstitial lung disease that can progress to 

pulmonary fibrosis is a condition termed hypersensitivity pneumonitis or 

extrinsic allergic alveolitis. This disease is mediated by an immunologic 

response in the lung to an inhaled organic antigen. Hundreds of types of 

organic antigens have been implicated. The most common types are due to 

ongoing exposure to birds such as parakeets or pigeons (bird fancier’s lung). 

The offending antigens are proteins present in the bird droppings that become 

aerosolized. Another common cause of hypersensitivity pneumonitis is 

exposure to mold, as in moldy hay (farmer’s lung). 

There are other types of chronic inflammatory lung disease of unknown 

cause that sometimes lead to fibrosis such as sarcoidosis. Sarcoidosis causes 

a specific pattern of inflammation that the pathologist recognizes as a 

granuloma, composed of activated macrophages (also called epithelioid giant 

cells) surrounded by lymphocytes in a spherical configuration. This disease is 

characterized by spontaneous remissions and exacerbations. A small minority 

of individuals with sarcoidosis will progress to irreversible pulmonary fibrosis. 

See the Chapter on Sarcoidosis for further information on this subject.

There are systemic connective tissue diseases associated with pulmonary 

fibrosis, such as rheumatoid arthritis and scleroderma. Usually the joint or skin 

disease is present for a long time before lung involvement occurs, but rarely, 

the lung disease can be the initial manifestation of these systemic disorders. 

These generally have a somewhat better prognosis than idiopathic pulmonary 

fibrosis, a condition of unknown cause. 

Pulmonary fibrosis can also occur as a complication of certain types of 

chemotherapy prescribed for cancer treatment. The best known example is 

bleomycin, a drug used to treat lymphoma and testicular cancer. This drug 

reproducibly causes pulmonary fibrosis in certain strains of laboratory mice, 

so is used as a standard animal model for research on pulmonary fibrosis. 

Another commonly-used cancer treatment, carmustine (BCNU), used to 

treat brain tumors can cause pulmonary fibrosis as late as decades after it is 

administered. Interstitial lung disease, which may be a consequence of prior 

chemotherapy, radiotherapy, graft versus host disease and acute lung injury, 

is also a complication of hematopoietic (bone marrow) transplantation. 

Another commonly-employed cancer treatment, external beam radiation 

therapy, can cause radiation pneumonitis and fibrosis in a minority of individuals. 

The acute symptoms may begin within several weeks following radiation to 

the chest for treatment of lung cancer, breast cancer or lymphoma. Fibrosis 

may occur months to years later. 

The remaining types of interstitial lung disease are termed ‘idiopathic’, 

meaning having no known cause. The most common types of idiopathic 

interstitial lung disease are termed idiopathic pulmonary fibrosis and 

nonspecific interstitial pneumonia. Another common disorder is termed 

cryptogenic organizing pneumonia. The reason that an accurate diagnosis of 

the specific type of interstitial lung disease should be made is that the prognosis 

and potential for response to treatment as well as the dose and duration of 

treatment recommended is dependent upon the specific diagnosis. 

Cryptogenic organizing pneumonia is an inflammatory disorder that follows 

a viral infection and a variety of other acute insults to the lung. Its importance 

is that it may often be confused with bacterial pneumonia, but responds readily 

to treatment with systemic steroids. 

In contrast, idiopathic pulmonary fibrosis and nonspecific interstitial 

pneumonia are generally diseases of much longer duration where symptoms 

may occur for months to years prior to a diagnosis. Of note, in a small minority 

of cases, idiopathic pulmonary fibrosis occurs in families. The genetics of the 

predisposition to develop idiopathic pulmonary fibrosis in both the familial 

and non-familial forms are only beginning to be understood. 

Symptoms of Pulmonary Fibrosis 

The main symptoms of pulmonary fibrosis are shortness of breath and frequent 

cough. The shortness of breath is usually only with exertion until the disease 

is very advanced. The cough is usually dry, without production of sputum. A 

minority of individuals will develop clubbing, a specific change in the soft 

tissue structure of the distal parts of the fingers that leads to widening of the 

end of the finger just after the last finger joint and a change in the angle that 

the nail-bed makes with surface of the finger. None of the symptoms and 


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signs are specific for interstitial lung disease and/or pulmonary fibrosis, so a 

careful diagnosis is necessary to distinguish these from other types of medical 

problems that can affect the chest. Swelling of the feet and legs may occur in 

advanced pulmonary fibrosis as explained below. 

Individuals with chronic interstitial lung disease and pulmonary fibrosis 

typically have symptoms for months to years before a diagnosis is made. Patients 

with this disease generally report a very gradual onset and progression of 

shortness of breath noted when exerting themselves. Sometime the interstitial 

disease is discovered accidentally when imaging of the chest is done for another 

reason. Often the individual is admitted to the hospital for “pneumonia” and 

only in retrospect is it apparent that interstitial lung disease is the underlying 

problem. 

A very small minority of individuals will present with an acute illness 

lasting for only a few weeks with rapidly progressive, interstitial lung disease. 

Biopsy of the lungs of these individuals shows a pattern that the pathologist 

calls diffuse alveolar damage which is the morphologic equivalent of acute 

lung injury or adult respiratory distress syndrome with or without evidence 

of a more chronic background process of interstitial lung disease. Usually no 

underlying cause for this illness is determined, which is then termed acute 

interstitial pneumonia. The disease has a significant mortality, particularly 

in individuals who develop respiratory failure of sufficient degree to require 

mechanical ventilation. 

Individuals with idiopathic pulmonary fibrosis are also susceptible to acute 

lung injury superimposed upon their underlying pattern of inflammation 

and scarring. This acute lung injury has been termed acute exacerbation of 

idiopathic pulmonary fibrosis. Its cause is unknown. Radiographically it appears 

a pattern of new ground glass opacities superimposed upon a background of 

chronic interstitial changes and pulmonary fibrosis. In this context, 'ground 

glass' does NOT mean actual inhaled glass. Rather, it is a radiology term based 

on the visual impression that the chest image is hazy as if the glass screen 

in which they view the chest film has lots of scratches or grindings on it. A 

ground glass appearance is actually the result of non-specific inflammation 

of the lung tissues. 

Hypersensitivity pneumonitis may present early in the course as acute 

attacks of cough and shortness of breath that occur within several hours after 

acute exposure to the inhaled antigen, which gradually resolve over time. A 

clue to the diagnosis is that the symptoms may disappear when the individual 

is removed from the offending antigen, as when taking a prolonged trip, only 

to recur on returning home. Symptoms linked to a specific place such as work, 

with improvement or worsening when away from work, may also provide a clue 

to the diagnosis. Hypersensitivity pneumonitis that has progressed to advanced 

fibrosis can be difficult to distinguish from idiopathic pulmonary fibrosis. 

Physiologic Consequences of Interstitial Lung Disease and 

Pulmonary Fibrosis 

The interstitial and intra-alveolar inflammation and scarring directly impairs 

the lungs’ ability to oxygenate the red blood cells. As a result, the oxygen 

saturation may drop, particularly with exercise. Exercise-induced shortness of 

breath occurs as a result of the impairment of gas exchange and the increased

demands placed upon the heart, since a compensatory increase in heart rate 

will occur at much lower levels of exercise than in individuals with normal 

lungs. Oxygenation of the blood may remain normal at rest until the disease is 

far advanced. Some types of exercise are more demanding in this regard than 

others. Stair and hill climbing, particularly while carrying heavy objects, are 

often the first noticeable symptoms of the disease. 

When pulmonary fibrosis progresses to an advanced stage, pulmonary 

hypertension may develop. This means the pressure in the system of blood 

vessels supplied by blood flow from the right-side of the heart to the vessels in 

the lungs may increase, particularly during exercise. If the average pulmonary 

arterial pressure exceeds 30 mm Hg (35 mm Hg with exercise), then pulmonary 

hypertension is said to be present. As pulmonary hypertension progresses, it 

can lead to right-sided heart enlargement and right heart failure. One of the 

major symptoms of right heart failure is swelling of the feet, ankles and legs. 

A large study sponsored by National Institutes of Health (NIH) is underway to 

address the issue of whether treating pulmonary hypertension in idiopathic 

pulmonary fibrosis will result in improvement in exercise capacity. 

If the fibrosis progresses to a point where respiratory failure occurs, death 

is the usual outcome. 

Diagnosis of Pulmonary Fibrosis 

The key elements of diagnosis of pulmonary fibrosis are the history, physical 

examination, pulmonary function tests and chest CT scan and lung biopsy. 3 

The chest CT should preferably be done with high resolution imaging 

techniques including inspiratory and expiratory views. Intravenous contrast 

does not aid in the diagnosis of interstitial lung disease, but can be very 

useful for diagnosis of pulmonary emboli. 3 The high resolution chest CT has 

become the gold standard imaging study to aid in the diagnosis of interstitial 

lung disease and pulmonary fibrosis and is mandatory in nearly all cases 

(Figure 2-7.1). 

Figure 2-7.1: Pulmonary Fibrosis 


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Certain features of the high-resolution chest CT may support a specific 

diagnosis of interstitial lung disease or suggest alternatives. The overall pattern 

of disease is very important in the classification. Certain diseases such as 

sarcoidosis and hypersensitivity pneumonitis tend to have the abnormalities 

distributed in a pattern that corresponds to bronchovascular bundles, the 

conglomeration of airways and attendant blood vessels and lymphatics. 

Hypersensitivity pneumonitis often is skewed toward a more upper-lobe 

distribution. In sharp contrast, idiopathic pulmonary fibrosis has a characteristic 

basilar (lower lung) distribution of disease. Pulmonary fibrosis appears on 

the CT scan as ‘reticular’, a type of abnormality characterized as increased 

relatively linear thin white lines. Active inflammation tends to cause a more 

dense and coarse increase in radiodensity appearing as nonlinear patchy 

areas of increased white attenuation on the chest CT which may fill in alveolar 

spaces completely and can be referred to as ‘ground glass opacities’. Ground 

glass opacities are characteristically seen in hypersensitivity pneumonitis, 

nonspecific interstitial pneumonia and during the acute exacerbation phase 

of idiopathic pulmonary fibrosis. More dense consolidation is often indicative 

of infection or cryptogenic organizing pneumonia. Advanced disease may be 

described as honeycombing due to its resemblance to the internal wax structure 

of a beehive. This finding when pronounced may add to the probability of the 

underlying disease process being idiopathic pulmonary fibrosis. Another finding 

known as traction bronchiectasis refers to the enlargement of airways in the 

periphery of the lung that are being tethered open by the centripetal forces 

exerted when extensive scarring occurs in the substance of the lung tissue. 

Radionuclide scanning with isotopes such as radioactively tagged gallium 

can be useful to demonstrate active lung inflammation. Gallium is injected 

into the patient’s vein, after which a scan of the chest is done to assess the 

distribution of the gallium within the lung. Areas of inflammation “light up” 

on the scan; but this test lacks specificity. 

Pulmonary function tests show a restrictive pattern, which means that 

measured lung volumes and rates of airflow from the lung on forced expiration 

are both reduced. The diffusing capacity, a test measuring the ability of gases 

to transfer from the atmosphere into the bloodstream, is usually reduced, even 

prior to the development of restriction. 

In the majority of cases, a surgical lung biopsy is required to obtain sufficient 

lung tissue so that a specific diagnosis may be rendered. 3 Generally this 

biopsy requires general anesthesia and can be obtained via video-assisted 

thoracoscopy, where three tiny incisions are made in the chest wall, through 

which the thoracic surgeon can insert a fiberoptic camera and tools to perform 

the biopsies (Figure 2-7.2). The procedure is safe for most people but can 

sometimes be obviated if the chest CT is diagnostic for a specific entity such 

as what is known as usual interstitial pneumonia. It is often not recommended 

to individuals who have increased risk for surgical procedures due to other 

medical conditions. 

Specific pathological findings are seen in the surgical lung biopsy specimens 

obtained from individuals with idiopathic interstitial lung diseases. Cryptogenic 

organizing pneumonia shows marked inflammation in the alveolar spaces 

along with plugs of fresh fibrous connective tissue extending into the lumen 

of small airways. Usual interstitial pneumonia, the histologic correlate of

Figure 2-7.2: Video-assisted thoracoscopic surgery (VATS) 

idiopathic pulmonary fibrosis, is characterized by dense fibrosis that has a 

subpleural distribution. In the subpleural region, a distinctive finding known 

as fibroblastic foci composed of ball-like structures of accumulating fibroblasts 

and myofibroblasts, the fibrosis-producing cells, are frequently present. 

There are typically very localized areas of very diseased lung immediately 

adjacent to relatively normal-appearing lung, a feature pathologists describe 

as temporal heterogeneity. There is microscopic honeycombing corresponding 

to the honeycomb change visible on high resolution chest CT. In contrast, 

the distribution of disease is much more uniform in nonspecific interstitial 

pneumonia. It also lacks the temporal heterogeneity characteristic of usual 

interstitial pneumonia. The degree of inflammation in nonspecific interstitial 

pneumonia tends to be more pronounced, although subtypes without much 

inflammation have also been described. 

Fiberoptic bronchoscopy, a procedure performed by medical pulmonary 

physicians with the patient under moderate sedation, generally cannot provide 

an adequate amount of tissue for diagnosis of interstitial lung disease. However, 

there are important exceptions which include sarcoidosis, where the yield of 

transbronchial biopsy is over 90%. Sometimes hypersensitivity pneumonitis 

can be diagnosed via transbronchial biopsy. Bronchoscopy is a good tool for 

the diagnosis of many lung infections and is often used first when infection is 

suspected to avoid the need for general anesthesia and surgery. 

In short, the definitive diagnosis of interstitial lung disease depends on a 

multidisciplinary approach between clinicians, radiologists and pathologists 

who have expertise in these types of disorders, working together to consider 

all of the relevant information to come to a diagnostic conclusion. 

Prognosis 

The prognosis in interstitial lung disease and pulmonary fibrosis depends 

upon an accurate diagnosis of the underlying disease process. The prognosis 

is different for the fiber and dust-induced fibrosis as opposed to the interstitial 


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lung diseases without a known cause. Within the lung diseases without a known 

cause, the prognosis is different in idiopathic pulmonary fibrosis as compared 

with nonspecific interstitial pneumonia. Individuals with idiopathic pulmonary 

fibrosis have a survival rate of three to five years, whereas the survival rate in 

nonspecific interstitial pneumonia is > 10 years. Connective tissue diseaserelated 

interstitial lung disease also tends to have a better prognosis than the 

idiopathic types. 

Certain findings are known to correlate with a worse prognosis. Severe 

pulmonary function test abnormalities, particularly if progressive, carry 

a worse prognosis, regardless of the underlying cause. The development of 

right-sided heart failure indicates far advanced disease. Oxygenation generally 

worsens as the disease progresses. 

Available Treatment 

The treatment of interstitial lung disease and pulmonary fibrosis depends 

upon the specific diagnosis. 4 For idiopathic interstitial lung diseases and those 

due to connective tissue diseases, if treatment is recommended, it usually 

includes systemic steroids such as prednisone. There is no evidence that 

inhaled medications have any significant effects in these disorders. Idiopathic 

pulmonary fibrosis in particular has no proven therapy and for which there is 

no FDA-approved drug. Anti-inflammatory immunosuppressive drugs such 

as azathioprine (Imuran®), cyclophosphamide (Cytoxan®) or mycophenolate 

mofetil (Cellcept®) are often added to or substituted for prednisone. These 

drugs have numerous significant side effects, not the least of which is increased 

susceptibility to infection. Any decision to begin any such supportive treatment 

must balance the potential benefit against the potential side effects of these 

medications. 

A large prospective randomized trial of an antioxidant N-acetylcysteine 

(NAC) is about to begin under sponsorship of the NIH. This study will compare 

treatment with NAC with and without concomitant prednisone and azathioprine 

therapy and will include a control group with all placebos. This study will 

follow up on a European study showing better preservation of lung function 

in individuals with idiopathic pulmonary fibrosis (IPF) treated with the 

combination of prednisone, azathioprine and NAC compared with prednisone 

and azathioprine alone. The rationale for the use of NAC, is that it is metabolized 

in the body to glutathione, an important antioxidant that is depleted in the 

epithelial lining fluid of individuals with IPF. Oxygen-free radicals and their 

metabolites may exacerbate the injury to the alveolar epithelial cells that is 

part of the current understanding of IPF pathophysiology. It is expected that 

this study will determine the standard of care for newly diagnosed IPF. 

In contrast, nonspecific interstitial pneumonia generally responds favorably 

to prednisone therapy. After the initial response, the medication dose is 

tapered over the course of months. If the disease worsens, the steroid dose is 

increased. The immunosuppressive drugs may be added as steroid-sparing 

agents in individuals intolerant of prednisone. Fibrosis due to hypersensitivity 

pneumonitis is best treated by removal of the individual from exposure to the 

offending antigen. A short course of prednisone is often helpful in treating 

shortness of breath and/or cough. 

Chemotherapy-induced pulmonary toxicity is usually treated with steroids

if the individual is symptomatic with shortness of breath or cough. The steroids 

are tapered over the course of weeks to months. If fibrosis is discovered years 

after chemotherapy, treatment is ineffective. 

For occupational and environmentally-induced fibrotic lung diseases due 

to inorganic dusts such as asbestos, there is no effective treatment; however 

supportive therapy that can be offered to individuals affected by these lung 

diseases Supplemental oxygen is prescribed for individuals whose oxygen 

saturation is below 88% either at rest or with exercise. While it does not alter 

prognosis, it can relieve symptoms and improve exercise tolerance. 

Pulmonary rehabilitation, including dieting where weight loss is indicated, is 

recommended for individuals with significant exercise limitation, as it positively 

impacts performance regardless of the nature of the underlying lung process. 

It is mandatory for individuals being considered for lung transplantation. 

For individuals with any type of interstitial lung disease or pulmonary 

fibrosis whose disease progresses to the advanced stage, lung transplantation 

may be the best option for those who qualify. Idiopathic pulmonary fibrosis 

is now the most common indication for which lung transplant is performed. 

Since the pre-transplant evaluation is very extensive and time consuming 

and donor lungs are in short supply, individuals who may require transplant 

in the future are encouraged to begin the evaluation process long before the 

transplant becomes necessary. 

Prevention of Pulmonary Fibrosis 

Pulmonary fibrosis due to occupational or environmental exposures is clearly 

preventable via the use of appropriate precautions such as the use of respirators 

when these agents are airborne at significant concentrations. During the 

fighting of an actual fire, the self-contained breathing apparatus (SCBA) worn 

by most fire fighters, if functioning and worn properly, will constitute adequate 

protection. In the absence of a SCBA, the minimal protection required when 

there is the possibility of environmental dust exposure is a NIOSH certified 

P-100 disposable filtering facepiece respirator (99.9% filtration of 0.3 micron 

particles) (Figure 2-7.3) or a NIOSH-certified respirator with a higher level of 

respiratory protection, including a full-facepiece or half-facepiece air purifying 

respirator (APR) (Figure 2-7.4) or powered air-purifying respirator (PAPR) with 

a HEPA filter/canister (Figure 2-7.5). 

Figure 2-7.3: NIOSH- 

Certified P-100 Filtering 

Facepiece Respirator 


Certified APR with a 

HEPA Filter 


Certified PAPR 


127

128 


An APR or PAPR will not protect against gases and chemicals unless it is 

fitted with cartridge(s) or canister specifically designed and approved for this 

purpose. Further, a P-100 respirator provides the highest levels of particulate 

or aerosol protection as compared to other filtering facepiece respirators such 

as the N-95 or N-99. Additionally, the P-100 is a disposable respirator and 

should be properly disposed of after each use where an exposure occurred. 

The P-100 must have seal-enhancing elastomeric components (e.g. rubber 

or plastic respirator-to-face seals) and must be equipped with two or more 

adjustable suspension straps. Without these components, it is very difficult 

to obtain and/or maintain a face seal so as to protect the wearer. 

Respirators that do not properly seal or do not fit will offer no respiratory 

protection. All respirator use must be administered as part of a comprehensive 

Respiratory Protection Program (RPP), according to the Occupational Safety 

and Health Administration (OSHA). The RPP contains mandatory provisions 

for training respirator users, selecting and maintaining respirator equipment, 

conducting fit checks and conducting fit tests. 

Increased Risk to Fire Fighters 

Increased occupational risk of interstitial lung disease and pulmonary fibrosis in 

fire fighters has not been demonstrated in large epidemiologic studies involving 

thousands of fire fighters, the largest of which studied over 10,000 individuals. 

These findings have been confirmed by large independent studies in several 

different countries. Two studies have reported an increased incidence of 

sarcoidosis in fire fighters pre- and post-World Trade Center (WTC). 5,6 Whether 

this represents a true occupational risk of fire fighters has not been definitively 

established. However, there is concern that fire fighters and rescue workers 

in certain types of large disasters may be at risk for interstitial lung disease. 

Relationship to World Trade Center Exposure 

Concern exists about the potential for the development of pulmonary fibrosis 

in those individuals that were exposed at the WTC on and after September 11, 

2001. This is due to the possibility that there may have been asbestos in the air 

during the first three days following the disaster; the increased level of particles 

in the air small enough to reach the airspaces of the lung; and the measurement 

of various building materials known to be associated with pulmonary fibrosis, 

especially with the abnormal alkalinity of these particles. To date, while many 

other types of respiratory abnormalities have been documented, no cases 

of pulmonary fibrosis have yet been reported in the peer-reviewed medical 

literature, but several have been noted anecdotally in the lay-press. There 

have been several case reports of hypersensitivity-like disease. This does not 

preclude the possibility that cases of pulmonary fibrosis may be identified 

in the future. Whether or not this occurs, first responders must be prepared 

to reduce the possibility of significant environmental exposure to inhaled 

fibrosis-inducing agents by properly wearing appropriately selected respiratory 

protection during firefighting or rescue efforts.

REFERENCES 

1. Gross TJ, Hunninghake GW. Idiopathic Pulmonary Fibrosis. N Engl J Med. 

2001; 345:517-525. 

2. Noth I, Martinez FJ. Recent Advances in idiopathic pulmonary fibrosis. 

Chest 2007;132:637-650. 

3. Ryu JH, Daniels CE, Hartman TE, Yi ES. Diagnosis of interstitial lung 

diseases. Mayo Clin Proc. 2007;82:976-986. 

4. Kim R, Meyer KC. Therapies for interstitial lung disease: past, preset and 

future. Ther Adv Respir Dis. 2008;5:319-338. 

5. Prezant DJ, Dhala A, Goldstein A, Janus D, Ortiz F, Aldrich TK, Kelly 

KJ. Incidence, prevalence, and severity of sarcoidosis in New York City 

Firefighters. Chest. 116:1183-1193, 1999 




Chest, 2007;131:1414-1423. 


129


Chapter 2-8 

Pulmonary Vascular 

Diseases 

By Dr. Alpana Chandra MD, Dr. Amgad Abdu MD, 

and Dr. Andrew Berman, MD 

The two sides of the heart have distinct functions. The right side of the heart 

receives venous blood from the body and then pumps it into the pulmonary 

circulation to pick up oxygen from the lungs. The oxygenated blood then drains 

into the left sided chambers of the heart that pump it through the body with 

each heart beat, providing energy to the organs of the body. Pressure in the 

left side of the heart is routinely measured as one’s blood pressure, and when 

it is elevated, we refer to this as systemic hypertension. When resistance in 

the pulmonary circulation circuit rises, pressure on the right side of the heart 

can rise and when this occurs, pulmonary hypertension results. In another 

condition known as pulmonary embolism, one or more blood clots travel to the 

lung where they eventually stop and cut off blood flow to part of the pulmonary 

circulation. These two diseases of the pulmonary vasculature will be the focus 

of this chapter. In addition, fluid accumulation in the air spaces of the lung, 

or pulmonary edema, will also be discussed. 

PULMONARY HYPERTENSION (PH) 

The pulmonary circulation is ordinarily a low resistance circuit between the left 

and right chambers of the heart. However, diseases involving the pulmonary 

vasculature can cause an increase in resistance in this circuit leading to an 

increase in pressure of the pulmonary artery, the large blood vessel conducting 

blood from the right side of the heart to the lungs. Pulmonary hypertension 

is defined as a clinical condition characterized by persistent elevation in the 

pressure of the main pulmonary artery. While less common than systemic 

hypertension, PH is a life-threatening disorder. Despite our increasing 

understanding of this condition, its cause remains unknown. 

Pathology 

The blood supply for the right lung and the left lung mostly comes from the 

pulmonary artery which branches into two large arteries supplying the respective 

lungs. Inside the lung, each pulmonary artery accompanies the appropriate 

bronchus or airway and continues to divide into smaller branches down to the 

level of small arterioles and finally capillaries, which are positioned around the 

air sac or alveolus. Gas exchange takes place here such that oxygen is transferred 

from the air in the alveolus to the blood in the capillary. The oxygenated blood 

then passes into the post capillary venules, which join up to form larger veins 

that finally form the pulmonary veins draining into the left chambers of the 

Chapter 2-8 • Pulmonary Vascular Diseases 131

132 Chapter 2-8 • Pulmonary Vascular Diseases 

heart. Pulmonary hypertension is the result of pathology or injury in any of 

these areas, and is often characterized by excessive muscularization of the 

small arteries (medial hypertrophy), scarring, inflammation and narrowing 

of the blood vessels (vasoconstriction). 1 In some cases there might also be 

blockage of these small arterioles with blood clots. 

Epidemiology 

PH affects over 25 million individuals worldwide and causes premature 

disability and death for many. 2 It is a deadly disease and the estimated median 

survival from the time of diagnosis is about 2.8 years. Time to death however 

varies widely among patients, with some dying within months of diagnosis 

and others living with the condition for decades. Underlying etiology may 

influence survival as those with PH related to congenital heart disease may 

live longer than patients with other underlying etiologies. 

Etiology 

This condition was previously designated as Primary Pulmonary Hypertension 

(PPH) in the absence of any demonstrable cause, and as secondary pulmonary 

hypertension, if otherwise. It is not surprising that as our diagnostic capabilities 

have increased, many cases of pulmonary hypertension originally designated 

as ‘primary’ are now considered "secondary". Infrequently, pulmonary 

hypertension has also been found to run in families. The standard classification 

of pulmonary hypertension is now etiology-based, and is reviewed in Table 2-8.1. 

Idiopathic (or “unknown cause”) pulmonary arterial hypertension (IPAH) 

is most commonly a disease of young adults with a peak incidence in the third 

and fourth decades of life. It is also more common in women as compared to 

men, especially in women of childbearing age. IPAH can only be diagnosed 

after all other causes are excluded. 

Pulmonary hypertension can result from heart disease. If the left side of the 

heart is not functioning optimally, the system can essentially get backed-up. 

Pressure can build up in the pulmonary circulation due to troubles pumping 

the blood out of the left heart chambers, which occurs in a condition called 

congestive heart failure. Certain types of congenital heart disease can also 

result in PH. 

Pulmonary hypertension often occurs in the setting of chronic lung disease. 

Patients with emphysema/COPD or pulmonary fibrosis may develop elevated 

right heart pressures due to periods of low oxygen. Similarly, patients with 

sleep apnea can develop PH due to the fall in oxygen that occurs when patients 

stop breathing during sleep. 

Occlusion in the pulmonary vessels due to chronic thrombotic/embolic 

disease is another category and is usually due to blood clots but may also be 

caused by tumor cells. The incidence of PH due to chronic thrombotic/embolic 

disease is approximately three to four percent after acute pulmonary embolism.

Standard Classification of Pulmonary Hypertension 

I - Pulmonary Artery Hypertension 

• Idiopathic Pulmonary Artery Hypertension (IPAH) 

• Familial Pulmonary Artery Hypertension (FPAH) 

• Collagenital systemic to pulmonary shunts (large, small, repaired or nonrepaired)) 

• Portal hypertension 

• HIV infection 

• Drugs and toxins 

• Other (glycogen storage disease, gaucher disease, hereditary hemorrhagic 

teleangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy) 

II - Associated with significant venous or capillary involvement 

• Pulmonary veno-occlusive disease 

• Pulmonary capillary hemangiomatosis 

• Pulmonary venous hypertension 

• Left-sided atrial or ventricular heart disease 

• Left-sided valvular heart disease 

III - Pulmonary hypertension associated with hypoxemia 

• COPD 

• Interstitial lung disease 

• Sleep-disordered breathing 

• Alveolar hypoventilation disorders 

• Chronic exposure to high altitude 

IV - PH due to chronic thrombotic and/or embolic disease 

• Thromboembolic obstruction of proximal pulmonary arteries 

• Thromboembolic obstruction of distal pulmonary arteries 

• Pulmonary embolism (tumor, parasites, foreign material) 

V - Miscellaneous 

• Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary 

vessels (adenopathy, tumor, fibrosing mediastinitis) 

Table 2-8.1: Standard Classification of Pulmonary Hypertension 

PH can also result from diseases outside the lung. Autoimmune disorders, 

specifically collagen vascular diseases, are associated with the development 

of PH. Such diseases include scleroderma, systemic lupus erythematosis 

(also referred to as SLE or “lupus”) and rheumatoid arthritis. In patients with 

liver cirrhosis, 2 - 10% may develop a form of PH indistinguishable from IPAH 

pathologically. Since the 1980s, increasing numbers of cases of pulmonary 

hypertension associated with HIV have been reported in literature, although 

a cause and effect relationship has not been perfectly established. 

Pulmonary hypertension can also be a complication of certain drugs or dietary 

supplements. The relationship between drug ingestion and development of 

pulmonary hypertension was first raised in the late 1960s when there was an 

epidemic of unexplained pulmonary hypertension in the users of an appetite 

Chapter 2-8 • Pulmonary Vascular Diseases 

133

134 


suppressant drug, amironex fumarate, reported out of Switzerland, Austria and 

Germany. Some commonly used diabetes medications, which have since been 

withdrawn from the market, have also been linked with causing the disease. 

In 1981 severe pulmonary hypertension developed in a large number of people 

in Spain who ingested rapeseed oil intended for industrial use but which had 

been sold as cooking oil. More recently, chronic pulmonary hypertension has 

been associated with the use of products containing L-tryptophan, a common 

dietary supplement. 

Signs and Symptoms 

Signs and symptoms of PH are non-specific and are frequently attributed to 

other diseases that can lead to a delay in diagnosis. The most common symptom 

is shortness of breath with exertion. Chest pain and easy fatigability are also 

commonly reported. Ten percent of patients, more often women, might also 

report a painful, bluish discoloration of their fingertips (Raynaud’s phenomenon). 

Infrequently patients report hoarseness of voice or blood streaked sputum. 

Fainting and leg swelling may develop later on in the course of the disease. 

The mean time between onset of symptoms and diagnosis is 27 months. 

On physical examination, the usual second sound of the heart beat is louder 

than the first, due to the loud closure of the pulmonic valve in the setting of 

elevated right heart pressures. A murmur may be heard along the border of 

the chest bone during systole or contraction phase of the heart. As the disease 

progresses, signs of heart failure like liver enlargement and fluid retention 

may occur. 

Classification 

The degree of symptoms and functional abilities determines the functional 

class of the disease, which has been outlined by the World Health Organization. 

Class I patients do not have symptoms or limitations of activity. Class II patients 

are comfortable at rest, but are slightly limited in physical activity, and may 

experience dyspnea or fatigue, chest pain, or near syncope. Class III patients 

are marked limited in their ability to perform physical activity. Like Class II 

patients, they are comfortable at rest, but now experience symptoms at less than 

ordinary activity. Class IV patients are unable to perform any physical activity 

without experiencing symptoms, and may have shortness of breath at rest. 

Diagnostic Testing 

A variety of diagnostic tests may be incorporated into the evaluation of a 

patient with PH. Although not a very sensitive test, a simple electrocardiogram 

(ECG) may be suggestive of pulmonary hypertension and/or reveal underlying 

changes seen in patients with coronary artery disease that may be associated 

with decreased function of the left side of the heart. A chest x-ray might reveal 

a prominent main pulmonary artery and enlargement of the hilar vessels, and 

may also reveal a pulmonary condition that may cause pulmonary hypertension. 

Alternatively, a normal chest x-ray may be helpful to rule out other lung diseases 

that can present in a similar manner. Pulmonary function testing may aid in 

the evaluation of a specific cause of pulmonary hypertension, such as severe 

emphysema. Ventilation and perfusion imaging and angiography (described

in the next section) might be required to rule out the presence of blood clots 

in the lung which can cause pulmonary hypertension. 

Echocardiography is a useful noninvasive test to screen for the presence of 

pulmonary hypertension and in most cases can determine the severity of the 

disease reasonably accurately. Right heart catheterization, however, is the gold 

standard for determining the presence and severity of pulmonary hypertension. 

This is when a catheter is introduced from the groin or the neck vein and 

passed through the chambers of the right heart into the pulmonary artery. A 

mean pulmonary artery pressure of greater than 25 mm Hg at rest or 30 mm Hg 

during exercise is considered to be consistent with pulmonary hypertension. 

Measured pressures determine disease severity and can predict mortality. 

It is usually an outpatient procedure performed under local anesthesia. An 

algorithm for the diagnostic workup of PH is shown in Figure 2-8.1. 

No 

Follow patient 

Consider evaluation for other 

causes of symptoms 

Yes 

Treat underlying 

cause 

Response to 

treatment? 

Yes No 

Follow patient 

Clinical suspicion of PAH 

Perform history & physical exam, 

EKG, CXR, and echocardiogram 

PAH likely present? 

Figure 2-8.1: Algorithm for diagnostic workup of pulmonary hypertension. 

Yes 

Evaluate for associated diseases/conditions: 

• Screen for connective tissue disease: ANA, 

RF, ESR 

• V/Q Scan 

• Pulmonary angiogram if indicated 

• PFT’s 

• High resolution chest CT if indicated 

• Liver function testing 

o Serology for Hepatitis B and C 

• HIV Testing 

• Exercise and overnight oximetry 

o Sleep study if indicated 

• Measurement of TSH 

Associated disease or condition 

requiring treatment identified 

No 

Right heart catheterization with acute 

vasodilator testing 


135

136 


MEDICAL MANAGEMENT 

General Measures 

Although there is no cure for this disease, there have been considerable 

developments in the last two decades in managing patients with PH. 3 Since 

physical activity can increase pulmonary artery pressures significantly, it is 

advisable that patients refrain from heavy exercise or any activity that causes 

chest pain or fainting. Patients are advised to be careful about medications 

they take for other illnesses, such as certain decongestants. Patients who wish 

to become pregnant should be seen by a high risk obstetrics physician as well 

as one who specializes in pulmonary hypertension, as labor can potentially 

lead to life threatening strain on the heart, and can cause abrupt deterioration 

of the disease. Safe and effective methods of contraception should always be 

discussed. Flying in non-pressurized airplanes and being at high altitudes can 

cause worsening of the disease by decreasing the amount of oxygen available. 

In these situations, supplemental oxygen should be used. 

Specific Measures 

Patients with pulmonary hypertension may be prescribed blood thinning 

medications by their physicians. Warfarin (brand name “coumadin”) is the 

most common such agent to be prescribed and has been shown in some 

patients to prolong life. Patients should be told not to overuse non-steroidal 

anti-inflammatory drugs (NSAIDS) if they are on a blood thinner, and should 

also be educated about medications that might interact with this blood thinner. 

Due to the risk of hemorrhage, however, the decision to initiate treatment is 

made by the treating provider after careful evaluation of the suitability of a 

particular patient. Supplemental oxygen therapy is also commonly prescribed, 

and may also have long term benefits, especially in patients with co-existing 

lung diseases. 

As the disease progresses, the heart continues to fail, and patients may 

begin to retain fluid as evidenced by swollen feet and weight gain. Diuretics or 

“water pills” are useful to alleviate this swelling and may lead to less shortness 

of breath. In some cases, medications like digoxin might be useful to improve 

the contractility of the failing heart. 

Calcium channel blockers like cardizem and nifedipine were the first class of 

drugs used to treat this disorder. These agents are beneficial in a small fraction 

of patients with pulmonary hypertension who demonstrate "reversibility" of 

their elevated pulmonary artery pressures during right heart cathetrizations. 

Systemic hypotension (low blood pressure) can limit the use of these drugs. 

The mainstay of therapy is now selective pulmonary vasodilator therapy. 

These medications fall into three main categories: prostacyclin analogues, 

endothelin receptor antagonists, and phosphodiesterase inhibitors. Each 

class of medication focuses on different parts of the pathway leading to PH. 

The prostocyclin drugs were the first studied and are effective, though their 

use can be limited by the way these drugs need to be administered. While 

originally an indwelling intravenous delivery system was needed, there 

are now medications in this class that can be given subcutaneously or via a 

special inhaler used several times throughout the day. Endothelin receptor 

antagonists and phosphodiesterase inhibitors are gaining acceptance rapidly,

at least in part due to their availability in pill form. Combination regimens of 

these medications are also now being studied. 

Patients treated with these classes of drugs are usually under the supervision 

of a pulmonary hypertension specialist. Treatment of this disease is lifelong, 

involving close monitoring. For patients who continue to deteriorate on 

optimum medical therapy, heart-lung transplantation or lung transplantation 

is an option. Hopefully, as our experience with the disease and its management 

increase, we can continue to significantly impact on the quality of life and 

survival of patients with PH. 

PULMONARY EMBOLISM 

A blood clot, or thrombus, in the pulmonary circulation is called a pulmonary 

embolism (PE). Most of the blood clots in the lungs are a result of propagation 

or dislodging of clots formed in the deep veins of the legs, arms or pelvis. 4 A 

thrombus in any large deep vein is referred to as a deep venous thrombosis, 

or DVT. The obstruction of blood flow in the pulmonary circulation can cause 

shortness of breath and even death, depending on the size and number of blood 

clots. Untreated recurrent small pulmonary embolisms over time can lead to 

pulmonary hypertension, discussed earlier in this chapter. Treatment centers 

on blood thinning to prevent the formation of future clots. 

Epidemiology 

The National Heart, Lung, and Blood Institute (NHLBI) reports there are at least 

100,000 cases of PE occurring each year in the United States. PE is the third 

most common cause of death in hospitalized patients. If left untreated, about 

30 percent of patients who have PE will die. Most of those who die do so within 

the first few hours of the event. 5 These numbers are likely underestimates of the 

true incidence, as signs and symptoms are nonspecific and may masquerade 

as other illnesses and therefore, not be recognized. 6 

Risk Factors 

The major risk factors for blood clot formation include significantly-reduced 

blood flow, injury to the lining of blood vessels and certain conditions that 

may promote clot formation. Reduced blood flow is the most common and can 

result from immobility, which can be due to severe medical illness, hip and 

knee surgery, broken limbs, or even long periods of travel in a car or airplane. 

There are also genetic factors that predispose individuals for DVTs, often due 

to either too little or too much of a protein involved in clot formation. Common 

deficiencies involve Factor V Leiden, protein S and C, and anti- thrombin III. 

Increased Factor VIII and elevated homocysteine levels are also associated 

with clot formation. 7 

The risk for PE in patients presenting with a suspicion for the disease can 

be calculated using a simple patient-based assessment tool. Patients with 

significant points need further work up to diagnose or exclude PE. One such 

point system is known as the Modified Wells Criteria: clinical assessment 

for PE8,9 ,in which certain clinical risk factors obtained via initial history and 

physical examination are assigned points. The point assignment is characterized 

in Table 2-8.2. 


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138 


Clinical Risk Factors Points 

Clinical symptoms of deep venous thrombosis (leg swelling, 

pain with palpation) 

Other diagnosis less likely than PE 3.0 

Heart rate > 100 1.5 

Immobilization > 3 days or surgery in prior month 1.5 

Previous DVT/ PE 1.5 

Hemoptysis (coughing up blood) 1.0 

Malignancy 1.0 

Table 2-8.2: Clinical Risk Factors 

If a patient accumulates four or less points and has a blood test with low 

D-dimer (a break down product of clots, which will be discussed later), then 

PE is unlikely. However, if the patient has more than four points on initial 

evaluation, then further work up is warranted. 

Clinical Presentation 

The clinical presentation of PE is often non-specific and variable. Signs and 

symptoms may be related to the initial site of DVT, such as lower extremity 

swelling, tenderness or pain. Once a clot travels to the lung and occludes a 

segment of the pulmonary circulation, signs and symptoms may be related 

to the heart, lung, or systemic signs such low grade fever or hypotension. The 

most often reported signs and symptoms are shown in Table 2-8.3 and patients 

can present with none or many of these findings. 7 

Circulatory collapse, or shock, is associated with massive PE and occurs 

with a frequency of about eight percent. 6 Clinically, the patient may present 

with fainting in the setting of low blood pressure. Unexplained anxiety is also 

a relatively-common presenting symptom. 

Signs and Symptoms % of Patients 

Shortness of breath 70% 

Increased Respiratory Rate 70% 

Chest pain 65% 

Rapid Heart Rate 37% 

Cough 37% 

Blood streaked sputum 15% 

Table 2-8.3: Signs and Symptoms of Pulmonary Embolisms 

3.0

Diagnostic Tests 

Once the diagnosis of DVT or PE is entertained, further diagnostic tests are 

performed. 8 Chest x-rays can be normal or abnormal, and therefore cannot be 

used to make this diagnosis. They may be helpful however when an alternative 

diagnosis is found such as pneumonia, heart failure or a rib fracture. ECG 

changes are common, but are also non-specific. Echocardiograms may show 

elevated pressure in the right side of the heart (i.e., pulmonary hypertension) 

due to an occluded pulmonary circulation, though this can also be seen in a 

number of conditions including heart failure, severe emphysema and sleep 

apnea, as discussed earlier. Arterial blood gases can also be normal, especially 

in younger patients. 

Evaluation for DVT 

Duplex ultrasound of the lower extremities may reveal a clot in the deep 

veins, even without lower extremity swelling. When this is found, it is more 

likely that the chest imaging studies described below will show a PE. Since 

both a DVT and a PE are treated similarly with blood thinners, a diagnosis 

of a DVT may avoid further testing. In the absence of a DVT, however, a PE 

may still have occurred, and perhaps the presence of a clot in the pulmonary 

circulation and not the lower extremities signifies that the clot dislodged and 

propagated. Since this test is relatively quick, portable, accurate, and relies on 

sound waves, and is therefore non-invasive, it is a common first approach to 

the diagnosis of PE. Its usefulness is limited however in patients with severe 

obesity or lower extremity edema. 

D-dimer Concentration 

A D-dimer assay is a blood test which looks for enzymatic break down 

products of clots. It is often positive in many conditions and is therefore nonspecific. 

However, it is rarely negative (< 5 % of patients) in patients who have 

a documented DVT or PE. In a low risk patient, a negative D-dimer may help 

exclude PE from the differential diagnosis. 9 

Ventilation-Perfusion (V/Q) Scan 

The V/Q scan was previously the most common diagnostic test for PE and has 

been well-studied. Interpretation is based on the probability of the patient 

having a PE and is determined by comparing the blood flow and the air flow 

in regions of the lung. A high probability study would show no blood flow to 

a region that is aerated. A normal V/Q scan would show intact blood flow and 

aeration and essentially rules out a clinically significant PE. Unfortunately, 

most scans are neither normal nor high probability. In addition, as many as 

40% of patients with a low probability study but with a high clinical likelihood 

for PE, turn out to have this diagnosis. 

Spiral CT or CT Angiogram 

CT pulmonary angiogram is an accurate, invasive test that is commonly used 

to diagnose PE. It involves injection of contrast dye through an intravenous 

line followed by CT scan of the chest. The dye will fill up the pulmonary 

vessels, and PE would be seen as filling defects (see Figure 2-8.2). The dye 

may occasionally cause renal insufficiency and should not be used in patients 


139

140 


with renal failure. In many patients, a negative duplex ultrasound of the lower 

extremities and a negative spiral CT rules out PE. 9 Another advantage of this 

test is that it permits visualization of the entire lung, which may lead to an 

alternative diagnosis when a PE is not identified. 

Figure 2-8.2: Filling Defects in Pulmonary Vessels 

Pulmonary Angiogram 

Pulmonary angiogram is considered the gold standard to diagnose PE. In 

this test, a catheter is inserted into a blood vessel in the groin or arm and 

then passed into the blood vessels of the lung. Injection of contrast dye then 

permits direct imaging of the pulmonary circulation. A negative pulmonary 

angiogram rules out PE. This test, however, is invasive, requires experienced 

support staff and has a small risk of serious complications such as bleeding 

and arrhythmias, and therefore is not commonly performed. 

MANAGEMENT 

PE is a potentially life-threatening disease and a high index of suspicion needs 

to be maintained in patients at risk or with suggestive symptoms. Management 

is in general, supportive, where the patient receives blood thinners to prevent 

the formation of new clots and the extension of existing clots. 

General Measures 

Supplemental oxygen is often given, especially if the oxygen saturation level is 

low. If the patient has low blood pressure, intravenous fluids are given. Patients 

are often monitored for irregular heart beats. 

Specific Measures 

Anticoagulation therapy with blood thinning agents is the initial treatment of 

patients with PE. For the most part, it should be initiated in all patients except 

those who have active internal bleeding. If no contraindication exists, heparin 

is started followed by long-term therapy with coumadin. The duration of 

therapy is decided based on assessment of risk versus benefit. For patients who 

are diagnosed for the first time with PE, blood thinning treatment commonly 

lasts for six months, while those with recurrent PE may be treated for the rest of

their life. The most common side effect of blood thinners is bleeding. This can 

be reduced by close monitoring of blood tests to keep the blood thin enough 

but not too thin. 

Filters placed in the superior or inferior vena cava, the major veins returning 

blood from the upper and lower parts of the body, respectively, can prevent 

clot dissemination to the lungs. They should be considered as a therapeutic 

modality in patients who either have a contraindication to the use of blood 

thinners or who have PE despite appropriate and adequate therapy with blood 

thinners. 

Prognosis 

Without treatment, PE has 30% mortality from recurrent emboli. With proper 

therapy, the mortality is reduced to two to eight percent. 6 

PULMONARY EDEMA 

Pulmonary edema signifies abnormal accumulation of fluid in the air sacs 

of the lungs. This occurs when there is (1) an increased pressure in the blood 

vessels of the lungs (cardiogenic pulmonary edema), or (2) an increase in the 

leakiness of these blood vessels (non cardiogenic pulmonary edema) or (3) some 

combination of the two. As fluid fills the lungs, oxygen cannot be absorbed 

and the patient develops low oxygen levels. 

Cardiogenic pulmonary edema is due to heart failure, which means the heart 

is not able to pump out enough of the blood it is receiving from the lungs and 

the system backs up. This can result from weakness in the left ventricle which 

can occur after a heart attack. Heart valves that don’t open wide enough or are 

too leaky can also cause fluid to accumulate. High pressure in the right side 

of the heart (pulmonary hypertension) can also lead to pulmonary edema. 

Non-cardiogenic pulmonary edema occurs when fluid builds up but the 

heart is functioning normally. This can occur as a result of lung infections, 

aspiration, near-drowning, high-altitude, or smoke inhalation, to name a few. 

Pulmonary edema due to toxic gas inhalation will be discussed separately at 

the end of this chapter. 

Patients with pulmonary edema complain of extreme shortness of breath 

similar to suffocating, which is worse when lying flat. They are often quite 

anxious. The physical exam in patients with pulmonary edema is nonspecific. 

Patients have a high respiratory rate. Some are coughing with frothy, blood 

tinged, sputum. Lung exam often reveals crackles, though occasionally 

wheezing is also heard. 

The diagnosis of pulmonary edema is made by combining the clinical 

presentation and physical exam with a good medical history. It is confirmed by 

the chest x-ray which shows bilateral patchy haziness, often accompanied by a 

collection of fluid (pleural effusion). Measurement of impaired gas exchange 

can be performed using noninvasive pulse oximetry or invasive arterial blood 

sampling. In some situations hemodynamic monitoring can be performed by 

catheterization of the heart. 


141

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Pulmonary Edema Associated with Inhalation of Foreign 

Material 

Pulmonary edema can occur as a result of toxic gas and smoke inhalation. 

This may occur during exposure to chemicals during building or vehicular 

fires or industrial accidents. Pulmonary edema in cases of toxic gas or smoke 

inhalation is due to lung injury which is thought to begin with chemical burns 

to the upper and lower airways. The incidence is thought to increase with the 

extent of burns. Two thirds of patients with more than 70% burns will also 

have inhalational injury. Inhalation injury adds significantly to the mortality 

in patients with burns. In one large cohort, the mortality rate was 29% when 

inhalation injury was present and only two percent in its absence. 10 

The diagnosis of inhalational injury is made by reported history of exposure, 

physical exam, and testing. Carbon monoxide is frequently inhaled during 

fires, and its levels in the blood can serve as a diagnostic marker of the extent of 

exposure. The severity of the inhalational injury can be estimated by fiberoptic 

examination of the airways. 

The simplest and best treatment for smoke inhalation is termination of exposure 

as soon as possible and then administration of 100% oxygen. Specific antidotes 

like sodium nitrite and thiosulfate may or may not be needed. Hyperbaric 

oxygen is also recommended although data proving its superiority is scarce. 

Patients with severe lung injury or upper airway edema may require intubation 

and mechanical ventilation. The efficacy of antibiotics and corticosteroids is 

not proven. 11 The administration of diuretics should be avoided. 12 

REFERENCES 

1. Rubin, L.J., Primary pulmonary hypertension. N Engl J Med, 1997. 336(2): 

p. 111-7. 

2. Elliot, C.G., R.J. Barst, W. Seeger, M. Porres-Aguilar, L.M. Brown, R.T. 

Zamanian, and L.J. Rubin. Worldwide physician Eeducation and training 

in pulmonary hypertension pulmonary vascular disease: The global 

perspective. CHEST. 2010, 137 (6 suppl): p. 85S-94S. 

3. Humbert, M., O. Sitbon, and G. Simonneau, Treatment of pulmonary 

arterial hypertension. N Engl J Med, 2004. 351(14): p. 1425-36. 

4. Goldhaber, S.Z., Pulmonary embolism. N Engl J Med, 1998. 339(2): p. 93- 

104. 

5. Pulmonary embolism. NHLBI. June 2009. Web. July 2010. . 

6. Dismuke, S.E. and E.H. Wagner, Pulmonary embolism as a cause of death. 

The changing mortality in hospitalized patients. Jama, 1986. 255(15): p. 

2039-42. 

7. Value of the ventilation/perfusion scan in acute pulmonary embolism. 

Results of the prospective investigation of pulmonary embolism diagnosis 

(PIOPED). The PIOPED Investigators. Jama, 1990. 263(20): p. 2753-9.

8. Fedullo, P.F. and V.F. Tapson, Clinical practice. The evaluation of suspected 

pulmonary embolism. N Engl J Med, 2003. 349(13): p. 1247-56. 

9. van Belle, A., et al., Effectiveness of managing suspected pulmonary 

embolism using an algorithm combining clinical probability, D-dimer 

testing, and computed tomography. Jama, 2006. 295(2): p. 172-9. 

10. Saffle, J.R., B. Davis, and P. Williams, Recent outcomes in the treatment 

of burn injury in the United States: a report from the American Burn 

Association Patient Registry. J Burn Care Rehabil, 1995. 16(3 Pt 1): p. 219- 

32; discussion 288-9. 

11. Monafo, W.W., Initial management of burns. N Engl J Med, 1996. 335(21): 

p. 1581-6. 

12. Kales, S.N. and D.C. Christiani, Acute chemical emergencies. N Engl J 

Med, 2004. 350(8): p. 800-8. 


143


Chapter 2-9 

Fire Fighters and 

Lung Cancer 

By Dr. Adrienne Flowers, MD and Dr. Melissa McDiarmid, MD 

THE FIRE FIGHTING ENVIRONMENT 

The toxic environments in which fire service members live and work have long 

been suspected to have an adverse effect on fire fighter health. Virtually every 

hazard class can be found in the fire fighting environment including physical 

hazards, such as ionizing radiation, biologic agents, musculoskeletal hazards 

and the psycho-social stress of responding to life-threatening emergencies. 1 

Chemical hazards, primarily the toxic products of combustion2,3,4 have been 

of particular concern as threats to health, especially when considering the 

work-relatedness of cancer development. 

Known or presumed carcinogens (cancer-causing agents) have been 

found in the fire fighting environment and include: benzene, formaldehyde, 

acrolein, perchloroethylene, cadmium, and some of the polycyclic aromatic 

hydrocarbons (PAH) such as benzo(a)pyrene and chrysene. 3 Asbestos exposure 

during overhaul operations has long been raised as a risk5,6 and the exposure to 

diesel exhaust at the fire house has also been flagged as potentially hazardous. 7 

There is evidence to support the belief that some of these hazards could 

cause respiratory disease through an inhalation exposure route. Health studies 

over the last 30 years have consistently shown excesses of non-malignant 

respiratory disease in fire service members. 8,9,10,11,12 Less consistent however, 

have been links between firefighting and malignancies of the lung. 12,13,,14 The 

following limitations of fire fighter health studies make the evaluation of 

lung cancer risk due to exposures received during firefighting activities very 

difficult. First, there is a general lack of detailed historic smoking information 

among fire fighters. Smoking is a primary cause of lung cancer and this lack of 

information makes it impossible to separate the contribution of work exposures 

and smoking in the development of lung cancer (Figure 2-9.1). Second, because 

lung cancer can take many decades to develop, insufficient years of observation 

can result in under identification of deaths. For example, if the study period 

is not of sufficient length, fire fighters who develop and die from lung cancer 

late in life, long after the typical 20-year fire fighter career span, may not be 

identified. The onset of lung cancer relatively late in life, long after fire service 

retirement would then elude researchers trying to link the diagnosis to work 

which ended several decades earlier. None the less, there are biologically 

plausible reasons to be concerned about lung cancer development from fire 

fighting work, especially among the more senior members who worked prior 

to regular use of self-contained breathing apparatus (SCBA). 

This chapter will provide an overview of lung cancer, its types, how it presents 

and is diagnosed, classified and treated and what is known about its work- 

Chapter 2-9 • Fire Fighter Lung Cancer 145

146 Chapter 2-9 • Fire Fighter Lung Cancer 

Per Capita Ci garette Consumpti on 

Tobacco Use in the US, 1900-2000 

5000 

4500 

4000 

3500 

3000 

2500 

2000 

1500 

1000 

500 

0 

Per capita cigarette consumption 

1900 

1905 

1910 

1915 

1920 

1925 

1930 

1935 

1940 

1945 

1950 

1955 

1960 

1965 

1970 

1975 

1980 

1985 

1990 

1995 

2000 

Figure 2-9.1: Tobacco Use and Lung Cancer in the United States 

relatedness among other occupations and exposed groups. Some prevention 

strategies applicable to fire service members will also be described. 

LUNG CANCER EPIDEMIOLOGY 

Although lung cancer is the second most common type of cancer diagnosed in 

both men and women (second to prostate cancer in men and breast cancer in 

women), it ranks first as the cause of cancer deaths annually in both genders. 15 

In fact, it accounts for more deaths annually than breast, prostate and colon 

cancer combined. 15 According to the National Cancer Institute, the estimated 

numbers of new cases and deaths from lung cancer in the United States in 2008 

was 215,020 and 161,840, respectively. It typically occurs in people older than 

50 years. Based on reports from cases between 2001-2005, the median age at 

diagnosis is 74 years and the number of new cases increases with age. 16 Lung 

cancer is rare in people less than 45 years old. 15 Because of the high mortality 

rate, survival statistics for lung cancer patients are quite poor with only 15% 

of patients achieving the five-year survival mark. 15 

A person’s risk of developing lung cancer, like any cancer, is dependent on 

two types of factors: (1) host factors involving a person’s genetic make up that 

ultimately influence susceptibility to cancer-causing agents and (2) environmental 

factors which include not only risks from exposure to the external environment 

such as contaminated air or workplace hazards, but also substances found in 

the diet or acquired through social habits such as smoking. 17 

In addition to the genetic host factors that influence lung cancer risk, there 

are other personal health factors that must be considered. For example, people 

with a history of chronic obstructive pulmonary disease also have an increased 

risk of developing lung cancer. As the obstruction on the pulmonary function 

test (PFT) worsens, so does the risk of lung cancer. 18 It remains controversial 

whether a medical history of other previous lung diseases may also predispose 

to certain types of lung cancer. 19 

Yea r 

Male lung cancer death rate 

Female lung cancer death rate 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Age-Adjusted Lung Cancer Death 

Rates* 

*Age-adjusted to 2000 US standard population. 

Source: Death rates: US Mortality Public Use Tapes, 1960-2000, US Mortality Volumes, 1930-1959, National 

Center for Health Statistics, Centers for Disease Control and Prevention, 2002. Cigarette consumption: US 

Department of Agriculture, 1900-2000.

That the principal risk factor for lung cancer development is cigarette smoking 

is undisputed. About 90% of all lung cancer in the United States is estimated to 

be attributable to cigarette smoking 20 which is thought to increase the risk of 

lung cancer development by 20-fold, compared to those who never smoked. In 

addition, secondhand smoke, or smoke from other people’s cigarettes, increases 

the risk of lung cancer in non-smokers. Public health experts state that current 

lung cancer statistics describe an "epidemic" that can be traced to the 1930s 

and reflect the increase in cigarette smoking at that time and which continued 

rise into the 1980s for men and which still continues to rise in women. 

While most of the studies on smoking and lung cancer have focused on 

cigarette smoking because the prevalence of such smoking was so high after 

World War II, exposure from pipes and cigar smoking is also thought also to 

raise the risk of lung cancer. 21 

There are many other environmental causes of lung cancer. In fact, lung 

cancer has been the most thoroughly studied of cancers regarding environmental 

causes, perhaps because of the obvious inhalation exposure route making 

deposition of cancer- causing agents directly into the lung, a plausible scenario 

for initiating a cancer. Table 2-9.1, displays a list of currently-recognized 

environmental causes of lung cancer. 15,17,21 

The occupational hazards which contribute to lung cancer risk include 

the polycyclic aromatic hydrocarbons which derive from coal products and 

energy production and from combustion of these products. Other chemicals 

including some metals are known lung carcinogens as is asbestos and diesel 

exhaust, which, as mentioned above are encountered in the fire service. Studies 

of cancer risk by occupational group tend to reinforce these observations 

about agents which increase lung cancer risk, as seen in Table 2-9.2. 22,23,24 It 

would be fairly easy to map the substances which are known to increase lung 

cancer risk from Table 2-9.1 to the occupations where they are encountered 

in Table 2-9.2. 

LUNG CANCER 

There are two main categories of lung cancer: Non-small Cell Lung Cancer 

(NSCLC) and Small Cell Lung Cancer (SCLC). As their appearance may be 

similar on chest x-ray or CT scan, the only certain way to distinguish between 

them is to examine specimens under a microscope. Each has different subclasses 

within the main categories that are based on the cell type in the lung 

that is growing abnormally. 

Non Small Cell Lung Cancer 

NSCLC is a broad category which encompasses all types of cancer that are not 

SCLC. This classification accounts for approximately 80% of lung cancer cases. 15 

This main category is further subdivided into seven classes of lung cancer 

based on the type of lung cell that is affected. This can be determined by the 

appearance of the cell under a microscope. Among this group of seven classes 

of NSCLC, the three most prevalent are adenocarcinoma, squamous cell, and 

large cell cancer, in that order. 


148 

Chapter 2-9 • Fire Fighter Lung Cancer 

Environmental Causes of Lung Cancer 

Smoking -- Active 

Smoking -- Passive (Second-hand exposure) 

Smoking -- Marijuana 

Diet (Low Fruit & Vegetable Consumption) 

Air Pollution 

Coal Cooking fires -- indoor exposures -- developing world 

Coke Oven Emissions (Benzo (a) pyrene) 

Soots 

Shale Oil 

Arsenic 

Chromium 

Nickel 

Beryllium 

Cadmium 

Vinyl Chloride 

Mustard Gas 

Chloromethyl ether 

Diesel exhaust 

Silica (crystalline) 

Asbestos 

Radiation 

Low LET (linear energy transfer – e.g. x-rays and gamma rays) 

High LET (e.g. neutrons, radon) 

Table 2-9.1: Environmental Causes of Lung Cancer (Adapted from Alberg and Samet, 2003; 17 

ACS, 2008; 15 IARC, 2009 21 ) 

Selected Occupations at Increased Risk of Lung Cancer Development 

Coal Gasification Workers 

Coal Tar Distillation Workers 

Coke Oven Workers 


Insulators 

Metal and Machining Workers 

Miners and Quarry Workers 

Painters 

Pavers and Roofers 

Rubber Workers 

Table 2-9.2: Selected Occupations at Increased Risk of Lung Cancer Development (Adapted 

from IARC, 2009; 22 MacArthur et al., 2008; 36 Bruske-Hohlfeld et al., 2000 24 ) 

• Adenocarcinoma is the most common form of NSCLC. This type of cancer 

is responsible for about 40% of all types of lung cancer. 15 In the lung, these 

cancers typically form on the peripheral of the lung. 25 Due to hormonal 

differences or other as yet unknown reasons, this is the form of lung cancer 

that is most frequently diagnosed in women.

• Squamous Cell Carcinoma makes up about 25 - 30% of all lung cancers 

and is slow growing. It usually takes three to four years to become evident 

on a chest x-ray. It tends to arise more centrally in the lung; therefore on 

presentation, there may be obstruction of bronchi with post-obstructive 

pneumonia. 25 

• Large Cell Cancer is a less commonly-occurring type of cancer representing 

about 10 - 15% of lung tumors. 15,25 

Clinical Presentation and Symptoms of NSCLC 

Because there are no screening protocols considered beneficial for large-scale 

population testing for lung cancer (i.e., testing of asymptomatic people for early 

detection), lung cancer is usually diagnosed when a patient presents to their 

physician with symptoms and a chest radiograph (x-ray) is obtained (Figure 

2-9.2). Almost 90% of people have symptoms at the time of diagnosis. Most in 

fact have at least two symptoms at diagnosis. 26 The most common symptoms 

reported are cough and generalized systemic complaints that include weakness, 

fatigue or anorexia (inability to eat). Other symptoms that may be present 

at the time of diagnosis include: dyspnea (shortness of breath), chest pain, 

bloody sputum (phlegm), and pneumonia. Some patients will present with 

a change in the shape of their nail beds called clubbing. Others may present 

with elevated blood calcium levels. 

Figure 2-9.2: Lung Mass (arrow) Subsequently Identified as Non Small Cell Lung Cancer 

on Biopsy 

Symptoms may occur that reflect the impact of the tumor behaving as a mass 

in the chest and pressing on other structures such as nerves or airways that 

could manifest as hoarseness, trouble swallowing, stridor (difficulty breathing 

in with resulting noise heard over the trachea [air-pipe] in the neck) or cough. 

Symptoms resulting from compression of major blood vessels such as facial or 

upper body swelling (superior vena cava syndrome) and lightheadedness may 

sometimes occur. Symptoms may occur from spread of the tumor to outside 

the chest (metastasis) to other organs. Examples include: bone pain from bone 

involvement; fatigue from brain and/or liver involvement, headaches and/or 

seizures from brain involvement and paralysis from spinal cord involvement. 



Figure 2-9.3 depicts the frequency of commonly-occurring symptoms 

reported by lung cancer patients at time of presentation. 

Common Reported Symptoms of Lung Cancer 

Cough 

20% 

No Symptoms 

14% 

Metastatic 

Symptoms 

10% 

Bloody Sputum 

19% 

Systemic Symptoms 

11% 

Chest Pain 

17% 

Infection 

9% 

Figure 2-9.3: Most Common Symptoms at the Time of Presentation: (Adapted from Buccheri, 

2004) 26 

Diagnosis 

The diagnosis of lung cancer is usually determined after a patient presents to 

the doctor with symptoms as described above. The process will begin with a 

thorough health history and physical examination. The history focuses on risk 

factors for cancer including cigarette smoking, environmental or occupational 

exposure to carcinogens and family history of lung cancer. Imaging of the 

chest is an important component of the diagnostic assessment. Most clinicians 

will start with a chest radiograph (x-ray) to determine if a lung mass (tumor) is 

present (see Figure 2-9.2). A normal chest x-ray can rule out this diagnosis in 

many instances: however, in some cases cancer can be missed. For example, 

a review of primary care records in England revealed that 10% of patients 

diagnosed with lung cancer had a chest x-ray interpreted as normal within the 

year prior to their diagnosis. 19 This is especially true if the tumor was less than 

1 cm or 10 mm in diameter or if it is hidden behind a normal chest structure 

such as a bone or lymph node. 

If an abnormality is seen on a chest x-ray, this can be further evaluated by 

Computed Tomography (CT) scanning. In addition to confirming abnormalities 

on chest x-rays, CT imaging may also find abnormalities that may not be visible 

on a chest x-ray, such as very small nodules less than 1 cm in diameter and 

swollen lymph nodes. Figure 2-9.4 depicts the diagnostic steps which are taken 

to evaluate a patient for lung cancer. 

Tissue Biopsy 

Once a mass has been identified, diagnosis is made by tissue biopsy or aspirate 

of the abnormal tissue. There are different types of procedures to obtain this 

biopsy material and the most appropriate procedure or approach depends

Peripheral Lesion 

+/- lymphadenopathy 

1. Fine Needle Aspiration 

2. Bronchoscopy 

3. Video-Assisted Thoracoscopy 

4. Thoracotomy 

Chest Radiograph 

Computed Tomography 

(CT Scanning) 

Central Lesion 

+/- lymphadenopathy 

1. Sputum Cytology 

2. Bronchoscopy 

3. Fine Needle Aspiration 

4. Thoracotomy 

Figure 2-9.4: Diagnostic Protocol for Lung Cancer Patients: (Adapted from Davita,200525 

and National Comprehensive Cancer Network (NCCN) 27 ) 

on numerous factors including: the location of the tumor, the likelihood that 

metastasis has already occurred, how ill the patient is, local expertise and 

patient preference. Choices include bronchoscopy, transthoracic needle, 

mediastinoscopy, video-assisted thoracoscopy and occasionally, open lung 

thoracotomy. These procedures are often performed by pulmonologists (lung 

doctors), invasive radiologists, or thoracic (chest) surgeons to obtain biopsy 

specimens and confirm involvement of tissues and lymph nodes that are seen 

on CT scan and other imaging studies. 28 A description of these approaches is 

detailed below. 

• Bronchoscopy is a procedure to view airways directly. A flexible scope is 

inserted into the airway through the mouth or nose. Through the scope, 

a tissue biopsy or other specimens (brushing or washings for cells) are 

obtained from a tumor in the airway (Figure 2-9.5) or from a tumor in the 

lung. New techniques coupling bronchoscopy and ultrasound guidance 

Figure 2-9.5: Tumor Mass within a Bronchus or Airway (arrow) that was Visualized and then 

Biopsied through a Bronchoscope. 



are allowing even small lung nodules and lymph nodes to be sampled. 

Local anesthesia and mild sedation is provided, so that the bronchoscopy is 

only mildly uncomfortable. This procedure does not require an overnight 

hospital stay. 

• Transthoracic Needle Biopsy or Aspirate is a procedure to sample 

peripheral lung nodules or masses. No incision is required. Rather, a 

needle is passed through the chest and then with X-ray guidance is directed 

into the nodule or mass to obtain the tissue sample. Local anesthesia is 

provided and mild sedation is available if needed. This procedure does 

not require an overnight hospital stay. 

• Mediastinoscopy is a procedure to examine and sample the lymph nodes 

inside the center of the chest. In this procedure a small incision (about 

2 inches) is made at the base of the neck and a scope is passed into the 

middle of the chest. Biopsy samples can be obtained from these centrally 

located lymph nodes but not from the airway or lungs. This procedure is 

done under general anesthesia and typically does not require an overnight 

hospital stay. 

• Video-Assisted Thorascopic Surgery (VATS) or Open Lung Thoracotomy 

is a procedure to sample and/or remove lymph nodes, lung nodules and 

other evidence of cancer in the chest. This procedure is done under general 

anesthesia and will require a hospital stay for several days or longer. 

Staging of NSCLC 

Staging of the disease refers to determining the extent of the cancer in the 

body. This includes how large the tumor is and whether there is evidence for 

metastasis (cancer spread) to other areas including lymph nodes within the 

chest or to distal organs outside the chest. One of the best indicators of the 

extent of cancer is involvement of the lymph nodes. Lymph nodes are tiny 

glands that help the body fight infection but are often the first areas for tumor 

metastasis. Staging for NSCLC, in contrast to SCLC, is critically important 

because although metastasis is far too common, it is not the presumption. 

The prognosis and treatment will depend on the stage or extent of disease at 

the time of diagnosis. 

Staging is done by radiographic imaging of the body. All patients should 

receive a chest CT that includes imaging to assess abdominal organs that are 

common sites of metastasis – the liver and adrenal glands. Any patient with 

neurologic symptoms should also have a magnetic resonance imaging (MRI) 

of the head and spinal cord to evaluate for metastasis to the brain or spine. A 

positron emission tomography (PET) scan is now becoming the test of choice 

for staging of non-neurologic organs (for details see chapter on chest imaging). 

Cancer is divided into five main stages: zero, one, two, three and four. The 

most commonly used staging classification system, the Tumor Nodal and 

Metastasis (TNM) system, grades tumors on the basis of tumor size and location 

and the consequences thereof such as local invasion, partial lung collapse, or 

obstructive pneumonia (T), the presence and location of regional lymph node 

involvement (N), and the presence or absence of distant metastases (M). The 

overall stage of the tumor is determined by the combination of the TNM score,

which defines the extent of disease, and is used to determine the prognosis and 

treatment. An A and B subgroup is applied to stages to separate those within a 

stage who have certain findings associated with a better or worse prognosis. 

Overall, the earlier the stage, the easier to treat and the better the prognosis. 

When diagnostic techniques and/or treatments are developed and impact on 

survival, the staging system is revised. Although there are complexities in the 

staging system that are beyond the scope of this chapter, the basic criteria for 

classification are as follows: 

• Stage 0 also known as carcinoma in situ is a very early stage of cancer 

where the cells are not yet invading. Stage 0 disease would not be evident 

on chest x-ray or CT. Rarely, if ever do we make the diagnosis of lung 

cancer at Stage 0 , but it is our hope that newer screening techniques will 

be developed to achieve this. 

• Stage I is early disease where the tumor is only on one side of the lung; 

is not greater than 3 cm in diameter; and does not involve the chest wall, 

pleura (the skin between the lung and chest wall), lymph nodes or main 

airway. Figure 2-9.6 shows a chest x-ray and CT scan of stage I lung cancer. 

• Stage II is a tumor on one side of the chest that is either not greater than 

3 cm in diameter but involves chest lymph nodes on the same side close 

to the tumor, or is greater than 3 cm in diameter without lymph node 

involvement or the inner surface of the pleura. Figure 2-9.7 shows a chest 

x-ray and CT scan of stage II lung cancer. 

• Stage III is a tumor of any size that involves chest lymph nodes distant 

from the tumor (same or opposite side), or diaphragm, main airways, or 

the outer surface of the pleura or pericardium (lining between lung and 

heart). Figure 2-9.8 shows a chest x-ray and CT scan of stage III lung cancer. 

• Stage IV is metastastatic cancer, where the disease has spread to other 

organs in the body. Lung cancer most commonly spreads to the other lung, 

or pleural fluid (between lung and chest wall), chest wall, bone, brain, 

liver, and/or adrenal glands. 25 Figure 2-9.9 shows a chest x-ray and CT 

scan of stage IV lung cancer based on metastasis to the liver. 

Prognosis 

The higher the stage, the more advanced the cancer and poorer the prognosis. 

The percentage of patients who live at least five years after being diagnosed 

is termed the five-year survival rate. For patients diagnosed with stage I lung 

cancer, the five-year survival rate is 56%, though rates are higher for the A 

subgroup (73%). This relatively favorable survival substantially decreases as 

the disease spreads. The five-year survival rate for stage IV is 2%. 29 

There are certain factors, called prognostic factors that may predict a 

better outcome of treatment and prognosis for a given stage of disease. Good 

prognostic factors at the time of diagnosis include early staging at the time of 

diagnosis, the patient’s good general functional ability called “performance 

status” which includes daily activities as well as function assessed by pulmonary 

and cardiac tests and either no weight loss or weight loss of less than 5% at the 

onset of disease. 



Figure 2-9.6: Chest X-ray and CT Scan Showing a Nodule (less than 3 cm in diameter) 

without Spread to Adjacent Structures (Stage I disease). 

Treatment of NSCLC 

Treatment is based on the staging at the time of diagnosis. The treatment 

of cancer has become a field involving multiple “modalities”, or types of 

interventions. Based on the type and extent of disease, a therapeutic plan is 

designed by a pulmonologist, thoracic surgeon, medical oncologist who may 

administer chemotherapy and a radiation oncologist who may administer 

radiation therapy. In latter stages of disease, pain or palliative physicians are 

an important addition to this process. 

Unfortunately, 75% of all lung cancer (NSCLC and SCLC) present with either 

regional or metastatic disease at the time of diagnosis. 29 For this reason, very 

few patients have disease that is amenable to cure by surgical resection alone;

Figure 2-9.7: Chest X-ray and CT Scan Showing a Nodule (greater than 3 cm in diameter) 

without Spread to Adjacent Structures (Stage II disease). 

however, for patients that present with localized disease, Stage I-II, surgical 

resection vs. surgical resection with low-dose chemotherapy is the current 

approach. Treatment decisions for some stage II and all stage III through IV 

disease are far more complex. There are no standard treatment regimens for 

NSCLC and each decision to treat must be made on an individual basis. The 

three modalities of treatment are outlined below. 



Figure 2-9.8: Chest CT Scan Showing a Tumor with Lymph Node (arrow) Involvement in 

a Location that Defines this as Stage III Disease. 

Figure 2-9.9: CT Scan Showing Metastasis to the Liver (larger ones identified by arrows) 

Thereby Defining this as Stage IV Disease. 

• Surgical Resection remains the mainstay of treatment for Stage I and 

Stage II NSCLC. It involves complete removal of the tumor. Depending on 

location and size of the tumor, the surgical approach can be performed 

by video assisted thoracoscopic surgery or by open lung thoracotomy. 

In general, when possible, the entire lobe of the lung where the cancer 

is found is removed (lobectomy). However, in certain patients removal

of a cone-shape piece of lung, or wedge resection may be performed. 

For carefully selected patients with Stage III disease, surgery may also 

be considered (usually those with negative mediastinal lymph nodes). 

Some patients with stage IV disease may benefit from surgical resection 

of an isolated metastasis (e.g., to the brain or adrenal gland) to improve 

functional status but this does not improve survival. 

• Chemotherapy is the mainstay of treatment for more advanced NSCLC. 

This involves the use of medications designed to kill cancerous cells in the 

body. As opposed to patients with Stage I NSCLC, those with Stage II disease 

who have undergone surgical resection, and who then receive adjuvant 

chemotherapy (treatment that is given as an add-on to the primary surgical 

treatment) have improved survival versus surgery alone. For patients with 

stage III disease, a combined modality approach using chemotherapy and 

radiation therapy is generally preferred. Patients with stage IV disease are 

generally treated with systemic therapy and/or palliative care. Side effects 

of chemotherapy vary depending upon the regimen used. There are many 

drugs for the oncologist to consider, and treatment choices (involving the 

selection and number of agents) are individualized to the patient. As new 

research is accepted and mainstreamed into general clinical practice, 

chemotherapy recommendations will change. 

• Radiation Therapy is often used in conjunction with chemotherapy in 

patients with an advanced stage of NSCLC. In those patients with early 

stage disease but who are not candidates for surgery (due to advanced 

age or coexisting medical problems), stereotactic body radiation therapy 

(SBRT), a technique that utilizes precisely-targeted radiation to a tumor, 

may also be an option. The goal of radiation therapy is to target x-ray 

beams directly at cancer cells while minimizing damage to adjacent 

tissue. Radiation therapy, when successful, shrinks the size of the tumor. 

For extensive disease, radiation helps to alleviate symptoms (e.g. pain) 

associated with the cancer burden. Radiation therapy to the brain may 

also help treat or prevent further metastasis. 

Small Cell Lung Cancer 

Annually, SCLC now represents about 15% of all lung cancers. 29 In 2008, 

approximately 32,000 new cases were diagnosed in the United States. This 

type of cancer is on the decrease from a peak in 1986 when it represented 18% 

of all lung cancers. 

SCLC has many environmental risk factors. This cancer is almost always 

associated with cigarette smoking. 1 As many as 98% of patients with SCLC 

have a history of smoking. 28 For smokers, the risk of developing SCLC is 25 

times higher than non-smokers. The same observations have been seen with 

cigars and pipes. 1 There is also concern that cigarettes with menthol may 

have higher levels of cancer because menthol allows for more inhalation of 

the cigarette smoke. 

Other environmental exposures that raise the risk for SCLC include: 

bischloromethyl ether, vinyl chloride, asbestos, radon and exposure to 

therapeutic radiation. It is also important to note that developed countries 

have higher incidences of SCLC, suggesting that air pollution exacerbates the 

development of SCLC. 



Certain types of SCLC can secrete biologically-active antibodies, hormones 

and proteins. When these tumors secrete these biologically-active substances, the 

condition is called a “paraneoplastic syndrome”. Most common paraneoplastic 

syndromes include the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), 

Cushing’s, Lambert- Eaton syndrome and paraneoplastic encephalomyelitis. 

These syndromes can cause a variety of symptoms depending on the substance 

released. 

Clinical Presentation and Symptoms 

The symptoms at the time of presentation are very similar to those of NSCLC 

including: cough, shortness of breath, hoarseness, chest pain or bloody sputum. 

These tumors tend to be closer to the bronchial tree or the airways and may 

present with an obstructive pneumonia. 

In contrast to NSCLC, this tumor has a more rapid doubling time and earlier 

development of metastasis. Seventy-five percent of cases have metastasis at the 

time of diagnosis. 28 The most common sites of metastasis are the liver, bone, 

bone marrow, adrenal glands and brain. Symptoms reflect metastatic organ 

involvement with bone pain due to bone involvement, fatigue and jaundice from 

liver involvement, and fatigue, headaches or seizures from brain involvement. 

In addition, the SCLCs may secrete circulating proteins, hormones and 

antibodies. Symptoms from these circulating factors may include: increased 

thirst, bone pain, rashes, nail bed changes, and/or neurologic abnormalities. 

Diagnosis 

The diagnostic pathway for SCLC is similar to NSCLC. 

Staging 

The staging pathway for SCLC is not as complex as for NSCLC and is shown in 

Figure 2-9.10. SCLC has two stages – limited and extensive. The limited stage 

refers to disease that is confined to one side of the chest and may be encompassed 

within a tolerable radiation field. Everyone with SCLC should have a full body 

CT (chest/abdomen/pelvis) and an MRI of the brain. Some centers are now 

doing a PET scan as well or instead of a full body CT. Approximately 30 - 40% 

of patients with SCLC have limited disease at the time of diagnosis. Extensive 

stage disease is more common and extends beyond that one side of the lung 

and may include collections of fluid around in the lungs and around the heart 

caused by cancer cells. 

Chest 

Radiograph 

(optional) 

Full Body 

Ct scan 

Head MRI 

Limited 

Extensive 

Bone Marrow Biopsy, 

Bone Scan, Pulmonary 

Function Test 

Began 

Chemotherapy 

Figure 2-9.10: Algorithm for Staging Small Cell Lung Cancer (adapted from NCCN Data).

Prognosis 

As was true with NSCLC, pre-treatment factors predict how well patients do 

with treatment. Again, the extent of the disease is the strongest prognostic 

factor. The more limited the disease at the time of diagnosis, the better 

the outcome. Other factors associated with a better prognosis include age 

less than 55 years, female gender, and higher functional status (the ability 

of the patient to carry out daily life activities). Poor prognostic factors 

include age 70 years or older, current tobacco use and an elevated lactate 

dehydrogenase (LDH) level in the blood. The latter is an indicator of more 

bulky and extensive disease. 

Without treatment, the prognosis for metastatic SCLC is very poor 

with a median survival of five to eight weeks. Treatment with combined 

chemotherapy and radiation therapy achieves a response rate of 80% but 

three-year survival even for limited disease is only 14 - 20%. 

Treatment 

Even for limited disease, microscopic metastasis not evident at the time 

of diagnosis precludes a surgical cure. Chemotherapy is the mainstay of 

treatment for SCLC. However, for patients with “very limited disease” (ex. 

single small lung nodule without lymph node involvement or any evidence 

of metastasis), some have improved survival rates with surgical resection 

followed by chemotherapy. Some studies suggest a five-year survival rate 

of 50 - 80% after surgical resection of a limited stage SCLC nodule. 

In contrast to NSCLC, SCLC is very sensitive to chemotherapy and radiation 

therapy. Chemotherapy combined with radiation achieves a response 

rate of 80% and a complete response rate in 40% of patients. The types of 

chemotherapy drugs used are beyond the scope of this chapter. The addition 

of radiation therapy can further improve response rates by about 75% and 

survival rates by about 5%. Radiation therapy is most effective when given 

early on and during the chemotherapy. For extensive disease radiation 

helps to alleviate symptoms (e.g. pain) associated with the cancer burden. 

Radiation therapy to the brain may also help treat or prevent metastasis. 

SCREENING FOR LUNG CANCER 

Screening is a medical term for a non-invasive test that can be used in 

asymptomatic persons for the early identification of disease at a stage 

when successful treatment is still possible. Examples of this are the Pap 

smear for cervical cancer, colonoscopy for colon cancer, mammography for 

breast cancer and the prostate screening antigen (PSA) for prostate cancer. 

Numerous studies have shown that chest radiographs and sputum cytology, 

either alone or in combination are not useful tests for screening high-risk 

populations such as tobacco smokers. Lung cancers were identified, but 

in most cases were found at an advanced stage that precluded successful 

treatment. 

Recently, a study using chest CT scans for the screening of lung cancer in 

tobacco smokers produced promising results, 30 though this type of screening 

cannot be recommended until large scale studies are completed. In 2007, 

based on a review of the data available, the American College of Chest 



Physicians Guidelines for the Diagnosis and Management of Lung Cancer 

concluded that “for high-risk populations, no screening modality has been 

shown to alter mortality outcomes.” The American College of Chest Physicians 

guidelines recommends that, “individuals undergo chest CT screening only 

when it is administered as a component of a well-designed clinical trial with 

appropriate human subjects’ protections.” 31 These guidelines will be updated 

depending on the results from a multi-center study on the effectiveness of 

serial CT scanning in reducing the death rate from lung cancer. 

It is also important for patients participating in this type of investigational 

Chest CT screening to first be aware that 20 - 40% of the population has small 

(

2. Brandt-Rauf PW, Fallon Lf Jr., Tarantini T, Idema C, Andrews L. Health 

hazards of fire fighters: Exposure assessment. Br J Ind Med. 1988;45:606- 

612. 

3. McDiarmid MA, Lees PSJ, Agnew J, Midzenski M, Duffy R. Reproductive 

hazards of fire fighting II. Chemical Hazards. Am J Ind Med. 1991;19:447- 

472. 

4. Lees PSJ. Combustion products and other firefighter exposures. In: Orris P, 

Melius J, Duffy RM, eds. Occupational Medicine: State of the Art Reviews. 

Philadelphia, PA: Hanley & Belfus, Inc. 1995;10(4):691-706. 

5. Heyer N, Weiss NS, Demers P, Rosenstock L. Cohort mortality study of 

Seattle fire fighters: 1945-1983. Am J Ind Med. 1990;17:493-504. 

6. Markowitz S. Garibaldi K, Lilis R, Landrigan PJ. Asbestos exposure and 

fire fighting. Ann N Y Acad Sci. 1992;643:573-576 

7. Froines JR, Hinds WC, Duffy RM, et. al: Exposure of fire fighters to diesel 

emissions in fire stations. Am Ind Hyg Assoc J. 1987;48:202-207. 


Am J Ind Med. 1986;9:517-527. 

9. Sparrow D, Bosse R, Rosner B, Weiss S. The effect of occupational exposure 

on pulmonary function. A longitudinal evaluation of fire fighter and nonfire 

fighters. Am Rev Respir Dis. 1982;125:319-322. 


on pulmonary function. N Engl J Med. 1974;291:1320-1322. 





12. Weiden M, Banauch G, Kelly KJ, and Prezant DJ. Firefighters Health and 

Health Effects of the World Trade Center Collapse. In: Environmental and 

Occupational Medicine. Pgs 477-490. 4th Edition, Edited by Rom WN and 

Markowitz S. Lippincott-Raven Inc. Philadelphia, 2007. 

13. Golden AL, Markowitz SB, Landrigan PJ. The risk of cancer in firefighters. 

In: Orris P, Melius J, Duffy RM, eds. Occupational Medicine: State of the 

Art Reviews. Philadelphia, PA: Hanley & Belfus, Inc. 1995;10(4):803-820. 

14. LeMasters GK, Genaidy AM, Succop P, Deddens J, Sobeih T, Barriera-Viruet 

H et al., Cancer risk among firefighters: a review and meta-analysis of 32 

studies. 2006. J Occ Environ Med. 48;1189-1202. 

15. American Cancer Society (ACS), Cancer Facts and Figures 2008 http:// 

monographs.iarc.fr/cgi-bin/htsearch. Accessed February 9, 2009. 

16. National Cancer Institute (NCI). SEER Fast Stat Sheet. http://seer.cancer. 

gov/statfacts/html/lungb.html. Accessed February 9, 2009. 



17. Alberg AJ and Samet JM. Epidemiology of Lung Cancer. Chest. 2003 

Supplement;122:21S-49S. 

18. Wasswa-Kintu S, Gan W, Man S, Pare P, and Sin D. Relationship between 

reduced forced expiratory voume in one second and the risk of lung cancer: 

a systematic review and meta-analysis. Thorax. 2005;60(7):570-575. 

19. Stapley S., Sharp D, and HamiltonW. Negative chest x-rays in primary care 

patients with lung cancer. Brit J of Gen Pract. 2006;56:570-573. 

20. Peto R, Lopez AD, Boreham J, et al. Mortality from smoking in developed 

countries 1950-2000: indirect estimates from national vital statistics. 

Oxford, UK: Oxford University Press. 1994. 

21. Boffetta P, Pershagen G, Jockel KH, et al. Cigar and pipe smoking and 

lung cancer risk: a multicenter study from Europe. J Natl Cancer Inst. 

1999;91:697-701. 

22. International Agency for Research on Cancer (IARC) Monographs on the 

Evaluation of Carcinogenic Risks to Humans. http://monographs.iarc.fr/ 

cgi-bin/htsearch. Accessed February 9, 2009. 

23. MacArthur AC, Le, ND, Fang, R, Band PR. Indentification of occupational 

cancer risk in British Columbia: A population-based case-control study 

of 2,998 cancers by histopathological subtype. Am J Ind Med. 2008;52: 

221-232. 

24. Bruske-Hohlfeld I, Mohner M, Pohlabeln H, Ahrens W, Bolm-Audorff U, 

Dreienbrock L, Kreuzer M, Jahn I, Wichmann HE and Jockel KH. Occupational 

lung cancer risk for men in Germany: results from a pooled case-control 

study. Am J Epidemiol. 2000; 151(4):384-395. 

25. Davita V, HellmanS, and Rosenberg SA. Lung Cancer: Principles and 

practice of oncology. 7th ed. Lippincott Williams & Wilkins (LWW);2005. 

26. Buccheri G, Ferrigno D: Lung Cancer: Clinical Presentations Specialist 

referral Time. Eur Respir J. 2004;24:898-904. 

27. The National Comprehensive Cancer Network (NCCN). Clinical practices. 

http://www.nccn.org. Accessed February 9, 2009. 

28. Fishman, AP, Elias JA, et al. Fishman’s pulmonary diseases and disorders. 

4th ed. New York, NY:McGraw-Hill Medical. 2008. 

29. SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. 

Bethesda, MD, http://seer.cancer.gov/crs/1975_2008, based on November 

2007 SEER data submission, posted to the SEER web site 2008. 

30. Survival of patients with stage I lung cancer detected on CT screening. 

International Early Lung Cancer Action Program Investigators, Henschke 

CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. N 

Engl J Med. 2006;355:1763-71.

31. Bach PB, Silvestri GA, Hanger M and Jett JR. Screening for Lung Cancer. 

Chest 2007; 132:695 - 775. 

32. Hrubec Z, McLaughlin JK. Former cigarette smoking and mortality among 

US veterans: a 26 year follow-up, 1954-1980. In: Burns DM, Garfinkel 

L, Samet JM, eds. Changes in Cigarette-related disease risks and their 

implication for prevention and control. Bethesda, MD: US Government 

Printing Office. 1997;501-530. 

33. Bars MP, Banauch GI, Appel DW, Andreaci M, Mouren P, Kelly KJ, Prezant 

DJ. “Tobacco Free with FDNY” – The New York City Fire Department World 

Trade Center Tobacco Cessation Study. Chest 2006; 129:979-987. 

34. Burgess WA, Treitman RD, Gold A. Air contaminants in structural firefighting. 

NFPCA Grant 7X008. Boston: Harvard School of Public Health. 1979 



Chapter 2-10 

Asbestos-Related 

Lung Diseases 

By Dr. Stephen Levin, MD 

INTRODUCTION 

In the course of their work, fire fighters may have recurrent exposure to asbestos 

dust, especially during the overhaul phase of a fire response when, although 

respiratory protection is required, self-contained breathing apparatus (SCBA) 

is infrequently worn. Insulation and other asbestos-containing materials are 

often disturbed when buildings undergo spontaneous collapse or demolition 

during firefighting, with asbestos fibers remaining airborne long after fire 

fighters have ceased using their SCBAs at the site. 

From 1890 to 1970, some 25 million tons of asbestos were used in the United 

States, approximately two-thirds of which were used in the construction 

industry. The natural resistance of asbestos to heat and acid, its tensile strength, 

and its remarkable thermal, electrical and sound insulating properties have 

led to its use in over 3,000 applications, including floor tiles, boiler and pipe 

insulation, roofing materials, brake linings, and cement pipes. More than 

40,000 tons of fireproofing material, containing 10- 20% asbestos by weight, 

was sprayed annually in high-rise buildings in the period from 1960 to 1969. 

Much of this material remains in buildings, factories, and homes. When fires 

occur in these structures, fire fighters disturb asbestos-containing materials 

and are at risk for exposure to asbestos dust, especially because fire fighters 

do not regularly wear respiratory protection during the overhaul phase of fire 

response. Measurements of asbestos fiber concentrations in the air during 

overhaul have been shown to exceed OSHA’s short-term exposure limits. 1 

Evidence that such exposures to asbestos have health consequences for fire 

fighters can be found in studies that have looked at abnormalities on chest 

x-rays consistent with asbestos-related scarring. New York City fire fighters, 

assigned 25 or more years earlier to ladder companies situated near large office 

and factory buildings, warehouses or poor residential areas with frequent 

fires, underwent examination with chest x-rays interpreted by “B-readers” 

who have certified expertise in recognizing asbestos-related changes. Among 

fire fighters who had no known exposure to asbestos outside of their work as 

fire fighters, 13% had lung tissue abnormalities and/or changes in the lining 

of the lungs typical of asbestos-related scarring 1 , compared with a rate of x-ray 

abnormality of only two percent among adult males examined in general 

population surveys. 3 

Increased lung cancer rates among fire fighters have been reported in some 

studies, 4 although not consistently. 5 Evaluating the available data on lung cancer 

among fire fighters is difficult because of their lower prevalence of tobacco 

Chapter 2-10 • Asbestos-Related Lung Diseases 165

166 Chapter 2-10 • Asbestos-Related Lung Diseases 

use. Cases of mesothelioma, a type of cancer caused in the great majority of 

cases by exposure to asbestos, have been reported among fire fighters with no 

history of exposure to asbestos other than during firefighting. 

WHAT IS ASBESTOS? 

The term 'asbestos' refers to a group of six, naturally-occurring fibrous 

mineral silicates of magnesium and iron that form in host rock. Asbestoscontaining 

ore is mined, crushed, and milled to obtain the fibrous material, 

which is then processed further into finer fibers. There are two main types of 

asbestos: amphiboles (straight fibers) and serpentines (curly fibers bundled 

together). The amphiboles that have been used commercially include amosite, 

anthophyllite, and crocidolite. Other amphiboles (tremolite and actinolite) 

are not used commercially but are frequently contaminants of other silicates, 

including vermiculites and talcs. Chrysotile is the only type of serpentine 

asbestos in commercial use and represents 95% of all asbestos imported into 

the United States and incorporated into commercial products (Figure 2-10.1). 

Figure 2-10.1: Chrysotile Asbestos Fibers. 

The Diseases Caused by Asbestos 

The inhalation of asbestos fiber is recognized as a cause of both non-malignant 

(i.e., non-cancerous) lung diseases, including asbestosis (scarring of the 

lung tissue), pleural scarring (scarring of the lining of the lung and/or the 

chest wall) and benign pleural effusions (fluid in the space between the lung 

and the chest wall). Exposure to asbestos dust also causes lung cancer and 

diffuse malignant mesothelioma, a cancer of the lining of the lung (pleural 

mesothelioma) and the lining of the organs in the abdomen (peritoneal 

mesothelioma). Exposure at high concentrations among asbestos insulators 

and other occupational groups has also been associated with increased rates of 

cancer of the gastrointestinal tract, kidney, pancreas, and larynx. It’s possible 

to develop asbestos-related scarring of the lung and not develop an asbestosrelated 

cancer, and asbestos-related lung cancer and mesothelioma can occur 

in the absence of lung scarring.

All types of asbestos fiber are associated with the development of asbestosrelated 

scarring and cancers. There has been considerable debate about whether 

chrysotile asbestos is a cause of mesothelioma and whether it is as potent as 

the amphibole fibers in causing this specific cancer. In the United States to 

date, exposure to asbestos is regulated without distinction as to fiber type. Fire 

fighters should be protected against the inhalation of asbestos dust of any type. 

How Asbestos Causes Disease 

Asbestos-related disease, with the exception of asbestos “warts” in the skin, 

results from inhaling asbestos fibers into the upper airways and the lung. 

Swallowing asbestos fibers has not been consistently shown to cause digestive 

tract cancer. Animal experimental studies of long-term, high-level ingestion 

of asbestos fibers have failed to demonstrate a reproducible effect on the 

likelihood of developing cancer. There is, however, epidemiological evidence 

from human population studies that indicates that swallowing asbestos fibers 

can cause human disease. Communities exposed to asbestos-contaminated 

drinking water have been found in some studies to have excesses of cancer of 

the stomach and pancreas. 

When asbestos-containing materials in place are disturbed, asbestos fibers 

of varying diameters and lengths can be suspended in the air. Once airborne, 

fine asbestos fibers remain in the air for many hours even when the air appears 

relatively still. Air movement created by wind or human activity easily resuspends 

asbestos fibers that may have settled on surfaces. When they are 

inhaled, the larger asbestos fibers are deposited in the nose and upper airway. 

Fibers with diameters in the range of 0.5 to 5 µm can penetrate deep into the 

recesses of the lung and deposit at the branching of the finest airways, the 

alveolar ducts (see Chapter on the Anatomy of the Lung). Asbestos fibers that 

reach the airways are to a limited extent cleared by the mucociliary escalator, 

the continuous movement of mucus and trapped particles from the airways 

in the lung to the back of the throat (usually to be swallowed un-consciously). 

This movement is driven by the action of microscopic hair-like structures (cilia) 

projecting from the inner lining of the airways into the mucus layer. The fibers 

that remain in the airways are transported into the lung’s interstitial tissue – the 

space between the alveoli (where gas exchange occurs and oxygen is absorbed) 

and the surrounding capillaries. The presence of these fibers then attracts 

macrophages (specialized scavenger cells) that attempt to engulf the fibers and 

dissolve them with digestive enzymes. The macrophages are themselves killed 

by the asbestos fibers and disintegrate, releasing enzymes and DNA-damaging 

oxygen free radicals into the surrounding tissue, damaging the cells lining 

the small airways, and initiating inflammation and the scarring process. Over 

time, there is an accumulation of interstitial macrophages, white blood cells, 

fibroblasts (cells that deposit scar tissue) and scar tissue itself. This fibrotic or 

scarring process progresses, usually slowly over years, in some cases leading 

to stiff, small lungs with impaired ability to oxygenate the blood. The scarring 

can continue to worsen even after the inhalation of asbestos fiber has stopped, 

since many fibers persist in the lung and continue to cause new scar formation 

and to increase the risk for asbestos-related cancers. Ongoing exposure will 

result in an increasing accumulation of fiber in the lung, thereby increasing 

the risk for asbestos-related scarring and cancers. 


168 

Chapter 2-10 • Asbestos-Related Lung Diseases 

The mechanism by which asbestos causes cancer is still not fully understood. 

The genetic changes, many of them already identified, caused by a cell’s 

exposure to asbestos (or to gene-modifying agents carried by the asbestos 

fiber to the cell) are now being investigated with the genetic research tools 

developed in recent years. 

Asbestos fibers that are swallowed up by macrophages may become coated 

with an iron-containing material, forming an asbestos body or ferruginous 

body. Only a small proportion (about one percent) of fibers becomes coated, 

so this cannot be considered an effective protective mechanism. There is 

evidence that amphiboles cause the formation of asbestos bodies more readily 

than chrysotile. The presence of asbestos bodies in lung tissue, fluid washed 

from the lungs (bronchoalveolar lavage fluid), or in sputum, has been used 

as a marker of exposure, although individuals appear to vary considerably in 

how likely they are to form these structures. The finding of abnormally high 

asbestos body concentrations in sputum, bronchoalveolar lavage fluid or lung 

tissue indicates a history of exposure to asbestos in excess of “background” 

and can support the diagnosis of asbestos-related disease. The absence of 

asbestos bodies does not rule out that asbestos fibers in the lung may have 

caused disease. High concentrations of asbestos fibers have been found in the 

lungs of exposed individuals who have developed scarring or fibrosis, but do 

not have unusual numbers of asbestos bodies in their lung tissue. 

Some asbestos fibers that penetrate into the interstitial lung tissue migrate 

to the pleural membrane that lines the lung and the chest wall, most likely by 

lymphatic channels. Some are distributed to other tissues in the body via the 

lymphatic circulation and via the bloodstream. 

HEALTH EFFECTS OF EXPOSURE TO ASBESTOS 

Non-Malignant Asbestos-Related Diseases 

Pulmonary Asbestosis 

Pulmonary asbestosis is the diffuse, interstitial fibrosis (scarring) in the lung 

tissue caused by the deposition of asbestos fibers of any type in the lung. The 

fibrosis results in a lung disease that generally becomes evident clinically after 

15 to 20 years or more have elapsed from the onset of exposure. While there 

are biological differences among individuals in susceptibility to the scarring 

caused by exposure to asbestos, the likelihood of developing asbestosis is 

related to the cumulative amount of fiber inhaled over time. Such scarring is 

most commonly seen among workers exposed recurrently on the job and family 

members exposed repeatedly to take-home dust. However, even short-term 

exposure (e.g., less than one month), when asbestos fiber concentrations in the 

air are high enough (e.g., in the manufacture of asbestos-containing products), 

can result in fatal asbestosis. There is no evidence that single or rare exposures 

to asbestos dust are associated with the development of scarring lung disease. 

The most prominent symptom of asbestosis is the gradual onset of shortness of 

breath on exertion, with progression over time. Cough, either dry or productive 

of small amounts of clear sputum, may be present. Chest pain, either sharp or 

aching in character, occurs in a small proportion of patients with asbestosis.

On physical examination, crackling sounds (rales) on expiration over the 

base of the lungs and that persist after coughing, may be heard. Clubbing, a 

rounding of the end of the fingers and a “spooning” of the fingernails may be 

present when scarring is advanced. The chest x-ray shows small, irregular 

lines of scarring in the mid and lower lung zones after sufficient fibrosis has 

accumulated, although the characteristic pathologic findings of interstitial 

scar formation may be evident on microscopic examination of tissue well 

before the abnormalities become detectable on the chest x-ray or CT scan. 

These physical and radiographic findings are not specific for asbestosis and 

can be found in other fibrotic lung diseases see Chapter on Pulmonary Fibrosis 

and Interstitial Lung Disease). 

Pulmonary function (breathing) test abnormalities (for details see Chapter 

on Pulmonary Function Tests) demonstrate a restrictive impairment, with a 

decreased forced vital capacity (FVC) – an inability to inflate the lung with a 

normal volume of inhaled air, a decreased total lung capacity (TLC) – the total 

volume of air in the lungs after a deep breath, and a decreased diffusing capacity 

(D CO) – a measure of the lung’s ability to transfer oxygen to the blood. Flow 

L 

rates through the large airways, measured as the forced expiratory volume at 

1-second (FEV and FEV /FVC ratio) are usually normal, but narrowing of the 

1 1 

small airways (decreased FEF25-75 values) has been reported to accompany 

asbestosis. Interestingly, this has also been found among non-smoking workers 

exposed to asbestos but without chest x-rays evidence of asbestosis, suggesting 

that asbestos dust may have some mild irritant properties in addition to its 

ability to cause scarring. Impaired ability to oxygenate the blood as it passes 

through the lung, due to the accumulation of interstitial scarring, can lead to 

arterial oxygen desaturation (low oxygen levels in the blood), evident at first 

only during and immediately after exercise, accounts for much of the shortness 

of breath on effort experienced by many people with asbestosis. 

In individual cases, there is often a poor correlation among the appearance of 

scarring on the chest x-ray, the degree of shortness of breath and the pulmonary 

function results. Some patients with marked abnormalities on the chest x-ray 

may have few symptoms and normal pulmonary function. The converse may 

also be true, with the severity of symptoms and/or pulmonary function test 

results seemingly out of proportion to the degree of x-ray abnormality. Studies 

of groups of exposed workers, however, demonstrate relationships among 

these effects of the scarring process. 

In severe cases of asbestosis, respiratory impairment can lead to death, 

often when the affected individual develops a chest infection (e.g., pneumonia) 

that further compromises lung function. When scarring becomes dense and 

extensive, increased resistance to blood flow through the small arteries in 

the lung may develop, from obliteration of the network of small arteries and 

capillaries and from pulmonary capillary constriction caused by low oxygen 

levels in the alveolar air sacs. This results in pulmonary hypertension and may 

ultimately cause the muscle of the right ventricle of the heart (which pumps 

blood through the lungs) to enlarge to overcome the increased resistance to 

blood flow. If the pulmonary hypertension is severe enough for a sufficient 

period of time, the right ventricle can fail, a condition known as cor pulmonale, 

a well-recognized potentially fatal complication of advanced asbestosis. 



There are a number of medical conditions that can look like asbestosis, 

both clinically and radiographically. A list of the most common of these 

conditions is presented in Table 2-10.1. Most important of the diseases listed 

are idiopathic pulmonary fibrosis (for details see the chapter on pulmonary 

fibrosis) and congestive heart failure. 

Most Common Conditions Mimicking Pulmonary Asbestosis 

Idiopathic pulmonary fibrosis 

Congestive heart failure (radiographic appearance) 

Hypersensitivity pneumonitis 

Scleroderma 

Sarcoidosis 

“Rheumatoid lung” 

Other collagen vascular diseases 

Lipoid pneumonia 

Desquamative interstitial pneumonia 

Other pneumoconioses (dust-related lung scarring) 

Table 2-10.1: Common Conditions Mimicking Pulmonary Asbestosis 

Pleural Thickening or Asbestos-Related Pleural Fibrosis 

Pleural thickening, or asbestos-related pleural fibrosis (scarring of the lining of 

the lung and/or the chest wall), is the most common consequence of exposure 

to asbestos in the occupational setting. The scarring can occur in localized 

areas in separate and discrete plaques (circumscribed pleural thickening) or 

can occur as a more extensive and diffuse scarring process over the surface 

of the pleura and involve the costophrenic angle (the angle or gutter made 

by the chest wall and the diaphragm where they come together) – defined as 

diffuse pleural thickening. Evidence of pleural scarring usually appears after 

20 or more years have elapsed since the onset of exposure to asbestos dust 

(the latency period), and a latency of 30 to 40 years after exposure begins is 

not uncommon. 

Under the microscope, the plaques appear as deposits of collagen, the protein 

that is deposited in early scar formation. Circumscribed pleural scarring more 

commonly involves the parietal pleura (the lining of the chest wall) and often 

can be found on the surfaces of the diaphragm. Pleural plaques can be found on 

the visceral pleura (the lining of the lung itself) as well. The pericardium (the 

lining around the heart) and the pleural surfaces in the center of the chest (the 

mediastinal pleura) may also be involved. Although non-calcified thickening 

is more common, calcium deposits in areas of pleural scarring, whether 

localized or diffused, is frequently evident on the chest x-ray and become 

more common with increasing time since onset of exposure. Conditions that 

can cause pleural thickening other than exposure to asbestos are presented 

in Table 2-10.2.

Conditions Mimicking Asbestos-Related Pleural Thickening 

Discrete or localized Diffuse 

Chronic mineral oil aspiration 

Chest trauma 

Infectious processes (old TB, pneumonia) 

Lymphoma 

Metastatic cancer 

Mica and talc exposure 

Myeloma 

Scleroderma 

Chronic beryllium disease 

Collagen vascular diseases 

Drug reactions 

Infection 

Loculated effusions 

Mica and talc exposure 

Sarcoidosis 

Silicosis 

Uremia 

Table 2-10.2: Conditions Mimicking Asbestos-Related Pleural Thickening )Adapted from 

Rosenstock and Cullen. 6 ) 

When pleural thickening deforms the underlying lung tissue, rounded 

atelectasis or a pseudotumor may develop and prompt concern about the 

presence of a cancer. These lesions are characteristically less than 2 cm in 

diameter, and are located next to an area of pleural thickening or fibrosis. 

Evaluation by comparison with old chest x-rays, or with a CT scan of the chest, 

will usually reveal the characteristic features of this form of scarring and avoid 

unnecessary biopsies. Nevertheless, given the increased risk of lung cancer 

among asbestos-exposed workers, the diagnosis of rounded atelectasis should 

be made with appropriate caution and biopsy obtained in cases where the 

radiographic findings are uncertain. 

In the past, pleural thickening was thought to represent only a marker of 

prior exposure to asbestos, without consequence for the individual’s health; but 

pleural thickening, even when circumscribed, has more recently been shown 

to impair lung function, measured by pulmonary function tests or by exercise 

testing. Diffuse pleural scarring is associated with restrictive lung disease and 

impaired gas exchange, even in the absence of asbestosis (interstitial fibrosis). 

The lung can become entrapped or encased by a thick rind of scar, and in severe 

cases can cause pulmonary impairment and death. Diffuse pleural thickening 

is thought to result almost invariably from the occurrence of a pleural effusion, 

a collection of fluid in the pleural space (see below). 

Both asbestosis and asbestos-related pleural fibrosis can be detected with 

greater sensitivity by CT scanning of the chest, especially by the high-resolution 

CT scan (HRCT). CT scans have been shown to detect asbestosis and pleural 

scarring when the chest x-ray appears normal. This technique may be useful 

in resolving cases that are uncertain on plain chest x-rays. The radiation 

exposure, time and cost involved in performing a CT scan have decreased as 

the technology has improved, making the CT scan more accessible as a tool 

for early detection. 

Benign Asbestos-Related Pleural Effusions 

Benign asbestos-related pleural effusions, collections of fluid in the pleural 

space between the lung and the chest wall, may occur within the first 10 

years after the onset of exposure and may, therefore, be the first evidence of 

asbestos-related illness. These effusions can occur once and never recur or 

can reappear multiple times, on the same or opposite side of the chest. The 


172 


diagnosis is made by excluding other causes after examining the pleural fluid 

and finding that microscopic examination of the cells in the fluid reveals no 

malignant (cancerous) cells and cultures for bacterial or tuberculosis infection 

are negative. The fluid is usually reabsorbed spontaneously within several 

weeks; but thoracentesis (draining the fluid from the chest) for relief of chest 

pain and/or shortness of breath, and thoracoscopy (inserting a tube with a 

camera into the chest) to obtain a pleural biopsy for diagnostic purposes, are 

frequently performed. Many patients with pleural effusions, however, have no 

symptoms. There is evidence that diffuse pleural thickening (see above) may 

be the result of benign asbestos-related effusions following their reabsorption. 

TREATMENT OF NON-CANCEROUS ASBESTOS-RELATED 

DISEASE 

There is no effective treatment available for asbestosis. Measures used for 

patients with other forms of interstitial fibrosis, including steroids and antiinflammatory 

medications, have not proven effective in controlling the 

asbestos-related scarring process or its consequences. The decreased blood 

oxygen levels associated with advanced scarring can be managed in part by the 

use of supplemental inhaled oxygen, and cor pulmonale is treated as for other 

causes of right heart failure. For patients with impending pulmonary failure 

due to asbestosis, a last resort option is lung or heart-lung transplantation, 

although experience with this approach remains limited. 

Asbestos-related circumscribed pleural scarring may be associated with 

a loss of exercise tolerance, but, as with asbestosis, no specific treatment for 

this condition is available. In cases of extensive, diffuse pleural thickening 

with entrapment of the lung, stripping of the lining of the lung (pleurectomy) 

may be necessary to permit lung expansion. 

Despite the lack of treatments that affect the scarring process itself, individuals 

with asbestos-related scarring of the lung tissue and/or pleura are advised to 

maintain an active aerobic exercise program and to avoid obesity in order to 

preserve and even improve exercise tolerance. 

Benign asbestotic pleural effusions are treated as are effusions from other 

causes, with careful evaluation to rule out the possibility of malignancy by 

removal of the fluid (thoracentesis) and microscopic examination of the cells 

present. In cases of multiple, recurrent effusions, introduction of an irritant 

material to fuse the pleural lining of the lung to the pleural lining of the chest 

wall (pleurodesis) has been utilized to prevent further accumulations of fluid. 

ASBESTOS-RELATED CANCERS 

Lung Cancer 

Lung cancer is the most common asbestos-induced malignancy and is the 

principal cause of death from asbestos in developed countries. Diagnosis of 

asbestos-related lung cancer generally occurs 20 or more years after onset 

of exposure. In a large study of the causes of death among heavily exposed 

asbestos insulators, over 50% of the cancer deaths were due to lung cancer.

Lung cancers associated with asbestos exposure are similar under the 

microscope to other primary cancers of the lung. All cell types of cancers arising 

in the airways occur at increased rates. Lung cancers occur with increased 

frequency in all locations of the lung following exposure to asbestos. Studies of 

lung cancer distributions by cell type and lobe of origin found no difference in 

anatomical site or microscopic characteristics between the cancers associated 

with asbestos exposure and those related to cigarette smoking. 

Cigarette Smoking and Exposure to Asbestos 

Cigarette smoking and exposure to asbestos dust have been shown to interact 

in a multiplicative (or synergistic) fashion in causing lung cancer, rather than 

a simple addition of the risks associated with each exposure. In a large group 

of heavily exposed asbestos insulators, lung cancer death rates were 5-fold 

increased for non-smokers and over 50-fold increased for smoking asbestos 

workers, compared with lung cancer mortality among non-smoking blue collar 

workers not exposed to asbestos. Lung cancer among blue collar cigarette 

smokers not exposed to asbestos was 11 times that of non-smokers. Table 2-10.3 

summarizes these results. 

Interaction between Smoking and Asbestos in Lung Cancer Mortality 

Group 

Exposure to 

Asbestos 

Cigarette 

Smoking 

Death Rate 

(per 100,000/yr) 

Mortality 

Ratio 

Controls NO NO 11.3 1.00 

Asbestos Workers YES NO 58.4 5.17 

Controls NO YES 122.6 10.85 

Asbestos Workers YES YES 601.6 53.24 

Table 2-10.3: Interaction Between Smoking and Asbestos in Lung Cancer Mortality 7 

The increase in lung cancer risk is proportionate to the degree of exposure 

to asbestos and the cigarette smoking “dose.” Cessation of smoking among 

asbestos-exposed workers has been shown to be associated with a decreased 

risk of lung cancer, although the risk never decreases entirely to the level of 

never-smokers. The cancers seen in significant excess among asbestos insulators 

other than lung cancer that have been shown to occur at even higher rates 

among cigarette-smoking asbestos workers included cancers of the esophagus, 

mouth and throat, and larynx. Smoking appears to have no influence on the 

risk of mesothelioma or cancers of the stomach, colon/rectum, and kidney 

among asbestos-exposed workers. 

Smoking has been associated with an increase in lung tissue scarring evident 

on chest radiographs among men with asbestos exposure. There is little evidence 

that smoking alone, without exposure to asbestos, can produce the appearance 

of scarring on the chest x-ray. Cigarette smoking among asbestos workers has 

been shown to increase the risk of death from asbestosis. Clearly, for any fire 

fighter who is a current smoker, quitting cigarettes is the most important step 

one can take to protect their health. 


174 


The role of lung scarring in the development of asbestos-associated lung 

cancer is a subject of considerable debate. Workers exposed to asbestos have 

been shown to have an increased risk of lung cancer, even when chest x-rays 

have shown no lung tissue fibrosis. Studies have demonstrated that scarring 

of the lung tissue may be visible under the microscope in cases of lung cancer 

where the chest x-ray has been normal. As a practical matter, it is not necessary 

to demonstrate asbestosis on the chest x-ray or in biopsied tissue in order to 

attribute a causal role to asbestos in cases of lung cancer. 

Treatment of Lung Cancer 

Until the past decade, the treatment of lung cancer has been persistently 

unsuccessful, whether the approach utilized surgery, chemotherapy or radiation 

– with cure rates of only 5 - 10% in advanced disease. The primary difficulty 

was that lung cancers were detected at an advanced stage in over two-thirds 

of the cases, with spread of the tumor to local tissues, lymph nodes or distant 

organs (for details see the Chapter on Lung Cancer). More recently, there is 

some evidence that screening for lung cancer with CT scans can identify new 

tumors at a time when they are still small and have not yet spread to local or 

distant sites. Cure rates when tumors are found in such early stages may be 

70% or greater. In 2007, based on a review of the data available, the American 

College of Chest Physicians Guidelines for the Diagnosis and Management of 

Lung Cancer concluded that “for high-risk populations, no screening modality 

has been shown to alter mortality outcomes.” 8 The American College of Chest 

Physicians recommends that, “individuals undergo chest CT screening only 

when it is administered as a component of a well-designed clinical trial with 

appropriate human subjects’ protections.” 8 These guidelines will be updated 

depending on the results from a multi-center study on the effectiveness of 

serial CT scanning in reducing the death rate from lung cancer. 8 

Malignant Mesothelioma 

Diffuse malignant mesothelioma is a tumor arising in the cells of the lining of 

the chest wall and/or lung (the pleura) and the lining of the abdominal organs 

(the peritoneum). Three microscopic patterns are recognized: epithelial, 

sarcomatous, and mixed or biphasic, each with its own likelihood of positive 

response to treatment, with the epithelial type most responsive. The great 

majority of patients with mesothelioma have a history of exposure to asbestos, 

and this has led to its description as a “signal neoplasm” because of its rarity 

in the absence of exposure to asbestos. 

Among heavily exposed asbestos insulators, over nine percent of all deaths 

have been shown to be due to malignant mesotheliomas. In comparison, rates 

of death from mesothelioma exceeds 10 per million deaths among adults in the 

U.S. general population. A latency of 20 years or more from the onset of exposure 

to asbestos is again observed, with most mesothelioma deaths occurring more 

than 30 years from onset of asbestos work. There is evidence that the risk of 

developing a mesothelioma appears to increase the longer the individual is 

from the onset of exposure, prompting special concern for exposures among 

young children who may inhale asbestos dust brought home on their parents’ 

contaminated work clothing.

Once occurring, diffuse malignant mesotheliomas generally spread rapidly 

over the surfaces of the chest and abdominal cavities and organs, often with 

little invasion of the organs involved. Penetration into the ribs and chest 

wall and spread to local lymph nodes is not uncommon. As the tumor grows 

more bulky, it can compress the underlying lung, markedly impairing lung 

function. The disease often presents with chest pain and shortness of breath, 

frequently due to pleural effusions, which prompt initial medical attention. The 

diagnosis is made on the basis of microscopic examination of cells separated 

from pleural fluid or, more commonly, tissue obtained by closed pleural biopsy 

or by thoracoscopy. Special tissue staining techniques (immunohistological 

staining) and/or assessment using high magnification electron microscopy 

is often necessary to establish the diagnosis with certainty. 

Treatment of Malignant Mesothelioma 

Advances in the treatment of malignant mesotheliomas of the chest and 

abdomen have occurred in the past 10 years. However, prognosis remains 

poor with the majority of patients surviving no more than 13 months after 

diagnosis. Chemotherapy alone with permatrexed (Alimta®) may extend 

life an average of three months and with a measurable improvement in the 

quality of life during that time compared with those who are untreated. For 

some, surgery, accompanied by washes of the chest or abdomen with heated 

chemotherapy solutions, has resulted in surviving more than five years after 

diagnosis. Nevertheless, treatment remains ineffective for the great majority 

of patients, and prevention remains the key approach to mesothelioma from 

a public health perspective. 

PREVENTING ASBESTOS-RELATED DISEASE 

AMONG FIRE FIGHTERS 

Fire fighters are most likely to be exposed to asbestos during overhaul, when 

asbestos-containing materials are frequently disturbed and when respiratory 

protection is infrequently worn. The key to preventing asbestos-related scarring 

and cancer is the use of respirators that will trap the great majority of the fine 

asbestos fibers before they are inhaled. The IAFF is working on a lighter weight 

and less bulky SCBA unit that could be more practical for the longer wear 

necessary during overhaul activities. Fire fighters are advised to wear their 

SCBA, especially in circumstances where they might be exposed to asbestos: 

for example, ripping out large areas of insulation that could contain asbestos. 

Studies of other asbestos-exposed occupations have demonstrated that 

family members can be placed at risk for asbestos-related disease when workers 

bring their dusty work clothing home to be laundered9 , often contaminating 

the family car in the process. Fire fighters should take appropriate measures 

to ensure that dust from the fire site is not brought home, especially because 

young children may be at special risk for mesothelioma decades later, even 

following relatively low exposure levels. 

Given the evidence of asbestos-related disease among fire fighters, 

consideration should be given to medical screening for asbestos-related 

scarring and cancers among particular groups of fire fighters whose risk of 

exposure to asbestos-containing materials is greatest. The IAFF supports 



screening through the use of the IAFF’s Wellness-Fitness Initiative. Screening 

exposed fire fighters has multiple benefits. Earlier disease detection may make 

curative treatment possible for some asbestos-associated cancers. Screening 

presents an opportunity for education on the health hazards of asbestos and 

for emphasizing the importance of eliminating further exposure. Prevention 

of disease can be achieved through the reduction of other risk factors, such as 

smoking. 10 Screening is a mechanism for fire fighters to gain access to medical 

care and appropriate follow-up treatment, and the diagnosis of illness related 

to asbestos exposure helps those affected to obtain medical monitoring and 

other compensation. Screening also assists in epidemiological surveillance 

of diseases caused by exposure to asbestos. 

REFERENCES 

1. Bolstad-Johnson DM, Burgess JL, Crutchfield CD, Storment S, Gerkin R, 

Wilson JR (2000): Characterization of fire fighter exposures during fire 

overhaul. AIHAJ September/October 2000; 61:636-641. 

2. Markowitz SB, Garibaldi K, Lilis R, Landrigan P. Asbestos exposure and 

fire fighting. Ann NY Acad Sci 1991 

3. Rogan WJ, Gladen BC, Ragan NB, and Anderson HA. (1987)US Prevalence 

of Occupational Pleural Thickening: A Look at Chest X-Rays from the First 

National Health and Nutrition Examination Survey. Am. J. Epidemiol. 126: 

893-900. 

4. Ma F, Lee DJ, Fleming LE, Dosemeci M, J. Race-specific cancer mortality 

in US firefighters: 1984-1993. Occup Environ Med. 1998 Dec; 40(12):1134- 

1138. 

5. Heyer N, Weiss NS, Demers P, et al. (1990) Cohort Mortality Study of Seattle 

Fire Fighters.: 1945 - 1983. Am J Ind Med 17: 493-504. 

6. Rosenstock L, Cullen MR (1994): “Textbook of Clinical Occupational and 

Environmental Medicine.” Pennsylvania: W.B. Saunders Company. 

7. Hammond EC, Selikoff IJ, Seidman H (1979): Asbestos exposure, cigarette 

smoking and death rates. Ann NY Acad Sci 330:473-490. 

8. Bach PB, Silvestri GA, Hanger M and Jett JR. Screening for Lung Cancer. 

Chest 2007;132:69S-77S. 

9. LeMasters GK, Genaidy AM, Succop P, Deddens J, Sobeih T, Barriera-Viruet 

H, Dunning K, Lockey J. Cancer risk among firefighters: a review and metaanalysis 

of 32 studies. J Occup Environ Med. 2006 Nov; 48(11):1189-202. 

10. Humerfelt S, Eide GE, Kvale G, Aaro Le, Gulsvik A (1998): Effectiveness of 

postal smoking cessation advice: a randomized controlled trial in young 

men with reduced FEV1 and asbestos exposure. Eur Resp J 11(2):284-290.

Chapter 2-11 

Sleep Apnea Syndrome 

By Dr. Jaswinderpal Sandhu MD and Dr. David Appel MD 

The word apnea in Greek language means “without breath”. Sleep apnea is a 

condition in which a person literally stops breathing repeatedly during sleep, 

sometimes hundreds of times during a single night. The medical definition 

of apnea means not breathing for ten seconds, but often in people with sleep 

apnea syndrome these episodes are longer. Although people wake up gasping 

for breath, often they are unaware of these apneic episodes. Commonly it is 

accompanied by habitual snoring and excessive daytime sleepiness. The 

disordered breathing that arises from these repeated episodes of apneas during 

sleep when also associated with daytime sleepiness is referred to as sleep 

apnea syndrome. Sleep apnea syndrome may result from obstructive apnea 

or non-obstructive apnea, but the vast majority of people have Obstructive 

Sleep Apnea (OSA) which will be the focus of this chapter. 

SLEEP 

Adult humans spend one third of their time sleeping and most of us need 

seven to eight hours of sleep everyday. Sleep disorders are very common. 

Approximately 50% of adults in the United States experience intermittent 

sleep problems and 20% of adults report chronic sleep disturbance. Sleep 

disturbances often lead to daytime sleepiness that may interfere with daytime 

activity and cause serious functional impairment. Normally, daily sleep and 

wake alternates on a circadian rhythm of approximately 25 hours, also known 

as the biological clock. During daytime, active humans accumulate sleep 

factor(s) that promote sleep. Typically there is a midday sleep surge, but the 

accumulated sleep factor(s) are offset by a circadian wake-sleep mechanism 

that maintains wakefulness during the day. Sleep ensues when the wake portion 

of the circadian mechanism is turned off and the accumulated sleep factor(s) 

become relatively unopposed. This circadian rhythm is initiated and controlled 

by an area of the brain called the suprachiasmatic nuclei of the hypothalamus, 

and the light-dark cycle is mediated through the retinohypothalamic tract. 

Even low intensity light signals reset this rhythm every day so that changes in 

duration of daylight during different seasons are accommodated accordingly. 

Along with other various clues, a pineal hormone called melatonin, mostly 

secreted at night, serves as a trigger for the need to sleep. 

Sleep Stages 

Humans exist in three states: wakefulness, non-rapid eye movement sleep 

(NREM), and rapid eye movement (REM) sleep. Surprisingly, NREM sleep 

and REM sleep are as distinct from each other as NREM and REM sleep are 

distinct from wake. 

Chapter 2-11 • Sleep Apnea Syndrome 177

178 Chapter 2-11 • Sleep Apnea Syndrome 

Normal nocturnal sleep is divided into NREM and REM sleep. NREM sleep 

is comprised of four stages: Stage I (light sleep), Stage II, and Stages III-IV 

(deep slow wave or delta-wave sleep). Normally, people enter sleep via NREM 

sleep with most Stage III and IV sleep occurring in the first third of the night, 

fulfilling the first restorative obligation of sleep to offset sleepiness. Typically, 

every 90-120 minutes a period of REM sleep occurs. In the early portion of 

sleep these REM sleep periods are short and eventually they become longer 

as the sleep period progresses, with the longest REM sleep period occurring 

shortly before the end of sleep and the onset of waking. REM sleep probably 

is important for the processing of memory. 

OBSTRUCTIVE SLEEP APNEA 

Obstructive sleep apnea occurs when during sleep complete obstruction of 

the pharyngeal airway results in total cessation of airflow from the nose and 

mouth despite effort by the respiratory muscles to breathe. When the pharyngeal 

obstruction is such that the airflow is shallow and not completely reduced the 

event is termed a hypopnea. An apnea-hypopnea index (AHI) is determined 

by assessing the frequency of apneas and hypopneas per hour of sleep. It is 

normal for some apnea and hypopnea to occur during sleep. Apnea-hypopnea 

occurring more frequently than five events per hour is abnormal, however. 

When associated with sleepiness the condition is termed obstructive sleep 

apnea syndrome (OSAS). Often apneas are associated with arousals and the 

number of arousals per hour of sleep is called the arousal index. The frequent 

sleep fragmentation and arousals produced by OSAS often results in profound 

daytime sleepiness. 

Historical Perspective 

Osler and later Burwell 1 used the name “Pickwickian Syndrome” to describe a 

condition involving obesity, chronic hypoventilation and hypersomnolence, 

based on the obese Charles Dickens character Joe, in the book, “The Posthumous 

Papers of the Pickwick Club.” Obstructive sleep apnea has also been noticed 

by bedside observation as early as in 1877. In 1964, an illustration showing an 

obese, hypersomnolent and myxedematous woman with airflow cessation was 

published, but the authors did not realize the importance of this observation 

at that time. Gastaut et al in 1965 2 , first described three types of apnea, in a 

patient with “Pickwickian Syndrome.” They also postulated that the excessive 

sleepiness was due to the repeated arousals with the resumption of breathing 

that terminated the episodes of apnea. 

Epidemiology 

Obstructive sleep apnea is an increasingly recognized disorder that affects 

more than 12 million people in the United States. Studies have shown that OSA 

is a common disorder and poses a significant public health problem. 3 There 

has been a 12-fold increase in the annual number of patients diagnosed with 

OSA between 1990 and 1998. 4 Epidemiological studies have established that 

approximately four percent of men and two percent of women who are 35 to 

65 years of age have OSA. 5,6 OSA has a higher incidence in post-menopausal 

women and is also more common in women than previously thought.

Risk Factors 

Typically a person with sleep apnea is an obese male who snores loudly and 

may report choking and apnea during sleep. However, many patients do not 

exhibit this pattern. For example non-obese patients with micrognathia (an 

abnormally small lower jaw) or retrognathia (a receding chin) may have sleep 

apnea. Therefore, presence of certain clues in the medical history and physical 

examination should heighten the suspicion of obstructive sleep apnea. 7 A list 

of features contributing to sleep apnea syndrome is shown in Table 2-11.1. 

Features Contributing to Sleep Apnea Syndrome 

• Obesity (increased body mass index) 

• Increased neck circumference (men 18+ inches; women 16+ inches) 

• Anatomic abnormalities (e.g. retrognathia (receding chin), micrognathia, 

adenotonsillar hypertrophy, enlarged soft palate and macroglossia) 

• Systemic disorders (e.g., hypothyroidism, acromegaly, amyloidosis) 

• Down’s Syndrome and post-polio syndrome 

• Neurological disorders (e.g., Parkinson’s disease) 

• Smoking 

• Alcohol consumption 

• Medications (e.g. sedatives, sleeping pills, antihistamines) 

• Nasal congestion 

Table 2-11.1: Features Contributing to Sleep Apnea Ayndrome 

Pathophysiology 

The pharynx is the space in the back of the throat behind the tongue (Figure 

2-11.1). It must be collapsible during speech and swallowing, but it must 

remain open during breathing. This complex function is accomplished by a 

group of muscles that can alter the shape of the pharynx during speaking or 

swallowing, while keeping it open during breathing. The upper airway muscles 

actually pull on the pharynx to maintain its open position during breathing. 

Figure 2-11.1: The panel on the left shows the pharynx during normal breathing. In a patient 

with OSAS, the airway closes and flow stops, as seen in the panel on the right. 

Chapter 2-11 • Sleep Apnea Syndrome 

179

180 


However, during sleep there is general muscular relaxation, including the 

upper airway respiratory muscles, and in turn the reduced effort of these upper 

airway muscles leads to narrowing of the pharyngeal space. While awake, 

breathing is stimulated by both cortical influences (laughing, thinking and 

speaking) and chemical influences (acid-base changes, carbon dioxide tension, 

oxygen tension) in the body. In contrast during sleep, breathing is stimulated 

by chemical influences only. 

Typically, people with OSA have a pharyngeal space that is smaller than 

normal, even when they are awake. This results in increased resistance of airflow 

in the upper airway. To compensate for this pharyngeal space narrowing, to 

overcome this increased upper airway resistance, and to maintain a patent 

upper airway, upper airway muscle activity in people with OSA while they are 

awake is actually greater than normal. 8 Sleep causes the following physiological 

changes: 

• Upper airway muscles relax 

• Reflex activity in the pharynx declines 

• The need for chemical stimuli to breathe during NREM sleep increases 

(increased chemoreceptor set point) 

• Surface tension of the upper airway increases 

An abnormal pharynx can be kept open in wakefulness by an appropriate 

compensatory increase in dilator muscle activity, 8 but during sleep upper 

airway muscle tone declines. Loss of needed compensatory mechanisms 

imposed by sleep may lead to partial or complete collapse of the upper airway. 

Partial collapse results in snoring and hypopnea, whereas complete collapse 

results in episodes of apnea. 

During the obstructive apneic episodes the individual continues to try to 

breathe against the closed upper airway. Carbon dioxide tension increases, 

oxygen tension decreases and secretion of an increased amount of flight or fight 

catecholamines (norepinephrine) intensify the effort to breathe. Ultimately 

this produces an arousal. During the aroused state the upper airway muscles 

are activated and in turn the pharynx opens. Breathing is restored, but this 

occurs at the cost of sleep. When the individual resumes sleep the upper airway 

events described above recur. Thus, a vicious cycle of breathing without sleep 

and sleeping without breathing is set in motion. Clinical consequences of this 

disordered breathing during sleep include excessive sleepiness, systemic 

hypertension, myocardial infarction, heart failure, fatal and non-fatal 

arrhythmias, stroke, metabolic syndrome and erectile dysfunction. While some 

of these mechanisms are summarized in Table 2-11.2, the exact mechanisms 

of how OSA leads to these clinical disorders are many, complex, and beyond 

the scope of this chapter. 

Clinical Manifestations 

The cardinal manifestations of OSA are excessive daytime sleepiness and sleep 

fragmentation caused by habitual snoring and nocturnal gasping. 9 However, 

a majority of the people with OSA under-report these symptoms and some 

might be totally unaware of their symptoms. Therefore, a focused history 

from people as well as their partners who have observed their disturbed sleep 

behavior can be crucial in identifying persons at risk for sleep apnea. People

with OSA commonly report that their sleep is unrefreshing. They wake feeling 

tired and often report dry mouth, grogginess, and headaches. They may doze 

off watching television, reading, at the dinner table, in waiting areas and 

during conversation. This disorder frequently impairs driving and is a major 

cause of serious automobile accidents. 10,11 Personality changes, depression 

and impaired memory may lead to a decline in work quality. Common clinical 

manifestations of obstructive sleep apnea are listed in Table 2-11.3. 

Mechanisms of Different Clinical Disorder Arising from OSA 

Disorders Mechanisms 

Cardiovascular and Cerebrovascular 

disorders 

Repeated episodes of negative 

intrathoracic pressure 

Increased right and left ventricular 

afterload 

Increased level of norepinephrine 

Increased levels of cytokines: Interleukin 

6, 8 and Tumor Necrosis Factor (TNF)- 

alpha 

Other inflammatory factors 

Metabolic syndrome Disruption of slow wave sleep 

Interruption of growth hormone 

Erectile dysfunction Reduced amount of REM sleep; increased 

pro-inflammatory mediators producing 

small vessel disease 

Table 2-11.2: Mechanisms of Different Clinical Disorders Arising from OSA 

Common Clinical Manifestations of Obstructive Sleep Apnea 

Hypertension 

Myocardial infarction 

Heart failure 

Stroke 

Disrupted sleep 

Trouble waking up in the morning 

Dry mouth in the morning 

Morning headaches 

Twitching or limb movement 

Memory impairment 

Morning confusion 

Intellectual impairment 

Inability to focus 

Personality changes 

Irritability 

Depression 

Automobile accidents 

Impotence 

Night sweats 

Table 2-11.3: Common Clinical Manifestations of Obstructive Sleep Apnea 

Clearly, OSA has been associated with cardiovascular disease, 12 diabetes 

mellitus, 13 stroke 14 , lipid abnormalities, 15 and pulmonary vascular disease. 16 

Diagnosis 

A carefully focused history and physical examination should identify individuals 

with sleepiness or sleep-breathing disorders. 17 The only way to objectively 

diagnose OSA, however, is to perform an overnight sleep study (polysomnogram) 

in a qualified sleep laboratory. Therefore people with reports of daytime 

sleepiness, loud snoring and choking should be considered for a sleep study. 18 

Typically, polysomnography is a comprehensive overnight study performed 

in a sleep laboratory by trained technicians who monitor sleep stages, arousals 


181

182 


from sleep, eye movements, breathing effort, airflow, snoring, heart rate 

and rhythm, body position, limb movements and oxygen saturation (Figure 

2-11.2). These measurements enable the diagnosis of both pulmonary and 

non-pulmonary disorders of sleep. 

Figure 2-11.2: A polysomnogram of a patient with obstructive sleep apnea. (Note the lack 

of flow in the setting of chest and abdominal effort, followed by an arousal.) 

People with OSA often have very rapid sleep onset, but their sleep is interrupted 

by apnea and is terminated by arousal. This cycle of events is captured on 

the polysomnogram recording. Soon after the resumption of the breathing, 

the person resumes sleep and apnea recurs to repeat the cycle. The duration 

and number of apneas vary among people with OSA. Because respiratory 

muscles typically lose their tone during REM sleep, OSA is often more severe 

during this sleep stage. Proper evaluation of the patient should include a sleep 

sample sufficient to establish the diagnosis and severity of sleep apnea. When 

moderate or severe sleep apnea is found, a second sleep sample should be 

obtained during which continuous positive airway pressure (CPAP) is titrated 

to establish effective CPAP. While mild, OSA may also be treated with CPAP, 

other treatment such as oral appliances and otolaryngological surgery may 

be effective. The effectiveness of any treatment of OSA should be validated 

with overnight sleep studies. 

A polysomnogram performed in a sleep laboratory is the gold standard to 

diagnose obstructive sleep apnea. Because of the relative scarcity of sleep 

laboratory availability for people with suspected OSA, there is a growing trend 

for in-home (unattended) sleep studies. We believe, however, that at this time 

these studies may provide ambiguous or limited information. We further 

believe that CPAP cannot be accurately titrated during an unattended sleep 

study. In-home sleep studies may be useful, however, to screen presumed 

at risk individuals for laboratory sleep studies. To further evaluate patients 

with sleep apnea and its clinical consequences, the tests often performed are 

listed in Table 2-11.4. These tests may be obtained to formulate a fuller picture 

regarding the clinical consequences of OSA in a person with the disorder, but 

in no way do these tests establish the diagnosis of OSA.

Commonly Used Laboratory Investigations 

Complete blood count (polycythemia) 

Arterial blood gas (obesity hypoventilation syndrome) 

Electrocardiogram 

Echocardiogram (right heart failure) 

Pulmonary function testing (lung volume and saw tooth pattern on flow volume loop) 

Cephalometrogram 

Table 2-11.4: Commonly Used Laboratory Investigations 

Treatment of OSA 

The goals of treatment of OSAS are to alleviate excessive daytime sleepiness 

(EDS) and to reduce the frequency of apnea-hypopnea (AHI) to levels not 

associated with increased cardiovascular and cerebrovascular risk. Attenuation 

of disruptively intense snoring may have important social implications, however, 

if the snoring is primary and not associated with OSA, then treatment of such 

snoring should be decided on its own merits. 

Mild OSA (AHI = 6 – 15 events/hour) has not been clearly associated with 

increased cardiovascular and cerebrovascular risk. Thus, those with mild OSA 

who lack sleepiness may be best treated with education regarding the causes 

and risks of OSA, counseling with regard to good sleep hygiene, diet and weight 

loss, avoidance of alcohol, sedatives, and antihistamines, and possibly use of 

positional therapy (techniques to avoid sleeping supine). 19 Even for people who 

lack OSA, regular sleep-wake hours, sufficient sleep hours (most adults require 

7 – 8 hours of sleep per day), exposure to sunlight in the early morning, daily 

exercise (30 – 60 minutes/day but not within two hours of bedtime), limiting 

caffeine consumption, and completing the evening meal three or four hours 

before bedtime should be encouraged strongly. Weight loss has been shown 

to reduce mean AHI. 20,21 

People with mild OSA and coexisting EDS and people with moderate or severe 

OSA (AHI = 16 – 29 events/hour, and 30 or more events/hour, respectively) with 

or without EDS need additional treatment specifically directed to attenuating 

the frequency of apnea and hypopnea. In successfully doing so, sleep becomes 

less fragmented so that daytime alertness is restored. Furthermore, the 

apnea-hypopnea-hypoxia associated release of catecholamines and proinflammatory 

mediators is sufficiently attenuated to remove cardiovascular 

and cerebrovascular risks from OSAS. CPCP, invented by Sullivan in 1981, 22 

is the most commonl-prescribed and overall most effective treatment of 

OSAS and has replaced tracheostomy (now rarely performed for OSAS) as the 

treatment of choice. Regular CPAP use has been shown to improve quality of 

life, reduce daytime sleepiness, improve neuropsychiatric function, 23,24 reduce 

the need for medication to treat hypertension, and reduce the risk for adverse 

cardiovascular and cerebrovascular events among people with OSAS. 25 With 

CPAP treatment, positive airway pressure (PAP) is applied to the nose, or nose 

and mouth, through nasal “pillows”, nasal mask, or full facemask that covers 

the nose and the mouth. The PAP is transmitted across the nasal and oral 

cavities to the pharynx. Optimal PAP is determined during an overnight sleep 

study and it is that PAP that keeps the pharynx open (like an air splint) while 

the person sleeps in all positions and all sleep stages so that the AHI while 

using CPAP is < 6 events per hour (Figure 2-11.3). 


183

184 


Figure 2-11.3: Effects of nasal CPAP. The top panel shows the occlusion of the upper 

airway and apnea. The lower panel shows the pneumatic stent properties of CPAP. 

There are two varieties of CPAP: (1) CPAP where the positive airway 

pressure is kept constant throughout both inspiration and expiration (this is 

termed CPAP) and (2) CPAP where the positive airway pressure is somewhat 

lower during expiration than during inspiration (this is termed bi-level 

positive airway pressure or Bi-PAP). The choice of CPAP or Bi-PAP is based 

on clinical and technical considerations made at the time of the sleep study. 

Once determined, the needed equipment is prescribed for this person to use 

at home on a nightly basis. CPAP corrects OSA while the CPAP is being used, 

but CPAP does not eliminate the underlying tendency for OSA. Thus, CPAP 

must be used every night throughout the entire sleep period until it can be 

shown on an overnight sleep study that the affected individual no longer 

has OSA (e.g., after sufficient weight loss in patients with OSA). Compliance 

with CPAP use is a major concern. Discomfort from the mask, dry mouth and 

nose, skin irritation, and claustrophobia are the more common problems 

contributing to non-compliance with CPAP use while nose bleeds, swallowing 

of air, and pneumothorax occur much less frequently. Often the reasons for 

non-compliance with CPAP use are not clear. Early acquisition and application 

of CPAP following the diagnostic sleep study, patient education, motivation, 

reassurance, relaxation techniques, and the sense of improved alertness all 

help to promote compliance with CPAP use. Several studies have shown a 

majority of patients used CPAP in excess of four hours/night for more than 

two-thirds of the observed nights. 23 

OSAS treatment other than CPAP may be considered when CPAP is ineffective, 

the treated individual cannot use the device, or the treated individual prefers 

an alternative treatment. Alternative treatments include surgical approaches 

(tracheostomy, uvulopalatopharyngoplasty (UPPP), genioglossal advancement, 

maxillomandibular advancement, splints) and non-surgical approaches 

(intra-oral mouthpiece appliances). To date, for almost all people with OSAS, 

there are no medications that safely, effectively, and reliably correct OSAS.

Tracheostomy was first introduced as a successful treatment for sleep apnea 

in 1969 and was widely accepted as the treatment of choice. Tracheostomy, 

performed by ear nose and throat surgeons, involves cutting a hole into the 

trachea through which a tube is inserted to create a continuously patent airway 

through which the patient breathes. This bypasses the site of upper airway 

obstruction that causes OSA. Typically, the individual closes the tracheostomy 

tube in the day and opens it for sleep at night. Similar to CPAP, sleeping with an 

open tracheostomy corrects symptoms and morbidity related to OSA, but does 

not “cure” one of OSA. Even after years of normal sleep and breathing through 

open tracheostomy, closing the tube results in immediate apnea. 26 Because 

of the medical and psychosocial morbidity associated with tracheostomy and 

the invention of CPAP, its use has greatly diminished. Tracheostomy is usually 

reserved for patients with severe OSA who cannot tolerate CPAP and are not 

effectively managed by other treatment options. 27,28 

A variety of surgical interventions are used to modify specific sites of upper 

airway obstruction. The goal of all these procedures has been to create a more 

capacious pharyngeal space. Tonsillectomy is very effective in children and 

often the treatment of choice. However, it is usually ineffective in adults. 

UPPP involves separation of the soft palate from the posterior pharyngeal 

wall and enlargement of the entire space by removing the tonsils and uvula. 

Defining a successful operation as one that reduced AHI by 50% one year after 

surgery, Sher, in his meta-analysis 29 , found that in about 40% of patients, UPPP 

successfully corrected OSAS. Many of the reports in his analysis were anecdotal, 

however. Importantly, if more stringent criteria for success are applied (AHI = 

6 – 10 events/hour), then even fewer people were helped by UPPP. Generally, 

the procedure is not recommended for people with moderate or severe OSA. 

This procedure should be performed by otolaryngologists experienced in the 

treatment of OSAS. Recently, laser uvulopalatopharyngoplasty has been tried 

for snoring but is not recommended for the treatment of OSA. Genioglossal 

advancement is performed for obstruction at or below the base of tongue and 

sometimes also involves resuspension of the hyoid bone. 

Mandibluar advancement also known as Le Fort Type I osteotomy and 

maxillomandibular advancement have been employed in the treatment of 

sleep apnea. Patients who have craniofacial abnormalities30,31 and those who 

have failed genioglossal advancement or uvulopalatopharyngoplasty may 

benefit from these procedures. Excessive advancement sometimes leads to 

temporo-manibular joint problems. 

Intra-oral mouthpiece appliances have been shown to be effective among 

people with mild OSA. The American Academy of Sleep Medicine does not 

recommend their use for moderately severe and severe OSA. They should 

be crafted by an oral surgeon or dentist with experience in treating OSA. 

Unfortunately, these mouthpieces do not always correct even mild OSA and 

there is no reliable way to be completely certain the mouthpiece will correct 

OSA before it is made. Once made, the individual should undergo an overnight 

sleep study while using the mouthpiece to assure its efficacy. Some find that 

sustained use of the mouthpiece overnight to be uncomfortable and temporomandibular 

joint problems from prolonged use have been described. 


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People with OSAS undergoing surgery with general anesthesia or who are 

undergoing procedures with use of sedation need special consideration. We 

suggest the following as cautious and prudent guidelines. When intubation 

is planned, the patient should be seen by the anesthesiologist well before the 

planned surgery to determine whether there are problems of intubation related 

to the patient’s crowded pharynx. Following surgery, the patient should be 

extubated when awake, in a monitored setting, and then should have CPAP 

applied at a pressure setting previously determined to be effective. CPAP should 

be administered whenever the patient is sleeping or receiving potentiallysedating 

medications. Such patients should be observed in a monitored setting 

over the first 24 to 36 post-operative hours. For those undergoing procedures 

under sedation, use of CPAP while the patient is sedated is recommended. 

CENTRAL SLEEP APNEA 

In contrast to OSA, in Central Sleep Apnea (CSA) there is no airflow from the 

nose or mouth because there is no effort to breathe. While people with OSA may 

have also some CSA, by itself CSA is relatively less common. Instability of the 

central respiratory mechanism produces a decrement or transient termination 

of neural signal output from the respiratory center in the brainstem to the 

respiratory muscles. This results in the absence of an effort to breathe, absence 

of airflow from the nose and the mouth (apnea), oxyhemoglobin desaturation, 

and arousal from sleep. 

Typically, people with CSA are men, in their fourth to fifth decade of life, 

who experience headaches, excessive sleepiness, lethargy, may snore and have 

hypercapnia. The most common condition associated with CSA is congestive 

heart failure (CHF) with Cheyne-Stokes breathing. 32 Other conditions 

associated with CSA include primary dysfunction of the central ventilatory 

drive (Ondine’s curse), 33 metabolic derangement or respiratory muscle 

disorders, high cervical cord injury, brainstem surgery, birth injuries, bulbar 

poliomyelitis, 34 encephalitis, 35 brainstem tumors, carotid endarterectomy, 36 

Parkinson’s disease, 37 hypothyroidism, metabolic alkalosis, 32 respiratory 

muscle dysfunction due to myasthenia gravis, amyotrophic lateral sclerosis, 

Guillain-Barre Syndrome and spinal muscle atrophy. 

Initially, people with CSA may be thought to have OSA due to the similarity 

of their clinical manifestations. Definitive diagnosis is made by a sleep study 

that shows repeated apneas without respiratory efforts. The mainstay of 

treatment of CSA is treatment of the underlying disorder and avoidance of 

sedating medications and alcohol. Patients with hypoxemia usually have a 

good response to nocturnal supplemental oxygen. Others, especially those 

with CHF and interventricular devices, have been shown to respond to CPAP. 

Patients with neuromuscular disorders should preferably sleep in an upright 

position and avoid sleeping in a supine position. In the earlier stages of 

neuromuscular disease, CPAP may be helpful. However, as the neuromuscular 

disease progresses and respiratory muscles weaken, often tracheostomy and 

assisted mechanical ventilation is needed. Some of these people may benefit 

from diaphragmatic pacing. 38

MIXED APNEA 

Mixed apnea occurs when a central apnea is terminated with an obstructive 

apnea. The mixed apnea is a manifestation of both abnormalities of central 

respiratory drive instability and of pharyngeal upper airway occlusion. 

Functionally, however, mixed apneas are more similar to obstructive apneas. 

Diagnosis of mixed sleep apnea is made by a sleep study. Nasal CPAP is the 

most effective treatment option and has been shown to improve quality of life 

similar to patients with OSA. 

UPPER AIRWAY RESISTANCE SYNDROME 

Upper airway resistance syndrome (UARS), first described by Guilleminault, 39 

is a milder form of disturbed breathing during sleep where increased upper 

airway resistance in the absence of frank apnea produces frequent arousals 

and in turn excessive daytime sleepiness. UARS is more common in women. 

People with excessive sleepiness and disturbed sleep due to UARS are diagnosed 

and treated similarly to those with OSA. 

NARCOLEPSY 

It is beyond the scope of this chapter to discuss narcolepsy in depth. A brief 

description is included here because there is a popular use of the word “narcolepsy” 

to describe any individual who has excessive daytime sleepiness. 40 While 

OSAS is a major cause of EDS, many conditions can produce EDS including 

(but not limited to) narcolepsy, restless leg syndrome, periodic limb movement 

disorder, insufficient sleep syndrome, and circadian sleep disorders. While 

narcolepsy causes EDS, EDS is not narcolepsy. Importantly, while narcolepsy 

and OSAS may coexist in some individuals, most afflicted with narcolepsy do 

not have OSAS and by far, most afflicted with OSAS do not have narcolepsy. 

Narcolepsy is a neurological condition most often resulting from lesions in 

the posterior hypothalamus where cells that produce the alerting neuro-peptide 

hypocretin (also called orexin) are in various stages of decay or death. As a result, 

lower amounts of hypocretin are produced and secreted and proportionally 

the alerting effects of this peptide are lost. Overnight sleep studies among 

people with narcolepsy typically show an earlier than usual onset of the first 

REM sleep period and highly-fragmented sleep from spontaneous arousals. 

Of interest, narcolepsy is a REM sleep dissociative condition where during 

wakeful states intrusions of REM sleep occur. Fragmentation of the major sleep 

period and REM sleep intrusion into the wakeful state account for the clinical 

features which include excessive daytime sleepiness, memory impairment, 

dissociative behaviors (i.e., disruptions of aspects of consciousness, identity, 

memory, motor behavior, or environmental awareness), hypnogogic or 

hypnopompic hallucinations (visual, tactile, auditory, or other sensory events 

that occur at the transition from wakefulness to sleep (hypnagogic) or from 

sleep to wakefulness (hypnopompic)), sleep paralysis (a period of inability to 

perform voluntary movements either at sleep onset or upon awakening), and 

cataplexy (condition in which a person suddenly feels weak and collapses 

at moments of strong emotion). While any sleep-depriving condition may 

produce EDS, hypnogogic hallucinations, sleep paralysis, and with rare 

exceptions, cataplexy occur exclusively in narcolepsy. Narcolepsy may exist 


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with or without cataplexy. The condition occurs equally in men and women. 

In the United States, one out of 2,000 people are affected. 41,42,43 

Typically, the illness first occurs most often in early teens and late in the third 

decade of life. There is a genetic association with human leukocyte antigens 

HLA DR2 and DQ1, however, this association is less strong among African- 

Americans. The diagnosis is made from a carefully-obtained medical history 

and is supported by the results of overnight sleep studies followed by a multisleep 

latency testing. The sleep study shows early onset to the first REM sleep 

period, fragmentation of sleep by spontaneous arousals, and absence of other 

sleep fragmenting phenomena such as apnea or periodic limb movements. 

A mean sleep latency of less than eight minutes and two sleep onset REM 

periods is seen on a multi-sleep latency test. In some cases, measurement of 

hypocretin-orexin levels in the cerebrospinal fluid is helpful. The condition is 

treated medically with sleep hygiene techniques that include sufficient hours 

of sleep (major sleep period), regularly timed naps, medications to promote 

alertness, and medications that promote sleep consolidation and inhibit 

cataplexy. The illness is chronic and education, counseling, and supportive 

measures are often crucial. 

REFERENCES 

1. Burwell CS, Robin ED, Whaley RD, et al. Extreme obesity associated with 

alveolar hypoventilation: Pickwickian Syndrome. Am J Med 1956; 21:811- 

18. 

2. Gastaut H, Tassarini CA, Duron B. Polygraphic study of the episodic diurnal 

and nocturnal (hypnic and respiratory) manifestations of the Pickwick 

syndrome. Brain Research 1965; 2:167. 

3. Pack AI. Obstructive sleep apnea. Adv Intern Med 1994; 39:517. 

4. Namen AM, Dunagan DP, Fleischer A, et al. Increased physician-reported 

sleep apnea: the national ambulatory medical care survey. Chest 2002; 

121:1741. 

5. Young T, Palta M, Dempsey J, Skatrud J, Weber S and Badr S. The occurrence 

of sleep-disordered breathing among middle-aged adults. NEJM 1993; 

328:1230-5. 

6. Kales A, Cadieux RJ, Bixler EO, et al. Severe obstructive sleep apnea-I: 

Onset, clinical course and characteristics. J Chron Dis 1985; 38:419. 

7. Shepard JW Jr, Gefter WB, Guilleminault C, et al. Evaluation of the upper 

airway in patients with obstructive sleep apnea. Sleep 1991; 14:361-71. 

8. Mezzanotte WS, Tangel DJ, White DP. Waking Genioglossal EMG in sleep 

apnea patients versus normal controls (a neuromuscular compensatory 

mechanism). J Clin Invest 1992; 89:1571. 

9. Westbrook PR. Sleep disorders and upper airway obstruction in adults. 

Otolaryngol Clin North Am 1990; 23:727. 

10. Teran-Santos J, Jimnez-Gomez A, et al. The association between sleep 

apnea and the risk of traffic accidents. NEJM 1999; 340:847-851.

11. Aldrich CK, Aldrich MF, Aldrich TK, and Aldrich RF. Asleep at the wheel: 

the physician’s role in preventing accidents “just waiting to happen”. 

Postgraduate Medicine 1986; 80: No 5: 233-240. 

12. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, 

sleep apnea and hypertension in a large community based study: Sleep 

Heart Health Study. JAMA 2000; 283: 1829-1836. 

13. Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea 

and type II diabetes: A population based study. Am J Respir Crit Care Med 

2005; 172:1590. 

14. Yaggi H, Concato J, et al. Obstructive sleep apnea as a risk factor for stroke 

and death. NEJM 2005; 353:2034-2041. 

15. Borjel J, Sanner BM, Bittlinsky A, et al. Obstructive sleep apnea and its 

therapy influence high-density lipoprotein cholesterol serum levels. Eur 

Respir J 2006; 27:121. 

16. Goring K, Collop N. Sleep Disordered Breathing in Hospitalized Patients. 

J Clin Sleep Med 2008; 4(2):105-110. 

17. Viner S, Szalai JP, Hoffstein V. Are history and physical examination a good 

screening test for sleep apnea? Ann Intern Med 1991; 115:356. 

18. Strollo PJ, Rogers RM. Obstructive sleep apnea. NEJM 1996; 334:99. 

19. Oksenberg A, Silverberg DS, Arons E, et al. Positional vs non-positional 

obstructive sleep apnea patients: anthropomorphic, nocturnal 

polysomnographic and multiple sleep latency test data. Chest 1997; 

112:629-39. 

20. Scheuller M, Weider D. Bariatric surgery for treatment of sleep apnea 

syndrome in morbidly obese patients: long-term results. Otolaryngol Head 

Neck Surg 2001; 125:299-302. 

21. Smith PL, Gold AR, Meyers DA, et al. Weight loss in mildly to moderately 

obese patients with sleep apnea. Ann Intern Med 1985; 103:850-5. 

22. Sullivan CE, Issa FA. Reversal of obstructive sleep apnea by continuous 

positive airway pressure applied through the nares. Lancet 1981; I:862-65. 

23. Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of 

nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir 

Dis 1993; 147:887-95. 

24. Derderian SS, Bridenbaugh RH, Rajagopal KR. Neuropsychologic symptoms 

in obstructive sleep apnea improve after treatment with nasal continuous 

positive airway pressure. Chest 1988; 94:1023-7. 

25 Cassar A, Morgenthaler TI, Lennon RJ, Rihal CS, Lerman A. Treatment of 

Obstructive Sleep Anpea isasociated with decreased cardiac death after 

percutaneous coronary intervention. Journ of Amer Coll of Cardiol 2007; 

50: 1310-1314. 


189

190 


26. Appel D, Schmidt-Nowarra WW, Pollack CP, Weitzman ED. Effects of 

tracheostomy closure on sleep and breathing in sleep apnea patients with 

long term tracheostomy. Sleep Research 1982; 11: 135. 

27. Guilleminault C, Simmons FB, Motta J, et al. Obstructive sleep apnea 

syndrome and tracheostomy: long term follow up experience. Arch Intern 

Med 1981; 141:985-8. 

28. Conway WA, Victor LD, Magilligan DJ Jr, et al. Adverse effects of tracheostomy 

for sleep apnea. JAMA 1981; 246:347-50. 

29. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modification 

of the upper airway in adults with obstructive sleep apnea syndrome. 

Sleep 1996; 19: 156-177. 

30. Kuo PC, West RA, Bloomquist DS, et al. The effect of manibular osteotomy 

in patients with hypersomnia sleep apnea. Oral Surg 1979; 48:385-92. 

31. Bear SE, Priest JH. Sleep apnea syndrome: Correction with surgical 

advancement of the mandible. J Oral Surg 1980; 38:543-9. 

32. Guyton AC, Crowell JW, Moore JW. Basic oscillating mechanism of Cheyne- 

Stroke breathing. Am J Physiol 1956; 187:395-8. 

33. Severinghouse JW, Mitchell RA. Ondine’s curse- failure of respiratory 

center automaticity while awake. Clin Res 1962; 10:122. 

34. Solliday NH, Gaensler EA, Schwaber JR, et al. Impaired central chemoreceptor 

function and chronic hypoventilation many years following poliomyelitis. 

Respiration 1974; 31:177-92. 

35. Cohen JE, Kuida H. Primary alveolar hypoventilation associated with 

Western equine encephalitis. Ann Intern Med 1962; 56:633-44. 

36. Beamish D, Wildsmith JAW. Ondine’s curse after carotid endarterectomy. 

Br Med J 1978; 2:1607-8. 

37. Strieder DJ, Baker WG, BaringerJR, et al. Chronic hypoventilation of central 

origin. Am Rev Respir Dis 1967; 96:501. 

38. Hyland RH, Jones NL, Powles ACP, et al. Primary alveolar hypoventilation 

treated with nocturnal electrophrenic respiration. Am Rev Respir Dis 1978; 

117:165-72. 

39. Guilleminault C, Stoohs R, Clerk A, Maistros P. A cause of excessive daytime 

sleepiness: Upper airway resistance syndrome. Chest 1993; 104: 781-787. 

40. Zeman A, Britton T, Douglas N, et al. Narcolepsy and excessive daytime 

sleepiness. BMJ 2004; 329:724. 

41. Ohayon MM, Priest RG, Zulley J, et al. Prevalence of narcolepsy symptomatology 

and diagnosis in the European general population. Neurology 2002; 58:1826. 

42. Coleman RM, et al. Sleep-wake disorders based on a polysomnographic 

diagnosis. A national cooperative study. JAMA 1982; 247:997. 

43. Silber MH, Krahn LE, Olson EJ, et al. The epidemiology of narcolepsy in 

Olmsted County, Minnesota a population based study. Sleep 2002; 25:197.

Chapter 2-12 

Cough 

By Dr. Peter V. Dicpinigaitis MD 

Cough is the most common complaint for which patients in the United States 

seek medical attention. 1 An estimated two billion dollars are spent annually on 

prescription and over-the-counter (OTC) cough remedies in the United States 

alone. Fortunately, cough is usually a temporary and self-limited condition. 

When cough lingers, however, it becomes a troubling problem for the patient 

and may indicate a more serious underlying condition that requires medical 

attention. The importance of cough as a clinical problem is reflected in the 

fact that recently, three major organizations of pulmonary physicians have 

published guidelines on the management of cough. 2,3,4 

Cough is classified according to its duration (Table 2-12.1). Acute cough 

refers to a cough present for three weeks or less. If a cough persists for greater 

than three but less than eight weeks, it is termed subacute. Chronic cough 

refers to a cough that has been present for greater than eight weeks. 2,3 This 

distinction is quite important because the various types of cough have different 

underlying causes. 

Acute 

Subacute 

Chronic 

Classification of Cough by Duration 

< 3 Weeks 

3 - 8 Weeks 

> 8 Weeks 

Table 2-12.1: Classification of Cough by Duration 

Although we typically consider cough an annoying symptom, it is important 

to realize that cough is an important defense mechanism. An intact cough 

reflex effectively clears secretions out of the lungs, and prevents foreign objects 

from entering the airways. 

MECHANISM OF COUGH 

The upper and lower respiratory tract are lined with receptors that, when 

stimulated by a variety of different triggers, can cause cough. The two main 

types of receptors that induce cough are the rapidly adapting pulmonary 

stretch receptors, or RARs, and the C-fibers. 5 When these receptors are 

stimulated, they send impulses to the brain that produce cough. The nature 

of the communication between the receptors in the respiratory tract and the 

brain remains poorly understood. 

More recently, a specific type of receptor, called the TRPV1 (transient 

receptor potential vanilloid 1), has been discovered. 6 The TRPV1 is likely one 

of multiple types of receptors important in causing cough. An active area of 

current research is the discovery of antagonists (blockers) of the TRPV1 receptor 

that might be effective future drugs for the treatment of cough. 

Chapter 2-12 • Cough 191

192 Chapter 2-12 • Cough 

ACUTE COUGH 

As mentioned above, a cough lasting less than three weeks is termed an acute 

cough. Most cases of acute cough are caused by viral upper respiratory tract 

infections (URI), i.e., the common cold. Acute cough due to URI is usually selflimited, 

lasting for only a few days. It is typically non-productive (dry) or is 

accompanied by small amounts of clear phlegm. Although acute cough due to 

the common cold is usually short-lived, many individuals seek OTC remedies at 

their pharmacy to help suppress this annoying symptom. Unfortunately, there 

is very little scientific evidence that many of the commonly-used cough and 

cold products sold worldwide are actually effective against cough due to the 

common cold. In fact, the recent cough management guidelines published by 

the American College of Chest Physicians (ACCP) recommend that individuals 

not rush to treat an acute cough, since the cough is usually temporary and 

few products commercially available have ever been shown to be effective. 2 

The only therapy for cough due to the common cold that has been 

demonstrated to be effective in adequately-performed clinical studies is a 

combination of an older-generation antihistamine (such as chlorpheniramine 

or brompheniramine) and a decongestant (such as pseudoephedrine). One 

potential drawback of the so-called older-generation antihistamines is that 

they may cause sedation (drowsiness). The newer-generation antihistamines, 

such as loratidine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra) are 

less likely to cause sedation and may be useful in relieving allergy symptoms, 

but they are ineffective in suppressing cough. 2,7 Thus, if relief from an acute 

cough due to URI is desired for fire fighters and other emergency responders, 

a combination of an older-generation antihistamine and decongestant is 

recommended. 2 An important exception to this statement is for acute cough 

in children. Because these medications have not been shown to be effective 

against cough in children, and because they can cause side effects that may 

lead to dangerous behavior in children, such as drowsiness induced by the 

antihistamines, or hyperexcitability due to pseudoephedrine, the 2006 ACCP 

guidelines do not recommend the use of any medications to treat acute cough 

due to the common cold in children. 2 

The previous discussion of acute cough has focused on cough due to URI 

(common cold). However, it is important to understand that the sudden onset 

of cough can represent a serious underlying condition that requires immediate 

medical attention. For example, if the cough is productive, meaning that sputum 

(phlegm) is produced, especially if the sputum is yellow, green, or bloodstreaked, 

a bacterial bronchitis may be present that would require antibiotic 

therapy. If these symptoms were associated with high fever, chest pain on 

breathing in, or significant illness, pneumonia would need to be excluded. 

Any significant amount of blood produced with coughing requires emergent 

medical attention, as this could indicate a serious underlying process such 

as bacterial infection (pneumonia), tuberculosis (TB) or lung cancer. The 

production of pink, frothy sputum in the setting of shortness of breath and/ 

or chest pain could indicate pulmonary edema (lungs filling up with fluid) 

that is a sign of heart failure.

Acute Cough and OTC Cough and Cold Products 

The ACCP cough guidelines, published in January, 2006 caused a great deal of 

controversy and gained significant media attention because of their statement 

that most OTC cough and cold preparations are ineffective against acute 

cough due to the common cold. There are several likely explanations for the 

guidelines’ conclusion, which was based on a thorough review of the medical 

literature. Firstly, the guidelines evaluated only studies that were performed in 

a scientifically rigorous manner. Many of the OTC cough and cold preparations 

currently available were approved decades ago when criteria for approval of 

new medications were less stringent and pharmaceutical companies were not 

obligated to perform and publish exhaustive and meticulous clinical trials. 

Secondly, studies of potential therapies for acute cough are difficult to perform. 

Since acute cough due to the common cold typically resolves spontaneously 

within a few days, it is challenging to design a study that could demonstrate a 

drug to be more effective than a placebo. For statistical reasons, a very large 

number of subjects would need to be evaluated, thus necessitating lengthy 

and expensive trials. Further complicating matters is the fact that there has 

been a strong placebo response noted in cough trials. 8 Many studies of cough 

syrups, for example, have used a placebo syrup to compare to the study drug. 

However, previous research has shown that a sweet, thick syrup, without any 

medication, can have a cough suppressing effect (demulcent effect). 8 

Another likely explanation for the failure of some cough medications to show 

efficacy in clinical trials is that they may contain insufficient amounts of the 

cough-suppressing (antitussive) agent. For example, dextromethorphan is a 

non-narcotic opioid drug that is a component of hundreds of cough and cold 

preparations sold worldwide. Studies have shown that dextromethorphan, 

at doses of 30 mg or more, is an effective cough suppressant. 9 However, many 

of the commonly-used cough preparations contain significantly less than 30 

mg of dextromethorphan per recommended dose. 

SUBACUTE COUGH 

When cough persists beyond three weeks (but less than eight weeks) it is termed 

a subacute cough. Most cases of subacute cough are likely the result of acute 

cough due to viral URI (common cold) failing to resolve. Why this so-called 

postviral (or postinfectious) cough lingers in a subgroup of individuals is not 

well understood. It is probably due to severe irritation of the cough receptors 

by the initial viral infection of the airways, and subsequent inability of the 

inflamed area to heal because of persistent coughing that continues to irritate 

the lining of the respiratory tract. 

Subacute, postviral cough has proven to be a difficult condition to treat. For 

severe cough, a 1-2 week course of oral steroid therapy (with prednisone, for 

example) is often effective. 10 However, there are few studies evaluating whether 

inhaled steroids, which are associated with significantly less side effects than 

oral steroids, are useful for this type of cough. 2,10 Over-the-counter cough and 

cold remedies tend to be ineffective for subacute, postviral cough. 

Another potential cause of subacute cough is pertussis, or whooping cough. 2 

Recently, whooping cough has re-emerged as a significant medical issue in the 

non-pediatric population. Indeed, in 2004, 27% of reported cases of whooping 

Chapter 2-12 • Cough 

193

194 


cough occurred in adults and adolescents. This rise in the incidence of whooping 

cough is likely due to the waning of immunity that was acquired by adults who 

had infection prior to the availability of the pertussis vaccine in the 1950s, and, 

the waning of immunity provided by vaccines that were administered more 

than a decade previously. Therefore, the ACCP cough guidelines recommend 

that adults receive the newly available acellular vaccine for protection against 

this infection. 2 The cough due to pertussis can take the form of violent episodes 

associated with vomiting, but the characteristic “whooping” sound is in fact 

present in only a minority of patients. 

Some cases of subacute cough will persist beyond eight weeks and therefore 

will fulfill the definition of chronic cough. A discussion of chronic cough 

follows below. 

CHRONIC COUGH 

Chronic cough is the result of one or more underlying conditions persistently 

stimulating the cough receptors that line the upper and lower respiratory tract. 

Chronic cough is a serious issue not only because it exposes an underlying 

illness, but also because of its effect on an individual’s quality of life. For 

example, chronic cough may result in physical problems such as difficulty 

sleeping, chest pain, throat soreness, exhaustion and, especially in women, 

urinary incontinence. Many patients who have suffered from chronic cough for 

months or years become socially isolated, afraid to go out in public for fear of 

a severe coughing attack drawing unwanted attention. Further worsening the 

situation is the effect that an individual’s chronic cough can have on spouses, 

family members and coworkers. It is not surprising, therefore, that a recent 

study demonstrated a very high incidence of symptoms of depression among 

patients presenting to a specialized cough center for evaluation and treatment. 11 

Causes of Chronic Cough 

Multiple studies have shown that in patients who are nonsmokers and who 

do not have an active pulmonary process demonstrated on chest x-ray, the 

vast majority of cases of chronic cough are due to one or more of the following 

conditions: 

• Postnasal drip syndrome (PNDS), renamed upper airway cough 

syndrome(UACS) 

• Asthma 

• Non-asthmatic eosinophilic bronchitis (EB) 

• Gastroesophageal reflux disease (GERD) 

Often, more than one of these conditions may be present simultaneously, 

so a partial response to a particular treatment may indicate that only one of 

multiple underlying causes of cough have been addressed. 

Postnasal Drip Syndrome (PNDS) 

Multiple studies performed in the United States have shown PNDS to be the 

most common cause of chronic cough. 2 PNDS is not a disease but a response 

to one of many possible stimuli, including viral URI (common cold), allergies,

and sinus infection. Cough may result from the inciting inflammatory process 

stimulating cough receptors in the upper airway, or from mucus “dripping” 

down into the back of the throat and mechanically inducing cough. PNDS 

has recently been renamed upper airway cough syndrome (UACS) to better 

describe what is likely a multifaceted condition or variety of processes. 2 

The most effective treatment for chronic cough due to UACS is the 

combination of an older-generation antihistamine (such as chlorpheniramine 

or brompheniramine) and a decongestant (such as pseudoephedrine). 2 This 

therapy was also discussed under acute cough due to the common cold. Other 

treatments that may be effective for chronic cough due to UACS include nasal 

steroids, nasal ipratropium (Atrovent), and nasal cromolyn. As is the case for 

acute cough due to the common cold, the newer-generation, non-sedating 

antihistamines are not effective for UACS-induced cough. 

Asthma 

Studies have shown that asthma may account for approximately 25% of cases 

of chronic cough in adults. 2 Cough likely results from the inflammatory 

stimulation of cough receptors that line the airways. Asthma may be suggested 

as the cause of chronic cough if the typical associated symptoms of shortness 

of breath and/or wheezing are present. However, in a subgroup of asthmatics, 

cough is the sole symptom. This condition is termed cough-variant asthma. 

The treatment of chronic cough due to asthma is identical to that of the 

typical form of the disease: inhaled bronchodilators and inhaled steroids. 

Studies have shown, however, that up to eight weeks of therapy with an inhaled 

steroid may be required for resolution of cough. 12 The newest class of asthma 

drugs, the leukotriene receptor antagonists (LTRAs), have been shown to be 

particularly effective in cough-variant asthma. 13 Since asthma is a disease of 

chronic airway inflammation, chronic anti-inflammatory therapy is required 

to prevent the permanent changes of untreated airway inflammation. Recent 

evidence suggests that cough-variant asthma should also be treated with 

chronic anti-inflammatory therapy to prevent irreversible changes. 14 

Non-Asthmatic Eosinophilic Bronchitis (EB) 

Only during the past two decades has the condition of non-asthmatic EB been 

identified and appreciated as an important cause of chronic cough. 15 The 

airway changes of EB are similar to those of asthma: there is an infiltration of 

inflammatory cells called eosinophils. Eosinophilic bronchitis differs from 

asthma in that there is no demonstrable reversibility of airway obstruction 

with inhaled bronchodilators, and there is no hyperresponsiveenss to 

methacholine, both of which are hallmarks of asthma. However, chronic cough 

due to EB responds very well to inhaled steroids and thus, it is likely that some 

cases of EB are misdiagnosed as asthma. Although the prevalence of chronic 

cough due to EB has not been formally investigated in the United Staes, two 

European studies have shown the incidence of EB among patients presenting 

for evaluation of chronic cough to be about 12%. 16,17 


195

196 


Gastroesophageal Reflux Disease (GERD) 

Multiple prospective studies have shown that GERD is among the most common 

causes of chronic cough. 2 Chronic cough due to GERD may be difficult to 

diagnose because more than half of patients with GERD-induced cough do not 

display the typical symptoms of GERD such as heartburn. 2 Thus, a high index 

of suspicion must be maintained when evaluating a patient with chronic cough. 

Cough due to reflux may result from multiple mechanisms. The mere presence 

of acid refluxing from the stomach into the distal esophagus may stimulate 

nerve endings to trigger an esophageal-tracheobronchial reflex resulting in 

cough. Alternatively (or, additionally), acid may travel further up the esophagus 

and penetrate the upper airway (larynx) to stimulate cough receptors. This 

phenomenon has been termed laryngopharyngeal reflux (LPR) and may be 

very important in terms of reflux-induced cough. 

Once the diagnosis of GERD-induced cough is suspected, aggressive medical 

therapy is required. Often, patients with chronic cough due to GERD need 

higher doses of medication and longer duration of therapy than patients with 

typical GERD symptoms (i.e., heartburn) without cough. For example, highdose 

therapy with twice-daily proton-pump inhibitors (PPIs; very strong acidsuppressing 

medications such as Protonix®, Nexium®, Aciphex® and Prevacid®) 

for at least two months is often required. In some patients, cough persists even 

though refluxing stomach acid is completely eliminated by the PPI medication. 

In this subgroup of patients, cough may be due to the reflux of non-acid 

material into the esophagus. In such cases, additional treatment in the form 

of prokinetic therapy is required with medications such as metaclopramide. 

The prokinetic agent limits the reflux of gastric contents into the esophagus 

and works together with the acid suppressing medication. 

When maximal medical therapy is inadequate to control chronic cough 

due to GERD, surgical intervention may be considered. A procedure called a 

laporoscopic Nissen fundoplication surgically tightens the junction between 

the stomach and esophagus to prevent reflux. Unfortunately, the procedure 

has not proven to be completely effective since some patients achieve only a 

partial or temporary response. 18 

It is important to realize that, in addition to taking medication, lifestyle 

measures are essential in treating GERD. Suggestions that GERD patients 

should follow in an attempt to minimize reflux, and hopefully improve cough, 

are as follows: 

• Sleep with head elevated (2-3 pillows) 

• Do not eat within 2 hours of bedtime 

• Avoid foods/beverages that worsen GERD 

→ Alcohol 

→ Caffeine (coffee, tea, cola drinks) 

→ Chocolate 

→ Peppermint 

→ Spicy foods 

→ Fatty foods

OTHER SPECIFIC ISSUES RELEVANT TO CHRONIC COUGH 

Cigarette Smoking 

Chronic cough in a cigarette smoker may be due to any of the causes discussed 

previously, however, smoking itself must be excluded as a cause of cough. 

Anecdotal experience suggests that cough due to smoking will resolve or 

significantly improve within four weeks of quitting. If cough does not resolve 

after four weeks of abstinence from tobacco, other causes need to be evaluated. 

A chest x-ray and pulmonary function tests (PFTs) should be performed to 

exclude evidence of infection, cancer, or chronic obstructive lung disease 

(chronic bronchitis, emphysema). 

Interestingly, research studies have shown that smokers have a diminished 

cough reflex sensitivity compared to nonsmokers. 19 In other words, it is more 

difficult to experimentally induce cough in a smoker compared to a nonsmoker. 

This is probably due to chronic cigarette smoke-induced desensitization of 

cough receptors lining the respiratory tract. Furthermore, after as little as 

two weeks of smoking cessation, the cough reflex becomes measurably more 

sensitive, even in subjects who had been smoking for many years. 20 Because 

cough is an important protective reflex, these recent findings are significant 

in that they reveal another potential adverse consequence of smoking. Indeed, 

cigarette smoke-induced suppression of the cough reflex might explain why 

smokers are more inclined to suffer respiratory tract infections compared to 

nonsmokers. 20 

Gender 

Multiple studies have shown that women have a more sensitive cough reflex 

than men, i.e., it is easier to experimentally cause cough in women. This has 

been shown in studies of healthy subjects 21,22 and in patients with chronic 

cough. 23 These findings likely explain why the majority of patients seeking 

treatment in specialized cough centers are women. 2,23 

Medications Taken for Other Reasons 

A group of medications known as the angiotensin converting-enzyme (ACE) 

inhibitors are commonly used to treat hypertension and congestive heart 

failure. This is the only class of drugs known to cause cough, and does so in 5 

- 20% of patients taking these medications. 2 The cough is typically associated 

with a dry, tickling sensation in the throat. Cough may occur within hours 

of the first dose of the ACE inhibitor, or may ccur months to years later. The 

only uniformly successful treatment for ACE inhibitor-induced cough is to 

stop the medication. In most patients, cough will resolve within one week, 

although in a subgroup of individuals, the cough may linger for several months. 

Fortunately, an alternative class of drugs, the angiotensin receptor blockers 

(ARBs), is available and is not associated with cough. 


197

198 


WORLD TRADE CENTER COUGH 

Immediately after the collapse of the World Trade Center on September 11, 2001, 

members of the New York City Fire Department and other rescue workers were 

exposed to high concentrations of dust and ash that spread throughout the 

area. Within several months of the attack, it was observed that many of those 

exposed developed a persistent cough, eventually termed “World Trade Center 

cough.” 24 As these exposed workers continued to be followed and evaluated 

over time, it was established that World Trade Center cough was likely a result 

of various conditions induced by the inhalation of toxic materials, including 

damage to the upper airways and sinuses (chronic rhinosinusitis); GERD (see 

discussion above); and damage to the lower airways inducing an asthma-like 

condition known as reactive airways dysfunction syndrome (RADS). 25 Treatment 

is aimed at the suspected underlying conditions in a given patient, including 

inhaled nasal steroids and decongestants for rhinosinusitis; acid-suppressing 

medications and dietary modifications for GERD (see discussion above); and 

inhaled bronchodilators and steroids for asthma-like symptoms. 25 

REFERENCES 

1. Burt CW, Schappert SM. Ambulatory care visits to physician offices, 

hospital outpatient departments, and emergency departments: United 

States, 1999-2000. Vital Health Stat 13 2004;157:1-70. 

2. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management 

of cough: ACCP evidence-based clinical practice guidelines. Chest 

2006;129:1S-292S. 

3. Morice AH, Fontana GA, Sovijarvi ARA, et al. The diagnosis and management 

of chronic cough. Eur Respir J 2004;24:481-492. 

4. Morice AH, McGarvey L, Pavord I, et al. Recommendations for the 

management of cough in adults. Thorax 2006;61(suppl. 1):1-24. 

5. Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J 

1995;8:1193-1202. 

6. Jia Y, McLeod RL, Hey JA. TRPV1 receptor: a target treatment of pain, 

cough, airway disease and urinary incontinence. Drug News Perspect 

2005;18:165-171. 

7. Dicpinigaitis PV, Gayle YE. Effect of the second-generation antihistamine, 

fexofenadine, on cough reflex sensitivity and pulmonary function. Br J 

Clin Pharmacol 2003;56:501-504. 

8. Eccles R. The powerful placebo in cough studies? Pulm Pharmacol Ther 

2002;15:303-308. 

9. Pavesi L, Subburaj S, Porter-Shaw K. Application and validation of a 

computerized cough acquisition system for objective monitoring of acute 

cough: a meta-analysis. Chest 2001;120:1121-1128. 

10. Poe RH, Harder RV, Israel RH, et al. Chronic persistent cough: experience 

in diagnosis and outcome using an anatomic diagnostic protocol. Chest 

1989;95:723-728.

11. Dicpinigaitis PV, Tso R, Banauch G. Prevalence of depressive symptoms 

among patients with chronic cough. Chest 2006;130:1839-1843. 

12. Irwin RS, French CT, Smyrnios NA, et al. Interpretation of positive results of 

a methacholine inhalation challenge and 1 week of inhaled bronchodilator 

use in diagnosing and treating cough-variant asthma. Arch Intern Med 

1997;157:1981-1987. 

13. Dicpinigaitis PV, Dobkin JB, Reichel J. Antitussive effect of the leukotriene 

receptor antagonist zafirlukast in subjects with cough-variant asthma. J 

Asthma 2002;39:291-297. 

14. Niimi A, Matsumoto H, Minakuchi M, et al. Airway remodeling in coughvariant 

asthma. Lancet 2000;356:564-565. 

15. Gibson PG, Dolovich J, Denburg J, et al. Chronic cough: eosinophilic 

bronchitis without asthma. Lancet 1989;I:1346-1348. 

16. Brightling CE, Ward R, Goh KL, et al. Eosinophilic bronchitis is an important 

cause of chronic cough. Am J Respir Crit Care Med 1999;160:406-410. 

17. Rytila P, Metso T, Petays T, et al. Eosinophilic airway inflammation as 

an underlying mechanism of undiagnosed prolonged cough in primary 

healthcare patients. Respir Med 2002;96:52-58. 

18. Novitsky Y, Zawacki JK, Irwin RS, et al. Chronic cough due to gastroesophageal 

reflux disease: efficacy of antireflux surgery. Surg Endosc 2002;16:567-571. 

19. Dicpinigaitis PV. Cough reflex sensitivity in cigarette smokers. Chest 

2003;123:685-688. 

20. Dicpinigaitis PV, Sitkauskiene B, Stravinskaite K, et al. Effect of smoking 

cessation on cough reflex sensitivity. Eur Respir J 2006;28:786-790. 

21. Fujimura M, Kasahara K, Kamio Y, et al. Female gender as a determinant 

of cough threshold to inhaled capsaicin. Eur Respir J 1996;9:1624-1626. 

22. Dicpinigaitis PV, Rauf K. The influence of gender on cough reflex sensitivity. 

Chest 1998;113:1319-1321. 

23. Kastelik JA, Thompson RH, Aziz I, et al. Sex-related differences in cough 

reflex sensitivity in patients with chronic cough. Am J Respir Crit Care 

Med 2002;166:961-964. 

24. Prezant DJ, Weiden M, Banauch GI, et al. Cough and bronchial responsiveness 

in firefighters at the World Trade Center site. N Engl J Med 2002;347:806- 

815. 

25. Prezant DJ. World Trade Center cough syndrome and its treatment. Lung 

2008;186(suppl. 1):S94-S102. 


199


Chapter 3-1 

Inhalation Lung 

Injury from 

Smoke,Particulates, 

Gases and Chemicals 

Dr. Dorsett D. Smith, MD and 

Dr. David J. Prezant, MD 

INHALATION RESPIRATORY ILLNESSES FROM 

AEROSOLIZED PARTICULATES 

Nearly all types of disasters (i.e., fire, building collapse, explosion, volcano, 

earthquake, hurricane, flood, etc.) liberate high concentrations of aerosolized 

particulate matter. Classically particles larger than 3 microns in diameter are 

thought to be deposited in the upper airway with the potential for causing 

or worsening rhinitis, sinusitis, pharyngitis and tracheitis1,2 , while only 

particles less than 3 microns in diameter are respirable with the potential 

for causing or worsening asthma, COPD, bronchiectasis, bronchiolitis and 

acute pneumonitis (when inhaled over a long period of time and in significant 

concentrations, particles of this size can cause chronic pulmonary disease, 

such as pneumoconiosis). 3,4 These assumptions are based on controlled 

laboratory studies where the overall concentration of particles is limited. 

However, in the setting of a man-made or natural disaster, dust clouds are 

generated with high concentrations of airborne particulates over a wide size 

distribution. The increased minute ventilation required for evacuation and 

subsequent rescue or recovery (i.e., “fight or flight”) efforts strongly favors 

mouth breathing and the large concentration of aerosolized dust overwhelms 

or impairs nasal and upper airway clearance mechanisms resulting in large 

particle penetration to the depth of the small airways and alveoli. 4 In addition 

to the acute and chronic inflammatory effects of particulate matter on the 

airways5 , these exposures are complicated by simultaneous exposures to the 

incomplete products of combustion that are liberated during disasters such 

as fires, building collapses, explosions and volcanoes and inhaled either as 

inhaled fumes, vapors and gases or as coated particulates. 

Toxic combustion products can have profound effects on the respiratory 

system, causing acute symptoms, physiologic changes, and chronic diseases. 

Respiratory irritants such as hydrochloric acid, phosgene, ammonia, oxides 

of nitrogen, aldehydes, and sulfur dioxide can cause direct damage to the 

proximal airways, distal airways, and alveolar-capillary membrane. The 

combustion products of synthetic materials in modern furniture and building 

Chapter 3-1 • Inhalation Lung Injury from Smoke, Particulates, Gases and Chemicals 

201

materials may produce smoke that is more toxic than that produced in the past. 

Clinical manifestations of acute and/or chronic smoke inhalation can range 

from mild irritant symptoms of the upper and lower airways to life-threatening 

adult respiratory distress syndrome; irritant-induced asthma, bronchiolitis 

obliterans, bronchiectasis, chronic bronchitis, airway injuries, and pulmonary 

fibrosis have also been described. 6 In Fire Department City of New York (FDNY) 

fire fighters, the incidence and prevalence of Sarcoidosis has also been found 

to be increased as compared to concurrent and historic control populations. 7 

Despite this varied list of smoke inhalation induced respiratory diseases, for 

FDNY fire fighters, asthma is by far the most common disease and is nearly 

always the cause of permanent respiratory disability. 

The frequency, severity, and duration of smoke exposures appear to be 

important determinants of clinical outcomes, as well as individual host 

susceptibility factors. 6,8,9,10 Chemical composition and reactivity, water 

solubility, particle size, and temperature characteristics of the combustion 

products also influence the pulmonary effects. Although the complexities of 

exposure assessment and unpredictable nature of fires have permitted only 

limited evaluation of acute dose-response relationships and even less refined 

assessments of the long-term effects of smoke inhalation, many important 

observations have been made about the acute and chronic effects of smoke 

inhalation in fire fighters. 

Several studies have examined changes in fire fighters lung function in 

conjunction with measures of airway reactivity. Sheppard and co-workers 

measured baseline airway reactivity to methacholine in 29 fire fighters, 

and then followed pre-shift, post-shift, and post-fire spirometry over an 

eight-week period. 11 Significant declines in the forced expiratory volume at 

1-second (FEV ) and/or the forced vital capacity (FVC) were more frequent 

1 

following work shifts with fires, and occurred regardless of fire fighters’ 

baseline airway reactivity. Sherman and co-workers performed spirometry 

and methacholine challenge testing before and after firefighting activities in 

18 Seattle fire fighters. 12 Firefighting was associated with acute reductions in 

FEV (3.4% ± 1.1%) and forced expiratory flow after 25% - 75% of vital capacity 

1 

had been expelled (FEF ), and an acute increase in airway responsiveness 

25–75 

to methacholine. Increased airway responsiveness has been identified as a 

requirement for the diagnosis of reactive airways dysfunction syndrome (RADS; 

new onset asthma in a non-allergic non-smoker after acute exposure to fumes, 

gases and possibly other pollutants) and as a risk factor for the development 

of chronic obstructive pulmonary disease. The finding of increased airway 

responsiveness in fire fighters suggests that they may be at risk for accelerated 

loss of ventilatory function. 

Chia and co-workers exposed 10 new fire fighter recruits and 10 experienced 

fire fighters with normal airway reactivity to smoke in a chamber without 

respiratory protection. Following exposure, the new recruits maintained 

normal airway reactivity 13 . However, 80% of the experienced fire fighters 

developed increased airway reactivity. The authors suggested smoke-induced 

chronic injury or inflammation of the pulmonary epithelium in experienced 

fire fighters might lead to increased risk of airway reactivity. Evaluating 13 

victims of smoke inhalation three days after the fire, Kinsella and co-workers 

found 12 of 13 (92%) to have airway reactivity, which was strongly correlated 

202 Chapter 3-1 • Inhalation Lung Injury from Smoke, Particulates, Gases and Chemicals

with carboxyhemoglobin levels. 14 Repeat assessment three months later 

showed most to have improvement in airway reactivity, but not FEV or specific 

1 

conductance. The authors speculated that airway obstruction following smoke 

inhalation might be more common and persistent than generally recognized. 

Recent studies of fire victims using bronchoalveolar lavage have provided 

insights into the cellular and biochemical effects of smoke inhalation. 

Following smoke inhalation, significant numbers of neutrophils are recruited 

to the airways. 15 Neutrophils are capable of releasing proteolytic enzymes 

and inflammatory cytokines, which may contribute to injury of the airway 

epithelium and the development of bronchospasm and airway hyperreactivity. 

In patients with inhalation injury and cutaneous burns, increased numbers 

of both alveolar macrophages and neutrophils have been demonstrated in the 

airways; the alveolar macrophage may further contribute to the inflammatory 

response by elaborating additional cytokines such as tumor necrosis factor and 

interleukin-1, interleukin-6, and leukotriene B . Although preliminary, these 

4 

findings suggest potential mechanisms for the decrements in lung function and 

increases in airway reactivity demonstrated in epidemiologic investigations. 

Longitudinal studies of lung function in fire fighters have provided conflicting 

results. Peters and co-workers reported accelerated loss of FEV and FVC over 

1 

a one-year follow-up of Boston fire fighters. 16 Rates of decline were more than 

twice the expected rate (77 ml/year vs. 30 ml/year for FVC), and were significantly 

related to the frequency of fire exposure. However, in subsequent follow-up 

studies at three, five and six year intervals, investigators found rates of decline 

comparable to the general population, which were unrelated to indices of 

occupational smoke exposure. 17,18,19,20 There was evidence of survival bias in 

the cohort, as fire fighters with respiratory difficulties were selectively moved 

to lesser exposed jobs. The authors concluded that selection factors within the 

fire department and increased use of personal respiratory protective equipment 

were important in reducing the effects of smoke inhalation; significant attrition 

in follow-up cohorts may also have influenced the results. A five-year study 

of fire fighters participating in the Normative Aging Study found fire fighters 

to have greater rates of decline in FEV and FVC than non-fire fighters (18 ml/ 

1 

year and 12 ml/year, respectively). 

It is important to note that the participants in these studies were evaluated 

before routine use of respiratory protective equipment, and may have sustained 

very significant smoke exposures. Two more recent studies of fire fighters from 

the United Kingdom have not shown evidence for longitudinal decline in lung 

function. 21,22 In FDNY fire fighters, pulmonary function was followed over nearly 

5 years (1997 to 2001) prior to the World Trade Center collapse and the mean 

adjusted decrease in FEV1 was 30 ml/year. 23 Overall, the evidence suggests that 

fire fighter cohorts using appropriate respiratory protective equipment do not 

have accelerated loss of ventilatory function, although additional research is 

needed in this area. It is important to note that wildland fire fighters, who are 

not provided with or do not typically wear protective respiratory equipment, 

have been shown to have decrements in lung function and increased airway 

responsiveness after a season of fighting fires. 24 

Chapter 3-1 • Inhalation Lung Injury from Smoke, Particulates, Gases and Chemicals 203

204 

The effects of frequent smoke exposure on mortality from chronic respiratory 

conditions have also been investigated. Studies comparing fire fighters to US 

population controls have demonstrated reduced chronic respiratory disease 

mortality rates in fire fighters, despite evidence of acute and chronic pulmonary 

effects of smoke inhalation. However, these results may be due to the healthy 

worker effect, where selections of healthy workers results in mortality rates 

lower than a general reference population. In a study of New Jersey fire fighters, 

Feuer and Rosenman found an excess of chronic respiratory disease compared 

to police controls (Proportionate Mortality Ratio = 1.98,

WTC small particulate matter (

the most intense exposure to air pollution at the WTC site, multiple studies have 

now described high rates of gastroesophageal reflux dysfunction (GERD). 36,40 

Though no clear mechanism for the development of GERD has been described 

in this setting, ingestion of airborne or expectorated respirable material are 

presumed etiologies that may be further exacerbated by disaster-related stress 

and dietary indiscretions. Questions which remain are: is GERD unique to 

the WTC exposure or does it represent a previously unrecognized aspect of 

inhalation injury in general; does it mark more severe total dust exposure as 

opposed to, or in conjunction with more severe host inflammatory reaction; 

and will this syndrome persist or resolve. What is clear is that when GERD is 

present in this setting, treatment should be initiated because of the known 

causal or exacerbating relationship between GERD and airway diseases such 

as sinusitis, asthma and chronic cough. 55,56 

Post-disaster, interstitial lung disease is much less common than upper and 

lower airways disease. An increased incidence of sarcoid-like granulomatous 

pulmonary disease (SLGPD) has been reported in FDNY fire fighters prior to 

the WTC, 57 raising the possibility of etiologic agents generated or aerosolized 

during combustion. Granulomatous pneumonitis has been described in 

one construction worker working in the recovery effort at the WTC58 and the 

incidence of WTC SLGPD was substantially increased in FDNY rescue workers 

(fire fighters and EMS) in the first five years post-WTC, especially in the first 12 

months (Figure 3-1.1). 59 During this time period, most reported no respirator 

use or “minimal” use of a “dust” or N-95 mask and none reported wearing a 

P-100 respirator. Other interstitial diseases after WTC exposure have been even 

rarer with several cases of idiopathic pulmonary fibrosis and two case studies 

of bronchiolitis obliterans, one with functional improvement after treatment 

with macrolide antibiotics. 60 One case of eosinophilic pneumonitis requiring 

mechanical ventilatory support was reported in a NYC fire fighter 6 weeks after 

the WTC collapse; bronchoalveolar lavage demonstrated particulate material 

and uncoated asbestos fibers; and there was a prompt resolution after a brief 

course of systemic corticosteroid treatment. 61 Recently, the U.S. military has 

reported 18 cases of eosinophilic pneumonitis in personnel deployed in or 

near Iraq (incidence of 9.1 per 100 000 person-years; 95% confidence interval, 

4.3-13.3). 62 All but one reported exposure to fine airborne sand/dust and all 

were smokers with 78% classified as new smokers. Mechanical ventilation was 

needed in 67% (median use seven days); two died; the remainder responded to 

corticosteroids or supportive care; and post-treatment all had normal or near 

normal spirometry. Taken together, these findings strongly argue for providing 

improved respiratory protection at future disasters and other significant 

environmental/occupational exposures. 

Following any urban disaster, those exposed will naturally be concerned 

about their risk for developing malignancies due to their potential exposures 

to multiple combustion or pyrolysis products, many of which are known 

carcinogens (e.g., polycyclic aromatic hydrocarbons, such as dioxins and 

brominated diphenyl ethers, as well as polychlorinated biphenyls, polychlorinated 

dibenzodioxins, and polychlorinated furans). 31,63 Furthermore, asbestos may 

become airborne during fires or collapse of older buildings and there are 

well-described synergistic carcinogenic effects of asbestos with polyaromatic 

hydrocarbons. 63 As asbestos-related cancers have long latency periods, 


Figure 3-1.1: The number of cases of biopsy proven World Trade Center Sarcoid-like 

Granulomatous Pulmonary Disease (WTC-SLGPD) since 9/11 as compared to pre-WTC 

cases of sarcoidosis or SLGPD starting from 1985 in rescue workers from the Fire Department 

of the City of New York (FDNY). With permission from: Izbicki G, Chavko R, Banauch 

GI, Weiden M, Berger K, Kelly KJ, Hall C, Aldrich TK and Prezant DJ. World Trade Center 

Sarcoid-like Granulomatous Pulmonary Disease in New York City Fire Department Rescue 

Workers. Chest, 2007;131:1414-1423. 

periodic long-term medical surveillance typically lasting approximately 30 

years should be considered for exposed individuals. In contrast, thyroid cancer 

and leukemia resulting from radiation or certain chemical exposures have 

short latency periods, especially in children. It is important to consider the 

biologic plausibility and latency periods in post-disaster exposure counseling 

and planning. 

INHALATION RESPIRATORY ILLNESSES FROM GASES 

AND VAPORS 

The most common chemical asphyxiants are carbon monoxide and hydrogen 

cyanide. Others include hydrogen sulfide, oxides of nitrogen and acrylonitrile. 

Hydrogen Cyanide 

Cyanide is a ubiquitous compound that is widely used in industry in its salt 

form and therefore, can be easily exploited by terrorists. Most information 

regarding cyanide toxicity comes from accidental disasters such as fires, 

explosions, industrial accidents, and poisonings (including consumption of 

apricot pits and cassava roots). Cyanide poisons aerobic metabolism by binding 

to the ferric ion (Fe3+) of mitochondrial cytochrome oxidase a . Cyanide binds 

3 

reversibly through the action of the enzymes rhodanese, 3-mercaptopyruvate 

sulfurtransferase, and thiosulfate reductase. These enzymes assist in the 

formation of the less toxic compound thiocyanate (SCN- ), which ultimately is 

excreted by the kidneys. Cyanide can readily diffuse through the epithelium 

and therefore is toxic through inhalation, ingestion, or topical contact. 

The clinical presentation of cyanide toxicity results from progressive tissue 

hypoxia. Initial effects include transient hyperpnea, headache, dyspnea, and 

excitability of the central nervous system (CNS) (manifested by anxiety and 

agitation). Late effects include hemodynamic compromise, arrhythmias, 


seizures, coma and death64 . Additional signs and symptoms not specific for 

cyanide toxicity include diaphoresis, flushing, weakness, and vertigo. The 

odor of bitter almonds, which is commonly thought to be characteristic, is 

described by fewer than 60% of persons exposed to cyanide. 64 Lactic acidosis 

is the primary laboratory abnormality noted. Assay of whole blood, needed 

to accurately measure cyanide concentrations, correlates with signs and 

symptoms (lethal dose, >three micrograms/ml) but, is not readily available in 

most clinical laboratories. Therefore, treatment is often empiric and should be 

considered from known or suspected exposures when symptoms are severe 

and not responding to conservative therapy. 

The primary goal of treatment is displacement of cyanide from cytochrome 

oxidase a through the formation of methemoglobin by sodium nitrite. 

3 

Methemoglobin values should be monitored and maintained at less than 30% 64,65 . 

Sodium nitrite and sodium thiosulfate must be administered intravenously. 

Owing to a lack of sulfur donors during acute intoxication, sodium thiosulfate 

is administered as additional therapy to enhance clearance of cyanide. Sodium 

thiosulfate combines with sequestered cyanide to form thiocyanate, which 

is excreted from the body. Recently, the FDA approved hydroxocobalamin as 

an intravenous treatment for cyanide poisoning. A potential advantage is that 

methemoglobinemia is not a consequence of hydroxocobalamin therapy. 66 

Carbon Monoxide 

Carbon monoxide (CO) is an odorless, colorless, nonirritating gas produced 

by incomplete combustion of organic materials, especially hydrocarbons. 

Although automobile exhaust systems, faulty heating systems and fires are 

the common sources of carbon monoxide intoxication, the improper use of 

temporary home generators during blackouts is the most common cause in 

disaster environments. 67 Carbon monoxide binds to hemoglobin forming 

carboxyhemoglobin (COHb) resulting in decreased hemoglobin oxygen 

saturation, shift of the oxygen-hemoglobin dissociation curve to the left and 

inhibition of oxygen delivery to the tissues. The affinity of the hemoglobin 

for carbon monoxide is over 200 times greater than that for oxygen. 67 Carbon 

monoxide also binds cytochrome oxidase chain interfering with cellular 

respiration. All of these properties result in chemical asphyxiation. 

Clinical findings of carbon monoxide poisoning are similar to cyanide 

poisoning, are non-specific and include general malaise, headache, nausea and 

vomiting, dyspnea and alteration in mental status at high levels of exposure. 67,68,69 

Severe exposure may cause coma, seizures, arrhythmias and death. Cyanosis 

is not found in carbon monoxide poisoning due to the cherry-red color of the 

carboxyhemoglobin. Carboxyhemoglobin can be measured in blood: levels 

lower than 6% may cause impairment in vision and time discrimination; levels 

of 40 - 60% are associated with arrhythmias, coma and death 

The most common symptoms following mild CO poisoning (10-20 ppm) are 

mild headache, fatigue, shortness of breath, and dizziness. Moderate exposures 

(20 - 30 ppm) commonly present with more severe headaches, fatigue and 

shortness of breath often accompanied by confusion, blurred vision, nausea 

and vomiting. Patients presenting with palpitations, dysrhythmias, myocardial 

ischemia, hypotension, noncardiogenic pulmonary edema, seizures, coma, 

and respiratory or cardiac arrest have severe toxicity (>30 ppm). The severity 


of symptoms is also influenced by their chronicity and by underlying comorbidity. 

Two special populations in whom to consider additional affects of 

CO poisoning are pregnant patients and children. In pregnancy, CO poisoning 

has been shown (even in the absence of toxic symptoms in the mother) to result 

in an increased rate of stillbirths or miscarriages, limb malformations, cranial 

malformations, cognitive disabilities, and even fetal death. These effects are 

due to the more dramatic effects of CO on fetal hemoglobin and prolonged 

elimination times from fetal circulation. 67 In children, the effects seen in their 

adult counterparts (i.e. parents) may be less dramatic than those seen in children. 

This results from the increased minute ventilation (respiratory rate multiplied 

by tidal volume). As a result, shorter exposure times are needed in order to 

achieve clinically significant levels of COHb. For this reason, particularly in 

very young children and infants in whom the history and neurologic findings 

may be limited, prehospital treatment should be applied liberally. 

The first and most critical treatment for a CO poisoning is the removal of 

the patient from the environment and the delivery of high-flow oxygen via a 

non-rebreather mask. High-concentration oxygen facilitates the elimination 

of CO from the body, in addition to increasing the amount of oxygen dissolved 

within the blood (but not carried by hemoglobin), thereby promoting tissue 

oxygenation. In the setting of oxygen provided by a non-rebreather mask, the 

half-life of CO is reduced from approximately four hours to 40 to 60 minutes. 

Treatment with oxygen should continue until the COHb level falls below five 

percent. 

Hyperbaric oxygen therapy (HBOT) provides high concentrations of oxygen 

at elevated atmospheric pressures, thereby increasing the amount of oxygen 

dissolved in the blood. Such therapy not only ensures adequate oxygen delivery 

to the body, but also enhances the elimination of CO by reducing the half-life 

of CO to 20 minutes. One commonly referenced set of criteria for HBOT use 

includes: neurologic findings (altered mental status, coma, seizures, or focal 

neurologic deficits), COHb >20% in adults, COHb >15% in pregnancy, loss of 

consciousness, metabolic acidosis, cardiovascular compromise (ischemia, 

infarction, or dysrhythmias), or persistent symptoms despite high-flow oxygen 

therapy. In the only large double blind randomized trial, hyperbaric-oxygen 

treatment was superior to high-flow oxygen therapy for reducing short-term 

(six weeks) and long-term (one year) cognitive dysfunction in patients with 

elevated COHb levels ≥20% or significant metabolic acidosis. A problem with 

interpreting these studies is that COHb levels measured in the hospital may 

have already been reduced by use of high flow oxygen therapy by EMS. Thus, 

appropriate care needs to be considered in outcome analysis and is why the 

above study is more accurately referred to as an analysis of patients with COHb 

levels >20% rather than ≥25%. 68 

EXPOSURE TO IRRITANT VAPORS AND GASES 

Gases, vapors and mists are non-solid suspended toxicants. Examples include 

chlorine, ammonia, isocyanates, sulfuric acid, nitrogen dioxide, phosgene, 

benzene and others. The solubility of the toxin affects their absorption and 

site of injury. 70 In general, the higher the water-solubility of the agent, the 

more the substance will be absorbed and injure the upper airways. Ammonia, 

cadmium oxide, hydrogen chloride, hydrogen fluoride and sulfur dioxide are 


highly water-soluble and, thus, will mostly be absorbed and injure the upper 

airways. Chlorine and vanadium pentoxide are moderately water-soluble 

causing upper and lower airway inflammation. Phosgene, mercury vapor, 

oxides of nitrogen, and ozone have low solubility and thus, penetrate deeply 

into the respiratory tract causing small airways inflammation, pneumonitis 

and pulmonary edema. 

Chlorine 

Chlorine is a highly reactive green-yellow gas that is 2.5 times denser than air. 

Exposure occurs in both industrial and non-industrial settings. 70,71 Chlorine 

is used in the production of chemicals, bleaching and plastics processing, and 

in a variety of recreational and household settings (swimming pools, cleaning 

solutions). Given its moderate solubility, most signs and symptoms are related 

to upper and lower airway inflammation (RUDS, RADS, irritant asthma). Severe 

and prolonged exposures can result in ulcerative tracheobronchitis, diffuse 

alveolar damage with hyaline membrane formation and pulmonary edema. 

Phosgene 

Phosgene is commonly used to manufacture dye and plastics. Exposure to 

phosgene also may occur during arc welding and in fires involving vinyl 

chloride. Phosgene and diphosgene are also agents used in chemical warfare. 70,71 

Phosgene, which is transported in liquid form, is deadly at a concentration of 2 

ppm. It appears as a white cloud and has a characteristic odor of sweet, newly 

mown hay in lower concentrations. These agents have low water solubility, 

so have a delayed onset of action (30 minutes to 8 hours). It readily reaches 

the respiratory bronchioles and alveoli and has direct toxic effects, leading 

to cellular damage of the alveolar-capillary membrane and subsequent 

pulmonary edema. Because there is no systemic absorption, other organs 

are not affected. 70,71 Initial exposure results in a burning sensation of the 

mucus membranes including eyes, nose, throat and upper respiratory tract. 

More severe exposures progress to development of cough, wheezing, stridor, 

dyspnea, hypotension, and non-cardiogenic pulmonary edema. The use of 

steroids has been advocated but is of unproven benefit. 

The clinical presentation depends upon level of exposure. Exposure to low 

concentrations causes mild cough, dyspnea, and chest discomfort. At high 

concentrations, airway irritation and alveolar damage occurs. After direct 

contact of skin to phosgene, there is an immediate burning sensation followed 

by erythema, blanching and, eventually, necrosis. Systemically, patients may 

experience dyspnea, chest tightness, cough, substernal discomfort, hypoxia 

and pulmonary edema within two to six hours of exposure; however, some 

signs and symptoms may not develop for 24 hours. Pulmonary edema occurring 

within four hours of exposure indicates a poor prognosis; death occurs if 

immediate intensive medical support is unavailable. 70,71 Physical exertion 

within 72 hours of exposure may trigger the development of pulmonary edema. 

Measurement of oxygen saturation and arterial blood gases is recommended 

in the initial evaluation of all symptomatic patients. A chest radiograph may 

show perihilar infiltrates or diffuse pulmonary edema, which may evolve 

and progress rapidly. Radiographic findings may lag behind clinical findings. 

Rarely, phosgene causes significant structural damage that may take many 


years to recover from completely. In patients who had symptoms following an 

initial exposure, clinical findings suggestive of bronchiolitis obliterans and 

chronic bronchitis some time after exposure have been reported. 72 It is prudent 

to monitor such patients with pulmonary function tests and radiographic 

imaging, especially those who have persistent symptoms of dyspnea, cough, 

or chest discomfort. 70,71,72 

DIAGNOSIS AND TREATMENT 

In any inhalational lung injury patient (smoke, particulates, gases or chemicals), 

medical complications range from patients who present with tachypnea due 

to anxiety to patients with cough from irritant-induced upper and/or lower 

airway inflammation (i.e., sinusitis, tracheobronchitis, asthma, reactive 

airways dysfunction syndrome) to those in acute respiratory distress (i.e., 

neuromuscular failure, status asthmaticus, pulmonary edema). The goal of 

this section is to concentrate on those aspects that might be unique or specific 

to an inhalational lung injury. 

History and Physical Examination 

In addition to a standard medical history and physical examination, a postinhalational 

lung injury evaluation should include questions to determine prior 

and current exposures (environmental and occupational), the intensity and 

duration of exposure(s), the temporal relationship of symptoms to exposure 

and whether these symptoms were new in onset or, for those with pre-existing 

disease, whether they were stable or exacerbations. Strategies for evaluating 

the intensity of exposure include: completing a timetable recounting exposure, 

the time of first exposure, the time of last exposure, the number of hours and 

days exposed, the individual’s location during exposure, a description of 

specific activities during exposure, and for respiratory protection the type and 

extent of use. 73 Prior pulmonary history is critical in understanding risk for 

exacerbations. Physical exam should focus on all areas of potential exposure 

including vital signs, skin, eyes, mucous membranes, upper and lower airways, 

lung, abdomen and any other exposure specific sites. 

An important consideration when obtaining the medical history is accounting 

for the “healthy-worker effect.” Because rescue workers are generally healthy 

and physically active prior to exposure, their symptoms and findings are 

expected to be above the average when compared to the general population. 

Post-exposure, they may remain asymptomatic at rest or even with mild exercise; 

therefore the history will only be useful if it includes extensive questioning 

as to provocability, such as the presence of symptoms with work activities, 

strenuous exercise, and exposures to common irritants in the work or home 

setting (smoke, diesel exhaust, noxious smells, perfumes and allergens), and 

extremes or changes in temperature and humidity. 73 Attention should be 

paid to the emotional impact, not only of the exposure itself, but also of the 

development of respiratory and physical impairments that may have resulted 

from the exposure to the mentally and physically stressful environment. 

Because post-traumatic stress is a common complication, some assessment 

of prior mental health history, current stress, support system and resilience 

is important. 

Chapter 3-1 • Inhalation Lung Injury from Smoke, Particulates, Gases and Chemicals 

211

Diagnostic Testing 

Initial pulmonary function evaluation includes spirometry. As these records 

may be used for diagnosis, treatment and future legal actions, careful attention 

to quality control should be maintained. Post-bronchodilator spirometry can 

be part of this initial evaluation or could be reserved for those patients with 

(a) symptoms, (b) spirometry that is abnormal (

Chest Imaging 

In asymptomatic individuals, chest radiographs generally find no acute 

abnormalities. However, there may be widespread interest amongst those 

exposed to have chest radiographs as new “baselines.” In symptomatic patients, 

chest radiographs and CT scans have been reported to show bronchiectasis, 

bronchiolitis obliterans, atelectasis, lobar consolidation and interstitial 

pneumonitis (hypersensitivity, eosinophilic pneumonitis, granulomatous 

disease and fibrosis). Inspiratory and expiratory CT scanning has been utilized 

to show air trapping, bronchial wall thickening and mosaic attenuation. 40,75 

Because the clinical utility of these findings in a non-research setting remains 

unclear, we recommend that inspiratory and expiratory CT scan of the chest be 

reserved for individuals with significant unexplained symptoms after complete 

pulmonary function tests have already been conducted. Another area of intense 

research is the use of CT scans of the chest for lung cancer screening. 76 Their 

future use in high-risk patients (high exposure; tobacco smokers) might be a 

consideration depending on the results of soon to be completed lung cancer 

screening studies in tobacco smokers from the general population. 

Invasive Diagnostic Methods 

Induced sputum, bronchoalveolar lavage and/or biopsy following exposure in 

asymptomatic and symptomatic rescue workers have been used to demonstrate 

increased markers of inflammation and particle deposition exposure. While 

these measures may have value in a research setting, they have limited 

diagnostic or prognostic value. In a clinical setting, bronchoscopy should be 

performed on those with significant abnormalities on chest imaging or when 

there is failure to respond to therapy. Sinus CT scan and direct laryngoscopy 

are recommended in those unresponsive to medical treatment for at least 

three months. 77 Gastroesophageal endoscopy is recommended for those 

unresponsive to medical treatment after two to three months, for those with 

reoccurrence after successful treatment has been concluded, or for those with 

risk factors for esophageal cancer. 78 

Treatment 

Not many references describing the treatment of inhalational lung injuryrelated 

chronic cough or dyspnea have been published. 79 Recently, expert 

consensus guidelines for the diagnostic evaluation and treatment of WTC 

related respiratory disease was published by the NYC Department of Health 

and Mental Hygiene. 80 The recommended approach includes a comprehensive 

plan of synergistic care treating the upper and lower airway (see Figures 3-1.2 

and 3-1.3) with (a) nasal steroids and decongestants, (b) proton pump inhibitors 

and dietary modification and (c) bronchodilators, corticosteroid inhalers and 

leukotriene modifiers. Most patients have reported symptoms and required 

treatment for involvement of at least two of the above organ systems. Consistent 

with published guidelines, only when the clinical presentation is atypical 

(for example, interstitial lung disease) or there is failure to respond after 

approximately three months of treatment do we recommend additional invasive 

diagnostic testing such as chest CT, bronchoscopy, sinus CT, laryngoscopy, and/ 

or endoscopy. 77-79 Our experience has proven the multi-causality of respiratory 


symptoms in an inhalation lung injury population, with contribution of any 

combination of these aerodigestive processes. 

Figure 3-1.2: Disaster Cough Diagnosis & Treatment Algorithm – Upper Airway 

Predominance 

Figure 3-1.3: Disaster Cough Diagnosis & Treatment Algorithm – Lower Airway 

Predominance 


REFERENCES 

1. Lippmann M. Particle Deposition and Pulmonary Defense Mechanisms. 

In: WN Rom, ed. Environmental and Occupational Medicine. 3rd edition. 

Philadelphia: Lippincott-Raven Publishers, 1998; pgs. 245-260 

2. Wilson WE, Suh HH. Fine particles and coarse particles: concentration 

relationships relevant to epidemiologic studies. J Air Waste Manage Assoc, 

1997; 47: 1238-1249 

3. Churg A. The uptake of mineral particles by pulmonary epithelial cells. 

Am J Respir Crit Care Med, 1996; 154: 1124-1140 

4. Toren K, Brisman J, Hagberg S, Karlsson G. Improved nasal clearance 

among pulp-mill workers after the reduction of lime dust. Scan J Work 

Environ Health, 1996; 22: 102-107 

5. Thurston GD, Bates DV. Air pollution as an underappreciated cause of 

asthma symptoms. JAMA, 2003; 290: 1915-1917 

6. Haponik EF. Clinical smoke inhalation injury: pulmonary effects. Occup 

Med 1993;8:431–468. 

7. Prezant DJ, Dhala A, Goldstein A, Janus D, Ortiz F, Aldrich TK, Kelly 

KJ. Incidence, prevalence, and severity of sarcoidosis in New York City 

Firefighters. Chest. 116:1183-1193, 1999. 

8. Loke J, Farmer W, Matthay RA, Putman CE, Smith GJW. Acute and chronic 

effects of fire fighting on pulmonary function. Chest 1980;77:369–373. 

9. Large AA, Owens GR, Hoffman LA. The short-term effects of smoke exposure 

on the pulmonary function of firefighters. Chest 1990;97:806–809. 

10. Musk AW, Smith J, Peters JM, McLaughlin E. Pulmonary function in 

firefighters: acute changes in ventilatory capacity and their correlates. 

Br J Ind Med 1979;36:29–34. 

11. Sheppard D, Distefano S, Morse L, Becker C. Acute effects of routine 

firefighting on lung function Am J Ind Med 1986;9:333–340. 

12. Sherman CB, Barnhart S, Miller MF, et al. Firefighting acutely increases 

airway responsiveness. Am Rev Respir Dis 1989;140:185–190. 

13. Chia KS, Jeyaratman J, Chan TB, Lim TK. Airway responsiveness of 

firefighters after smoke exposure. Br J Ind Med 1990;47:524–527. 

14. Kinsella J, Carter R, Reid WH, Campbell D, Clark CJ. Increased airway 

reactivity after smoke inhalation. Lancet 1991;337:595–596. 

15. Clark CJ, Pollock AJ, Reid WH, Campbell D, Gemmel C. Role of pulmonary 

alveolar macrophage activation in acute lung injury after burns and smoke 

inhalation. Lancet 1988;2:872–874. 


on pulmonary function. N Engl J Med 1974;291:1320–1322. 


17. Musk AW, Peters JM, Wegman DW. Lung function in firefighters, a three 

year follow up of active subjects. Am J Public Health 1977;67:626–629. 

18. Musk AW, Peters JM, Berstein et al. Lung function in firefighters: a six year 

follow up in the Boston fire department. Am J Ind Med 1982;3:3–9. 

19. Musk AW, Peters JM, Wegman DW. Lung function in firefighters, a five 

year follow-up of retirees. Am J Public Health 1977;67:630–635. 

20. Sparrow D, Bosse R, Rosner B, Weiss ST. The effect of occupational exposure 

on pulmonary function. Am Rev Respir Dis 1982;125:319–322. 

21. Douglas DB, Douglas RB, Oakes D, Scott G. Pulmonary function of London 

firemen. Br J Ind Med 1985;42:55–58. 

22. Horsfield K, Guyatt AR, Cooper FM, Buckman M, Cumming M. Lung function 

in west Sussex firemen: a four year study. Br J Ind Med 1988;45:116–121. 





24. Liu D, Tager IB, Balmes JR, Harrison RJ. The effect of smoke inhalation on 

lung function and airway responsiveness in wildland fire fighters. Am Rev 

Respir Dis 1992;146:1469–1473. 


Am J Ind Med 1986;9:517–527. 

26. Demers PA, Heyer NJ, Rosenstock L. Mortality among firefighters from 

three northwestern United States cities. Br J Ind Med 1992;49:664–670. 

27. Rosenstock L, Demers P, Barnhart S. Respiratory mortality among firefighters. 

Br J Ind Med 1990;47:462–465. 

28. Baxter PJ, Ing R, Falk H, Plikaytis B. Mount St. Helens eruptions: the acute 

respiratory effects of volcanic ash in a North American community. Arch 

Environ Health 1983; 38: 138-143 

29. Cullinan P, Acquilla S, Ramana Dhara V. Respiratory morbidity 10 years 

after the Union Carbide gas leak at Bhopal: a cross sectional survey. BMJ, 

1997; 314: 338-343 

30. Hodgkins P, Henneberger PK, Wang ML, Petsonk EL. Bronchial responsiveness 

and five-year FEV1 decline: a study in miners and nonminers. Am J Respir 

Crit Care Med, 1998; 157: 1390-1396 

31. Peil JD, Vette AF, Johnson BA, Rappaport SM. Air levels of carcinogenic 

polycyclic aromatic hydrocarbons after the World Trade Center disaster. 

Proc Natl Acad Sci, 2004; 101: 11685-8. Epub 2004 Jul 27 


32. Lioy PJ, Weisel CP, Millette JR, Eisenreich S, Vallero D, Offenberg J, Buckley 

B, Turpin B, Zhong M, Cohen MD, Prophete C, Yang I, Stiles R, Chee G, 

Johnson W, Porcja R, Alimokhtari S, Hale RC, Weschler C, Chen LC. 

Characterization of the dust/smoke aerosol that settled east of the World 

Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 

September 2001. Environ Health Perspect. 2002; 110:703-714 

33. Yiin L, Millette JR, Vette A, Illacqua V, Quan C, Gorczynski J, Kendall M, 

Chen LC, Weisel CP, Buckley B, Yang I, Lioy P. Comparisons of the Dust/ 

Smoke Particulate that Settled Inside the Surrounding Buildings and 

Outside on the Streets of Southern New York City after the Collapse of the 

World Trade Center, September 11, 2001. J Air Waste Managm, 2004; 54: 

515-528 

34. Swartz E, Stockburger L, Vallero DA. Polycyclic aromatic hydrocarbons 

and other semivolatile organic compounds collected in New York City in 

response to the events of 9/11. Environ Sci Technol, 2003; 37: 3537-3546 

35. Centers for Disease Control and Prevention. Occupational exposures 

to air contaminants at the World Trade Center disaster site--New York, 

September-October 2001. JAMA, 2002; 287:3201-3202 

36. Feldman DM, Baron SL, Bernard BP, Lushniak BD, Banauch G, Arcentales 

N, Kelly KJ, Prezant DJ. Symptoms, respirator use, and pulmonary function 

changes among New York City firefighters responding to the World Trade 

Center disaster. Chest, 2004; 125: 1256-1264 

37. Centers for Disease Control and Prevention: Use of respiratory protection 

among responders at the World Trade Center site--New York City, September 

2001. Morb Mortal Wkly Rep, 2002; 51, Spec No: 6-8 

38. Gavett SH, Haykal-Coates N, Highfill JW, Ledbetter AD, Chen LC, Cohen 

MD, Harkema JR, Wagner JG, Costa DL: World Trade Center fine particulate 

matter causes respiratory tract hyperresponsiveness in mice. Environ 

Health Perspect, 2003; 111: 981-991 

39. Fireman EM, Lerman Y, Ganor E, Grief J, Fireman –Shoresh S, Lioy PJ, 

Banauch GI, Weiden M, Kelly KJ, Prezant DJ. Induced Sputum Assessment 

in New York City Firefighters Exposed to World Trade Center Dust. Environ 

Health Perspect, 2004; 112: 1564-1569 

40. Prezant DJ, Weiden M, Banauch GI, McGuinness G, Rom WN, Aldrich TK, 

Kelly KJ. Cough and bronchial responsiveness in firefighters at the World 

Trade Center site. N Engl J Med, 2002; 347:806-815. Epub 2002 Sep 09 

41. Banauch GI, Alleyne D, Sanchez R, Olender K, Cohen HW, Weiden M, Kelly 

KJ, Prezant DJ. Persistent hyperreactivity and reactive airway dysfunction 

in firefighters at the World Trade Center. Am J Respir Crit Care Med, 2003; 

168: 54-62. Epub 2003 Feb 25 


42. Herbert R, Moline J, Skloot G, Metzger K, Baron S, Luft B, Markowitz S, 

Udasin I, Harrison D, Stein D, Todd r, Enright P, Stellman J, Landrigan P, 

Levin S . 2006. The World Trade Center Disaster and the Health of Workers: 

Five-Year Assessment of a Unique Medical Screening Program Environ 

Health Perspect: doi:10.1289/ehp.9592. [Online 6 September 2006] 

43. Salzman SH, Moosavy FM, Miskoff JA, Friedmann P, Fried G, Rosen MJ. 

Early respiratory abnormalities in emergency services police officers at 

the World Trade Center site. J Occup Environ Med, 2004; 46:113-122 

44. Skloot G, Goldman M, Fischler D, Goldman C, Schechter C, Levin S, Teirstein 

A. Respiratory symptoms and physiologic assessment of ironworkers at 

the World Trade Center disaster site. Chest, 2004; 25: 1248-1255 

45. Centers for Disease Control and Prevention. Self-reported increase in 

asthma severity after the September 11 attacks on the World Trade Center- 

-Manhattan, New York, 2001. JAMA. 2002 Sep 25;288(12):1466-7 

46. Reibman J. Respiratory health of residents near the former world trade 

center: the WTC Residents Respiratory Health Survey [Abstract]. Am J 

Respir Crit Care Med, 167; A335 

47. Szema AM, Khedkar M, Maloney PF, Takach PA, Nickels MS, Patel H, 

Modugno F, Tso AY, Lin DH. Clinical deterioration in pediatric asthmatic 

patients after September 11, 2001. J Allergy Clin Immunol, 2004; 113: 420- 

426 

48. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome. 

Chest 1985; 88: 376-384 

49. Bardana EJ Jr. Reactive airways dysfunction syndrome (RADS): guidelines 

for diagnosis and treatment and insight into likely prognosis. Ann Allergy 

Asthma Immunol, 1999; 83: 583-586 

50. Banauch GI, Dhala A, Alleyne D, Alva R, Santhyadka G, Krasko A, Weiden 

M, Kelly KJ, Prezant DJ. Bronchial hyperreactivity and other inhalation 

lung injuries in rescue/ recovery workers after the World Trade Center 

collapse. Crit Care Med, 2005; 33: S102-S106 

51. Meggs WJ, Elsheik T, Metzger WJ, Albernaz M, Bloch RM. Nasal pathology 

and ultrastructure in patients with chronic airway inflammation (RADS 

and RUDS) following an irritant exposure. J Toxicol Clin Toxicol, 1996; 34: 

383-396 

52. Demeter SL, Cordasco EM, Guidotti TL. Permanent respiratory impairment 

and upper airway symptoms despite clinical improvement in patients with 

reactive airways dysfunction syndrome. Sci Total Environ, 2001; 270: 49-55 

53. Lieberman AD, Craven MR. Reactive Intestinal Dysfunction Syndrome(RIDS) 

Caused by chemical Exposures. Archives of Environmental Health, 1998; 

53: 354-358 

54. Harding SM. Acid reflux and asthma. Curr Opin Pulm Med, 2003; 9: 42-45 

55. Canning BJ, Mazzone SB. Reflex mechanisms in gastroesophageal reflux 

disease and asthma. Am J Med, 2003; 115 Suppl 3A: 45S-48S 


56. Irwin RS and Madison JM. Diagnosis and treatment of chronic cough due 

to gastro-esophageal reflux disease and postnasal drip syndrome. Pulm 

Pharmacol Ther, 2002; 15: 261-266 

57. Prezant DJ, Dhala A, Goldstein A, Janus D, Ortiz F, Aldrich TK, Kelly KJ. 

The incidence, prevalence, and severity of sarcoidosis in New York City 

firefighters. Chest, 1999; 116: 1183-1193 

58. Safirstein BH, Klukowicz A, Miller R, Teirstein A. Granulomatous pneumonitis 

following exposure to the World Trade Center collapse. Chest, 2003; 123: 

301-304 




Chest, 2007;131:1414-1423 

60. Mann JM, Sha KK, Kline G, Breuer FU, Miller A. World Trade Center dyspnea: 

bronchiolitis obliterans with functional improvement: a case report. Am 

J Ind Med, 2005; 48: 225-229 

61. Rom WN, Weiden M, Garcia R, Yie TA, Vathesatogkit P, Tse DB, McGuinness 

G, Roggli V, Prezant D. Acute eosinophilic pneumonia in a New York City 

firefighter exposed to World Trade Center dust. Am J Respir Crit Care Med, 

2002; 166: 797-800 

62. Shorr AF, Scoville SL, Cersovsky SB, Shanks GD, Ockenhouse CF, Smoak 

BL, Carr WW, Petrucelli BP. Acute Eosinophilic Pneumonia Among US 

Military Personnel Deployed in or Near Iraq. JAMA, 2004; 292: 2997-3005 

63. Banauch GI, Dhala A, Prezant DJ. Pulmonary disease in rescue workers 

at the World Trade Center site. Curr Opin Pulm Med, 2005; 11: 160-168 

64. Guidotti T. Acute cyanide poisoning in prehospital care: New challenges, 

new tools for intervention. Prehosp. Disast Med. 2005; 21:s40-s48. 

65. Eckstein M and Maniscalco PM. Focus on smoke inhalation – the most 

common cause of acute cyanide poisoning. Prehosp. Disast Med. 2005; 

21:s49-s55. 

66. Keim ME. Terrorism involving cyanide: the prospect of improving 

preparedness in the prehospital setting. Prehosp Disast Med. 2005; 

21:s56-s60. 

67. Ilano A, Raffin T. Management of carbon monoxide poisoning. CHEST 

1990: 97; 165-169. 

68. Weaver KL, Hopkins RO, Chan KJ, Churchill S et al. Hyperbaric oxygen 

for acute carbon monoxide therapy. N Eng J Med. 347:1057-1067; 2002 

69. Prezant DJ, Smith DD, and Mohr L. Acute Inhalational Lung Injury: Irwin 

RS, Rippe JM, eds. Intensive Care Medicine, 6th Edition. Philadelphia: 

Lippincott, Williams and Wilkins; 2007. 

70. Medical management of chemical casualties handbook 3rd ed. USAMRICD, 

Aberdeen Proving Ground. MD. July 2000. 


71. Kales S, Christiani D. Acute chemical injuries. N Engl J Med. 2004; 350:800- 

808. 

72. Thomason J, Rice T, Milstone A. Bronchiolitis obliterans in a survivor of a 

chemical weapons attack. JAMA. 2003; 290(5): 598-599. 

73. Parker J. The occupational and environmental history. In: Rom WN and 

Markowitz SB eds. Environmental and Occupational Medicine, 4th Edition. 

Lippincott Williams and Wilkins Philadelphia PA 2007: p. 22-31. 

74. American Thoracic Society. Guidelines for Methacholine and Exercise 

Challenge Testing – 1999. Am J Respir Crit Care Med, 2000; 161: 309-329 

75. Mendelson D, de la Hoz RE, Roggeveen M, Levin SM, Herbert R. Air trapping 

detected on end-expiratory high resolution CT in symptomatic World Trade 

Center rescue and recovery workers. Abstracts of the Radiological Society 

of North America (RSNA) meeting, Chicago, 2004 

76. Mulshine J, Sullivan D. Lung cancer screening. New Engl J Med. 2005; 

352:2714-2720. 

77. Gwaltney JM Jr., Jones JG, Kennedy DW. Medical management of sinusitis: 

educational goals and management guidelines. The International Conference 

on sinus Disease. Ann Otol Rhinol Laryngol Suppl, 1995; 167: 22-30 

78. DeVault KR, Castell DO, American College of Gastroenterology. Updated 

guidelines for the diagnosis and treatment of gastroesophageal reflux 

disease. Am J Gastroenterol, 2005; 100: 190-200. 

79. Prezant DJ. World Trade Center Cough Syndrome and its Treatment. Lung. 

2008 ; 186 :94S-102S. 

80. Friedman S, Cone J, Eros-Sarnayai, Prezant D, Szeinuk J, Clark N, Milek 

D, Levin S, Gillio R. Clinical Guidelines for Adults Exposed to the World 

Trade Center Disaster. City Health Information. 2006;25:47-58. Available 

on-line at : http://www.nyc.gov/html/doh/downloads/pdf/chi/chi25-7. 

pdf. 


Chapter 3-2 

Inhalation Lung Injury 

and Radiation Illness 

By Dr. Lawrence C. Mohr, MD 

Injuries and illness associated with exposure to ionizing radiation can be caused 

by two types of radiological disasters: dispersion of radioactive particles or by 

a nuclear explosion. The dispersion of radioactive particles can occur during 

an accident involving a nuclear facility, such as a nuclear power plant, or by 

a man-made radiological dispersion device that is detonated for the purpose 

of harming others. Radiological dispersion devices, or “dirty bombs”, consist 

of radioactive materials that are placed around a conventional explosive 

charge. “Dirty bombs” are easy to construct and raw materials are readily 

available throughout the world. It is important to note that “dirty bombs” are 

not nuclear weapons and are not weapons of mass destruction. Their adverse 

health effects depend upon the type and amount of explosive used, the type 

and amount of radioactive material used and atmospheric conditions at the 

time of detonation. Most injuries from a “dirty bomb” will come from the blast 

effects of the conventional explosion. Acute and delayed (i.e., cancer) radiation 

health effects are unlikely. The risk of developing cancer following a “dirty 

bomb” attack is low because for most such devices the radiation exposure 

dose would be minimal. Long-term psychological trauma is likely to occur 

among some members of a population that have been exposed to radioactive 

material from a "dirty bomb." Indeed, long-term psychological trauma may 

be the most significant health effect. 

A nuclear explosion results from nuclear fission or from thermonuclear 

fusion, in which a tremendous amount of energy is suddenly released in the 

form of heat, blast and radiation. Human injury is caused by exposure to a 

combination of these three forms of energy following a nuclear detonation. 

The radiation exposure from a nuclear explosion can be very intense and lead 

to a life-threatening acute radiation illness, in addition to radiation burns, 

thermal burns and blast injuries. For survivors, radiation exposure from a 

nuclear explosion can also result in the development of various long-term 

health effects such as leukemia, thyroid cancer and other malignancies. 

Acute radiation illness is a serious, complex, life-threatening illness that 

occurs shortly after a high-dose radiation exposure, such as may occur following 

a nuclear explosion. It requires prompt assessment and management in order 

to minimize loss of life. In general, the higher the radiation dose, the greater 

the severity of acute effects, the higher the probability of delayed illnesses 

and the higher the mortality rate. It is essential that any physician who may be 

called upon to treat these seriously ill patients following a nuclear explosion 

be familiar with this unique illness. Acute radiation illness will be the focus 

of this section. 

Chapter 3-2 • Inhalation Lung Injury and Radiation Illness 221

222 Chapter 3-2 • Inhalation Lung Injury and Radiation Illness 

DECONTAMINATION OF RADIOLOGICAL CASUALTIES 

The decontamination of radiation-exposed patients should occur outside of 

the emergency department after the patient is stabilized. Health care workers 

must be educated to understand that their exposure to this “dirty dust” is of 

minimal risk as long as they do not inhale or ingest it. Therefore, recommended 

personal protective equipment for all health care workers is scrubs, gowns, 

appropriate respirators, gloves and shoe covers during the treatment and 

decontamination of radiation casualties. The decontamination process is 

quite simple. All of the patient’s clothing must be removed and discarded into 

a clearly-labeled and secure container, so that it does not further contaminate 

people and surroundings after removal. The patient is then thoroughly washed 

with soap and water. This simple soap-and-water process has been shown to 

be effective in removing more than 95% of residual radioactive material from 

radiation-exposed patients. 

INTERNAL RADIATION CONTAMINATION 

In the assessment of patients for acute radiation exposure, it is important to 

ascertain whether or not they have experienced any internal contamination. 

Internal radiation contamination can occur by the inhalation, ingestion or 

transdermal penetration of radioactive material. It can occur via a variety of 

portals, such as the nose, the mouth, a wound, or, with a large enough dose, 

by the penetration of gamma rays or neutrons directly through intact skin. 

Internal organs commonly affected by internal radiation contamination are 

the thyroid, the lung, the liver and bone. These are the areas where radioactive 

isotopes tend to accumulate within the human body. Leukemia and various 

types of cancers can develop in these organs many years after an acute radiation 

exposure with internal contamination. 

The patient history is crucial to determining whether or not they may have 

experienced internal contamination. Any history which suggests that a patient 

may have inhaled, ingested, or internalized radioactive material through open 

wounds should prompt further evaluation for internal contamination. This 

assessment should attempt to identify both the radiation dose received and, 

if possible, the specific isotopes that caused the internal contamination. An 

initial survey of the patient should be performed with a radiac meter, especially 

around the mouth, nose and wounds, to give some idea of the extent of any 

possible internal exposure. The analysis of nasal swabs, stool samples and 

urine samples are the most practical methods of determining the type and 

extent of internal radiation contamination by hospital-based physicians. 

If it is suspected that a person has inhaled a significant amount of radioactive 

material, bronchoalveolar lavage can be considered for the purposes of 

identifying inhaled radioactive isotopes as well as for removing residual 

radioisotopes from the lungs. Chest and whole-body radiation counts can also 

be helpful in determining the extent of any internal radiation contamination. 

However, most medical institutions don’t have the capability to do either 

chest or whole-body radiation counts. Patients who have experienced internal 

radiation contamination should be treated. Specific agents are used to treat 

internal contamination by specific radioactive isotopes. Such treatment is 

most effective when given as soon as possible after the radiation exposure. In

deciding whether or not to treat a patient for internal radiation contamination, 

the physician may need to act on preliminary information and may have to treat 

potentially-exposed individuals empirically, based upon the information that is 

available. The treatments for internal contamination by specific radionuclides 

are summarized in Table 3-2.1. 

Specific Treatment for Internal Radiation 

Radionuclide Treatment Route 

Cesium-137 

Iodine-125/131 

Strontium-90 

Americium-241 

Plutonium-239 

Cobalt-60 

Prussian blue 

Potassium iodide 

Aluminum phosphate 

Ca-DTPA and Zn-DTPA 



Table 3-2.1: Specific Treatment for Internal Radiation. 

Oral 

Oral 

Oral 

IV Infusion 

IV Infusion 

IV Infusion 

RADIATION DOSES 

Since the severity, prognosis and management of acute radiation illness are 

all related to the radiation dose received by the patient, it is important for 

physicians to have a basic understanding of how radiation doses are measured. 

There are two units of radiation dose that physicians must be familiar with: the 

Rad and the Gray. It is not essential for physicians to understand the physics 

that underlie the determination of these doses, but it is important for them to 

know that these are the units which are used to express the amount of radiation 

that is absorbed by human tissues. The Rad is the traditional unit of radiation 

absorbed dose. One Rad is defined as 100ergs/gram. The Gray (abbreviated 

Gy) is the newer Standard International unit of radiation exposure. One Gy is 

equal to 100 Rads, which is defined as 1 Joule/kilogram. One hundred centi- 

Gray (100cGy) are equal to one Gray. 

Radiation doses can be measured by several techniques. The radiac meter 

is an instrument that directly measures radiation dose using a Geiger-Müller 

tube or similar device. There are many different types of radiac meters, each 

of which may be more sensitive to specific types of radiation. Most radiac 

meters in use today are highly portable and will accurately measure alpha, 

beta, gamma and neutron radiation. The measurement of serial lymphocyte 

counts can provide a useful biological estimate of radiation dose, especially 

in the clinical setting (Table 3-2.2). 


224 

Procedure for Determining Approximate Dose Based on Lymphocyte Count 

Determine initial lymphocyte count (L1) and subsequent counts (L2) at 6 or 12 hours. Divide (L1) 

by (L2) and take natural log of quotient. Divide result by the time change in 24 hours (number of 

hours between counts divided by 24) to determine "K". Refer below for estimated dose: 

K 

0.1 

0.2 

0.4 

0.6 

0.8 

Est. 

Dose 

in Gy 

1.24 

2.27 

3.90 

5.11 

6.06 

Chapter 3-2 • Inhalation Lung Injury and Radiation Illness 

99% Confidence 

Limits 

0.98 - 1.5 

1.87 - 2.68 

3.36 - 4.43 

4.5 - 5.73 

5.33 - 6.79 

K 

1.0 

1.5 

2.0 

2.5 

3.0 

Est. 

Dose in 

GY 

6.82 

8.18 

9.09 

9.73 

10.22 

99% Confidence 

Limits 

5.95 - 7.69 

6.9 - 9.46 

7.43 - 10.74 

7.76 - 11.71 

7.98 - 12.45 

Figure 3-2.2: Procedure for Determining Approximate Dose. (Adapted from Early Dose 

Assessment Following Severe Radiation Accidents 1 ) 

Chromosomal aberrations and translocations can provide a useful estimates 

of both the type of radiation that one has been exposed to as well as the 

radiation dose. This method requires considerable expertise in fluorescent 

in situ hybridization techniques as well as expertise in the interpretation of 

the chromosomal abnormalities. As a result, the analysis of chromosomal 

aberrations is primarily used as a research tool. 

In considering the human dose-response to radiation exposure, a measurement 

known as the LD 50/60 (radiation dose that causes a 50% mortality rate in an 

exposed population within 60 days following exposure) is useful. For wholebody 

radiation exposure, the LD 50/60 with no treatment, is three to four Gy. 

Therefore, 50% of a population that receives a radiation dose of three to four 

Gy will die within 60 days unless they receive treatment. With treatment 

following radiation exposure, the LD 50/60 is five Gy or more. 

ACUTE RADIATION ILLNESS 

Acute radiation illness is a continuum of dose-related organ system abnormalities 

that develops after an acute radiation exposure of greater than one Gy. There 

are three main clinical syndromes that occur in acute radiation illness: the 

hematopoietic syndrome, the gastrointestinal syndrome and the central nervous 

system syndrome. Each of these syndromes occurs in a dose-related fashion. 

The hematopoietic syndrome occurs with radiation exposures greater than 

one Gy. The gastrointestinal syndrome occurs in addition to the hematopoietic 

syndrome at radiation exposures greater than six Gy. The central nervous 

system syndrome occurs in addition to the hematopoietic and gastrointestinal 

syndromes at radiation exposures greater than 10 Gy. 

All cases of acute radiation illness begin with a prodromal phase that lasts 

for two to six days. This phase is characterized by nausea, vomiting diarrhea 

and fatigue. The higher the dose, the more rapid the onset and severity of 

symptoms associated with the prodromal phase. After two to six days of the 

prodromal phase, the patient enters a latent phase, in which he or she appears 

to recover and is totally asymptomatic. The latent phase lasts for several days

to one month, with the time period inversely proportional to the radiation 

exposure dose (i.e., the higher the dose the shorter the latent period). After the 

asymptomatic latent period, the patient enters the manifest illness phase. This 

phase of acute radiation illness lasts from several days to several weeks and 

is characterized by the manifestation of the hematopoietic, gastrointestinal 

and central nervous system syndromes, according to the exposures dose that 

the patient received. 

The hematopoietic syndrome is characterized by bone marrow suppression 

resulting from the radiation-induced destruction of hematopoietic stems cells 

within the bone marrow. Hematopoietic stem cell destruction results in a 

pancytopenia which is characterized by a progressive decrease in lymphocytes, 

neutrophils and platelets in the peripheral blood. Both the magnitude and 

the time course of the pancytopenia are related to the radiation dose. In 

general, the higher the radiation dose the more profound the pancytopenia 

and the quicker it occurs. Lymphocytic stem cells are the most sensitive and 

erythrocytic stem cells the more resistant to radiation. Therefore, the red 

blood cell count and hemoglobin concentration typically do not decrease to 

the same extent as lymphocytes, neutrophils and platelets following radiation 

exposure. Hematological effects that occur in the manifest illness phase of the 

hematopoietic syndrome following radiation exposures of one Gy and three 

Gy are depicted in Figure 3-2.1. 

Figure 3-2.1: Hematological Effects of the Hematopoietic Syndrome (manifest illness 

phase) (Adapted from Acute Radiation Syndrome in Humans 2 ) 



Following a three Gy exposure, lymphocytes decrease very rapidly and 

remain low for approximately 90 days. Neutrophils, after an initial period of 

intravascular demargination, will also begin to decline fairly rapidly following 

a three Gy exposure. Neutrophils do not fall as rapidly as lymphocytes, 

but between three and five days following exposure such patients will be 

significantly neutropenic. Platelets also decrease steadily following a three 

Gy exposure and patients will become significantly thrombocytopenic at two 

to three weeks. Both platelets and neutrophils will reach a nadir, with values 

close to zero, at about 30 days following a three Gy exposure. Platelets and 

neutrophils then recover gradually during the next 30 days. Thus, there is a 

period of about a month or so following a three Gy exposure, when patients 

will be significantly lymphopenic, neutropenic and thrombocytopenic. Such 

patients are susceptible to developing serious infections and serious bleeding 

problems during that time. 

The gastrointestinal syndrome of acute radiation illness typically occurs 

following a radiation dose of greater than six Gy. It develops as a result of 

radiation damage to the intestinal mucosa. Following the asymptomatic latent 

phase, patients enter a manifest illness phase characterized by fever, vomiting 

and severe diarrhea. Malabsorption and severe electrolyte derangements will 

follow. Sepsis and opportunistic infections commonly occur as the result of 

mucosal breakdown. The resulting sepsis can be very severe, and typically 

involves enteric organisms that migrate into the systemic circulation through 

the damaged gastrointestinal mucosa. Approximately 10 days after the onset of 

the manifest illness phase, these patients typically develop fulminate bloody 

diarrhea that usually results in death. 

The central nervous system syndrome is seen with radiation doses greater 

than or equal to 10 Gy. Following the asymptomatic latent period, such patients 

develop rapid onset of microvascular leaks in the cerebral circulation and 

cerebral edema. Elevated intracranial pressure and cerebral anoxia develop 

rapidly. Mental status changes develop early in the manifest illness phase 

and the patient eventually becomes comatose. Seizures may occur. Patients 

typically die within hours after onset of the manifest illness phase of the central 

nervous system syndrome. 

The prognosis of patients with acute radiation illness depends upon the 

radiation dose to which they were acutely exposed. Patients who are exposed 

to one to two Gy will probably survive. Survival is possible in patients who 

are exposed to doses of two to six Gy, but these patients will require intensive 

medical care in order to survive. Survival is possible, but improbable, in patients 

who are exposed to doses of seven to nine Gy. Even with the most aggressive 

treatment, survival is extremely rare following exposure doses of 10 to 15 Gy 

and impossible following doses greater than 15 Gy. 

Treatment 

All patients with acute radiation illness should receive basic supportive care. 

This consists of fluid and electrolyte balance, antiemetic agents to manage 

vomiting, antidiarrheal agents to manage diarrhea, proton pump inhibitors for 

gastrointestinal ulcer prophylaxis, pain management, psychological support 

and pastoral care if death is likely. In patients with acute radiation illness, it is

important not to instrument the gastrointestinal tract, since this could result 

in perforations that precipitate fulminate bleeding or sepsis. 

Cytokine therapy with a colony stimulating factor should be given to patients 

with a 2 Gy or greater exposure in order to stimulate neutrophil production in 

the bone marrow 1 . However, in an extreme mass casualty situation, it may be 

necessary to maximize the use of cytokines by providing only supportive care 

to the expectant (seven Gy or greater exposure) 1 . Various types of granulocyte 

colony stimulating can be given to individuals with acute radiation illness: 

G-CSF (Filgrastim – 5 mg/kg per day subcutaneously, continued until the 

absolute neutrophil count is greater than 1.0 x 109 cells/L); Pegulated G-CSF 

(Pegfilgrastim – 6 mg as a single subcutaneous dose); or GM-CSF (Sargramostim 

– 250 mg/m2 per day subcutaneously, continued until the absolute neutrophil 

count is greater than 1.0 x 109 cells/L). 

Antibiotics are also recommended for all with a two Gy exposure or greater, 

due to expected absolute neutropenia, especially in the setting of burns or 

other traumatic injuries 1 . Similarly, in an extreme mass casualty situation, it 

may be necessary to maximize use by providing only supportive care to the 

expectant (seven Gy or greater exposure) 1 . The specific antibiotic regimen 

used in the management of acute radiation illness should depend upon the 

antibiotic susceptibilities of any specific organisms that are able to be isolated. 

It is generally recommended that a fluoroquinolone with streptococcal coverage 

be used, along with acyclovir or one of its congeners for viral coverage, and 

fluconazole for the coverage of fungi and candida. Once again, antibiotic 

treatment should be given for any specific organisms that can be isolated, 

such as Pseudomonas aeruginosa. Antibiotics should be continued until the 

absolute neutrophil count is greater than 0.5 x 109 cells/L, until they are no 

longer effective, or as indicated for specific organisms that have been isolated. 

Blood transfusions are indicated for patients with acute radiation syndrome 

who have severe bone marrow damage or who require concurrent trauma 

resuscitation. The purpose of blood transfusions in such patients is to provide 

erythrocytes for the improvement of oxygen-carrying capacity, blood volume 

to improve hemodynamic parameters and platelets to help prevent bleeding. 

Cytokines, not blood transfusions, are used to increase absolute neutrophil 

counts, according to the criteria and doses previously discussed. All cellular 

products in the blood to be transfused should be leukoreduced and irradiated 

to 25 Gy in order to prevent a graft versus host reaction. Leukoreduction also 

helps to protect against platelet alloimmunization and the development of 

cytomegalovirus (CMV) infections. 

Stem cell bone marrow transplantation should be considered for certain 

patients with acute radiation illness. Allogenic stem cell transplantation is 

indicated for individuals who have a radiation exposure dose of 7 to 10 Gy. 

Patients with acute radiation illness who are fortunate enough to have a 

stored autograft bone marrow specimen or a syngenetic donor, preferably an 

identical twin, should be consider for stem cell transplantation if they have 

had a radiation exposure dose of 4 to 10 Gy. 

There are several special considerations that need to be taken into account 

during the management of acute radiation illness. These include concurrent 

acute radiation dermatitis, combined acute radiation illness and trauma, 



decontamination of the patient and appropriate precautions for health care 

workers. 

Acute radiation dermatitis may occur in conjunction with acute radiation 

illness. The symptoms and signs of acute radiation dermatitis typically appear 

several days after an acute radiation exposure. Although acute radiation 

dermatitis is essentially a radiation burn, it is different from the thermal burns 

that may occur immediately after exposure of the skin to a nuclear explosion. 

Exposure of the skin to radiation causes loss of the epidermal layer at radiation 

doses greater than two Gy. This leads to erythema and blisters. Loss of the 

dermis occurs at radiation exposure doses of greater than 10 Gy; this results 

in skin ulcers that heal very slowly over many months, if they heal at all. These 

patients are predisposed to serious infections. 

The combination of acute radiation illness and trauma is a unique management 

challenge. First, there is a significant increase in mortality among patients 

who have this combination of illness and injury and they typically require 

very intensive medical care. Their care is complicated by the fact that any 

surgery that is required should be done within the first 48 hours after radiation 

exposure or delayed for two to three months, depending upon the radiation 

dose and the extent of the hematopoietic syndrome. These patients are very 

susceptible to operative and postoperative infections as a result of decreased 

neutrophil and lymphocyte counts. 

REFERENCE 

1. Groans RE, Holloway EC, Berger ME, Ricks RC. Early Dose Assessment 

Following Severe Radiation Accidents. Health Physics, 1997: 72(4), pp. 

513 - 518. 

2. Cerveny TJ, McVitte TJ, Young RW. Acute Radiation Syndrome in Humans. 

In: Texbook of Military Medicine: Medical Consequences of Nuclear War. 

Zajtchuk R, Jenkins DP, Bellamy RF, Ingram VMI, Walker RI and Cerveny 

TJ, editors. Office of the Surgeon General, United States Army, 1989: p. 19 

3. Waselenko JK, McVittie TJ, Blakely WF et al. Medical management of the 

acute radiation syndrome: Recommendations of the Strategic National 

Stockpile Radiation Working Group. Annals of Internal Medicine 2004; 

140: 1037-1051

Chapter 3-3 

Inhalation Lung Injury 

Vesicants and Nerve 

Agents 

By Dr. James A. Geiling, MD 

Chemical weapons are divided into four major classifications based upon 

their physiologic effects and mechanisms of action. Blood agents such as 

AC (hydrogen cyanide), (SA) arsine, cyanogen, and hydrogen sulfide were 

discussed in Chapter 1-2. Pulmonary irritants such as phosgene and chlorine 

were discussed in chapter 3-1. The remaining two classical categories include 

the vesicants and nerve agents. These agents can be dispersed from a variety 

of munitions. 

VESICANTS 

Vesicants derive their name from the vesicles or blisters that these agents 

produce. Two agents comprise this group: mustard (HD; bis-2-Chloroethyl 

sulfide) and Lewisite (L; 2-Chlorovinyl dichloroarsine). They have also been 

used as a combined mixture. Phosgene oxime (agent CX) is a also vesicant 

(as well as an urticant). 

Clinical Syndrome 

Topical exposure to these irritants causes conjunctivitis, corneal opacification, 

skin erythema and vesicles (blisters). Inhalation injury ranges from mild upper 

respiratory complaints to marked airway damage including asthma, chronic 

bronchitis, bronchiectasis, pulmonary fibrosis, and bronchiolitis obliterans. 1,2,3,4 

The principle difference between these agents is the latency of mustard, 

with an asymptomatic period of hours. Mustard can also cause gastrointestinal 

effects and bone marrow suppression. These agents can be detected by a variety 

of chemical agent or hazardous material (HAZMAT) monitoring devices. 

Decontamination 

The recommended decontamination solution is hypochlorite in large amounts, 

though large quantities of soap and water are more practically employed. 

Treatment 

Early treatment with nonsteroidal anti-inflammatory drugs has been shown to 

be beneficial against the cutaneous injury caused by mustard. 5 Skin lesions are 

Chapter 3-3 • Inhalation Lung Injury — Nerve Agents 229

230 Chapter 3-3 • Inhalation Lung Injury — Nerve Agents 

treated as per standard burn protocol. 6 Respiratory management is symptom 

targeted though patients may benefit from bronchoscopy, including bougienage 

and laser photoresection if findings progress. 7 Lewisite has a specific antidote 

known as British Anti-Lewisite that may mitigate systemic effects 8,9 . 

NERVE AGENTS 

Nerve agents are highly toxic and include: GA (tabun): Ethyl N, 

N-dimethylphosphoramidocyanidate; GB (sarin): Isopropyl methyl 

phosphonofluoridate; GD (soman): Pinacolyl methyl phosphonofluoridate; 

GF: O-Cyclohexyl-methylphosphonofluoridate; and VX: O-Ethyl S-(2- 

(diisopropylaminoethyl) methyl phosphonothiolate. 8,9 

Clinical Syndrome 

They act through their inhibition of organophosphorous cholinesterases, 

specifically plasma butyrylcholinesterase, red blood cell (RBC) 

acetylcholinesterase, and acetylcholinesterase (AChE) at tissue cholinergic 

receptor sites. 8,9 Following an acute exposure, the RBC enzyme activity best 

reflects the tissue AChE activity during recovery. Nerve agents irreversibly 

bind to AChE and thereby prevent the hydrolysis of the neurotransmitter 

acetylcholine (ACh); the resultant excess ACh produces the clinical effects of 

nerve agent toxicity. Because the binding of agent to enzyme is permanent, 

its activity returns only with new enzyme synthesis or RBC turnover (1%/day). 

Excess ACh affects both muscarinic and nicotinic sites. Affected muscarinic 

sites include postganglionic parasympathetic fibers, glands, pulmonary and 

gastrointestinal smooth muscles, and organs targeted by central nervous 

system efferent nerves, such as the heart via the vagus nerve. Nicotinic sites 

include autonomic ganglia and skeletal muscle. 

Nerve agents produce a clinical syndrome similar to that of organophosphate 

insecticide poisoning but, with far greater toxicity. The symptom complex has 

been previously described by the “SLUDGE” toxidrome: increased salivation, 

lacrimation, urination, defecation, gastric distress and emesis. 9 The principal 

effect on the eyes is miosis, which occurs as a consequence of direct contact 

with vapor. The symptoms appear shortly after exposure, often within seconds. 

The pupillary constriction is often associated with intense pain (which may 

consequently induce nausea and vomiting). Miosis results in dim or blurred 

vision; the conjunctiva often become injected and lacrimation occurs. Exposure 

results in increased salivary gland secretion as well as other gastrointestinal 

glandular secretions. Victims may present with significant nausea, vomiting, 

and diarrhea. Localized sweating may occur at the site of exposure to nerve 

agent droplets. Generalized sweating appears with high-dose exposure. 

Skeletal muscles initially develop fasciculations and twitching, but they 

become weak, fatigued, and eventually flaccid. Respiratory effects include 

rhinorrhea, bronchorrhea and bronchoconstriction depending upon the 

severity of exposure. Respiratory compromise develops with diaphragm and 

other muscle weakness. High dose exposure may result in loss of consciousness, 

seizure activity and central apnea. Normally, a vagally-mediated bradycardia 

may be expected with these agents. However, typically these patients have a 

“fight or flight”-induced tachycardia. Blood pressure remains normal until 

terminal decline. A variety of dysrhythmias may develop, including QTc

prolongation and Torsade de pointe. 10,11 In survivors, a chronic decline in 

memory function, post-traumatic stress and depression have been noted after 

the Tokyo sarin gas release. 12 

While initial effects from nerve agent exposure can be seen within seconds 

to minutes, the rapidity and severity of symptoms are dose-dependent. Highdose 

vapor exposure may present as seizures or loss of consciousness in less 

than one minute, whereas low-dose skin contact may not present as long as 

18 hours later when the victim appears with gastrointestinal complaints. 

Measurement of red cell cholinesterase (ChE) inhibition is more sensitive than 

measurement of plasma ChE activity in the setting of nerve agent exposure. 

However, although helpful in confirming exposure, results are not immediately 

available as few clinical laboratories can perform these tests and levels do not 

generally correlate with physical findings. 

Decontamination 

Decontamination is the key element in mitigating the effects of nerve agent 

poisoning on patients and health care workers. All suspected casualties should 

be decontaminated prior to entering a medical facility. “Casualties” who remain 

asymptomatic minutes after an event are unlikely to have sustained a significant 

vapor exposure. However, if exposed to a liquid agent, even asymptomatic 

victims should be observed for 18 hours. When triaging multiple casualties, 

patients recovering from exposure and treatment in the field can normally be 

placed into a “delayed” category. Ambulatory patients and those with normal 

vital signs can be categorized as “minimal”. “Immediate” patients are those 

with unstable vital signs or seizure activity. Triaging of patients who are apneic, 

pulseless, or without a blood pressure will depend on available resources. 

Airway and breathing management is paramount. Ventilatory support is 

complicated by increased secretions and airway resistance (50 to 70 cm H 2 O). 

Treatment 

Treatment of nerve agent casualties, like other poisons, requires appropriate 

administration of antidotes. Atropine is an anti-cholinergic and serves as 

the primary antidote for nerve agent exposure, with its greatest effect at 

muscarinic sites. The standard two-milligram dose when administered to nonexposed 

person will result in mydriasis, decreased secretions and sweating, 

mild sedation, decreased gastrointestinal motility, and tachycardia. The 

recommended atropine dose is two-milligrams every three to five minutes, 

titrated to secretions, dyspnea, retching or vomiting. 13,14 Atropine should not 

be dosed to miosis, which is treated with topical atropine or homatropine, or 

more recently tropicamide. Nebulized ipratropium bromide may be of help 

in managing secretions and bronchospasm. Fasciculations can persist after 

restoration of consciousness, spontaneous ventilation, and even ambulation. 

Atropine will normally not be effective in terminating seizures, though other 

antcholinergics (scopolamine, benactyzine, procyclidine, and aprophen) may 

be successful if given early. 12,13 

In addition to atropine, pralidoxime chloride (2-PAMCl) is used in an attempt 

to break nerve agent-enzyme binding. This oxime is effective only at nicotinic 

sites thereby, improving muscle strength but not secretions. 2-PAMCl is only 

effective if administered early before binding has become permanent. The 

Chapter 3-3 • Inhalation Lung Injury — Nerve Agents 

231

232 


time course for this phenomenon, referred to as “aging”, varies according to 

the nerve agent involved – approximately two minutes for Soman and three to 

four hours for Sarin. Other oximes, including obidoxime, the H oximes (HI-6, 

Hlö-7), and methoxime may eventually provide additional options to reactivate 

the ChE. 15 Atropine and 2-PAMCl are often combined into an injector kit system 

known as the MARK I kit (Meridian Medical Technologies, Inc; Columbia, 

MD) or more recently the Duodote Kit (Meridian Medical Technologies, Inc; 

Columbia, MD) used by the US military and civilian EMS personnel. For 

seizures, Diazepam is the anticonvulsant of choice, based primarily on its 

historical use and demonstrated effectiveness, but other benzodiazepams may 

be substituted. Ketamine has also been used as an anticonvulsant because of 

its neuroprotective and antiepileptic activities 15 . More aggressive therapy may 

include the use of hemodiafiltration followed by hemoperfusion, which was 

successfully employed in the management of one victim of the Tokyo sarin 

attack. 16 Future therapies may include bacterial detoxification, the use of 

nerve agent scavengers such as organophosphorous acid anhydride hydrolase, 

benzodiazepine receptor partial agonists (e.g., bretazenil) in the prophylactic 

treatment of nerve agent poisoning, or paraoxonases that enzymatically break 

down nerve agent. 17,18,19,20 . 

OTHER CHEMICAL AGENTS 

Urticants or nettle agents such as phosgene oxime (agent CX, also a vesicant) 

produce instant and sometimes intolerable pain upon contact with skin and 

mucous membranes. Vomiting agents such as Adamsite (agent DM) can cause 

regurgitation, as well as coughing, sneezing, pain in the nose and throat, nasal 

discharge, and/or tears, as well as dermatitis on exposed skin. Corrosive 

smoke agents such as titanium tetrachloride (agent FM smoke) and sulfur 

trioxide-chlorosulfonic acid (agent FS smoke) cause inflammation and general 

destruction of tissues and can lead to swelling of lung membranes, pulmonary 

edema, and death following inhalation. Tear agents such as acrolein (no 

military designation), mace (agent CN), and pepper spray (agent OC) cause 

tears and intense eye pain and may also irritate the respiratory tract and skin. 

REFERENCES 

1. Medical management of chemical casualties handbook 3rd ed. USAMRICD, 

Aberdeen Proving Ground. MD. July 2000. 

2. Newmark J. Chemical warfare agents: a primer. Mil Med. 2001; 166:9-10. 

3. Kales S, Christiani D. Acute chemical injuries. N Engl J Med. 2004; 350:800- 

808. 

4. Thomason J, Rice T, Milstone A. Bronchiolitis obliterans in a survivor of 

a chemical weapons attack. JAMA. 2003; 290(5): 598-599. 

5. Emad A, Rezaian G. The diversity of the effects of sulfur mustard gas 

inhalation on respiratory system 10 years after a single, heavy exposure. 

Analysis of 197 cases. Chest. 1997;112:734-738.

6. Karayilanoglu T, Gunhan Ö, Kenat L, Kurt B. The protective effects of zinc 

chloride and desferrioxamine on skin exposed to nitrogen mustard. Mil 

Med. 2003; 168:614-617. 

7. Freitag L, Firusian N, Stamatis G, Greschuchna D. The role of bronchoscopy 

in pulmonary complications due to mustard gas inhalation. Chest. 1991; 

100:1436-1441. 

8. Sidell F. Nerve agents. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical 

aspects of chemical and biological warfare. The Textbook of Military 

Medicine. Washington, DC: Office of the Surgeon General, Department 

of the Army, 1997; 129–179. Available at: http://stinet.dtic.mil/oai/oai?&v 

erb=getRecord&metadataPrefix=html&identifier=ADA398241 . Accessed 

March 24, 2007. 

9. Heck J, Geiling J, Bennett B, et al. Chemical weapons: history, identification, 

and management. Critical Decisions in Emergency Medicine 1999; 13(12):1–8 

10. Abraham S, Oz N, Sahar R, Kadar T. QTc prolongation and cardiac lesions 

following acute organophosphate poisoning in rats. Proceedings of the 

Western Pharmacology Society. 2001; 44:185-186. 

11. Chuang F, Jang S, Lin J, et al. QTc prolongation indicates a poor prognosis 

in patients with OP poisoning. Am J Emerg Med. 1996; 14:451-453. 

12. Nishiwaki Y, Maekawa K, Ogawa Y, et al. Effects of sarin on the nervous 

system in rescue team staff members and police officers 3 years after the 

Tokyo subway sarin attack. Environ Health Perspect 2001; 109(11):1169- 

1173 

13. Lee E. Clinical manifestations of sarin nerve gas exposure. JAMA. 2003; 

290(5):659-662. 

14. McDonough J, Zoeffel L, McMonagle J, et.al. Anticonvulsant treatment 

of nerve agent seizures: anticholinergics versus diazepam in somanintoxicated 

guinea pigs. Epilepsy Research 2000; 38:1-14. 

15. Kassa J. Review of oximes in the antidotal treatment of poisoning by 

organophosphorus nerve agents. J Toxicol Clin Toxicol. 2002:40:803-816. 

16. Mio G, Tourtier JP, Petitjeans F, et al. Neuroprotective and antiepileptic 

activities of ketamine in nerve agent poisoning. Anesthesiology. 2003; 

98(6):1517. 

17. Leikin J, Thomas R, Walter F, et al. A review of nerve agent exposure for 

the critical care physician. Crit Care Med 2002; 30(10): 2346-2354. 

18. Raushel, FM. Bacterial detoxification of organophosphate nerve agents. 

Curr.Opin.Micro. 2002; 5: 288-295. 

19. Broomfield C, Kirby S. Progress on the road to new nerve agent treatments. 

J.Appl.Tox. 2001; 21:S43-S46. 

20. Tashma Z, Raveh L, Liani H, et.al. Bretazenil, a benzodiazepine receptor 

partial agonist, as an adjunct in the prophylactic treatment of OP poisoning. 

J. Appl. Tox. 2001; 21:S115-S119. 


233


Chapter 3-4 

Disaster-Related 

Infections: Pandemics, 

Post-Disaster and 

Bioterrorism 

By Dr. Asha Devereaux M.D., Angie Lazarus MBBS, 

and Dr. David J. Prezant M.D. 

There are three broad categories of disaster-related respiratory infections. The 

first is worldwide pandemic infection, itself the cause of a healthcare disaster. 

The second is an epidemic that follows a natural or man-made disaster. And the 

third is bio-attacks such as the inhalational anthrax exposures that occurred 

in the United States in 2001. 

PANDEMIC 

Pandemic planning is currently focused on response to the Novel H1N1 

influenza A virus. As of June 2010, worldwide more than 214 countries and 

overseas territories or communities have reported laboratory confirmed cases 

of pandemic influenza H1N1 2009, including over 18,209 deaths. Far greater 

numbers have been infected as many countries, including the United States 

and Canada, have not been counting milder cases and only using laboratory 

testing to confirm more severe cases. The United States and Canada are both 

reporting rates of influenza-like illness well above seasonal baseline rates. 

For hospitalized patients with H1N1, the most common symptoms include 

fever (93%), cough (83%), shortness of breath (54%), fatigue/weakness (40%), 

chills (37%), body aches (36%), nasal drip/congestion (36%), sore throat (31%), 

headache (31%), vomiting (29%), wheezing (24%) and diarrhea (24%). Important 

differences exist between H1N1 influenza and seasonal influenza. Because, 

most individuals less than 65 do not have natural immunity to H1N1, disease 

has been more severe in the young than in the elderly. According to the Centers 

for Disease Control and Prevention (CDC), groups at particular risk include, the 

young (especially between six months and 24 years old), pregnant women, or 

persons with chronic diseases (lung disease including asthma, heart disease 

excluding hypertension, kidney, liver, hematologic including sickle cell disease, 

diabetes, cancer especially those receiving chemotherapy, immunologic 

disorders including those caused by medication or HIV, neuromuscular 

diseases that could compromise respiratory function or increase the risk for 

pneumonia, and persons younger than 19 years old who are receiving longterm 

aspirin therapy because of increased risk for Reye Syndrome. These 

Chapter 3-4 • Disaster-Related Infections: Pandemics, Post-Disaster, and Bioterrorism 

235

groups have been identified to be at increased risk because of their high rates 

of influenza complications leading to hospitalization, intensive care unit stays, 

mechanical ventilation and death. 

For example, in the United States during 2009, 32% of those hospitalized 

due to H1N1 influenza have had pre-existing asthma. In an effort to reduce 

their risk, the CDC recommends that these patients at risk receive not only 

the seasonal influenza vaccine but also the H1N1 vaccine and also, in certain 

cases, Pneumovax® (vaccination affords protection against common types of 

pneumococcal pneumonia). In addition, the CDC recommends that these 

groups at risk receive early treatment with antiviral medications (oseltamivir or 

zanamivir) if influenza-like illness was to occur. Further, the CDC recommends 

that all healthcare personnel (including EMS personnel and fire fighters 

who respond to medical emergencies) receive seasonal influenza and H1N1 

vaccinations. The CDC recommends that these vaccinations should not be 

given to those with severe allergy to chicken eggs, prior severe reaction to 

influenza vaccination, the rare person who developed Guillan-Bare syndrome 

within six weeks of getting an influenza vaccine, children less than six months 

of age, people who currently have moderate-to-severe illness with fever (they 

should wait until they recover). Those with immunologic disorders or who 

have household members with immunologic disorders should only receive 

the flu-shot which contains inactivated vaccine (killed virus) and should not 

receive the flu-nasal-spray which contains live weakened virus. 

H1N1 is not the only novel influenza virus that is of concern. The potential 

still remains for avian influenza A subtype H5N1 developing the capacity for 

widespread, efficient, and sustainable human-to-human contagion. The first 

recognized human outbreak of avian influenza H5N1 occurred between May 

and December 1997 in Hong Kong3 infecting 18 persons, mostly children and 

young adults (half less than 19 years old and only two older than 50 years). 4,5 

Between 2003 and January 2007, 265 additional cases, with a 60% mortality rate, 

were reported to the World Health Organization (WHO) but only a few were 

suspected to be the result of human-to-human transmission 6 . Fever, cough 

and dyspnea occur in nearly all patients, and abdominal symptoms, including 

diarrhea, appear in about half the patients. 4, 5 Pneumonia, lymphopenia and 

elevated liver enzymes are poor prognostic factors with death occurring on 

average 10 days after onset of illness, typically from progressive respiratory 

4, 5 

failure and Acute Respiratory Distress Syndrome (ARDS). 

The incidence of pneumonia complicating influenza infection varies widely, 

from 2 - 38%, and is dependent on viral and host factors. 7,8,9 During an influenza 

pandemic, pneumonia should be considered in all patients with severe or 

worsening respiratory symptoms, especially those with pre-existing chronic 

disease. Influenza-related pneumonia can be viral or a secondary bacterial 

or mixed infection. 7,8,9,10 Typically, viral pneumonia (bilateral interstitial 

infiltrates) occurs early in the presentation while secondary bacterial pneumonia 

(lobar infiltrates) occurs four to five days after onset of initial symptoms. The 

predominant organisms responsible for secondary bacterial pneumonia vary 

with Hemophilus influenza, beta-hemolytic streptococci and Streptococcus 

pneumonia during the 1918 influenza pandemic; Staphyloccus aureus during 

the 1957 pandemic; and S pneumonia, Staphylococcus aureus (26%) and 

Hemophilus influenza during the 1968 pandemic. 7, 11 Mixed bacterial and viral 

236 Chapter 3-4 • Disaster-Related Infections: Pandemics, Post-Disaster, and Bioterrorism

pneumonia can occur concurrently. 12 In these instances, the chest radiograph 

may demonstrate lobar consolidation superimposed on bilateral diffuse lung 

infiltrates. The mortality rate in mixed viral – bacterial pneumonia is as high 

as for primary viral pneumonia (>40%) 7,6,9,10 . 

The current recommendation during a pandemic flu alert is to treat with 

an appropriate antiviral medication early on in the presentation of flu-like 

symptoms and fever (< 2 days). 6, 13 Antibiotics should be added if pneumonia 

is present or considered if risk factors for poor outcome are present such as 

age over 64 years, nursing home patient, immunosuppression or chronic 

disease (i.e. respiratory, cardiac, liver, renal or diabetes). Proper respirators 

and universal droplet precautions are current CDC recommendations. 14 Using 

CDC computer projections based on the 1918 flu pandemic (35% attack rate, 

week five of an eight-week pandemic), a city the size of New York today would 

require approximately 39,000 hospital beds, 19,000 ICU beds, and over 9,000 

mechanical ventilators. 15 

EPIDEMICS POST-DISASTER 

Epidemics post-disaster are, despite popular misconceptions, actually 

uncommon and when they do occur are the result of organisms and vectors 

already endemic to the area or displaced population. 16 The risks of epidemics 

are increased only when disaster produces large displacements of people to 

crowded shelters lacking adequate sanitation, climate control, food, vaccines 

and medications. 17 Dead bodies do not increase infectious disease risk, unless 

the dead were victims of a communicable disease. Corpses do not need to be 

buried or burned rapidly and instead victims should be identified and dealt 

with consistent with legal, cultural and religious beliefs thereby, diminishing 

psychological stress for the large number of potentially-affected survivors. 

Disease-related mortality and epidemics17 can be prevented or reduced if 

public health infrastructure is maintained or quickly re-established to provide: 

safety and security of the victims, safe water and food, sanitation services 

(including human and animal waste removal), shelters with adequate space and 

ventilation, adequate hygiene, medications, immunization programs, vector 

control, disease surveillance, and the isolation of patients with communicable 

diseases. Malnutrition is associated with higher mortality rates from diarrheal 

illness, measles, malaria, and acute respiratory illness. The interdependency 

between malnutrition and infectious disease on mortality rates is most evident 

in vulnerable populations such as children and patients with pre-existing 

co-morbidity. 

During a disaster, the majority of all infectious disease mortality is related 

to diarrheal disease (not the subject of this review), respiratory infections18 and 

measles. 19 In 1992, following the Mount Pinatubo eruption in the Philippines, 

these three diseases caused nearly all of the infectious disease-related mortality 

in nearly equal proportion. 20 Knowledge of local endemic diseases and vectors 

provides a basis for educated surveillance in shelters and refugee camps. 

Surveillance should be coordinated by a single agency. Clinical field data 

should be routinely collected, shared, collated, and disseminated at regular 

meetings among various relief organizations to inform and respond to potential 

outbreaks. Surveillance case recognition should be based on easily identified 

clinical scenarios. Cough with fever suggests respiratory infection. Cough with 


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fever accompanied by mouth sores and rash raises suspicion for measles in an 

area with poor immunization programs. Immediately after Hurricane Andrew 

hit Florida in 1992, a surveillance system was initiated utilizing data from over 

40 sites. Surveillance focused on five presenting complaints (diarrhea, cough, 

rash, animal bite and “other infectious symptoms”) that were targeted for 

rapid intervention with the result that morbidity and proportional mortality 

was not increased for diarrhea or cough. 21 

Respiratory illnesses include all of the viral and bacterial infections 

common to the area or displaced population. Poor hygiene, overcrowding and 

malnutrition add to the risk for endemic infections becoming epidemic. Public 

health measures and early treatment is the mainstay. Tuberculosis22 can also 

occur in refugee camps in the developing world but, mortality is typically low. 23 

In Bosnia in 1992, tuberculosis cases increased dramatically as the result of 

medication shortages, overcrowding and malnutrition. 22 In areas with high 

HIV rates pre-disaster, mortality from co-infection with tuberculosis would 

be substantially higher. 

Measles, prior to mass immunization programs, was the infection most 

associated with high mortality rates. 19 In the first three months after the 

Mount Pinatubo eruption, measles accounted for nearly 18,000 cases, 25% 

of all clinic visits and 22% of all deaths. 24 Measles transmission is by direct 

contact with respiratory droplets and less commonly by airborne inhalation. 

The incubation period is 7 to 14 days from exposure to first signs of disease 

and patients are contagious from approximately one to two days prior to onset 

of illness until approximately four days after the rash appears. Respiratory 

complications include pneumonia from measles and bacterial super-infection. 

Disaster-induced disruption in a region’s routine vaccination program may lead 

not only to measles but to other respiratory diseases such as pneumococcal 

pneumonia, Hemophilus influenza and pertussis, especially in areas where 

large numbers of displaced persons are crowded together and pre-disaster 

immunization programs were ineffective. Standard post-disaster immunization 

recommendations emphasize measles immunization program in areas with 

low pre-disaster immunization rates. For children older than nine months, 

vitamin A should be given simultaneously, because it can decrease ophthalmic 

complications, disease severity and mortality by 30 - 50%. 25 

Post-disaster vector-borne disease epidemics are also uncommon. However, 

large areas of stagnant water and suspension of pre-existing vector control 

programs may increase breeding sites, and were the cause of increased malaria 

rates in Haiti after Hurricane Flora in 1963. 26 P. falciparum has the shortest 

incubation period (weeks to months) and is responsible for significant morbidity 

and mortality including respiratory complications such as pulmonary edema. 27 

Because chemotherapy resistance for malaria is quite variable worldwide, 

treatment should be based on local chemosensitivity. Other diseases transmitted 

by mosquito vectors include St. Louis encephalitis, eastern or western equine 

encephalitis, West Nile encephalitis and Dengue fever. 28 When considering 

epidemics, dengue is classified by the World Health Organization (WHO) 

as a major international public health concern. Dengue hemorrhagic shock 

syndrome is the most serious consequence of this infection and is likely to 

occur by cross infection with multiple serotypes of the virus. The hallmark 

of dengue hemorrhagic fever is capillary leakage four to seven days following 

Chapter 3-4 • Disaster-Related Infections: Pandemics, Post-Disaster, and Bioterrorism

the onset of disease, usually at the time of defervescence. A sudden change 

to hypothermia, altered level of consciousness, and gastrointestinal (GI) 

symptoms associated with thrombocytopenia herald the onset of capillary leak 

phenomenon. Emphasis should be on prevention programs for populations 

that are exposed to mosquitoes, including long-sleeved shirts and pants, insect 

repellents, bed-nets, and chemoprophylaxis. Infections related to adverse 

weather conditions can also be caused by other vectors or environmental 

exposures. For example, the increased incidence of Hantavirus (deer mice 

in New Mexico following flooding) 29 and coccidioidomycosis (dust clouds in 

California following the Northridge earthquakes) . 30 

Aspiration pneumonia is not usually thought of as a disaster-related infection. 

However, following the large earthquake in Indonesia in December 2004, over 

100,000 people were swept away by a massive tsunami. Many of the survivors 

clung to trees and debris as the seawater engulfed them. In this setting, 

aspiration pneumonia was “common” but, exact numbers were difficult to 

record. 31, 32 Resultant pulmonary infections from this exposure can be divided 

into early and late based on the pathogens involved. The initial manifestation 

of "submersion injury" (early aspiration pneumonia) is aspiration of 3-4 ml/kg 

of liquid due to reflex laryngospasm. This typically results in an immediate 

cough and chemical pneumonitis that can progress to Acute Lung Injury or 

ARDS. Chronic sequelae may include hyperreactive airways dysfunction, 

bronchiectasis, and recurrent infection. Late tsunami-lung includes necrotizing 

pneumonia and empyema secondary to aspiration of "tsunami water", mud, and 

particulate matter. This results in a pneumonic process clinically presenting 

four to six weeks after the initial aspiration, with radiographic features of 

cavitation, effusion, empyema, and secondary pneumothorax. Pathogens are 

polymicrobial and indigenous to the region, including aeromonas, pseudomonas, 

and streptococcal species. Fungi such as Pseudeallescheria boydii can result 

in disseminated brain abscesses. Burkholderia pseudomallei, the etiology of 

meliodosis, require prolonged antibiotic therapy. 32 Wounds contaminated 

with "tsunami water", soil, and particulate matter included staphylococcus, 

streptococcus, vibrio, aeromonas, pseudomonas, burkholderia, tetanus and 

fungi endemic to the area. 32 

Mold exposures may result from water damage during hurricanes and floods, 

especially in hot climates. Sufficient evidence has been found for an association 

between damp indoor spaces and mold and upper respiratory symptoms (nasal 

congestion and throat irritation) and lower respiratory symptoms (cough, 

wheeze and exacerbation of asthma), and opportunistic fungal infection in 

immunocompromised patients. 33 Levels of endotoxin, a by-product of bacteria 

metabolism, and (1-3)-b-D-glucan, a cell-wall component of fungi and other 

microorganisms, were shown to be elevated after the Katrina disaster in New 

Orleans. 34 Both these toxins have been associated with respiratory effects. 

Molds, the common term for multicellular fungi, and other fungi, may affect 

35, 36 

human health through three processes: allergy, infection and toxicity. 

Allergic responses to molds may be IgE or IgG mediated. 35 Exposure to fungal 

proteins can result in generation of IgE responses in the susceptible host (i.e., 

atopic individuals), which can lead to the development of allergic rhinitis and 

asthma. 33, 35, 36 Mold spores and fragments can produce allergic reactions in 

sensitive individuals, regardless of whether the mold is dead or alive. Penicillium 


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and Aspergillus species which are usually indoor molds, and the outdoor molds 

Cladosporium and Alternaria can all induce IgE responses. IgG-mediated 

responses and cell-mediated immunity against inhaled fungal proteins 

can result in development of hypersensitivity pneumonitis. This abnormal 

response may result after short or long-term exposure, but usually requires 

the inhalation of large quantities of fungal protein. 35 Finally, IgE responses to 

molds in allergic patients may result in allergic bronchopulmonary mycosis 

(also known as allergic bronchopulmonary aspergillosis when it is induced 

by Aspergillus sp.), or allergic fungal sinusitis. 

A very limited number of pathogenic fungi may cause pulmonary and systemic 

infection in non-immune compromised subjects. Blastomyces, Coccidioides, 

Cryptococcus, Hystoplasma and Paracoccidioides have all been reported 

as systemic pathogens in both, immune compromised and non-immune 

compromised subjects. Other fungi, such as Aspergillus and Candida have 

been associated with systemic infection in immune-compromised individuals. 

Different species of molds have been associated with superficial skin and 

mucosal infections that are extremely common. 

Irritant and toxic effects due to exposure to molds and mold products 

affecting the eyes, skin, nose, throat and lungs, have been described. Volatile 

compounds produced by molds and released directly into the air, known as 

microbial volatile organic compounds, and particulates from the cell walls 

of molds, including glucans and mannans in spores and hyphae fragments, 

have been reported as capable of inducing transient inflammatory reactions. 

Mycotoxins, low-molecular-weight chemicals produced by molds as secondary 

metabolites that are not required for the growth and reproduction of these 

organisms, have been associated with systemic toxicity especially via the 

ingestion of large amounts of moldy foods, especially in the veterinary setting. 37 

Ingestion of aflatoxins, mycotoxins produced by Aspergillus flavus and A. 

parasiticus, has been demonstrated as an important risk factor for hepatocellular 

carcinoma in humans. Organic dust toxic syndrome, a noninfectious, febrile 

illness associated with chills, malaise, myalgia, dry cough, dyspnea, headache 

and nausea in the presence of normal chest films, no hypoxemia and no 

sensitization, has been reported upon exposure to high concentration of fungi, 

bacteria and organic debris in settings such as agricultural works, silage and 

exposures to soiled grain. 38 

BIOLOGICAL TERRORISM AGENTS 

Biological terrorism agents have been classified by the Centers for Disease 

Control and Prevention (CDC) into three groups based on their potential 

for adverse health impact, mass casualties and death (Table 3-4.1). 39 As they 

have the greatest potential for mass casualties and death, category A agents 

(smallpox, anthrax, tularemia, plague and botulism) are the subject of this 

review and are described based on their pathogenesis and clinical presentation, 

laboratory diagnosis, treatment and infection control. 


Bioterrorism Agents and Threat Categories 

Category A Category B Category C 

Bacillus anthracis (Anthrax) 

Yersinia pestis (Plague) 

Variola Major (Smallpox) 

Clostridium Botulinum (Botulism) 

Francisella tularensis (Tularemia) 

Viral Hemorrhagic Fevers 

Coxiella Burnetti (Q Fever) 

Brucella species (brucellosis) 

Burkholderia mallei (Glanders) 

Ricin 

Clostridium perfringens Epsilon toxin 

Staphylococcus enterotoxin B 

Nipah virus 

Hantavirus 

Tickborne hemorrhagic fever viruses 

Tickborne encephalitis viruses 

Yellow fever 

Multi-drug resistant tuberculosis 

Table 3-4.1: Bioterrorism Agents and Threat Categories. (Adapted from Public Health 

Assessment of Potential Biological Terrorism Agents 39 ) 

Smallpox 

Smallpox last occurred in Somalia in 1977, but in recent years there has been 

renewed concern about its’ potential for use as a biological weapon. 40 The 

causative agent of smallpox, the variola virus, is a member of the Poxviridae 

family, sub-family Chordopoxvirinae, and genus Orthopoxvirus. This genus 

also includes vaccinia (used in the smallpox vaccine), monkeypox virus, 

camelpox, and cowpox. The variola virus is stable and maintains infectivity for 

long periods of time outside the human host. 41 Person-to-person transmission 

occurs by respiratory droplet nuclei dispersion. Although infrequent, infection 

has also been known to occur from contact with infected clothing, bedding, 

or other contaminated fomites. 42 

Pathogenesis and Clinical Presentation 

Following inhalation, the variola virus seeds the mucus membranes of the 

upper and lower respiratory tract and migrates to regional lymph nodes, where 

replication occurs, leading to viremia and end-organ dissemination. During the 

incubation phase (7 to 17 days) infected individuals are most likely asymptomatic, 

but may have low-grade temperature elevation or a mild, erythematous rash. 

Smallpox is not contagious during the incubation phase, but may be so during 

the prodrome phase which lasts two to four days and is characterized by 

the abrupt onset of high fever (greater than 104oF/40 oC), headache, nausea, 

vomiting and backache. These symptoms are sometimes accompanied by 

abdominal pain and delirium. 42,43 The eruption phase occurs two to four days 

later, beginning as small, red maculopapular lesions approximately two to three 

millimeters in diameter on the face, hands and forearms. Lower extremity 

lesions appear shortly thereafter. During the next two days, the skin lesions 

become distinctly papular and spread centrally to the trunk. Lesions on the 

mucous membranes of the oropharynx and oropharyngeal sections are highly 

infectious. Over the next two weeks, skin lesions progress synchronously from 

papules to vesicles to crusts. Desquamation then begins, virus particles are 

found in the fallen-off crusts, and patients remain infectious until all crusts 

fall off, a process that may take several more weeks. 

The mortality rate from smallpox is three percent in vaccinated individuals and 

30% in the unvaccinated. 44, 45 Death from smallpox is presumed to be secondary 

to a systemic inflammatory response syndrome, caused by overwhelming 

quantities of immune complexes and soluble variola antigen, which may 

result in severe hypotension during the second week of illness. Respiratory 

complications, including pneumonia and bronchitis are common. 44, 45 Severe 

intravascular volume and electrolyte imbalance may occur that may lead to 

Chapter 3-4 • Disaster-Related Infections: Pandemics, Post-Disaster, 

and Bioterrorism 

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242 

renal failure. Encephalitis and bacteremia may contribute to mortality. Two 

atypical manifestations of smallpox have higher mortality rates. 45 Hemorrhagic 

smallpox occurs in less than three percent of infected individuals, and is 

characterized by a short incubation period and an erythematous skin eruption 

that later becomes petechial and hemorrhagic, similar to the lesions seen in 

meningococcemia. The malignant form, or “flat smallpox,” also occurring in 

about 3% of infected individuals, is characterized by a fine-grained, reddish, 

non-pustular and confluent rash, occasionally with hemorrhage. Patients with 

hemorrhagic or malignant forms of smallpox have severe systemic illness and die 

within several days. Pulmonary edema occurs frequently in both hemorrhagic 

and malignant smallpox and contributes to the high mortality rates. 45 

The differential diagnosis of papulovesicular lesions that can be confused 

with smallpox includes: chickenpox (varicella), shingles (varicella zoster), 

disseminated herpes simplex, monkeypox, drug eruptions, generalized vaccinia, 

eczema vaccinatum, impetigo, bullous pemphigoid, erythema multiforme, 

molluscum contagiosum and secondary syphilis. Chickenpox (varicella) is the 

most common eruption that can be confused with smallpox. In contrast to the 

synchronous and centrifugal nature of the smallpox skin lesions, chicken pox 

(varicella) skin lesions are greatest on the trunk, spare the hands and soles, 

and are at multiple stages at any given time, with papules, vesicles, and crusts 

all present simultaneously (Table 3-4.2). 43,44 

Prodrome: 

Rash: 

Clinical Features in Smallpox and Chickenpox 

Smallpox Chickpox 

2-4 days of high fever, headache, 

backache, vomitting, 

and abdominal pain 

Starts in oral mucosa, 

spreads to face and expands 

centrifugally 

Palms/Soles: Common Rare 

Timing: 

Lesions appear and progress 

at same time 

Absent-mild, 1day 

Starts on trunk and expands 

centripetally 

Lesions occur in crops and 

at varied stages of maturation 

Pain: May be painful Often pruritic 

Depth Pitting and deep scars Superficial, doesn't scar 

Table 3-4.2: Distinguishing Clinical Features in Smallpox and Chickenpox 

Laboratory Diagnosis 

Confirmation of smallpox can be performed by the analysis of skin scrapings, 

vesicular fluid, and oropharyngeal swabs. Serologic testing is not useful in 

differentiating the variola virus from other orthopoxviruses. Laboratory 

specimens should only be manipulated and processed at laboratories with 

biosafety level 4 (BSL4) facilities. Local public health departments can assist 

in getting specimens to an appropriate laboratory. 


Treatment 

There is no FDA-approved drug for the treatment of smallpox. Patients should 

be vaccinated if the disease is in its early stage as vaccination may decrease 

symptom severity. 45 At the present time, treatment is supportive and includes 

appropriate antibacterial therapy for secondary skin infections, daily eye 

irrigation for severe cases, adequate nutrition and hydration. Topical treatment 

with idoxuridine can be considered for corneal lesions. Recent studies in 

animals suggest that cidofovir has activity against orthopoxviruses, including 

variola. Cidofovir®, given at the time of, or immediately following exposure, 

has the potential to prevent cowpox, vaccinia, and monkeypox in animal 

studies. 46 There is no evidence that the use of vaccinia immune globulin offers 

any survival or therapeutic benefit in patients infected with smallpox. 

Infection Control 

If an outbreak were to occur, it is anticipated that the rate of transmission may 

be as high as 10 new cases for every infected person. All individuals who have 

direct contact with the index case should be quarantined for 17 days. Home 

quarantine will be necessary in mass casualty situations. Healthcare workers 

caring for infected individuals should be vaccinated and use strict airborne 

and contact isolation procedures. 47,48,49 Infected patients should be placed in 

respiratory isolation and managed in a negative-pressure isolation room, if 

possible. Patients should remain isolated until all crusted lesions have fallen off. 

Inhalational Anthrax 

Inhalational anthrax occurred in 2001 after envelopes containing anthrax 

spores were sent through the United States Postal System and resulted in five 

out of 22 fatalities. 50, 51 Bacillus anthracis is a large, gram-positive, aerobic, 

spore-forming, non-motile bacillus. 


Virulence is determined by two plasmids that produce exotoxins. 52 One of 

these exotoxins, known as lethal factor, stimulates the over-production of 

cytokines, primarily tumor necrosis factor-alpha and interleukin-1-beta 

that cause macrophage lysis. The sudden release of inflammatory mediators 

appears to be responsible for the marked clinical toxicity of the bacteremic 

form of anthrax. 

The three forms of anthrax infection are determined by the route of entry – 

Cutaneous anthrax, 53 Gastrointestinalpharyngeal anthrax, 44, 45 and Inhalational 

anthrax. 54 The latter two forms can be fatal. 55 Anthrax spores are 1 to 1.5 

micrometers in size and easily deposit in the alveoli following inhalation. 

There, the endospores are phagocytosed by the pulmonary macrophages 

and transported via lymphatics to the mediastinal lymph nodes where they 

may remain dormant as “vegetative cells” for 10 to 60 days, or longer. Once 

germination in the lymph nodes is complete, replication occurs, releasing 

edema and lethal toxins that produce a hemorrhagic mediastinitis. In some 

patients, the initial symptoms are relatively mild and non-specific, resembling 

an upper respiratory tract infection. Fever, chills, fatigue, non-productive 

cough, nausea, dyspnea, chest pain and myalgias are common presenting 

complaints. 52, 55 These symptoms typically last for two to three days and then 


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244 

progress to severe, fulminant illness with dyspnea and shock. Some patients 

present with fulminant illness without prodromal symptoms. The number of 

spores inhaled, age of the patient and the underlying immune status most likely 

effect the clinical course of the disease. 56 Chest radiographs show mediastinal 

widening and pleural effusions. 57, 58 B. anthracis bacilli, bacillary fragments 

and anthrax antigens can be identified by immunohistochemistry (IHC). 57, 

58 Almost 50% of patients with inhalational anthrax develop hemorrhagic 

meningitis as a result of the hematogenous spread of B. anthracis. According 

to the Defense Intelligence Agency, the Lethal Dose to kill 50% of persons 

exposed (LD ) to weapons-grade anthrax is 2500 - 55,000 spores but, as few 

50 

as one to three spores may be sufficient to cause infection. 45,52 

A high index of suspicion is necessary to make the diagnosis of anthrax 

when patients present with a severe flu-like illness. One hundred percent of the 

patients with inhalational anthrax in 2001 had an abnormal chest radiograph 

with mediastinal widening, pleural effusions, consolidation and infiltrates. 

In this setting, the presence of mediastinal widening should be considered 

diagnostic of anthrax until proven otherwise. 57, 58 Hemorrhagic necrotizing 

44, 45 

lymphadenitis and mediastinitis are pathologic findings. 


B. anthracis is easily cultured from blood and other body fluids with standard 

microbiology techniques. The laboratory should be notified when the diagnosis 

of anthrax is being considered, as many hospital laboratories will not further 

characterize Bacillus species unless requested. Bio-safety level two conditions 

apply for workers handling specimens because most clinical specimens have 

spores in the vegetative state that are not easily transmitted. 52 The presence of 

large gram-positive rods in short chains that is positive on India ink staining 

is considered presumptive of B. anthracis, until culture results and other 

confirmatory tests are obtained. Nasal swabs are not recommended due to 

false negatives in patients with fatal inhalational anthrax. In June 2004, the 

FDA approved the Anthrax Quick Enzyme-linked Immunosorbent Assay 

(ELISA) test that detects antibodies to the PA (protective antigen) of B. anthracis 

exotoxin. The test can be completed in less than one hour and is available at 

hospital and commercial laboratories. 59 

Treatment 

Treatment improves survival if instituted promptly. 52 Ciprofloxacin® (400 mg) 

or doxycycline (100 mg) given intravenously, every 12 hours, with one to two 

other antibiotics is currently recommended. 52 Additional effective antibiotics 

include rifampin, vancomycin, imipenem, chloramphenicol, penicillin, 

ampicillin, clindamycin, and clarithromycin. Two survivors of inhalation 

anthrax during the United States outbreak received parenteral ciprofloxacin, 

clindamycin and rifampin. The addition of clindamycin may attenuate toxin 

production. 52 Ciprofloxacin® and Rifampin®, due to their excellent central 

nervous system penetration, should be used when meningitis is suspected. 

Although ciprofloxacin and doxycycline are relatively contraindicated for 

pregnant women and children, one of these agents should be given for the 

treatment of inhalational anthrax because of its high mortality rate. Therapy 

should continue for 60 days. Patients can be switched to oral therapy with 


ciprofloxacin (500mg twice daily) or doxycycline (100 mg twice daily) after 

fulminant symptoms have resolved. The use of systemic corticosteroids has 

been suggested for meningitis, severe edema, and airway compromise. 

Infection control 

All those exposed to anthrax should receive prophylaxis with oral ciprofloxacin 

(500mg twice daily), levofloxacin (500mg daily) or doxycycline (100mg twice 

daily) for 60 days, regardless of laboratory test results. 52 Nasal swabs can confirm 

exposure to anthrax, but cannot exclude it. High-dose penicillin or ampicillin 

may be an acceptable alternative for 60 days in patients who are allergic or 

intolerant to the recommended antibiotics. 52 More than 5,000 people received 

post-exposure prophylaxis following the 2001 United States outbreak, but only 

about half completed the 60-day course. 52 The main reasons for discontinuing 

therapy were gastrointestinal or neurologic side effects (75%) or a low-perceived 

risk (25%). The anthrax vaccine is not available to the general public. 

Tularemia 

Tularemia is a zoonosis found in a wide range of small mammals and is 

caused by Francisella tularensis, an intracellular, non-spore forming, aerobic 

gram-negative coccobacillus. It can survive in moist soil, water, and animal 

carcasses for many weeks. Transmission of F. tularensis to humans occurs 

predominantly through tick and flea bites, handling of infected animals, 

ingestion of contaminated food and water, and inhalation of the aerosolized 

organism. There is no human-to-human transmission of F. tularensis. In the 

United States, most cases are reported in spring and summer. As a biologic 

weapon, the organism would most likely be dispersed as an aerosol and cause 

mass casualties from an acute febrile illness that may progress to severe 

pneumonia. 60, 61 Hunters and trappers exposed to animal reservoirs are at high 

risk for exposure. 62 The WHO estimated that 50 kg of aerosolized F. tularensis 

dispersed over a metropolitan area of five million people could cause 19,000 

60, 61 

deaths and 250,000 incapacitating illnesses. 


The clinical manifestations of tularemia depend on the site of entry, exposure 

dose, virulence of the organism, and host immune factors. Tularemia can have 

various clinical presentations that have been classified as primary pneumonic, 

typhoidal, ulceroglandular, oculoglandular, oropharyngeal, and septic. 

The ulceroglandular form is the most common naturally occurring form of 

tularemia. After an incubation period of three to six days (range 1 to 25 days) 

following a vector bite or animal contact, patients present with symptoms 

of high fevers (85%), chills(52%), headache (45%), cough (38%) and myalgias 

(31%). They may also have malaise, chest pain, abdominal pain, nausea, 

vomiting, and diarrhea. Pulse-temperature dissociation is often seen. At the 

site of inoculation, a tender papule develops that later becomes a pustule and 

ulcerates. Lymph nodes draining the inoculation site become enlarged and 

painful (85%). Infected lymph nodes may become suppurative, ulcerate and 

remain enlarged for a long period of time. Exudative pharyngitis and tonsillitis 

may develop following ingestion of contaminated food or inhalation of the 

aerosolized organism. Pharyngeal ulceration and regional lymphadenopathy 


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may be present. A systemic disease caused by F. tularensis without lymph node 

enlargement and presenting with fever, diarrhea, dehydration, hypotension, 

and meningismus is referred to as the typhoidal form. 

The pneumonic form of tularemia may occur as a primary pleuropneumonia 

following the inhalation of aerosolized organisms or as a result of hematogenous 

spread from other sites of infection or following pharyngeal tularemia. 63 

After an inhalational exposure, constitutional symptoms, such as fever and 

chills, typically precede the onset of respiratory symptoms. The respiratory 

symptoms include a dry or minimally-productive cough, pleuritic chest pain, 

shortness of breath and hemoptysis. Pleural effusions, either unilateral or 

bilateral, can occur. Pneumonic tularemia can rapidly progress to respiratory 

failure with acute respiratory distress syndrome (ARDS), multi-organ failure, 

disseminated intravascular coagulation, rhabdomyolysis, renal failure, and 

hepatitis. 63,64 Rarely, peritonitis, pericarditis, appendicitis, osteomyelitis, 

erythema nodosum, and meningitis may occur. The mortality rate for untreated 

tularemic pneumonia is 60%, but with proper antibiotic therapy is decreased 

to less than three percent. 61 Chest radiographic findings in 50 patients with 

tularemia65 showed the following abnormalities: patchy airspace opacities 

(74%- unilateral in 54%); hilar adenopathy (32%- unilateral in 22%); pleural 

effusion (30%-unilateral in 20%); unilateral lobar or segmental opacities (18%); 

cavitation (16%); oval opacities (8%); and cardiomegaly with a pulmonary 

edema pattern (6%). Rare findings such as apical infiltrates, empyema with 

bronchopleural fistula, miliary pattern, residual cyst, and residual calcification 

occurring in less than five percent of patients were also reported. 65 


F. tularensis is difficult to culture. Culture media must contain cysteine or 

sulphydryl compounds for F. tularensis to grow. Notification of laboratory 

personnel that tularemia is suspected is essential. Routine diagnostic procedures 

can be performed in Biosafety Level Two conditions. Manipulation of cultures and 

other procedures that might produce aerosols or droplets should be conducted 

under Biosafety Level Three conditions. 61,62 Examination of secretions and biopsy 

specimens with direct fluorescent antibody or immunochemical stains may 

help to identify the organism. The diagnosis is often made through serologic 

testing using enzyme-linked immunosorbent assay (ELISA). Serological titers 

may not be elevated early in the course of disease. A four-fold rise is typically 

seen during the course of illness. A single tularemia antibody titer of 1:160 

or greater is supportive of the diagnosis. 61, 64 The combined use of ELISA and 

confirmatory Western blot analysis was found to be the most suitable approach 

to the serological diagnosis of tularemia. 66 Other diagnostic methods include 

antigen detection assays and polymerase chain reaction (PCR). 66 

Treatment 

Treatment for tularemia is streptomycin, one gram given intramuscularly (IM) 

twice daily. Gentamicin®, 5 mg/kg, given IM or intravenously (IV) once daily, can 

be used instead of streptomycin. 60,61,62,67 For children, the preferred antibiotics 

are streptomycin, 15 mg/kg, given IM twice daily (not to exceed 2 g/day) or 

gentamicin, 2.5 mg/kg, given IM or IV three times daily. Alternate choices are 

doxycycline, chloramphenicol, or ciprofloxacin. Gentamcin® is preferred over 


streptomycin for treatment during pregnancy. Treatment with streptomycin, 

gentamicin, or ciprofloxacin should be continued for 10 days. Treatment 

with doxycycline or chloramphenicol should be continued for 14 to 21 days. 

In a mass casualty setting caused by tularemia, the preferred antibiotics for 

adults and pregnant women are doxycycline, 100 mg, taken orally twice daily, 

or ciprofloxacin 500 mg, taken orally twice daily. For children, the preferred 

choices are doxycycline, 100 mg, taken orally twice daily if the child weighs 45 

kg or more, doxycycline, 2.2 mg/kg, taken orally twice daily if the child weighs 

less than 45 kg, or ciprofloxacin, 15 mg/kg, taken orally twice daily and not to 

exceed one gram/day. In immunosuppressed patients, either streptomycin or 

Gentamicin® is the preferred antibiotic in mass casualty situations. 61 


Individuals exposed to F. tularensis may be protected against systemic infection 

if they receive prophylactic antibiotics during the incubation period. For 

postexposure prophylaxis, either doxycycline, 100 mg, taken orally twice daily, 

or ciprofloxacin, 500 mg, taken orally twice daily for 14 days, is recommended. 

Both doxycycline and ciprofloxacin can be taken by pregnant women for 

postexposure prophylaxis, but ciprofloxacin is preferred. Postexposure prophylaxis 

for children is the same as treatment during mass casualty situations. 61 The 

current vaccine does not offer total protection against inhalational exposure 

and is not recommended for post-exposure prophylaxis. 60,61,62 

Plague 

Plague is a zoonotic infection, primarily seen in rodents and rabbits. 68 Plague 

is caused by Yersinia pestis, a gram negative, non-motile coccobacillus of the 

family Enterobacteriaceae. Plague is naturally transmitted by the bite of a 

plague-infected flea. Rodents, particularly rats and squirrels, are the natural 

reservoirs that transmit Y. pestis to fleas. Transmission to humans also occurs 

by direct contact with infected live or dead animals, inhalation of respiratory 

droplets from patients with pneumonic plague, or from direct contact with 

infected body fluids or tissue. 69,70,71 Over 90% of plague cases reported in the 

United States come from Arizona, New Mexico, California and Colorado. The 

majority of cases occur in spring and summer, when people come in contact 

with rodents and fleas. Aerosolized droplets of Y. pestis could be used as a 

biowarfare agent, resulting in the highly fatal pneumonic form of plague. 69 

Pneumonic plague is contagious from person to person and can result in a 

greater number of casualties than those initially exposed and infected. The 

WHO estimates that 50 kg of Y. pestis aerosolized over a population of five 

million people may result in 150,000 infections and 36,000 deaths. Intentional 

dispersion of Y. pestis as an aerosol will lead to pneumonic plague, while the 

release of infected fleas will usually result in bubonic or septicemic plague. 69 


The lipopolysaccharide endotoxin is responsible for the systemic inflammatory 

response, acute respiratory distress syndrome, and multiorgan failure. 69-71 

The incubation period and clinical manifestations of plague vary according 

to mode of transmission. Of the plague cases seen in the United States, 85% 

are bubonic plague, 10 - 15% are primary septicemic plague and less than 


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one percent are primary pneumonic plague. Bubonic plague may progress to 

septicemic or pneumonic plague in 23% and 9% of cases respectively. 68,69,70,71 

Inhalation of infected droplets of Y. pestis results in primary pneumonic plague. 

The primary pneumonic form is rapid in onset with an incubation period of 

one to six days (mean: two to four days). Presenting features are fevers, chills, 

cough, and blood-tinged sputum. Following inhalation into the lungs, Y. 

pestis organisms are engulfed by macrophages, transported to the lymphatic 

system and regional lymph nodes, followed by bacteremia that may seed 

other organs such as the lung, spleen, liver, skin, and mucous membranes. 

Secondary pneumonic plague can occur as sequelae of bubonic or primary 

septicemic plague. Primary septicemic plague occurs when there is direct 

entry of Y. pestis bacilli into the bloodstream. Other rare forms of plague are 

plague meningitis and plague pharyngitis. 70 

Bubonic plague involves lymphadenitis, buboes and severe pain (Figure 

3-4.1). Based on site of inoculation, palpable, regional buboes appear in the 

groin, axillae or cervical regions, with erythema of the overlying skin. A 

minority of patients exposed to Y. pestis develop septicemic plague, either as 

a primary form (without buboes) or secondary to the hematogenous spread 

of bubonic plague. 

Figure 3-4.1: Bubonic plague with the characteristic bubo. From CDC website: http://www. 

cdc.gov/ncidod/dvbid/plague/diagnosis 

The clinical features are similar to those of gram-negative sepsis, with fever, 

chills, nausea, vomiting, hypotension, renal failure and ARDS. Untreated, the 

mortality rate of septicemic plague is 100%. 68-71 Primary pneumonic plague 

is characterized by a severe, rapidly progressive pneumonia with septicemic 

features that is rapidly fatal if not treated within 24 hours. Following an 

incubation period of one to six days, there is a rapid onset of fever, dyspnea, 

chest pain, and cough that may be productive of bloody, watery, or purulent 

sputum. Tachycardia, cyanosis, nausea, vomiting, diarrhea, and abdominal 

pain may occur. Buboes are generally absent, but may develop in the cervical 

area. Acute respiratory failure requiring mechanical ventilation may occur. 

Strict respiratory isolation should be observed, as pneumonic plague is highly 

contagious. 68 Chest radiographs show bilateral alveolar opacities (89%) and 

pleural effusions (55%). Cavitations may occur. 72, 73 Alveolar opacities in secondary 

pneumonic plague may have a nodular appearance. Mediastinal adenopathy is 

very rare in primary pneumonic plague. This can help to distinguish primary 


pneumonic plague from anthrax if bioterrorism is suspected and a causative 

agent has not yet been identified72, 73 . Without prompt treatment, the mortality 

rate of primary pneumonic plague is 100%. 70, 71 Secondary pneumonic plague, 

from hematogenous spread, occurs in approximately 12% of individuals with 

bubonic plague or primary septicemic plague. It typically presents as a severe 

bronchopneumonia (Figure 3-4.2). Common symptoms include cough, dyspnea, 

chest pain and hemoptysis. Chest radiographs typically show bilateral, patchy 

alveolar infiltrates that may progress to consolidation. In contrast to primary 

72, 73 

pneumonic plague, mediastinal, cervical and hilar adenopathy may occur. 

Figure 3-4.2: A 38-year old male from Himachal Pradesh admitted with complaints of fever, 

cough, hemoptysis and dyspnea. There is endemicity of pneumonic plague where the 

patient came from due to the prevalent custom of hunting wild rats and rodents. Sputum 

examination showed Yersinia pestis. Patient was successfully treated with antibiotics. (Chest 

radiograph is courtesy of Dr Sanjay Jain, Additional Professor, Dept of Internal Medicine and 

Dr. Surinder K. Jindal, Professor of Medicine, Postgraduate Institute of Medical Education 

and Research, Chandigarh, India) 


The presence of gram-negative rods in bloody sputum of an immunocompetent 

host should suggest pneumonic plague. Cultures may be positive for Y. pestis 

within 24 to 48 hours. 69 Misidentification of Y. pestis may occur with automated 

bacterial identification devices. Direct fluorescent antibody staining for Y. 

pestis and dipstick antigen detection tests are highly specific. 69 

Treatment 

Recommendations of the Working Group on Civilian Biodefense for treatment 

of adult patients with plague in a small, contained casualty setting is 

streptomycin one gram IM, given twice daily; gentamicin, five mg/kg IM or 

IV, once daily; or a 2 mg/kg loading dose of gentamicin followed by 1.7 mg/ 

kg IM or IV three times daily. 68-71 For children, the preferred antibiotics are 

streptomycin, 15 mg/kg IM, given twice daily (maximum dose of two grams/ 

day), or Gentamicin®, 2.5 mg/kg IM or IV, given three times daily. Alternate 

choices include doxycycline, ciprofloxacin or chloramphenicol. The duration 

of treatment is 10 days. In pregnant or breast-feeding mothers, the treatment of 

choice is Gentamicin®. For breast-feeding mothers and infants, treatment with 


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250 

gentamicin is recommended. In a mass casualty situation from the intentional 

release of plague, the Working Group on Civilian Biodefense recommends the 

use of doxycycline, 100 mg, taken orally twice daily, or ciprofloxacin, 500 mg, 

taken orally twice daily for adults and pregnant women, both for treatment and 

post-exposure prophylaxis. For children, the preferred choices are the adult 

dose of doxycycline if the child is over 45 kg weight and 2.2 mg/kg orally twice 

daily for child under 45 kg weight. Children may also be given ciprofloxacin, 

20mg/kg, taken orally twice daily. For breast-feeding mothers and infants, 

treatment with doxycycline is recommended. The duration of treatment is 

10 days. 


All individuals who come within two meters of a pneumonic plague patient 

should receive postexposure prophylaxis. 74 The vaccination against pneumonic 

plague does not provide adequate protection and therefore is not recommended 

biowarfare setting. 74 Patients suspected of plague should be isolated and antibiotic 

therapy should be instituted promptly. 75 Universal exposure precautions, 

respiratory isolation using droplet precautions and special handling of blood 

and discharge from buboes must be followed. In cases of pneumonic plague, 

strictly enforced respiratory isolation in addition to the use of masks, gloves, 

gowns and eye protection must be continued for the first few days of antibiotic 

therapy. Following two to four days of therapy with appropriate antibiotics, 

patients may be removed from isolation. 75 Laboratory workers must be warned 

of potential plague infection. 

Botulinum 

Botulinum is an extremely-potent toxin produced by Clostridium botulinum, 

an anaerobic, spore-forming bacterium that is present in the soil. Botulinum 

toxin has been designated as a Category A bioterrorism threat by the CDC. 1 

It has been estimated that one gram of botulinum toxin added to milk that is 

commercially-distributed and consumed by 568,000 individuals can result in 

100,000 cases of botulism. One gram of botulinum toxin has the capacity to 

kill over one million persons if aerosolized. 76 Botulinum is not a respiratory 

infection; if aerosolized the route of transmission would be through lungs, 

but the effects would still be neurologic. 

Pathogenesis and Clinical Manifestations 

There are three forms of naturally-occurring botulism: foodborne botulism, 

wound botulism, and intestinal (infant and adult) botulism. 76,77 All forms of 

botulism can produce a serious paralytic illness leading to respiratory failure 

and death. 

Treatment 

Treatment of botulism includes supportive care, mechanical support for 

76, 77 

inadequate ventilation and the administration of botulinum antitoxin. 

Prompt administration of botulinum antitoxin can reduce nerve damage and 

disease severity. However, any muscle paralysis existing prior to antitoxin 


administration will not be reversed. The goal of antitoxin therapy is to prevent 

further paralysis by neutralizing unbound botulinum toxin in the circulation. 

If the type of botulinum toxin is known, a type-specific antitoxin can be given. 

If the toxin type is not known, the trivalent antitoxin containing neutralizing 

antibodies against botulinum toxin types A, B and E should be given. Botulinum 

antitoxin is available from the CDC through state and local health departments. 

If another type of toxin is intentionally dispersed during a bioterrorism attack, 

consideration may be given for the use of an investigational heptavalent 

antitoxin (A B C D E F G), maintained by the United States Department of 

Defense. Patients should be carefully assessed for refractory problems, such 

as rapidly-progressing paralysis, severe airway obstruction or overwhelming 

respiratory tract secretions. 


Person-to-person transmission does not occur. In the United States, a pentavalent 

botulinum toxoid is available from the CDC for the immunization of laboratory 

workers who may be exposed to botulinum toxin and for the protection of 

military personnel in the event of a biowarfare attack. 78 Mass immunization 

of the public with botulinum toxoid is not recommended or available. It takes 

several months to attain acquired immunity following the administration of 

botulinum toxoid and, therefore, it is not effective for post-exposure prophylaxis. 

REFERENCES 

1. Rosenberg J, Israel LM. Clinical Toxicology. In: J. LaDou, ed.: Current 

Occupational and Environmental Medicine, 3rd edition. New York: Lange 

Medical Books, 2004; 179-187). 

2. Harber P. Environmental Monitoring. In: P Harber, MB Schenker, JR 

Balmes. Occupational and Environmental Respiratory Disease, 1st edition. 

St Louis: Mosby, 1996; pg. 151-166. 

3. Webster RG, Peiris M, Chen H, and Guan Y. H5N1 outbreaks and enzootic 

influenza. Emerg Infect Dis. Available from http://www.cdc.gov/ncidod/ 

EID/vol12no01/05-1024.htm. Accessed April 6, 2007. 

4. de Jong MD Bach VC, Phan TQ, Vo MH, et al. Fatal influenza A (H5N1) in 

a child presenting with diarrhea followed by coma. N Engl J Med 2005; 

352:686-91. 

5. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat 

S, Sawanpanyalert P, Kijphati R, et al. Human disease from influenza A 

(H5N1), Thailand, 2004. Emerg Infect Dis. Available from http://www.cdc. 

gov/ncidod/EID/vol11no02/04-1061.htm. Accessed April 6, 2007. 

6. World Health Organization. Confirmed human cases of avian influenza 

A(H5N1). 2005 [cited 2005 Oct 31]. Available from http://www.who.int/csr/ 

disease/avian_influenza/country/en/ Accesssed April 6, 2007. 

7. Nicholson KG. Human Influenza. In: Nicholson K, Webster R, Hay A, eds. 

Textbook of Influenza. Second ed. Oxford: Blackwell, 2000. 

8. Potter CW. Influenza viruses. Clinical Virology, 1998 


251

252 

9. Kilbourne E. Influenza. 1st ed. New York: Plenum Publishing, 1987. 

10. Cox NJ, Subbarao K. Influenza. Lancet 1999; 354:1277-82. 

11. Schwarzmann SW, Adler JL, Sullivan RJ, Jr., Marine WM. Bacterial pneumonia 

during the Hong Kong influenza epidemic of 1968-1969. Arch Intern Med 

1971; 127:1037-41. 

12. Ruben FL, Cate TR. Influenza pneumonia. Semin Respir Infect 1987; 2:122- 

9. 

13. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD et al. Avian 

influenza A (H5N1) infection in humans. N Engl J Med 2005; 353:1374-85. 

14. Centers for Disease Control and Prevention. Interim Interim Guidance 

for the use of masks to contorl influenza transmission. [cited 2005 Aug 8]. 

www.cdc.gov/flu/professionals/infectioncontrol/maskguidance.htm. 

Accessed April 6, 2007. 

15. Centers for Disease Control and Prevention. FluSurge 2.0 software program. 

[cited 2006 Dec 28]. www.cdc.gov/flu/tools/flusurge/. Accessed April 6, 

2007. 

16. McClain DJ. Smallpox. In: Hogan DE and Burstein JL eds. Disaster Medicine. 

Lippincott Williams and Wilkins, Philadelphia PA, 2002 pg 23-33. 

17. Disaster Epidemiology. Lancet 1990: 336:845. 

18. Cosgrave J. Refugee density and dependence: practical implications of 

camp size. Disasters. 1996;20:261-270. 

19. Toole MJ, Waldman RJ. Prevention of excess mortality in refugee and 

displaced populations in developing countries. JAMA. 1990; 263:3296- 

3302. 

20. Surmieda MR, Lopez JM, Abad-Viola G, et al. Surveillance in evacuation 

camps after the eruption of Mt. Pinatubo, Philippines. MMWR. 1992; 41:9. 

21. Lee LE Fonesca V, Brett KM, et al. Active morbidity surveillance after 

Hurricane Andrew – Florida, 1992. JAMA. 1993;270:591-594. 

22. Toole MJ, Galson S, Brady W. Are war and public health compatible? Lancet. 

1993;341:1193-1196. 

23. World Health Organization. TB/HIV: a clinical manual, 2nd ed. 

Geneva: World Health Organization. http.://whqlibdoc.who.int/ 

publications/2004/9241546344.pdf. 

24. Centers of Disease Control and Prevention. Surveillance in evacuation 

camps after the eruption of Mt. Pinatubo, Philippines. MMWR 1992; 41:9. 

25. Cohen S. Measles. In: Antosia RE and Cahill JD eds. Handbook of Bioterrorism 

and Disaster Medicine. Springer Science and Business Media, NY, NY, 

2006 pgs. 245-247 

26. Mason J, Cavalie P. Malaria epidemic in Haiti following a hurricane. Am 

J Trop Med Hyg. 1965;14:533. 


27. Cahill JD. Malaria. In: Antosia RE and Cahill JD eds. Handbook of Bioterrorism 

and Disaster Medicine. Springer Science and Business Media, NY, NY, 

2006 pgs. 253-257 

28. Wilder-Smith A, Schwartz E. Dengue in Travelers. N Engl J Med, 2005; 353: 

924-932 

29. Brillman JC, Sklar DP, David KD, et al. Hantavirus emergency department 

response to a disaster from an emerging pathogen. Ann Emerg Med. 

1994;24:429-436. 

30. Schneider E, Hajjeh RA, Spiegel RA, et al. A coccidiodomycosis outbreak 

following the Northridge California earthquake. JAMA. 1997;227:904-908. 

31. Wattanawaitunechai C, Peacock SJ, Jitpratoom P. Tsunami in Thailand 

–Disaster Management in a District Hospital. N Engl J Med, 2005; 352: 

962-964 

32. Kao AY, Munandar R, Ferrara SL, et. Al. A 17 year-old girl with respiratory 

distress and hemiparesis after surviving a tsunami. N Engl J Med, 2005; 

352: 2628-2635 

33. Institute Of Medicine. Damp indoor spaces and health. Washington, D.C.: 

National Academic Press; 2004 

34. Centers for Disease Control and Prevention. Health concerns associated 

with mold in water-damaged homes after Hurricanes Katrina and Rita – 

New Orleans area, Louisiana, October 2003. Morb Mortal Wkly Rep, 2006; 

55: 41-44 

35. American College of Occupational and Environmental Medicine. Evidence 

Based Statements: Adverse Human Effects Associated with Molds in the 

Indoor Environment. J Occup Environ Med, 2003; 45: 470-478. 

36. Bush RK, Portnoy JM, Saxon A, Terr AI, Wood RA. The medical effects of 

mold exposure. J Allergy Clin Immunol, 2006; 117: 326-333. 

37. Etzel RA. Mycotoxins. JAMA, 2002; 287: 425-427. 

38. Von Essen S, Robbins RA, Thompson AB, Rennard SI. Organic dust toxic 

syndrome: an acute febrile reaction to organic dust exposure distinct from 

hypersensitivity pneumonitis. J Toxicol Clin Toxicol, 1990; 28: 389-420. 

39. Rotz LD, Khan AS, Lillibridge SR, et al. Public health assessment of potential 

biological terrorism agents. Emerg Infect Dis 8: 225, 2002. 

40. Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a biological 

weapon: medical and public health management. JAMA 281: 2127, 1999. 

41. Noble J, Rich JA. Transmission of smallpox by contact and by aerosol routes 

in Macaca irus. Bull World Health Organ 40: 279, 1969. 

42. Breman JG, Henderson DA. Diagnosis and management of smallpox. N 

Engl J Med 346: 1300, 2002. 

43. MacCallum FO, McDonald JR. Survival of variola virus in raw cotton. Bull 

World Health Organ 16: 247, 1957. 


253

254 

44. Marik PE, Bowles SA. Medical aspects of biologic and chemical agents of 

mass destruction. In: Irwin RS, Rippe JM, eds. Intensive Care Medicine, 

5th Edition. Philadelphia: Lippincott, Williams and Wilkins; 2003: p. 823. 

45. McClain DJ. Smallpox. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical 

Aspects of Chemical and Biological Warfare. In: Zajtchuk R, Bellamy RF, 

eds. Textbook of Military Medicine, Part I: Warfare, Weaponry and the 

Casualty. Washington, D.C.: United States Department of the Army, Office 

of the Surgeon General and Borden Institute; 1997: p. 539. 

46. Harrison SC, Alberts B, Ehrenfeld E, et al. Discovery of antivirals against 

smallpox. Proc National Acad Sci USA 101: 11178, 2004. 

47. Centers for Disease Control and Prevention. Recommendations for using 

smallpox vaccine in a pre-event vaccination program: Supplemental 

recommendations of the Advisory Committee on Immunization Practices 

(ACIP) and the Healthcare Infection Control Practices Advisory Committee 

(HICPAC). Morb Mortal Wkly Rep 52(RR07): 1, 2003. 

48. Mientka M. Department of Defense smallpox policy revised after deaths. 

U.S. Medicine; May 2003: p. 8. 

49. Casey CG, Iskander JK, Roper MH, et al. Adverse effects associated with 

smallpox vaccination in the United States, January-October 2003. JAMA 

294: 2734, 2005. 

50. Bush LM, Abrams BH, Beall A, Johnson CC. Index case of fatal inhalational 

anthrax due to bioterrorism in the United States. N Engl J Med 345: 1607. 

2001. 

51. Hughes J, Gerberding JL. Anthrax bioterrorism: Lessons learned and future 

directions. Emerg Infect Dis 8: 1013, 2002. 

52. Inglesby TV, O’Toole T, Henderson DA, et al. Anthrax as a biological weapon. 

JAMA 287: 2236, 2002. 

53. Freedman A, Afonja O, Chang, MW, et al. Cutaneous anthrax associated 

with microangiopathic hemolytic anemia and coagulopathy in a 7-monthold 

infant. JAMA 287: 869, 2002. 

54. Shafazand S, Doyle R, Ruoss S, et al. Inhalational anthrax: epidemiology, 

diagnosis and management. Chest 116: 1369, 1999. 

55. Mina B, Dym JP, Kuepper F, et al. Fatal inhalational anthrax with unknown 

source of exposure in a 61-year-old woman in New York City. JAMA 287: 

858, 2002. 

56. Guarner J, Jernigan JA, Shieh WJ, et al. Pathology and pathogenesis of 

bioterrorism-related inhalational anthrax. Am J Path 163: 701, 2003. 

57. Krol CM, Uszynski M, Dillon EH, et al. Dynamic CT features of inhalational 

anthrax infection. AJR 178: 1063, 2002. 


58. Earls JP, Cerva D, Berman E, et al. Inhalational anthrax after bioterrorism 

exposure: spectrum of imaging findings in two surviving patients. Radiology 

222: 305, 2002. 

59. Centers for Disease Control and Prevention. CDC collaboration yields 

new test for anthrax (press release). Atlanta, Georgia: Centers for Disease 

Control and Prevention; June 7, 2004. Available at URL: http://www.cdc. 

gov/od/oc/media/pressre/r040607.htm 

60. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and 

management of patients exposed to biological warfare agents. JAMA 278: 

399, 1997. 

61. Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological 


62. Centers for Disease Control and Prevention. Tularemia – United States, 

1990-2000. MMWR Morbid Mortal Wkly Rep 51: 182, 2002. 

63. Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak of primary 

pneumonic tularemia on Martha’s Vineyard. N Engl J Med 345: 1601, 2001. 

64. Ellis J, Oyston PCF, Green M, et al. Tularemia. Clin Microbiol Rev 15 : 631, 

2002. 

65. Rubin SA. Radiographic spectrum of pleuropulmonary tularemia. Am J 

Roentgenol 131: 277, 1978. 

66. Johansson A, Forsman M, Sjostedt A. The development of tools for diagnosis 

of tularemia and typing of Francisella tularensis. APIMS 112: 898, 2004. 

67. Enderlin G, Morales L, Jacobs RF, et al. Streptomycin and alternative agents 

for the treatment of tularemia: review of the literature. Clin Infect Dis 19: 

42, 1994. 

68. Inglesby TV, David T. Dennis DT, Henderson DA, et al. Plague as a biological 


69. Centers for Disease Control and Prevention. Recognition of illness associated 

with the intentional release of a biologic agent. MMWR Morbid Mortal 

Wkly Rep 50: 893, 2001. 

70. Centers for Disease Control and Prevention. Human plague – United States, 

1993-1994. MMWR Morbid Mortal Wkly Rep 43: 242, 1994. 

71. Centers for Disease Control and Prevention. Pneumonic plague - Arizona, 

1992. MMWR Morbid Mortal Wkly Rep 41:737, 1992. 

72. Alsofrom DJ, Mettler FA, Mann JM. Radiographic manifestations of plague 

in New Mexico, 1975-1980. A review of 42 proved cases. Radiology 139: 561, 

1981. 

73. Ketai L, Alrahji AA, Hart B, et al. Radiologic manifestations of potential 

bioterrorist agents of infection. Am J Roentgenol 180: 565, 2003. 


255

256 

74. Advisory Committee on Immunization Practices, Centers for Disease 

Control and Prevention. Prevention of plague: recommendations of the 

Advisory Committee on Immunization Practices (ACIP). MMWR Morbid 

Mortal Wkly Rep 45(RR14): 1, 1996. 

75. Centers for Disease Control and Prevention. Plague: Prevention and 

Control. Atlanta, Georgia: Centers for Disease Control and Prevention; 

2006. Available at URL: http://www.cdc.gov/NCIDOD/DVBID/plague/ 

prevent.htm. Accessed March 24, 2007. 

76. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological 


77. Centers for Disease Control and Prevention. Botulism in the United States, 

1899-1996. Handbook for epidemiologists, clinicians, and laboratory 

workers. Atlanta, Georgia: Centers for Disease Control and Prevention; 

1998. 

78. Taysse L, Daulon S, Calvet J, et al. Induction of acute lung injury after 

intranasal administration of toxin botulinum a complex. Toxicol Pathol 

33: 336, 2005. 


Chapter 3-5 

World Trade Center 

Respiratory Diseases 

By Dr. David J. Prezant MD, Dr. Kerry J. Kelly MD, 

Dr. Stephen Levin MD, Dr. Michael Weiden MD, 

and Dr. Thomas K. Aldrich, MD 

INTRODUCTION 

After the attack on and the collapse of the World Trade Center (WTC) towers, 

fire fighters, other rescue/recovery workers, volunteers and community 

members were exposed to high concentrations of aerosolized particulate 

matter and to incomplete products of combustion that were produced during 

the fires that continued from the first day on September 11, 2001 (9/11) to the 

middle of December 2001. Fire fighters from the Fire Department City of New 

York (FDNY) operated continuously during the days, weeks and months that 

followed, suffering some of the greatest exposures. Because environmental 

monitoring was not available immediately, we may never know the full extent 

of the chemical gaseous exposure but the dust has been well-characterized 

and shown to be highly-alkaline and inflammatory in nature. Approximately 

70% of the buildings’ structural components were pulverized 1 and the collapse 

produced a plume of dust and ash that spread throughout lower Manhattan 

and beyond. Hydrocarbons, PCBs (polychlorinated biphenyls), dioxins, volatile 

organic compounds, asbestos, silicates, heavy metals and other potentiallycarcinogenic 

compounds were found in WTC dust. 1,2 Environmental controls 

and effective respiratory protection (e.g., fit-tested P-100 respirators) are often 

unavailable during the initial rescue effort and adherence with proper use 

guidelines is typically difficult to achieve during prolonged rescue/recovery 

efforts and the WTC response was no exception. 3 

The subject of this chapter is to review what we currently know about the 

respiratory health consequences of WTC dust exposure. Much of this work 

has been previously published in various forums. 4,5,6,7 Because there has been 

little scientific study on the respiratory consequences of acute and/or subacute 

exposures to respirable particulates and chemical vapors/gases/fumes 

after other disasters, much of what we learn about the WTC is groundbreaking 

science. Important for all fire fighters and first responders, this knowledge 

will help not only those who were exposed to WTC dust but, should also be 

transferable to help those who may be exposed at future disasters. 

What we do know from prior disasters is that after smoke inhalation, asthma 

(bronchial hyperreactivity or reversible airways obstruction that increases with 

irritant exposures and reverses with bronchodilators) and bronchitis (productive 

cough) may occur within hours8,9,10 and one study showed persistent airway 

hyperreactivity in 11 of 13 subjects at three-months post-exposure. 10 Following 

Chapter 3-5 • World Trade Center Respiratory Diseases 257

258 Chapter 3-5 • World Trade Center Respiratory Diseases 

the Mt. St. Helens eruption in 1980, hospital visits for pediatric asthma were 

increased in Seattle Washington, presumably related to exposures to aerosolized 

volcanic dust. 11 During building collapses, aerosolized exposure to construction 

materials (ex. gypsum-containing wallboard, cement, glass, and man-made 

vitreous fibers, heavy metals) have been implicated in inflammatory syndromes 

involving the respiratory mucosa and lung parenchyma. 12,13 Acute exposures 

to chemical gases, vapors and fumes may result in airway hyperreactivity and 

when this occurs in non-smokers without a prior history of asthma or allergies, 

it is often referred to as the reactive airways disorders syndrome (RADS), a 

variant of irritant-induced asthma. 14 After the Union Carbide Chemical Plant 

explosion in Bhopal, India, studies documented an increased loss of pulmonary 

function and an increase in the prevalence of obstructive airways diseases 

such as asthma and chronic bronchitis. 15,16,17 Although the most common 

respiratory disease pattern after disaster-related exposures to dusts, gases, 

vapors and fumes is obstructive airways diseases, lung inflammation and 

fibrosis can occur. For example, pneumonitis (a life-threatening disease that 

results in fibrosis thereby blocking oxygen absorption) has been reported in 

US military personnel deployed in or near Iraq after exposure to fine airborne 

sand/dust18 and has been reported in chronic occupational exposures to coal, 

silica, asbestos, heavy metals and other dusts. 19,20,21,22,23,24 

After the WTC, there is abundant evidence that the upper and lower respiratory 

symptoms were the result of aerosolized WTC dust, coated with numerous 

chemicals, that was inhaled and ingested. A clear exposure-response gradient, 

with the highest symptom prevalence found in those directly exposed to the 

dust cloud, arriving during the morning of 9/11 was first demonstrated in FDNY 

fire fighters25 and confirmed in other exposed groups. 26 Ninety-five percent 

of the respirable WTC dust was composed of large particulate (≥10 microns in 

diameter) matter. 1 Particles of this size have conventionally been thought to 

be filtered by the upper respiratory tract, rarely entering the lower respiratory 

structures. 27 However, there are a number of reasons to expect lower airways 

also to be at risk from the dust cloud. First, it has been shown that alkaline dust 

impairs nasal clearance mechanisms, 27 and most WTC dust samples had a pH 

greater than 101 . Second, the nasal filtration system is optimally functional 

during restful breathing. WTC rescue/recovery workers, as a consequence of 

their work activities (moderate to high level physical exertion), were breathing 

at high minute ventilations where mouth breathing predominates. Third, 

although only five percent of the WTC dust was smaller than 10 microns in 

diameter, the extraordinary volume of dust in the air meant that the respirable 

fraction (particles less than 10 microns) still represented a significant amount 

of the dust. Similarly, although only a small percentage of particles larger than 

10 microns tend to impact in lower airways, the huge magnitude of the WTC 

dust cloud meant that a small percentage of the larger particles that penetrated 

deep into the lung may have added up to a significant amount. In fact, in a study 

of 39 FDNY fire fighters 10 months after exposure, 28 it was demonstrated the 

WTC dust did make it down into the lower airways, as particulate matter (>10 

microns) consistent with WTC dust, with associated increases in inflammatory 

cells and cytokines in induced sputum. Finally, compared to dust, inhalation 

of vapors, fumes, and gases during the first days at Ground Zero had equal if 

not greater potential for inducing airway or lung injuries.

Respiratory health consequences after aerosolized exposures to highconcentrations 

of particulates and chemicals during any disaster are thought 

to occur from chronic inflammation and can be grouped into four major 

categories: 

1. Upper respiratory disease including chronic rhinosinusitis sometimes 

referred to in this setting as reactive upper airways dysfunction syndrome 

(RUDS). 

2. Lower respiratory disease including asthma sometimes referred to in 

this setting as reactive (lower) airways dysfunction syndrome (RADS), 

bronchitis and chronic obstructive airways diseases. 

3. Parenchymal or interstitial lung diseases including pneumonitis, 

sarcoidosis, pulmonary fibrosis, bronchiolitis obliterans (fixed airways 

obstruction) and incidental pulmonary nodules. 

4. Cancers of the lung and pleura. Cancers are late emerging diseases, but 

the first three categories (upper, lower and parenchymal respiratory 

diseases) have already been well documented in WTC exposed rescue/ 

recovery workers, presenting early on as the “WTC Cough Syndrome.” 

The WTC Cough Syndrome was first reported by the FDNY Bureau of Health 

Services after 9/11, in a 2002 article published in the New England Journal of 

Medicine 25 and is a chronic cough syndrome, thought to be a consequence of 

persistent bronchitis (usually asthmatic), rhinosinusitis, gastroesophageal 

disorder (GERD), or any combination of the three after exposure to WTC 

dust. During the first six months following the WTC attack, FDNY described a 

syndrome of clinical, physiologic and radiographic abnormalities associated 

with airway inflammation in an initial cohort of 332 FDNY rescue workers. 

Because so many were affected, the case definition specified a persistent cough 

severe enough to require at least four weeks of continuous leave (medical, 

light duty or retirement) with onset during the six months following the WTC 

collapse, but future studies have not had medical leave as a requirement. 

In 2007, FDNY reported that between 9/11 and 6/30/07, 1,847 (~13%) FDNY 

members had met this strict case definition and 728 have qualified for permanent 

respiratory disability benefits based on persistent abnormal pulmonary function 

tests including, when indicated, methacholine challenge testing. 29 By 2009, 

over 1,000 have qualified for permanent respiratory disability benefits. Clinical 

symptoms were consistent with aero-digestive mucosal inflammation, with a 

high rate of GERD complaints (87%). 25 Physiologic evidence of asthmatic airway 

inflammation in those with the syndrome included response to bronchodilators 

(63% of those diagnosed) and nonspecific bronchial hyperreactivity determined 

by methacholine challenge testing (24% of those diagnosed), indicating that 

these FDNY members had a high rate of asthmatic physiology. 25 Radiological 

confirmation of airway inflammation in these fire fighters included CT scan 

evidence of air-trapping (abnormal retention of air in the lungs after expiration 

in 51%, and bronchial wall thickening in 24%). 25 Both air-trapping and bronchial 

wall thickening are typically due to airways obstructions such as asthma, 

chronic bronchitis or emphysema. The incidence of WTC Cough Syndrome 

increased as WTC dust exposure intensity (estimated by initial arrival time at 

the WTC site) increased. Nearly all FDNY fire fighters and EMTs who developed 

WTC cough syndrome had been exposed during the first 48 hours post-collapse 

and most had been exposed during the morning of 9/11. 25,30 

Chapter 3-5 • World Trade Center Respiratory Diseases 

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UPPER RESPIRATORY DISEASE 

Reactive Upper Airways Dysfunction Syndrome (RUDS) & 

Chronic Rhinosinusitis 

RUDS is defined as chronic rhinosinusitis (nasal and/or sinus inflammation) 

initiated by high level exposure to inhaled irritants, with recurrence of symptoms 

after re-exposure to irritants. Diagnosis depends largely on symptoms (nasal 

congestion, drip, sinus tenderness, sore throat and/or headaches), and there is 

no simple way to quantify the severity of the condition. Upper airways symptoms 

have been described in various occupational groups involved in rescue, 

recovery and cleanup at the WTC site, with higher prevalence of symptoms 

in those workers that were more highly exposed. In 10,378 previously-healthy 

FDNY rescue workers, stratified for severity of exposure by arrival time at the 

WTC site, self-reported chronic sinus congestion and/or drip was reported by 

less than five percent pre-WTC and was present in 80% on day one (9/11), 48% 

during the first year post-collapse and remained at 45% during the next two 

to four years 29,30 (Figure 3-5.1). In this same group, sore or hoarse throat was 

reported in 63% during the first year post-collapse and 36% during the next two 

to four years 29,30 (Figure 3-5.1). As with the WTC Cough Syndrome, an exposure 

intensity gradient was evident. In the NY/NJ Consortium of non-FDNY rescue 

workers/volunteers, 66% of those directly exposed to the dust cloud reported 

upper respiratory symptoms such as congestion, runny nose, headache, sinus 

pain, sore throat, ear pain or blockage, hoarse voice, etc. 31 They found that 

rescue workers arriving in the afternoon of 9/11 were similarly affected with 

62% reported experiencing upper respiratory symptoms. 31 In 96 ironworkers, 

who were on the pile from the afternoon of 9/11, usually on long shifts, without 

respiratory protection, 52% had persistent sinus complaints, with corresponding 

physical signs such as nasal mucosinusitis and swollen turbinates in at least 

30% of the cohort. 35 In 240 New York City Police Department's Emergency 

Services Unit (ESU)officers, between one to five months after the collapse, 41% 

had persistent nasal and/or throat symptoms. 34 The main diagnoses associated 

with these symptoms are chronic rhinosinusitis but as discussed later on there 

is considerable overlap with asthmatic and gastroesophageal reflux (GERD) 

symptoms. Furthermore, the literature pre- and post-WTC shows that without 

successful sinus treatment, it is difficult to successfully treat those patients 

who also have asthma. 42,43,44 

LOWER RESPIRATORY DISEASE 

During the first five years post-9/11, high rates of respiratory irritant symptoms 

have been described in at least seven WTC rescue/recovery worker groups: 

1. In 10,378 previously-healthy, exposure-stratified FDNY rescue workers, 

self-reported daily cough was present in 99% on day one (9/11), 54% 

during the first year post-collapse and 16% during the next two to four 

years29,30 (Figure 3-5.1). 

2. In the NY/NJ WTC consortium that follows the non-FDNY cohort of 

WTC rescue workers and volunteers (police, sanitation, transportation, 

construction, and others), 69% of the first 9,442 responders reported new 

or worsened upper (62.5% of 9,442) or lower (46.5% of 9,442) respiratory

Figure 3-5.1: Trends in Symptoms in 10,378 Fire Fighters from 2001 through 2005. 

symptoms during their WTC-related efforts, with symptoms persisting 

to the time of examination in 59% (on average eight months after they 

stopped their rescue/recovery/clean-up activities) 31 ; and in another study, 

they found that in the previously asymptomatic group, 44% developed 

lower respiratory symptoms during their work at the WTC site. Analysis 

again demonstrated that the incidence of lower respiratory symptoms 

was directly related to arrival time. 32 

3. 77% of 240 previously-healthy ESU police officers had upper and/or 

lower respiratory symptoms during the first five months post-collapse. 33 

4. In 471 NYC police officers (426 with no pre-9/11 chronic respiratory 

disease), 44% reported having a cough at both one and 19 months postcollapse 

but over this same time interval reported increasing prevalence 

of shortness of breath (18.9% to 43.6%) and wheeze (13.1% to 25.9%). 34 

5. 77% of 96 ironworkers had upper and/or lower respiratory symptoms 

six months post-collapse. 35 

6. In a study of 269 transit workers, those caught in the dust cloud had 

significantly higher risk of persistent lower respiratory and mucous 

membrane symptoms. 36 

7. In 183 clean-up workers, the prevalence of upper and lower respiratory 

symptoms increased as the cumulative number of days spent at WTC 

increased. 37 

Respiratory consequences have also been noted in WTC studies on community 

residents, children and office workers in lower Manhattan. 38,39,40 The WTC 

Health Registry study confirmed that out of 8,418 adults who were caught in 

the collapse on 9/11, 57% experienced new or worsening respiratory symptoms 

after the attacks. 41 


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Pulmonary function declines or abnormalities were significantly related 

to WTC exposure intensity (based on arrival time) in FDNY and non-FDNY 

workers and this remained true even after accounting for pre-existent disease 

and/or cigarette smoking. 25, 31,45,46,47,48,49 For 12,079 FDNY rescue workers in 

the first year post-WTC, a significantly greater average annual decline in 

forced expiratory volume in one-second (FEV1, a measure of airflow speed 

that decreases with increased resistance or obstruction) of 372 ml was noted 

in the first year post-9/11 when compared to the normal annual decline of 

31 ml found in the five years of pre-WTC testing – a substantial accelerated 

decline in pulmonary function. 49 Similar findings were found for the forced 

vital capacity (FVC, a measure of lung capacity), leading to a normal FEV1/FVC ratio. Preservation of the FEV1/FVC ratio is unusual in airways obstruction but, 

can be found when air-trapping is present. In the NY/NJ consortium report on 

8,384 non-FDNY workers/volunteers, 28% had abnormal pulmonary function 

test results31 during exam one performed between July 2002 and April 2004. 

They also found that a low FVC was five times more likely among the nonsmoking 

portion of their cohort than expected in the general U.S. population 

(which includes smokers and non-smokers). 31 Overall, WTC dust exposure 

intensity was related to lower FVC and a higher rate of pulmonary function 

test abnormalities 31 , demonstrating that WTC exposure had a substantial 

impact on lung function. 

In a follow up FDNY study50 , pulmonary function (FEV1) in 12,781 FDNY 

rescue workers was followed for seven years post-WTC (Figure 3-5.2). The 

average follow up was over six years for fire fighters and EMS workers and 

included those who had retired. Over the first post-9/11 year, FEV1 decreased 

substantially, more for nonsmoking fire fighters (439 ml) than for nonsmoking 

EMS (267 ml). Over the next six years, these declines in FEV1 were persistent 

and without meaningful recovery in lung function. By the end of the study 

(9/10/2008), the proportion of nonsmokers left with abnormal lung function 

was 13% for fire fighters and 22% for EMS. Smoking, although a significant 

factor in predicting post-WTC lung function decline, was dwarfed by the 

impact of WTC dust exposure. 

Adjusted FEV1 (L) 

4.5 

4.0 

3.5 

3.0 


Fire, Never Smokers (n=7,364) EMS, Never Smokers (n=967) 

predicted predicted 

02.5 

-1.5 0 1.5 3 4.5 6 

Years since 9/11/2001 

Figure 3-5.2: Lung function (FEV-1) decline in non-smoking FDNY fire fighters and 

EMS rescue workers pre- and 7 years post-WTC exposure. A substantial decline in 

lung function was noted within 12 months after 9/11 and then this decline persisted 

without meaningful recovery over the next six years.

In a follow up study, from the NY/NJ consortium, 3,160 non-FDNY workers/ 

volunteers who returned for a second pulmonary function test at exam two 

(performed anytime between September 2004 and December 2007, with a 

minimum of 18 months between exam one and two) were compared to their 

original pulmonary function test at exam one (between July 2002 and April 

2004). More than one-third had abnormal spirometry at exam two. The most 

common abnormality was a low FVC – with 16% having a lower than normal 

predicted FVC at exam two as compared to 20% at exam one. 51 Most importantly, 

the average decline in lung function (FVC or FEV 1) between these two exams 

was not greater than expected after adjusting for normal aging and for the 

majority of workers, further accelerated declines in lung function were not 

occurring during this time period. However, for those who did have greater 

than expected declines, bronchodilator responsiveness (asthma) and weight 

gain were significant predictors. 51 

Reactive (Lower) Airways Dysfunction Syndrome (RADS) and 

Asthma 

Occupational RADS is defined as persistent respiratory symptoms and nonspecific 

airway hyperreactivity in patients with a history of acute exposure to an inhaled 

agent (gas or aerosol) and no prior history of allergies, smoking or asthma. 52 

Strictly speaking, RADS can only be diagnosed by demonstrating abnormally 

brisk or intense lower airways obstruction (measured by spirometry) in response 

to standard provocations (ex. methacholine, histamine, mannitol, cold air, 

exercise challenge). However, for practical purposes, RADS can be assumed to 

be present when there are new episodic respiratory symptoms (chest tightness 

and cough) with spirometric evidence of lower airways obstruction, especially 

when the obstruction can be reversed by administration of bronchodilating 

drugs. Asthma or RADS may progress to irreversible lower airways obstructive 

disease due to chronic inflammation and airway remodeling. 

Although RADS was initially reserved for acute exposures to chemical gases 

and fumes 52 , it’s use has been extended by some to include acute and even 

chronic exposures to respirable particulates. Others prefer to use the term 

irritant-induced or occupational asthma for such exposures. WTC studies 

have allowed us to describe the incidence of bronchial hyperreactivity and 

RADS (or irritant-induced asthma) after a major disaster and to evaluate its 

persistence longitudinally in a large cohort. 

In a sample of FDNY rescue workers whose bronchial hyperreactivity was 

measured six months after 9/11, those who arrived at the WTC site on 9/11 were 

7.8 times more likely to experience bronchial hyper-reactivity than were those 

fire fighters who arrived to the site at a later date and/or had lower exposure 

levels. 45 In this FDNY study, RADS emerged in 20% of highly exposed (present 

during the morning of collapse) and 8% of moderately-exposed rescue workers 

(present after the morning of 9/11 but within the first 48 hours). 26,45 Consistent 

with human observational studies, mice acutely-exposed to high levels of 

WTC particulate matter developed pulmonary inflammation and airway 

hyperreactivity. 53 Findings in FDNY rescue workers demonstating RADS with 

documented continuing bronchial hyperreactivity 47,49 or obstructive airways 

disease 54 are consistent with non-WTC scientific literature indicating persistance 

even after exposure had ceased and even with appropriate therapy. 47,48 


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Currently, for asthma in general and for WTC-exposed subjects specifically, 

not enough is understood about the mechanism of disease to know if there 

are important distinctions (mechanism of occurrence, degree of severity, 

response to treatment, prognosis, etc.) between RADS, irritant-induced asthma 

and occupational asthma. Currently, treatment regimens remain identical, 

regardless of the term used to describe the airways disease. All we know is 

that these conditions are lower airway inflammatory diseases that present 

with provocability (reaction to airborne irritants, cold air and exercise) and 

at least partially reversible airways obstruction. In the first year of the NY/ 

NJ Consortium Program for non-FDNY workers/volunteers, it was found that 

45% reported symptoms consistent with lower airway disorders, including 

asthma and asthma variants. 32 The WTC Registry has published its findings on 

self-reported “newly diagnosed asthma (post-9/11) by a doctor or other health 

professional” in WTC rescue and recovery workers. 55 Of the 25,748 WTC workers 

without a prior history of asthma, newly-diagnosed asthma was reported by 

926 workers, for a three-year incidence rate of 3.6%, or 12 times higher than the 

expected rate of 0.3% in the general adult population. 56 Increased incidence 

of newly-diagnosed asthma was associated with the following: 

• Being caught in the dust cloud on 9/11, 

• Earlier arrival time relative to the collapse, 

• Work on the pile, 

• Cumulative exposure (especially greater than 90 days). 

When all of the above factors were adjusted for in a multivariate analysis, 

occupation and work tasks were not significant predictors of risk. 55 Similarly, 

increases in airway hyperreactivity or asthma severity have been reported in 

exposed residents living near the WTC 38,39,40 

Gastroesophageal Reflux Disease (GERD) 

In the general population, GERD is increased in middle-aged males and has 

been described as a causal or exacerbating factor for upper and lower airway 

diseases such as sinusitis, laryngitis, asthma and chronic cough syndrome. 42,43,44 

It is unclear if GERD is a cause, effect or complication of these illnesses but, 

it is clear that concurrent treatment is important if therapeutic success is to 

be optimized; and for these reasons some investigators prefer to describe 

this group of upper and lower respiratory diseases as aerodigestive diseases. 

Because disaster-related GERD is a new finding after the WTC, we could find 

no reports after other major disasters. Among FDNY rescue workers, several 

studies have now described high rates of reflux disease. In 10,378 previously 

healthy FDNY rescue workers, stratified for severity of exposure by arrival time 

at the WTC site, self-reported GERD symptoms were reported by five percent 

pre-WTC, 42% during the first year post-collapse and remained between 40 

and 45% during the next two to four years29,30 (Figure 3-5.1). However, the 

prevalence of GERD symptoms was far higher (87%) in those FDNY rescue 

workers requiring treatment for WTC Cough Syndrome. 25 

Reports of GERD have not been limited to FDNY rescue workers, as the NY/NJ 

consortium of non-FDNY worker/volunteers has also reported that in their first 

year of operation, 54% of their patients had GERD. 31 The WTC Health Registry 

reported that out of a cohort of 8,418 adult survivors caught in the collapse, 23.9%

eported heartburn or acid reflux, not dissimilar from the general population. 41 

The authors’ personal experience shows that many responders have persistent 

symptoms that have required prolonged or even chronic use of medications to 

control acid production. Though no clear mechanism for the development of 

GERD has been described in this setting, ingestion of airborne particulate WTC 

material or particulates cleared from the airways, along with stress, dietary 

triggers, alcohol, weight gain and medication use (GERD is increased with 

antibiotics, theophylline and oral steroids, medications used for WTC-related 

conditions) are the presumed causes, often acting in combination. Whether 

GERD is unique to the WTC exposure or represents a previously unrecognized 

aspect of inhalational injury in general; whether it marks more severe total 

dust exposure in conjunction with more severe host inflammatory reaction or 

exacerbation of prior disease; what the mechanism is by which highly alkaline 

dust can cause GERD; and whether this GI syndrome will persist or resolve, are 

all unresolved questions. Regardless of the mechanism, consensus treatment 

guidelines show that without successful GERD treatment there can be only 

minimally effective treatment for upper/lower respiratory conditions such as 

sinusitis, laryngitis, asthma and chronic cough. 42,43,44 

PARENCHYMAL LUNG DISEASES 

Reports have shown a higher than expected rate of sarcoidosis or sarcoid-like 

granulomatous lung disease in FDNY WTC rescue workers. 57 Sarcoidosis is a 

disorder of the immune system in which groups of white blood cells congregate 

together to cause lymph node enlargement and the formation of small 

inflammatory nodules called granulomas. Most cases have unknown cause, 

but environmental causes of sarcoidosis or sarcoid-like granulomatous disease 

are well established, especially after industrial exposure to beryllium. 58,59,60 Any 

organ can be affected, but the most common is the lung and its intra-thoracic 

lymph nodes. In the first five years post-WTC (9/11 to 9/10/06), pathologic 

evidence consistent with new-onset sarcoidosis was found in 26 FDNY rescue 

workers (Figure 3-5.3); all with intra-thoracic adenopathy (enlarged lymph 

nodes) and six (23%) with additional disease outside the chest. 57 

Figure 3.5.3: The number of cases of biopsy-proven WTC Sarcoidosis or Sarcoid-like 

Granulomatous Pulmonary Disease in the five years since 9/11 as compared to pre- 

WTC cases of sarcoidosis starting from 1985 in FDNY rescue workers. 


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266 


Thirteen were identified during the first year post-WTC (yielding an incidence 

rate of 86/100,000) and 13 during the next four years (yielding an 

average annual incidence rate of 22/100,000; as compared to 15/100,000 for 

the FDNY personnel during the 15 years pre-WTC and 5-7/100,000 for a male 

Caucasian population). 57,61 Early arrival time was not a predictor of disease, and 

cumulative exposure time was not reported, but the number of patients with 

disease was too small to reliably demonstrate an effect. This abnormally-high 

incidence raises the possibility that unknown causative environmental agents 

were generated or aerosolized during the WTC collapse/combustion. 57 Thus 

far, studies of WTC patients with sarcoidosis have not identified definitively 

which environmental agent(s) may be responsible for this disease, and the 

role of individual immunologic susceptibility to such exposures remains to 

be studied. Urine beryllium levels were not increased in WTC FDNY rescue 

workers with or without sarcoidosis but specialized t-cell studies for beryllium 

exposure remain to be performed. 57 

To date, with the exception of sarcoidosis, interstitial lung diseases have not 

been reported in any population study of WTC workers, but single-case reports 

of eosinophilic pneumonia62 , bronchiolitis obliterans, 63 and granulomatous 

pneumonitis64 have been described and the lay press has reported at least 

four case fatalities in non-FDNY WTC-exposed subjects due to interstitial 

pulmonary disease. 65 In addition, the FDNY WTC Medical Monitoring and 

Treatment Program has identified two cases of eosinophilic pneumonitis62 (both resolved on systemic corticosteroids without reoccurrence) and two 

cases of severe pulmonary fibrosis requiring lung transplantation (personal 

communication D. Prezant). 

PULMONARY MALIGNANCIES 

Because of the various carcinogenic compounds (ex. dioxins, polychlorinated 

biphenyls, and polycyclic aromatic hydrocarbons) that were found either in 

the WTC dust or as combustion products from WTC fires 1,2 , there remains 

the potential for late emerging malignancies. In the only bio-monitoring 

study, a sample of 321 exposed FDNY fire fighters tested four weeks after the 

collapse had measurements of over 100 analytes, with elevations in only a 

few (urinary PAH metabolite, antimony, and two dioxin congeners) reaching 

statistically significant differences from background, all falling far short of 

levels associated with clinical illness. 66 In addition, over 10,000 FDNY rescue 

workers were tested for urine beryllium, urine mercury, serum lead and 

serum total PCB. Only one individual showed significant mercury elevation 

(thought to be unrelated to WTC), and fewer than 50 had elevated PCB levels, 

none of which was clinically significant. 29 Samples of sedimented WTC dust 

from surfaces have shown the presence of asbestos fibers at varying amounts 

and PAHs adherent to particulates. 1 As yet, there has not been any correlation 

shown between WTC exposure and increased cancer rates. Since cancers are 

latent diseases that can develop long after carcinogen exposure, it is crucial 

that long-term monitoring be implemented for those who were exposed to the 

WTC contaminants if we are to ever determine if cancer rates are altered by 

WTC exposures.

The Impact of Exposure Time on Respiratory Disease 

In prior environmental and occupational disasters, much has been made 

of linking disease to long-term cumulative rather than short-term acute 

exposures, because diseases such as cancers typically correlate best with 

cumulative unprotected chronic exposure (e.g., mesothelioma and asbestos 

exposure). However, increased rates of disease have been reported following 

short-term, high intensity asbestos exposures. 67 The critical role of long-term 

exposure, does not apply to asthma and sinus conditions, where disease can 

result from either a single acute exposure in previously healthy non-allergic 

non-smokers (RADS) or from recurrent, relatively short-term exposures 

(occupational asthma, irritant asthma or sensitization). Similar findings 

have also been reported for acute and chronic rhinosinusitis (RUDS). And, of 

course, exacerbations of previously well-controlled asthma and sinusitis are 

common after exposures to allergens, irritants and stress. WTC studies have 

documented increased respiratory symptoms, severe persistent cough (“WTC 

Cough”), persistent airways hyperreactivity, RADS or asthma, and declines in 

pulmonary function among surviving first responders and rescue/recovery 

workers. 25,29,31,32,33,34,35,36,45,46,47,48,49,49,50,51,68 In these studies, there was a significant 

exposure-response gradient, with declines in respiratory health correlating 

with earlier time of arrival relative to the collapse of the towers. 25,29,31,32,33,34,35, 

36,45,46,47,48,49 Likewise, for surviving occupants, being caught in the dust cloud 

on 9/11 was significantly associated with increased respiratory symptoms. 41 

For upper and lower respiratory illnesses, given the high volume of aerosolized, 

respirable dust on 9/11, and the lack of appropriate respiratory protection early 

on, it is not surprising that arrival time provides the best practical measure for 

a WTC exposure-response index. For nearly all of the FDNY rescue workers, 

WTC aerodigestive disease has occurred primarily in those arriving during 

the first 48 hours after the collapse, with the greatest incidence in those 

arriving during the morning of the collapse. 25,29,31,45,46,47,48,49 This is not to say 

that there is no one in the FDNY WTC cohort with WTC aerodigestive disease 

whose first exposure occurred more than 48 hours post-collapse. And, in fact, 

a recent WTC registry study on newly-diagnosed (post-9/11) asthma in rescue 

and recovery workers showed an effect of cumulative exposure (especially 

greater than 90 hours) even after controlling for initial dust cloud exposure 

and early arrival time. 53 Aerosolized dust was re-suspended during the rescuerecovery 

operations and during clean-up of surrounding interior spaces, and 

fires continued to burn until mid-December 2001. Although relatively far 

less common, occurrences of WTC aerodigestive disease in rescue workers/ 

volunteers whose first exposure was more than 48 hours post-collapse could 

be explained either by “high-level” exposures generated by activities that 

disturbed dust in place, while entering enclosed, poorly-ventilated areas, or 

by the accumulation of repeated “low-level” exposures over time. Of note, 

in none of these studies has smoking status been found to be a significant 

confounder. 25,29,31,32,33,34,35,36,45,46,47,48,49 

TREATMENT OF WTC UPPER AND LOWER 

AIRWAYS DISEASE 

Consensus treatment guidelines have been published and recently updated 

as a joint collaborative effort between the three WTC Centers of Excellence 


267

268 

(FDNY, NY/NJ consortium coordinated by Mt. Sinai Medical Center and the 

Environmental Health Center at Bellevue Hospital) and the WTC Registry. 42 

The recommended approach includes a comprehensive plan of synergistic 

care treating the upper and lower airway including: 

• Nasal/sinuses with nasal steroids and decongestants (Figure 3-5.4). 

• Gastroesophageal reflux with proton pump inhibitors and dietary 

modification (also Figure 3-5.4). 

• The lower airway with bronchodilators, corticosteroid inhalers and 

leukotriene modifiers (Figure 3-5.5). 

For the minority that uses tobacco products, a multi-modality tobacco cessation 

program similar to that initiated by FDNY after WTC 69 should be used to 

reduce the incidence of late-emerging diseases such as lung, heart, cancer and 

cerebral vascular (stroke) disease. Most patients have reported symptoms and 

required treatment for involvement of at least two of the above organ systems. 

Our experience has proven the multi-causality of respiratory symptoms in a 

disaster-exposed population, with contribution of any combination of upper 

and lower respiratory processes. When the clinical presentation is atypical 

(for example, interstitial lung disease) or there is failure to respond after 

approximately three months of treatment, we recommend additional invasive 

diagnostic testing such as chest CT, bronchoscopy, sinus CT, laryngoscopy, 

and/or endoscopy. 42,43,44,70,71 

“World Trade Center (WTC) Cough” 

Diagnosis & Treatment Algorithm – Upper Airway Predominance 

Abnormal Cxray 

&/or 

Spirometry 

Sinus / GERD Treatment 

As Shown Here To The Right 

-------->> 

Also Pursue 

Lower Airway Workup 

For Details See Lower Airway Algorithm 


DISASTER COUGH 

Diagnosis & Treatment Algorithm 

Questionnaire & Exam 

UPPER AIRWAY 

Signs & Symptoms = 

Sinus, GERD, Cough, Drip, Reflux 

Sinus Treatment 

Nasal Steroids & Decongestant 

Cough Suppressant 

Antibiotics ? 

If No Response: 

Sinus CT Scan 

Modify treatment based on CT results 


ENT Consult 

Laryngoscopy ? 

Normal Cxray 

& 

Spirometry 

GERD Treatment 

Diet Modification 

Proton Pump Inhibitor 

Cough Suppressant ? 


Upper GI Imaging or Endoscopy ? 

Figure 3-5.4: Treatment algorithm for “WTC Cough” when presentation suggests 

that the primary causes are upper airway related – chronic rhinosinusitis and/or 

gastroesophageal reflux disorder.

“World Trade Center (WTC) Cough” 

Diagnosis & Treatment Algorithm – Lower Airway Predominance 

Figure 3-5.5: Treatment algorithm for “WTC Cough” when presentation suggests 

that the primary causes are lower airway related – obstructive airways (ex. asthma, 

bronchitis) or restrictive (parenchymal diseases). 

CONCLUSION 

A growing body of literature has developed that describes the respiratory 

health consequences of disaster-related exposures to victims, rescue workers, 

volunteers and nearby residents. Compared to most occupational exposures, 

disaster-related exposures are far more acute, are often to a wider range of 

contaminants and are more difficult to prepare for. Yet, the consequences 

are similar to many occupational and environmental respiratory diseases. 

For both occupational and disaster-related exposures the primary emphasis 

should be instituting preventive measures through the use of environmental 

controls and respiratory protection. However, the disaster environment is 

difficult to control given the unexpected nature and often overwhelming 

magnitude of the incident, the immediate imperative to rescue survivors, the 

lack of or difficulty accessing stockpiled respiratory protective equipment, and 

the widespread use of volunteers. Even after fit-tested respirators have been 

provided, there are far greater challenges to their effective use in a disaster than 

in a controlled occupational environment. Valid issues affecting adherence 

with respirator use include: 

• Comfort, especially during prolonged use and temperature extremes 

• Inability to communicate in a potentially-dangerous environment 

• Training 

• On-site supervision 


269

270 


For example at the WTC site, FDNY has reported that respirators were not 

available early on and were not used “most of the time” even when available. 3,46 

The WTC registry recently reported that for rescue/recovery workers who arrived 

on 9/11 and worked in all subsequent time periods, use of masks or respirators 

did not eliminate the risk for newly diagnosed asthma; but that delays in the 

initial use of a mask or respirator were associated with an increased incidence 

of newly diagnosed asthma. 55 

To better prepare for the next disaster a multi-pronged effort is needed that 

begins with an understanding that the immediacy of the event will lead to 

acute exposures, but that this time period should be limited by a dedicated, 

system-wide approach to provide (as rapidly as possible) and to wear (as 

frequently as possible) respiratory protection. A thorough understanding of 

user difficulties in wearing respirators should prompt a re-design of respirators 

for this environment and if this is not possible then work protocols, especially 

during the recovery phase should be adjusted to minimize unprotected 

exposures. Workers and volunteers, untrained for this environment should 

not be allowed on-site but instead should used off-site as support personnel. 

Exposures can be reduced but can never be prevented and therefore a robust 

health program for pre-screening, monitoring, disease surveillance and 

early treatment should be planned for in advance and then rapidly instituted 

beginning with on-site registration of all workers and volunteers. 

REFERENCES 

1. Lioy PJ, Weisel CP, Millette JR, et al. Characterization of the dust/smoke 

aerosol that settled east of the World Trade Center (WTC) in lower Manhattan 

after the collapse of the WTC 11 September 2001. Environ Health Perspect. 

2002, 110(7):703-14. 

2. McGee JK, Chen LC, Cohen MD, et al. Chemical analysis of World Trade 

Center fine particulate matter for use in toxicologic assessment. Environ 

Health Perspect. 2003, 111: 972-80. 

3. Centers for Disease Control and Prevention: Use of respiratory protection 

among responders at the World Trade Center site--New York City, September 

2001. Morb Mortal Wkly Rep. 2002; 51, Spec No: 6-8. 

4. Weiden M, Banauch G, Kelly KJ, and Prezant DJ. Firefighters Health and 

Health Effects of the World Trade Center Collapse. In: Environmental and 

Occupational Medicine. Pgs 477-490. 4th Edition, Edited by Rom WN and 

Markowitz S. Lippincott-Raven Inc. Philadelphia, 2007. 

5. Prezant DJ. World Trade Center Cough Syndrome and its Treatment. Lung. 

2008 ; 186 :94S-102S. 

6. Prezant DJ, Levin S, Kelly KJ, and Aldrich TK. Pulmonary and Airway 

Complications Related to September 11th. In: Interstitial Pulmonary and 

Bronchiolar Disorders, Pgs 573-590. Edited by Lynch JP; Lung Biology in 

Health and Disease Vol 227 Ex Editor Lenfant C. Informa Healthcare USA 

Inc., New York, 2008

7. Prezant DJ, Levin S, Kelly KJ, and Aldrich TK. Upper and Lower Respiratory 

Diseases after Occupational and Environmental Disasters. Mt. Sinai 

Medical Journal 2008; 75:89-100. 

8. Sherman CB, Barnhart S, Miller MF, et al. Firefighting acutely increases 

airway responsiveness. Am Rev Respir Dis 1989; 140,185-90. 


firefighters after smoke exposure. Br J Ind Med 1990; 47:524-27. 

10. Kinsella J, Carter R, Reid W, et al. Increased airways reactivity after smoke 

inhalation. Lancet 1991; 337:595-7. 

11. Baxter PJ, Ing R, Falk H, Plikaytis B. Mount St. Helens eruptions: the acute 

respiratory effects of volcanic ash in a North American community. Arch 

Environ Health 1983; 38: 138-143 

12. Cavalcanti dos Santos Antao V, Pinheiro GA and Parker JE. Lung diseases 

associated with silicates and other dusts. In: Rom WN and Markowitz SB 

editors. Environmental and Occupational Medicine. 4th ed. Philadelphia: 

Lippincott, Williams and Wilkins. 2007. pp 525-542. 

13. Lockey JE, Kapil V and Wiese NK. Man-made vitreous fibers, vermiculite 

and zeolite. In: Rom WN and Markowitz SB editors. Environmental and 

Occupational Medicine. 4th ed. Philadelphia: Lippincott, Williams and 

Wilkins. 2007. pp 330-344. 

14. Brooks SM, Tuncale T, and McCluskey. Occupational and environmental 

asthma. In: Rom WN and Markowitz SB editors. Environmental and 


Wilkins. 2007. pp 418-463. 

15. Cullinan P, Acquilla S, Ramana Dhara V. Respiratory morbidity 10 years 

after the Union Carbide gas leak at Bhopal: a cross sectional survey. BMJ, 

1997; 314: 338-343. 

16. Dharva RV. The union carbide disaster in Bhopal: a review of health effects. 

Arch Environ Health. 2002;57:391-404. 

17. Dikshit RP, Kanhere S. Cancer patterns of lung, oropharynx and oral cavity 

cancer in relation to gas exposure at Bhopal. Cancer Causes and Control. 

1999;10:627-636. 

18. Shorr AF, Scoville SL, Cersovsky SB, et al. Acute Eosinophilic Pneumonia 

among US Military Personnel Deployed in or Near Iraq. JAMA, 2004; 292: 

2997-3005. 

19. Rom WN. Asbestosis, pleural fibrosis and lung cancer. In: Rom WN and 

Markowitz SB editors. Environmental and Occupational Medicine. 4th 

ed. Philadelphia: Lippincott, Williams and Wilkins. 2007. pp 298-316. 

20. Attfield MD, Castranova V, and Wagner GR. Respiratory disease in coal 

miners. In: Rom WN and Markowitz SB editors. Environmental and 


Wilkins. 2007. pp 345-364. 


271

272 


21. Jalloul AS and Banks DE. The health effects of silica exposure. In: Rom WN 

and Markowitz SB editors. Environmental and Occupational Medicine. 

4th ed. Philadelphia: Lippincott, Williams and Wilkins. 2007. pp 365-387. 

22. Lison DF. Hard metal disease. In: Rom WN and Markowitz SB editors. 

Environmental and Occupational Medicine. 4th ed. Philadelphia: Lippincott, 

Williams and Wilkins. 2007. pp 1039-1046. 

23. Cormier Y and Lacasse Y. Hypersensitivity pneumonitis. In: Rom WN and 

Markowitz SB editors. Environmental and Occupational Medicine. 4th ed. 

Philadelphia: Lippincott, Williams and Wilkins. 2007. pp 388-401. 

24. Hart MB, Sprince NL, and Kline JN. Agricultural dust-induced lung 

disease. 570-581. In: Rom WN and Markowitz SB editors. Environmental 

and Occupational Medicine. 4th ed. Philadelphia: Lippincott, Williams 

and Wilkins. 2007. pp 570-581. 

25. Prezant DJ, Weiden M, Banauch GI, et al. Cough & bronchial responsiveness 

in firefighters at the World Trade Center site. N Eng J Med 2002; 347:806-15. 

26. Banauch, G.I., Dhala, A., Prezant DJ et al. “Pulmonary Disease in Rescue 

Workers at the World Trade Center Site”. Current Opinion in Pulmonary 

Medicine 2005; 11:160-8. 

27. Toren K, Brisman J, Hagberg S, Karlsson G. Improved nasal clearance 

among pulp-mill workers after the reduction of lime dust. Scand J Work 

Environ Health. 1996; 22:102-7. 

28. Fireman EM, Lerman Y, Ganor E, et al. Induced sputum assessment in 

New York City firefighters exposed to World Trade Center dust. Environ 

Health Perspect, 2004; 112: 1564-1569. 

29. Kelly, KJ, Niles J, Corrigan M, et al. FDNY WTC Health Effects – a six year 

assessment. Fire Department of the City of New York. 9/11/2007. Available 

on-line at: http://www.nyc.gov/html/om/pdf/2007/wtc_health_impacts_ 

on_fdny_rescue_workers_sept_2007.pdf. 

30. Webber M, Jackson G, Lee R, et al. Trends in Respiratory Symptoms of 

Firefighters Exposed to the World Trade Center Disaster: 2001-2005. 

Environ. Health Perspectives, 2009; 117:975-980. 

31. Herbert, R, Moline, J, Skloot G, et al. “The World Trade Center Disaster and 

Health of Workers; Five Year Assessment of a Unique Medical Screening 

Program” Environmental Health Perspectives. 2006; 114:1853-8. 

32. Centers for Disease Control and Prevention. Physical Health Status of 

World Trade Center Rescue & Recovery Workers & Volunteers – New York 

City, July 2002 – August 2004. Morb Mortal Wkly Rep. 2004;53:807-812. 

33. Salzman SH, Moosavy FM, Miskoff JA, et al. Early respiratory abnormalities 

in emergency services police officers at the World Trade Center site. J Occup 

Environ Med. 2004;46:113-22. 

34. Buyantseva LV, Tulchinsky M,Kapalka GMet al. Evolution of lower respiratory 

symptoms in New York police officers after 9/11: a prospective longitudinal 

study. J. Occup. Environ Med. 2007; 49: 310-317.

35. Skloot G, Goldman M, Fischler D, et al. Respiratory symptoms & physiologic 

assessment of ironworkers at the World Trade Center disaster site. Chest. 

2004;25:1248-55. 

36. Tapp LC, Baron S, Bernard B, et al. Physical and mental health symptoms 

among NYC Transit Workers seven and one half months after the WTC 

attacks. Am J. Ind. Med. 2005;47:475-483. 

37. Herbstman JB, Frank R, Schwab M, et al. Respiratory effects of inhalation 

exposure among workers during the clean-up effort at the WTC disaster 

site. Environ Res. 2005; 99: 85-92. 

38. Centers for Disease Control and Prevention. Self-Reported Increase in 

Asthma Severity After the September 11 Attacks on the World Trade Center 

--- Manhattan, New York, 2001 Morb Mortal Wkly Rep. 2002; 51:781-784. 

39. Reibman J, Lin S, Hwang S, et al. The World Trade Center residents’ 

respiratory health study: new onset respiratory symptoms and pulmonary 

function. Environ Health Perspect 2005;113:406–11. 

40. Szema AM, Khedkar M, Maloney PF, et al. Clinical deterioration in pediatric 

asthmatic patients after September 11, 2001. J Allergy Clin Immunol. 

2004;113:420-6. 

41. Brackbill, R. Thorpe L, DiGrande L, et al. “Surveillance for World Trade 

Center Heath Effects Among Survivors of Collapsed and Damaged Buildings”. 

Morb Mortal Wkly Rep. 2006; 55:1-18. 

42. Friedman S, Cone J, Eros-Sarnyai M, et al. Clinical guidelines for adults 

exposed to World Trade Center Disaster (Respiratory and Mental Health). 

City Health Information, NYC Department of Health and Mental Hygiene. 

September 2006 and updated 2008. Available online at: http://www.nyc. 

gov/html/doh/downloads/pdf/chi/chi25-7.pdf 

43. Pratter MR. Chronic upper airway cough syndrome secondary to rhinosinus 

diseases (previously referred to as postnasal drip syndrome): ACCP 

evidence-based clinical practice guidelines. Chest. 2006; 129: 63S-71S. 

44. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP 

evidence-based clinical practice guidelines. Chest. 2006;129:80S-94S. 

45. Banauch GI, Alleyne D, Sanchez R, et al. Persistent bronchial hyperreactivity 

in New York City firefighters & rescue workers following collapse of World 

Trade Center. Am. J. Resp. Crit. Care Med. 2003; 168:54-62. 

46. Feldman DM, Baron S, Mueller CA, et al. Initial symptoms, respiratory 

function & respirator use in New York City firefighters responding to the 

World Trade Center (WTC) disaster. Chest 2004;125:1256-64. 

47. Banauch GI, Dhala A, Alleyne D, et al. Bronchial hyperreactivity & other 

inhalation lung injuries in rescue/recovery workers after the World Trade 

Center collapse. Crit Care Med. 2005;33:S102-S106. 

48. Banauch GI, Dhala A, Prezant DJ. Airway dysfunction in rescue workers 

at the World Trade Center site. Curr Opin Pulm Med 2005; 11:160-8. 


273

274 


49. Banauch GI, Hall C, Weiden M, et al. Pulmonary function loss after World 

Trade Center exposure in the New York City Fire Department. Am. J. Respir. 

Crit. Care Med. 2006; 174:312-319. 

50. Aldrich TK, Gustave J, Hall CB, et al. Lung Function in Rescue Workers 

at the World Trade Center after 7 years. New England J Medicine 2010; 

362:1263-1272. 

51. Skloot GS, Schechter CB, Herbert R, et al. Longitudinal Assessment of 

Spirometry in the World Trade Center Medical Monitoring Program. Chest 

2009; 135:492-498. 

52. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome. 

Chest 1985, 88:376-84. 

53. Gavett S. Haykal-Coates N, Highfill J, et al. World Trade Center fine 

particulate matter causes respiratory tract hyperresponsiveness in mice. 

Environ Health Perspect. 2003; 111:981-991. 

54. Wheeler K, McKelvey, Thorpe L, et al. Asthma diagnosed after September 

11, 2001 among rescue and recovery workers: findings from the World 

Trade Center registry. Environ Health Perspect. 2007; 115:1584-1590. 

55. Reed CE. The natural history of asthma. J Allergy Clin Immunol. 2006;118:543- 

548. 

56. Weiden MD, Ferrier N, Nolan A, Rom WN, Comfort A, Gustave J, Zheng 

S, Goldring RM, Berger KI, Cosenza K, Lee R, Zeig-Owens R, Webber MP, 

Kelly KJ, Aldrich TK, Prezant DJ. Obstructive Airways Disease with Airtrapping 

among Firefighters Exposed to World Trade Center Dust. CHEST 

2010; 137:566-574. 

57. Izbicki G, Chavko R, Banauch GI, et al. World Trade Center “Sarcoid-Like” 

Granulomatous Pulmonary Disease in New York City Fire Department 

Rescue Workers. Chest 2007; 131:1414–1423. 

58. Kreider ME, Christie JD, Thompson B, et al. Relationship of environmental 

exposures to the clinical phenotype of sarcoidosis. Chest. 2005; 128:207- 

15. 

59. Drent M, Bomans PH, Van Suylen RJ, et al. Association of man-made mineral 

fiber exposure and sarcoid like granulomas. Respir Med. 2000;94:815-820. 

60. Culver DA, Newman LS, Kavuru MS. Gene-environment interactions in 

sarcoidosis: challenge and opportunity. Clin. Dermatol. 2007; 25:267-275. 

61. Prezant D, Dhala A, Goldstein A, et al. The incidence, prevalence and 

severity of sarcoidosis in New-York City firefighters. Chest 1999;116:1183- 

1193. 

62. Rom WN, Weiden M, Garcia R, et al. Acute eosinophilic pneumonia in a 

New-York city firefighter exposed to World Trade center dust. Am J Respir 

Crit Care Med 2002;166:797-800.

63. Mann JM, Sha KK, Kline G, et al. World Trade Center dyspnea: bronchioloitis 

obliterans with functional improvement: case report. Am J Ind Med. 2005; 

48:225-229. 

64. Safirstein BH, Klukowitcz A, Miller R, et al. Granulomatous pneumonitis 

following exposure to the World Trade center collapse. Chest 2003; 123: 

301-304. 

65. DePalma Anthony. Medical views of 9/11 dust shows big gaps. The New 

York Times. October 26, 2006. 

66. Edelman P, Osterloh J, Pirkle J, et al. Biomonitoring of chemical exposure 

among New York City firefighters responding to the World Trade Center 

fire and collapse. Environ Health Perspect. 2003; 111: 1906-11. 

67. Seidman H, Selikoff IJ, Hammond EC. Short-term asbestos work exposure 

and long-term observation. Ann NY Acad Sci. 1979; 330:61-89. 

68. Levin S, Herbert R, Skloot G, et al. Health effect of World Trade Center site 

workers. Am J Industrial Med. 2002; 42: 545-547. 

69. Bars MP, Banauch GI, Appel DW, et al. “Tobacco Free with FDNY” – The 

New York City Fire Department World Trade Center Tobacco Cessation 

Study. Chest 2006; 129:979-987. 

70. Gwaltney JM Jr., Jones JG, and Kennedy DW. Medical management of 

sinusitis: educational goals and management guidelines. The International 

Conference on sinus Disease. Ann Otol Rhinol Laryngol Suppl, 1995; 167: 

22-30. 

71. DeVault KR, Castell DO, et al. American College of Gastroenterology: 

Updated guidelines for the diagnosis and treatment of gastroesophageal 

reflux disease. Am J Gastroenterol. 2005; 100:190-200. 


275


Chapter 4-1 

Pulmonary Function 

Tests for Diagnostic and 

Disability Evaluations 

By Dr. Andrew Berman, MD and Dr. Naricha Chirakalwasan, MD 

INTRODUCTION 

Pulmonary function tests (PFTs) are a group of studies designed to evaluate 

how the lung functions in health and in disease. They are usually performed 

in a lab or in a doctor’s office and can be used to diagnose, assess severity and 

progression, and guide treatment of pulmonary diseases. PFTs can uncover 

clinically undetected dysfunction. 

Most pulmonary function measurements are routinely expressed as a 

percent predicted of normal so that the patient can see how they are doing 

compared to the population. Since pulmonary function measurements are 

known to be lower in shorter, older or female subjects, the percent predicted 

normal value automatically adjusts for age, height and gender. While obesity 

also has a direct effect in lowering pulmonary function measurements by 

placing a greater stress on the lungs, heart and skeletal muscles, the impact of 

obesity is not adjusted for automatically in the percent predicted equations. 

Therefore, if your values are low and you have central obesity (chest and/or 

abdomen) your values would likely be higher if you lost weight. 

For PFTs to be accurate and to provide the correct diagnosis it is important 

that the patient, physician and technician performing the test remember the 

following points: 

• Most PFTs are effort dependent and the patient must be coached to 

breathe in as deep as possible and to blow out as hard as possible. 

• Reproducibility is required and multiple efforts may be needed. As 

with the Olympics, the best effort counts and not the number of efforts 

required to produce that best effort. 

• Tobacco smoke should be avoided as it can negatively influence both 

your health and these measurements. 

Unless otherwise advised by your physician, bronchodilator medications (ex. 

albuterol, ventolin, proventil, ipratropium bromide or Atrovent, Combivent, 

Seravent, Foradil, Advair, Symbicort and Spiriva) and caffeine should not be 

taken the morning of the test. However, if you have a history of taking these 

medications you should bring them with you, tell the technician administering 

the test about them and be prepared to use them, if necessary, after the test. 

This chapter will review some of the many ways lung function can be evaluated. 

Chapter 4-1 • Pulmonary Function Tests for Diagnostic and Disability 277

278 Chapter 4-1 • Pulmonary Function Tests for Diagnostic and Disability 

PEAK FLOW/SPIROMETRY/BRONCHODILATOR 

RESPONSIVENESS 

Peak Flow Meter 

A peak flow meter is a portable handheld device that measures air flow. It is 

easy to use, inexpensive, and patients can do this in their own home. Simply, 

the patient blows as hard and fast as they can into a tube that measures the 

highest (or “peak”) flow rate. The peak flow measurement occurs very early in 

expiration, when the flow rates are effort dependent. It is important to take a 

full breath in and blow out as hard as you can but after the first few seconds you 

don’t have to blow out any further. Because of that, some patients find this easier 

to do. Peak flow measurements are helpful in monitoring the status of chronic 

asthma, assessing the severity of acute exacerbations, evaluating therapy, and 

evaluating temporal (time-related or seasonal-related) relationships to triggers 

(ex. humidity, heat, irritants, smells) that my cause asthma attacks. Patients 

can manage their own asthma by knowing their best peak flow and referring 

to a written action plan with recommendations from their physician regarding 

what to do when the peak flow is reduced to different levels (Figure 4-1.1). 

Figure 4-1.1: A typical Peak Flow meter with colored zones that can be set to a percentage 

of the individual’s best score. An asthma action plan can be written with instructions of what 

to do if the peak flow falls into these zones. 

Of note, falls in peak flow can occur even before symptoms worsen, making 

this a tool which potentially can lessen the severity of an exacerbation if the 

results are acted upon early on. Disadvantages of this test are that the results 

are not always reproducible and are effort dependent. A peak flow measurement 

does not obviate the need for spirometry to make the diagnosis of asthma. 

Spirometry 

Spirometry measures how much and how fast air moves in and out of the 

lungs. After placing a clip over the patient’s nose to direct all respiration to 

the mouth, the patient is coached to breathe in deeply and then blow out for at 

least six seconds, as fast and as hard as possible, and then to breathe in again, 

all through a tube which is connected to a device called a spirometer. The 

spirometer records the forced flow of air throughout the respiratory cycle, as

opposed to the peak flow which only provides one measure early in exhalation. 

It is important when doing spirometry, that you breathe all the way in, and 

then blow all the way out until you have reached the end of your expiration 

(typically, this takes about six seconds of expiration, however healthy, young 

fire fighters may empty their lungs sooner than six seconds). 

Spirometry, therefore, provides more data than a peak flow measurement and 

allows for a more accurate and reproducible measurement of asthma control. 

In addition, by plotting inhaled and exhaled flow against the amount of air 

(i.e., the volume) inhaled and exhaled, a graphic figure can be drawn called a 

flow-volume loop, which may reveal characteristic patterns associated with 

certain pulmonary diseases, as described in the next section. A typical study 

involves repeating the maneuver at least three times and the best of the three 

trials is accepted. Just like in the Olympics, it is your best recording that counts. 

Because spirometry tells us about disease and about breathing capacity, it is 

used in fire fighter candidate evaluations and duty determinations (NFPA 1582) 

and is the best measure of how you are doing (IAFF/IAFC Wellness-Fitness 

Initiative). Every fire fighter and HAZMAT worker should have a baseline 

measurement and then a repeat measurement annually. The following is a 

list of measurements obtained during spirometry: 

• FVC (forced vital capacity) is the maximum volume of air which can 

be forcefully exhaled after full inspiration. FVC is similar to a slow 

vital capacity in normal lungs, but lower when airflow obstruction is 

present. 

• FEV (forced expired volume in one second) is the volume of air expired 

1 

in the first second of forced expiration after a full inspiration; it is a 

measure of how quickly full lungs can be emptied. 

• FEV /FVC is the FEV expressed as a percentage of the FVC. A reduced 

1 1 

ratio is how we define airflow obstruction. 

• FEF (Forced expiratory flow at 25% point to the 75% point of FVC) 

25-75% 

is the average expired flow over the middle half of the FVC maneuver 

and is felt to be a measure of small airway obstruction. This result may 

be a more sensitive indicator of mild airway obstruction than the FEV / 1 

FVC ratio, though is less reproducible and non-specific and frequently 

does not correlate with challenge tests (see below). Therefore, the 

clinical significance of this measurement remains controversial and 

it is not used for candidate evaluations of duty determinations (NFPA 

1582). 

Individual results are compared to normal values (predicted values) which 

are defined by a healthy population, adjusted for age, height and gender, 

and are expressed as a percentage of the predicted value. In healthy adults, 

spirometry results are normally distributed, meaning that 95% of test results in 

healthy adults will be between 80% - 120% of a predicted value. An abnormal 

result then is one that falls outside of this range: an FEV or FVC of less than 

1 

80% of the predicted value, since it is uncommon (less than 5%) for a normal 

patient to have measurements in this range. Perhaps more useful, however, is 

whether there is a rise or fall in these values in an individual patient over time. 

Because there are day-to-day variations in breathing capacity, a decline that is 

15% or greater from your typical past recordings should be further evaluated 

by a physician. 


280 

Spirometry results can usually differentiate obstructive lung disease 

from restrictive lung disease. In obstructive lung diseases (such as asthma, 

emphysema and chronic bronchitis), the total amount of air that gets exhaled 

is normal or close to normal, but it takes more time for it to come out due to 

air flow limitation. The FEV 1 , therefore, is reduced, while the FVC is close to 

normal, making the ratio (FEV 1 /FVC) reduced. Airway obstruction is often 

defined by a reduced FEV 1 /FVC to less than or equal to 0.70, though some 

question this cut-off value and require further confirmatory tests (see below). 

In restrictive lung diseases (such as pulmonary fibrosis, asbestosis, moderate 

to severe sarcoidosis, kyphoscoliosis, obesity or neuromuscular disease), the 

lung cannot fill completely and so the amount of air exhaled initially is reduced 

as is the total amount exhaled. The FEV 1 /FVC ratio in this case is normal or 

elevated since both the FEV 1 and FVC are low. A combination of restrictive 

and obstructive disease (mixed pattern) can also be seen and is suggested by 

a reduced FEV 1 , a reduced FVC and a reduced to normal FEV 1 /FVC ratio. Table 

4-1.1 reviews the finding of spirometry results and lung diseases. 

Lung Diseases and Spirometry Results 

Interpretation FVC FEV 1 FEV 1 /FVC 

Normal Spirometry Normal Normal Normal 

Airway Obstruction 

Low or 

Normal 

Low Low 

Lung Restriction Low Low Normal 

Combination of 

Obstruction & 

Restriction 

Table 4-1.1. Lung Disease and Spirometry Results 

Low Low Low 

As opposed to a reduced FEV 1 / FVC ratio which defines obstruction, a 

normal FEV 1 / FVC ratio does not define restriction. A reduced FEV 1 and FVC 

(and therefore a normal ratio) can also be seen during testing of some patients 

with severe airway obstruction who may not be able to exhale fully because 

their air tubes close as they try to force air out. These patients may stop testing 

before the lungs are fully emptied (i.e., the air is trapped), which leads to a 

falsely reduced FVC. For this reason, bronchodilator tests and full lung volumes 

(discussed later in this chapter) are necessary to distinguish obstructive from 

a restrictive abnormality. 

Flow Volume Loop 

The flow volume loop is a graph plotting forced expiratory and inspiratory flow 

against volume, and may reveal characteristic patterns associated with certain 

pulmonary diseases. The contour of expiratory portion of the flow volume 

loop can be used to differentiate obstructive lung disease from restrictive lung 

Chapter 4-1 • Pulmonary Function Tests for Diagnostic and Disability

disease, while the inspiratory contour may suggest upper airway pathology. 

The latter might be due to vocal cord abnormalities or obstruction in the upper 

trachea or larynx (voice box). 

Patterns in normal and disease states are shown in Figure 4-1.2. In those 

without lung disease, there is a straight contour in the expiratory loop and a 

rounded appearance in the inspiratory loop (see Figure 4-1.2a). In patients 

with obstructive lung disease, the expiratory curve is curvilinear or scooped 

in appearance, due to a reduction in flow as the volume of the lung decreases, 

which occurs as the patient exhales. As the obstruction becomes worse, the 

expiratory curve becomes more scooped (see Figures 4-1.2b and 4-1.2c). In 

restrictive diseases, the curve is tall and narrow (see Figure 4-1.2d). A sawtooth 

pattern is sometimes seen in patients with obstructive sleep apnea. 

Upper airway lesions alter inspiratory flow and will show as a flattening of 

the inspiratory loop. When there is limited flow during both inspiration and 

expiration, there is a fixed obstruction and this appears as a box pattern (see 

Figure 4-1.2e). This can occur in patients with tracheal stenosis (scar in the 

wind pipe), which may occur after severe upper airway burns, prolonged 

intubation and mechanical ventilation. 

Figure 4-1.2 a-e: Flow-volume curves showing different patterns. a: Normal. b: Airway 

obstruction. c: Severe airway obstruction. d: Restriction. e: Fixed airway obstruction. (Adapted 

from Johns D, Pierce R. Pocket Guide to Spirometry. 2003. McGraw-Hill. Australia) 

Bronchodilator Responsiveness or Reversibility 

As discussed in Chapter 1, there is smooth muscle in parts of the bronchial tree. 

When the smooth muscle contracts, the diameter of the airways is reduced, 

resulting in a decrease in airflow. Certain inflammatory lung conditions, 

such as asthma or reactive airway disease (both discussed in later chapters), 

are characterized by hyperreactive (irritable/twitchy/spasmodic) airways, 

whereby certain triggers (ex. humidity, temperature change, exercise, irritants, 

noxious fumes) may lead to smooth muscle contraction and the development of 

symptoms such as cough, shortness of breath and/or wheezing. A characteristic 


281

282 

of these conditions on spirometry is a decrease in the FEV 1 and the FEV 1 / 

FVC ratio (an obstructive pattern) that is at least partially reversible after 

the patient receives a medication that causes the bronchi to dilate (i.e., a 

bronchodilator such as albuterol). This relieves the airflow obstruction and 

can be demonstrated by repeating the spirometry after the bronchodilator is 

administered and waiting 10 minutes. The American Thoracic Society (ATS) 

recommends that vital capacity (slow or forced) and the FEV 1 , be the primary 

spirometric indices used to determine bronchodilator response. A 12% increase 

above the pre-bronchodilator value and a 200-ml increase in either FVC or 

FEV 1 indicate a significant response in adults. FEF 25-75% should be considered 

only secondarily in evaluating reversibility. 

TEST OF LUNG VOLUME AND DIFFUSION CAPACITY 

Lung Volume Measurements 

Lung volume is the amount of air in the lungs, and measurement often requires 

further testing in addition to spirometry. Recall, spirometry only measures 

the amount of air entering or leaving the lungs and even after fully breathing 

out we always have some air left in our lungs. Therefore, in order to know the 

total amount of air in the lungs, one needs to know how much air is left in the 

lung after a complete exhale, or the residual volume. This amount can vary in 

disease states and by gender. Listed below and shown in Figure 4-1.3 are the 

volumes and capacities (defined as two or more primary volumes) of the lung. 

Figure 4-1.3: Lung Volumes. 


The primary volumes are as follows: 

• VT = Tidal Volume: volume of air normally inhaled or exhaled during 

each respiratory cycle. This value can be obtained during spirometry. 

• IRV = Inspiratory Reserve Volume: the additional volume of air inhaled 

after a normal inspiration, achieved by taking a full deep breath in; it 

is the maximal volume of air inspired from end-inspiration.

• ERV = Expiratory Reserve Volume: the additional volume of air exhaled 

after a normal exhalation, achieved by forcing out a full deep breath 

until no more air can be expired; it is the maximal volume of air exhaled 

from end-expiration. 

• RV = Residual Volume: the volume of air that remains in the lungs 

following a maximal exhalation; this volume may be increased in 

patients with severe airway obstruction. Residual volume can only be 

measured indirectly by gas dilution methods or body plethysmography. 

The capacities are as follows: 

• VC = Vital Capacity: maximal volume of air that can be forced out of 

the lungs following a maximal inspiratory effort, regardless of the 

amount of time it takes. This is the same as the FVC measured during 

spirometry if air does not get trapped due to collapsing airways, as can 

occur in obstructive lung disease. When airway obstruction is present, 

a slow vital capacity measurement may be more reflective of the true 

value. The VC equals IRV + VT + ERV or alternatively, the TLC – RV. 

• TLC = Total Lung Capacity: the total amount of air in the lungs. The 

TLC includes the maximal volume of air that can be exhaled (VC) plus 

whatever air remains in the lung afterwards (the RV). 

• FRC = Functional Residual Capacity: the amount of air in the lungs 

after one breathes out normally. This equals ERV + RV. 

• IC = Inspiratory Capacity: the maximal volume of air that can be 

inspired at the end of a resting exhale. This equals IRV + VT . 

There are three methods to determine lung volumes: spirometry, the gas 

dilution technique and body plethysmography (also known as a body box). 

Spirometry has been discussed earlier and is limited by the inability to measure 

residual volume and therefore total lung capacity and functional residual 

capacity, because both contain the residual volume as part of their capacity. 

The other two techniques allow for the measurement or calculation of 

all lung volumes. Usually, after FRC is measured, other lung volumes are 

measured including ERV. RV is calculated by subtracting ERV from FRC. By 

adding the residual volume to the vital capacity, total lung capacity can then 

be calculated. Since restrictive lung disease is defined by a reduced TLC, gas 

dilution or body plethysmography must be performed to make this diagnosis. 

Typically, labs using the gas dilution technique utilize either the closed 

circuit helium (He) method or an open circuit nitrogen (N2) method. The helium 

dilution method (as depicted in Figure 4-1.4) starts with the patient breathing 

a gas mixture containing helium via a closed circuit. The starting volume of 

gas containing the helium is known and the amount of helium in the lungs at 

the start is zero. Since helium is inert, it does not diffuse across the alveolarcapillary 

membrane, and the gas equilibrates throughout the entire system. 

The total amount of helium does not change during the test. After the patient 

breathes normally for up to 10 minutes, equilibration usually occurs, and the 

amount of helium in the system is again measured. The equilibrated volume is 

subtracted from the starting volume enabling calculation of the volume of the 

lung at the end of a normal breath which is FRC. One limitation of this method 

is that the volume of gas measured is only that which communicates with the 


283

284 

Figure 4-1.4: Helium dilution technique of lung volume measurement. 

airways, which does not include lung bullae which can occur in patients with 

emphysema. In obstructive airway diseases, especially emphysema, TLC 

may be underestimated. Body plethysmography would be a better method of 

measuring TLC in these patients. 

The open circuit nitrogen method is based on a similar principle of the 

helium technique, except here the expired concentration of nitrogen normally 

present in the lungs is now measured. In this technique, the patient is given 

100% oxygen to breath in order to wash out the air (mostly made up of nitrogen) 

from the lungs. The concentration of nitrogen is continuously monitored in the 

expired gas, and when the exhaled concentration of nitrogen is essentially zero, 

the test ends. The volume of nitrogen-containing gas present in the lungs can 

be measured. The difference in nitrogen volume at the initial concentration 

and at the final exhaled concentration allows a calculation of intrathoracic 

volume, usually FRC. This measurement is subject to the same limitations as 

the helium technique. 

Body Plethysmography 

Body plethysmography is another technique used to measure lung volumes. 

This method incorporates the physiologic principle of Boyle’s law which states 

that the product of the pressure times the volume of a gas is constant if the 

temperature is unchanged, or P1V1=P2V2. In plethysmography, the patient sits 

inside an airtight box that resembles a telephone booth (thereby accounting 

for the alternative test name of body box, see Figure 4-1.5). The initial box 

volume and pressure are known (P1V1). The patient then breathes in and out 

through a mouthpiece. At the end of a normal exhale (FRC), the mouthpiece 

gets occluded and the patient is instructed to gently pant in and out against the 

closed shutter. This causes the chest volume to expand which in turn causes a 

decrease in the box volume and a corresponding increase in box pressure. The 

pressure change in the box is recorded and thereby allows for a calculation of 

the change in box volume, which is equal to the change in lung volume. This 


At beginning of gas dilution test After several minutes of testing

Figure 4-1.5: Body plethysmography, or body box. 

volume is referred to as thoracic gas volume (TGV) and represents the lung 

volume measured when the shutter was closed, typically at FRC. 

Lung volumes measured by body plethysmography, may be higher than 

volumes measured by using gas dilution method. This is primarily due to the 

measurement of both communicating and non-communicating compartments 

of the lungs with plethysmography, as opposed to just measuring the 

communicating compartments alone using the gas dilution techniques. It 

is therefore a more accurate test in patients with severe airway obstruction 

(where there is trapped air from airways that collapse at low lung volumes) 

as well as those with bullous lung disease or emphysema. Disadvantages are 

that the values may be off if the shutter is closed at a volume which is not FRC, 

as well as the need for a patient to sit in a small enclosed space. 

Diffusing Capacity 

Diffusing capacity is a measurement of the ability of gases like oxygen to 

transfer from the alveoli into the pulmonary capillary blood. A low diffusing 

capacity is rarely a cause for hypoxia (low oxygen levels) at rest but can be a 

cause during physical exertion. 

Diffusing capacity is a non-invasive test which involves the inhalation of 

a gas mixture containing a small amount of carbon monoxide because this 

gas is normally not present in the lungs or blood, and is very soluble in blood. 

This small amount will not be harmful to the patient and does not last long 

in the body so it will not be present later that day if a fire fighter has carbon 

monoxide level taken at a fire or in an emergency room. During the diffusing 

capacity test, a known amount of carbon monoxide is breathed in and then 

whatever is not subsequently breathed out should represent the amount that 

diffused through the lung and into the pulmonary capillary system. The most 

widely used and best standardized method of measuring diffusing capacity 

is known as the “single-breath diffusing capacity using carbon monoxide,” 

or the DLCO. In this technique, the patient exhales completely, and then 

inhales a gas mixture deeply, that contains 0.3% carbon monoxide and a low 

concentration of inert gas (usually 10% helium). The patient then holds their 

breath for 10 seconds, during which time the carbon monoxide leaves the air 

spaces and enters the blood. The exhaled helium concentration is used to 


286 

calculate a single-breath estimate of total lung capacity. DLCO is calculated 

from the total volume of the lung, breath-hold time, and the initial and final 

alveolar concentrations of carbon monoxide. 

The amount of gas diffused from the lung into the pulmonary capillary system 

is related to the surface area of the lung, the capillary blood volume, and the 

thickness of the alveolar-capillary membrane. Any condition which alters any 

one of these factors can cause a reduction in diffusion. In emphysema, the walls 

between the alveoli break down, creating fewer alveoli, and this loss of surface 

area is associated with reduced diffusion. Pulmonary embolism (blood clots) 

or pulmonary hypertension results in the obliteration and/or obstruction of 

pulmonary arteries. In these patients, the measurement of gas transfer for carbon 

monoxide is usually reduced. Interstitial lung diseases affect the meshwork of 

lung tissue (alveolar septa) other than the air spaces (alveoli), and can result 

in thickening of the alveolar-capillary membrane making it harder for gas to 

diffuse. Examples of interstitial lung disease include Idiopathic Pulmonary 

Fibrosis (IPF), moderate to severe sarcoidosis, lung diseases caused by certain 

dusts (e.g., asbestosis) and certain drug reactions. Pulmonary diseases that 

essentially just affect the airways, such as asthma or chronic bronchitis, do 

not demonstrate a reduced diffusion capacity. Increased diffusion capacity 

is rarely important but may occur if the patient is bleeding into their lung. 

Diffusion capacity is a valuable tool in the diagnosis and monitoring of 

pulmonary diseases. While a reduced TLC signifies restrictive disease, the 

DLCO may suggest the etiology. For example, a reduced DLCO with a reduced 

TLC suggests interstitial disease (e.g., pulmonary fibrosis), while a normal 

DLCO with reduced TLC suggests the lung parenchyma is not damaged and 

the restriction is extrapulmonary (as in obesity, chest wall or neuromuscular 

diseases). A decreased DLCO with an obstructive pattern on spirometry can 

be seen in patients with emphysema, while those with chronic bronchitis 

often have obstruction with a normal diffusion capacity. Pulmonary vascular 

disease and anemia may present with normal spirometry and lung volumes 

and a decreased DL . It should be noted however that there are some patients 

CO 

with interstitial lung disease who are found to have diffusion abnormalities 

before lung volume abnormalities are present. Typically, these patients also 

have evidence for interstitial lung disease on high-resolution chest CT scans. 

Diffusing capacity can also be low in the absence of lung disease. It is low in 

some patients with obesity due to compression of the lung and its circulation. It 

can be low, normal or high in cardiac disease. Low hemoglobin concentration 

(as in anemia) also leads to a reduced diffusion capacity as there is less blood 

to diffuse onto; a correction for anemic patients is sometimes used. Likewise, 

diffusing capacity can be elevated in a condition called polycythemia (increased 

number of red blood cells). It can also be low in patients with carbon monoxide 

intoxication (acute or chronic exposures even from tobacco smoke). 

PROVOCATIVE CHALLENGE TESTING 

(METHACHOLINE, COLD AIR AND EXERCISE) 

In patients with a history suggestive of asthma, but with a normal physical exam 

and spirometry, further testing is sometimes required to document bronchial 

hyperreactivity. Provocative challenge testing incorporates the delivery of 

Chapter 4-1 • Pulmonary Function Tests for Diagnostic and Disability

a medication to provoke constriction of the airways (bronchoconstriction) 

leading to asthma symptoms and a fall in lung function. People with asthma 

will respond to bronchoprovocation with a greater degree of airway obstruction 

than will normal subjects. Methacholine is a commonly used provocative agent 

that is a nonspecific stimulus of bronchoconstriction, though cold air and 

exercise testing are also sometimes used. In methacholine challenge testing, 

a baseline FEV is recorded following the inhalation of saline. Methacholine is 

1 

then delivered in increasing concentrations with a repeated FEV measurement 

1 

following each dose. In contrast to normal subjects, asthmatics will report 

typical asthma symptoms, such as coughing, wheezing and shortness of 

breath, and their FEV will fall as the dose increases. The test is terminated 

1 

following any dose that lowers the FEV by 20%. This is termed the PD 1 20, or 

the provocative dose that produces a 20% fall in FEV. 

Following testing, a bronchodilator is administered and lung function returns 

to normal and symptoms resolve. Hyperresponsiveness is deemed present 

when the PD20 is less than or equal to 8 micromol or mg/ml of methacholine. 

Some physicians believe that a more liberal definition (higher PD20 such as 

16 mg/ml) should be used in workers where the risk for irritant exposure is 

high (e.g. fire fighters and other HAZMAT workers). The lower the dose that is 

required, the more hyperreactive the individual’s airways are. Cough variant 

asthma, in which the patient has asthma though only coughs as the main 

presentation, can also be diagnosed by this method. It also has been used 

to follow subjects with exertional asthma, occupational asthma, document 

the severity of asthma and to assess the response to treatment. Presence of 

increased airway responsiveness is a significant predictor of subsequent 

accelerated decline in pulmonary function. 

It is important to understand that provocative testing is only of use in patients 

with normal lung function when the diagnosis of asthma is in question. It should 

never be performed in patients with moderate to severe reductions in lung 

function at rest (FEV1


is often referred to as cardiopulmonary exercise testing (CPET). CPET can 

also be utilized to evaluate disability, prescribe exercise rehabilitation, and 

to determine risk from major surgery. 

Before beginning a CPET, it is important to evaluate patients for any 

contraindications to exercise testing. This would include any individual who 

has severe physical or emotional impairments where testing is deemed unsafe. 

Examples include patients with severe arthritis or neuromuscular disorders 

who may not be able to perform the required maneuvers. Patients with severe 

cardiac disease such as unstable angina or aortic stenosis should not be tested. 

In addition, patients with uncontrolled asthma should not be tested until their 

asthma is under better control. 

Standard exercise testing is performed on a treadmill or stationary bicycle. 

Prior to initiating the exercise, a blood pressure cuff, EKG leads, and a pulse 

oximetry probe are applied. A mask that allows for expired air to be monitored 

and a nose clip are placed on the patient. An indwelling arterial canula for blood 

gas sampling is sometimes inserted. The patient then performs progressive 

step-wise exercise at multiple work loads. Figure 4-1.6 shows a standard clinical 

exercise protocol using cycle ergometry. 

Figure 4-1.6: Recommended incremental exercise protocol using cycle ergometer 

The test continues until the target heart rate is reached. After exercise 

testing, the subject “recovers” for about two to three minutes by pedaling 

at a low work rate to prevent hypotension caused by pooling of blood in 

dilated vessels. Exercise testing can also be terminated if the patient 

develops exhaustion, severe shortness of breath, chest pain, dizziness, or 

pallor. In addition, the test is stopped if there are significant EKG changes, 

serious arrhythmias, a dramatic rise or fall in blood pressure, abnormal 

rapid respiration or significant drop in oxygen saturation (

determinant of whether there is normal or reduced exercise capacity. A reduced 

VO2max can be seen in several diseases and conditions such as cardiovascular 

disease, lung disease, or anemia. An integrative approach using clinical data 

and patterns of physiologic responses based on measured indices is used to 

determine the cause; no one single index is considered diagnostic of a cause 

for exercise limitation. 

Six-Minute Walk Test 

The six-minute walk test (6MWT) is a test that measures the maximal distance 

that a patient can walk on a flat hard surface in a period of six minutes. Patients 

walk at their own pace and are allowed to rest when necessary. It is felt that 

since most activities of daily living are performed at this level, the 6MWT 

may better reflect the functional capacity of the individual for daily physical 

activities than complete cardiopulmonary exercise testing. This would not 

be true for fire fighters and EMS rescue workers who must be able to perform 

at a much higher level of physical exertion. The primary advantage is that 

the test is simple and practical; no exercise equipment is necessary. The 

disadvantage is that the test does not provide specific information on the role 

of the different organ systems that can contribute to exercise limitation. This 

test is used for preoperative and postoperative evaluations, and to monitor 

patients with cardiac and pulmonary vascular disease as well as to measure 

the response to therapeutic interventions. Lastly, it can used to measure the 

response to pulmonary rehabilitation, as patients may increase either or both 

their maximum capacity and endurance for physical activity, even though 

lung function does not change. 

DISABILITY EVALUATION 

Dyspnea, a sensation of uncomfortable awareness of breathing, is the most 

common complaint in a disability evaluation. Disability evaluations incorporate 

objective quantitative measures, such as the pulmonary function tests 

described earlier, with other factors such as age, gender, education, and job 

requirements. Two individuals with the same degree of physiologic impairment 

may therefore have different levels of disability. For example, asthma would 

be a disability for fire fighters who work in an irritant environment but would 

not be a disability (unless severe) for most EMS workers. 

Respiratory impairment is often determined using certain spirometric 

measures, such as the FEV and FVC. The diffusion capacity for carbon 

1 

monoxide is also used (Table 4-1.2). Many clinicians, however, feel that a percent 

predicted cut-off value used in isolation to determine whether an individual 

can perform their job or not may be inaccurate. Interpretation in the context 

of other diagnostic tests and patient history is more informative. The U.S. 

Social Security Administration, for example, considers asthma disabling if 

severe attacks occur at least once every two months or an average of at least 

six times a year. 


Class 1, 0%–9%: 

No Impairment of 

the Whole Person 

FVC ≥ lower limit of 

normal* and FEV1 

≥ lower limit of 

normal* and DLCO 

≥ lower limit of 

normal* 

VO2 max > 25 mL/ 

kg/min 


Classification of Respiratory Impairment 

Class 2, 10%–25%: 

Mild Impairment 

of the Whole 

Person 

FVC between 60% 

and lower limit of 

normal or FEV 1 

between 60% and 

lower limit of normal 

or DLCO between 

60% and lower limit 

of normal 

Class 3, 26%–50%: 

Moderate 

Impairment of the 

Whole Person 

FVC between 51% 

and 59% of predicted, 

or FEV 1 between 41% 

and 59% of predicted, 

or DLCO between 

41% and 59% of 

predicted 

Class 4, 51%–100%: 

Severe 

Impairment of the 

Whole Person 

FVC ≤ 50% of 

predicted, or FEV 1 

≤ 40% of predicted, 

or DLCO ≤ 40% of 

predicted 

or or or or 

VO2 max between 20 

and 25 mL/kg/min 

VO2 max between 15 

and 20 mL/kg/min 

VO2 max < 15 mL/ 

kg/min 

DLCO is diffusing capacity for carbon monoxide; FVC is forced vital capacity; FEV 1 is forced expiratory 

volume in one second; VO2 max is maximal oxygen uptake. 

Table 4-1.2: American Medical Association Classification of Respiratory Impairment 

Exercise testing and the measurement of VO2max has been advocated as 

the gold standard for assessing a patient’s capacity to perform work, though is 

not part of the routine evaluation of pulmonary impairment. CPET, however, 

may be helpful when dyspnea is greater than either spirometry or the diffusing 

capacity would indicate, or the results of these tests are inconclusive. In 

patients suspected of malingering, review of prior test results may show 

evidence of consistent lack of effort over time. In such cases, exercise testing 

will demonstrate the relationship of heart rate and ventilatory rate at workloads 

actually achieved. In general, individuals with VO2max value under 15 ml/kg/ 

min can be declared unfit or incapacitated for work. However, they may be able 

to perform work if their maximal oxygen uptake is in the range of 15-24 ml/kg/ 

min, depending on the physical activity required. Individuals with VO2max 

greater than 25 ml/kg/min are expected to be able to perform vigorous work 

(see Table 4-1.2) and it has been advocated that fire fighters should be able to 

reach a level of 37 ml/kg/min. Unfortunately, CPETs are expensive and require 

a highly trained staff to perform and interpret testing, and may, therefore, not 

be readily available. 

REFERENCES 

1. American Thoracic Society. Lung function testing: Selection of reference 

values and interpretative strategies. Am Rev Respir Dis. 144: 1991; 1202- 

1218. 

2. American Thoracic Society. ATS Statement: Guidelines for the Six-Minute 

Walk Test. Am J Respir Crit Care Med. 166: 2002; 111–117. 

3. American Thoracic Society. Evaluation of impairment/disability secondary 

to respiratory disorders. Am Rev Respir Dis 1986; 133:1205. 

4 Celli B, Halbert RJ, Isonaka S, B. Schau B. Population impact of different 

definitions of airway obstruction. Eur Respir J 2003; 22: 268–273.

5. Cockcroft DW, Hargreave FE. Airway hyperesponsiveness. Relevance to 

randon population data to clinical usefulness. Am Rev Respir Dis. 142: 

1990; 497-500. 

6. Light R. Clinical pulmonary function testing, Exercise Testing, and 

Disability Evaluation. In: George RB, Light RW, Matthay MA, Matthay RA. 

Chest Medicine 3rd Ed. Philadelphia PA: Lippincott Williams&Wilkins, 

1995: 132-159. 

7. NFPA 1582 Standard on Comprehensive Occupational Medical Program 

for Fire Departments, 2007 edition. National Fire Protection Association, 

Batterymarch Park, Quincy MA. 2007. 

8. Principles of exercise testing and interpretation. By K. Wasserman, J.E. 

Hansen, D.V. Sue, and B.J. Whipp. Philadelphia: Lea & Febiger, 1987. 

9. U.S. Department of Health and Human Services, Social Security 

Administration. Disability evaluation under Social Security. SSA Publication 

#05-10089, February 1986. 



Chapter 4-2 

Imaging Modalities in 

Respiratory Diseases 

By Dr. Subha Ghosh, MD and Dr. Linda B. Haramati, MD 

COMMONLY USED MODALITIES 

Chest X-Ray (CXR) 

X-rays are the oldest and most commonly-used form of medical imaging. Chest 

x-ray (CXR) is the most commonly-performed x-ray examination. A CXR is a 

picture of the chest that shows the heart, lungs, airways, blood vessels and 

bones of the spine and chest wall. It is a painless medical test that involves 

exposing the chest to a small dose of ionizing radiation to produce images of the 

chest contents. It may help physicians diagnose and treat respiratory diseases. 

Science Behind X-Rays 

X-rays, like radio waves, are a form of electromagnetic radiation that can pass 

through most objects including the human body. After careful positioning, 

the x-ray tube emits x-rays aimed at a specific body part (like the chest). 

While passing through the human body, these rays are absorbed by different 

body parts in varying degrees. Dense bone absorbs more radiation while soft 

tissues (for example, skin, muscle, body fat or glands) of the body absorb less 

and air-filled lungs allow most of the x-rays to pass through. The x-rays that 

pass through record an image of the body part on the special photographic 

plate. As a result, bones appear white, air in the lungs appears black and soft 

tissues appear different shades of gray. These images can either be stored as 

film (hard copy) or electronically (digital image). A technologist who is trained 

to perform radiology examinations performs the entire procedure. Studies 

are read by radiologists, who are physicians specially trained to interpret 

radiology examinations. The reports and films are then communicated to 

the patient’s physicians. 

Equipment and Procedure 

Equipment consists of a source of x-rays (x-ray tube) and a special recording 

plate (image plate). The patient is positioned with the plate in contact with the 

patient’s chest and the x-ray tube positioned six feet away. The test requires no 

prior preparation except for removal of jewelry, eyeglasses, metallic objects or 

clothing that may obscure underlying body parts. Patients are asked to remove 

their clothing and wear a gown. Women should inform the technologist if they 

are pregnant or if there is any chance of pregnancy. 

Patients who are able to stand are positioned such that they are against an 

image recording plate. Typically, two views are obtained. The PA (front) view is 

Chapter 4-2 • Imaging Modalities in Respiratory Diseases 293

294 Chapter 4-2 • Imaging Modalities in Respiratory Diseases 

taken with the plate pressed against the chest of the patient with the patient’s 

hands on the hips. The x-ray tube is located six feet behind the patient’s back 

(thus, the patient faces away from the x-ray source). The patient is then asked 

to stop breathing and not move for a few seconds while the x-ray tube is fired 

and an image is obtained. In the lateral (side) view, the patient is turned to face 

the x-ray tube sideways with the arms elevated and the image plate pressed 

at the patient’s side. Patients may be positioned lying down on a table if they 

are unable to stand. Several other views of the chest are also possible. One of 

the most common is the anteroposterior (AP) view performed with portable 

x-ray machines on patients who are sick and bed bound in the intensive care 

unit. The patient typically faces the x-ray source and the x-ray plate is placed 

behind the patient’s back. Additional views include decubitus views (for 

example, a left lateral decubitus film would mean a film taken with the left 

side down , which are useful for diagnosing pleural effusions (fluid); lordotic 

views (an apical lordotic film is taken with the x-ray film cassette behind the 

patient’s back while the patient tries to bend backwards), to better visualize 

the lung apices for hidden tumors or tuberculosis; Expiratory views to diagnose 

pneumothorax, air-trapping; and Oblique views to delineate rib fractures. 

Common Uses 

A CXR is usually the first imaging test to be performed on patients complaining 

of persistent cough, fever, difficulty breathing and trauma to the chest leading 

to chest pain. 

Commonly-diagnosed conditions on a CXR include pneumonia, tuberculosis, 

pleural effusion (fluid around the lung), heart failure and other heart problems, 

chronic obstructive lung disease (emphysema), scarring or inflammation 

within the lungs (pulmonary fibrosis, sarcoidosis), cancer within the lungs 

(primary lung cancer and metastatic cancer), rib fractures and collapsed lung 

from air leak (pneumothorax). 

Benefits of Procedure 

This procedure is painless, relatively inexpensive and widely available with 

equipment which can be operated easily and gives relatively quick results; 

making the test ideally suitable for use in both office settings as well as in 

emergency rooms. 

Risks of Procedure 

There is risk of radiation exposure. The typical dose of radiation received by 

an adult during a CXR is small. It is similar to the dose received by an average 

person from the earth’s background radiation in 10 days (calculated as 0.06 to 

0.1 mSv or 6 to 10 mRem). However, there is always a small chance of developing 

cancer from the exposed radiation. This risk is negligible and estimated to be 

less than 1 in 1,000,000. Benefits of obtaining a diagnosis by getting the x-ray 

often easily outweigh this risk. Another risk with x-rays involves their use in 

pregnancy. Ionizing radiation, such as that used in x-rays, has been implicated 

in several harmful effects on the embryo or fetus within the womb. Women 

should always inform the staff that they are pregnant or may be pregnant. It 

may be advisable in certain cases to do a urine screen for pregnancy before 

obtaining any x-ray examination. Several steps are taken to minimize the

adiation exposure in a CXR. Certain radiation safety organizations monitor 

standards and update techniques used by radiology personnel. Modern x-ray 

machines have devices built-in to reduce scatter or stray radiation. This, as 

well as protective x-ray proof shields, are often employed to ensure that body 

parts not being imaged receive only minimal radiation exposure. 

Limitations 

In proper settings, a CXR is a very useful examination. However, some parts 

of the chest remain hidden on standard views. Some chest conditions like 

asthma, COPD, smoke inhalation or blood clot(s) within the lungs (pulmonary 

embolism) cannot be detected on a CXR examination. Any abnormal finding 

on a CXR would typically prompt additional imaging (e.g., Chest CT scan) 

which may confirm or rule out the initial CXR findings. 

Abnormal Patterns on CXR 

• Nodules: Nodule is a term given to a rounded lesion seen on a CXR 

(Figure 4-2.1a). It may be due to pneumonia, scar, inflammation, 

tuberculosis, or cancer (lung cancer or metastases). If the nodule is 

old (unchanged for last two years) and/or calcified it is unlikely to be 

or become a cancer. 

Figure 4.2.1a: Chest x-ray showing a nodule (less than 3 cm in diameter) without spread 

to adjacent structures. 

• Rate of Growth: Since most tumors start as rounded nodules, a 28% 

increase in their size on an x-ray would mean doubling of the tumor 

volume (e.g., a two millimeter increase in size for a nodule that was 

seven millimeters in size). Rarely, some highly-aggressive tumors, 

like small cell lung cancers, can double their volume in 30 days while 

other slow-growing tumors may take as long as 18 months to double 

their size. In contrast, most benign lesions take less than one month 

or more than 18 months to double their size. 

Chapter 4-2 • Imaging Modalities in Respiratory Diseases 

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• Granulomas: Small nodules, often calcified, that are related to old 

insults such as tuberculosis, fungal disease or sarcoidosis. These too 

are unlikely to be or become cancer. 

• Calcifications: Usually indicate benign (non-cancerous) scar, granuloma 

or hamartoma (non-cancerous congenital tissue). 

• Margins: Typically, smooth in benign nodules and spiculated (irregular, 

serrated) in cancers but exceptions to the rule exist. 

• Cavities: “Holes” in the lung; may be due to congenital causes, infection, 

lung disease or cancer. 

Pleural Abnormalities 

The pleura is a double-layered skin between the lung and chest wall. A CXR is 

able to detect collections of fluid within the pleural space (which is a potential 

space between the lining or membranes covering or surrounding the lungs). 

At least 200 ml, 75 ml and 5 ml of fluid are necessary for detection on the PA 

view, lateral view and decubitus views, respectively). Pleural nodules may be 

due to cancer. Pleural plaques, especially when calcified and on both sides, 

may be due to asbestos-related pleural disease (Figure 4-2.2). Pleural plaques 

when on only one side are more likely due to healed infection or trauma. Pleural 

fluid may be due to infection, heart failure, rheumatologic diseases, cancer, 

to name just a few. 

Figure 4-2.2: Chest x-ray showing asbestos plaques and pleural calcifications (arrow). 

Shadows And Other Markings 

The list of different conditions that can be associated with theses patterns 

are long. Correlation with clinical symptoms is necessary to help determine 

if the abnormality is related to infection, inflammation or an exposure. CT 

scanning and lung biopsy may be necessary.

Examples are as follows: 

• Reticular pattern (crisscrossing lines) may be due to interstitial lung 

disease, sarcoidosis, or heart failure. 

• Nodular pattern (small rounded lesions in large numbers) may be 

due to interstitial lung disease, sarcoidosis, metastatic cancer (spread 

from other organs to lung) and infections like tuberculosis or fungal 

infections. 

• Cysts (ring like) may be due to bronchiectasis (dilated airways from 

old infection or inflammation). 

• Honeycombing are small cysts within reticular lines seen in fibrosis. 

• Ground glass (hazy areas) is a sign of acute or chronic inflammation. 

When acute it is typically due to infection or inhalation injury. When 

chronic it is typically interstitial lung disease or rarely heart failure. 

• Consolidations (dense, opaque, with “air-bronchograms”) are typically 

due to infectious pneumonias and less commonly due to alveolar 

hemorrhage, lung cancers and even rarer conditions like eosinophilic 

pneumonia. 

Computerized Tomography (CT) Scan 

CT scanning is a medical imaging test that uses special x-ray equipment to 

produce multiple pictures of the inside of the human body. These pictures 

are then integrated with the help of a computer to produce a cross-sectional 

image of a particular body part. The test in itself is painless and generates 

images of internal organs which are of much higher clarity (resolution) than 

conventional x-ray images. 

Equipment and Procedure 

CT scanners typically comprise of a CT table, which moves in and out of a small 

tunnel. The patient is positioned to lie down on the CT table. The tunnel consists 

of a ring of x-ray tubes and x-ray detectors, which are opposite one another in a 

machine called the gantry. The gantry rotates around the patient while the CT 

table slides in and out of the tunnel. A separate computer workstation located 

in a different room processes the data generated by the CT scanner to produce 

crisp images of “slices” of the human body (cross-sectional images). In many 

ways, CT scanners follow the same principle of image formation making use 

of x-rays which pass through the body and are absorbed to different extents by 

different body tissues leading to differences in their contrast on the resultant 

image. Thus, bone (which absorbs most of the x-rays) appears white, air (which 

allows most x-rays to pass through) appears black and most soft tissues and 

fluid appear different shades of gray. 

The x-ray beam in a CT scanner traces a spiral path. This is because the gantry 

which hosts multiple arrays of x-ray tubes and detectors rotate around the 

patient who is on the CT table which slides in and out of the tunnel containing 

the gantry. This data is processed to generate cross-sectional images (resembles 

“slices” of the human body). Newer CT scanners have the ability to acquire 

multiple image slices in a single rotation. Thus, thinner slices with greater 


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clarity can be obtained in a shorter time, making these scanners particularly 

useful in scanning unstable, sick patients and children. 

All necessary precautions that are followed before obtaining a CXR should also 

be followed for a CT scan, including awareness of patient’s coexistent medical 

problems, medications and possible pregnancy. Patients are often asked to fast 

overnight (8 to 12 hours) before scanning, particularly if intravenous or oral 

contrast material needs to be given. These are iodinated dyes, which are used 

to opacify blood vessels and intestines to allow better contrast from adjacent 

un-opacified structures. All jewelry and metallic objects are removed from 

the patient who is positioned to lie down either on his back or on his stomach 

on the CT table. Loose fitting gowns and straps, which secure the patient to 

the CT table, may be used. If contrast is necessary, it is administered shortly 

before starting the scan and the patient is instructed on breath holding for a 

few seconds while the scan is taken (actual scan time is less than 30 seconds, 

while the entire process may take less than a half-hour). 

Some common side effects of injected dye include a feeling of warmth 

while the injection is in process. Minor itching and hives are not uncommon 

and can be treated with medications. More serious side effects from injected 

dye are discussed below. Ingested contrast may not taste palatable and rectal 

contrast may cause minor abdominal discomfort. After an uncomplicated 

study is completed, the patient can return to normal baseline activities and 

usually no special instructions are necessary. 

Common Uses 

• Primary comprehensive diagnostic imaging test for evaluation of 

several respiratory symptoms and disease states. 

• Problem-solving tool for further evaluation of potentially-abnormal 

findings on a CXR. 

• Diagnosis and staging of cancer: both for primary lung tumors as well 

as for tumor that has spread to the lungs from elsewhere within the 

body. 

• Planning radiation therapy and assessing treatment response. 

• Detection of disease of the blood vessels and circulation. 

Role of Chest CT in the Diagnosis of Respiratory Diseases 

The chest CT is a powerful tool to evaluate for diseases in the lung. It can be 

used to determine if there is spread of a malignant tumor to the lungs from 

elsewhere in the body (like breast cancer, abdominal cancers, or female 

genital tract cancers). Cancerous growths within the lungs often start off as 

small nodules (Figure 4-2.1b), which can only be detected with a CT, and not 

be visible on a CXR. In addition, a CT may detect presence of enlarged lymph 

nodes, which may harbor tumor cells. A CT may help in staging of tumor and 

evaluate for tumor progression or recurrence after surgery, chemotherapy or 

radiation treatment. A CT scan is commonly-used to detect non-cancerous 

lung diseases as well, such as pulmonary fibrosis (Figure 4-2.3).

Figure 4-2.1b: Chest x-ray and CT scan showing a nodule (less than three centimeters in 

diameter) without spread to adjacent structures. 

Figure 4-2.3: CT showing pulmonary fibrosis with reticular linear shadows, honeycombing 

and traction bronchiectasis. 


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CT findings may be non-specific and require further testing. Additional 

imaging tests such as PET scanning (see below) or obtaining a biopsy (tissue 

sample) from the abnormal area within the lungs for microscopic analysis 

can be performed. A CT can be used in either instance to improve diagnostic 

yield. CT images can be electronically combined with PET images to generate 

“fusion” images. Such PET-CT scans help to provide anatomical and functional 

information at the same time (as an example, CT may localize a rounded lung 

nodule and the PET scan may show the nodule to have no metabolic activity, 

thus both in combination would help characterize the lesion as potentiallybenign, 

non-cancerous in nature). CT scanning can be used to help guide 

biopsy needles with precision to abnormal areas within lungs, thereby allowing 

sampling of tissue for microscopic analysis. 

A Chest CT can also demonstrate diseases such as bacterial pneumonia 

(Figure 4-2.4) and tuberculosis. It can be used to detect complications of 

infections such as pleural effusion (fluid around the lung), lung abscess (pus 

forming cavity within the lungs), bronchiectasis (abnormal dilatation of 

airways) and chronic scarring. 

Figure 4-2.4: Chest CT showing infiltrate with air bronchogram consistent with pneumonia. 

An important role of a CT scan in the lungs is the diagnosis of air-trapping 

and diffuse lung disease (Figure 4-2.5). Air trapping is a non-specific sign of 

small airway disease and can be seen in asthma, bronchitis, emphysema, or 

bronchiolitis obliterans. This is manifest on a CT scan (particularly on scanning 

done at the end of expiration) as areas of relative lucency, which do not show 

a decrease in volume with expiration. Air trapping was the most common 

radiological sign of “WTC Cough” (a disease term coined after several fire 

fighters were affected with the disease while engaging in rescue and recovery 

operations after the September 11, 2001 attacks on the World Trade Center), 

which correlated with other markers of airway hyperreactivity (pulmonary 

function tests and chemical challenge tests). Other findings include a mosaic 

pattern of lung attenuation and non-specific bronchial wall thickening.

Figure 4-2.5: Upper panel shows CT scan taken during inspiration with bronchial thickening 

(white arrow). Bottom Panel shows CT scan taken during expiration with air-trapping (white 

arrow). 

Presence of discrete small nodules along small airways in a “budding tree” 

pattern may suggest acute or active inflammatory bronchitis. Treatment 

with antibiotics can often lead to resolution. Bronchiolitis obliterans can go 

unrecognized (in the absence of chest CT or lung biopsy) or can be mislabeled 

as asthma. In the absence of appropriate therapy, bronchiolitis obliterans can 

progress and lead to disability or death. 

Diffuse lung diseases include several forms of interstitial lung disease which 

cause fibrosis or inflammation of the lungs leading to progressive shortness of 

breath and impaired oxygen-carrying capacity. Disease progression may lead 

to chronic respiratory failure (end stage lungs). Some forms of the disease may 

not be amenable to any form of treatment except for lung transplantation. While 

it is not feasible to describe the chest CT findings of all forms of interstitial lung 

disease, some are particularly relevant to fire fighters and are highlighted below. 


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Sarcoidosis is a common chronic granulomatous disease, which is of 

uncertain cause. It affects lungs and other organ systems. Sarcoidosis and/ 

or Sarcoid-Like-Granulomatous-Pulmonary Disease (SLGPD) have been 

detected with a higher incidence in fire fighters who were exposed to the dust 

and debris that were released into the surrounding environment after the 

collapse of the WTC towers. On imaging, the disease within the lungs has four 

characteristic stages. Patients may present at any stage and the stage may not 

correlate with symptoms or pulmonary function tests. Stage I is symmetric 

enlargement of lymph nodes within the both sides of the chest. Stage II shows 

both involvement of lymph nodes and lung tissue (Figure 4-2.6). The latter is 

present as reticular and nodular opacities, hazy ground glass opacities and 

ring-like cystic opacities which are predominantly seen along the airways and 

vessels (peribronchovascular bundles). Stage III no longer shows lymph node 

enlargement on imaging but continues to show lung tissue involvement. With 

shrinking of the lymph nodes, they can occasionally show a characteristic pattern 

of calcification. Stage IV can show lung cavities and fibrosis. Most patients do 

not progress and many resolve spontaneously without treatment. For those 

with progression or significant functional impairment, corticosteroids and/ 

or other anti-inflammatory medications are very useful (see separate chapter 

on Sarcoidosis for further details). 

Figure 4-2.6: Chest radiograph showing Stage II Sarcoidosis with lymph node (arrow pointing 

up) and lung tissue involvement (arrow pointing down). 

Several rarer forms of diffuse lung disease have been reported in fire 

fighters including case reports of chronic eosinophilic pneumonias with its 

own characteristic CT findings of patchy peripheral pulmonary opacities and 

pleural effusions which resolved after treatment with steroids.

Other chronic fibrotic lung diseases with particular importance for fire 

fighters include idiopathic pulmonary fibrosis, which is characterized by chronic 

progressive scarring of predominantly both lower lobes of lungs, which start 

at the periphery of the lung surfaces. On CT imaging, this is characterized by 

diffuse architectural distortion, ground glass opacities, reticular and nodular 

opacities, cystic lesions (honey combing) and traction bronchiectasis or any 

combination of these findings, but without lymph node involvement (refer 

to Figure 4-2.3). No proven medical treatment exists and currently when 

progressive, lung transplantation is the only therapeutic option. 

Asbestos is no longer used in the United State but can be released from 

damaged insulation found in older houses and commercial buildings during 

renovation, fires and overhaul. Asbestos exposure may lead to a spectrum of 

disease ranging from pleural effusions, pleural plaques, pleural calcifications 

and fibrosis (usually 10 to 50 years after exposure). Chronic asbestos exposure 

(more so in combination with cigarette smoking) increases risk of lung cancer. 

Finally, chronic asbestos exposure may lead to malignant mesothelioma (usually 

20 to 40 years after initial exposure to asbestos), a cancer affecting the outer 

lining of the lungs (pleura) and the inner lining of the abdomen (peritoneum). 

CT scanning of the lungs very well depicts all of these changes. 

CT Angiography is a valuable tool used to diagnose diseases of blood vessels 

and circulation. This test involves injection of iodine-containing dye (contrast 

media) intravenously into the arm of a patient followed by appropriately 

timing the images taken with the help of a CT scanner to opacify the blood 

vessel of interest. The captured data can then be used to reconstruct thin 

sections with detail, which can help to diagnose disease within the arteries 

(pulmonary arteries, aorta) or the veins (systemic or pulmonary veins). The 

injected dye helps delineate blood vessels better by opacifying the vessels 

selectively and thus serving as effective contrast from non-vascular structures 

which are not opacified. Diseases such as clot formation within the pulmonary 

arteries (pulmonary embolism) and abnormalities of the aorta including tears 

(dissections) and dilatations (aneurysms) which can rupture, can be diagnosed 

effectively by this technique. 

Benefits 

• Painless, fast and easy to perform, making it ideal for use in medical 

emergencies. 

• Able to accurately detect disease within the lungs when a CXR is nondiagnostic. 

• Able to image bone and soft tissues including lungs simultaneously. 

Hence, a CT scan done for one indication may help diagnose unsuspected 

disease elsewhere. 

• Can be fused with functional imaging in an attempt to differentiate 

benign from malignant cancerous disease. 

• Can be used to guide needle biopsies (see section below). 

• In many conditions, a CT scan eliminates the need for exploratory 

surgery by giving a definite diagnosis. In surgical cases, it often helps 

in pre-operative planning. 


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Risks 

Risks from the procedure include those associated with radiation exposure 

and risks from injected dye (when contrast material is used in a study). 

Effective radiation dose from a CT chest is roughly equal to that received 

by an average person from background radiation in three years (5mSv). This 

carries a slight increased risk of cancer, which needs to be weighed against the 

benefits of obtaining a diagnosis. Pregnant women have an increased risk to 

themselves and to the fetus from radiation exposure. Women referred for CT 

scanning should inform their physician or technologist if there is a possibility 

that they are pregnant. 

Risks from the injected contrast material include an allergic-like reaction 

to dye and damage to kidney functions. Allergic reactions, like minor rashes 

occur with some frequency, while serious (anaphylactoid) reactions are 

exceedingly rare. A history of asthma or COPD confers an increased risk for 

a flare of these diseases. 

When the risk-benefit ratio supports the use of contrast, patients can be 

pre-medicated with steroids and other medications before the study. 

Risk of contrast induced kidney damage is more common in patients who have 

borderline or pre-existing impaired renal function. Certain medications and 

disease states predispose to development of contrast induced kidney disease 

and need to be stopped or the dosages modified after consulting a physician. 

Ample hydration and pre-medication with kidney protective agents has shown 

some value in preventing severe renal damage from injected radio contrast. 

Limitations 

• Very obese patients may not fit into the CT scanner. 

• MRI may be superior to CT scan for diagnosis of vascular conditions 

(especially when injection of iodinated contrast material is 

contraindicated). Chest CT is superior to MRI for diagnosis of lung 

conditions (such as nodules, interstitial lung disease, and emphysema). 

Future Advances 

Advancement in detector technology has led to the development of new multislice 

CT scanners which allow thinner slice acquisition in a shorter time 

resulting in greater clarity of image. This is particularly useful in imaging of 

children and very sick, medically-unstable patients. 

ROLE OF SPECIAL IMAGING MODALITIES: 

PET & MRI SCANS 

PET Scan 

PET is an abbreviation for Positron Emission Tomography. PET is a powerful, 

non-invasive imaging modality that focuses on biochemical changes that occur 

in diseased tissue like cancer, sarcoidosis, tuberculosis and certain infections. 

The rapid cell growth that occurs in tumor and infection leads to a higher

metabolic activity and more glucose consumption than in normal healthy 

tissue. PET scanners detects this increased metabolic activity as “hotspots” 

that light up on the image (Figure 4-2.7). 

Figure 4-2.7: PET and CT fusion image showing hot area (arrow) is nodule subsequently 

proven to be a cancer. 

PET scans are performed in the nuclear medicine laboratory. The imaging 

study involves injection of a radioactive glucose into the blood stream. The 

radioactive tracer accumulates in the organ system or body tissues which 

are most metabolically active. In these tissues, the radiotracer releases small 

amounts of energy in the form of gamma rays. These rays are then detected by 

a special camera, which converts the signal into computer-processed images 

of that part of the human body. 

PET scanning can be combined with low dose CT scanning to form “fusion” 

images with a single machine. The two techniques complement one another. 

While a CT shows anatomical structures with detail, PET shows increased 

metabolic and biochemical activity in the affected regions. For example, a 

small nodule in the lung, which is barely noted on a plain CXR, is accurately 

detected and localized on CT scanning, and the PET study done on the same 

subject may highlight increased glucose consumption within that nodule as 

a “hot spot.” The fusion PET-CT images reveal the "hot spot" to be localized 

within the nodule, thereby suggesting tumor or infection as possible causes. 

PET may help guide further management and treatment planning. The 

study may determine that a suspicious nodule is metabolically inactive and 

may be benign. A metabolically active lesion may be either due to infection 

or cancer and a decision on whether to biopsy the nodule can then be made. 

PET scanning is helpful in determining spread of tumor in distant organs and 

lymph nodes and thus in tumor staging. Similarly, response to treatment of 

cancer may be well depicted by performing a post treatment follow-up PET 

scan that may reveal residual or recurrent tumor. 

Several caveats are important to note. First, certain benign conditions 

like active infection or inflammation (ex., sarcoidosis) may be PET positive, 


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while certain slow growing tumors (ex. Bronchoalveolar lung cancer) may 

not demonstrate PET positivity, owing to their relatively-slow metabolic rate. 

Second, PET scans are not accurate in their characterization of nodules less 

than eight millimeters in diameter. Third, PET scans are not accurate in their 

characterization of tumor spread to neurologic tissues (ex. brain and spinal 

cord). Of course, the technology continually improves and newer generation 

PET scans will hopefully overcome these diagnostic barriers. Finally, the use 

of PET radioactive tracers involves exposure to ionizing radiation (like gamma 

rays) with low risk for radiation-induced side effects. Lactating women must 

be instructed to stop breast feeding for 24 hours after the procedure. 

MRI Scan 

MRI is an abbreviation for Magnetic Resonance Imaging. It is a non-invasive 

imaging modality which uses a powerful magnetic field and radio waves 

to generate signals from different body parts, which are then processed by 

computer to generate detailed images of the human body. An MRI images of 

the chest provide increased soft tissue contrast. This is particularly useful in 

imaging the beating heart and the great blood vessels in the chest. Use of an MRI 

within the lungs is limited because air within the lungs is not well imaged with 

an MRI. The role of an MRI in the context of lung disease lies predominantly 

in the assessment of lung cancer when it can depict the relationship of the 

cancer to adjacent nerves, blood vessels and chest wall. Hence, an MRI for 

lung cancer is not useful in characterizing nodules but is of value if there are 

questions about metastatic spread to vessels, heart, or chest wall. 

An MRI scan has some major drawbacks. The study is contraindicated in 

patients with cardiac pacemakers and defibrillators. Moreover, the limited 

availability of an MRI as compared to a CT, relative length of the scan time 

making it unacceptable for unstable patients and claustrophobia in selected 

patient groups may limit the role of this tool. 

IMAGE GUIDED TISSUE SAMPLING 

Imaging of lungs often leads to detection of abnormal findings such as nodules 

or masses. It is sometimes difficult to ascertain whether they are benign (such 

as a result of infection or scar) or malignant (cancerous). Image-guided needle 

biopsy or aspiration of the nodule or mass is a procedure by which a narrowgauge, 

hollow needle is introduced using imaging such as a CT, fluoroscopy or 

ultrasonography to guide the path of the needle into the abnormality. A sample 

(not the entire nodule) is removed and examined directly under a microscope 

to look for signs of cancer or other diseases. 

Preparatory Instructions 

Patients are instructed to fast for at least six to eight hours before the procedure. 

They may, however, take certain medications with sips of water. It is important 

to inform the radiologist of all medications. Certain medications, like insulin, 

need dose adjustments, because of overnight fasting, while others like blood 

thinners may have to be stopped for days prior to the procedure. Any history of 

allergy and prior complication to anesthesia needs to be recognized. As with

all procedures that involve radiation exposure, women need to inform their 

physicians and radiologist if there is a possibility that they are pregnant. Most 

of these procedures are performed on an outpatient basis. Although all patients 

are given local anesthetic injections around the skin puncture site, some may 

need additional dose of intravenous sedation to alleviate anxiety and fear. 

Hence, it is important that all patients are accompanied by family or friend(s) 

who can accompany the patient or drive them home after the procedure. 

Nature of the Procedure 

Needles 

A biopsy needle is a hollow needle, which varies in length (can be several 

inches in length) and in diameter, but is usually no wider than a paper clip. 

Two different types of needles may be used depending on the type of sample 

being obtained. One is a fine needle (thinner than a blood drawing needle) 

and the other is a core needle (slightly thicker and contains an inner needle 

attached to a spring device). 

Image Guidance 

Image guidance is usually provided by CT or fluoroscopy and rarely by 

ultrasonography. CT scanner details have been provided earlier. The fluoroscopy 

equipment consists of a radiographic table, x-ray tube and a monitor with 

screen. Real time video or still images are obtained. Ultrasound scanners use 

high frequency sound waves emitted from devices called transducers that are 

used to scan the body. These sound waves are reflected off different tissues 

within the human body and are captured by the transducer as they echo. A 

computer console then integrates these echo signals to process an image of 

the body parts, which are displayed on a video display screen. Several factors 

like the amplitude (strength), frequency and time it takes for the sound waves 

to return from the different depths of the tissues, influence the nature of the 

image. Ultrasound has a role in localizing and draining fluid collections in the 

pleural space. This is because of the ability of the sound waves to propagate 

through fluid. Fluid inside the pleural space appears dark and casts fewer 

echoes than air or solid tissues within the lungs. Ultrasound does not produce 

a radiation exposure. 

Procedure 

Using imaging guidance, the physician inserts the needle through the skin 

and into the abnormal tissue and collects samples, which are analyzed in the 

pathology laboratory for diseases. The process is usually performed on an 

outpatient basis. Written informed consent is obtained after explaining all 

probable risks, complications, and alternatives to the patient. An intravenous 

line is inserted into one of the veins of the hand or elbow. This is helpful in 

two ways. Some patients may need mild sedation before the procedure. More 

importantly, in case of any complications during the procedure, the venous 

access may save time administering medications into the veins. The patient 

may either be positioned lying down (usually the case) or rarely be sitting down 

(if procedure is performed under fluoroscopy or ultrasound). Sterile antiseptic 

precautions are obtained. Adequate local anesthetic is injected at the site of 


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the insertion of needle after preliminary imaging has localized the exact site 

of needle insertion. The patient is given proper breathing instructions and 

asked to hold the breath for a few seconds while the needle is inserted. The 

positioning of the needle may require multiple images to be taken to help 

guide the needle into the appropriate location. Once the lesion is reached, 

the radiologist aspirates samples from the lesion(s) and a cytopathologist 

technician prepares a microscopic slide of the sample in order to examine 

the material under microscope. If the sample seen under microscopy is not 

considered adequate to make a diagnosis, additional tissue can be collected. 

After the procedure, pressure is applied to the injection site to control any 

local bleeding. The injection site is covered by sterile dressing and the patient is 

monitored usually in the radiology observation area for a few hours. A follow-up 

CXR is usually performed to rule out complications like lung collapse due to 

air leak (pneumothorax) or collection of blood within the chest (hematoma 

or hemothorax). After reviewing the follow up CXR and confirming patient 

stability, the patient is discharged home with instructions. Physical exertion 

like lifting heavy weights, running, and contact sports, as well as air travel, are 

prohibited for 24 hours after the procedure. Pain medications may be taken 

as instructed by the patient’s physician. Patients are made aware that they 

should report to the emergency room if they experience increased shortness 

of breath, sharp chest pain, rapid pulse or excessive hemoptysis (coughing 

blood). Slight streaks of blood mixed with cough are not uncommon after the 

procedure and should not be a cause for alarm. 

Benefits 

• Reliable and relatively safe (in experienced hands), quicker and less 

invasive way of differentiating a benign (treated non surgically) from 

malignant lung lesion or nodule (treated by surgery, chemotherapy or 

radiation). 

• Done on outpatient basis, with faster recovery time than open surgical 

biopsy. 

Risks 

• As high as a 25% risk of collapsed lung due to air leak (pneumothorax). 

This is usually self-limiting and treated with oxygen while the patient 

is positioned with the affected lung in the dependant position and 

monitoring of the patient’s vital signs and CXR(s) over a period of 

time. Rarely, the air leak may be severe enough to require a chest 

tube insertion and hospital admission for several days. Warning signs 

include shortness of breath, cough, sharp chest and shoulder pain 

increased on breathing. In making the decision as to whether biopsy 

should be obtained by CT guided needle or surgery, it should be noted 

all surgical patients leave the operating room with chest tubes. 

• Risk of bleeding: minor bleeding from the site is not uncommon as is 

minor coughing up of blood from the biopsied lung. Serious bleeding 

is rare. 

• Infection at the biopsy site is rare.

Limitations 

• The material obtained from a needle biopsy may not be sufficient to 

make a diagnosis. 

• Needle may not be in an active site of lesion and thereby give a false 

negative result (false reassurance). This possibility must be carefully 

considered when the diagnosis appears to be non-cancerous. 

• Small nodules less than one centimeter are difficult to diagnose on 

needle biopsy. 

• Certain diseases like cystic lungs, emphysema, severe heart failure, 

bleeding disorders and patients with poor oxygenation may be 

contraindications for this procedure. 

IMAGING OF PULMONARY ARTERIES AND VEINS 

The pulmonary arteries carry de-oxygenated blood from the right ventricle of 

the heart to the lungs for oxygenation. The oxygenated blood is then returned 

by the pulmonary veins into the left atrium of the heart. The main pulmonary 

artery starts as a trunk approximately two inches long and slightly over one 

inch wide that arises from the right ventricle outflow tract. It then branches 

into right and left pulmonary arteries, which further divide to supply the 

corresponding lung. 

The pulmonary arteries are involved in several disease processes. A pulmonary 

embolism (PE) is a sudden blockage of one or more pulmonary arteries, caused 

by a blood clot, which forms, usually in the leg or pelvic veins. 

In fire fighters, probably the most common cause for a blood clot is leg 

trauma with subsequent prolonged inactivity (casting and or bed rest). See 

the separate chapter on pulmonary embolism for further details. Once the 

blood clot goes to the lung, the patient experiences sudden shortness of breath, 

chest pain and depending on the relative size of the clot, sudden death, if 

not promptly treated. Another vascular disease is pulmonary hypertension 

which is a more insidious disease of the pulmonary arteries, which occurs as 

a consequence of several chronic lung conditions including interstitial lung 

diseases and severe emphysema. It can also be caused by severe sleep apnea 

and certain cardiac conditions. It results in poor exercise tolerance and may 

lead to a progressive, fatal course. 

Pulmonary Angiography 

The classic test for imaging pulmonary arteries is pulmonary angiography. It 

involves injection of iodinated dye into the circulation with subsequent direct 

x-ray visualization (fluoroscopy) of the lungs. The test can be done in either 

invasively or in a non-invasive manner using CT scanning. 

Conventional (Catheter) Pulmonary Angiography 

Conventional pulmonary angiography is invasive because a catheter is 

introduced into the right heart through one of the thigh veins. Contrast or 

dye is then injected through this catheter into the pulmonary artery. Catheter 

pulmonary angiography is now infrequently performed as a CT pulmonary 

angiography, a non-invasive test has gained wide acceptance. 


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CT Pulmonary Angiography (CTPA) 

CTPA is a non-invasive imaging test for visualizing the pulmonary arteries 

using CT with iodinated contrast. The contrast is injected through a small 

vein in the arm or leg. The scanning is optimally timed such that the contrast 

is within the pulmonary arteries at the time that the image is acquired. The 

scanning time is usually about five seconds and the entire time within the 

scanner is approximately five minutes. CTPA demonstrates normal pulmonary 

arteries as white (because these are opacified by radio contrast dye). A blood 

clot (pulmonary embolism) would show up as dark (filling defect) within the 

blood vessels (Figure 4-2.8). The size of the vessels can be accurately measured 

to see if these are dilated, which can be a sign of pulmonary hypertension. 

Figure 4-2.8: Chest CT Angiogram showing pulmonary artery emboli (blood clots) appearing 

as intravascular filling defects (arrows) in this contrast (dye) study. 

Benefits 

The advantages of CTPA are its non-invasive nature, fast speed, wide acceptability 

and availability for patients. CTPA can also depict disease elsewhere within 

the lungs or adjacent structures which can explain the symptoms. CTPA is a 

highly-effective and widely-used test for diagnosing PE and has the ability to 

identify PE in small branches of pulmonary arteries. 

Limitations 

The disadvantage of CTPA is the difficulty in detecting small peripheral blood 

clots. As technology improves this becomes less of a limitation as each newer 

generation CT scan has greater resolution. 

Risks 

See risks of CT with contrast (iodinated dye) (above).

Ventilation Perfusion Scintigraphy (VQ Scanning) 

VQ scan is another non-invasive medical imaging test used to diagnose PE. 

This test is one of several nuclear imaging techniques used in medicine. It is 

less widely used owing to wider availability of CT technology. The test uses 

radioactive materials in relatively low doses, which are inhaled and injected 

into the human body. While passing through the human body, these radioactive 

materials emit certain rays such as gamma rays which can be detected by 

special cameras (gamma cameras) to create a computer generated image of 

that part of the body. 

The test involves two phases, namely ventilation and perfusion phases. These 

two phases evaluate how well air and blood are able to circulate through the 

bronchial airways and the pulmonary circulation, respectively. The ventilation 

phase of the scan involves inhalation of a gaseous radionuclide like xenon or 

technetium DTPA through a mask or mouthpiece. Impaired uptake of these 

inhaled radiotracers due to airway obstruction or pneumonia leads to image 

voids from the corresponding lung on the ventilation scan. The perfusion phase 

of the scan involves injection of a radionuclide tracer (usually radioactive 

technetium tagged to macro aggregated albumin) into one of the arm veins. 

The tracer circulates through the lungs via the blood stream. 

Blood clots within pulmonary arteries result in impaired circulation of the 

radionuclide in that lung or part of the lung without hampering ventilation or 

airflow. This is reflected in the perfusion scan classically as wedge-shaped 

area(s) of decreased uptake of radio tracer in that part of lung which has a 

normal ventilation image and is described as a mismatched defect. 

In addition to using VQ scans for the diagnosis of PE, VQ scans are sometimes 

used for : 

• Determining lung performance before and after lung surgery 

• Determining extent of smoke inhalation injury (typically in a research 

setting). 

Benefits 

• Useful in patients whose CXRs are normal and in those with allergy 

to iodinated contrast or in renal failure where CTPA would be 

contraindicated. 

• Lower radiation dose than CTPA 

• Can detect smaller more peripheral pulmonary blood clots than can 

be done by current CTPA. 

Limitations 

The disadvantage of VQ scans is that a large number of the scans yield 

intermediate or non-diagnostic results. The scan is only useful if the result is 

negative or positive (high probability). Matched defects (abnormal ventilation 

and perfusion in the same area of the lung) are non-diagnostic because although 

they are mostly often due to pneumonia or obstructive airways diseases, they 

can less commonly be due to PE. Clinical judgment then determines whether 

additional testing is needed. 


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Risks 

• Although the total amount of radiation exposure is low, it is not 

negligible. 

• Lactating mothers must be warned to stop breast-feeding for 24 hours 

after the procedure. 

Role of Ultrasonography in Imaging of Pulmonary Embolism 

Most blood clots, which cause PE, arise from the lower limb veins in the thighs. 

Ultrasonography of the veins of the thigh and calves (Venous Doppler) can 

be performed to detect blood clot in these veins. A positive venous doppler 

test along with presence of a blood test call D-Dimer (a surrogate marker for 

blood clots), greatly increases the patient’s probability of having a PE. These 

tests in isolation or when considered together, can dictate treatment with 

anti-clot medications without the need for further testing such as CTPA or VQ 

scans. This is particularly useful in cases like pregnancy where confirmatory 

tests such as CTPA or VQ scanning should be avoided when possible due to 

radiation risk to the fetus. 

REFERENCES 

1. Diagnosis of Disease of the Chest. Fraser and Pare, Volumes 1 through 4. 

W.B. Saunders Co., Philadelphia, Pa. 

2. Murray and Nadel’s Textboook of Respiratory Medicine. Mason, Broaddus, 

Murray and Nadel. Volumes 1 and 2. Elesevier Saunders, Philadelphia Pa. 

3. Pulmonary Diseases and Disorders. Fishman. Volumes 1 through 3. 

McGraw-Hill Inc. New York.

Chapter 4-3 

The Solitary 

Pulmonary Nodule 

By Dr. David Ost, MD 

An isolated nodule in the lung, often called a solitary pulmonary nodule, has 

long challenged physicians. At the heart of the dilemma, the question remains: 

“Is it cancer?” Bronchogenic carcinoma, a form of lung cancer, is the most 

common cancer (malignancy) found in solitary pulmonary nodules, and it 

remains the leading cause of cancer death in the United States. When faced 

with a solitary pulmonary nodule, the physician and the patient usually have 

one of three choices: 

1. Observe it with serial chest computed tomography (CT) scans. 

2. Perform additional diagnostic tests (imaging and/or a biopsy). 

3. Remove it surgically. 

The proper choice depends on radiographic appearance, assessment of 

probabilities based on epidemiology, assessment of surgical risk, and patient 

preferences. Surgical resection of an early solitary malignant lesion still 

represents the best chance for cure. On the other hand, unnecessary resection 

of benign nodules exposes patients to the morbidity and mortality of a surgical 

procedure. The aim of this chapter is to review what we know about the solitary 

pulmonary nodule in order to formulate a systematic approach to thinking 

about this common and often controversial problem. The goal will be to arrive 

at a solution that will facilitate prompt identification of malignant lesions so 

that they can be brought to surgery while avoiding surgery in patients with 

benign nodules. Finally, we will review the risk factors that are of particular 

relevance to fire fighters and related personnel with respect to solitary 

pulmonary nodules. 

DEFINITION 

A solitary pulmonary nodule is defined as a single discrete pulmonary opacity 

that is surrounded by normal lung tissue that is not associated with enlargement 

of the lymph nodes (adenopathy) or collapsed lung tissue (atelectasis). 

Previously there was controversy as to what constituted the upper size limit 

for defining a solitary pulmonary nodule. Some early series included lesions 

up to six centimeters in size. However, it is now recognized that lesions larger 

than three centimeters are almost always malignant, so current convention is 

that solitary pulmonary nodules must be three centimeters or less in diameter. 

Larger lesions should be referred to as lung masses and should be managed 

with the understanding that they are most likely cancerous. Prompt diagnosis 

and surgical resection if possible is usually advisable. 

Chapter 4-3 • The Solitary Pulmonary Nodule 313

314 Chapter 4-3 • The Solitary Pulmonary Nodule 

INCIDENCE AND PREVALENCE 

The frequency with which a solitary pulmonary nodule is identified on 

chest x-ray is about one to two per thousand chest radiographs. 1 Most of these 

are clinically silent, and about 90% are noted as an incidental finding on 

radiographic examination. The percentage of these nodules that are cancerous 

(prevalence) varies widely, depending on the patient population; thus, many 

case series may not be directly comparable. Surgical series in the era before 

a CT, including both calcified and noncalcified nodules, reported an overall 

prevalence of cancer of 10 - 68%. 

In younger patients the probability of cancer being present in a given nodule 

is less. In a Veterans Administration Armed Forces Cooperative Study in 1963 

there was an overall 35% malignancy rate. This group included a significant 

number of young military recruits, and nearly half were under the age 50. 2 Of 

those over the age of 50, a 56% malignancy rate was noted, with a 30% incidence 

of benign granulomas. Of those under the age of 35, only three patients had a 

malignancy, only one of which was a primary lung carcinoma. 

Today, a CT is used to screen out benign-appearing calcified nodules. 

Densely-calcified nodules are usually benign (discussed below). If we eliminate 

the densely calcified lesions, the probability of cancer in the remaining non- 

1, 3 

calcified lesions is significantly higher: 56 - 100% in various studies. 

Importantly, most prior series were based on patients who had been referred 

to surgery for the lung nodule. When nodules are detected incidentally while 

looking for other problems, or as part of a lung cancer screening program, the 

probability of cancer is much less. In these instances, if the lesion is small (less 

than eight millimeters) then the overall prevalence of malignancy is under 

five percent. 

Geographic region also matters. In some areas of the world, certain diseases 

are very common (endemic). For example, in the southwestern United States, 

a fungal infection of the lung, coccidioidomycosis, is quite common. This is 

usually a self-limited infection, also known as Valley fever. However, it can 

often leave a small scar on the lung, which appears as a solitary pulmonary 

nodule. Nodules detected in patients from this area can be expected to have 

a lower probability of malignancy, since many of the lung nodules seen are 

actually due to old infection. Other infectious diseases, such as tuberculosis 

(TB) and histoplasmosis, can cause old scars in the lung that appear as solitary 

nodules just like coccidioidomycosis. TB is common in some areas of the 

developing world. Histoplasmosis is common through the midwestern United 

States. As an example, in an Air Force Medical Center study from Illinois of 

137 patients, only 22 (16%) had a malignancy. Granulomas were diagnosed in 

103 patients (75%); 53 of them were attributable to histoplasmosis endemic to 

the area. Most of these patients (77%) were under age 45, and no malignant 

nodules were diagnosed in patients less than 35 years of age. 

MALIGNANT SOLITARY PULMONARY NODULES 

Risk factors for malignancy have been identified from studies of large series of 

solitary pulmonary nodules and include patient age, smoking history, nodule 

size, and prior history of cancer.

Age is one of the most consistent risk factors. Cancer is very rarely found 

in patients under the age of 35. 2, 4, 5 In a series of 370 indeterminate solitary 

pulmonary nodules, the incidence of malignancy increased from 63% for 

patients between the ages of 45 and 54 to 74% for ages between 54 and 64 and 

continued to rise with age to 96% for those above the age of 75. 3 

Smoking is closely correlated with the development of lung cancer, particularly 

squamous and small cell carcinoma. The Surgeon General’s report of 1964 and 

subsequent studies have demonstrated that the risk of lung cancer increases with 

the duration of smoking and the number of cigarettes smoked. Average smokers 

have about a 10-fold risk, and heavy smokers a 20-fold risk of developing lung 

cancer when compared to nonsmokers. Smoking is responsible for about 85% 

of the cases of lung cancer. Cessation of smoking will reduce this risk after 10 

to 20 years, but it now appears that former smokers have a slightly higher risk 

of cancer throughout their lifetimes. Overall, smoking avoidance or cessation 

is the single best preventive measure against lung cancer. 

Nodule size is closely correlated to risk of cancer, with larger nodules having 

a higher probability of cancer than smaller ones. Nodules larger than three 

centimeters will be cancerous about 80 to 99% of the time, while those under 

two centimeters in size will be cancerous about 20 t 66% of the time. 

A history of current or prior cancer in an organ other than the lung greatly 

increases the probability that a lung nodule is cancerous. Depending on the 

study, 33- 95% of such nodules are cancerous. Most of these represent spread of 

cancer from the other organ to the lung. This spread of cancer from one organ 

to another is called metastasis. So lung nodules in this case may represent 

metastasis of a previously-diagnosed cancer to the lung. The most common types 

of cancer that spread to the lung and cause nodules are cancers of the colon, 

breast, kidney, head and neck tumors, sarcoma, and melanoma. Because of the 

high likelihood of cancer, a nodule in a patient with an established diagnosis 

of cancer should be treated differently from other solitary nodules. If there is 

no other metastatic spread (cancer outside of the lung), one should consider 

proceeding directly to biopsy of the nodule. Even in the presence of a known 

cancer, some of these nodules may represent a second primary pulmonary 

malignancy. A second primary means that the patient has two cancers- one 

in the other organ system and a separate lung cancer. This is different than 

having a cancer in another organ which has spread to the lung (metastatic to 

the lung). Special microscopic techniques (immunohistochemistry) can be 

used to distinguish between these two possibilities. In either case, if cancer is 

demonstrated and there is no evidence of spread of the cancer outside of the 

lung, then resection of the nodule should be considered. 

BENIGN SOLITARY PULMONARY NODULES 

Non-cancerous (benign) solitary pulmonary nodules are more common in the 

young and in nonsmokers. They include both infectious and noninfectious 

granulomas, benign tumors such as hamartomas, vascular lesions, and rare 

miscellaneous conditions. Benign tumors are those that usually are not life 

threatening and do not spread to other organs (metastasize). 

Chapter 4-3 • The Solitary Pulmonary Nodule 

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Hamartomas are the most common benign tumors presenting as solitary 

pulmonary nodules. They are believed to be developmental malformations 

composed mainly of cartilage, fibromyxoid stroma (connective tissue), and 

adipose tissue (fat). A review of six studies of resected solitary pulmonary 

nodules since 1974 shows five percent were histologically proven hamartomas. 

In a series of 215 hamartomas resected at the Mayo Clinic, the peak incidence 

was in the seventh decade of life; male-to-female ratio was 1:1; and the 

average size was one and one half centimers, although some were as big as 

six centimeters. Most hamartomas were asymptomatic (97%), and 17% were 

noted to grow slowly on serial radiographic examination. Hamartomas may 

be identified radiographically by a pattern of “popcorn” calcification, which 

is often intermixed with areas of low attenuation on a CT scan representing 

fat deposits within the nodule. A CT appearance will be diagnostic in about 

50% of hamartomas. 

Infectious granulomas make up more than 90% of all benign nodules. They 

arise as a result of healing after infection from a variety of organisms. The 

offending agents will vary, depending on geographic location. Among the most 

common causes are histoplasmosis, coccidioidomycosis, and tuberculosis. 

Other, less common causes are dirofilariasis (dog heartworm), mycetoma, 

echinococcal cyst, and ascariasis. A history of exposure is important in 

establishing a possible infectious origin. Clues such as prior travel history, 

places of residence, occupation, and pets may be invaluable in some instances. 

Noninfectious granulomas sometimes occur as solitary pulmonary nodules in 

systemic diseases such as sarcoidosis. Sarcoidosis is an inflammatory condition 

which actually affects multiple organs but the lung is the most commonly 

affected. Sarcoidosis may cause lung nodules. When it does, the nodules are 

frequently accompanied by enlargement of the lymph nodes. Other signs and 

symptoms of sarcoidosis include uveitis (inflammation of part of the eye), skin 

problems, arthritis, and fevers. Other systemic diseases that may cause lung 

nodules include rheumatoid arthritis and Wegener’s granulomatosis. 

Miscellaneous causes of solitary pulmonary nodules have been described. 

Some of the more common conditions are lung abscess; pneumonia; pseudotumor 

(which represents fluid in a fissure that actually lies between lobes of the 

same lung); hematomas after thoracic trauma or surgery; and fibrosis or 

scars resulting from prior infections. Rarer conditions presenting as solitary 

pulmonary nodules include silicosis (often due to certain types of coal mining), 

bronchogenic cyst (a congenital abnormality), amyloidosis, pulmonary infarct 

due to a blood clot, and congenital vascular anomalies. Sometimes smaller 

blood vessels may form connections and these can appear as nodules as well. 

These connections are usually between arteries and veins, and are known as 

arteriovenous malformations. They often appear as a solitary pulmonary nodule, 

and they may grow slowly over years. They have a characteristic appearance 

on a contrast-enhanced CT scan that is usually diagnostic. 

IMAGING TECHNIQUES 

Imaging techniques are often helpful in distinguishing benign from cancerous 

causes of solitary pulmonary nodules, and as such they play a key role in 

evaluation and management. During the last decade, rapid advances in both

CT and positron emission tomography (PET) have dramatically changed the 

diagnostic approach to solitary pulmonary nodules. The primary technologies 

that need to be considered are plain chest radiography, CT, and PET. 

Plain Chest Radiography 

Most solitary pulmonary nodules are discovered on routine plain chest 

radiograph while asymptomatic. Malignant nodules are usually identifiable on 

chest radiograph by the time they are 0.8 to 1 centimeter in diameter, although 

nodules 0.5 to 0.6 cm can occasionally be seen. 1 Most will be identified on 

posteroanterior (PA) projection, but some will be seen only on lateral projection, 

so standard PA and lateral chest radiography should be obtained whenever 

possible. When a nodule can be seen only on one projection, the physician 

should question whether it is truly in the lung parenchyma. Structures overlying 

the skin of the chest wall—such as leads used for cardiac monitoring, nipple 

shadows, skin lesions, bone lesions, and pulmonary vessels on end—can all 

mimic pulmonary nodules. 

Once it has been ascertained that a true nodule exists, the first step is to 

make every effort to obtain previous radiographs for comparison. Cancers 

have a typical growth rate. If a lesion does not grow it is not likely to be cancer. 

Conversely, if a lesion grows over days, then it is growing too fast to be cancer. 

As a rule of thumb, if a nodule has remained stable with no increase in size for 

two years, it is very probably benign and warrants no further investigation. 

Conversely, a large nodule that was not present on a comparable radiograph 

within the past two months is unlikely to be cancerous, since a cancer would 

not have grown so rapidly. 

Computed Tomography 

Computed Tomography (CT) is the main tool for diagnosis and follow-up of 

lung nodules. CT is indicated when one is assessing indeterminate nodules 

less than three centimeters in diameter. It can pinpoint the exact location of 

the nodule and provides three-dimensional images of the lesion. Thin-section 

high-resolution CT (HRCT) can better define the borders and the nodule’s 

relation to adjacent structures, such as blood vessels and the pleura (the 

outside lining of the lung where it meets the chest wall). It is more sensitive 

than standard chest x-ray in detecting calcification patterns which are useful 

in determining if a lesion is cancerous or not. It can also detect fat within a 

nodule—which, when coupled with calcification, is highly suggestive of a 

benign hamartoma. A CT is also useful in looking for hilar or mediastinal 

adenopathy (enlargement of the lymph nodes), and in evaluating accessibility 

of nodules for biopsy or resection. 

The morphology or shape of a nodule, in particular its borders, provides 

useful information and insight into whether or not the lesion is likely to be 

cancerous. Nodules that are very smooth and perfectly rounded are less likely 

to be malignant. Malignant nodules often have irregular or “spiculated” 

borders (Figure 4-3.1). 

Another CT technique that may be helpful is incremental dynamic CT, 

which uses increasing doses of iodinated intravenous contrast to look for 

enhancement of nodules. 6 Malignant nodules enhance more than benign 


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Figure 4-3.1: Spiculated lesion on CT highly suggestive of malignancy. 

ones when given contrast. Occasionally, benign lesions, such as hamartomas 

and tuberculomas, may also enhance. In centers with expertise with this 

methodology, the sensitivity and specificity of this test is good. However, few 

centers at the present time are using this approach. 

In summary, when using CT imaging, attention should be paid to the lesions 

size, location, shape of the border, density, and contrast enhancement if 

available. Nodules that are bigger than three centimeters or that have suspect 

characteristics in the right clinical setting (e.g., an older smoker, spiculated 

borders) should be considered for biopsy or resection. 

Positron Emission Tomography (PET) 

Newer imaging methods, such as PET, can be used to differentiate noninvasively 

between malignant and benign nodules. PET takes advantage of the fact that 

tumor cells have increased metabolism and therefore have higher glucose uptake. 

PET scanning uses a radioactive form of glucose, fluorine-18 radioisotope (FDG), 

which is injected into the patient, to measure metabolism. This radioactive 

glucose is not dangerous to the patient. After it is injected, it is taken up by 

the nodule. Malignant nodules, since they are more metabolically active, 

will take up more, while benign lesions will take up less. Since the glucose is 

radioactive, this can then be measured by a PET scanner. This system is both 

highly sensitive and specific. One review, combining the results of 13 different 

studies, estimated that PET scan was 94.3% sensitive detecting cancer in 

solitary pulmonary nodules and was also fairly specific at 83%. 

However, a PET scan has some significant limitations. It appears to be less 

sensitive for lesions less than one centimeter in size, so its use should be limited 

to those lesions one centimeter or greater in size. 7 False negative findings have 

also been seen in patients with bronchioloalveolar cell carcinoma, carcinoid 

tumors, and mucinous adenocarcinomas. 8, 9 False positive results have been 

seen in patients with granulomatous infections, such as tuberculosis or 

endemic fungi, as well as in patients with inflammatory conditions, such as 

10, 11 

rheumatoid arthritis and sarcoidosis.

DISTINGUISHING BETWEEN BENIGN AND 

MALIGNANT NODULES 

The goal of management algorithms for solitary pulmonary nodules is to bring to 

surgery all patients with potentially curable disease while avoiding unnecessary 

surgery in those who do not need it. As such, distinguishing between benign 

and malignant nodules is critical. Assessing image characteristics from a PET 

scan at a given moment in time is one method to help distinguish benign from 

malignant pulmonary nodules. However, there are other methods that can 

help. These include assessment of a nodule’s shape and calcification pattern, 

the nodule’s growth rate, and assessment of the probability of malignancy 

based on epidemiologic risk factors. 

Nodule Shape and Calcification Patterns 

Certain shapes make a nodule more likely to be malignant. Although nodules 

may appear to be spherical on a plain chest radiograph, further study by a CT 

may disclose irregular borders and shapes (Figure 4-3.2). The borders of benign 

nodules are often well circumscribed, with a rounded appearance. On the 

other hand, malignant nodules tend to have irregular, lobulated, or spiculated 

borders. A malignant nodule may have pleural tags or tails extending from its 

body, or a notch may be present in the border of the nodule (Rigler’s sign). None 

of these radiographic signs is entirely specific for malignancy. As a general 

rule of thumb, the more irregular the nodule, the more likely it is to be cancer. 

Figure 4-3.2: Calcification patterns. Patterns A-D are usually benign, E and F are 

indeterminate. A. Central, B. Laminated, C. Diffuse, D . Popcorn, E. Stippled, F. Eccentric. 

Calcification is generally an indication of benignity in a solitary pulmonary 

nodule. Infectious granulomas tend to calcify with central, diffuse, or stippled 

patterns. Laminar or concentric calcification is characteristic of granulomas 

caused by histoplasmosis. Popcorn calcification, when present, is suggestive of 

a hamartoma. Eccentric calcification patterns should make one suspicious for 

malignancy. It should be noted that, in general, 6 - 14% of malignant nodules 

exhibit calcification. When present in cancerous lesions, calcifications are 

usually eccentric and few. Benign patterns of calcification (central, diffuse, 

laminar, or popcorn) are very rare in malignant nodules. Most nodules with 

a benign calcification pattern can be observed with serial CT scans. 


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Assessment of Nodule Growth Rate and Frequency of Follow-up Imaging 

Assessing a nodule’s growth rate can further assist in distinguishing 

between benign and malignant nodules, provided serial images over time 

are available for comparison. Determination of nodule growth is based on 

the assumption that nodules are more or less spherical. Growth of a sphere 

must be considered in three-dimensional volume, not in two-dimensional 

diameter. The formula for volume of a sphere is 4/3(π)r3 , or 1/6(π)D3 , where 

r = radius and D = diameter. A nodule originally one centimeter in diameter 

whose diameter is now 1.3 centimeters has actually more than doubled in 

volume. Similarly, a two centimeter nodule has doubled in volume by the 

time its diameter reaches 2.5 cm. A nodule that has doubled in diameter has 

undergone an eightfold increase in volume. When old radiographs are available, 

growth rate and nodule doubling time (i.e., the time for a nodule to double in 

volume) can be estimated. Accepting the assumption that a tumor arises from 

serial doublings of a single cancerous cell, we can estimate that it will take 27 

doublings for it to reach one half a centimeter, the smallest lesion detectable 

on chest radiography. By the time a nodule is one centimeter in diameter, it 

represents 30 doubling times and about one billion tumor cells. Depending 

on the exact growth rate, this theoretical one centimeter nodule has probably 

existed for years before it is detected, as malignant bronchogenic tumors have 

doubling times estimated at between 20 and 400 days. The natural history of 

a tumor usually spans about 40 doublings, whereupon the tumor is 10 cm in 

diameter and the patient has usually died. 12 Squamous and large cell tumors 

have an average doubling time of 60 to 80 days. Adenocarcinomas double at 

about 120 days, and the rare small cell carcinoma that presents as a solitary 

pulmonary nodule can have a doubling time of less than 30 days. A nodule 

that has doubled in weeks to months is probably malignant and should be 

removed when possible. 13 

Benign nodules have doubling times of less than 20 days or more than 400 

days. A nodule that doubles in size in less than 20 days is usually the result of 

an acute infectious or inflammatory process, while those that grow very slowly 

are usually chronic granulomatous reactions or hamartomas. Such nodules 

can be observed with serial radiographs. 

Nodule growth rate and doubling times become clinically relevant when we 

have to decide how often to order follow-up imaging when observing a solitary 

pulmonary nodule. The question often arises whether observing a solitary 

pulmonary nodule for an extra three to six months increases the likelihood 

of metastatic disease, since that nodule has probably been growing for years. 

There is no convincing empiric evidence to support this hypothesis. Whether 

delays longer than three to six months are safe is unknown. However, estimating 

this hazard of delay is clinically relevant, since the optimal frequency of serial 

CT follow-up imaging to monitor nodules for growth is predicated on limiting 

this hazard of delay. The question is, how frequently do follow-up scans need to 

be done to minimize the hazard of delay while containing costs and avoiding 

excessive radiation exposure. 

Traditional practice, based on little empiric evidence, recommended 

that when a careful observation strategy was warranted, repeat CT scans be 

done at 3, 6, 12, and 24 months. However, more recent data from lung cancer

screening trials using CT imaging suggests that a less aggressive practice 

may be reasonable in some patients with very small nodules. 14-17 Therefore, 

decisions about the frequency and duration of follow-up for patients with 

solitary pulmonary nodules need to consider multiple dimensions of the 

problem, including clinical risk factors, nodule size, the probable growth rate 

as reflected by CT morphology, the limits of imaging technology resolution and 

volume measurement (especially at sizes less than five millimeters), radiation 

dose, surgical risks, patient preferences, and cost. 18-20 All of these can affect 

the optimal frequency of CT follow-up significantly. For example, in patients 

who are not considered to be surgical candidates due to other comorbidities, 

such as severe emphysema, the utility of follow-up CT imaging is questionable 

and less aggressive approaches, such as no imaging at all, are reasonable. 

Given this framework, it is reasonable to apply more recent expert consensus 

based guidelines to help guide the frequency of follow-up CT imaging for 

the solitary pulmonary nodule. 21 For follow-up studies, imaging should be 

performed with the lowest possible radiation dose that provides adequate 

imaging (with current technology between 40 and 100mA). The key variables 

that determine optimal imaging frequency are surgical risk, size and lung 

cancer risk. For patients who are potential surgical candidates with no lung 

cancer risk factors the frequency of repeat CT imaging is: 

• Nodule size < 4 mm: No follow-up needed. 

• Nodule size > 4 mm but less then 6 mm: re-evaluate in 12 months. If 

there is no change then no additional follow-up is warranted. 

• Nodule size > 6 to 8 mm: followed in 6 to 12 months and then again at 

18-24 months if there is no change. 

• Nodules size > 8 mm: traditional schedule with serial CT imaging at 

3, 6, 12, and 24 months if there is no change. 

For patients who are potential surgical candidates with one or more lung 

cancer risk factors, the frequency of repeat CT imaging is: 

• Nodule size < 4 mm: once at 12 months, no additional imaging if there 

is no change. 

• Nodule size > 4 mm but less then 6 mm: initially at 6-12 months, and 

if no growth repeat again at 18-24 months if there is no change. 

• Nodule size > 6 to 8 mm: initially at 3 to 6 months and then again at 

9-12 months, and then again at 24 months if there is no change. 

• Nodules size > 8 mm: traditional schedule with serial CT imaging at 

3, 6, 12, and 24 months if there is no change. 

It should also be noted that controversy remains regarding how long 

follow-up should be continued. While traditional teaching has recommended 

observing lesions for a maximum of two years, it is now recognized that for 

some lesions, longer follow-up may be warranted. Long doubling times have 

been observed in malignant lesions that presented as ground-glass nodules or 

as partially-solid nodules. 22-24 As a consequence, longer follow-up extending 

over years may be appropriate in some special instances, especially if there is 

an antecedent history of lung cancer. For most nodules, two years of follow-up 

without evidence of growth is sufficiently long to warrant discontinuation of 

CT imaging. 


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Estimating Probability of Malignancy 

Several authors have attempted to develop mathematical models to estimate 

the probability of malignancy of indeterminate solitary pulmonary nodules. 

Using clinical and radiographic characteristics of malignancy derived from 

the literature, these authors have analyzed some combination of malignant 

risk factors by Bayesian, neural network, and other methods to obtain a 

mathematical estimate of the probability of malignancy. Risk factors analyzed 

have included nodule size, location, growth rate, margin characteristics, age 

of the patient, smoking history, prevalence of malignancy in the community, 

and calcification on CT. 25-27 

One of the problems with these and other methods is the quality of the input 

data (i.e., the likelihood ratios), which may not be representative of all patient 

populations. In addition, Bayesian analysis presupposes that the likelihood 

ratios for a particular risk factor are not affected by the presence or absence 

of any other factor. It is not clear that this is true of the likelihood ratios. 

Therefore, although mathematical models to predict probability of malignancy 

may seem attractive, the complexity of the issue once again leaves us with an 

uncertain answer. This may explain why the above-described methods are 

not in widespread clinical use. 

However, assessment of the pretest probability of malignancy is central 

to optimal strategy selection making when managing solitary pulmonary 

nodules. 28, 29 While formulas and neural networks may lack precision on an 

individual patient level, they can serve to inform decision making as to what 

risk factors to pay attention to and how important they are relative to each other. 

Risk factors associated with a low probability of malignancy include diameter 

less than 1.5 cm, age less than 45 years, absence of tobacco use, having quit 

smoking for seven or more years, and a smooth appearance on radiography. 

Risk factors associated with a moderately-increased risk of malignancy include 

diameter 1.5-2.2 cm, age 45-59, smoking up to 20 cigarettes per day, being a 

former smoker within the last seven years, or a scalloped edge appearance on 

radiography. Risk factors associated with a high risk of malignancy include a 

diameter of 2.3 cm or greater, age greater than 60 years, being a current smoker 

of more than 20 cigarettes per day, a history of prior cancer, and a corona radiate 

or spiculated appearance on radiography (irregular edge). 

BIOPSY TECHNIQUES 

The issue of whether it is useful to biopsy an indeterminate solitary pulmonary 

nodule and, if so, how to do it remains controversial. Most experts agree that in 

certain clinical circumstances, a biopsy procedure is warranted. For example, 

in a patient who is at high surgical risk, it may be useful in establishing a 

diagnosis and in guiding decision making. If the biopsy reveals malignancy, 

it may convince a patient who is wary of surgery to undergo thoracotomy or 

thoracoscopic resection of a potentially-curable lesion. Another indication for 

biopsy may be anxiety to establish a specific diagnosis in a patient in whom the 

nodule seems to be benign. Some chest physicians argue that all indeterminate 

nodules should be resected if the results of history, physical examination, and 

laboratory and radiographic staging methods are negative for metastases.

Others argue that this last approach exposes patients with benign nodules 

to the risks of needless surgery. In such cases, a biopsy procedure sometimes 

provides a specific diagnosis of a benign lesion and obviates surgery. 

Once it has been decided to biopsy a solitary pulmonary nodule, the choice 

of procedure is a matter of debate but includes fiberoptic bronchoscopy, 

percutaneous needle aspiration, thoracoscopic biopsy (usually with video 

assistance), and open thoracotomy. 

Bronchoscopy 

Traditionally, bronchoscopy has been regarded as a procedure of limited 

usefulness in the evaluation of solitary pulmonary nodules. Studies have 

shown variable success rates, with an overall diagnostic yield of 36 - 68% for 

malignant nodules greater than two centimeters in size. In general, the yield 

for specific benign diagnoses has ranged from 12 - 41%. 

For smaller nodules, the sensitivity of bronchoscopy is significantly worse. 

For example, for nodules larger than two centimeters in diameter, a sensitivity 

as high as 68% (average 55%) can be obtained. However, this dropped to 11% for 

nodules smaller than two centimeters. Location also matters: nodules located 

in the inner or middle one-third of the lung fields have the best diagnostic 

yield; nodules in the outer one-third have a much lower diagnostic yield and 

as such are probably best approached with percutaneous needle aspiration 

if biopsy is needed. 

After an extensive evidence-based review of the various studies, it was 

concluded that bronchoscopy can play a role in the evaluation of the solitary 

pulmonary nodule under rare circumstances but that most of the time 

bronchoscopy will not be the best choice. 30 In those cases in which there is 

a bronchus leading to the lesion on a CT scan, or in cases in which there are 

very central lesions abutting the large airways, bronchoscopy may be of use. 

Similarly, if there is a suspicion for unusual infections, such as tuberculosis or 

fungal infections, then bronchoscopy may be warranted. However, for most 

31, 32 

patients bronchoscopy will not play a major role. 

Percutaneous Needle Aspiration 

Percutaneous needle aspiration can be performed under fluoroscopic or CT 

guidance, the choice often depending on the availability and the experience 

of the operator. It involves placing a very thin needle through the chest wall 

into the lesion to get an aspirate. It is most useful when nodules are in the 

outer third of the lung and in lesions under two centimeters in diameter. It can 

establish the diagnosis of malignancy in up to 95% of cases and can establish 

specific benign diagnosis (granuloma, hamartoma, and infarct) in up to 68% 

of patients. The use of larger-bore biopsy needles—such as a 19 gauge, which 

provides a core specimen in addition to cytology—improves the yield for both 

malignant and benign lesions. 

The major limitation of percutaneous needle aspiration is its high rate of 

pneumothorax (10- 35% overall); pneumothorax is more likely when lung 

tissue lies in the path of the needle. Because of the high rate of pneumothorax 

and its possible complications, the following patients should not undergo 

percutaneous needle aspiration: those with limited pulmonary reserve (e.g., 


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advanced emphysema); those with bullous emphysema or blebs in the needle 

path; and postpneumonectomy patients. Other general contraindications are: 

bleeding problems, inability to hold breath, and severe pulmonary hypertension. 

Thoracotomy and Thoracoscopy 

Lobectomy (resecting a lobe of the lung) using either open thoracotomy or 

video-assisted thoracoscopic surgery with lymph node resection and staging 

remain the standard of care for stage I bronchogenic carcinoma, the most 

common malignancy among solitary pulmonary nodules. Nodules greater 

than three centimeters in diameter have a greater than 90% chance of being 

malignant, and in the face of a negative metastatic workup and adequate 

pulmonary reserve, indeterminate nodules of this size should be resected. 

Smaller nodules that remain indeterminate after appropriate radiographic 

evaluation and possibly biopsy (bronchoscopic and/or percutaneous needle 

aspiration where indicated) either can be resected or can be observed with 

close serial CT follow-up. The decision will depend on the patient and on the 

physician, who must educate the patient on the alternatives and possible 

consequences. 

Thoracotomy has a reported mortality of three to seven percent. It is higher 

in patients over age 70 and in patients with malignancy. These patients will 

usually have other coexisting illness, such as chronic obstructive pulmonary 

disease (COPD), coronary artery disease, etc. The mortality risk increases with 

the extent of the procedure. In one series by Ginsberg and coworkers, mortality 

was 1.4% for wedge resection (a small piece), 2.9% for lobectomy, and 6.2% 

for pneumonectomy (resection of a whole lung). 33 More recent observational 

studies of lung cancer surgery reported similar 30-day mortality rates. 

Video-assisted thoracoscopic surgery (VATS) uses fiberoptic telescopes and 

miniaturized video cameras to facilitate biopsies and resection. VATS represents 

a complementary approach to traditional thoracotomy and can be very useful 

in some patients. This approach still requires general anesthesia but does not 

require a full thoracotomy incision or spreading of the ribs. VATS allows the 

experienced surgeon to identify and wedge out peripheral nodules in many 

cases with minimal morbidity and mortality. In a series by Mack and colleagues, 

242 nodules were resected with no mortality and minimal morbidity. 34 Average 

hospital stay was 2.4 days. Video-assisted thoracic surgery can spare some 

patients with benign nodules the risks of open thoracotomy and can be useful 

for wedging out nodules in patients who have limited pulmonary reserve who 

cannot otherwise tolerate a lobectomy. However, in a significant percentage 

of cases, conversion from VATS to a mini-thoracotomy will still be required. 

However resection is performed, whether by VATS or by thoracotomy, 

lobectomy remains the procedure of choice for malignant solitary pulmonary 

nodules. Wedge excisions or segmental resections for smaller cancers have 

been evaluated, but the role of these limited pulmonary resections in the 

management of lung cancer remains controversial. Because of the higher 

death rate and locoregional recurrence rate associated with limited resection, 

lobectomy has been recommended as the surgical procedure of choice for 

patients with malignant solitary pulmonary nodules who have adequate 

reserve to tolerate the procedure.

For patients with insufficient pulmonary reserve to tolerate a lobectomy, 

segmentectomy or wedge resection remains a viable alternative. This involves 

resecting a part of a lobe (segment). At the present time, it is reasonable to 

recommend lobectomy for all patients with malignant solitary pulmonary 

nodules who have sufficient pulmonary reserve to tolerate the procedure, with 

consideration of segmentectomy for those patients with inadequate pulmonary 

function to tolerate a lobectomy. 

DIAGNOSTIC APPROACH 

As is often the case in medicine, it is unwise to presume that an infallible 

algorithm can be provided for the evaluation of all solitary pulmonary nodules. 

Since no consensus can be reached on the basis of available data, the best that 

can be done is to offer recommendations. The pathway to be taken and final 

decision will rest on the individual physician and patient. Individual patient 

preferences also play a key role. The following recommendations represent 

one possible approach to this complex clinical problem: 

1. On discovering a solitary pulmonary nodule, the clinician should 

determine whether it is a true solitary nodule, spherical, and located 

within the lung fields. CT imaging should be part of the initial evaluation. 

2. A thorough history and physical may provide clues about the nodule’s 

possible cause. Most of the time, solitary pulmonary nodules are 

asymptomatic. The history should include an assessment of risk factors 

for cancer, including smoking history, occupational exposures, exposure 

to endemic fungi, and any history of prior malignancy. Patient risk 

preferences should be obtained as part of the discussion. 

3. If it is established that the nodule is truly solitary, and a benign pattern 

of calcification is present, the nodule is considered benign and no 

further workup is necessary. Follow-up with serial CT imaging may 

be warranted based on the size of the lesion and risk factors for cancer 

as described above. 

4. All prior chest radiographs and CT images should be obtained and 

compared with the present images. 

a. If prior chest radiographs are available, and the nodule has remained 

unchanged for two years or longer, no further workup is necessary. 

Follow-up with serial CT imaging may be warranted if there is a 

concern for a slow growing bronchioloalveolar cell carcinoma or 

there if there are other risk factors for cancer as described above. 

b. If the nodule has grown and the doubling time is more than 20 days 

but less than 18 months, it is considered malignant and should be 

resected. If the doubling time is more than 18 months, consideration 

of a slow growing bronchioloalveolar cell carcinoma or a carcinoid 

is warranted and, depending on the patient’s preferences and 

surgical risk, a biopsy procedure may be useful to provide further 

reassurance to the patient. Alternatively, the nodule may be benign 

and close serial CT follow-up is also reasonable, perhaps every 

three months for the first year and every six months for the next 

year. 


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326 


c. If old chest images are available but the nodule was not present 

on prior radiographs, an upper-limit doubling time is calculated. 

If the doubling time is again less than 18 months, it is considered 

to be malignant and resected. If the doubling time is more than 

18 months, the nodule remains indeterminate. Nodules for which 

previous radiographs are unavailable are also indeterminate. 

5. The physician should arrive at an estimate of the probability of malignancy 

based upon the history, physical, and CT imaging characteristics. 

a. Those with a low probability (under 10%) of malignant disease, such 

as those that have been demonstrated to be stable on serial CXR 

for two years or more, have a characteristic benign calcification 

pattern, or are present in patients less than 35 years of age in the 

absence of other risk factors, can be observed with serial CT scans 

depending on their size. The follow-up would be as described 

above, with surgery for those with evidence of progression. 

b. Those with a high probability of malignant disease who are surgical 

candidates should be considered for VATS or thoracotomy. Examples 

would be patients with a new nodule of large size in an older patient 

with a heavy smoking history and an irregular border (spiculated 

pattern) on CT. Staging would include a PET scan plus investigation 

of any other symptoms. When the probability of malignant disease 

is this high, even if the PET scan is completely negative, biopsy 

or resection is warranted. Note that PET in this instance is more 

of a staging tool (determine extent and respectability of cancer), 

rather than a diagnostic tool (determine whether or not there is 

cancer present). 

c. The third category, which many patients fall into, consists of those 

patients who are surgical candidates with nodules with a moderate 

probability (10-60%) of cancer. These nodules are considered 

indeterminate. The management of these nodules remains 

controversial. PET scanning for those with nodules measuring one 

centimeter or greater in size is warranted. Transthoracic fine needle 

aspiration, occasionally bronchoscopy, or a contrast-enhanced CT 

are reasonable options. If the results are positive, then surgery is 

warranted. If a specific benign diagnostic result (example: core 

biopsy demonstrates hamartoma or bronchoscopy demonstrates 

tuberculosis) is obtained then this is usually sufficient to guide 

management. However, a nonspecific nondiagnostic result should be 

interpreted with caution. Depending upon the patient’s preferences, 

surgical risk, and probability of cancer, VATS or thoracotomy or 

careful follow-up CT imaging may be warranted. 

Fire Fighters and Lung Nodules 

The two main factors that should be considered when evaluating solitary 

pulmonary nodules in fire fighters are whether there is an increased risk of 

cancer associated with firefighting and whether there is an increased risk of 

developing benign nodules due to occupational exposure with subsequent 

inflammation and scarring. With respect to lung cancer, the evidence from large 

epidemiologic studies is conflicting. There is evidence for some association

etween lung cancer and firefighting, but the magnitude of the risk is not 

strong. Specifically, the magnitude of the effect in terms of risk for lung cancer 

at an individual level is very small, such that it can be outweighed by other 

factors, such as smoking, age and the health-worker effect. The standards of 

evidence for occupational injury are different than those used for scientific 

consideration, and in taking care of patients, clinical decisions should be based 

on balancing science with individual exposure histories. 

This is further complicated by the fact that firefighting and the nature of fires 

have changed over the decades, making comparisons between studies over 

time difficult. In studies relevant to the present day, the risk is only elevated in 

certain groups, mainly those with the highest and longest exposure histories. 

The introduction of synthetic polymers and building materials in the 1950s 

poses a theoretical basis for increased risk, but epidemiologic studies have 

not consistently demonstrated an association. This is further confounded by 

improvements in respiratory protective devices and the frequency of their 

utilization. The frequency of respiratory protective device utilization was 

suboptimal in the past and therefore the impact of these devices in older 

studies probably is too small to determine. However, as utilization rates have 

improved in recent years, it is likely that future studies may show the benefits 

of such devices in the form of even lower risks. 

The other main clinical concern is whether or not fire fighters might develop 

more benign solitary pulmonary nodules due to intermittent minor lung injury. 

Solitary pulmonary nodules are not an uncommon finding among fire fighters. 

However, there is no rigorous data comparing the frequency of lung nodules 

in fire fighters as compared to that of the general population. 

Based on the available evidence, the approach to a solitary pulmonary 

nodule, once it has been identified, is the same for fire fighters as it is for other 

individuals. The risk of cancer should be assessed based on traditional risk 

factors, such as age, smoking history, size of the nodule, and prior history of 

malignancy. In making clinical decisions whether a non-smoking firefighter 

has added risk similar to a cigarette-smoking non-fire fighter is a topic of great 

controversy and concern. Accordingly, it should be openly discussed between 

patient and clinician. Diagnostic strategies based on probability of cancer and 

patient preferences are also similar and would include careful observation, 

biopsy, or proceeding directly to resection as described above. 

REFERENCES 

1. Ost D, Fein AM, Feinsilver SH. Clinical practice. The solitary pulmonary 

nodule. N Engl J Med. Jun 19 2003;348(25):2535-2542. 

2. Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with lowdose 

spiral computed tomography. Am J Respir Crit Care Med. Feb 15 

2002;165(4):508-513. 

3. Libby DM, Smith JP, Altorki NK, Pasmantier MW, Yankelevitz D, Henschke 

CI. Managing the small pulmonary nodule discovered by CT. Chest. Apr 

2004;125(4):1522-1529. 


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328 


4. Henschke CI, Yankelevitz DF, Naidich DP, et al. CT screening for lung 

cancer: suspiciousness of nodules according to size on baseline scans. 

Radiology. Apr 2004;231(1):164-168. 

5. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of 

small pulmonary nodules detected on CT scans: a statement from the 

Fleischner Society. Radiology. Nov 2005;237(2):395-400. 

6. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative 

management strategies for patients with solitary pulmonary nodules. Ann 

Intern Med. May 6 2003;138(9):724-735. 

7. Diagnosis and management of lung cancer: ACCP evidence-based guidelines. 

American College of Chest Physicians. Chest. Jan 2003;123(1 Suppl):D-G, 

1S-337S. 

8. Guidotti TL. Occupational mortality among firefighters: assessing the 

association. J Occup Environ Med. Dec 1995;37(12):1348-1356. 

9. Mahaney FX, Jr. Studies conflict on fire fighters’ risk of cancer. J Natl 

Cancer Inst. Jul 3 1991;83(13):908-909. 

10. Guidotti TL. Evaluating causality for occupational cancers: the example 

of firefighters. Occup Med (Lond). Oct 2007;57(7):466-471. 

11. Guidotti TL. Mortality of urban firefighters in Alberta, 1927-1987. Am J Ind 

Med. Jun 1993;23(6):921-940.

Chapter 4-4 

Where There’s Smoke… 

There’s Help! 

Self-Help for Tobacco Dependent 

Fire Fighters and Other First 

Responders 

By Matthew P. Bars, MS, CTTS 

Although this chapter can be of use to many readers (tobacco users, non-user 

with family, friends and co-workers who use tobacco and health professionals), it 

is written to speak directly to you the tobacco user. Like every chapter on health 

and disease, we will introduce the topic with information on why tobacco use 

is unhealthy and we will stress those issues that are of primary concern to fire 

fighters and other first responders. But we will be brief because this information 

is well known to you. Most tobacco users already know the dangers and want 

to quit but have not been adequately informed that there are now modern quit 

methods with excellent success rates and minimal discomfort. In 2002, the 

Fire Department City of New York (FDNY) launched a free, voluntary, nonpunitive, 

modern tobacco cessation program for all its employees and their 

families. This effort was funded in part by the IAFF's Counseling Service Fund. 

This chapter will describe to you that program and how you and your health 

care professional can use this approach to become tobacco free. 

Tobacco smoke contains over 4,000 chemicals, 69 of which are known 

carcinogens, many more are known toxins. These chemicals are absorbed 

in the lungs and via the blood travel to virtually every organ, every tissue, 

and every cell in the human body. Tobacco can affect any part of the body 

but primarily and most directly affects the lungs and heart. Throughout this 

chapter the term "smoker” or “tobacco user” will refer to the use of any and all 

tobacco products including cigarettes, cigars, pipes, and all forms of smokeless 

tobacco, unless otherwise specified. 

The four major areas of tobacco’s health effects on the human body involve 

cancers (and not just lung cancer), non-cancerous respiratory (lung) diseases, 

diseases of the heart and blood vessels and miscellaneous other effects. Under 

this miscellaneous category, smoking affects parts of the body not commonly 

thought of including hearing loss, erectile dysfunction, premature wrinkling 

of the skin, earlier menopause and more menstrual difficulties, and sleep/ 

wake abnormalities, to name just a few. 

Chapter 4-4 • Where There's Smoke...There's Help! Self-Help for Tobacco Dependent Fire Fighters and other First-Responders 329

While most people are aware that smoking causes lung cancer, most smokers 

do not know that tobacco increases the risk of a tremendous variety of cancers 

including colon, liver, cervix, brain, esophagus, throat, kidney and even penile 

cancer in men, to name just a few. 

Smoking affects the lungs in other ways in addition to causing lung cancer. 

Chronic obstructive pulmonary disease (COPD) is the single largest non-cancer 

lung disease caused by smoking and, of course, these risks are greater for fire 

fighters who are exposed to smoke and chemicals as a matter of routine and 

who must maintain normal lung function to do their job safely. COPD includes 

emphysema, chronic bronchitis, asthma (asthma is also referred to as reactive 

airways disease) and several less common diseases. Further, many if not all 

lung diseases are made worse by tobacco smoke exposure. 

As dramatic as the effects of lung disease and cancer are, the greatest impact 

on morbidity and mortality is tobacco caused cardiovascular disease. This 

includes heart and blood vessel disease such as atherosclerosis (hardening 

of the arteries), myocardial ischemia (poor blood flow and low oxygen to the 

heart muscle), myocardial infarctions (heart attacks), hypertension (high 

blood pressure) and peripheral vascular disease (poor blood flow and low 

oxygen to the peripheral tissues such as the legs, feet, hands and fingers). The 

fact that the number one cause of fire fighter deaths is myocardial infarction 

(heart attacks) makes tobacco cessation a priority for fire fighters and other 

first responders. 

National statistics reveal several things. Anywhere from a third to half 

of all smokers die as a direct result of their tobacco use; many years sooner 

than if they didn’t smoke. Many more become cardiac or respiratory cripples, 

eventually unable to do the simplest activities. These risks are even greater for 

fire fighters and other first responders who every day must depend on their 

own cardiopulmonary fitness and that of their coworkers. 

While every smoker knows tobacco kills, most are not aware of new methods, 

new medications and the combinations of medications available to help smokers 

(and other tobacco users) quit. If you are a smoker, odds are you have tried 

multiple times to quit and chances are great that you wish you were successful. 

Some reports show that the average smoker makes between six to nine serious 

attempts until they enjoy success and that over 70% of all smokers, wish they 

could quit. Indeed, if the negative effects of tobacco abstinence such as “missing 

not smoking” could be eliminated, the percentage of smokers wanting to quit 

would climb dramatically. 

FDNY has treated approximately 1,500 first responders (fire fighters, EMTs, 

and paramedics), retirees, civilian employees and family members since 

September 11, 2001. Indeed, it is now possible to help smokers quit with virtually 

no pain and little, if any, discomfort. At the FDNY, smokers were able to achieve 

one year quit rates of 40%. These successes are even more remarkable because 

they were obtained immediately after the devastating and traumatic effects 

of the terrorist attacks of 9/11. You can quit too! Here’s how: 

TOBACCO ADDICTION 

First, it is important to realize that the addiction to tobacco is extremely 

powerful. Smoking is the fastest, most powerful way to deliver nicotine to the 

330 Chapter 4-4 • Where There's Smoke...There's Help! Self-Help for Tobacco Dependent Fire Fighters and other First-Responders

human brain. After a puff, nicotine reaches the brain in only seven seconds. 

There it affects the brain like a shotgun blast, changing the brain’s chemistry 

increasing the sensation of pleasure, altering mood, decreasing appetite, and 

enhancing performance. Other parts of the brain learn “that was really good, 

let’s do that again soon.” Studies show that for most people, tobacco addiction 

occurs after a remarkably few number of cigarettes. 

Measuring Your Tobacco Addiction 

Karl Fagerström, a renowned Swedish tobacco addiction researcher over 20 

years ago, designed a simple six question test to measure the severity of a 

smoker’s nicotine addiction. The Fagerström Test for Nicotine Dependence has 

also been adapted for smokeless oral tobacco as well (Tables 4-4.1 and 4-4.2). 

Fagerström Test for Nicotine Dependence 

How many cigarettes per day do you usually smoke? 

How soon after you wake up do you smoke your first? 

Do you find it difficult to not smoke in no-smoking 

areas? 

Which cigarette would you most hate to give up? 

Do you smoke more frequently in the first hours after 

waking than during the rest of the day? 

Do you smoke if you are ill? 

10 or less 

11 to 20 

21 to 31 

31 or more 

Within 5 minutes 

6-30 minutes 

30-60 minutes 

More than 61 minutes 

No 

Yes 

The first one 

Any other one 

Scoring: 0-1 Very Low 2-3 Low 5-7 Moderate 7-8 High 9-10 Very High 

Table 4-4.1: Fagerström Test for Nicotine Dependence 

For you the patient, there are ways to determine how severe the level of 

nicotine addiction is. For example, has a doctor told you that your health is 

being damaged by your smoking and yet, you continue to smoke? Do you have a 

heart or lung condition? Even if smoking is not the direct cause of your illness, 

for most illnesses smoking is contributing to your continued deteriorating 

health and if despite knowing this you continue to smoke then your addiction 

is severe. Do you wake at night and smoke? Nocturnal smoking is common 

in severely-addicted smokers. This does not mean after a midnight run but 

rather if you wake up and smoke. Are you avoiding family members, friends or 

events because smoking is difficult or forbidden? Years ago, we had a smoking 

patient who refused to visit her grandchildren because her son-in-law forbade 

her smoking in the presence of the children. If you are avoiding significant 

people and events in your life so your smoking is undisturbed, your addiction 

is severe. If your workplace prohibits smoking and you are risking termination 

by smoking where it is forbidden, you are severely addicted. 

No 

Yes 

No 

Yes 

Chapter 4-4 • Where There's Smoke...There's Help! Self-Help for Tobacco Dependent Fire Fighters and other First-Responders 

331 

0 

1 

2 

3 

3 

2 

1 

0 

0 

1 

1 

0 

0 

1 

0 

1

332 

Modified Fagerström Test for Smokeless Oral Tobacco Use 

After a normal sleeping period, do you use smokeless 

tobacco within 30 minutes of waking? 

Do you use smokeless tobacco when you are sick or have 

mouth sores? 

How many tins do you use per week? 

How often do you intentionally swallow your tobacco juice 

rather than spit? 

Do you keep a dip or chew in your mouth almost all the 

time? 

Do you experience strong cravings for a dip or chew when 

you go for more than two hours without one? 

On average, how many minutes do you keep a fresh dip or 

chew in your mouth? 

What is the length of your dipping day? (total hours from first 

dip/chew in the AM to last dip/chew in PM) 

On average, how many dips/chews do you take each day? 

Yes 

No 

Yes 

No 

2 or less 

>2 but 15 ½ 

him that (to use firefighting language) the patch started to “knock down” his 

smoking addiction, it just did not go far enough. 

Let’s explain. The 21 mg nicotine patch which delivers nicotine s-l-o-w-l-y 

through the skin (compared to smoking nicotine), was not designed to replace 

100% of the inhaled nicotine from all the cigarettes for every smoker. Think 

about this: Elephants and mice like all mammals can develop bacterial upper 

respiratory infections. Like humans, both elephants and mice can be treated 

with antibiotics. Does it make sense to give the same dose of medicine to an 

elephant as a mouse? Of course, it does not! Does it make sense to fight a fire 

with the same number of fire fighters that has involved an entire city block as 

it does to knockdown a simple mattress fire? Of course, it doesn’t! Similarly, 

why would we want to treat a 30 or 40 cigarette per day smoker the same as, 

say, a person who smokes five cigarettes per day? It makes much more sense 

to treat every smoker individually. 

Actually in our clinical experience there are a number of smokers who 

continued to smoke (but less than usual) after taking an US Food and Drug 

Administration's (FDA) tobacco treatment medication such as the nicotine 

gum, nicotine patches and lozenges, nicotine inhalers and nasal sprays, what 

used to be called Zyban® (i.e., wellbutrin, bupropion) and Chantix® (varenicline). 

At this point you are probably wondering “Isn’t it unsafe to continue to smoke 

while using, say, the nicotine patch or gum?” In a word: No! In fact, this a great 

way to help ambivalent or less than fully ready smokers to start on the road 

to better health as long as they make the commitment to eventually become 

tobacco free. 

Reduction to Cessation Treatments (Reduce then Quit) 

Let’s say you smoke 25 cigarettes per day and want to cut-down but you’re not 

ready to quit. Perhaps you refuse to quit now or maybe prior quit attempts failed 

due to severe cessation anxiety (the anxiety that occurs when contemplating 

quitting). Such patients can benefit from a reduction to cessation treatment 

approach where medication is started prior to quitting. For example, if you 

smoke 20 to 30 cigarettes per day, do you think you could use a 21 milligram 

transdermal nicotine patch to cut-down gradually to 10-15 cigarettes daily? 

In May 2008, the U.S. Public Health Service working out of the Office of 

the Surgeon General released new guidelines to help clinicians treat tobacco 

addiction. These researchers and clinicians, chaired by Michael Fiore, MD a 

world-renowned tobacco cessation expert from the University of Wisconsin 

Medical School, reviewed thousands of peer-reviewed, high quality scientific 

studies. They concluded, among other things, that Reduction to Quit treatment 

plans are not only safe and effective, but some studies show that they may even 

increase success rates. Certainly they can engage smokers who are not ready 

to stop smoking today. 

Over the years, we have treated many hundreds of smokers with a Reduction 

to Cessation protocol. The number of smokers who experienced any problems 

with this type of plan could be counted on one hand. The most common 

difficulty was mild nausea. This was transient and usually eliminated by 

reducing the daily number of smoked cigarettes. Sometimes the smoker will 

continue to smoke fewer and fewer cigarettes spontaneously until they just 

stop. Other smoking patients may need to add additional medications such as 


333

334 

nicotine gum, inhalers, or nicotine nasal spray to reach complete abstinence. 

Combinations of these medications are also recommended by the new federal 

tobacco addiction treatment guidelines. We will discuss these medications in 

greater detail later in this chapter. 

Whether you are ready to establish a Target Quit Date (TQD) now, start a 

Reduction to Cessation treatment plan, or contemplate your next move, there 

are several simple steps that you can take to move you closer to a lifetime of 

freedom from tobacco. 

Keep a Cigarette Log 

Below is an example of a cigarette log (Figure 4.4.1). If you, a member of your 

family, friend or co-worker smokes, photocopy this page, cut out the log and 

wrap it around your cigarette pack with a rubber-band and a small pencil or 

pen. The cigarette log serves several purposes. First, it is impossible to change 

a behavior if you are unaware of precisely what that behavior is. 

Cigarette Use Log: 

M M M M 

Tu Tu Tu Tu 

W W W W 

Th Th Th Th 

F F F F 

Sa Sa Sa Sa 

Su Su Su Su 

Figure 4-4.1: Cigarette Log. 

Here is an example of a smoker who recorded smoking 22 cigarettes on 

Monday (Figure 4-4.2). 

Cigarette Use Log: January 

M |||| |||| |||| |||| || =22 M M M 

Tu Tu Tu Tu 

W W W W 

Th Th Th Th 

F F F F 

Sa Sa Sa Sa 

Su Su Su Su 

Figure 4-4.2: Sample Use of Cigarette Log. 

Chapter 4-4 • Where There's Smoke...There's Help! Self-Help for Tobacco Dependent Fire Fighters and other First-Responders

Second, the action of recording a cigarette in real-time (as it is smoked) 

helps the smoker become more aware of the act of smoking and this can 

help eliminate those cigarettes smoked just out of habit. Many cigarettes are 

smoked automatically without much of a real desire. Keeping a cigarette log 

can help understand patterns and that in itself may reduce tobacco use and 

will certainly help you and your doctor/ healthcare professional and tobacco 

treatment specialist create an individualized cessation treatment program 

and gauge your progress. 

No Ashtrays Instead Use a Cigarette “Coughee” Jar 

Another good technique is to eliminate all the ashtrays from wherever you 

smoke and to substitute a “cigarette coughee jar”. Just like it sounds take a 

clean clear glass or plastic jar with a screw-cap. Fill it about one-quarter of 

the way with water. Use this now as your one and only ashtray into which you 

deposit all your cigarette ashes and discarded butts. Especially if you live 

with small children or other non-smokers, it is best to bring your cigarette jar 

with you and smoke outside. All non-smokers are affected by tobacco smoke 

and the health of children is dramatically harmed by the smoking of adults. 

Before lighting up a new cigarette unscrew the jar and inhale a deep whiff of 

all those stale butts and ashes. Doing this regularly, each and every time you 

smoke will help break the positive association to your cigarettes and help you 

to conquer your addiction. When not smoking, for example, when watching 

TV, eating a meal, or drinking coffee, keep your cigarette jar with you. 

Increase the Inconvenience of Smoking 

Buy only one pack at a time, no more cartons of cigarettes or multiple packs 

lying around. It is also helpful to keep your cigarettes in an inconvenient place 

such as the trunk of your car, behind pipes in your basement, or a little used 

room, cabinet, or closet. During a Reduction to Cessation plan, you can smoke 

up to your cut-down goal but you do not want to smoke automatically when 

you don’t really want to, simply because they are lying around. 

Take Inventory and Do a Balance Sheet 

It is important to understand why you are thinking of quitting the smoking 

habit, trying to be as specific as you can. For example, don’t just say you are 

“quitting for health”, instead state “I am more short of breath climbing up stairs 

on a run or forcing entry than I was a few years ago” or “my doctor says my lungs 

and heart are being damaged by my smoking.” Write these reasons down and 

carry this list with you. A great place to keep this list is in your cigarette pack 

itself or your wallet. Take the list out and review it frequently; a great time to 

review your list is while smoking. Figure 4-4.3 shows some common reasons 

fire fighters express for quitting tobacco. 

A particularly good technique: One fire fighter who was quitting for his wife 

and family placed a picture of them without him between the cellophane and 

his pack of cigarettes. Every time he smoked, he imagined his family surviving 

without him after he died from a disease caused by tobacco. 


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Common Reasons Fire Fighters Express for Quitting Tobacco 

Check all that apply: 

☐ Increased risk for heart attack 

☐ Expense of smoking 

☐ Wife pregnant 

☐ Shortness of breath 

☐ Increased risk for lung disease 

☐ To set example for my children 

☐ To please spouse / co-workers / friends 

☐ I get enough smoke and chemicals fighting fires 

☐ I want to conquer my tobacco addiction and take control of my life 

☐ My doctor told me to quit 

☐ Cigarette money can be better spent: college educations, vacations, 

house 

☐ I am not getting any younger 

☐ Smoking lowers sexual energy and ability 

☐ Other: _______________________________________________ 

_______________________________________________ 

_______________________________________________ 

Figure 4-4.3: Common Reasons Fire Fighters Express for Quitting Tobacco 

No reason to quit is a bad reason if it is your reason. It is also important to 

assess honestly why you smoke. Most people smoke for many reasons in addition 

to their addiction to tobacco. Are you smoking out of boredom? To deal with 

stress? Hunger? Do you smoke because you associate with other smokers (i.e., 

your spouse or members of your firehouse)? Do you feel cigarettes help you 

relax? Do you use cigarettes to pick you up? To stimulate you or organize your 

energies? Do you smoke as a work break or after a run? 

Avoid People, Places, Things You Associate with Smoking 

Take some time to detail the things that make you smoke automatically or 

more than usually. Check all that apply and/or add your own. Where possible, 

change these behaviors to make smoking inconvenient, difficult, or impossible. 

For example, if you smoke while drinking coffee simply hold the coffee cup 

in a different hand; stand instead of sitting (or vise-a-versa), and/or hold a 

handling substitute such as a pencil or pen or eating can help you disassociate 

coffee from cigarettes. If you always smoke while driving to and from work try 

taking a different route and use oral or handling substitutes such as sugarless 

chewing gum or cinnamon sticks. Figure 4-4.4 can be used for this purpose. 


Check all that apply: 

☐ Alcohol 

Likely Times for Smoking or Using Tobacco 

☐ Coffee / Other beverages 

☐ After meals 

☐ While driving 

☐ Boredom 

☐ Work break/After a run 

☐ After awakening 

☐ Before bedtime 

☐ Before / during a bowel movement 

☐ During stress / anxiety 

☐ After sex 

☐ With negative feelings (anger, sadness, etc.) 

☐ Social activities (bowling, softball) 

☐ Family gatherings 

☐ Other: _______________________________________________ 

_______________________________________________ 

_______________________________________________ 

Figure 4-4.4: Common Reasons Fire Fighters Express for Quitting Tobacco 

Alcohol and Tobacco Use 

A word to the wise: alcohol can be a trump card. Alcohol consumption can 

sabotage the most earnest individual's quit smoking attempt. This is true for 

both the occasional "partier" as well as the problem drinker. Many people 

smoke at bars or parties just because everyone is. This is not to say that a 

smoker must forever abstain from alcohol to quit, but it is probably a good idea 

to avoid alcohol while you are attempting to quit. 

A comprehensive discussion of the relationship between alcohol and tobacco 

is beyond the scope of this chapter. That said, alcohol and fire fighter social 

activities often go hand and hand and the stress first responders experience 

in dealing with life and death events can lead to alcohol use, which then can 

trigger tobacco use in smokers and (even more unfortunate) can precipitate 

a return to tobacco in ex-smokers. 

Sadness, Depression and Post Traumatic Stress 

Unfortunately, first responders see things that civilians only dream about in 

their nightmares. Witnessing tragedy up close and personal can cause feelings 

of despondency and other emotional problems. While an in-depth discussion 

of depression and post-traumatic stress are beyond the scope of this chapter 


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and while anyone can temporarily experience one or a few of the symptoms 

described below, if the symptoms are recurrent and cause significant problems 

in your life, seek professional assistance. Both depression and post-traumatic 

stress can increase the difficulty of conquering your tobacco addiction. 

• Difficulty sleeping. 

• Loss of interest or the ability to enjoy oneself. 

• Excessive feelings of guilt or worthlessness. 

• Loss of energy or fatigue. 

• Difficulty concentrating, thinking or making decisions. 

• Changes in appetite. 

• Observable mental and physical sluggishness. 

• Thoughts of death or suicide. 

• Recurrent and intrusive distressing recollections of a traumatic event, 

including images, thoughts, dreams or perceptions. 

The Money You Save 

Calculate how much you are saving by smoking less (or not smoking at all) and 

place this money in another clean clear jar. As you watch your savings grow, 

plan on what you will do with the money. If you smoke one pack per day at $6/ 

pack, the savings after one year can pay for a large ticket item such as a vacation. 

If you prefer more immediate gratification, you can use the money saved for 

something small each week such as an article of clothing, book, CD or dinner 

at a special restaurant with someone special. All that matters is that you are 

cognizant of the fact that you are rewarding yourself for this important step. 

Exercise – Start Slow, Start with Your Doctor’s Input, but Start! 

Changing unhealthy habits and replacing them with healthy ones is always 

a great idea. Starting an exercise program or increasing the intensity and/ or 

session length of a current program is one of the best things you can do to help 

you quit tobacco. Studies show even small to moderate amounts of exercise can 

reduce the urge to smoke and help you remain tobacco free. If you were in the 

habit of lighting-up while watching TV, try doing a few minutes of push-ups or 

sit-ups during the commercial breaks. This is a new habit to take the place of 

the deadly habit and addiction of smoking. Even simple stretching exercises 

can work wonders and they feel great. Exercise naturally “burns off” tension 

and increases heart and respiration rates. Exercise increases endorphin and 

other brain chemicals that tobacco increase artificially. Exercise can also help 

reduce the weight gain (averages about five pounds) during tobacco cessation. 

Again we recommend anyone and everyone receive medical clearance regarding 

an exercise program. 

Keep Oral Low-Calorie Substitutes Handy 

Sugarless gum, candy, and mints, cloves, crunchy fruits and vegetables, 

cinnamon sticks or straws are all wonderful to keep your mouth and hands 

busy without cigarettes. Chewing gum works great while driving, around the 

house or at work. Fruits and vegetables are wonderful while sitting at home 

reading or watching TV. Again, healthy low-calorie substitutes will reduce the 


few pounds of weight gain that may accompany tobacco cessation efforts. In 

addition, nicotine replacement medications have been found to be exceptionally 

helpful in reducing appetite and weight gain. 

Associate Only with Non-Smokers for a While 

We don’t want you to abandon all your smoking associates but for a while 

it’s a good idea to spend more time with the non-smokers in your life. This 

is especially true if you tended to smoke automatically or tended to smoke 

more around other smokers. If you must socialize with other smokers, advise 

all who know you that you have decided to no longer smoke. If feasible, ask 

them if they could refrain from smoking around you. In small groups of one 

or two, you may be pleasantly surprised by their response. Other smokers are 

probably interested in quitting as well. Instead of a cigarette, offer them a piece 

of sugarless chewing gum. 

Unfortunately, sometimes smokers may attempt to sabotage your efforts 

to become tobacco free. We have found this is more common in firehouses 

where there are a sizable and vocal number of smokers. It is important to 

remember that for some smokers your success highlights their own difficulties 

in conquering the addiction to tobacco. Sometimes it is better to simply state, 

especially when offered cigarettes, “I don’t smoke” rather than "I am trying to 

quit." Remember you can’t control the behavior of others but you can control 

your own. If the situation becomes too tempting, simply walk away. You can 

return when cigarettes are extinguished. 

Avoiding parties where smokers can smoke freely is certainly a good idea; 

especially where a large number of smokers would congregate. If that is not 

possible, make a commitment to your self that you will not smoke. Use of rescue 

medications (nicotine gum, nicotine spray or nicotine inhaler—see more 

information about these medications later in this chapter) can be extremely 

important in these settings. Use them instead of a cigarette. Remember the 

vast 75 - 85% of Americans do not smoke. At any social or work setting, you 

can find people who do not smoke. 

MEDICATIONS ARE ESSENTIAL TO INCREASE YOUR 

CHANCES OF SUCCESS 

Fortunately, as we discussed earlier, there are seven FDA-approved tobacco 

treatment medications. These include several strengths of nicotine gum, 

nicotine patches and lozenges, nicotine inhalers and nasal sprays, as well as 

Zyban® (i.e. Wellbutrin, Bupropion) and Chantix® (Varenicline). 

There are hundreds of well-researched studies that prove without question 

that medications help you quit. However, many people don’t believe that and 

choose not to use medications or they discontinue these medications too 

soon and/ or don’t take enough to begin with. This is usually a mistake and 

sabotages many efforts. 

For example, many smokers fear (incorrectly) that nicotine replacement 

medications are dangerous because they deliver nicotine into the human 

body. Actually, even in cigarettes nicotine is not the dangerous chemical. 

Nicotine, as we discussed earlier, makes and keeps the tobacco user addicted, 

but nicotine is not what kills. The 4,000 other chemicals are what damage the 


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heart and lungs, increasing the risk for cancers of many organs, while carbon 

monoxide (the odorless, colorless gas which kills many fire victims) robs the 

body of oxygen. 

The only active ingredient in nicotine replacement medications is nicotine. 

Each of the five FDA-approved nicotine replacement medications are designed 

to deliver nicotine slower than a cigarette. Clean and slow nicotine is better 

than dirty cigarette-delivered nicotine. Nicotine replacement products have 

been used by millions of smokers in the last quarter century. 

Not one smoker has know to have died from a nicotine replacement medication. 

Conversely, during the past 25 years, over 12 million Americans have been 

killed as a direct result of their tobacco addiction. That is about 1,200 each 

day, equaling about 50 smoker deaths each hour. 

Every medication for every condition has certain risks associated with its 

use. The question is always do the benefits exceed the risks? Does the potential 

good outweigh the potential harm? According to some studies, more than half 

of all smokers will die many years or decades earlier than if they did not smoke. 

While no medication is right for everyone, every one of the FDA-approved 

medications is safe and effective. While four of the FDA medications are 

available only by prescription and the other three are over-the-counter, every 

smoker is advised to address medications with their physician or healthcare 

professional. 

Chantix ® (Varenicline) or Champix ® (outside the United States) 

Chantix® is the first new medication approved for the treatment of tobacco addiction 

in almost 10 years and it was specifically designed to simultaneously bind and 

block the nicotine receptors in the human brain. Chantix® is a prescription 

medication and must be prescribed by a physician or other licensed health 

professional. The effect of this tablet medication is to release the same pleasure 

neurochemical that nicotine stimulates while also preventing nicotine from 

having the same positive reinforcing effect on the smoker’s brain. 

Simply stated, the smoker does not get the same pleasure or “high” from 

their tobacco but also does not miss smoking as much. Research demonstrates 

that Chantix® allows the smoker to quit with greater ease. After 12 weeks of 

treatment, 44% of Chantix® users were tobacco free. The FDA product instructions 

recommend quitting within seven days of starting this medication. As with all 

tobacco treatment medications, smokers who have difficulty establishing a 

quit date can focus on reducing their tobacco consumption without a specific 

planned quit date as long as they are in a treatment program and are committed 

to eventually becoming tobacco free. Approved by the FDA in 2006, at the 

time of this writing there have been over five million Chantix® users. The most 

common side-effects are nausea, abdominal gas, constipation, insomnia and 

vivid dreams. Rare instances of depression have been reported. Many clinicians 

believe that this depression is most commonly due to nicotine withdrawal 

rather than Chantix® use but it rarely may be drug related. As we discussed 

previously, no medication is right for everyone. As always, discuss this and 

all medications with your physician. Your doctor should be an integral part 

of your tobacco treatment plan. 


Bupropion® (Wellbutrin, Zyban) 

In 1997, Bupropion®, an antidepressant, was the first non-nicotine medication 

approved for the treatment of tobacco addiction. Years before, Dr. Linda Ferry 

observed at the Jerry L. Pettis Veterans Administration Hospital in Loma Linda, 

California that the Bupropion® molecule was significantly more effective in 

helping her smoking military veterans quit. Every smoker and those of us in 

the tobacco treatment field owe Dr. Ferry a debt of gratitude. In our experience, 

Bupropion tablets are particularly effective in smokers, who after stopping, 

experience depression, dysphoria or sadness. Bupropion® is a prescription 

medication and must be prescribed by a physician or other licensed health 

professional. After years of using Bupropion®, we observed and subsequently 

demonstrated in a large placebo-controlled multi-center study that this 

medication reduces the amount of nicotine the smoker consumes prior to a quit 

date and even increases the motivation to quit. Side-effects include dry-mouth, 

headache, constipation, light-headedness, and a reported one in 1,000 risk for 

a seizure. Like every medication, Bupropion® is not right for every smoker. Talk 

to your physician to determine if Bupropion® is a wise choice for you. 

Bupropion® works well with Chantix® and the nicotine replacement products. 

However, the correct use of multiple medications can require the assistance 

of a trained tobacco treatment specialist. For a listing of tobacco specialists 

in your area, see the resource section at the end of this chapter. 

Nicotine Replacement Medications 

The four other FDA-approved products are all Nicotine Replacement medications. 

Remember we cannot say it enough: clean nicotine is always better than dirty 

(4,000 chemicals, 69 of which are known to cause cancer) nicotine. All nicotine 

replacement medications are safe! 

Nicotine Nasal Spray 

The Nicotine Nasal Spray delivers clean nicotine to the inside of the smoker’s 

nose. There, the nicotine is rather rapidly absorbed by the nasal mucus 

membranes (nasal mucosa) and delivered to the brain within 4-15 minutes 

(depending on the individual). In fact, other than by smoking a cigarette, this is 

the fastest way to deliver nicotine to the brain. This makes the Nicotine Nasal 

Spray an extremely effective tobacco treatment. It can be used repeatedly and 

on a regular schedule as a “continuous” tobacco cessation medication and/or 

intermittently as a “rescue” medication for severe tobacco cravings. One spray 

of nicotine nasal spray to each nostril delivers approximately the same amount 

of nicotine as the average smoker can receive from the average cigarette. 

While the nasal spray can be irritating and can result in sneezing, runny 

nose, tearing eyes and less seldom an occasional bloody nose, these effects are 

usually minor and transient, easing or disappearing entirely after the nasal 

passages are acclimated. The ability to tolerate the nasal spray’s side effect 

is quite dependent on the technique used in the application. First, direct the 

spray towards the sides of each nostril, rather than the center, and allow the 

sprayed fluid to coat the inside of the nostril rather than straight up into the 

sinus. Hold your breath while spraying and after administration continue to 

breathe through your mouth for a few minutes and avoid sniffing the solution 

deep into the nose. Nicotine Nasal Spray is a prescription medication. Talk to 


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your doctor, healthcare professional, and tobacco treatment specialist to help 

determine if the nicotine nasal spray is right for you. 

Nicotine Inhaler 

The nicotine inhaler is also a prescription medication. It consists of a nicotine 

gel cartridge, which is placed in a plastic tube vaguely resembling a cigarette. 

The nicotine gel releases a nicotine vapor, which is absorbed in the mouth’s 

oral mucosa. Each puff delivers approximately one-tenth the amount of 

nicotine delivered in a cigarette puff. For some smokers, the cigarette shape 

and the use of the nicotine inhaler also helps in reducing tobacco cravings by 

simulating the hand to mouth ritual of smoking. Some users may experience 

a sore throat, nasal irritation, cough, heartburn, stomach upset, hiccups or 

nausea. The most common side effects being mild mouth or throat irritation 

and cough. These side effects are usually minor, do not occur for most users, 

and can be eliminated or minimized by correct use. 

The nicotine inhaler, which is actually a puffer, should be puffed similar to a 

cigar so that the Nicotine Vapor is deposited onto the mouth’s lining. Nicotine 

is absorbed by the mouth’s lining rather than the lung so the most effective 

use of the nicotine inhaler is a series of shallow puffs. This also minimizes or 

eliminates side effects by avoiding inhaling the vapor into the back of the throat 

where it can irritate the vocal cords and the airways leading into the lungs. The 

inhaler cartridges are designed to deliver the most nicotine at roughly four 

puffs per minute for 20 to 30 minutes and then discarding the cartridge. Most 

smokers puff each cartridge too infrequently and use, on average, between 

one and two cartridges per day. This is far too little to receive an adequate 

amount of therapeutic nicotine. For use as a “continuous” tobacco cessation 

medication, the FDA product insert recommends using anywhere from 6 to 16 

cartridges each day. The nicotine inhaler is also suitable for use as a “rescue” 

medication for severe tobacco cravings. Like all medications, correct use is 

essential for the desired therapeutic effect and increased quit rates. 

Nicotine Polacrilex Gum 

In the United States, nicotine polacrilex gum is an over-the-counter medication 

that does not require a physician’s prescription and in 1983 was the first tobacco 

cessation medication ever approved by the FDA. Nicotine gum delivers nicotine 

in a resin matrix directly to the lining of the mouth, similar to the nicotine 

inhaler. Nicotine gum is not like regular chewing gum. Chewed like ordinary 

gum, nicotine gum will not work very well. It is important to chew the nicotine 

gum very slowly until you notice a peppery taste or slight tingling sensation 

(usually after about 15 chews, but can vary individual to individual) in your 

mouth. Then “park” the gum between your cheek and gums (below your teeth 

line) until the peppery or tingling sensation disappears, then keep repeating 

these steps. One piece, chewed correctly can be used for about one half hour. 

Chewing incorrectly can increase unpleasant side effects. Do not eat or drink 

immediately before gum use. 

Although the gum is available in two and four milligram strength, The 

FDNY program recommended the four milligram gum. The consistency and 

flavors have improved significantly over the original gum and is now available 

in mint, orange, cinnamon, and fruit flavors. Begin by chewing at least one 


piece every one to two hours. Side effects include mouth irritation, hiccups, 

nausea, and on rare occasion jaw pain. The nicotine gum is contraindicated 

in smokers with TMJ (temporal mandible joint) syndrome or significant 

dental work or numerous missing teeth. Like all FDA-approved medications, 

nicotine gum also significantly increases quit rates. It can be used frequently 

as a “continuous” tobacco cessation medication and/or intermittently as a 

“rescue” medication for severe tobacco cravings. 

Nicotine Polacrilex Lozenges 

Nicotine polacrilex lozenges are an over-the-counter medication that does 

not require a physician’s prescription. Similar to the nicotine polacrilex 

gum, the nicotine polacrilex lozenge releases nicotine directly through the 

lining of the mouth, temporarily relieving craving and nicotine withdrawal 

symptoms. It is recommended to use one to two lozenges each hour and at 

least nine lozenges per day. We have found many smokers may need much 

more than this minimum. Unlike ordinary lozenges, these are not meant to be 

chewed or swallowed. Place the lozenge in your mouth and allow the lozenge 

to dissolve slowly over 20 to 30 minutes while trying to swallow minimally. 

It is important to minimize swallowing so the dissolved medicine can be 

absorbed in the mouth. Of course, the lozenges deliver a lower, slower level of 

nicotine than a cigarette. It is not surprising that side effects are similar to the 

nicotine polacrilex gum and that it can be used frequently as a “continuous” 

tobacco cessation medication and/or intermittently as a “rescue” medication 

for severe tobacco cravings. 

Nicotine Patches 

In the United States, the nicotine patch is an over-the-counter medication that 

does not require a physician’s prescription. Nicotine transdermal patches deliver 

a steady dose of nicotine directly through the skin. There it enters the blood 

circulation and slowly enters the brain easing craving and tobacco withdrawal 

symptoms and increasing quit rates. A constant low dose of nicotine may be 

all that is needed to eliminate tobacco cravings in light smokers (e.g. , five to 

six cigarettes per day). For those with heavier tobacco use and/or more severe 

cravings, the other nicotine products (spray, inhaler, gum or lozenge) can be 

used in addition as “rescue” medications for breakthrough cravings. 

Some suggestions for proper application of the patch: after a shower or 

cleaning a non-hairy area of skin with a non-moisturizing soap, let the area 

dry completely. The upper arm is a good choice for most people, but the 

patch can be worn on almost any non-hairy area. It is important to avoid 

using lotions, cream, and skincare products on the area you choose. Try not 

to touch the sticky part of the patch. Firmly press the patch on your skin with 

the heel of your palm for at least 10 seconds. Wash your hands after applying 

or removing a transdermal nicotine patch. Safely dispose of any foil pouch, 

wrapping in plastic that protected the patch. Used patches should be folded in 

half and disposed of safely as well. Make sure these materials are out of reach 

of children and pets. 

The nicotine patch can be worn for either 16 (removed at bedtime) or 24 

hours. If you crave cigarettes when you wake up, or feel like you want extra 


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protection from tobacco cravings, wear the patch for 24 hours. Some patients 

can experience vivid dreams while wearing the patch after bedtime. In actuality, 

some patients enjoy the vivid colorful dreams. If vivid dreams present a problem, 

simply remove the patch at bedtime and apply a fresh patch first thing in the 

morning. Some smokers experience skin irritation caused by the adhesive. 

This can often be effectively treated with over the counter cortisone cream. 

Cortisone cream can be applied after the patch is removed. In more severe 

instances the area can be pre-treated the night before but, wash off the area 

of the remaining pre-treatment cortisone cream before applying the patch 

in the morning. Some patients may prefer one brand to another because of 

differences, real or perceived in effectiveness, stickiness and/or skin irritation. 

Combination Medications 

The FDNY Tobacco Cessation Program has used all of these medications in 

every possible combination safely and effectively with first responders and 

their families. Tobacco users who have a specific target quit date or those 

that prefer a reduction to cessation treatment plan can use each one of these 

medications, individually or in combination. Again, you should discuss 

medications, combination of medications or treatment plan with your physician 

or healthcare provider. 

Tobacco Treatment Decision Guidelines 

The first thing to examine is your readiness to quit now. Are you on fire to quit 

now or are you ambivalent? Are you concerned about “failing” (remember there 

are no failures, only smokers who have not yet quit) or are you experiencing 

“cessation anxiety?” If you are concerned, it has been recommended to use 

a reduction to cessation (RTC) plan that will eventually lead to a quit date. 

Another consideration: Have you made serious quit attempts in the past? 

Do you consider those attempts successful? Partially successful? Did you quit 

or significantly reduce your tobacco consumption for a period of time during 

those attempts? Did you use an FDA-approved medication during that attempt 

and did you use it correctly? Depending on your results, it may make sense 

to re-challenge your tobacco addiction with the same medication (assuming 

of course it did not cause any significant problems) or to add an additional 

“rescue” medication. 

If you reduced your cigarette consumption significantly (for example from 20 

or 25 cigarettes per day down to 15 or less) or even if you were totally abstinent 

but you experienced craving and tobacco withdrawal symptoms, it may be 

helpful to consider multiple tobacco treatment medications that combine 

“continuous” medications with “rescue” medications. When considering 

multiple medications, it is important to add only one medication at a time. 

While it is always recommend that every smoker consult with his or her 

physician, healthcare provider and a tobacco treatment specialist, we realize 

that this is not always possible. The simplest treatment plan for many smokers 

may to rely only on over-the-counter medications. In the FDNY program, 

recommendations were made to members to use a transdermal nicotine patch 

(for most a 21 mg patch) that provided continuous nicotine in an attempt to 

reduce cigarette consumption by approximately 50%, if not more. Then for 

“breakthrough” cravings, the program recommended “rescue” medication using 


either gum or lozenge; four milligram nicotine polacrilex gum or lozenges can 

address further reductions in cigarettes per day toward total cessation as well 

as breakthrough cravings. Remember to begin only one medicine at a time. 

Some smokers prefer to add the nicotine inhaler to a nicotine transdermal 

patch. This is often helpful with smokers who enjoy (or would miss) the handto-mouth 

ritual of smoking or benefit from the oral stimulation or the cigarette 

handling aspects of smoking. Collaborating with a licensed health care provider 

is required because the nicotine inhaler is a prescription medicine. Forming 

a partnership with a concerned healthcare provider, knowledgeable in the 

stressful demands regularly placed on fire fighters and other first responders 

can have many other beneficial effects both in designing an effective cessation 

program, preventing or treating any adverse effects that may have occurred 

from prior tobacco use and ultimately in improving cardiopulmonary fitness. 

A number of well-designed research studies have shown that high-dose 

multiple nicotine patches can increase quit rates. For those with intermittent 

rather than constant cravings, “rescue” medications are a better option. For 

severe urgent cravings, we recommend the nasal spray for “rescue” therapy. 

For less urgent cravings, we recommend the inhaler, gum or lozenge depending 

on patient preferences. 

While multiple patches are safe and almost universally produce no 

difficulties or side effects (other than occasional and mild skin irritation), these 

combination treatment plans are complicated and require the assistance of 

trained healthcare professionals. 

U.S. Federal and State Programs 

The National Network of Tobacco Cessation Quitlines is a state/federal 

partnership that provides tobacco users in every state with access to the 

tools and resources they need to quit smoking; ensuring the highest level of 

assistance to tobacco users who want to quit. The toll-free number 1-800 QUIT 

NOW (1-800-784-8669) serves as a single point of access to all state-based 

programs. The federal government website, Smokefree.gov, is maintained by 

the Tobacco Control Research Branch of the National Cancer Institute (NCI) 

and provides choices that best fit the needs of tobacco users. 

The site provides assistance in the form of: 

• An online step-by-step cessation guide; 

• Local and state telephone quitlines; 

• NCI's national telephone quitline and instant messaging service; and 

• Publications, which may be downloaded, printed, or ordered 

IAFF: A TOBACCO FREE UNION 

The IAFF and Pfizer are collaborating to help the IAFF become the first smokefree 

union. This initiative, modeled after the successful FDNY program, was 

begun to encourage all IAFF members and their families to take on healthier 

lifestyles by quitting smoking. This program provides information on the 

health risks of smoking and the benefits of quitting as well as tips on how 

friends and family can help a smoker quit. Information is also provided on 

how to encourage health insurance plans to make sure they cover smoking 


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cessation. The entire program is accessible on the IAFF website at: http:// 

www.iaff.org/smokefree/. 

A FINAL WORD 

Smokers often say that quitting tobacco is the hardest thing they have ever 

done. Tobacco cessation programs, like the one offered at FDNY and now by 

the IAFF, make the battle easier and often pain free. If you are a first responder 

who has been on the job for more than a few years, you have probably tried to 

force an entry or knock down a fire that was difficult and didn’t go as planned. 

Sometimes you have to reassess a situation and try again. Living a tobaccofree 

life can be a lot like that. That said, nothing should be more important to 

you, your family, and your friends than eliminating tobacco from your life. 

REFERENCES 

1. Information on the IAFF Campaign for a Smoke-Free Union can be found 

at: http://www.iaff.org/smokefree/. 

2. Stop Smoking Doctors can be found at: www.StopSmokingDoctors.com 

3. Information regarding Chantix® (Champix®) can be found at: www.Chantix. 

com. 

4. Information on the GlaxoSmithKline Consumer Healthcare program can 

be forund at: www.CommittedQuitters.com 

5. Information regarding the Nicoderm® nicotine transdermal patches can 

be found at: www.nicodermcq.com. 

6. Information regarding the Nicotine Inhaler and Nicotine Nasal Spray can 

be found at: www.nicotrol.com. 

7. Information regarding Nicorette® nicotine polacrilex gum can be found 

at: www.nicorette.com. 

8. US Surgeon General’s Tobacco Webpage can be found at www.surgeongeneral. 

gov/tobacco/. 

9. Information regarding the Association for Treatment of Tobacco Use and 

Dependence Programs can be found at: www.ATTUD.org. 

10. Information regarding the Tobacco Control Research Branch of the National 

Cancer Institute's National Network of Tobacco Cessation Quitlines can 

be found at: www. smokefree.gov. 

11. Information regarding the International Association of Fire Fighters' 

Campaign for a Smoke-Free Union can be found at: http://www.iaff.org/ 

smokefree/. 


Chapter 4-5 

Respiratory Failure, 

Assisted Ventilation, 

Mechanical Ventilation 

and Weaning 

By Dr. Thomas K. Aldrich, MD 

The respiratory system is built to accomplish gas exchange, bringing air into 

close proximity of blood, so as to allow oxygen to diffuse from air to blood 

and carbon dioxide to diffuse from blood into air. Respiratory failure occurs 

when the respiratory system cannot adequately maintain gas exchange, most 

commonly because of a failure to provide and maintain adequate ventilation 

(the movement of air into and out of the lungs). 

The major structures of the respiratory system and the processes that determine 

the adequacy of their functioning is illustrated in Figure 4-5.1. Respiratory 

Components of of the the Respiratory respiratory System 

system 

Cerebral cortex 

Volition 

Medulla 

Drive 

Respiratory Muscles 

Strength 

Chest Bellows 

Load 

Ventilation 

Gas Exchange 

Perfusion Metabolism 

(blood flow) 

Figure 4-5.1: Structures and functions of the respiratory system (structures are in blue, 

functions in red). The goal is exchange, determined by the balance of ventilation, perfusion 

and metabolism 

Chapter 4-5 • Respiratory Failure, Assisted Ventilation, Mechanical Ventilation and Weaning 347

. 

drive, the neural control of breathing, originates in the brainstem (primarily 

the medulla), and proceeds unconsciously, but can be influenced by higher 

structures for voluntary control of breathing (e.g., during breath-holding, 

playing musical instruments, etc.). The respiratory muscles, depending on 

their strength and endurance, enlarge (and sometimes contract) the volume 

of the chest (the “chest bellows”). It is more difficult to inflate the lungs if they 

are stiff (e.g., pneumonia, pulmonary fibrosis, etc.) or if airways resistance is 

increased (e.g., asthma, chronic bronchitis, etc.). Normally, the load faced by 

the chest bellows is so low that ventilation occurs effortlessly. Stiff lungs or 

increase airway resistance results in an increased workload and depending 

on the magnitude of the load and other factors, the chest bellows may fail 

resulting in respiratory failure. 

TYPES OF RESPIRATORY FAILURE 

Two types of respiratory failure can occur: hypoxemic (low oxygen) or 

hypercapnic (high carbon dioxide) 1 (Table 4-5.1). Normally room air is 21% 

oxygen and the partial pressure of oxygen in arterial blood (PaO2) at sea level is 

~90mmHg. For practical purposes, hypoxemic respiratory failure is considered 

to be present if PaO2 cannot be corrected to >50mmHg on a nontoxic level of 

supplemental oxygen (

Hypoxic Respiratory Failure 

The common causes of hypoxemic respiratory failure are diseases of the lung 

or the pulmonary blood vessels (see Table 4-5.1), impairing gas exchange 

because there is not adequate exposure of the perfusing blood to ventilating 

gas. In such cases, the ventilatory pump is able to increase overall ventilation 

adequately to prevent a rise in carbon dioxide partial pressure (pCO2), but 

the continuing maldistribution of ventilation prevents full correction of the 

hypoxemia. 

Hypercapnic Respiratory Failure 

The common causes of hypercapnic failure are diseases of any of the components 

of the respiratory system leading up to the lungs: the brainstem, the respiratory 

muscles, the chest wall, or the airways (see Table 4-5.1). In hypercapnic 

respiratory failure, relatively mild hypoxemia occurs, primarily for the same 

reason that hypercapnia occurs: the level of ventilation is not adequate to 

refresh the oxygen within the lungs, just as it is not adequate to eliminate a 

normal amount of carbon dioxide. 

Hypercapnic respiratory failure results when the ventilatory pump is 

inadequate to meet the metabolic and ventilatory demands because of reduced 

central drive (brain), impaired respiratory muscle function (nerves or muscles), 

excessive respiratory workload, or some combination of these three factors2 (Table 4-5.2). Of the three potential causes of hypercapnic respiratory failure, 

the least common is impaired central drive. It occurs in drug overdose, rarely in 

hypothyroidism, and even less commonly in brain lesions, such as catastrophic 

bilateral brainstem strokes or central alveolar hypoventilation syndrome 

(Ondine’s curse), an exceedingly rare congenital impairment in brainstem 

function. Most brain lesion (strokes, tumors, etc) and most metabolic disorders 

(cirrhosis, uremia, and other deliriums) are associated with hyperventilation 

rather than hypoventilation and do not cause respiratory failure. 

Causes of Hypercarbia (CO2 Retention) 

Ventilatory pump failure 

• Reduced central drive 

• Impaired ventilatory muscle endurance 

• Increased respiratory workload 

Contributing factors 

• Increased CO2 production 

• Increased dead space 

• Impaired intrapulmonary gas exchange 

Table 4-5.2: The Causes of CO2 Retention. 

Thus, most cases of hypercapnic respiratory failure are due to impaired 

respiratory (mostly inspiratory) muscle strength and endurance and/or excessive 

respiratory workload (Figure 4-5.2). In chronic obstructive pulmonary disease 

(COPD), for example, the major problem is excessive workload, due mostly to 

Chapter 4-5 • Respiratory Failure, Assisted Ventilation, Mechanical Ventilation and Weaning 

349

350 

Figure 4-5.2: The balance between inspiratory muscle performance (strength and 

endurance) and respiratory workload. 

increased airway resistance. But, in COPD, inspiratory muscle strength is also 

commonly impaired by a number of concomitant mechanical and metabolic 

conditions. Similarly, in neuromuscular diseases, although inspiratory muscle 

weakness is the major problem causing ventilatory pump failure, a number of 

factors increase inspiratory workload, such as increased airways resistance 

and lung stiffness caused by recurrent aspiration pneumonia. 

CLINICAL ASSESSMENT OF RESPIRATORY FAILURE 

Symptoms and signs of both types of respiratory failure are primarily those 

of the underlying disease. There may be shortness of breath, cough, and/or 

chest pain. Unfortunately, symptoms correlate poorly with the severity of 

respiratory failure. Findings on physical examination might include evident 

labored breathing and, depending on the type of underlying disease, prolonged 

expiratory phase (in COPD or asthma), diminished breath sounds (in COPD), 

crackles (in pulmonary edema, pneumonia, or pulmonary fibrosis), wheezing 

(primarily in asthma, but occasionally in COPD), or bronchial breath sounds 

(in pneumonia). Stridor, a harsh or musical wheeze-like sound, most prominent 

in or confined to the inspiratory phase of ventilation, strongly suggests upper 

airway obstruction, often a medical emergency. Cyanosis of the mucous 

membranes and nail beds is an unreliable sign of hypoxemia. Somnolence 

(falling asleep inappropriately) can be an important clue to the presence of 

inadequately compensated CO2 retention, but, of course, there are many other 

possible causes of somnolence. 

Laboratory Findings 

Arterial blood gases (measurements of pH, PaCO2, and PaO2 in arterial blood) 

are the definitive tests to diagnose both types of respiratory failure. They allow 

for precise assessment of the adequacy of oxygenation, along with determination 

of acid/base status and of the adequacy of ventilation. Drawbacks are the 

painful nature of the necessary arterial puncture, the small risk of arterial 

injury, and the fact that they provide only a “snapshot” look at the status of 

respiratory function. 

Chapter 4-5 • Respiratory Failure, Assisted Ventilation, Mechanical Ventilation and Weaning

Other non-invasive tests can be of value. The venous bicarbonate (often 

identified as “CO2” on blood electrolyte reports), rises in compensation for 

rising pCO2. Thus, although bicarbonate measurements without blood gases 

do not rule in or rule out respiratory failure, a normal venous bicarbonate can 

be reassuring, especially when the pulse oximeter reading is normal and the 

patient’s mental status is well preserved. 

Pulse oximetry is a noninvasive technique to allow measurement and 

monitoring of blood oxygen (SpO2). A patient’s fingertip is transilluminated 

by two wavelengths of light, typically 660nm (red) and approximately 900 nm 

(infrared), in rapid alternation. Changes in absorbance of each of the two 

wavelengths, caused by pulsing arterial blood is measured, and the ratio of 

the two is used to calculate percent oxygen saturation. 

Pulse oximetry has become an indispensable vital sign for all emergency 

rooms (ER), operating rooms and procedure rooms, and it is fast becoming a 

part of emergency medical service (EMS) evaluations and even routine medical 

visits. It is rapid, painless, inexpensive, and (generally) accurate. It can quickly 

rule in or rule out most cases of hypoxic respiratory failure and those cases of 

hypercapnic respiratory failure where the oxygen level is also low. The only 

drawbacks are (1) false negative results in cases of carbon monoxide poisoning 

(and even those may soon be routinely covered by multiwavelength models 

that measure carboxy hemo globin as well as oxyhemoglobin), (2) a few cases 

of failure to achieve estimates of oxygenation when the pulse is too weak, 

usually due to shock or peripheral vascular disease, and (3) although it can 

perhaps screen for hypercapnia (significantly hypercapnic patients will not 

have normal S O when breathing room air), it cannot rule out hypercapnia 

p 2 

in a patient breathing oxygen, so it may provide a false sense of security. 

Pulmonary function testing is usually valuable in the evaluation of the 

underlying pulmonary condition(s) that cause or contribute to respiratory 

failure. Forced expiratory volume in one second (FEV1, the maximal amount 

of air that can be exhaled in one second) is a good overall estimate of the ability 

of the respiratory system to accomplish ventilation. The pattern of impairment 

in pulmonary function may also be revealing; if FEV1 and the forced vital 

capacity (the maximum total volume exhaled in one breath, FVC) are down 

in proportion, that suggests a restrictive pattern of respiratory dysfunction – 

pulmonary parenchymal (pneumonia, pulmonary fibrosis, etc.), chest wall 

(rib fractures, chest surgery, etc.), or respiratory neuromuscular impairment 

(Guillain Bare Syndrome, Lou Gehrig’s disease, etc.). When FEV1 is more 

severely impaired than is the FVC, then this suggests an obstructive airways 

disease (COPD or asthma). Another common pulmonary function test, the 

diffusing capacity for carbon monoxide (DLCO), can be of use. Severe reductions 

suggest pulmonary parenchymal disease (pneumonia, pulmonary fibrosis, 

etc.) or pulmonary vascular disease (pulmonary embolism or pulmonary 

hypertension). The DLCO can also be low if the blood carbon monoxide level is 

elevated due to either smoke inhalation of any type including tobacco smoke. 


351

352 

TREATMENT OF RESPIRATORY FAILURE 

Treatment of both types of respiratory failure normally hinges on treatment of 

the underlying condition. Thus, central drive impairment due to drug overdose 

can often by treated by specific antidotes (e.g., naloxone for opioid overdose), 

pulmonary edema with cardiac medications, pneumonia with antibiotics, 

and asthma with bronchodilators and corticosteroids. Adjunctive treatments, 

especially the administration of supplemental oxygen, can be beneficial, while 

awaiting improvement in the underlying disease or in the situations in which 

the underlying disease cannot be corrected. 

Supplemental oxygen is normally provided by one of three delivery systems, 

all of which are routinely available in all Fire/EMS units. They are nasal 

cannula, Venturi mask, and non-rebreather mask. Some EMS units are also 

able to supply oxygen at elevated continuous positive airway pressures (CPAP), 

which is discussed later in this chapter. The fractional concentration of oxygen 

(FiO2) in room air is 21 percent. The FiO2 actually delivered by nasal cannulae 

is quite variable and not reliably predictable by the liter per minute flow rate, 

in part because of variable amounts of mouthbreathing, but more importantly 

because inspiratory flow rates and consequent entrainment of room air are 

tremendously variable. The Venti-mask uses a jet of oxygen at high flow rate 

(5-15 liters per minute) through a delivery device shaped to entrain predictable 

amounts of room air (using the Venturi principle), so that FiO2 can be adjusted 

relatively precisely. The Venti-mask results in more predictable FiO2 than does 

nasal cannula, but it still suffers from entrainment of variable amounts of room 

air around the edges of the mask and through the holes that are built into the 

mask to allow egress of excess flow. The non-rebreather mask provides 100% 

oxygen from a bag reservoir into the mask and uses one-way valves to direct 

exhaled gases out of the mask. Even a non-rebreather mask, however, entrains 

a variably small but not negligible amount of room air around the mask and 

through one of the expiratory one-way valves, which is routinely left open so 

as to avoid suffocation if the reservoir runs dry. 

Supplemental oxygen is the major adjunctive treatment for respiratory failure, 

and in patients with hypoxic respiratory failure, it can be used safely (for short 

periods) at any dose and for indefinite periods at “nontoxic” concentrations 

(FiO2

Mechanical Ventilation 

Mechanical ventilation is of obvious benefit in people undergoing surgery, 

anesthetized and paralyzed, unable to breathe for themselves, and in people 

in respiratory arrest or severe intractable hypercapnic respiratory failure. 

Mechanical support is most clearly indicated in hypercapnic respiratory failure, 

but it can also be beneficial for hypoxemic respiratory failure, by “blowing open” 

collapsed regions of the lung and by improving the distribution of ventilation 

even in regions already open. 

In addition to correcting hypoxemia and hypercapnia, there are other 

benefits of mechanical ventilatory support , including: 

• Maintenance of oxygenation and acid/base balance 

• Comfort 

• Improved sleep 

• Prevention of inspiratory muscle fatigue 

Perhaps most important is the comfort issue. Dyspnea (shortness of breath) 

comes in many different varieties and has many potential physiologic causes, 

but in hypercapnic respiratory failure, one of the main problems appears to 

be the perception of the need for excessive respiratory effort. Although mechanical 

ventilation does not totally take over the work of breathing, it can 

substantially reduce the load on the respiratory muscles, especially if adequate 

inspiratory flow rates are used. 

Mechanical ventilatory support also has a clear and established role 

in obstructive sleep apnea, being able to “splint” the upper airways open, 

preventing the upper airway collapse that is the major pathophysiologic cause 

of obstructive sleep apnea. 

Noninvasive vs. Invasive Mechanical Ventilatory Support 

Ventilatory support can be accomplished by noninvasive or invasive means, 

the latter via endotracheal intubation or tracheostomy. The most common 

noninvasive techniques deliver positive pressure support (continuous or 

bilevel positive pressure breathing [CPAP or BiPAP], or volume ventilation), 

by a tight-fitting nasal mask or full face mask 3 . The noninvasive techniques 

have the advantages of (usually) less discomfort, preserved ability to talk and 

to cough, less risk of airway (laryngeal and tracheal) injury and of ventilator 

associated pneumonia and the likelihood that the duration of support will be 

shorter (Table 4-5.3). The invasive methods have the advantage that ventilation 

is more effective. When respiratory failure is severe, noninvasive methods are 

just not adequate to provide the necessary volumes to correct it. With invasive 

mechanical ventilation, although secretions can still be aspirated alongside 

the endotracheal or tracheostomy tube, the risk of massive aspiration is 

considerably less than with noninvasive techniques. There is also easier access 

to secretions, both for culture and for therapeutic purposes. And, finally, 

aerophagia (swallowing air), a common complication of noninvasive nasal or 

face-mask positive pressure breathing, is not a problem in patients invasively 

ventilated via an endotracheal tube or tracheostomy. 


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354 

• Less discomfort 

Mechanical Ventilatory Support Factors 

Noninvasive Invasive 

• Less risk of tracheal or 

laryngeal injury 

• Less risk of ventilatorassociated 

pneumonia 

• Shorter duration of support 

• Preserved ability to talk/cough 

• More effective 

• Less need for minute to minute 

monitoring 

• Less risk of aspiration 

• Easier access to secretions 

• No risk of aerophagia 

Table 4-5.3: Mechanical Ventilary Support Advantages and Disadvantages 

Types or Modes of Mechanical Ventilation 

Assist/Control 

The simplest mode of mechanical ventilation in general use is known as “Assist/ 

Control.” It is perhaps more accurately described as it is used in practice as 

“volume ventilation, triggered by assist efforts, with back-up timed triggering if 

needed.” The ventilator is triggered to deliver a breath, either when its computer 

senses the patient’s effort by detection of an abrupt decline in airway pressure 

(assisted ventilation), or when a set period of time has passed without a patient 

effort (controlled ventilation). The ventilator then delivers a set volume of a 

set mixture of air and oxygen at a set inspiratory flow pattern and rate and 

a set level of positive end-expiratory pressure (PEEP). The advantage over 

the previously-available pressure ventilation, is that the ventilator adapts to 

changing mechanics by essentially guaranteeing the delivery of a reasonable tidal 

volume, thereby avoiding the unexpected hypoventilation that were problems 

of the old pressure ventilation mode. A disadvantage is that over-ventilation 

is a constant threat; every effort by the patient results in a full tidal volume, so 

patients with severe shortness of breath often are found to “over-breathe” or 

over-ventilate, with consequent respiratory alkalosis (hypocapnia), elevated 

pressures and subsequent difficulties with weaning. Another disadvantage is 

that patients who are not sedated often find the set flow rates too low to satisfy 

their perceived need, so shortness of breath and discomfort may persist, despite 

mechanical ventilation. 4 

Pressure Support and CPAP (PS/CPAP) 

PS/CPAP is a technique to reduce the effort required to take spontaneous breaths. 

CPAP (continuous positive airway pressure) is the pressure that the ventilator’s 

computer maintains in the airway during the expiratory phase by providing 

sufficient inflow of the set air/oxygen mixture (essentially the same as positive 

end-expiratory pressure or PEEP). When the patient makes an inspiratory 

effort, the ventilator switches to the higherpressure support (PS) level of airway 

pressure maintenance and provides a higher and constantly adjusted level 

of inflow, so as to maintain the set PS level. When the patient terminates the 

inspiratory effort, the abrupt increase in airway pressure (occurring because 


air is no longer entering the lungs) is sensed by the ventilator, which switches 

back to the CPAP level of airway pressure for the expiratory phase. 

Originally developed as a technique to ease the transition from mechanical 

ventilator to spontaneous breathing (weaning), PS/CPAP is now used both as a 

weaning tool and as a primary mode of mechanical ventilation, especially for 

patients who do not have impaired mental status. As such, because patients 

are able to control their own flow rate, PS/CPAP may be a more comfortable 

mode of ventilation than is Assist/Control for some patients. A disadvantage 

is that staff may be lulled into a false sense of security; the fact that a patient 

breathes comfortably on PS/CPAP 15/5 cm H2O does not mean that he or she 

can tolerate lower levels of PS/CPAP. 

Synchronous Intermittent Mandatory Ventilation (SIMV) 

In the SIMV mode, the ventilator delivers a set number of breaths per minute 

at a set volume, flow rate and pattern, and PEEP, but, when the patient makes 

an inspiratory effort between ventilator breaths, instead of triggering another 

ventilator breath, as in the Assist/Control mode, the patient breathes “on 

his own” (usually assisted to some degree by pressure support). As with PS/ 

CPAP, SIMV was originally developed as a weaning tool. SIMV has generally 

fallen out of favor for weaning but can be used for relatively-stable respiratory 

failure patients. 

Specialized Modes 

A number of specialized modes of mechanical ventilation have been developed 

but are beyond the scope of this chapter. They include Inverse Ratio Ventilation 

(IRV), Airway Pressure Release Ventilation (APRV), High Frequency Ventilation 

(HFV) and other modes that could be useful in patients with severe lung disease. 

To date, none has been unequivocally demonstrated to improve outcomes 

over conventional modes. The only mechanical ventilation strategy that has 

proven better outcomes than its competitors is ventilating at low volumes (

356 

WEANING OR REMOVING A PATIENT 

FROM MECHANICAL VENTILATION 

In this situation, medical dictionaries define “weaning” as the gradual withdrawal 

of a patient from dependency on mechanical ventilation life-support systems. 

The vast majority of patients do not need weaning. They were intubated for 

surgical procedures or for a clearly temporary medical condition (ex., seizures, 

asthma exacerbation, drug overdose, etc.). Shortly after the anesthesia wears 

off or the acute medical condition resolves, the patient is assessed and in most 

cases, the patient is breathing well, mechanical ventilation is discontinued and 

the endotracheal tube removed. However, in a minority of cases, the condition 

responsible for the respiratory failure is complex (COPD, sepsis, severe trauma, 

etc.) and is often complicated by multiple other medical problems. In these 

cases, weaning may be necessary to help re-train the patient’s muscles or more 

likely to provide repetitive assessments to allow both the patient and medical 

team to gain confidence that the underlying condition has improved to the 

point where spontaneous ventilation could be successful. 

Weaning can be accomplished by daily trials of spontaneous breathing 

(usually using low-level PS and CPAP). Some clinicians favor one daily trial 

with gradually lengthening duration, while other favor several daily trials 

of shorter duration. SIMV can also be used, with gradual reductions in the 

frequency of ventilator breaths. In practice, at least at the beginning of the 

weaning process, most clinicians wean patients primarily during the day and 

return them to a more comfortable mode of mechanical ventilation during the 

night. No technique for weaning has been unequivocally shown to be better 

than any other. 6,7 

In my view, only three elements are required for weaning: 

• Nurse (or Respiratory Therapist) 

• Pulse Oximeter 

• Enthusiasm 

As long as progress is being made, any technique can be used. The patient 

should be observed for evidence of discomfort, airway secretions, myocardial 

ischemia, hypoxemia, and hypotension, and returned to a comfortable mode 

of ventilation if such problems occur. 

THE DECISION TO USE INVASIVE VENTILATORY SUPPORT 

AND THE IMPORTANCE OF ADVANCE DIRECTIVES IN 

PATIENTS WITH CHRONIC DISEASE 

In patients with clearly-reversible respiratory failure, not adequately managed 

by noninvasive means, intubation and mechanical ventilation are almost 

always indicated. On the other hand, for patients with terminal illnesses, facing 

the onset of respiratory failure from which they are not expected to recover, 

especially when there is no substantial likelihood of meaningful cognitive 

function in the future, mechanical ventilation would simply prolong the process 

of dying. In most jurisdictions, intubation and mechanical ventilation can 

legally be withheld in such cases on the basis of medical futility. 


The decision is more difficult when the results of ventilatory support cannot 

be accurately predicted, but when intubation (or tracheostomy) is necessary 

to prevent immediate death or in cases when chronic mechanical ventilation 

is necessary but death is not imminent. For most patients, life on long-term 

chronic mechanical ventilation is difficult and unpleasant, so many patients 

with chronic disease prefer to issue written advance directives documenting 

their desire not to be intubated (“do-not-intubate” or “DNI” directives). Decisions 

regarding DNI directives are optimally made prior to the emergent need for 

mechanical ventilation, 8,9 but the majority of patients unfortunately do not 

make such advanced decisions and are forced to make these decisions when 

respiratory failure is imminent or to rely on a family member or legal guardian 

to determine their wishes. All patients with chronic disease and their families 

should be encouraged to avoid this stress and instead to make their wishes 

known early on, before the threat of respiratory failure. They should not be 

concerned that DNI decisions are set in stone. They remain empowered to 

change their decision at any time as their condition, circumstances or outlook 

changes. 

CONCLUSIONS 

Respiratory failure is a common serious, life-threatening consequence of many 

other pulmonary and non-pulmonary conditions. It is defined as a failure of 

gas exchange, either for oxygen, for carbon dioxide, or both. Treatment is most 

satisfactory when the underlying cause can be corrected, but is otherwise 

focused primarily on supplemental oxygen, and, in severe cases, mechanical 

ventilation. Considerable progress has been made in improving the delivery of 

ventilatory support, especially in the relatively recent development of safe and 

effective forms of “noninvasive ventilatory support.” Nonetheless, respiratory 

failure, especially when the underlying cause is chronic respiratory disease, 

remains a major cause of death in this country. 

REFERENCES 

1. Pierson DJ. Indications for mechanical ventilation in adults with acute 

respiratory failure. Respir Care 2002. 47:249-62. 

2. Aldrich TK, Prezant DJ. Indications for Mechanical Ventilation. In, Tobin 

MJ, editor, Principles and Practice of Mechanical Ventilation, McGraw- 

Hill. pp. 155-89, 1994. 

3. Brochard L. Mechanical ventilation: invasive vs noninvasive. Eur Respir 

J 2003 47:31S-37S. 

4. Tobin MJ. Advances in mechanical ventilation. N Engl J Med 2001 344:1986- 

96. 

5. ARDSnet. Ventilation with lower tidal volumes for acute lung injury and 

the acute respiratory distress syndrome. N Engl J Med 2000 342:1301-8. 

6. Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto 

A, and Lemaire F. Comparison of three methods of gradual withdrawal 

from ventilatory support during weaning from mechanical ventilation. 

Am J Respir Crit Care Med1994 150:896-903. 


357

358 

7. Esteban A, Frutos F, Tobin MJ, Alfa I, Solsona JF, Valverdú I, Fernández 

R, de la Cal MA, Benito S, Tomás R, et al. A comparison of four methods 

of weaning patients from mechanical ventilation. Spanish Lung Failure 

Collaborative Group. N Engl J Med 1995 332:345-50. 

8. Wilson KG, Aaron SD, Vandemheen KL, et al. Evaluation of a decision aid 

for making choices about intubation and mechanical ventilation in chronic 

obstructive pulmonary disease. Patient Educ Counsel 2005 57:88-95. 

9. Hofman JC, Wenger NS, Davis RB, et al. Patient preferences for communication 

with physicians about end-of-life decisions. Annals Intern Med 1997 127:1- 

12. 




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