Occupational and Environmental Lung Diseases: Diseases from Work, Home, Outdoor and Other Exposures

Occupational and Environmental Lung Diseases

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

Occupational and Environmental Lung Diseases Editors

Susan M. Tarlo Department of Medicine and Dalla Lana School of Public Health, University of Toronto, and Division of Respiratory Medicine, University Health Network, Toronto, Ontario, Canada

Paul Cullinan Occupational and Environmental Respiratory Disease, National Heart and Lung Institute (Imperial College), London, UK

Benoit Nemery Toxicology and Occupational Medicine, Department of Public Health, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium

This edition first published 2010, Ó 2010 John Wiley & Sons, Ltd Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wileys global Scientific, Technical and Medical business with Blackwell Publishing. Registered office: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Other Editorial Offices: 9600 Garsington Road, Oxford, OX4 2DQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Occupational and environmental lung diseases : diseases from work, home, outdoor and other exposures/ [edited by] Susan M. Tarlo, Paul Cullinan, Benoit Nemery. p. cm. Includes index. Summary: ‘‘Documents both environmental and work-related causes of lung disease. Unlike other books on the subject, this new volume approaches occupational and environmental lung disease from the starting point of the patient who comes to the physician with respiratory symptoms. The authors recognize that potentially harmful exposures occur not only in the work environment, but also as a result of hobbies or other leisure activities, or from outdoor air pollution, and it is up the physician to identify whether a particular job or hobby is the cause of the patient’s respiratory symptoms. To help you arrive at a differential diagnosis, chapters in the book are arranged by job or exposure, and are divided into 5 sections: Personal environment. Home environment. Other indoor environments. Work environment. General environment. Each is written by an expert in the specific topic and provides pragmatic information for the practicing physician. This practical book is an invaluable resource that belongs close at hand for all physicians dealing with patients experiencing respiratory symptoms’’– Provided by publisher. ISBN 978-0-470-51594-5 (hardback) 1. Lungs–Diseases–Environmental aspects. 2. Occupational diseases. I. Tarlo, Susan M. II. Cullinan, Paul. III. Nemery, Benoit. RC756.O227 2010 616.20 4071–dc22 2010025645 ISBN: 978-0470-51594-5 A catalogue record for this book is available from the British Library. Set in 10.5/12.5 pt Minion-Regular by Thomson Digital, Noida, India Printed in Singapore by Markono Print Media Pte Ltd First Impression

2010

Contents Contributors Preface

xxiii

Introduction Paul Cullinan and Susan M. Tarlo Asthma Hypersensitivity pneumonitis (extrinsic allergic alveolitis) COPD Bronchiolitis Pneumoconiosis Lung cancer and mesothelioma Attribution Further reading Part I 1

2

xv

The personal environment

1 1 3 4 5 5 7 8 10 11

Cosmetics and personal care products in lung diseases Howard M. Kipen

13

1.1 1.2 1.3 1.4

Introduction: historical context of cosmetics and respiratory illness Epidemiological context Description of exposures Respiratory diseases associated with exposure to cosmetics and personal care products 1.5 Diagnosis and management of occupational asthma in hairdressers References Further reading

13 14 15

Passive smoking Maritta S. Jaakkola

23

2.1 Introduction 2.2 Exposure to second-hand smoke 2.3 Health effects of passive smoking in children 2.4 Health effects of passive smoking in adults 2.5 Diagnostic and management issues related to passive smoking 2.6 Prevention of SHS-related diseases References

23 24 27 33 39 40 41

17 19 21 21

vi

CONTENTS

3

Emissions related to cooking and heating Debbie Jarvis

45

3.1 Introduction 3.2 Description of exposures 3.3 Pollutants produced when using gas appliances in the home 3.4 Diseases associated with exposures References Further reading

45 46 46 50 54 54

Cleaning and other household products Jan-Paul Zock

55

4.1 Introduction 4.2 Description of exposures 4.3 Diseases associated with exposures 4.4 Diagnosis and management issues 4.5 Summary and conclusions References Further reading

55 56 61 65 67 67 67

Building materials and furnishing Jouni J.K. Jaakkola and Reginald Quansah

69

4

5

5.1

Introduction to building materials and furnishing as sources of indoor air pollution 5.2 Emission of formaldehyde from building and interior surface materials 5.3 Emissions of volatile organic compounds 5.4 Emission of phthalates from PVC building and interior surface materials 5.5 Damp buildings and emissions of biological particles 5.6 Specific diseases associated with exposures from building materials and furnishing 5.7 Diagnosis and management issues References Further reading 6

69 70 72 74 75 76 77 78 79

Mites, pets, fungi and rare allergens Frederic de Blay, Magdalena Posa, Gabrielle Pauli and Ashok Purohit

81

6.1 Introduction 6.2 Mites 6.3 Cat and dog allergens 6.4 Rodents and other pets 6.5 Cockroaches 6.6 Fungi (molds) 6.7 Rare allergens 6.8 Diagnosis and management issues Further reading

81 81 82 84 85 86 90 92 93

CONTENTS

7

Hobby pursuits Paul D. Blanc 7.1 Definitions and general approach 7.2 Arts, crafts, and related activities in the plastic arts 7.3 Hobbies and pastimes involving pets and other animals 7.4 Sports and the performing arts 7.5 Miscellaneous hobbies, pastimes and avocations 7.6 Specific diseases associated with hobby activities 7.7 Diagnosis and management Further reading

Part II 8

9

10

Other indoor environments

vii 95 95 96 99 100 102 104 104 105

107

Day-care and schools Eva Ro€nmark and Greta Smedje

109

8.1 Introduction 8.2 Description of exposures 8.3 Diseases associated with exposures in the school environment 8.4 Viral infections 8.5 Ventilation 8.6 Room temperature 8.7 Diagnosis and management issues 8.8 Summary 8.9 Recommendations Further reading

109 110 114 115 115 115 117 119 119 119

Secondhand smoke exposure and the health of hospitality workers Mark D. Eisner

121

9.1 Introduction 9.2 Exposure of hospitality workers to SHS 9.3 Diseases and health conditions associated with exposures 9.4 Diagnosis and management issues 9.5 Conclusions References

121 121 123 127 127 128

Health effects of environmental exposures while in automobiles Madeline A. Dillon and David B. Peden

129

10.1 Environmental exposures in automobiles 10.2 Air pollution exposure while driving in cars 10.3 Smoking exposure 10.4 Other exposures in cars 10.5 Diseases associated with exposures 10.6 Diagnosis and management issues 10.7 Helpful websites Further reading

129 130 132 132 133 134 135 135

viii 11

CONTENTS

Indoor sports Harman S. Paintal and Ware G. Kuschner

137

11.1 11.2 11.3

137 139

11.4 11.5 11.6 11.7 11.8 11.9 11.10 11.11 11.12 11.13 11.14 11.15 11.16

Part III 12

13

Introduction Ice sports and arenas Ice arena air pollution: exposures and practical hints when taking a history Indoor ice arena toxicant syndromes Standards, guidelines and public health considerations Cold air-exacerbated asthma and dyspnea Water sports Exposures Diseases and health effects Extrinsic allergic alveolitis (hypersensitivity pneumonitis) Infections Swimming-induced pulmonary edema Trauma Equestrian arenas and horseback riding Gymnastics, weightlifting, athletics (track and field) and rock wall climbing Further reading

139 140 143 144 144 145 147 149 151 151 152 152

The work environment

159

155 155

Agricultural environments and the food industry Jakob Hjort Bønløkke, Yvon Cormier and Torben Sigsgaard

161

12.1 Introduction 12.2 Agriculture and agribusiness 12.3 Case 1 12.4 Case 2 12.5 Symptoms not related to allergen exposure 12.6 Other agrobusiness 12.7 Seafood and meat processing 12.8 Case 3 12.9 Bakeries 12.10 Other food industry 12.11 International perspective References

161 161 166 166 167 169 170 172 172 173 174 175

Mining Robert L. Cowie

177

13.1 13.2 13.3 13.4 13.5 13.6

177 178 178 179 184 185

Introduction Population at risk The mine environment Pneumoconiosis Obstructive pulmonary disease Tuberculosis and nontuberculous mycobacterial diseases

CONTENTS

14

15

13.7 Malignant disease 13.8 Pleural disease 13.9 Connective tissue and renal diseases 13.10 Mining and tobacco smoking 13.11 Acute lung and airway inhalational injury 13.12 Trauma 13.13 Conclusion Further reading

185 186 186 187 188 189 189 189

Metal industry and related jobs (including welding) William S. Beckett

191

14.1 Introduction 14.2 Metals defined 14.3 Workplace hazards from metals 14.4 Metal industry processes 14.5 Pulmonary responses to metals 14.6 Beryllium: lung and systemic effects 14.7 Cobalt disease (hard metal pulmonary disease) 14.8 Welding-related lung disease Acknowledgment Further reading

191 191 192 192 193 195 197 197 201 201

Automobile maintenance, repair and refinishing Meredith H. Stowe and Carrie A. Redlich

203

15.1 15.2 15.3 15.4 15.5 15.6 15.7

203 204 204 205 205 209

Introduction – the industry Exposures from automobile maintenance and repair Exposures in auto body workshops Respiratory diseases in auto mechanics and repair workers Work-related asthma Other lung diseases in auto mechanics and repair workers Other nonpulmonary occupational diseases among auto repair workers Further reading 16

17

ix

210 210

Automotive industry Kenneth D. Rosenman

211

16.1 Introduction 16.2 Respiratory hazards and disease 16.3 Vehicle parts manufacturing Further reading

211 213 213 222

Wood and textile industries Kjell Tore
n

223

17.1 17.2 17.3

223 226 227

Wood industry The pulp and paper industry The textile industry

x

18

19

CONTENTS

17.4 Prevention References Further reading

231 231 231

Chemical, coatings and plastics industries Oyebode A. Taiwo and Carrie A. Redlich

233

18.1 18.2 18.3 18.4

Introduction and definitions Overview of the chemical, coatings and plastics industry Major types of paints, coatings and plastics Major respiratory disorders in chemical, coatings and plastics workers 18.5 Diagnosis and management Further reading

233 234 235

Work with electronics Sherwood Burge

247

19.1 19.2 19.3 19.4 19.5 19.6 19.7

247 247 248 248 249 249

Introduction The history of soldering Diseases in those exposed to soft soldering flux fumes Epidemiological context Definition of scope (and limitations) Exposures and processes in the electronics industry Practical hints (and pitfalls) when taking a history from patient 19.8 How to document exposure, including biomonitoring 19.9 Diseases associated with colophony and isocyanate exposure in the electronics industry 19.10 Diagnosis and management issues 19.11 Management and prevention 19.12 Medicolegal considerations and compensation 19.13 Public health issues 19.14 The spectrum of occupational diseases in electronics workers Further reading 20

241 244 245

249 251 252 254 256 256 257 257 258

The services industry George L. Delclos, Lea Ann Tullis and Arch I. Carson

259

20.1 20.2 20.3 20.4 20.5 20.6

259 260 265 266 268

Introduction Health diagnosing and treating occupations Personal care and service – cosmetology professionals Protective services Food preparation and serving-related occupations Building and grounds cleaning and maintenance occupations – janitors/cleaners 20.7 Conclusions Further reading

269 270 270

CONTENTS

21

22

23

24

xi

The construction industry Gary M. Liss, Edward L. Petsonk and Kenneth D. Linch

273

21.1 Introduction 21.2 Inhalation hazards in the construction industry 21.3 Diseases associated with exposures in construction work 21.4 Asthma and selected immunologic conditions 21.5 Occupational cancers 21.6 Other conditions Further reading

273 274 276 280 283 287 288

Police, firefighters and the military Aaron M. S. Thompson and Stefanos N. Kales

291

22.1 22.2

Introduction First responders: potential exposures common to police, firefighters and the military 22.3 Police 22.4 Firefighters 22.5 Military 22.6 Compensation Further reading

291

Office workers and teachers Jean M. Cox-Ganser, Ju-Hyeong Park and Kathleen Kreiss

313

23.1 Introduction 23.2 Exposures in office buildings and schools 23.3 Diseases associated with exposures 23.4 Diagnosis and management issues Further reading

313 316 330 333 336

Research workers Paul Cullinan

337

24.1 24.2 24.3 24.4 24.5 24.6 24.7

337 338 340 341 345 347

Introduction Respiratory hazards and diseases Respiratory sensitization: asthma and rhinitis Making a diagnosis of respiratory sensitization Management of respiratory sensitization in the research setting Respiratory disease arising from exposures to irritant substances Immediate effects of acute exposures to respiratory irritants at relatively high intensity 24.8 Management of the acute effects of high-dose irritant exposure 24.9 Longer-term effects of acute exposures at relatively high intensity 24.10 Nonasthmatic diseases 24.11 Asthma 24.12 Management of irritant-induced asthma 24.13 Other respiratory diseases in research workers 24.14 Other occupational diseases among research workers Further reading

292 302 303 306 309 310

348 350 350 350 351 352 353 354 354

xii 25

26

CONTENTS

Work in hyperbaric environments Mark Glover

357

25.1 Introduction 25.2 Respiratory hazards, diseases and their management 25.3 Further information Further reading

357 361 373 374

Effects of travel or work at high altitudes or low pressures Michael Bagshaw

377

26.1 Introduction 26.2 Physics of the high-altitude environment 26.3 Physiology of flight 26.4 Altitude illness Further reading

377 378 379 385 388

Part IV 27

28

29

The general environment

389

Natural sources – wildland fires and volcanoes Sverre Vedal

391

27.1 Introduction 27.2 Biomass burning 27.3 Volcanoes 27.4 Management/prevention Further reading

391 392 399 402 404

Traditional urban pollution Sam Parsia, Amee Patrawalla and William N. Rom

405

28.1 Introduction 28.2 Particulate matter 28.3 Sulfur oxides 28.4 Nitrogen oxides 28.5 Ozone 28.6 Air toxics References Further reading

405 407 411 413 415 417 418 418

Traffic-related urban air pollution Steven M. Lee and Mark W. Frampton

421

29.1 Introduction 29.2 History of traffic-related air pollution 29.3 Engines and emissions 29.4 Traffic-related air pollutants 29.5 Health effects of traffic-related air pollution 29.6 Conclusions References Further reading

421 422 425 428 430 439 440 442

CONTENTS

30

xiii

Outdoor sports  Kai-Hakon Carlsen

445

30.1 30.2 30.3

445 446

Introduction Epidemiological context Definition of exposures related to asthma and respiratory disorders in athletes – pathogenetic mechanisms 30.4 Diseases related to physical activity, training and competition in sports 30.5 Diagnostic considerations and medicolegal issues 30.6 Treatment of asthma and exercise-induced bronchoconstriction in athletes 30.7 International regulations for use of asthma drugs in sports 30.8 Controller treatment of EIA 30.9 Reliever treatment of EIA 30.10 Recommendations for the treatment of exercise induced asthma in athletes References Further reading Index

447 448 450 450 451 452 453 454 455 456 457

Contributors Michael Bagshaw

Jakob Hjort Bønløkke

Professor of Aviation Medicine King’s College London Visiting Professor Cranfield University WC2R 2LS, UK

Department of Environmental and Occupational Health Institute of Public Health Aarhus University Denmark

William S. Beckett

Sherwood Burge

Associate Professor of Medicine Harvard Medical School, Boston, MA Attending Physician, Medicine Mount Auburn Hospital 330 Mount Auburn St Cambridge, MA 02138, USA

Consultant Physician Occupational Lung Disease Unit Birmingham Heartlands Hospital Birmingham B9 5SS, UK

Paul D. Blanc Professor of Medicine and Endowed Chair Occupational and Environmental Medicine University of California, San Francisco Box 0924 San Francisco, CA 94143-0924, USA Fr
ed
eric de Blay Division of Pulmonology Asthma and Allergology Chest Diseases Department 1SB401 Hoˆpitaux Universitaires de Strasbourg BP426, 67091 Strasbourg Cedex, France

Kai-Ha˚kon Carlsen Professor of Paediatric Respiratory Medicine and Allergology University of Oslo Professor of Sports Medicine Norwegian School of Sport Sciences Oslo University Hospital, Rikshospitalet Department of Paediatrics NO 0027 Oslo, Norway Arch I. Carson Southwest Center for Occupational and Environmental Health Division of Environmental and Occupational Health Sciences The University of Texas School of Public Health Houston, Texas, USA

xvi

CONTRIBUTORS

Yvon Cormier

Madeline A. Dillon

Pulmonologist Institut Universitaire de Cardiologie et de Pneumologie de Qu
ebec (IUCPQ) Professor of Medicine Department of Medicine Universit
e Laval Qu
ebec, Canada

Center for Environmental Medicine Asthma and Lung Biology University of North Carolina Chapel Hill North Carolina, USA

Robert L. Cowie

Associate Professor of Medicine University of California, San Francisco San Francisco, CA 94143, USA

Professor of Medicine and of Community Health Sciences University of Calgary Director, Tuberculosis Services, Calgary Director, Calgary COPD and Asthma Program Respirologist, Alberta Health Services Health Research and Innovation Centre 3280 Hospital Drive NW Calgary, Alberta, T2N 4Z6, Canada Jean M. Cox-Ganser Division of Respiratory Disease Studies National Institute for Occupational Safety and Health Morgantown, West Virginia, USA Paul Cullinan Professor in Occupational and Environmental Respiratory Disease National Heart and Lung Institute (Imperial College), and Royal Brompton Hospital, London, UK George L. Delclos Professor Southwest Center for Occupational and Environmental Health The University of Texas School of Public Health Houston, Texas, USA

Mark D. Eisner

Mark W. Frampton Professor of Medicine and Environmental Medicine Pulmonary and Critical Care University of Rochester Medical Center 601 Elmwood Ave., Box 692 Rochester, NY, 14642-8692 585-275-4861, USA Mark Glover Medical Director Hyperbaric Medicine Unit St Richard’s Hospital Spitalfield Lane Chichester West Sussex PO19 6SE, UK Jouni J.K. Jaakkola Professor of Public Health Center for Environmental and Respiratory Health Research University of Oulu, Finland Professor of Environmental and Occupational Medicine Institute of Occupational and Environmental Medicine University of Birmingham UK

CONTRIBUTORS

xvii

Maritta S. Jaakkola

Kathleen Kreiss

Professor and Chief Physician of Respiratory Medicine Respiratory Medicine Unit Institute of Clinical Medicine University of Oulu and Oulu University Hospital P.O. Box 5000 90014 Oulu, Finland

Division of Respiratory Disease Studies National Institute for Occupational Safety and Health Morgantown, West Virginia, USA

Debbie Jarvis Respiratory Epidemiology and Public Health Group Emmanuel Kaye Building Manresa Road National Heart and Lung Institute Imperial College London SW3 6LR, UK Stefanos N. Kales Medical Director Employee & Industrial Medicine Cambridge Health Alliance Assistant Professor Harvard Medical School Director Occupational & Environmental Medicine Residency Harvard School of Public Health 1493 Cambridge Street Cambridge, MA 02139, USA Howard M. Kipen Professor and Interim Chair Department of Environmental and Occupational Medicine Acting Associate Director Environmental and Occupational Health Sciences Institute UMDNJ-Robert Wood Johnson Medical School 170 Frelinghuysen Road Piscataway, NJ 08854, USA

Ware G. Kuschner Associate Professor of Medicine Stanford University School of Medicine Division of Pulmonary and Critical Care Medicine United States Department of Veterans Affairs Palo Alto Health Care System 3801 Miranda Avenue, 111P Palo Alto, CA 94304, USA Steven M. Lee Pulmonary and Critical Care Medicine Southern California Permanente Medical Group Kaiser Permanente Fontana Medical Center 9985 Sierra Avenue, Fontana, CA 92335, USA Kenneth D. Linch Division of Respiratory Disease Studies Surveillance Branch National Institute for Occupational Safety and Health Morgantown, West Virginia, USA Gary M. Liss Assistant Professor Gage Occupational and Environmental Health Unit Dalla Lana School of Public Health University of Toronto (and Ontario Ministry of Labour) Toronto, Ontario, Canada

xviii

CONTRIBUTORS

Harman S. Paintal

David B. Peden

Clinical Assistant Professor of Medicine Stanford University School of Medicine Division of Pulmonary and Critical Care Medicine United States Department of Veterans Affairs Palo Alto Health Care System 3801 Miranda Avenue, 111P Palo Alto, CA 94304, USA

Center for Environmental Medicine Asthma and Lung Biology University of North Carolina Chapel Hill North Carolina, USA

Ju-Hyeong Park Division of Respiratory Disease Studies National Institute for Occupational Safety and Health Morgantown, West Virginia, USA

Edward L. Petsonk Professor of Medicine Section of Pulmonary and Critical Care Medicine West Virginia University School of Medicine PO Box 9166 Morgantown, West Virginia 26506, USA

Sam Parsia Assistant Professor Division of Pulmonary, Critical Care, and Sleep Medicine Department of Medicine New York University School of Medicine New York, NY, USA Amee Patrawalla Assistant Professor Division of Pulmonary and Critical Care Medicine University of Medicine and Dentistry of New Jersey New Jersey School of Medicine Newark, NJ, USA Gabrielle Pauli Division of Asthma and Allergy Chest Diseases Department University Hospital Strasbourg BP 426, 67091 Strasbourg Universit
e Strasbourg 4 rue Blaise Pascal 67000 Strasbourg, France

Magdalena Posa Division of Asthma and Allergy Chest Diseases Department University Hospital Strasbourg BP 426, 67091 Strasbourg Universit
e Strasbourg 4 rue Blaise Pascal 67000 Strasbourg, France Ashok Purohit Division of Asthma and Allergy Chest Diseases Department University Hospital Strasbourg BP 426, 67091 Strasbourg Universit
e Strasbourg 4 rue Blaise Pascal 67000 Strasbourg, France Reginald Quansah Institute of Occupational and Environmental Medicine University of Birmingham Birmingham, UK

CONTRIBUTORS

Carrie A. Redlich

Greta Smedje

Professor of Medicine Occupational and Environmental Medicine and Pulmonary & Critical Care Medicine Yale University School of Medicine New Haven, CT, USA

Department of Public Health and Clinical Medicine Occupational and Environmental Medicine Umea˚ University SE-901 85 Umea˚, Sweden

William N. Rom Sol and Judith Bergstein Professor of Medicine and Environmental Medicine Director Division of Pulmonary, Critical Care and Sleep Medicine Department of Medicine New York University School of Medicine 550 First Avenue New York, NY 10016, USA

Meredith H. Stowe

€nmark Eva Ro Associate Professor Department of Public Health and Clinical Medicine Occupational and Environmental Medicine Umea˚ University SE-901 85 Umea˚, Sweden Kenneth D. Rosenman Professor of Medicine Chief, Division of Occupational and Environmental Medicine College of Human Medicine Michigan State University 117 West Fee East Lansing MI 48824, USA Torben Sigsgaard Professor Department of Environmental and Occupational Health Institute of Public Health Aarhus University Denmark

xix

Associate Research Scientist Department of Medicine Yale Occupational and Environmental Medicine Lecturer Epidemiology and Public Health Yale University School of Medicine New Haven, CT 06510, USA Oyebode A. Taiwo Associate Professor of Medicine Director, Fellowship Training Occupational and Environmental Medicine Program Yale University School of Medicine 135 College Street, 3rd Floor New Haven, CT 06510-2483, USA Susan M. Tarlo Department of Medicine and Dalla Lana School of Public Health University of Toronto Division of Respiratory Medicine University Health Network Toronto, Ontario, Canada Aaron M. S. Thompson Occupational & Environmental Medicine Clinic St. Michael’s Hospital 30 Bond Street Toronto, Ontario M5B 1W8, Canada

xx

CONTRIBUTORS

Kjell Tor
en

Jan-Paul Zock

Professor/Senior Consultant of Clinical Allergology and Occupational Medicine Head Section of Occupational and Environmental Medicine University of Gothenburg Box 414, 405 30 Gothenburg, Sweden

Associate Research Professor Centre for Research in Environmental Epidemiology (CREAL) and Municipal Institute of Medical Research (IMIM-Hospital del Mar) Barcelona Biomedical Research Park (PRBB) Doctor Aiguader 88 08003 Barcelona, Spain

Lea Ann Tullis Southwest Center for Occupational and Environmental Health The University of Texas School of Public Health Houston, Texas, USA Sverre Vedal Professor of Environmental and Occupational Health Sciences University of Washington School of Public Health Adjunct Professor of Medicine University of Washington School of Medicine Seattle, WA, USA

Editors Susan M. Tarlo, MB BS, MRCP(UK), FRCP(C) Department of Medicine and Dalla Lana School of Public Health, University of Toronto, and Division of Respiratory Medicine, University Health Network, Toronto, Ontario, Canada Paul Cullinan, MD, FRCP Occupational and Environmental Respiratory Disease, National Heart and Lung Institute (Imperial College), London, UK Benoit Nemery, MD, PhD Toxicology and Occupational Medicine, Department of Public Health, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium

Preface This book was initially the concept of Dr Ben Nemery, who identified that no current textbooks approach the topic of Occupational and Environmental Lung Diseases from the starting point of the patient who comes to a physician with respiratory symptoms. Early in the clinical history the patient should be identified as having a particular job or ‘environmental’ exposure(s). A natural question then should be ‘Is this job (or other exposure or even hobby) the cause of the respiratory symptoms in this patient, and if so, what could be the differential diagnosis?’ The chapters in this book are therefore arranged by job or exposure(s) rather than by specific causative agents. Each is written by an expert in the specific topic and aims to provide pragmatic information for the practicing physician. The format of various chapters varies in keeping with the emphases considered to be most useful by the invited authors. In keeping with the aims of the book we have asked authors to provide practical information and to keep specific references to a minimum, but to include some key review articles that the reader may access for more detailed references if wished. With this format, the information presented represents the views of the author of each chapter, and there may be small differences expressed in different chapters. We also recognize that there is some degree of repetition in the book, but we felt it most useful to include this if it pertains to different jobs or exposures in different chapters. We recognize that potentially harmful exposures occur not only in work environments but also as part of hobbies or other leisure activities such as sports, and also from outdoor air pollutants; we have included sections on each of these. We have not included a chapter on the personal effects of tobacco products (since these effects are well recognized by all physicians), on the smoking of marijuana (for which there are far fewer published data) or on exposures to nanoparticles other than as outdoor ultrafine particulates (since the knowledge of their effects is currently very sparse). However we believe that most of the important exposures are addressed. We hope that this book will not be a reference guide on a bookshelf but will be a useful and much-used adjunct in the clinical setting, finding a place at your right hand. The editors

Introduction Paul Cullinan1 and Susan M. Tarlo2 1 2

Imperial College and Royal Brompton Hospital, London, UK University of Toronto and University Health Network, Toronto, Ontario, Canada

In this Introduction we aim to set the stage by giving a brief overview of the lung diseases that are alluded to in this book. While their details and those of the investigations used in their diagnosis may be familiar to the specialist respiratory physician, they may be more useful to review for other readers. Conversely, the discussion of disease attribution at the end of this chapter, which is probably familiar to occupational physicians, may be more useful for the pulmonary and primary care physician. We again wish to emphasize the importance of taking a detailed occupational and environmental history. Important in all patients, it is particularly so in those with respiratory symptoms, as can be clearly seen in the chapters that follow. There is a limited number of ways in which the lungs can respond to an environmental exposure, whether this is at work, home, outdoors or as part of a hobby. While the specific cause for the disease is important in diagnosis, and in allowing appropriate management to prevent further disease in the patient (and potentially in others), nevertheless, the pattern of disease can be similar from many different causes. The diagnosis of an occupational (and sometimes other environmental) disease may lead to disease-related compensation for the individual affected, but in particular should serve as a sentinal event, leading to appropriate consideration of co-workers who may also be at risk. Confirmation of an occupational disease, and where possible, identification of the cause can potentially lead to changes at work to protect others and reduce their risk of disease, and readers are encouraged to determine the appropriate steps locally to allow workplace interventions, e.g. by public health agencies or company physicians.

Asthma Asthma is a common condition that can start at any age. It affects between 5 and 10% of adults and can be caused or exacerbated by work or other environmental exposures, or Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

2

INTRODUCTION

may start incidentally and be provoked without a clear environmental trigger. It has been estimated that 10–15% of adult asthma may be attributed to occupation, and cohort studies have shown that up to 20% or more of working asthmatics can have exacerbations of their asthma due to exposures or conditions at work. Occupational asthma is defined as asthma that is caused by a specific exposure at work. It may be due to a demonstrated or presumed immunologic response to a work agent (sensitizer-induced occupational asthma), or can be due to a high-level irritantexposure (irritant-induced asthma, for which the most clear example is reactive airways dysfunction syndrome, RADS). Work-exacerbated asthma comprises unrelated asthma (preceding or with concurrent onset to work), which is worsened either on a sporadic or frequent basis by conditions at work. Both occupational and work-exacerbated asthma are included in the term ‘work-related asthma’. The features from the history which should increase suspicion of sensitizer-induced occupational asthma are primarily: (a) asthma beginning during a work period; (b) asthma symptoms improving on days or holidays away from work and/or worsening on work days; and (c) a known or presumed sensitizer exposure at work. Investigations for suspected occupational asthma include: objective confirmation of asthma with pulmonary function tests showing a significant bronchodilator response or positive methacholine or equivalent test of airway responsiveness; serial peak flow monitoring, with recordings of peak flow rates in triplicate at least four times a day during days at work and periods off work over several weeks, concurrently recording asthma symptoms and medications; repeat of methacholine or equivalent tests near the end of a work week and after 10 days or more off work to assess changes in PC20 related to work exposures; skin prick or in-vitro tests to identify specific IgE antibodies to a work sensitizer (when feasible); induced sputum cytology to identify changes in eosinophil and neutrophil counts during work period and off-work periods; and specific inhalation challenges with the suspected work substance (if needed and if available). Published guidelines, standards of care and consensus statements are available to provide more detail for investigations and interpretation of results. The best prognosis for sensitizer-induced occupational asthma occurs with early diagnosis and complete removal from further exposure to the sensitizer. Irritant-induced asthma resulting from a high-level, usually accidental exposure at work has different diagnostic features. The most definitive form, RADS, requires: absence of pre-existing airway disease; onset within 24 hours of high-level irritant exposure, usually leading to an urgent-care visit; objectively confirmed asthma by bronchodilator response or methacholine challenge; and asthma symptoms that persist for at least 3 months after the exposure. Somewhat more lax criteria may allow a diagnosis of irritant-induced asthma when RADS cannot be diagnosed. Work-exacerbated asthma is often diagnosed from history in a patient with preexisting asthma who has a transient exacerbation of asthma symptoms and/or increased need for asthma medications when there is an unusual exposure at work to conditions that may be expected to worsen asthma (e.g. construction in an office building or exposure to dusts or fumes). However, if work-related symptoms are frequent, then investigations as for sensitizer-induced occupational asthma should be performed. If the trigger for worsening of asthma is a specific workplace sensitizer, then management would be the same as for occupational asthma. If the trigger is a common allergen (such as dust mite) or a non-specific fume or dusts then

HYPERSENSITIVITY PNEUMONITIS (EXTRINSIC ALLERGIC ALVEOLITIS)

3

management may require adjustment of exposures, and/or optimization of pharmaceutical management.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) This is a hypersensitivity response in the small airways and alveoli involving production of IgG antibodies to the triggering antigen and also a cell-mediated immune response characterized by a lymphocytic alveolitis, non-caseating granulomas and interstitial foreign body granulomas, and can lead to eventual fibrosis. The triggering antigen is commonly an inhaled microbe which can be an atypical mycobacterium, fungus, a thermophilic actinomycete or a protozoa. Organic dusts such as soy dust or avian proteins, and some chemicals such as methylene diphenyl diisocyanate or phthalic anhydride, can also cause this response. The acute form has features similar to pneumonia, with fever, chills, cough, chest tightness (with or without wheezing), often with basal crackles and radiographic findings similar to pneumonia. Typically symptoms begin 4–8 hours after exposure to the inhaled antigen and clear within a few days, usually spontaneously. However they may be severe enough to cause hypoxia and require hospital admission with steroid treatment. Patients may require intubation and may be (unnecessarily) treated for pneumonia with unexpectedly fast recovery and recurrence when they are re-exposed again to the inciting agent. More chronic forms can occur with or without a preceding history of acute attacks. The presentation is then similar to that of idiopathic pulmonary fibrosis (IPF), with chronic cough, dyspnea, fatigue, weight loss and basal crackles. Chest radiograph may be normal or show changes similar to IPF, and the CT scan may show ground glass opacities and tree-in-bud appearance, or eventually may show changes of chronic interstitial fibrosis. The differential diagnosis also includes other causes of interstitial lung disease but bronchoalveolar lavage typically shows lymphocytosis, predominantly CD8 T cells, unlike findings in IPF or sarcoidosis. When feasible, a useful investigation for hypersensitivity pneumonitis (acute and occasionally chronic) is to look for serum precipitins identifying specific precipitating antibodies to the suspected antigen. Unfortunately there is a limited range of commercially available antigens for this test, and results can be positive in up to 50% of exposed asymptomatic individuals. Nevertheless, with a high pre-test probability of disease, this test can be very useful. Lacasse and colleagues have reported high diagnostic value for hypersensitivity pneumonitis from a combination among six features in patients with interstitial lung disease: known antigen exposure; positive precipitins; recurrent episodes of symptoms; timing 4–8 hours after exposure; inspiratory crackles on auscultation of the chest; and weight loss. Their study provided predictive values for various combinations of these tests and often prevents the need for more invasive diagnostic tests such as open lung biopsy or specific inhalation challenge, which can carry significant risk. Management as for those with occupational asthma requires complete avoidance of further exposure to the causative agent. Occasionally, when this is not possible for financial reasons, an air-supply respirator may prevent progressive changes, especially if exposure is occasional and for short periods.

4

INTRODUCTION

COPD ‘Chronic obstructive pulmonary disease’ is an awkward disease label, encompassing as it does a mix of symptoms (e.g. chronic sputum production), pathology (e.g. emphysema) and functional limitation (e.g. fixed airflow obstruction). Each of these may exist in isolation but their combination – especially in heavy smokers – is common. Indeed the link with cigarette smoking is so strong that the diagnosis of COPD is rare in nonsmokers; where it does occur in patients who have never smoked, an environmental cause – frequently occupational – is probable. For the same reason, establishing an environmental cause in a smoker is very difficult and generally, in the individual case, impossible. On a population level, however, it is estimated that 15% of the total burden of COPD is attributable to irritant exposures in the workplace often acting, probably, in synergy with cigarette smoking. Most current definitions of COPD rely heavily on the presence of irreversible airflow limitation measured by spirometry. Spirometry is a more challenging technique than is commonly recognized and requires considerable attention to detail; fortunately, guidelines for good practice are widely available. An ‘obstructive’ picture is one with a reduced FEV1/FVC ratio with or without a reduction in FEV1. There is no universal consensus as to what constitutes a ‘reduction’ in either of these measures but almost all authorities use some form of proportional comparison with expected values based on age and sex. Thus, for example, the Global Initiative on Obstructive Lung Disease advises that mild COPD exists where the measured FEV1/FVC ratio is less than 70% in the presence of a ‘normal’ (>80% predicted) FEV1. More severe disease is suggested by an FEV1/FVC ratio less than 70% and lower values of FEV1 such that measurements between 50 and 79% of the predicted value indicate ‘moderate’ COPD and lower values ‘severe’ or ‘very severe’ disease. There are innate problems with this approach. First, FEV1/FVC ratio declines with age and using a fixed ratio as the cutoff will tend to under-diagnose airflow limitation in the young and over-diagnose it in the elderly. FEV1 declines with age in both men and women but its variance does not; thus proportionate (‘% predicted’) methods of labeling ‘normality’ and ‘abnormality’ will lead to an over-diagnosis of obstruction in those with smaller absolute FEV1 values reflective of their age. A more meaningful approach would take advantage of the normal distribution of FEV1 at any age so that, for example, only spirometric values which lay two or more standard errors away from the predicted mean would be considered ‘abnormal’. This approach is not commonplace yet but is likely to become so in the near future. A second difficulty with purely spirometric approaches to the diagnosis of COPD arises in the situation – not uncommon in working populations – where an individual has an ‘abnormally’ large FVC but a ‘normal’ or mildly sub-normal FEV1; their spirometry will thus appear, at times wrongly, to be obstructed. Finally, single measurements of spirometry are representative only of the present and tell the clinician nothing about the past. Patients with apparently normal values may, a few years previously, have had higher values and thus be suffering an accelerated decline in lung function that cannot be detected without access to serial measurements. Most diagnostic algorithms for COPD include, in addition to the measurement of simple lung function, the presence of symptoms. These are typically of breathlessness (which may crudely be quantified) and/or of persistent sputum production (‘chronic

PNEUMOCONIOSIS

5

bronchitis’). Accompanying emphysema is sometimes apparent on a simple chest radiograph but is detectable with far greater sensitivity on CT scanning. Evidence of a reduction of oxygen uptake attributable to emphysema may be found through measurement of gas transfer (TLCO (DLco) and KCO) in the pulmonary function laboratory. The ‘fixed’ nature of the airflow obstruction in COPD is poorly responsive to pharmacological treatments but most physicians will advise a trial of inhaled bronchodilators with or without inhaled corticosteroids. Some patients respond well to oral corticosteroids but any improvement needs to be balanced against the likelihood of adverse ‘side effects’ of such treatment. The timely treatment of infective bacterial exacerbations is important as is prophylaxis with pneumococcal and annual influenza vaccination. Exercise – particularly if formalized as ‘pulmonary rehabilitation’ - is of proven benefit in improving function and reducing breathlessness, reflecting the systemic nature of disability in COPD.

Bronchiolitis COPD that arises from cigarette smoking typically affects both small and large airways; and, unfortunately, a great deal of damage can be inflicted on the former before symptoms develop and any changes on simple spirometry are apparent. Some rarer forms of pulmonary obstructive disease affect more specifically the smaller airways. Bronchioles are those distal airways that do not contain cartilage in their walls and have a diameter of less than 2–3 mm. Bronchiolar inflammation (‘bronchiolitis’) arises from a large number of causes which include the inhalation of irritant fumes, dusts or gases usually, but not necessarily, at high intensities. The eventual result may be ‘obliterative bronchiolitis’ (or ‘bronchiolitis obliterans’) in which there is irreversible occlusion of the small airways. In some cases the inflammatory response will include adjacent air spaces, a form of organizing pneumonia. Obliterative bronchiolitis presents with breathlessness and is easily mistaken for COPD. The distinction is generally made using high-resolution pulmonary CT scanning in which bronchiolitis can be detected by a mosaic pattern of oligaemia and by evidence of expiratory air trapping. In some cases, transbronchial or surgical biopsy is required. There is no clearly effective treatment for obstructive bronchiolitis but most physicians will offer a trial of treatment with oral and/or inhaled corticosteroids. Unless there is clear evidence of benefit, such treatments should not be prolonged.

Pneumoconiosis ‘Pneumoconiosis’ is yet another rather unsatisfactory respiratory disease label. Strictly it means nothing more than a disease of the lung caused by the deposition of dust but most specialists would restrict the term to conditions of diffuse, nonmalignant – sometimes fibrosing – parenchymal lung disease caused by occupational exposures to mineral dusts. Much, but not all, pneumoconiosis is apparent on chest radiography. The adjective ‘simple’ is used when the radiographic abnormalities are discrete and separated by areas of normal tissue; ‘complicated pneumoconiosis’

6

INTRODUCTION

(sometimes called ‘progressive massive fibrosis’) describes disease where the changes are confluent. There are corresponding degrees of breathlessness and lung function abnormality. Many airborne dusts that are inhaled at work remain in the lung but their effects are very variable, determined in large part by their innate toxicity and the kinetics of their excretion, but also by factors such as particle size, by co-exposures to other toxic substances, notably cigarette smoke, and by differences in individual susceptibility. Some mineral dusts or fumes – such as those from tin – cause little or no pulmonary damage but because they are highly radio-dense produce an alarmingly abnormal chest radiograph. Others – most infamously, asbestos – are innately fibrogenic while others (silica, coal dust, kaolin) cause disease by largely non-fibrogenic means. The pathological and radiological patterns of different types of pneumoconiosis are sometimes characteristic. Inhaled beryllium, for example, uniquely induces a pulmonary granulomatosis akin to idiopathic sarcoidosis; and cobalt, encountered in ‘hard’ metals, induces pulmonary fibrosis characterized by the presence of ‘giant cells’ in lung tissue or lavage specimens. In most cases the starting point in the diagnosis of a pneumoconiosis is – on a background of a history of occupational dust exposure – the presence of an abnormal chest radiograph. Again the patterns are often characteristic but a detailed description of each is beyond the scope of this book. Importantly, CT scanning of the lungs is a far more sensitive technology and will detect abnormalities that are not visible on a plain radiograph. The correlation between radiological abnormalities and functional limitation is imperfect. Minor degrees of (simple) pneumoconiosis, visible on a chest X-ray film, rarely give rise themselves to symptoms, changes in lung function or reductions in longevity. With more extensive disease, symptoms of breathlessness and cough develop and are accompanied by abnormalities in lung function. These latter are classically ‘restrictive’ with concomitant reductions in both FEV1 and FVC and an increased FEV1/FVC ratio. In practice these are often obscured by evidence also of ‘obstructive’ airflow limitation (generally from many years of cigarette smoking) so that a ‘mixed’ picture emerges. More sophisticated testing will often reveal deficiencies in gas transfer due to even minor pulmonary fibrosis or emphysema. Pneumoconiosis may be complicated by the development of other respiratory diseases. Silicosis, for example – and possibly even silica exposure alone – increases the risk of pulmonary tuberculosis, especially in settings where the latter is endemic. Coal workers’ pneumoconiosis, in those with sero-positive rheumatoid arthritis, may be complicated by the development of large, rounded ‘rheumatoid’ shadows in the midzones of the chest radiograph, so-called Caplan’s syndrome. Asbestosis, and perhaps asbestos exposure without evidence of pulmonary fibrosis, increases the risk of lung cancer in smokers and non-smokers, although the effect is much stronger in those who smoke. Any extensive pneumoconiosis – but most commonly asbestosis – may be complicated by the development of pulmonary hypertension, which is often the explanation of abrupt clinical deterioration. The management of pneumoconiosis is both limited and non-specific. The disease is generally of long latency and many patients will be retired from work at the time of their diagnosis. Those who are still working should be advised that further exposure is detrimental. Other treatment is entirely supportive; immunosuppressive therapies used

LUNG CANCER AND MESOTHELIOMA

7

in other forms of pulmonary fibrosis have no proven benefit in pneumoconiosis. In rare cases lung transplantation is offered.

Lung cancer and mesothelioma Most lung cancers arise in bronchial epithelial cells; squamous cell carcinomas account for about 40% of all male cases and about 30% of those in women. Most other types are either adenocarcinomas (20 and 40% respectively) or small cell carcinomas (20%). Rarer pulmonary tumors include ‘large cell’ and alveolar cell types. There is no clear evidence that the histological type correlates with etiology. Lung cancer tends to present ‘late’ and usually beyond a time when curative (surgical) treatment would be effective. Common presentations include a persistent cough, hemoptysis, pneumonia (a result of bronchial obstruction), pleural effusion or an abnormality on chest radiograph. The diagnosis is generally confirmed by a combination of cytological sputum examination, bronchoscopy with biopsy and more extensive radiology including, in some instances, the use of CT-PET scanning. The distribution of presentations and diagnostic methods is likely to change if there is increasing use of population-based screening for lung cancer. Except in those cases where complete resection is both appropriate and feasible, the treatment of lung cancer is not curative; it often includes the use of chemotherapy and radiotherapy alongside symptomatic treatment. Most cases of lung cancer occur in cigarette smokers which, as with COPD above, often makes it difficult to establish with any certainty an additional or alternative etiological explanation; this is particularly true in individual cases. Thus most of the evidence concerning other causes is derived from large-scale epidemiological studies – in almost all cases of occupationally exposed populations. There is very little evidence in relation to other ‘environmental’ exposures. An exception is mesothelioma, a highly malignant disease of the pleura. In almost all cases, this tumor arises as a result of exposure to asbestos, and particularly to amphibole types of asbestos (crocidolite, amosite and anthophyllite), with a latency of 30–40 years. In most cases the exposure is acquired at work (particular attention should be paid to occupations before the age of 30) but sometimes vicarious exposure – for example to the dusty overalls of a spouse or parent – is responsible. In many parts of the world – notably most of Europe, North America and Australasia – the import and use of asbestos have been banned since the early 1990s but the mineral is still used widely elsewhere. In countries where there has been no primary use for many years, most cases of mesothelioma arise in those who worked in the construction/refurbishment industry, their exposure being to asbestos used in buildings erected in the decades before any ban. This trend is predicted to continue, and indeed accelerate, for 10 years or more and, importantly, give rise to an increasing proportion of patients with mesothelioma who do not recall a clear history of asbestos exposure. As with other types of respiratory cancer, mesothelioma tends to present late and in a state of advanced growth. The median life expectancy after diagnosis is about 14 months; in some instances it is much longer, presumably reflecting disease that was ascertained at an earlier stage. There is no curative treatment for mesothelioma.

8

INTRODUCTION

Attribution Most patients are interested in the cause of their respiratory disease, a concern that is shared by many physicians and presumably all those who will use this book. Sometimes a cause is readily apparent; this is generally the case, for example, for infective and congenital respiratory diseases. In many other instances establishing etiology is less straightforward and, especially in the case of diseases that are common and at a population level have several important risk factors, it may in the individual case be essentially impossible. Thus, and uncomfortably for all concerned, the only honest answer to the question ‘is X responsible for my illness?’ has to be, in many cases, ‘I don’t know’. Such nihilism is not, however, always necessary and the prime purpose of this book is to help the physician determine, in a wide variety of circumstances, which diseases need to be considered, how they might be recognized or excluded, and how secure is the evidence that each may be attributed to an environmental exposure. Before embarking on a search for an environmental explanation, the wise doctor will have already considered the consequences of arriving at one; and the penalties of reaching the wrong one. For some respiratory diseases, both the consequences and any penalties are fairly trivial. The prescription of an antibiotic for acute bronchitis, for example, presumes a diagnosis of bacterial infection even if the physician knows that in most cases a viral cause is more probable. In the individual case – even if not at a global level – the issue matters little since most antibiotics are effective, cheap and safe and need not to be taken for very long; and most viral infections of the airways are self-limiting. Whether or not the infection is bacterial, most patients will rapidly and comfortably recover. In other cases, of course, the risk–benefit equation is more complex as is frequently the case when considering occupational or environmental issues. A diagnosis of occupational asthma, for example, generally leads to a change, and too often a loss, of employment. If the diagnosis is correct then this can be at least partly offset by the likelihood of improvement in the condition and its prognosis. It is not difficult to see, however, that a mistaken diagnosis can be disastrous and arguably worse than a missed diagnosis. Thus in this case the physician owes their patient a very high standard of certainty. A similar situation applies to diagnoses that demand an important change in lifestyle, such as the renovation of a damp home or a change in residence (or schooling) altogether. In other cases a lesser standard of proof may be acceptable. For example, it may matter little to the ex-baker who has decided that he will never again work in a bakery, whether or not his asthma was caused by his previous employment. The same may be the case for patients with other occupational diseases of long latency or for those who do not much mind abandoning a hobby or losing a pet; or even for those who have no intention of avoiding the exposure that is responsible for their disease. Balanced further against these considerations are often issues of compensation, whether sought through civil action or through the state. It is incumbent on all those who look after patients with occupational diseases at least that they be familiar with their local jurisdiction in this respect; and to remember that a weak diagnosis is likely to make a weak case in the courts. It is usually best to be honest and open, and it is our experience that most patients are perfectly happy to listen to and discuss such issues but that they may need time enough to do so. It is very rarely the case that such matters need to be decided in any hurry.

ATTRIBUTION

9

Figure I.1 A hierarchy of attribution in occupational lung diseases

Finally, we address the question of ‘certainty’. How certain is it possible to be when considering an environmental cause of respiratory disease? The simple answer is that it depends; the more complex answer is illustrated in Figure I.1, where we present a ‘hierarchy’ of attribution using occupational causes of lung disease as examples. .

At the top of the hierarchy we have placed ‘catastrophic’ events where an occupational exposure is followed rapidly by the onset of respiratory disease. Examples include asphyxiation or ‘toxic pneumonitis’ in the immediate aftermath of a heavy exposure to irritant fumes in the workplace. Here – on the basis of both the time relationship and the biological reasonability of the outcome – the establishment of cause and acute effect is secure, although effects may be worsened by pre-existing disease. If this seems obvious to the reader, we ask them to consider the question of other outcomes – such as asthma or ‘chemical sensitivity’ – following similar exposures, either of which could have other explanations.

.

Below this we place the few instances where it is possible, with a reasonable degree of certainty, to demonstrate a cause–effect relationship. The prime example here is occupational asthma where a casual relationship with a workplace exposure can usually be observed through the use of serial lung function measurement or specific provocation testing.

.

The third setting where attribution is generally possible at an individual level is where the disease is (relatively) specific to an occupation. While it is true that, as with most organs, the lung has a limited repertoire of reactions to adverse exposures, there is still a reasonably long list of ‘peculiar’ patterns of response. Many types of pneumoconiosis, pleural plaques in certain distributions and mesothelioma are examples of diseases that have both characteristic features and a very rare occurrence outside the occupational context. In these cases, attribution is relatively straightforward and can be achieved with a reasonable degree of certainty.

10

INTRODUCTION

.

The final two levels in the hierarchy describe situations where certainty is far less clear. The first, the ‘probabilistic’, refers to settings where the disease in question is both non-specific and has other important determinants but where there is consistent epidemiological evidence of a independent workplace risk. Where, under certain circumstances of exposure, this risk is more than doubled then it is possible to claim that, for a patient with such a level of exposure, it is more likely than not that, on average, their disease can be attributed to their occupation. Note that any greater degree of certainty is rarely possible and that certainty in the individual case is impossible. Examples in this category include COPD in coal miners with histories of extensive work underground, emphysema in those who have worked with cadmium fumes, and lung cancer in those with heavy exposure to asbestos.

.

In too many instances, there is insufficient epidemiological evidence to make even this level of certainty possible and here the clinician has nothing more to rely on than ‘analogy’. This is the case, for example, in most patients with COPD who have smoked but who also have a history of exposure at work to ‘dusts’ or ‘fumes’. While there is reasonable evidence that such exposures increase the rate of COPD at a population level, very few risk estimates are above 2, their relationship to smoking is unclear and there is very little information on specific exposures. Here attribution can only ever be weak at best.

In summary, the diagnosis of occupational lung disease can be challenging. Suspicion of an occupational cause should start with the primary care physician. Referral to an occupational lung specialist may be needed for complex cases but, for many cases, general internists, and especially other specialists such as respiratory physicians (pulmonologists), allergists and occupational medicine physicians can provide diagnosis and management.

Further reading Fishwick, D., Barber, C.M., Bradshaw, L.M., Harris-Roberts, J., Francis, M., Naylor, S., Ayres, J., Burge, P.S., Corne, J.M., Cullinan, P., Frank, T.L., Hendrick, D., Hoyle, J., Jaakkola, M., Newman-Taylor, A., Nicholson, P., Niven, R., Pickering, A., Rawbone, R., Stenton, C., Warburton, C.J., Curran, A.D. (2008) Standards of care for occupational asthma. Thorax 63: 240–250. Gibson, G.J., Geddes, D.M., Costabel, U., Sterk, P.J., Corrin, B. (2003) Respiratopry Medicine, 3rd edn. Saunders: London. Lacasse, Y., Selman, M., Costabel, U., Dalphin, J.C., Ando, M., Morell, F., Erkinjuntti-Pekkanen, R., Muller, N., Colby, T.V., Schuyler, M., Cormier, Y. (2003) Clinical diagnosis of hypersensitivity pneumonitis. Am. J. Respir. Crit. Care Med. 168: 952–958. Newman Taylor, A.J., Nicholson, P.J., Cullinan, P., Boyle, C., Burge, P.S. (2004) Guidelines for the Prevention, Identification and Management of Occupational Asthma: Evidence Review and Recommendations. British Occupational Health Research Foundation: London; available from: http:// www.bohrf.org.uk/downloads/asthevre.pdf Parkes, W.R. (1994) Occupational Lung Disorders, 3rd edn. Butterworth and Heinmann: Oxford. Tarlo, S.M., Balmes, J., Balkissoon, R., Beach, J., Beckett, W., Bernstein, D. et al. (2008) Diagnosis and management of work-related asthma. American College of Chest Physicians Consensus Statement. Chest 134: 1S–41S. The Global Initiative for Chronic Obstructive Lung Disease (GOLD); http://www.goldcopd.com/

Part I The personal environment

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

1 Cosmetics and personal care products in lung diseases Howard M. Kipen UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ, USA

1.1 Introduction: historical context of cosmetics and respiratory illness Cosmetics may be associated with respiratory illness through two different but overlapping mechanisms. One is via causation of pathological disease, most prominently related to allergen-mediated mucosal and airway responses. The second mechanism is through symptoms and illness behavior associated with odors from the cosmetics. The extent to which these symptoms may also interact with mucosal irritant properties of the agents makes differentiation between airway pathology and symptoms unrelated to airway pathology at times problematic. This chapter will describe the data supporting different disease mechanisms and appropriate clinical and preventive responses. A wide range of individuals, rather than typically ‘healthy workers’, regularly come into contact with personal care products such as soaps, perfumes and hair products. Many of these products are designed to announce their presence to those nearby (perfume odors), and they encompass a diverse array of chemical substances. Odordriven responses may be from the essential product, such as a perfume essence, or added material contained in a mix, such as fragrances added to a hairspray or after-shave. While behavioral effects of agents such as perfumes are intentional and legendary, the association of physical pulmonary conditions with cosmetic products was not reported until the late 1950s. Around 1960 a series of cases reporting a ‘storage disease’ (thesaurosis) or pneumonitis (‘hairspray lung’) were published. However a prevalent condition of the pulmonary parenchyma was never established (possibly due to various

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

14

CH 1 COSMETICS AND PERSONAL CARE PRODUCTS IN LUNG DISEASES

changes in hairspray formulations) and all subsequent concern with respiratory effects of cosmetic and personal care agents has centered on the airways, particularly asthma. The first report of allergic occupational asthma in hairdressers is attributed to Jack Pepys [1] in 1976. The remainder of this chapter will consider both allergic airway disease from cosmetics and personal products and the more complex nonallergic responses to odors.

1.2 Epidemiological context 1.2.1 Occupational exposure to cosmetics and personal care products Data from the USA reveal the substantial size of the workforce involved in cosmetology. According to the US Bureau of Labor Statistics, barbers, cosmetologists and other personal appearance workers held about 790,000 US jobs in 2004. Of these, barbers, hairdressers, hairstylists and cosmetologists held 670,000 jobs; manicurists and pedicurists 60,000; skin care specialists 30,000; and shampooers 27,000. Because most of the relevant scientific literature pertains specifically to hairdressers, this term will be used for the remainder of the chapter. There is no available data on the number of individuals involved in the perfume industry. Although methods for ascertainment differ greatly between countries, the burden of airway disease in hairdressers has been quantitiated in many different nations. Methodologies of varying rigor, including some that are population-based, have documented apparent excesses of asthma and respiratory symptoms relative to the general population among hairdressers working in Sweden, France, Germany, Belgium, Norway, Turkey and Italy. A 2002 questionnaire study of all active Swedish hairdressers showed an asthma incidence rate ratio of 1.6 in never smokers, comparable to the effect of smoking alone in the same group. There was also a nonsignificant excess risk of asthma for self-reports of more frequent exposure to bleaching agents or hairsprays. Interestingly, there was no effect modification by reported atopy and no dose–response relationships for use of persulfates, at variance with much of the clinical data cited below that emphasize the role of persulfate exposure. Iwatsubo and colleagues [2] found no increased respiratory symptoms among hairdressing apprentices compared with office apprentices, but there was a significant decline in FEV1 and FEF25–75 (forced expratory flow), not linked to any specific hairdressing activities. Other studies from France are based on the voluntary national physician reporting program for occupational asthma (Observatoire National des Asthmes Professionels). French asthma incidence rates for hairdressers are 308/million, placing hairdressers at the third highest risk for occupational asthma after bakers and pastry makers (683/million) and car painters (326/million). In Belgium questionnaires completed by hairdressing students showed that 14.1% had already had asthma and 26.7% reported wheezing over the past 12 months. A 1996 study estimated that the burden of work-related asthma in Turkish hairdressers was 14.6%. In Italy about half of a group of hairdressers referred for work-related respiratory symptoms were found to have occupational asthma by specific inhalation challenge, along with a strong association with occupational rhinitis.

1.3 DESCRIPTION OF EXPOSURES

15

1.2.2 Non-occupational exposure to cosmetics and personal care products In a Danish nonoccupational population-based study that included methacholine challenge and skin prick testing it was found that there was no relationship between perfume-associated significant symptoms and atopy, serum ECP or FEV1. However, 42% of subjects reported ocular or airway symptoms from exposure to fragrance, and these 42% were 2.3 times as likely to have bronchial hyperreactivity (BHR) as those without symptoms, suggesting a link between fragrance responses and this defined physiological vulnerability. The fact that 30–40% of those who reported respiratory symptoms in this population-based study had a positive BHR test suggests the possible import of fragranceinduced symptoms, although physiological studies in vulnerable or symptomatic individuals, discussed below, suggest that these relationships are quite complex. Reported provocation of symptoms by environmental chemicals, prominently including perfumes and cosmetics, typically detected by odor, has been shown to be common, averaging about 10–20% of random samples with a range of 10–60% of more specific subpopulations, asthmatics being a prominent subgroup. A more extreme form of such reported sensitivity to chemicals is multiple chemical sensitivities (MCS) or idiopathic environmental intolerance (IEI). In this case the sensitivity to odors affects behavior and social interactions, becoming potentially disabling. No clear physiological abnormalities or explanations have been discovered. Although many clinicians and researchers favor psychological mechanisms for such odor-induced symptoms, there is substantial disagreement. Of particular interest to pulmonologists, individuals fitting the description of MCS seem to have a high rate of pulmonary symptoms. Although data come from clinical series, when compared with age- and sex-matched controls, MCS individuals reported on questionnaires from 1.5 to over 10 times the rate of upper and lower respiratory symptoms, and as suggested above, individuals with asthma report higher rates of provocation by cosmetics and personal care products.

1.3 Description of exposures 1.3.1 Major work processes Hairdressers, besides cutting and shampooing hair, are involved in permanent wave applications and rinsing, in applications of neutralizing agent, in preparing, applying and rinsing hair color, and in preparing, applying and rinsing hair bleaches. Mixing of bleaching powder takes 2–5 minutes per treatment, and it is thought that most exposure to persulfates occurs in this phase, often done in a back room of the salon, rather than during application in the salon per se.

1.3.2 Occupational exposures Hair dressers have three main classes of workplace exposures: 1.

para-phenylamine diamine based dyes, generally associated with delayed hypersensitivity contact dermatitis;

16

CH 1 COSMETICS AND PERSONAL CARE PRODUCTS IN LUNG DISEASES

2. henna (vegetable dye), a rare cause of occupational asthma; and 3. lacquers and bleaching agents with persulfate salts, known to cause dermatitis, rhinitis and asthma. We focus on the latter for this respiratory disease text. There are three categories of hair-dye formulation used respectively for temporary, semi-permanent and permanent hair coloring. The latter are also known as oxidative dyes and are resistant to shampooing. The permanent dyes almost invariably contain ammonium, potassium and sodium persulfates. Persulfate salts are reactive, low-molecular weight compounds widely used in many industries, but particularly cosmetics. The persulfates (H2S2O8) are mixed with an oxidant (H2O2) immediately before use. Improved hair penetration is achieved with the addition of ammonia releasers such as ammonium chloride or ammonium phosphate. Permanent waving chemicals can be either alkaline or slightly acidic aqueous solutions. They contain thioglycolic acid or hydrogen peroxide, with ammonia added to enhance hair penetration. Thus, potent irritants/oxidants including ammonia, hydrogen peroxide (H2O2) and persulfates (H2S2O8) are commonly found in the hairdressing environment. Hair bleaching agents are generally felt to be the most common cause of occupational asthma in hairdressers; however not all studies report that duration of exposure was significantly greater in those who became sensitized. They are the leading causes implicated in specific occupational asthma reports from France and Italy.

1.3.3 Perfumes and nonoccupational exposures Perfumes are blends of odiferous ingredients made from a diluent (commonly ethanol) and mixtures of up to 3000 natural and synthetic fragrance ingredients including volatile oils and aldehydes, potential irritants and sensitizers. Because many of the ingredients are volatile, exposure is widespread, either intentionally or incidentally in proximity to users. Cleaning agents for home or commercial use are associated with asthma, and also contain perfume agents as well as cleaning agents that may be respiratory irritants or sensitizers.

1.3.4 Quantitation of exposures in hair salons In a Swedish study exposures to persulfates during mixing were associated with personal exposures of 35–150 mg persulfates/m3 and mixing area exposures ranged from 23–50 mg persulfates/m3. In a study of exposure in French salons, H2O2 showed mean personal exposure levels of 51 mg/m3, NH3 was 900 mg/m3 and persulfate was 190 mg/m3. These values are below applicable workplace standards, although many deficiencies in ventilation were noted in this study and would seem to be common in the industry.

1.4

EXPOSURE TO COSMETICS AND PERSONAL CARE PRODUCTS

17

1.3.5 Exposure history: practical advice and pitfalls It is important to understand the layout of a salon, including any separate rooms in which mixing of hair products takes place. Specific questions about windows or mechanical ventilation are important. Although ventilation in salons is often reported as substandard, in the rare instances when exposures have been measured, they have been typically less than applicable threshold limit values (TLV) (H2O2, NH3 and H2S2O8) on either side of the Atlantic. This may reflect that the salons studied were not completely representative of all salons. Of course, for individuals who have become sensitized, adherence to threshold limit values cannot be relied upon to prevent future reactions.

1.3.6 Documentation of exposure and biomonitoring Exposure monitoring in salons is not commonly performed, and measures of persistent body burden do not exist and are probably not appropriate to the natural history of the relevant conditions. Moscato [3] reports that, although some hairdressers with asthma have positive skin tests to persulfate, it is not a reliable test of sensitization, because many individuals with disease and apparent exposure have negative tests. As with other prominent causes of occupational asthma, especially for low molecular weight antigens, the available skin test is not clearly immunologically (IgE) mediated. One caveat is that anaphylaxis to persulfate skin testing has been reported.

1.4 Respiratory diseases associated with exposure to cosmetics and personal care products 1.4.1 Occupational asthma Occupational asthma in hairdressers is felt to arise most commonly from sensitization to persulfate salts, although there are case reports with henna as the sensitizer. Pulmonary function test changes and development of asthma are reported during apprenticeship, although latencies of up to 10–15 years appear in the literature. Most published descriptions of occupational asthma in hairdressers is of the allergic sensitization variant; however, there are a limited number of publications describing more immediate responses apparently independent of sensitization. The immunological basis of the sensitization has not been elucidated. One provocative study implicated hairsprays as triggers of pre-existing asthma. Schleuter and colleagues [4] studied immediate responses to hairspray in 1979. They reported a 10–20% decrease in mid flows in eight asthmatics, with no response in 13 healthy subjects to a 20 second spray of two hairsprays. The investigators attributed this bronchoconstriction response to the perfume content of the hairspray rather than the plasticizer, diethyl phthalate. However, this and other phthalates in indoor air from building products have been subsequently epidemiologically implicated in asthma induction, and they are still prevalent in hairspray at concentrations of up to 3%. Further examination of a potential role for phthalates in respiratory irritation and

18

CH 1 COSMETICS AND PERSONAL CARE PRODUCTS IN LUNG DISEASES

asthma is warranted, in both occupational and nonoccupational settings. For more information on the use of phthalates in cosmetics see: http://www.safecosmetics.org/ docUploads/NotTooPretty_r51.pdf

1.4.2 Responses to odors Cone and Shusterman [5] discussed the health effects of indoor odors. They emphasized variability in the human odor response, and that perfumes are a commonly reported exacerbating agent for asthma. The citation supporting the relationship between perfume and asthma derives from a commonly cited convenience sample of 60 asthmatics specifically recruited by Shim and Williams [6] with sensitivity to odors in mind. They documented that physiological responses to odor provocation could occur; and that atropine, beta agonists and cromolyn abrogated responses in three out of four subjects tested. However, subjects were not blind to test exposures and thus the response could have been perceptual rather than irritant. In fact, they raised the possibility of behavioral sensitization to odorants. The differentiation between irritant/ allergic airway effects as opposed to behaviorally or perceptually mediated effects is a recurring theme when considering the human (respiratory) response to cosmetics and personal care products. This differentiation is more frequently an issue in general environmental contexts rather than occupational contexts. Relationships have been documented in individuals among asthma symptoms, hay fever and chemical odorants. A number of well-controlled studies have shown that perfume stimuli induce respiratory symptoms in asthmatics but not always with accompanying physiological change. Millquist [7–9] exposed nonasthmatics, with a history of respiratory symptoms (but no airway obstruction) following nonspecific irritating stimuli, to perfume. She elicited respiratory symptoms (as well as hoarseness, eye irritation, headache and fatigue) without airway obstruction. The symptomatic responses persisted even after using a carbon filter to block odor. In a subsequent study of ocular exposure to perfume, she again elicited asthma symptoms, even in the absence of hyperventilation, as documented by stable end-tidal CO2. A sensory mechanism, possibly via the trigeminal nerve, was hypothesized, and this integrative approach is a promising avenue for further exploration of individual responses, as well as for therapy. Lastly, she exposed 10 asthmatics (all with provocative concentration for 20% fall in FEV1 < 2 mg/ml) to a commercial perfume and found no change in FEV1 compared with a saline exposure and no increase in symptoms. Similarly Opiekun et al. [10] studied mild and moderate asthmatics following a 30 minute controlled exposure to a prototypical fragranced air-sanitizing product. They found increased nasal symptoms, but there were no explanatory physiological changes in nasal mucosal swelling (measured by acoustic rhinometry), no ocular hyperemia, and no significant changes in FEV1 (other spirometric values were not reported) at 5 or 30 minutes after exposure. These investigations document that both asthmatics and nonasthmatics can respond to perfumes with respiratory symptoms, yet no significant bronchoconstriction. Making this determination between physiological airway responses and perceived respiratory distress can be challenging for the clinician. There are reports of those with immediate asthmatic (symptom) responses to perfume; however no analytic epidemiology addresses this issue per se. There is

1.5 OCCUPATIONAL ASTHMA IN HAIRDRESSERS

19

substantial literature on how professional cleaners/janitors and users of cleaning sprays have increased asthma morbidity; however this may be more associated with some of the cleaning agents as opposed to the scents and is addressed elsewhere in this book. Attempts to separate the effects of the alcohol vehicle from the active perfume ingredients have suggested that both may play a role in production of spirometric effects and symptoms, with more severe and atopic asthmatics showing greater responses to perfume challenge.

1.4.3 Unexplained symptoms and psychophysiological responses As suggested in Millquist’s work above, many individuals suffer from episodic respiratory symptoms, sometimes triggered by environmental exposures, but do not meet diagnostic criteria for asthma or other conditions: they do not have bronchospasm. Prominent among reported triggering exposures are cosmetics, with frequently described exposures including cosmetic counters at department stores, churches and office or classroom environments where coworkers use perfumes and other cosmetics. The limited epidemiology has been described above, but there are a number of pertinent clinical studies that have been carried out and suggest the importance of odor-triggered neural mechanisms as explanations for these symptoms. Van den Bergh suggested learned responses to odors of a Pavlovian nature that can be conditioned or deconditioned. A group in Toronto found that panic symptoms could be triggered by standardized stimuli much more readily in those with unexplained symptoms and suggested a relationship between unexplained symptoms, panic attacks and hyperventilation. Although this has not been studied in asthmatics, and does not directly concern perfume scents, it provides a potential mechanistic underpinning to understand individuals with complaints of respiratory distress attributed to scents, and suggests the design of behaviorally based therapeutic strategies where pathological pulmonary disease has been excluded.

1.5 Diagnosis and management of occupational asthma in hairdressers There are no randomized trials to guide diagnosis or management of occupational asthma in hairdressers. Diagnosis of occupational asthma in hairdressers is not always straightforward due to the lack of reliable markers of sensitization to persulfate salts as discussed above, but general methods have been reviewed [11]. Both immediate and delayed symptom responses are reported. Because an underlying IgE mechanism is not reliably demonstrated, immunological tests by skin prick or serum-specific IgE lack both sensitivity and specificity. Thus, reliable confirmation of clinical suspicion relies on specific inhalation challenge testing. Various techniques have been described, although such challenges are not in widespread use in many areas of the world, particularly the USA. Treatment of allergic occupational asthma is via standard protocols with avoidance of exposure at the top of the list. Once a diagnosis of occupational asthma in a hairdresser, usually to persulfate salts, has been made, exposure reduction or

20

CH 1 COSMETICS AND PERSONAL CARE PRODUCTS IN LUNG DISEASES

elimination is the most desirable therapeutic alternative. Use of respiratory protection is described but without apparent success, and improved hygiene of salons is often difficult to accomplish. In one study of eight cases, mean exposure duration prior to diagnosis was 15 years and mean duration of symptoms before diagnosis was 38 months, suggesting that improved surveillance could be a key to reducing morbidity.

1.5.1 Medical management of reactions to scented products Once physiological responses to environmental or occupational exposures have been excluded, a more difficult set of management challenges faces the practitioner. Pulmonary medications have little relevance unless there is comorbid asthma. Speech therapy or behavioral approaches may be useful for upper airway (vocal cord) dysfunction, which may be triggered by irritants and possibly nonirritating odors. Psychotherapy, anxiolytic medication, cognitive–behavioral therapy (CBT) and biofeedback have all been tried clinically, and have shown responses for individual cases in resolving respiratory and other symptoms associated with odiferous stimuli. More rigorous randomized trials have been conducted in broader groups of somatizing patients, and shown significant, 20–40%, improvement in symptoms and limitations, with courses of cognitive–behavioral therapy. Blind referrals to mental health practitioners are often ineffective. The referring pulmonologist must clearly communicate that organic lung disease has been excluded, freeing the mental health practitioner to concentrate on reducing symptomatic responses, possibly even in the face of continued exposure to moderate levels of nonsensitizing cosmetics. The ideal CBT takes place in the setting of a physician’s office, as some patients with these symptoms are reluctant to view their symptoms as psychological. It is sometimes useful to convey to the patient that they need to demonstrate the power of ‘mind over matter’, developing their mental strength to overcome as yet unidentified, but not lifethreatening, problems in their body.

1.5.2 Other illnesses Upper extremity musculoskeletal complaints are associated with work as a hairdresser, and can largely be addressed through client chairs that are adjustable in height. Use of nail cosmetics in nail salons is gaining increasing popularity worldwide. Although a number of irritant compounds are used, there are no reports of respiratory disease in the literature. Ethyl methacrylate, formerly used in artificial nail processing, has been linked to asthma. Its use is largely discontinued.

1.5.3 Medicolegal and compensation Individual countries and states vary in their system of compensation and requirements. In those places where specific inhalation challenge is a component of compensation evaluation, this bodes well for specific identification of cases, allowing for appropriate

FURTHER READING

21

compensation. In the USA, where specific challenge testing is not common, less direct evidence probably leads to less efficient, and likely more contentious, determinations.

1.5.4 Public health Some of the epidemiology has indicated an increased prevalence of asthma among hairdressing apprentices. In one study of hairdressers there was a mean of 38 months between symptom onset and diagnosis, accounting for fairly poor outcomes with persistent symptoms and a decline in FEV1, despite cessation of exposure. This emphasizes the importance of surveillance and early recognition of occupational disease if there is to be any confidence of avoiding long-term impairment. Development of nonsensitizing products for hair bleaching is clearly a goal.

References 1. Pepys, J., Hutchcroft, B.J., Breslin, A.B. (1976) Asthma due to inhaled chemical agents – persulphate salts and henna in hairdressers. Clin. Allergy 6(4): 399–404. 2. Iwatsubo, Y., Matrat, M., Brochard, P., Ameille, J., Choudat, D., Conso, F., Coulondre, D., Garnier, R., Hubert, C., Lauzier, F., Romano, M.C., Pairon, J.C. (2003) Healthy worker effect and changes in respiratory symptoms and lung function in hairdressing apprentices. Occup. Environ. Med. 60(11): 831–840. 3. Moscato, G., Pignatti, P., Yacoub, M.R., Romano, C., Spezia, S., Perfetti, L. (2005) Occupational asthma and occupational rhinitis in hairdressers. Chest 128(5): 3590–3598. 4. Schlueter, D.P., Soto, R.J., Baretta, E.D., Herrmann, A.A., Ostrander, L.E., Stewart, R.D. (1979) Airway response to hair spray in normal subjects and subjects with hyperreactive airways. Chest 75(5): 544–548. 5. Cone, J.E., Shusterman, D. (1991) Health effects of indoor odorants. Environ. Health Perspect. 95 53–59. 6. Shim, C., Williams, M.H. Jr. (1986) Effect of odors in asthma. Am. J. Med. 80(1): 18–22. 7. Millqvist, E., Bengtsson, U., L€ owhagen, O. (1999) Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity. Allergy 54(5): 495–499. 8. Millqvist, E., L€ owhagen, O. (1998) Methacholine provocations do not reveal sensitivity to strong scents. Ann. Allergy Asthma Immunol. 80(5): 381–384. 9. Millqvist, E., L€ owhagen, O. (1996) Placebo-controlled challenges with perfume in patients with asthma-like symptoms. Allergy 51(6): 434–439. 10. Opiekun, R.E., Smeets, M., Sulewski, M., Rogers, R., Prasad, N., Vedula, U., Dalton, P. (2003) Assessment of ocular and nasal irritation in asthmatics resulting from fragrance exposure. Clin. Exp. Allergy 33(9): 1256–1265. 11. Moscato, G., Galdi, E. (2006) Asthma and hairdressers. Curr. Opin. Allergy Clin. Immunol. 6(2): 91–95.

Further reading Albin, M., Rylander, L., Mikoczy, Z., Lillienberg, L., Dahlman H€ oglund, A., Brisman, J., Tor
en, K., Meding, B., Kronholm Diab, K., Nielsen, J. (2002) Incidence of asthma in female Swedish hairdressers. Occup. Environ. Med. 59(2): 119–123. Baur, X., Schneider, E.M., Wieners, D., Czuppon, A.B. (1999) Occupational asthma to perfume. Allergy 54(12): 1334–1335.

22

CH 1 COSMETICS AND PERSONAL CARE PRODUCTS IN LUNG DISEASES

Bornehag, C.G., Sundell, J., Weschler, C.J., Sigsgaard, T., Lundgren, B., Hasselgren, M., H€agerhedEngman, L. (2004) The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case–control study. Environ. Health Perspect. 112(14): 1393–1397. Committee on the Assessment of Asthma Indoor Air (2000) Clearing the Air: Asthma and Indoor Air Exposures. Division of Health Promotion and Disease Prevention, Institute of Medicine: Washington, DC. Das-Munshi, J., Rubin, G.J., Wessely, S. (2007) Multiple chemical sensitivities: review. Curr. Opin. Otolaryngol. Head Neck Surg. 15(4): 274–280. Elberling, J., Linneberg, A., Dirksen, A., Johansen, J.D., Frølund, L., Madsen, F., Nielsen, N.H., Mosbech, H. (2005) Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity. Clin. Exp. Allergy 35(1): 75–81. Kipen, H.M., Fiedler, N., Lehrer, P. (1997) Multiple chemical sensitivity: a primer for pulmonologists. Clin. Pulmon. Med. 4(2): 76–83. Kumar, P., Caradonna-Graham, V.M., Gupta, S., Cai, X., Rao, P.N., Thompson, J. (1995) Inhalation challenge effects of perfume scent strips in patients with asthma. Ann. Allergy Asthma Immunol. 75 (5): 429–433. Mun˜oz, X., Cruz, M.J., Orriols, R., Torres, F., Espuga, M., Morell, F. (2004) Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts. Occup. Environ. Med. 61(10): 861–866. Mounier-Geyssant, E., Oury, V., Mouchot, L., Paris, C., Zmirou-Navier, D. (2006) Exposure of hairdressing apprentices to airborne hazardous substances. Environ. Health 5: 23. Tarlo, S.M., Poonai, N., Binkley, K., Antony, M.M., Swinson, R.P. (2002) Responses to panic induction procedures in subjects with multiple chemical sensitivity/idiopathic environmental intolerance: understanding the relationship with panic disorder. Environ Health Perspect. 110 (suppl. 4): 669–671.

2 Passive smoking Maritta S. Jaakkola University of Oulu and Oulu University Hospital, Oulu, Finland

2.1 Introduction Passive smoking is defined as exposure of a (nonsmoking) person to tobacco combustion products from smoking by others. Several synonyms are used in the literature, including involuntary smoking, exposure to environmental tobacco smoke (ETS) and exposure to second-hand smoke (SHS). SHS exposure has been recently recommended as the term to be used, for example by the Tobacco Free Initiative of the World Health Organization [1]. The term ETS was previously used widely, but it seems to have been introduced originally by the tobacco industry and it is recommended to be used less, as it can obscure the preventable nature of this exposure. The term ‘involuntary’ could imply that voluntary smoking would not be as bad for the health, so this term will also be used less in the future. Passive smoking is still common in homes, workplaces and public places in many countries, although in recent years there has been some progress, with increasing number of countries introducing smoke-free workplace legislation and other tobacco control measures. Some studies have suggested that smoke-free workplaces also reduce smoking at home, and thus lead to reduced passive smoking at home [2]. This may be explained by both increased awareness of the adverse health effects of passive smoking and the reduced active smoking detected in many studies as a consequence of the legislation. However, it is not possible to introduce legislation to protect directly those who are most vulnerable to the harmful effects of SHS exposure at home, i.e. infants, children and the elderly. To protect the health of these susceptible population groups, it is important to increase emphasis on educating people about the adverse effects of passive smoking, and to support smokers to quit or at least to behave in a way that does not expose others to tobacco smoke. In this work, healthcare personnel are among the key players.

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

24

CH 2 PASSIVE SMOKING

This chapter will first introduce definitions related to passive smoking and describe exposure to tobacco smoke, then review the current knowledge on health effects of SHS exposure in children and adults, and finally discuss clinical applications and preventive measures. In reviewing health effects, assessment of whether the relation between SHS exposure and the health condition is causal is based on the criteria usually used by the recent reviews. These include: (i) the number of studies that have been published on the topic and whether these studies come from different parts of the world; (ii) consistency of findings; (iii) validity of the studies, including control for confounding factors (i.e. other risk factors) and potential biases; (iv) evidence of an exposure–response relation (also called a dose–response relation); (v) evidence of biologically plausible mechanisms; and (vi) evidence of meaningful temporal relation. The best estimate of the effect is given based on recent meta-analyses, which have combined the results of studies published on the health outcome in question. If such a summary estimate is not available, the best effect estimate is given based on a recent, high-quality study.

2.2 Exposure to second-hand smoke 2.2.1 Definitions and constituents of tobacco smoke Second-hand smoke is composed of sidestream smoke (SS), which is formed from the burning of tobacco products and emitted directly into the environment from the smouldering end of the cigarette between puffs, and exhaled mainstream smoke (MS), which is first inhaled by the smoker before being released into the environment. Other smaller contributors to SHS include smoke that diffuses through the wrapper of the cigarette and smoke that escapes while the smoker inhales. SS is the principal constituent of SHS. Tobacco smoke is a mixture of thousands of chemicals released into the air as gases, vapors and particles [3]. Over 4000 individual constituents have been identified and these include more than 50 carcinogenic substances as well as many toxic and irritant compounds [4,5]. In addition, several compounds have adverse effects on reproduction. Many constituents are released in higher concentrations in SS than MS because of different burning conditions and less complete combustion of SS. Thus, SS contains higher concentrations of many harmful substances, but is usually then diluted into a larger volume (Table 2.1) [6]. The US National Toxicology Program estimated that at least 250 chemicals in SHS are known to be toxic or carcinogenic. In addition, it is possible that exposure to the mixture of different compounds in SHS is more harmful to health than exposure to any of the individual chemicals, as the compounds may have synergistic effects, i.e. they may have together a larger effect than would be expected from summing up the effects of individual compounds [7]. There is some evidence suggesting that evaporation of biologically less active components may cause aged sidestream smoke to be more toxic on a weight-for-weight basis. SHS exposure usually means passive smoking by nonsmokers. However, smokers are exposed to particularly high concentrations of sidestream smoke, because their own smoking is the major source of it and because they spend more time in smoky environments. Thus, SS may contribute to the adverse health effects detected in active

25

2.2 EXPOSURE TO SECOND-HAND SMOKE

Table 2.1 Emissions of selected tobacco smoke constituents in fresh, undiluted mainstream smoke (MS) and diluted sidestream smoke (SS) from nonfiltered cigarettes [6] Constituent

Amount in MS per cigarette

SS:MS ratio

12–48 mg 1.7 ng 4.6 ng 20–80 ng

5–10 30 2–4 13–30

12–23 mg 70–100 mg 60–100 mg 100–600 mg

2.5–4.7 0.1–50 8–15 4–10

Established carcinogensa Benzene 2-Naphthylamine 4-Aminobiphenyl Nickel Toxic or irritant Carbon monoxide Formaldehyde Acrolein Nitrogen oxides IARC category 1 ¼ carcinogenic to humans.

a

smokers, but as this has not been studied much, this chapter will focus on the health effects of passive smoking in nonsmoking populations, which have been studied extensively. It should be noted that a fetus can be exposed to tobacco smoke by either the mother’s active smoking during pregnancy or a nonsmoking mother’s exposure to SHS. Both of these influence the development of the fetus, as tobacco smoke constituents are transferred across the placenta, so both of them result in fetal passive smoking. This chapter will focus on fetal passive smoking from the mother’s SHS exposure during pregnancy.

2.2.2 Sources of SHS exposure For young children, smoking adults at home, especially the parents, form the principal source of SHS exposure. With increasing age, other places contribute as sources of SHS exposure: first day-care facilities and then school and many social environments. Among adults, home and workplace are the major sources of SHS exposure, because of the long time periods usually spent in these environments. However, some social environments, such as bars, restaurants and public transport, have been found to have particularly high concentrations of SHS. This chapter will focus on SHS exposure at home. It will briefly also mention SHS exposure at work, but other chapters will discuss SHS exposure in other environments.

2.2.3 Occurrence of SHS exposure The prevalence of SHS exposure varies considerably between countries and is influenced by the prevalence of active smoking, the traditions and behavioral cultures, the tobacco control legislation and the healthcare and educational systems. Multicenter studies from North America and Europe have measured cotinine in body fluids as an indicator of passive smoking and found that, in the 1980s, more than 80% of the

26

CH 2 PASSIVE SMOKING

nonsmoking populations were exposed to SHS. They also showed an alarming trend for the highest exposures to be detected in children and young adults. Today there is more variability in SHS exposure within Europe and between different states of the USA, as some countries and states have adopted smoke-free workplace and other forms of stricter tobacco control legislation, while others have not yet taken these preventive steps. For example, estimates of the prevalence of passive smoking of children from Europe have ranged from 7–15% in Finland and Sweden to 70–75% in Bulgaria and Poland. SHS still remains the most important preventable indoor exposure even in many high-income countries. The smoking epidemic in low-income countries seems unfortunately to continue, meaning that a high proportion of children in such countries are exposed to SHS. These children may be especially vulnerable to the harmful effects of SHS, as they may suffer also from malnutrition and may be exposed to other harmful compounds, for example from use of solid fuels that may act synergistically with SHS. WHO has databases on smoking prevalences and tobacco control legislations across the world (http://www.who.int/tobacco/global_data/en/index.html).

2.2.4 Measuring exposure to SHS Exposure to SHS can be assessed using different methods depending on the purposes of the measurements [7]. The most direct method to measure SHS exposure is to use personal monitors available for individual tobacco smoke components, such as nicotine or respirable suspended particles (RSP). However, this method requires a lot of labor, is rather expensive and only measures current exposure for a short interval. Individual tobacco smoke components can also be measured by fixed monitors in defined spaces. When combining the results of such measurements with information on time–activity patterns, an individual’s or a population’s exposure to SHS can be assessed. Again, this method only measures current exposure for a rather short interval, is expensive, and only measures exposure to specific compounds rather than to the entire mixture. However, such measurements may be useful, for example, when assessing the effectiveness of smoke-free workplace policy. Studies of health effects have most commonly applied questionnaires or diaries to assess SHS exposure. These methods have the advantages of being cheap and providing the possibility to measure long-term exposure which may be more relevant for many health effects [8]. Questionnaires can also inquire into past exposures. This is the relevant exposure, for example, when investigating lung cancer, as the relevant exposure has taken place at least 10 years earlier because of the long lag time. A potential problem related to questionnaires and diaries is whether people remember and report their exposures correctly. Many studies that have compared questionnaires with other exposure assessment methods suggest that questionnaires provide valid information, i.e. the majority of people report correctly whether they have been or have not been exposed to SHS, but that the exact quantification of exposure may not be very precise. However, it is still likely that people are able to recall rather well whether they have been exposed heavily or lightly. Another way to assess exposure to SHS is to measure biomarkers, i.e. compounds, their metabolites, hemoglobin or DNA adducts in biological samples, which are influenced by the uptake, metabolism and elimination mechanisms in addition to

2.3 HEALTH EFFECTS OF PASSIVE SMOKING IN CHILDREN

27

the exposure concentration. These may give relevant information about exposure to some target organs. The most commonly measured biomarker of tobacco smoke is cotinine in serum, saliva or urine. Cotinine is a major metabolite of nicotine. Its half-life is about 20 h, so it measures only recent exposure over the last 1–3 days. As a consequence of this, it may not be good assessment method for diseases for which long-term exposure is relevant. Hair nicotine concentration has been measured in some recent studies and seems to reflect exposure over the last 2 months. Some studies have also measured biomarkers of the carcinogenic substances, for example amino biphenyl hemoglobin adduct. Biomarkers are indicators for total exposure across different microenvironments, including home, workplace and social settings. For health effect studies, it has been recommended to use a combination of a questionnaire and some other method, if there are enough resources available.

2.3 Health effects of passive smoking in children Children are more susceptible to the adverse effects of SHS than adults for several reasons. Their respiratory system is not fully mature at birth and continues to develop both immunologically and physiologically. Children have higher breathing rate and inhale more air per body volume than adults, which results in higher exposure with a similar SHS concentration. In addition, children’s liver metabolism and other clearing mechanisms are not yet fully developed, so the harmful substances remain longer in the body. Some studies have suggested that children who were exposed to tobacco smoke in utero through either active or passive smoking by the pregnant mother are at greater risk for developing SHS-related diseases later, so tobacco smoke exposure in the very early phases of lung development may also make children more vulnerable later in life. This section will first discuss health effects related to SHS exposure from the mother’s passive smoking during pregnancy and then health effects related to the child’s passive smoking after birth. However, these exposures are highly correlated, as is maternal smoking during pregnancy and the child’s postnatal SHS exposure, so it has not been easy to disentangle the effects of these exposures.

2.3.1 Health effects of mother’s passive smoking during pregnancy Health effects related to mothers’ SHS exposure during pregnancy are summarized in Table 2.2. Lung function impairment Maternal smoking during pregnancy has been linked to reduced lung function in infants in many studies. According to recent reviews [5,9], there is also evidence of adverse effects of maternal passive smoking during pregnancy on the child’s lung function. However, as the number of studies looking at this question is limited, no definite conclusions concerning effects of mother’s SHS exposure during pregnancy on child’s lung function can be made.

28 Table 2.2

CH 2 PASSIVE SMOKING

Summary of health effects of mothers’ passive smoking during pregnancy

Condition

Best estimate of OR or RR

Reduced lung function Asthma Low birth weight Preterm delivery Other developmental effects

— — 1.2 1.57 —

95% Confidence interval

1.1–1.3 1.35–1.84

Reference

Causality (scale 0 to þþþ )a

[5] [9] [10] [11] [5]

þ þ þþþ þþ þ

0 ¼ no evidence of a relation between passive smoking and this condition; þ ¼ some evidence of a relation between passive smoking and condition; þ þ ¼ strong but not definitive evidence of a causal relation between passive smoking and condition; þ þ þ ¼ established causal relation between passive smoking and condition.

a

Asthma Maternal smoking during pregnancy has been strongly linked to the risk of childhood asthma [12], but again, the overall number of studies looking at the effects related to mother’s SHS exposure during pregnancy is limited [9]. Low birth weight Active smoking by the mother is a well-known cause of low birth weight (LBW). There is increasing literature also on nonsmoking mothers’ exposure to SHS and low birth weight [9,13]. Low birth weight has usually been defined as birth weight 8 mg/gc

Cat allergen in dust

Table 23.7 Studies investigating levels of dust mite, cat and cockroach allergens in dust in offices or schools

—

22%

3.7%

—

% >1 mg/gd

Median Bla g 1i ¼ 2.6 25% >10 U/g

3/160 (2%) samples above limit of detection, maximum Bla g 2 ¼ 25 U/g Not measured

Not measured

Cockroach allergen in dust U/g

326 CH 23 OFFICE WORKERS AND TEACHERS

Median Der f1 ¼ 1.13

Median Der p1 ¼ 4.46

Not measured

—

—

—

—

Geometric mean Fel d1 ¼ 2.2 (carpet) Geometric mean Fel d1 ¼ 0.33 (no carpet) Median range Fel d1 ¼ 0.02–0.4

b

Threshold level for sensitization to dust mites and the development of asthma. Major risk factor for the development of acute asthma in mite-allergic individuals. c Threshold level for sensitization to cat allergen and the development of asthma. d Threshold level for symptoms. e Detectable Der p 1 levels found in 54% of workplaces and detectable Der f1 levels found in 55% of workplaces. f Detectable Fel d 1 levels found in 54% of workplaces. g Detectable Der p 1 levels found in 70% of workplaces and detectable Der f1 levels found in 63% of workplaces. h Detectable Fel d 1 levels found in 99% of workplaces. i Detectable Bla g1 levels found in 69% of samples of dust from schools. j Sensitization threshold levels for dust mite, cat and cockroach allergens were exceeded in many schoolrooms.

a

Patchett et al. (1997) J. Allergy Clin. Immunol. 100: 755–759; floor dust from 11 classrooms in 9 New Zealand primary schools Abramson et al. (2006) J. Sch. Health 76(6): 246–249;41 US schoolsj (results are for the lower grade carpeted rooms of Birmingham schools in spring). —

—

Bla g2 found in all schools and rooms. Median range Bla g2 ¼ 0.08–0.28

Not measured

23.2 EXPOSURES IN OFFICE BUILDINGS AND SCHOOLS

327

328

CH 23 OFFICE WORKERS AND TEACHERS

Pontiac fever. These bacteria, when present, can become aerosolized from cooling towers or humidifiers and be spread throughout a building via the ventilation system. L. pneumophila serogroup 1 is the main causative agent of disease. The dose of L. pneumophila needed to cause disease is not known. In the USA there are currently no federal or state guidelines for monitoring Legionella or regulations specifying exposure limits. The US Occupational Health and Safety Administration (OSHA) recommends testing for the presence of Legionella in water samples. Although dose– response relationships are not understood, and there is still discussion among experts as to the usefulness of regular water testing in the absence of disease, there are action levels recommended by US OSHA. Action level 1 involves prompt cleaning and/or biocide treatment of the system with levels of 100 colony forming units per milliliter (CFU/ml) in cooling tower water, 10 CFU/ml in domestic water, or 1 CFU/ml in humidifier water. Action level 2 involves immediate cleaning and/or biocide treatment, as well as taking prompt steps to prevent employee exposure, with levels of 1000 CFU/ml in cooling tower water, 100 CFU/ml in domestic water or 10 CFU/ml in humidifier water. The European Working Group for Legionella infections has also published action levels following Legionella sampling, which are based on levels of 1 and 10 CFU/ml. The Centers for Disease Control and Prevention (CDC) has a topic site for Legionella: http://www.cdc.gov/legionella/. The European working group has a website: http:// www.ewgli.org/index.htm.

23.2.7 Histoplasma capsulatum Histoplasma capsulatum is a mold which grows in soils throughout the world. In the USA, the proportion of people infected by H. capsulatum is higher in central and eastern states, especially along the Ohio and Mississippi river valleys where Histoplasma is endemic. The dose of spores needed to cause disease is not known, and the level of response to exposure varies among people, depending on age, susceptibility to the infection and likely the number of spores inhaled. Prior infection with Histoplasma can induce immunity and lessen responses to future infections. This mold is not generally associated with damp indoor environments but with soils rich in bird and bat droppings. Thus if birds or bats roost in or around buildings where spores from contaminated soils become carried into the occupied spaces, people in the building are at risk for infection and development of histoplasmosis. Reports exist of histoplasmosis occurring due to Histoplasma spores entering office and school buildings through HVAC air intakes after surrounding soil had been disturbed by construction activities or by rototilling. Environmental samples can be tested for the presence of Histoplasma using a PCR technique. Further information can be found at http://www.cdc.gov/ niosh/docs/2005-109/.

23.2.8 Work-process-related exposures Carbonless copy paper, copier and printer fumes and paper dust Carbonless copy paper (CCP) was introduced in the early 1950s, and within 10 years office workers were complaining of health effects. Irritation of the skin, eyes and upper

23.3

EXPOSURES IN OFFICE BUILDINGS AND SCHOOLS

329

respiratory system were common and cases of allergic contact dermatitis and some systemic effects were reported. In 2000 NIOSH published a hazard review which concluded that there was enough evidence to support exposure to carbonless copy paper or its components as a cause of symptoms of irritation and dermatitis. Symptoms of irritation in office workers have also been linked to exposure to copier and printer fumes. Newer research has provided evidence that adult-onset asthma in office workers may be associated with exposure to CCP as well as to paper dust, but not with exposure to copier and printer fumes. It is possible that components of CCP may cause sensitization, but this has not been well studied. Dose–response relationships are not understood for these exposures.

Pesticides Although there are no published data on the health effects of pesticides in office workers, information on pesticide exposure in schools is pertinent to the office environment. Exposure to pesticides in schools is associated with acute heath effects in both school children and school employees, including respiratory symptoms and aggravation of asthma. Analysis of surveillance data in the USA from 1998 to 2002 indicated an incidence rate of 27.3 cases per million employee full-time equivalents for acute illnesses associated with pesticide exposure in school employees. The incidence rate for the school children was 7.4 cases per million. Exposure to insecticides accounted for 35% of the cases, followed by disinfectants (32%), repellents (13%) and herbicides (11%). Almost 70% of the illness cases were associated with pesticides used at schools as opposed to drift from pesticides used on nearby land. Respiratory effects were reported in 49% of the cases. In the USA there are no federal regulations limiting exposure to pesticides in schools. Some states have regulations regarding the use of pesticides in schools. Useful websites are http://www.cdc.gov/niosh/docs/2007-150/ and http://www .beyondpesticides.org/children/asthma/AsthmaBrochureCited.pdf.

Cleaning agents There is no direct information on health effects of cleaning agents in office workers and teachers, but exposure to cleaning agents is associated with asthma onset and exacerbation in professional cleaners and in healthcare professionals. Furthermore, a recent population-based study in Europe showed that the use of spray cleaners and air fresheners in the home was associated with adult-onset asthma. Although more work is needed to understand the mechanisms by which various cleaning agents cause asthma, certain constituents, such as benzylkonium chloride and the ethanolamines, have been shown in the literature to be sensitizers. There is little information as to dose–response relationships. Certainly cleaning agents may act as irritants and trigger asthma symptoms, especially if cleaning concentrate products are inadvertently used in stronger concentrations than recommended, or components like ammonia and bleach are mixed together.

330

CH 23 OFFICE WORKERS AND TEACHERS

Table 23.8 Indoor-related exposures associated with asthma Source

Example or agent

Dampness

Mold or mold-associated products Bacteria Endotoxin Phthalates Dust mites and their feces Cockroaches Cat allergen Phthalates Pesticides, e.g. pyrethrums Cleaning agents, e.g. amines Paints, glues from renovation Carbonless copy paper emissions Formaldehyde and other emissions from furnishings and building materials Alkaline dusts, e.g. drywall remodeling Toner cartridge products Paper-related dusts, e.g. from damp environments

Living creatures

Chemicals

Particulates

23.3 Diseases associated with exposures 23.3.1 Asthma Asthma is a common disease with both environmental etiologies and genetic propensities. Occupational asthma induced by workplace sensitizers can be cured if the inciting sensitizer is identified early in the disease course and the patient can be removed from exposure. The challenge for the practicing physician is to identify the plausibility of potential asthmagen exposure in the patient’s work environment so that the patient management maximizes cure or at least prevention of further inflammatory injury and remodeling of the airways to a permanent asthmatic phenotype. In office workers and teachers, the etiologic candidates for asthma are many (Table 23.8). Chief among the contributors to asthma in office and school workers is dampnessassociated exposures. The specific antigens, allergens and mechanisms remain undetermined. However, the epidemiologic evidence for asthma risk in relation to both residential and indoor workplace water damage is incontrovertible. In the residential setting, investigators in Europe and North America have found increased risk of wheeze, cough, nasal and throat symptoms, and asthma symptoms in sensitized persons associated with exposure to damp indoor environments. Some evidence exists for dyspnea, lower respiratory illness in otherwise-healthy children, and asthma development in association with damp indoor environments. Since the IOM review of literature published in 2004, additional evidence has mounted that some water-damaged buildings are associated with considerable increases in asthma incidence, consistent with adult-onset asthma being caused by exposures in such damp buildings. With respect to offices and schools in North America, no general population-based studies of building occupants exist with which to describe population-based frequency of asthma in relation to such buildings and damp building-related risk factors.

23.3

DISEASES ASSOCIATED WITH EXPOSURES

331

Nevertheless, within particular damp buildings, risks as high as 7.5-fold increases in adult asthma onset have been documented post-occupancy, as compared with preoccupancy, with many additional co-workers having building-related respiratory symptoms for which they have not sought care or been diagnosed with asthma. A quarter of employees in some damp buildings have new-onset physician-diagnosed asthma. The complex microbial and chemical exposures arising in damp buildings makes identification of a specific verifiable etiology unlikely, even within a particular building subject to extensive environmental characterization. In the absence of an environmental measurement of risk for asthma, a shift in physician and public health paradigm is required. Protection of the asthmatic patient with symptoms arising in a damp building requires exposure cessation. In the short run, this may require restriction from the implicated work area. In the long run, exposure cessation requires remediation of the conditions leading to water incursion from the outside or leaks from indoor sources, as well as replacement of water-damaged materials in a way that precludes further dissemination of microbially contaminated sources. Public health agencies responding to indoor air quality concerns in relation to asthma can consider affected persons as sentinels of risk to co-workers and hence a public health problem. Asthma in office workers and teachers associated with animal allergens come to public health attention less commonly. Chemical causes of asthma in offices and schools are often recognized by patients in association with symptom exacerbation with respect to odors or indoor activities. Lower respiratory symptoms and asthma can be associated with particulates in indoor air. In a series of 80 buildings with indoor air quality complaints investigated by NIOSH, dry wall renovations within the previous 3 weeks was associated with building-related respiratory symptoms. Whether the renovation-associated symptoms are a marker for previous water damage and bioaerosol exposure or alkaline dust from dry wall remains in question. Particulates from copy rooms are sometimes associated with asthma and such work areas merit exhaust ventilation rather than contributing particulate load to the recirculated air as is common in modern buildings. Finally, office workers frequently complain of exacerbation of their building-related asthma symptoms when working with papers moved from previously water-damaged environments to new work environments. Whether such papers with high surface area carry contaminated dust or were sources of bioaerosol amplification in previous damp environments remains unclear, but such anecdotes recur in many building settings.

23.3.2 Hypersensitivity pneumonitis In contrast to building-related asthma, which is a newly recognized phenomenon, this granulomatous interstitial pneumonitis, also known as allergic alveolitis, has been recognized in relation to indoor nonindustrial environments for decades. Early publications of outbreaks usually implicated microbial dissemination from humidification and ventilation systems, although the specific organism(s) were rarely identified. Rather, the epidemiologic distribution of affected persons and resolution with remedial measures for the implicated sources were the basis of attribution to a building component. In fact, serum precipitins were often interpreted as identifying specific microbial etiology, but such immunologic findings are markers of exposure and not disease. Indeed, the precipitins may be markers of exposure to another agent which is correlated with the etiologic agent rather than the etiologic agent itself. The inability of

332

CH 23 OFFICE WORKERS AND TEACHERS

some hypersensitivity pneumonitis cases to reoccupy implicated environments after remediation and cleaning is well established. Ventilation- and humidifier-related hypersensitivity pneumonitis may have decreased with recognition of the need for design changes and maintenance of cleanliness in these systems. More recent publications have implicated damp indoor environments in causing hypersensitivity pneumonitis. Buildings with long-standing water damage from roof leaks, other building envelope water incursion, plumbing leaks and below-grade moisture problems have all had reported clusters of hypersensitivity pneumonitis. Unlike asthma, hypersensitivity pneumonitis is rare in the general population, and even one case with building-related symptoms justifies public health investigation. In the presence of a building-related hypersensitivity pneumonitis case, there is usually a spectrum of other building-related respiratory symptoms and diseases among coworkers. Employee-reported physician-diagnosed asthma is frequently elevated in comparison to the general population. Cough, chest tightness, wheezing and shortness of breath without reported physician diagnoses are also often present in excess. In some damp buildings, clusters of sarcoidosis have occurred. Although pulmonary sarcoidosis might be misdiagnosed hypersensitivity pneumonitis, extra-pulmonary sarcoidosis cases have also been seen in case clusters. Specific etiologies for sarcoidosis in building-related clusters are under investigation.

23.3.3 Rhinitis/sinusitis For three decades, nasal and throat symptoms have been attributed to indoor environments when they occur in tight temporal association with ‘sick buildings’. These nonspecific symptoms did not generate much scientific investigation with objective tests in the era in which ‘sick building syndrome’ was considered subjective and difficult to study. More recently, interest has increased in these upper respiratory tract symptoms because of the robust information coming from study of damp residential environments associated with such symptoms, in which skepticism about secondary gain in the work environment is not a factor. A substantial body of information exists linking asthma exacerbation to upper respiratory tract symptoms. Indeed, the vast majority of occupational asthma cases have work-related rhinitis. In the occupational setting of increased building-related asthma risk, physicians have been impressed that rhino-sinusitis frequently precedes development of asthma with a work-related pattern. To date, little research exists to document the degree of risk of longitudinal progression of building-related rhinosinusitis to asthma. Correlations between symptoms or objective measures of rhinosinusitis and environmental measurements are also in their research infancy. To this end, measurements of nasal peak flow, acoustic rhinometry and nasal markers of inflammation and infection can be adapted to field epidemiology settings to establish a scientific basis for clinical understanding and management.

23.3.4 Other illnesses associated with office and school environments The exposure section above addresses some of the environmental risks in office and school settings associated with the illnesses listed in Table 23.1. These do not require

23.4

DIAGNOSIS AND MANAGEMENT ISSUES

333

Table 23.9 Other illness associated with indoor-related exposures Condition

Example or agent

Environmental contribution

Legionnaire’s disease Histoplasmosis Tuberculosis Communicable virus infection Cough

Legionella pneumophila Histoplasma capsulatum Mycobacterim tuberculosis Influenza, rhinovirus Detergent dust

Contaminated water Disruption bird/bat roosts Ventilation Ventilation Poorly diluted carpet shampoo

further description here, since they may not present to the clinician as building-related or work-related. Nevertheless, their occurrence may trigger a reporting requirement to public health authorities, e.g. legionellosis. Noncommunicable infections often have environmental sources in specific office or school environments. Historically, legionellosis occurred as a result of entrainment of contaminated cooling tower effluents in ventilation systems. Histoplasmosis has occurred in employees exposed to construction dusts from outdoor work, particularly when topsoil with bird droppings is disturbed. Ventilation effects on communicable respiratory infections is an active area of investigation pertinent to pandemic planning and studies of workforce productivity affected by the short-term absenteeism associated with communicable viral respiratory disease. Finally, specific irritant syndromes, such as respiratory irritation due to carpet residual of inadequately diluted carpet shampoo, are discovered by tight temporal association with building occupancy (Table 23.9).

23.4

Diagnosis and management issues

23.4.1 Diagnosis Eliciting a history of symptoms in temporal relation to occupying the work environment is the most critical step in identifying those with building-related asthma, hypersensitivity pneumonitis and rhinitis/sinusitis. Unlike sick building syndrome, which remits when employees exit an implicated building, the temporal pattern of building-related asthma and hypersensitivity pneumonitis is generally more subtle. Examples are occurrence on the evenings of work days in comparison to evenings on the weekend; progressive deterioration over the working week; and remission with sickness absence. Certainly cases can be missed in the history of work-relatedness, particularly for subacute hypersensitivity pneumonitis and sinusitis complicated by infection. Nevertheless, even in these situations, exploration of improvement with prolonged work absence, e.g. over summer holidays in teachers, can be suggestive of a work-related pattern. Exploring whether similar illness is reported by co-workers is also useful. Certainly, report of environmental risk factors, as described above, should increase the clinician’s efforts to explore potential work-relatedness. In 2004, the Center for Indoor Environments and Health of the University of Connecticut Health Center published a document: ‘Guidance for Clinicians on the Recognition and Management of Health Effects Related to Mold Exposure and Moisture Indoors’. This document includes suggestions for taking a patient history

334

CH 23 OFFICE WORKERS AND TEACHERS

in relation to work-related dampness exposures. This document can be accessed at: http://www.oehc.uchc.edu/clinser/MOLD%20GUIDE.pdf. For other respiratory illness related to offices and schools, e.g. noncommunicable infections, there is no history of work-relatedness, and the patient may have little insight into environmental risks for such illnesses, e.g. contaminated water systems or construction activities. Although some evidence exists for increased transmission of common respiratory infections as a function of ventilation rate and crowding in office workers and teachers, physicians may not be aware of these risks. The tools for making a diagnosis of any of these diseases in office workers and teachers are the same as for any patients. Physical examination, spirometry, bronchodilator responsiveness, bronchial hyperreactivity, diffusing capacity, radiology, bronchoalveolar lavage, transbronchial biopsy and other tests are applied in order to narrow the differential diagnosis. The major additions to consider in documenting work-relatedness include symptom and medication logs in relation to work hours and tasks; serial peak flow or hand-held spirometry logs over several weeks to examine a work-related pattern of obstruction or restriction; serial bronchial reactivity tests before and after prolonged work absence; and serial exercise capacity with a focus on respiratory parameters and gas exchange for interstitial disease. Most clinicians do not have the option of specific inhalation challenge to document reactivity to single allergens or antigens, as this test is performed by few referral hospitals. In any case, for most building-related illness, specific single etiologies are unlikely and uncharacterized. Precipitin testing has not been useful in most outbreak situations, in part because relevant antigens may not be commercially available for the complex exposures present in the environments of damp buildings.

23.4.2 Management Building-related respiratory diseases are best managed by exposure cessation. Indeed, for building-related asthma diagnosed early in its course, removal from exposure can be curative. With prolonged symptomatic exposure and steroid dependency, buildingrelated asthma may not remit with removal from exposure, as is the case with most etiologies of occupational asthma. The challenge for patient and clinician is how to achieve exposure cessation to the implicated environment. Medical restriction from a damp building may threaten continued employment. If water damage is limited to part of a building, a trial of relocation within the building or to another part of the enterprise may be justified. These concerns are common to all occupational lung diseases. The pharmacologic treatment of the disease is identical to that of other patients without work-related etiology. In the intermediate and long term, remediation of the environmental conditions resulting in work-related respiratory disease is critical both for individual patients and for prevention of disease in coworkers. Such intervention is a decision beyond the control of most office and school staff, being a prerogative of management or building owner. Notification of the responsible parties of occupational disease is critical, but patients may request that the clinician not do so, for fear of job loss or retribution. In such instances, involvement of public health investigators can protect patient confidentiality where it might otherwise be threatened.

23.4

DIAGNOSIS AND MANAGEMENT ISSUES

335

23.4.3 Medicolegal considerations The provisions for work-related illness compensation vary from country to country and state to state in the USA. Some jurisdictions require etiology to be established by objective tests, specific inhalation challenge or occurrence in a previously recognized industrial setting with specific listed chemical exposure. Other jurisdictions are less restrictive in diagnostic criteria. In general, however, workers’ compensation is an adversarial process for occupational respiratory disease in comparison to work-related traumatic injury, and many patients have their cases denied until they appeal with expert legal and clinical resources. With building-related illness, in particular, the science of the health impact of damp indoor spaces is new enough that compensation systems have little experience with these claims. In the USA, the litigation surrounding alleged health effects of mold has spawned an aggressive defense medicolegal coalition against such claims in residential tortes, insurance proceedings and workers’ compensation.

23.4.4 Public health issues Occupational respiratory illness in educational staff and office workers is a sentinel for co-workers at risk. Apart from occupational physicians employed by a specific business entity, few clinicians have the time or resources to follow back an index case to a working population. However, a clinician can ‘activate’ public health investigation by reporting suspected cases. Public health agencies can bring together multidisciplinary teams to aid in the screening of co-workers and in ascertaining remediable causes of dampness, recommending interventions and even evaluating the effectiveness of interventions. This model of public health preventive action triggered by case reporting is an ideal. In reality, many public health agencies are understaffed, financially stretched and have little experience with occupational disease, either in industrial or nonindustrial environments. The reporting of asthma or hypersensitivity pneumonitis should be to state epidemiologists or physicians, who can recognize the public health implications and request additional resources, for example from federal occupational health agencies. One pitfall is contacting federal or state labor agencies which are regulatory in mission. No permissible exposure limits exist in most jurisdictions for agents associated with dampness. Without regulations to enforce, compliance officers are at a loss to help. In the USA, the research and service agency with expertise in building-related respiratory disease is NIOSH, which is part of the CDC. This agency investigates building-related health concerns in response to requests from three employees (who need not be personally affected), labor unions or managers. In addition, the agency has frequently provided consultation or on-site technical assistance to state and local public health agencies requesting its assistance. As an emerging public health issue, dampness in indoor spaces is currently an emphasis area for both research and service. Similar efforts exist in occupational and public health agencies in other countries such as Canada, Finland and Sweden. Since regulations regarding indoor environmental quality are largely absent in the USA, patients often remain powerless in getting adverse conditions fixed. In schools, parental concern for student health risk and performance can lead to a logical alliance

336

CH 23 OFFICE WORKERS AND TEACHERS

with staff with similar health concerns. In office workers, motivating remediation is a difficult task, since the expense can be considerable, and public health investigation of specific employee populations to develop data for priority setting and policy is a rarity. With the increasing evidence of work-related disability in relation to these nonindustrial settings, perhaps societal consensus can be shifted toward both primary prevention of dampness problems and prompt remediation when necessary.

Further reading Daisy, J.M., Angell, W.J., Apte, M.G. (2003) Indoor air quality, ventilation and health symptoms in schools: an analysis of existing information. Indoor Air 13: 53–64. Guidance for Clinicians on the Recognition and Management of Health Effects Related to Mold Exposure and Moisture Indoors (30 September 2004) Published by the Center for Indoor Environments and Health at University of Connecticut Health Center with support from a grant by the US EPA. Available online at: http://www.oehc.uchc.edu/clinser/MOLD%20GUIDE.pdf. Institute of Medicine of the National Academies of Science (2004) Damp Indoor Spaces and Health. National Academies Press: Washington, DC. Institute of Medicine of the National Academies of Science (2000) Clearing the Air: Asthma and Indoor Exposures. National Academies Press: Washington, DC. Li, Y., Leung, G.M., Tang, J.W., Yang, X., Chao, C.Y.H., Lin, J.Z., Lu, J.W., Nielsen, P.V., Niu, J., Qian, H., Sleigh, A.C., Su, H.-J. J., Sundell, J., Wong, T.W., Yu, P.L. (2007) Role of ventilation in airborne transmission of infectious agents in the building environment – a multidisciplinary systematic review. Indoor Air 17 (1): 2–18. Mudarri, D. and Fisk, W.J. (2007) Public health and economic impact of dampness and mold. Indoor Air 17: 226–235. The IAQ Scientific Findings Resource Bank. Contains summary information and down loadable papers on the relationship of IEQ with people’s health and work performance. This site was developed in conjunction by Lawrence Berkeley National Laboratory in collaboration with the US Environmental Protection Agency; available from: http://eetd.lbl.gov/ied/sfrb/.

24 Research workers Paul Cullinan Imperial College and Royal Brompton Hospital, London, UK

24.1 Introduction The exposures encountered by research workers are as numerous and varied as the research they do. Thus the term ‘research worker’ is a broad one and encompasses a very wide range of individuals with an unusually wide range of potentially hazardous exposures. Moreover, at least in economically developed countries, the total population of research workers is large. Many researchers will be working in universities or other places of higher education – in some cities these are major employers with many thousands of research staff. Others will be employed in the research departments of the commercial sector, often in the pharmaceutical or biotechnology fields; again these workforces are often large although there is an increasing trend, particularly in the biotechnology sector, towards small companies employing just a few research staff. The term ‘research worker’ might also be applied to those who work in developmental or quality control laboratories within industry. In this context, any meaningful clinical assessment of a potentially ‘occupational’ lung disease will require close attention to particular exposures relating both to materials that are used in primary research and those that represent finished products. In many cases such exposures will be obvious; these include, for example, research work with laboratory animals, the use of chemicals widely recognized to cause respiratory irritation and the wearing of latex gloves. Other exposures will be more obscure and will require careful questioning and/or consultation of reference information obtainable either through an employer or directly from the producers or suppliers of chemical agents. Research workers are, in general, highly educated and highly motivated. They will have a better understanding of their work than will their clinician; at the same time they may have a mildly cavalier attitude to the hazards associated with their work, especially

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

338

CH 24 RESEARCH WORKERS

if they have been involved in it for many years. Many will be reluctant, at least initially, to consider an occupational etiology for their disease and more reluctant still to consider leaving or changing their work; this poses special difficulties for those who have developed an occupational hypersensitivity. On the other hand their levels of education – and the relatively liberal environments where they work – mean that career options are often wider than for those who work in industry. Most institutes of higher education and most large companies involved heavily in research will have a well organized system of occupational healthcare including regular health surveillance. Thus their employees are, in this respect, relatively well supported. Furthermore, most research settings are carefully regulated and most research processes are on a fairly limited scale. For these reasons, researchenvironment exposures – with some exceptions, notably those relating to laboratory animals – tend to be considerably less intense than those encountered on the shop floor.

24.2 Respiratory hazards and diseases The most important occupational respiratory diseases in this workforce are those characterized by (variable) airflow limitation (Figure 24.1). Asthma and rhinitis may airborne exposures in research setting

sensitizing sensitising agent

irritant chemical

high low molecular molecular mass mass

high dose

lower dose - repeated

acute

new asthma and/or rhinitis

provocation of pre-existing asthma

toxic damage to airways: nose pharynx trachea bronchi toxic pneumonitis pulmonary oedema edema

? new asthma and/or rhinitis

chronic

asthma (RADS*) OB* OB* COP* other interstitial lung disease

Figure 24.1 Overview of occupational respiratory disease in a research setting; RADS
¼ reactive airways dysfunction syndrome; OB
¼ obliterative bronchiolitis; COP ¼ (cryptogenic) organizing pneumonia

24.2

RESPIRATORY HAZARDS AND DISEASES

339

be induced through sensitization to a workplace agent or, less commonly, by exposure to a toxic dose of a respiratory irritant. Other respiratory diseases arising from research work are far less common. Acute exposures to high doses of respiratory irritants (‘inhalation accidents’) can give rise to toxic damage to the upper and lower airways and even to the gas-exchanging parts of the lung. Irritant exposures of sufficient intensity to cause severe disease appear, fortunately, to be rare in the laboratory. Various forms of interstitial lung disease including hypersensitivity pneumonitis have been attributed to chemical and biological exposures, but again rarely in research workers. More rarely still, in this context, exposures in the laboratory have been considered as contributory to some cases of lung cancer. In each case of occupational respiratory disease in a research worker it is helpful to establish precisely the causative agent; and where appropriate to distinguish disease that has arisen de novo as a result of an exposure at work from pre-existing disease that has been provoked by one or more such exposures. Most commonly the need for this distinction arises in cases of work-related asthma. In the strict sense, ‘occupational asthma’ is that which has been induced by a sensitizing or irritant agent in the workplace, while ‘workexacerbated asthma’is that fromanother (nonoccupational) cause that is provoked by one or more exposures at work (Figure 24.2). Such a distinction may not be easy but has important diagnostic, management, prognostic, employment and legal implications. Most of the common occupational respiratory diseases in research workers are of short – or relatively short – latency. Thus the adverse outcomes of inhalation accidents are generally immediate, with even the longer term sequelae becoming apparent within a few months. The risks of respiratory sensitization are highest within the first few years of first exposure. It is generally easier to establish (or otherwise) an occupational etiology for a disease that is of relatively brief latency. On the other hand they tend to give rise to important employment and related consequences that may be more prominent than for diseases, such as many pneumoconioses, whose onset is only apparent many decades later. high molecular mass (protein)

respiratory sensitizing agent

new (‘occupational’) asthma

low molecular mass (chemical – R42)

high (‘toxic’) dose single exposure

respiratory irritant (airborne)

new (‘occupational’) asthma low dose repeat exposures

high/low dose repeat exposures

provocation of pre-existing asthma

Figure 24.2 Asthma and occupational exposures at work. Note that those with pre-existing asthma can also become sensitized to a workplace agent and develop worsened asthma as a consequence. ‘R42’ is a chemical hazard identification for a recognised respiratory sensitising agent

340

CH 24 RESEARCH WORKERS

24.3 Respiratory sensitization: asthma and rhinitis Asthma and rhinitis may readily be induced as immunological reactions to an airborne sensitizing agent in the research workplace. There are many such agents, generally categorized as of high or low molecular mass. The former group is composed largely of proteins, the latter of reactive chemicals. Some groups of research workers are exposed to high concentrations of well recognized respiratory sensitizing agents in the course of their work; examples are given in Table 24.1. The most common are high-molecularmass proteins, particularly but not exclusively those found in the excreta and/or secreta of laboratory animals. Less commonly, researchers may develop respiratory sensitization to an inhaled drug or other reactive chemical. The list in Table 24.1 is by no means exhaustive and any case of asthma or rhinitis arising in a laboratory worker should prompt a search for an occupational etilogy – especially where there is exposure to an airborne protein, any one of which is probably capable of inducing asthma. Laboratory animal allergy in those who carry out in-vivo animal research is common, with a prevalence of around 15% and an annual incidence of about 5% among those with regular exposure. The risks are higher in those with highest exposure and in those with other atopic disease such as hayfever or cat allergy. Most cases now arise from contact with mice, reflecting the increased use of this species in medical and Table 24.1 Respiratory sensitizing agents – and the relative frequency with which they cause disease – encountered by research workers Agent (examples) Laboratory animal proteins Mice Rats Guinea pigs Hamsters Ferrets Dogs Cats Primates Locusts, grasshoppers Drosophila spp. (fruit fly) Mealworms Butterflies, moths Cockroaches Serum albumen (bovine, mouse, etc.) Animal feedstuff (corncob, etc.) Pollen (grass, oil seed rape, sunflower, etc.) Latex Molds (Aspergillus spp., Dictyostelium, etc.) Enzymes (papain, pancreatin, xylanase, bromelin, etc.) Egg white Drugs (piperazine, penicillins, morphine, cimetidine, etc.) Cleaning agents (glutaraldehyde, benzyl ammonium chloride, etc.) Other chemicals (ninhydrin, iso-nonayl oxybenzene sulfonate, etc.)

Relative frequency of published cases þþþ þþþ þþþ þþ þ þþ þ þ þþ þþ þ þ þ þ þ þ þþ þ þ þ þ þ þ

24.4

MAKING A DIAGNOSIS OF RESPIRATORY SENSITIZATION

341

pharmaceutical research. Other commonly implicated species are rats, guinea pigs and larger mammals such as dogs (Table 24.1). Sensitization to primates appears to be rare. The major allergens in small mammals are found in their urine and are easily transmitted to the pelt and to bedding material and thus, when dried, become airborne. Direct handling of whole animals, anesthetized or otherwise, and changing bedding (cage cleaning) are common causes of respiratory exposure. Many animal research workers will have only intermittent exposure relating to the timing of their experiments; those tasked with animal husbandry are likely to have higher and more consistent exposures. Chemicals that are recognized to induce respiratory sensitization should carry a specific label, generally to be found on the relevant safety data sheet. Currently their label is ‘R42’ (‘may cause sensitization by inhalation’); with the soon to be enacted ‘Globally Harmonized System’ for chemical classification this will become ‘H334’. Lists – albeit incomplete – of biological and chemical agents that have been reported to cause occupational respiratory sensitization are available in print (see Further Reading) or via the web (www.asmanet.com, www.asthme.csst.qc.ca, www.eaaci.net). Additionally there is increasing interest in the structural characteristics that distinguish (inorganic) chemicals that are capable of inducing respiratory sensitization. Quantitative structure–activity relationship analysis of such chemical is becoming increasingly sophisticated and appears to have near-perfect negative predictive value. Access to analysis of this sort and appropriate interpretation is freely available on the web and may prove helpful when considering the etiological role of an unfamiliar chemical (http:// homepages.ed.ac.uk/jjarvis/research/hazassess/hazassess.html).

24.4

Making a diagnosis of respiratory sensitization

The clinical manifestations of laboratory animal allergy are well recognized and are instructive. They probably apply to most other causes of respiratory sensitization among research workers: .

Most cases arise within two years of first exposure, a reflection of the responsible immune process and of innate individual susceptibility. It is unusual for a laboratory animal researcher to develop disease after many years of similar work. Beware, however, the researcher who has been employed for many years but has recently started work with a different species or process, and the researcher who has elected previously to deny the presence of work-related symptoms.

.

For much the same reasons, laboratory animal allergy does not generally manifest within the first few months of exposure. This period of latency is an important clinical clue to the distinction of ‘occupational’ asthma from the exacerbation of asthma due to another cause.

.

Symptoms of asthma due to animal sensitization are universally accompanied by nasal and eye symptoms similar to those that characterize hayfever. Thus the absence of eye and nose symptoms at work makes a diagnosis of laboratory animal asthma improbable.

342

CH 24 RESEARCH WORKERS

.

Both lower and upper respiratory symptoms are related to exposures at work in as much as they are provoked by being at work and are, at least in early cases, relieved when away from work. Immediate (‘early’) symptoms may be accompanied by those that occurlater(‘delayed’),perhapswhileathomeafterwork.Thiscangiverisetosome diagnostic confusion. In more chronic cases there may be relatively little – or no – relief when away from work, a reflection of ongoing bronchial and nasal hyper-reactivity.

.

Similarly, hyper-reactivity as a result of immunological sensitization may also give rise to symptoms on contact with nonspecific and nonoccupational irritant exposures such as perfumes or cold air; again this may confuse the clinical picture.

.

Laboratory animal asthma – and most cases of laboratory animal rhinoconjunctivitis – is almost always accompanied by evidence of specific immunological sensitization. This is characterized by the production of specific IgE antibodies and is detectable by skin prick testing with appropriate allergens or by measurement of specific IgE antibodies in serum. Suitable reagants for many animal species are available commercially but in more unsusual cases it may be necessary to communicate directly with an experienced laboratory. For small mammals, testing with urinary antigens is more sensitive than testing with epithelial extracts. Skin prick testing should include the use of positive and negative control solutions; the latter is especially important to avoid false positive findings.

.

Once sensitized, patients with laboratory animal allergen may be exquisitely sensitive to even very small concentrations of airborne allergen. This is reflective of the hypersensitive immunology that gives rise to the disease; it can make management of an individual case very difficult.

The diagnostic process in research workers suspected of laboratory animal allergy reflects the manifestations and processes listed above. History taking requires careful attention to the nature and duration of appropriate exposures. It is helpful especially to enquire: .

What exactly is their occupational contact with animals in terms of direct handling of live, anesthetized or dead animals? Are they handling only harvested tissues? For how long and how frequently do they have such contact? Does their work include cleaning cages or the handling of bedding or foodstuffs? In occasional cases sensitization arises not from animal proteins but from biological material used as feed.

.

How often are they in the animal facility without direct animal contact? Is their animal work only within the animal house or do they also carry out experiments in other laboratories?

.

How close and how often are they working to and with others who handle animals? Similarly, is this only within the animal house or does it occur in other settings?

.

Do they wear latex gloves when working with animals? Where powdered gloves are (or have been) used, then these may be responsible for immune sensitization (latex allergy) rather than the animal species which they are used to handle.

.

Do they wear protective respiratory equipment when working with animals? How often do they wear it – and how often is it serviced? Are simple half-face masks

24.4

MAKING A DIAGNOSIS OF RESPIRATORY SENSITIZATION

343

re-used and in any case do they fit properly? Some animal research facilities require the use of powered full-face ventilators; if used routinely and properly, these are extremely effective in reducing exposures to airborne allergens. .

What has been their previous experience with laboratory animal work – including as an undergraduate? Do they – or have they in the past – kept similar animals as pets at home? Pet rats, for example, are remarkably adept at inducing sensitization in their domestic owners.

While it is possible to measure air levels of, and personal exposures to, animal allergens within the laboratory the methodology is complicated, poorly standardized and seldom if ever useful in clinical practice. In the same way as above, a careful account of the character, latency and timing of symptoms is crucial. Here, helpful information includes: .

A history enquiring into previous respiratory allergy – even if quiescent at the time of starting work. It is of course perfectly possible to acquire an occupational asthma or rhinitis on the back of a prior history of such allergic disease; disentangling the two can be difficult.

.

The timing of first symptoms at work. Those that begin very shortly after starting a new job are likely to reflect the provocation of pre-existing disease or asymptomatic bronchial hyper-reactivity. Those that start several months later are more likely to reflect immune sensitization.

.

The use of asthma or nasal treatments and an assessment of the degree of control of any pre-existing condition.

.

The co-existence of work-related nasal and lower respiratory symptoms and their relative timing of onset. Classically in laboratory animal allergy rhinitis is reported before the onset of asthma symptoms.

.

The current temporal relationship between symptoms and work. Recall that any improvement away from work may be less obvious if symptoms have been present for a long time.

.

The current temporal relationship between symptoms and specific tasks at work. Advantage can be taken of the often very variable daily schedule of many research workers. Note that patients with bronchial hyper-reactivity may relate their symptoms to irritant exposures at work. Most respiratory irritants do not induce specific sensitization and reactions to them may reflect an immunologically induced bronchial hyper-reactivity to another agent.

It is unwise to make a diagnosis of animal allergy on the basis of a history alone; such a practice will inevitably give rise to false positive diagnoses. In the presence of a characteristic history from an animal research worker with appropriate exposure, the next step is the establishment or otherwise of specific sensitization using, as above, either skin prick testing or measurement of serum specific IgE antibodies – or preferably both. The absence of an identifiable IgE response – assuming this has been done rigorously – should prompt serious consideration of an alternative diagnosis.

344

CH 24 RESEARCH WORKERS

24.5

MANAGEMENT OF RESPIRATORY SENSITIZATION IN THE RESEARCH SETTING

345

Conversely the presence of IgE sensitization alone is insufficient to make a diagnosis of laboratory animal asthma since there clearly exists a state of ‘asymptomatic sensitization’. Even with an appropriate history and with evidence of IgE sensitization, most clinicians will search for further evidence of an occupational etiology. This is most easily done through measurements of peak expiratory flow serially at home and work; the sensitivity and specificity of this diagnostic approach is considerably enhanced (to about 75 and 90% respectively) if measurements are made more than four times a day for a period of at least a month. By plotting daily mean, maximum and minimum values and comparing these between periods at home and at work it is generally possible to establish – or disprove – a functional relationship with work (Figure 24.3a). Asthma and rhinitis that arise from other high molecular mass allergens in the research setting (Table 24.1) have features that are essentially identical to those described above and should be investigated in the same way. Respiratory sensitization to a low molecular mass chemical agent typically shares most of the same clinical characteristics but there are a few important differences: .

Recourse to technical information on the chemical(s) in question is often necessary – especially where they are not widely recognized as being capable of inducing respiratory sensitization. Examination of the relevant safety data sheets (and in particular for R42 or H334 codes) may be helpful.

.

Rhinitis may be less common.

.

Very few such chemical agents elicit an identifiable specific IgE response. This can make diagnosis more difficult and, where there are suitable facilities, often gives rise to the necessity for specific provocation testing under controlled conditions. Here specialist and experienced advice is essential.

.

For some chemical sensitizing agents it is possible, using validated methods, to make measurements in air including in the breathing zone. These are unlikely to be helpful in diagnosis but may be useful in guiding management.

24.5

Management of respiratory sensitization in the research setting

The first step in the effective management of an established case of laboratory animal allergy – or indeed other respiratory hypersensitivity – lies in a firm diagnosis, a clear 3 Figure 24.3 (a) Serial peak flow record in research worker with prior sensitization to rat urinary proteins. Days at work are depicted by shaded columns, those away from work by unshaded columns. On each day only the mean (solid line), maximum (squares) and minimum (circles) values of six daily readings are shown. There is clear evidence of a fall in peak flow and increased diurnal variability (see boxes) when the patient is at work. Note: during this record the patient had no direct contact with rats and nor did he enter a room where rats were being held. The changes in peak flow and his accompanying symptoms of asthma were caused by very low exposures encountered in the corridors adjacent to rat-containment rooms (see also Figure 24.4). Only by complete avoidance of the workplace was he able to abolish his symptoms – and record a flat peak flow record (b)

346

CH 24 RESEARCH WORKERS

understanding of the responsible species (agent) and a good working knowledge of the workplace (Figure 24.4) and available options. In this setting, a false positive diagnosis can be disastrous since it is likely to give rise to needless and often major professional disruption for the patient with little likelihood of clinical improvement. Where a firm diagnosis has been reached then management relies primarily on avoidance of further exposure to the causative antigen in the knowledge that even very small exposures may give rise to continuing bronchial inflammation and symptoms. It

animal facility changing room

lab

lab

lab

species 1

species 2

species 1

barrier system

office

stock holding rooms

designated laboratory

departmental offices and laboratories

office

office

office

office histology room store 34

office lift

toilet

Figure 24.4 Schematic diagram of research laboratories and office space with adjacency to animal holding facility. Animal experiments may be carried out within the animal facility laboratories or in other ‘designated’ laboratories. Staff may move freely between different areas. Thus animal allergens may contaminate a wide area – potentially all the rooms and corridors shown here, not only those where animals are present. This is important to understand when managing hypersensitivity

24.6

RESPIRATORY DISEASE ARISING FROM EXPOSURES TO IRRITANT SUBSTANCES

347

is believed, with reasonable evidence, that continuing exposure to the causative agent at intensities sufficient to cause ongoing symptoms is harmful to prognosis and diminishes the chances of eventual recovery. On the other hand, if further such exposure can be avoided then there is almost always a major reduction in symptoms and a high probability of eventual cure. Avoidance of exposure will naturally require a major re-consideration – and sometimes even abandonment – of a career. Research workers are especially reluctant in this respect and many will choose to continue with their work. In such cases, expert advice on reducing exposure and on the use of protective respiratory equipment is helpful. Even with great care in this respect, symptoms may persist, causing considerable management difficulties (Figure 24.3b). Animal workers sensitized to, for example, rats may question whether they can safely work with another species, say mice. This strategy is seldom successful for very long, although those who move to work with a very different species – say, in this case, dogs – appear to fare well. In the face of continuing exposure, phamacological treatment with antihistamines and standard asthma/rhinitis regimens can be helpful but rarely gives rise to complete or lasting disease control. There is very limited evidence that treatment with an inhaled corticosteroid may hasten recovery in those who have avoided further exposure. All patients with occupational respiratory sensitization should be advised that continuing exposure is probably detrimental to their prognosis. Knowledgeable advice on statutory compensation – available in many countries – should be provided. Evidence-based guidelines on the diagnosis and management of occupational asthma – including laboratory animal allergy – has been published by the British Occupational Research Foundation (see Further Reading). Using a question-andanswer format it is a handy and practical tool.

24.6

Respiratory disease arising from exposures to irritant substances

Respiratory disease in research workers may also arise from exposures to agents that are irritating to the upper and/or lower respiratory tract. This is an area where some (potential) outcomes are well understood and characterized but others are far less so and can give rise to considerable controversy. It should be emphasized that in most research settings exposures to respiratory irritants are unlikely to give rise to any new disease. As with potentially sensitizing agents, those that are irritant and may be encountered in the laboratory are many and varied. They include irritant gases such as chlorine and ammonia, organic chemicals such as acetic acid, formaldehyde and numerous solvents, metals and metallic compounds such as oxides or halides of zinc or cadmium and complex mixtures such as smoke from fires or the pyrolytic products of burning plastics. High-intensity exposures to irritants in a research setting are inevitably unpredictable or accidental and seem, fortunately, to be rare. Repeated exposures at lower intensities are far more common.

348

CH 24 RESEARCH WORKERS

In this context some issues are relatively clear: .

Acute exposures to high intensities of respiratory irritants can induce – with relative ease – acute nasal, oro-pharyngeal or lower respiratory diseases. These include cough, hoarseness, tracheo-bronchitis, pulmonary edema, adult respiratory distress syndrome and very occasionally death; further details are given below.

.

Similarly, high-concentration exposures over a very short-time period can induce persistent respiratory disease. Examples include bronchiolitis obliterans and/or organizing pneumonia, bronchiectasis and an asthma-like syndrome; these too are described in more detail below.

.

The mechanisms under consideration here are not those of immunological sensitization but those of toxic injury, inflammation and consequent repair processes.

.

In such cases – especially those of self-limiting or unusual disease – attribution of cause and effect is usually on the basis of the temporal association between an extraordinary event and the apparent onset of new disease.

.

Lower and sometimes repeated exposures to respiratory irritants – not uncommon in research laboratories, for example – can readily exacerbate pre-existing asthma. In general this is easily managed by careful attention to the reduction of such exposures and to pharmacological asthma control.

Other issues are far less clearly understood: .

In some circumstances, less intense exposures over longer time periods (‘sub-acute’ exposures) can give rise to respiratory disease. This is much more difficult to determine, especially in an individual case, and often requires the identification and epidemiological investigation of a number of similarly exposed cases. This is more likely to occur where the disease phenotype is uncommon or unusually severe. Outbreaks of such disease have not yet been reported among research workers but have been recognized in several industrial settings, giving rise to ‘new’ diseases such as ‘nylon-flock workers’ lung and ‘Ardistyl’ lung.

.

The question of whether repeated, ‘low-dose’ exposures to respiratory irritants can give rise to novel asthma is contentious – and of considerable importance to the research community where such exposures are probably not uncommon. Difficulties arise – particularly in individual cases – because asthma is a common disease in the (research) population and naturally follows a course of remission and relapse. The firm attribution of apparently new disease to ‘not-so-sudden’ irritant exposures in an individual case is essentially impossible.

24.7 Immediate effects of acute exposures to respiratory irritants at relatively high intensity Unusually, in clinical practice the starting point in this setting is generally not in the investigation of disease (‘effect’) but in the consideration of an ‘event’ and its possible

24.7

ACUTE EXPOSURES TO RESPIRATORY IRRITANTS AT RELATIVELY HIGH INTENSITY

349

Table 24.2 Selection of respiratory irritants that may be encountered in the laboratory with a measure of their relative water solubility and reported outcomes after acute, intense exposure. All, at high enough does, can cause ‘toxic pneumonitis’ Water solubility

Reported effects Acute

Ammonia Acetic acid Hydrogen chloride Sulfur dioxide Chlorine Oxides of nitrogen Ozone Zinc oxide

High High High High Medium Low Low

Long-term

Acute upper airway irritation

Irritant-induced asthma

Interstitial lung disease

þþþ þþþ þþþ þþþ þþ þ / þ / þ /

þ þþ

þ

þþ þþ þ

þ þþ

sequelae. This highlights the importance of understanding in considerable detail the nature of the apparently initiating incident and in particular the agent(s) involved and the probable intensity of exposure(s). The likely outcomes – and the likelihood of a particular outcome – of any particular exposure are thus more predictable. Almost any irritant gas, chemical, metallic compound or other irritant agent may be encountered by research workers in the course of their job; a list of some of these is provided in Table 24.2. High-intensity exposures in the research setting are stochastic and follow equipment failure or are due to human error. Some agents are well recognized as noxious to the respiratory tract; others are less commonly encountered and both their chemistry and likely toxic effects less well understood. Gaseous respiratory irritants are often classified by their solubility in water which, to some extent, determines the site of any lung injury consequent on their inhalation. Highly soluble compounds such as ammonia, hydrogen chloride or sulfur dioxide immediately induce upper airway and ocular symptoms; chlorine, of intermediate solubility in water, has a similar effect. Because these effects are of very brief latency and are perceived as very unpleasant, exposed persons generally seek an early escape. Lower respiratory effects are less common with such agents unless exposures are intense enough to overwhelm upper airway absorption. Other irritant gases – notably ozone, oxides of nitrogen and phosgene – are far less soluble in water. They rarely give rise to immediate upper airway symptoms but if inhaled in sufficient quantities can induce terminal bronchial and alveolar disease. Other important characteristics of gaseous and other irritants include their pH and whether they are reactive oxygen species, and the presence and size of any particulate matter. Together with solubility and dose these determine, respectively, the mechanism and site of damage consequent on their inhalation. The range of potential outcomes from high-does irritant exposure is broad and includes disease in: 1. The upper airways – a burning sensation in the eyes, nose and throat is common in exposure to respiratory irritants; it is often accompanied by eye watering, sneezing,

350

CH 24 RESEARCH WORKERS

nasal discharge, hoarseness and, prominently, a cough. There may be evidence of corneal, conjunctival, oropharyngeal and dermal burns or ulceration. Very heavy exposures can cause upper airway obstruction due to edema and/or laryngeal spasm. This may require emergency treatment. 2. The large and small airways – acute pain, breathlessness, chest tightness and wheeze may each or all follow an inhalational injury. Again, exceptionally heavy exposures can cause epithelial sloughing and airway obstruction. 3. The alveoli – so-called ‘pneumonitis’ may result from inhalation of poorly soluble irritants or from very heavy exposure to those of higher solubility. Depending on the intensity of the insult, the features of ‘toxic’ or ‘chemical’ pneumonitis include increasing breathlessness, sputum (typically frothy-pink), bilateral radiographic shadowing (consistent with pulmonary edema) and the development of respiratory failure. These may not develop for as long as 72 hours after exposure; later complications may include adult respiratory distress syndrome and infection.

24.8 Management of the acute effects of high-dose irritant exposure Upper airway damage following exposure to a respiratory irritant is generally selflimiting but may require attention to burned or ulcerated areas in order to prevent their infection. There are no specific treatments for lower airway and alveolar damage, their management being essentially supportive and conservative, sometimes requiring intensive care. Because the effects of respiratory irritants (at high concentrations) may be delayed, careful observation for a period of up to 48 hours (or longer) may be necessary. Where there is a suggestion of widespread epithelial damage it is probably wise to administer oxygen sparingly. While corticosteroids are often used there is no convincing evidence for their efficacy in reducing immediate or long-term morbidity. Appropriate treatment with antibiotics is important.

24.9 Longer-term effects of acute exposures at relatively high intensity It must be stressed that most exposures to respiratory irritants do not induce any identifiable long-term respiratory disease. Recovery may, however, be delayed by the psychological effects of what can be a very traumatic experience.

24.10 Nonasthmatic diseases Intense exposures – usually acute but in some cases repeated (sub-acute) – giving rise to severe ‘pneumonitis’ may be followed by evidence of increasing and irreversible small airways obstruction. Obliterative bronchiolitis of this type may be accompanied by early inspiratory crackles on auscultation of the chest and by evidence of gas trapping (high

24.11

ASTHMA

351

residual volume) on pulmonary function testing. While chest radiography is usually normal, expiratory CT scanning will also suggest a mosaic pattern of gas trapping. Histological confirmation is rarely required but typically will confirm the obliteration of small airways with granulation tissue and fibrosis. Other, nonasthmatic sequelae of an inhalational injury include organizing pneumonia; this appears to be rare but has been best described following the inhalation of oxides of nitrogen at high intensities. Other interstitial lung diseases have been described after irritant inhalation but most often in small case series or by single case reports and their true frequency – and indeed relation to the incident – is unknown.

24.11

Asthma

Relatively high-intensity, acute exposures to respiratory irritants may also be followed by asthma – or at least a disease that shares many clinical features of asthma. Originally known as ‘reactive airways dysfunction syndrome’ (RADS) this was first described in 1985 in a series of 10 cases where very heavy respiratory exposures on a single occasion to toxic compounds (including fire smoke) were followed by the apparently new development of bronchial hyper-reactivity, variable airflow obstruction and symptoms of asthma. The criteria for establishing a diagnosis of RADS – as first set out – are shown in Table 24.3. Subsequently the question has arisen as to whether lower dose, perhaps repeated, exposures to respiratory irritants can similarly give rise to RADS – or, as it is more often termed now, irritant-induced asthma. This is a controversial area and the available literature, most of it epidemiological, is not consistent. Perhaps the most common consequence of an inhalational accident is a constellation of asthma-like symptoms in the absence of any detectable deficit in lung function, or increase in airflow variability or bronchial reactivity. In these cases symptoms of cough, chest tightness of breathlessness may be provoked by exposure to a very wide variety of commonly encountered irritants such as household aerosols, cleaning materials, perfumes, wet paint and petrol fumes. Accompanying symptoms such as fatigue and headache produce a picture of ‘multiple chemical sensitivity’. Alternatively, or in addition, a vocal chord dysfunction may develop. These outcomes are not necessarily

Table 24.3 The original criteria for a diagnosis of reactive airways dysfunction syndrome (RADS) – after Brooks, S., Weiss, M.A., Bernstein, I.L. (1985) Reactive airways dysfunction syndrome: persistent asthma syndrome after high-level irritant exposure. Chest 88: 376–384 Onset after a single, toxic exposure Onset within 24 hours of the exposure Symptoms consistent with asthma Evidence of subsequent airflow obstruction Evidence of subsequent nonspecific bronchial hyper-reactivity (metacholine or histamine challenge test) Documented absence of prior respiratory symptoms Other pulmonary disease excluded Nonsmoker

352

CH 24 RESEARCH WORKERS

relatable to any pre-incident psychological features but may be color by persisting anxiety.

24.12 Management of irritant-induced asthma For patients, and the clinicians of patients, with (suspected) irritant-induced respiratory disease, a common point of focus is the causative relationship between the inhalational incident and their disease. This may especially be so when a claim for personal injury is being made through the civil courts. While this is obviously important, it is not always possible to establish causation with any satisfactory degree of certainty. In some, perhaps many, cases an ultimately fruitless focus on etiology may hinder recovery. In any case it is important to establish with great care and as far as possible the details of the incident and those of the immediate clinical aftermath. Information on the nature of the released chemicals should be collected. Direct measures of exposure intensity are rarely available but estimates can be made from the quantity of released material, the nature of the environment in which the incident took place and the duration of exposure. Inthe research setting,mostincidents willtake place indoors; information onthe distance of the incident from the patient, the size of the room where it took place and the presence of any ventilation is helpful. In outdoor incidents, the prevailing weather (especially wind direction) may be an important determinant of exposure. A record of immediate responses – such as the use of protective equipment – and of immediate symptoms – such as burning of the eyes or nose – should be made. It is also helpful to establish whether colleagues were also exposed and, where possible, what has been their experience. Early measurements of lung function are valuable; as a minimum these should include measurement of basic spirometry but an early assessment of bronchial reactivity and, in some cases, of lung volumes and diffusion capacity is often helpful. It is generally appropriate to maintain clinical follow-up of patients with persistent symptoms until a clear prognosis and management can be established. This may require several years. Repeated measurements of lung function (often including bronchial reactivity), at judicious intervals, are advisable. As always with such measurements, their results are informative about the current state of the patient – but not of the past. Thus it is important, especially when considering etiology, to make an enquiry into the existence of any pre-incident measurements. In the research environment these are quite commonly made and retained by occupational health services. Irritant-induced asthma should be treated with usual asthma protocols but appears to respond less favorably to standard pharmacotherapies. On the whole, severe asthma is uncommon but any symptoms may be difficult to treat. The ultimate prognosis is uncertain but is probably dependent on the severity of the initiating incident and on age – and perhaps on psychological issues also. As always, and as in particular with work-related disease, careful attention to continuing work ‘fitness’ is important. In almost all cases, provided that there is minimal risk of a further incident, an early return to work is both appropriate and helpful. This should be organized in close liaison with the occupational health service. Organizing pneumonia – with or without obliterative bronchiolitis – may respond well to systemic steroids. Other types of interstitial lung disease and obliterative

24.13

OTHER RESPIRATORY DISEASES IN RESEARCH WORKERS

353

bronchiolitis itself are, in this context, essentially untreatable. Very severe cases may need to be considered for lung transplantation.

24.13

Other respiratory diseases in research workers

24.13.1 Pulmonary infection Research workers who handle infectious material or work with infected animals or patients may themselves develop respiratory infection. Inhaled viral, bacterial, mycobacterial and even protozoal agents may be responsible. The diagnosis of such infections requires a low threshold of suspicion and a careful enquiry into potentially relevant exposures. Their management is by standard chemotherapy and the eradication of any further exposure to the infecting agent.

24.13.2 Beryllium sensitization and chronic beryllium disease Research workers in electronics and communications may, in the course of their work, be exposed to airborne particles of beryllium. Copper–beryllium alloys, for example, are commonly used in electrical components. Exposure is generally during grinding or other mechanical handling. In sensitive subjects, inhalation of beryllium can induce an asymptomatic state of beryllium sensitization that is detectable on lymphocyte transformation testing – an investigation available only in a few, specialized laboratories. While there is no evidence that beryllium sensitization alone has any short or longterm adverse consequences, further exposure to beryllium (unlikely in laboratory conditions) may cause chronic beryllium disease, a pulmonary condition that is clinically similar to sarcoidosis.

24.13.3 Lung cancer There is a long list of occupationally encountered agents that have been related, epidemiologically, to lung cancer. They include asbestos, arsenic, polycyclic hydrocarbons, chromates, beryllium, sulfuric acid mist, chloromethyl ethers, nickel compounds and tetrachlorodibenzene–para-dioxin. Laboratory exposures to any of these are very unlikely to be sufficiently high to induce carcinogenesis and in any case establishment of cause and effect at an individual level would be very difficult. However there are a few case reports of lung cancers in research staff that have been attributed, at least in part, to exposures they encountered at work.

24.13.4 Work with nanoparticles The use of artificial nanostructures in the research environment, as in a wider industrial context, will increase substantially. Such structures are very varied and include particles of solid, tubular and fibrous forms all of which, due to their size, are readily inhalable

354

CH 24 RESEARCH WORKERS

and have the potential for deposition deep within the lungs. There has been extensive research – not all of it encouraging – into their toxicity and there are considerable concerns around the hazards they may pose. The magnitude of any real risks to human respiratory health are as yet unknown.

24.14 Other occupational diseases among research workers Given the vast range of research it is unsurprising that those engaged in it face a large variety of other, nonrespiratory hazards. These are generally unconnected with the respiratory diseases described above. The most important of them include: 1. Infection, most probably following ‘needle-stick’ injuries, with blood-borne viruses such as hepatitis B. 2. Physical hazards such as those from lasers, from extremes of temperature (including hot and cold burns), from electrical equipment and from spilt liquids (falls). 3. Chemical splashes to eyes and skin. 4. Eye and musculo-skeletal strain from prolonged use of visual display equipment. 5. Radiation-induced diseases. Most research institutions will have high-quality health and safety management programmes that render the actual risks of most of the above low.

Further reading 1. For a referenced list of known respiratory sensitizing agents: Bernstein, I.L., Chan-Yeung, M., Malo, J.L., Bernstein, D.(eds) (2006) Asthma in the Workplace, 3rd edn. Taylor & Francis: New York; 415–435 and 825–866. 2. Similar material, albeit less complete, is available for free on the following websites: . www.occupationalasthma.com . www.asmanet.com . www.asthme.csst.qc.ca . www.eaaci.net 3. For those who wish to investigate for themselves the likely sensitizing potential of an inorganic chemical, free software and interpretation is available through: http://www.medicine.manchester. ac.uk/coeh/research/asthma/. The original paper is published as: Jarvis, J., Seed, M.J., Elton, R., Sawyer, L., Agius, R. (2005) Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds. Occup. Environ. Med. 62(4): 243–250. 4. For evidence-based guidance, based on a systematic literature review, on the diagnosis and management (and prevention) of occupational asthma including that arising in the research setting: Newman Taylor, A.J., Nicholson, P.J., Cullinan, P., Boyle, C., Burge, P.S. (2004) Guidelines for the Prevention, Identification and Management of Occupational Asthma: Evidence Review and Recommendations. British Occupational Health Research Foundation: London; available from: http://www.bohrf.org.uk/downloads/asthevre.pdf.

FURTHER READING

5.

6.

7.

8.

355

Tarlo, S.M., Balkissoon, R., Beach, J., Beckett, W., Bernstein, D. et al. (2008). Diagnosis and management of work-related asthma, American College of Chest Physicians Consensus Statement. Chest 134: 1S–41S. A good summary of laboratory animal allergy is included in the following book chapter: Gordon, S., Bush, R.K., Newman Taylor, A.J. (2006) Laboratory animal, insect, fish and shellfish allergy. In Bernstein, I.L., Chan-Yeung, M., Malo, J.L., Bernstein, D. (eds), Asthma in the Workplace, 3rd edn. Taylor & Francis: New York; 415–435. Excellent summaries of irritant-induced respiratory disease are available in two chapters from the same book: Nemery B. (2002) Toxic pneumonitis: chemical agents. In Occupational Disorders of the Lung, Hendrick, D.J., Burge, P.S., Beckett, W.S., Churg, A. (eds). W.B. Saunders: London; 201–220. Schwartz, D.A. (2002) Toxic tracheitis, bronchitis and bronchiolitis. In Occupational Disorders of the Lung, Hendrick, D.J., Burge, P.S., Beckett, W.S., Churg, A. (eds). W.B. Saunders: London; 93–104. The original description of RADS: Brooks, S., Weiss, M.A., Bernstein, I.L. (1985) Reactive airways dysfunction syndrome: persistent asthma syndrome after high-level irritant exposure. Chest 88: 376–384. For a good study of the usual outcomes of inhalation accidents see: Sallie, B., McDonald, C. (1996) Inhalation accidents reported to the SWORD surveillance project 1990–1993. Ann. Occup. Hyg. 40: 211–221.

25 Work in hyperbaric environments Mark Glover St Richard’s Hospital, Chichester, West Sussex, UK

25.1 Introduction This chapter summarizes issues of both direct and indirect relevance to the respiratory tract that are encountered when exposed to environmental pressure raised above that found at sea level (normobaric). Raised (hyperbaric) environmental pressure is achieved either by diving in a fluid or by entering dry pressurized environments such as underground works and recompression chambers. Humans have been exposed to elevated pressures for subsistence, work or pleasure ever since the first person dived underwater. Over many thousands of years breath-hold diving developed from a means to collect food for survival into profitable, if hazardous, industries which harvested food and other desirable natural items and salvaged lost valuables from shallow waters. Man’s desire to go deeper for longer was realized in the sixteenth century through the use of diving bells. These upturned air-filled vessels could be lowered underwater and the diver could enter to take a breath of air without needing to return to the surface. Various methods of delivering breathing gases to individual divers have since been developed and are broadly divided into those that are self-contained and those that are supplied via hoses. Each of these categories is further divided into equipment that recycles exhaled breath for re-inhalation and equipment that does not. As early as the seventeenth century well-intentioned and innovative individuals built precursors to modern hyperbaric chambers. Patients sitting inside these vessels were exposed to minimally raised or lowered pressure in an attempt to treat a range of diseases. In the nineteenth century, mining and building works proliferated and became increasingly ambitious. Ingress of water was a problem for underground works near to an expanse of water, and also for a caisson sitting on a sea or river bed. Increased

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

358

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

pressure was used to minimize this problem. The miners, tunnelers and caisson workers who worked in these conditions were also subjected to elevated pressure, but without immersion. These techniques are still used today. Working breath-hold divers exist to the present day. There is now also a welldeveloped competitive sport based on breath-hold diving, although increasingly elaborate equipment, from suits and fins to weights and buoyancy devices, is required to allow the boundaries to be pushed ever further. The current record for depth on a single breath-hold is in excess of 200 meters. Most recreational divers breathe compressed air, via a demand valve, supplied from a cylinder worn by the diver in an assembly known as self-contained underwater breathing apparatus (SCUBA). The diver’s exhaled air is released into the surrounding water. Equipment using this principle is known as ‘open circuit’. See Figure 25.1. Other gases mixed with oxygen are used for breathing by commercial divers and by ‘technical divers’ amongst the recreational fraternity when they wish to dive deeper than the usual recreational range. It is not unusual for breathing gas to be delivered to commercial divers by hose from the surface or from a bell with the advantage of greater endurance and assured communication with the surface but the disadvantage of limited mobility. Another form of underwater breathing apparatus allows the diver to rebreathe exhaled gas once it is scrubbed clean of carbon dioxide and the oxygen is replaced. These ‘rebreathers’ minimize wastage of expired gas. The advantage of greater gas economy comes at the cost of greater complexity and a requirement for more extensive maintenance and training. As depth and ambient pressure increase, the inhaled gas is compressed more, so that a greater ‘surface equivalent’ volume of gas is wasted in each breath in an open-circuit system. Rebreathers avoid this depth-related increase in gas consumption. In ‘closed’ rebreathers no gas escapes from the system when at a steady depth. ‘Semi-closed’ sets produce a constant stream of excess gas, but in volumes that are generally much less than from an ‘open-circuit system’ (Figures 25.2–25.4).

Figure 25.1 Open-circuit SCUBA. 1, Compressed gas. 2, First stage reduces gas pressure to a few bars above ambient. 3, Second stage delivers gas to diver at ambient pressure. 4, Exhaled gas bubbles disperse in water

25.1

INTRODUCTION

359

Figure 25.2 Closed circuit oxygen rebreather. 1, Oxygen added to counterlung either manually or by a demand valve mechanism. 2, Relief valve to allow expanding gas to escape from counterlung on ascent. 3, Mouthpiece – one-way valves ensure that gas goes only in one direction in the circuit. 4, Exhaled gas passes through a carbon dioxide absorbent before returning to the counterlung

Figure 25.3 Semi-closed circuit rebreather. 1, Reducer delivers a constant mass of gas per unit time to the counterlung throughout dive and at all depths; proportion of oxygen is calculated to avoid hypoxia and hyperoxia between surface and maximum intended depth; rate is calculated to accommodate expected oxygen consumption; extra gas added either manually or automatically to make up for volume lost on descent. 2, Relief valve to allow gas to escape from counterlung 3, Mouthpiece – one-way valves ensure that gas goes only in one direction in the circuit. 4, Exhaled gas passes through a carbon dioxide absorbent before returning to the counterlung

360

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

Figure 25.4 Automated closed circuit mixed gas rebreather. 1, Sensors monitor oxygen levels in the circuit and oxygen or mixture is added to the counterlung to maintain oxygen at the desired level; nonautomated versions require the diver to add the required gas; extra gas added either manually or automatically to make up for volume lost on descent. 2, Relief valve to allow expanding gas to escape from counterlung on ascent. 3, Mouthpiece – one way valves ensure that gas goes only in one direction in the circuit. 4, Exhaled gas passes through a carbon dioxide absorbent before returning to the counterlung

For deep, long dives commercial divers can remain at pressure for weeks at a time, traveling between working depth and the surface in a pressurized diving bell. Shifts of some 6–8 hours are spent working in the water with rest periods in a dry, pressurized chamber facility on-board a diving support vessel. This is known as saturation diving (Figure 25.5).

Figure 25.5 Hyperbaric exposures. 1, Tunnel. 2, SCUBA. 3, Surface supply. 4, Bell. 5, Saturation

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

361

Hyperbaric chambers are now used to treat decompression illness (DCI) and a range of other conditions which, for therapeutic effect, require inspired partial pressures of oxygen greater than those that can be achieved at sea level. Commercial and recreational divers are exposed to both raised pressure and immersion. Tunnelers, caisson workers and hyperbaric chamber staff are, in general, exposed solely to raised pressure. Surface-oriented working divers return to normobaric conditions after each dive. The depth and duration of the dive dictate the rate at which they may ascend. These divers are transported to and from their worksite in the water either by their own propulsion, by small powered vehicles, or lowered in a basket or in a bell which can be fully closed or partially enclosed. Tunnelers and hyperbaric chamber workers enter enclosed spaces which are compressed to allow them to work in a pressurized environment and then decompressed to allow them to return to normal atmospheric pressures. In the UK the annual fatal accident rate for all diving at work activities is estimated at 6–7 per 100,000. There are approximately three cases of DCI each year in the offshore sector. This can be compared with the UK recreational sector in which, among perhaps 100,000 divers, there are approximately 16 fatalities and 200–250 cases of DCI per year – and with compressed air work which is associated with some 25 cases of DCI (in approximately 2000 workers) per year. An exposure is quantified primarily by the mixture(s) of gases breathed, the ambient pressure and duration for which each is breathed and whether the individual is immersed. Pressure is typically expressed as a depth in diving, increasing by approximately 100 kPa for each descent of 10 m (or 33 feet) in seawater. In compressed air work pressure is typically measured in bars of overpressure above atmospheric (1 bar is approximately 100 kPa). The permitted overpressure is usually limited to 3.5 bars in the UK. There is a considerable amount of information beyond basic quantification of the exposure that can be collected to assist in diagnosis and management of pressure-related disorders. This information, and its significance, is summarized in Tables 25.1 and 25.2. Exposures are typically recorded in the individual’s personal logbook and, in the case of commercial exposures, in the records kept by the employer. Each entry will usually describe pressure/depth, duration, environmental conditions, breathing equipment, gas(es) and decompression schedule used plus a note of any adverse incidents.

25.2

Respiratory hazards, diseases and their management

25.2.1 Acute pulmonary effects of immersion Water is much denser than air. Differential pressures applied to the body are negligible in air. They become significant in water to the extent that effort of ventilation may be noticeably affected unless the mouth is at the same depth as the lungs. The pressure also neutralizes gravitational pooling of blood in dependent limbs, redistributing blood to the thorax, increasing right heart filling, inducing an immersion diuresis and reducing lung capacity. This redistribution is potentiated by cold so, while head-out immersion in thermoneutral water at 35 C reduces vital capacity by 5%, it will fall by 10% in water at 20 C.

362

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

Table 25.1 Points to explore in the history of an individual with symptoms and signs attributed to exposure to raised environmental pressure – details regarding the exposure Item

Significance

Occupation/pastimes

Useful for identifying any relevant additional exposures, e.g. respiratory sensitizers For example, surface-orientated, saturation, dry, immersed Immersion pulmonary edema, saltwater aspiration syndrome and near-drowning require immersion Immersion increases the risk of cerebral oxygen toxicity For example, SCUBA, open-circuit or rebreather, semi-closed, fully-closed Resistive load or large dead space in any diving equipment and absorbent failure or one-way valve malfunction in a rebreather are potential causes of hypercapnia Elevated PICO2 increases risk of cerebral oxygen toxicity Potential for diver to consume oxygen faster than it is delivered in a semi-closed rebreather can cause dilution hypoxia or hypoxia of ascent Potential for exhaled inert gas to accumulate in a closed-circuit pure oxygen rebreather leading to risk of dilution hypoxia or hypoxia of ascent It is possible to rupture the respiratory tract with forceful exhalation against resistance or by overpressurizing the breathing circuit Hyperventilation before a breath-hold dive increases the risk of hypoxia For example, temperature, visibility, current, surface conditions Immersion pulmonary edema typically occurs in divers in cold water or who have been working hard, such as swimming against a current, exercise, shivering This might not be an illness induced by immersion or pressure. Remember to ask about other potential exposures, e.g. breathing gas contaminants, dust, hydrocarbon fumes, welding fumes, underwater blast, and their relationship to the onset of symptoms Anxiety is a risk factor for cerebral oxygen toxicity These data are required to calculate decompression obligation. Post-incident gas analysis data might be available CNS oxygen toxicity unlikely to occur in a dry chamber at PIO2 below 200 kPa CNS oxygen toxicity can occur if PIO2 exceeds approximately 140 kPa while immersed. A hyperoxic seizure can lead to drowning, near-drowning, aspiration or an uncontrolled ascent with closed glottis causing pulmonary barotraumas  DCI Pulmonary oxygen toxicity can occur if PIO2 exceeds 50 kPa. Units of Pulmonary Toxic Dose can be calculated to assess potential Acute hypoxia can occur if PIO2 falls below 15 kPa A depressurization from a depth of 1 m or greater in water can cause rupture by pulmonary overinflation. A dive on air or another oxygen nitrogen mixture at a depth of 30 m or deeper increases risk of hypercapnia in a CO2 retainer

Type of exposure

Equipment

Other environmental information

Timing and nature of untoward incidents

Depths/durations/inspired gas mixtures

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

Table 25.1 (Continued) Item Gas consumption

Rapid or uncontrolled ascents Omitted decompression stops Method used to calculate decompression Activities during dive

363

Significance Voluntary hypoventilation in order to conserve open circuit gas supply is a risk factor for hypercapnia It is possible to rupture the respiratory tract with a maximal inhalation; this might be an important mechanism in the rupture of lungs in divers who ‘skip-breathe’, deliberately holding themselves in prolonged inspiration in an attempt to reduce gas consumption Risk factor for pulmonary barotrauma and for DCI Risk factor for DCI For example, decompression table, computer, instinct Allows potential for omitted decompression to be assessed Hypercapnia typically occurs in divers who have been working hard at depth Working hard is a risk factor for cerebral oxygen toxicity

25.2.2 Pulmonary oxygen toxicity Atelectasis can occur when breathing a high fraction of oxygen in normobaric and hyperbaric conditions. Breathing oxygen at partial pressures greater than 50 kPa can cause additional pathological changes of inflammation spreading from the carina, suppression of surfactant production and eventual fibrosis of respiratory epithelium. The greater partial pressures of oxygen achievable in hyperbaric environments accelerate the pathological process. Symptoms and signs range from an isolated sensation of airway irritation through crackles and wheezes, fever, thick secretions and bronchial breathing, to respiratory failure due to impaired gas exchange across inflamed respiratory epithelium. Lung volumes, flows, compliance and gas transfer all deteriorate, and the earliest changes usually precede symptoms. Large, rapidly reversing flow changes are more likely to be due to bronchoconstriction mediated vagally following a direct toxic effect of oxygen on the central nervous system. Management of pulmonary oxygen toxicity Clinical findings and results of investigations will depend on the severity of the condition. Sometimes bilateral opacities are seen on chest X-ray. Treatment requires the inspired partial pressure of oxygen to be reduced to 50 kPa or lower. Most changes apart from fibrosis are reversible and symptoms will start to improve within 2 hours. They are expected to resolve within 3 days of cessation of exposure, although an upper respiratory tract infection soon after the exposure can provoke symptom recurrence. Lung function improves rapidly at first, but a complete return to normal can take several weeks. It is possible to predict the likely pulmonary consequences of an oxygen exposure using the concept of units of pulmonary toxic dose (UPTD). The relationship between UPTDs and clinically measurable variables is non-linear (see Figures 25.6 and 25.7) and there is considerable inter-individual variation. Oxygen toxicity is prevented by limiting duration and/or magnitude of exposure. Saturation divers, for instance, often spend several weeks at pressure and breathe

364

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

Table 25.2 Points to explore in the history of an individual with symptoms and signs attributed to exposure to raised environmental pressure – post-exposure details Item

Significance

Flying or other altitude exposure after dive

Risk factor for DCI, impact decreases the longer the delay after diving. Recommended delay can be up to 48 hours depending on type of diving Working hard after a dive increases the number of circulating bubbles and is believed to be a risk factor for DCI DCI, pulmonary barotrauma of ascent and hypoxia of ascent can arise only once decompression has begun Signs and symptoms of pulmonary oxygen toxicity, DCI, pulmonary barotraumas, immersion pulmonary edema, saltwater aspiration syndrome and neardrowning persist for some time beyond acute provocative exposure. Signs and symptoms of hypoxia typically do not. The respiratory symptoms of hypercapnia will resolve rapidly on termination of the exposure but a throbbing headache typically persists DCI can occur during decompression in saturation diving. In most other circumstances 50% of DCI cases will manifest within 1 hour of surfacing and 90% within 6 hours The initial symptoms of arterial gas embolism typically present during the ascent or within the first 10 minutes after surfacing. Hemiplegia, hemiparesis and reduced level of consciousness commonly occur. It is not unusual for the condition to improve then relapse later In view of the indiscriminate nature of the bubbles, it is not unusual to have a number of manifestations, for them to appear at different times and to evolve in different ways For example, normobaric oxygen, fluids, recompression Although normobaric oxygen is an important first aid measure it can mask symptoms and signs of DCI which then appear when the treatment is discontinued Remember that a response to recompression does not necessarily confirm a diagnosis of DCI and that a failure to respond does not necessarily exclude DCI Remember that other disorders can present coincidentally Pyrexia is thought to be a risk factor for cerebral oxygen toxicity

Activities after dive Timing, severity, nature, rate of onset and subsequent evolution of manifestations

Response to treatment

Past medical history, including any previous diving illness

oxygen at partial pressures of around 50 kPa without clinically important deterioration in lung function. Tolerable exposure will depend on necessity. If a patient with serious DCI required aggressive hyperbaric oxygen therapy, it would be reasonable to allow some reversible lung changes in order to maximize resolution of a functionally important neurological deficit. The wide variation in individual susceptibility means that a decision on the amount of oxygen administered is often empirical, being guided by the response of the patient.

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

365

Figure 25.6 Units of pulmonary toxic dose accumulated per minute plotted against inspired partial pressure of oxygen

25.2.3 Decompression illness At raised environmental pressure gas accumulates in the tissues in increasing quantities until, eventually, a dynamic equilibrium is reached. At this point equal amounts of gas diffuse into and out of the tissues and they are ‘saturated’ at that pressure. An increase in ambient pressure will encourage more gas to dissolve. A decrease will cause excess gas to be released. The amount of gas that needs to be safely eliminated from each tissue during the return to surface pressure, and hence the decompression schedule required, will depend on the pressure and duration of the exposure. If the tissues are all saturated, however, no more gas will accumulate and the required decompression schedule will

Figure 25.7

Change in vital capacity plotted against units of pulmonary toxic dose

366

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

Table 25.3 Decompression obligations of different durations of exposure at approximately 3.5 bar above atmospheric pressure. All from the 6th revision of the US Navy Diving Manual except asterisked entry which is from UK Blackpool tables for compressed air workers Gas breathed

Time at pressure

Time required to depressurize

Air Air Air  Oxygen in helium, PIO2 < 130 kPa Oxygen in helium, PIO2 < 130 kPa Oxygen in helium, PIO2 < 48 kPa and >44 kPa

10 minutes 40 minutes 4 hours 15 10 minutes 40 minutes Saturation – potentially unlimited

4 minutes 56 minutes 344 minutes 35 minutes 78 minutes 2700 minutes

not change thereafter. This is the basis of saturation diving. See Table 25.3 for some representative decompression times. Decompression illness is caused by gas bubbles that can arise in the body in two ways. Gas can ‘escape’ from ruptured lungs, enter the pulmonary veins, return to the left side of the heart and then be distributed around the body causing arterial gas embolism. Alternatively, as the excess gas dissolved in tissues at pressure is liberated (or ‘evolved’) on depressurization, it can form bubbles. Bubbles usually accumulate intravascularly but can be extravascular if the decompression is of sufficient rate and magnitude. It is not unusual for bubbles to appear in venous blood on decompression. Moderate quantities are harmlessly trapped in the alveolar capillaries where the gas they contain diffuses out rapidly and is exhaled. The filtered blood then returns to the left heart. A right–left circulatory shunt, such as a patent foramen ovale or a pulmonary arteriovenous shunt, can potentially allow venous gas emboli to bypass the pulmonary ‘filter’. If the filtering capacity of the lungs is overwhelmed, bubbles can spill over into the systemic circulation or even compromise the lungs’ abilities to exchange gas. In more severe cases, the pulmonary circulation can be threatened. Inert gases such as nitrogen and helium are the primary sources of ‘evolved’ bubbles. Oxygen is constantly consumed by aerobic metabolism. Carbon dioxide is highly soluble, is buffered extensively and diffuses rapidly. As a result, oxygen and carbon dioxide are believed to contribute insignificantly to ‘evolved’ gas disease in normal circumstances. A higher fraction of inert gas in the breathing mixture will, therefore, increase the decompression obligation for a given pressure exposure. Bubbles can block vessels from inside (as arterial emboli or by venous congestion) or outside, causing ischemia, they can tear apart structures and cause bleeding, they can damage vascular endothelium and can act as foreign bodies which trigger pathological reactions such as inflammation and activation of clotting mechanisms. Decompression illness can manifest in many ways. Bubbles do not necessarily respect normal anatomical boundaries and patchy or multi-system presentations are not uncommon. It is a dynamic disease. Manifestations can be progressive, static, relapsing, resolved or spontaneously improving and their evolution can change. The disease can range in severity from trivial and self-limiting to disabling or life-threatening. Cardiopulmonary manifestations are rare but range from cough or mild dyspnea, through shortness of breath, chest pain, hemoptysis, cyanosis and edema, to frank

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

367

cardiopulmonary arrest. This extreme is associated with very severe decompression stress such as explosive decompression to altitude and is, fortunately, seen only very rarely. Neurological symptoms are common and can range from subjective sensory alteration through subtly impaired higher mental function to loss of consciousness, motor weakness, incoordination and sphincter dysfunction. Limb pain is also common, typically beginning as an ill-defined pain which settles in one or more large limb joints. Girdle pain, which has a distribution along one or more thoracolumbar dermatomes, is often a herald of more severe decompression illness. Cutaneous decompression illness ranges from pruritis through erythema, papular rash to skin marbling due to ischemia. The marbling, known as cutis marmorata, is often painful and tender and, if it presents acutely, is usually considered an indicator of severe decompression stress and a precursor of more serious symptoms. DCI can cause enlarged or painful lymph nodes and/or swelling of the area drained by the affected lymph vessels. Constitutional manifestations are those that cannot be readily associated with any one organ system and include malaise, loss of appetite, nausea, vomiting, headache and inappropriate fatigue. Management of decompression illness The first step is prompt diagnosis. Bear in mind that:

1.

decompression illness can mimic many other conditions and vice versa;

2.

pressure exposures can cause problems other than decompression illness, some unique to the hyperbaric environment and some found in other circumstances; and

3.

there might be other medical conditions in addition to decompression illness; a traumatic incident with a riveting tool or an acute myocardial infarction might, for example, prompt the diver to make a rapid return to the surface.

First aid treatment for decompression illness is the same as for most other conditions. Airway, breathing and circulation take priority. Oxygen should be given at as high an inspired fraction as possible. Hypovolemia is common, caused by immersion diuresis, vomiting and/or bubble-mediated endothelial damage. Restore circulating volume by oral or intravenous administration of fluid, as appropriate. Avoid intravenous glucose if there are any neurological manifestations. In the event of prolonged immobility, consider thromboprophylaxis. The definitive treatment for decompression illness is recompression. Many cases caused by surface-oriented diving are treated at 284 kPa breathing 100% oxygen following a ‘standard recompression therapy’ schedule that returns to surface pressure in slow steps over 4 hours and 45 minutes. Other schedules are used and the choice depends on circumstances and the response to the initial recompression. Outcome of recompression therapy depends primarily on the severity of the illness prior to treatment. Typically, approximately 50 % require only one treatment to achieve complete resolution and 70% require one or more treatments. The remainding 30% are left with residual symptoms ranging in severity from minor sensory symptoms to profound neurological deficit. In the event of ‘undeserved’ decompression illness where decompression was adequate yet sufficient inert gas accumulated to create venous gas emboli, it is

368

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

appropriate to screen the individual for right–left shunt using bubble-contrast echocardiography prior to a return to hyperbaric exposures.

25.2.4 Pulmonary barotrauma of descent Although thoracic blood shift compensates for loss of gas volume and the lungs can tolerate compression far beyond residual volume, extreme exposures will cause damage leading to edema and hemoptysis.

25.2.5 Pulmonary barotrauma of ascent Pressure-related change in volume in gas-filled spaces in or next to the body can inflict mechanical damage known as barotrauma. Injury can be avoided if the spaces are ventilated and gas can pass in and out as it expands and contracts. Studies have shown that fresh cadaveric lungs rupture if overpressurized by approximately 9 kPa. If the chest is bound, hence limiting lung expansion, rupture occurs at 14 kPa overpressure and the damage occurs at different sites compared with when the chest is not bound. A similar overpressure could be generated by an ascent in water of the order of 1 m in a fully inflated, obstructed lung segment or in lungs held at full capacity against a closed glottis. Gas can escape from the respiratory tract, including extrapulmonary sites, resulting in one or more of pneumothorax, pneumomediastinum, subcutaneous emphysema, pulmonary interstitial disruption and arterial gas embolism. Management of pulmonary barotrauma of ascent Symptoms and signs are the same as those of lung injury and rupture by other mechanisms. First aid management of symptomatic cases is directed at care of airway, breathing and circulation and administration of high fraction inspired oxygen. Arterial gas embolism is a form of decompression illness and requires recompression. A pneumothorax is managed in the same way as one caused by trauma or that has occurred spontaneously. Pneumomediastina are often asymptomatic, can present solely with voice change, and only 50% are visible on a P-A chest X-ray. High fraction inspired oxygen, rest and observation are often required in symptomatic cases. In studies of submarine escape trainees, victims of pulmonary barotrauma are more likely to have a low forced vital capacity. Reduced compliance and lack of support from the chest wall are two theoretical reasons offered to explain this finding. A low expiratory ratio (FEV1/FVC), however, has not been shown to be a risk factor. This might be because candidates with significant obstructive defects are likely to have been disqualified from submarine escape training. Nevertheless, a low forced vital capacity (less than 80% of predicted), peak expiratory flow (less than 80% of predicted) or low expiratory ratio (less than 70%) deserves investigation to exclude airway narrowing or gas trapping prior to hyperbaric exposures. Further investigation is indicated following pulmonary barotrauma of ascent or following a decompression illness consistent with arterial gas embolism even if there were no lung symptoms. Gas trapping, fixed or reversible airway narrowing or any other predisposition to pulmonary rupture or overinflation should be excluded.

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

369

High-resolution CT may be required if there is any uncertainty. Even if no abnormality is found, sufficient time should be allowed for the respiratory tract to heal; recommended periods typically vary between one and three months.

25.2.6 Barotrauma of other structures Other targets of barotrauma of descent include the middle and external ear, paranasal sinuses, carious teeth, whole body and soft tissues under dry suit or mask. Barotrauma of ascent can affect the middle ear, paranasal sinuses, gastro-intestinal tract and carious teeth. Bleeding from sinuses or from the Eustachian tube following a barotraumatic injury can present as hemoptysis and can usually be distinguished from pulmonary barotrauma by examining the ear, nose and throat to establish the most likely source of bleeding.

25.2.7 Hypoxia Hypoxia is less likely to occur in a pressurized environment as the partial pressure of oxygen is elevated in proportion to the ambient absolute pressure. It can, however, occur if the wrong gas mixture is selected, if the wrong procedure is adopted when using rebreather equipment and in breath-hold diving. As the inspired partial pressure of oxygen falls progressively below 20 kPa, mental and physical function deteriorate in the same manner as from hypoxia in other circumstances. The clinical picture and the rapidity of onset depend on the rate of oxygen depletion and the final partial pressure reached. Consciousness will be prolonged if PACO2 is elevated, causing cerebral vasodilatation and enhancing brain perfusion.

25.2.8 Hypoxia of ascent If a mixture of gases is compressed, the partial pressure of each component gas increases in proportion to the total pressure. As the gas is depressurized, such as when a diver returns to the surface, the partial pressure of each component gas falls. In normal circumstances the rising partial pressure of carbon dioxide, rather than the drop in oxygen, will force a breath-hold diver to take a breath. As the diver surfaces the partial pressure of oxygen falls, but usually not far enough to compromise consciousness. Hyperventilation before a dive reduces the PACO2. This delays the hypercapnic stimulus to take a breath and loss of consciousness on ascent due to hypoxia can potentially result in fatality. This can even occur in a relatively shallow swimming pool.

25.2.9 Dilution hypoxia A fault in equipment design or set up can allow a diver to consume oxygen faster than it is delivered to a semi-closed rebreather circuit. The fraction of oxygen falls but, because

370

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

diluent inert gas remains in the circuit, the diver has limited warning of any problem until the inspired partial pressure of oxygen is dangerously low. The diver can either lose consciousness at depth or as the partial pressure of oxygen drops further during the ascent. Management of hypoxia Treatment of hypoxia is administration of oxygen in addition to basic supportive measures. Hypoxia is prevented by maintaining inspired partial pressure of oxygen at a minimum of 15 kPa, and ideally above 20 kPa. Inert gas diffuses out of tissues when 100% oxygen is breathed. Divers using closed-circuit oxygen rebreathers avoid dilution hypoxia by flushing the breathing circuit with oxygen early in the dive to ensure that the inert gas does not accumulate. Divers using semi-closed rebreathers anticipate how hard they will be working and ensure that their oxygen delivery will be sufficient to avoid dilution hypoxia; they also flush the breathing circuit with fresh gas prior to ascent to avoid hypoxia of ascent.

25.2.10 Immersion pulmonary edema Some divers develop pulmonary edema while immersed and in the absence of any obvious aspiration or pulmonary or cardiac abnormality. The diver complains of cough, sometimes productive of blood and/or frothy sputum. Syncope has also been reported but not chest pain. Typically the immersion has involved either cold water or strenuous exercise. Investigation of individuals who have suffered from immersion pulmonary edema has revealed that they have higher peripheral vascular resistance and an atypical dramatic further rise in response to cold challenge. It is thought that the balance between pulmonary capillary pressure and plasma oncotic pressure is disrupted by hemodynamic changes associated with immersion plus either cold-induced systemic vascular resistance or increased cardiac output on exercise. Excessive rehydration and inspiratory resistance from airway narrowing or faulty equipment have also been suggested as potential additional factors. Management of immersion pulmonary edema Exclude other causes of acute pulmonary edema. Symptoms typically resolve within hoursbut thirdheartsounds,basalcrackles andX-raychanges consistentwithpulmonary edema might be found earlier. Treatment is rest and oxygen. The edema usually resolves within hours although diuretics may be required in more severe cases. Some 1.1% of respondents reported symptoms suggestive of pulmonary edema in one survey of divers. Some have experienced recurrent episodes and should be advised against diving.

25.2.11 Saltwater aspiration syndrome Aspiration of small amounts of salt water can induce a cough, sometimes productive, and with frothy hemoptysis in a minority, immediately after a dive. The diver then develops more respiratory symptoms, typically dyspnea, cough and retrosternal discomfort with wheeze on chest examination and patchy consolidation in a proportion

25.2

RESPIRATORY HAZARDS, DISEASES AND THEIR MANAGEMENT

371

of chest X-rays. These symptoms develop rapidly in severe cases and after a latent period of 1–2 hours in milder cases. In addition, systemic features of pyrexia, rigors, anorexia, nausea and vomiting, headaches, malaise, aches and even impaired consciousness may occur. Management of saltwater aspiration syndrome This occurs less frequently now as diving equipment has improved, reducing the risk of aspiration. Investigation is required to exclude any other cause of the symptoms. White cells can be elevated, PAO2 is often low and PACO2 low or normal. Respiratory symptoms are treated with oxygen and the systemic symptoms often respond to warming. Most cases resolve within 6–24 hours.

25.2.12 Drowning and near-drowning Despite the many illnesses unique to diving, the most common end-point in fatal incidents is drowning. The clinical features, diagnosis and management of drowning and near-drowning are not unique to hyperbaric exposure and are not dealt with in this chapter.

25.2.13 Hypercapnia Hypercapnia is an important complication and a limiting factor in hyperbaric environments. Experienced divers often hypoventilate involuntarily. The reason for this is not fully understood. Gas density increases in proportion to ambient pressure and breathing equipment introduces extra resistance, so work of breathing, oxygen consumption and carbon dioxide production all increase in hyperbaric conditions. Oxygen is typically delivered at higher than normal partial pressures so it is seldom limiting. It has been suggested that the body adapts to this situation by tolerating a higher PACO2 in order to minimize the work of breathing. Hyperoxia might have an additional effect of reducing basal ventilatory drive and response to exercise. The denser gas also directly affects the ventilation of the lungs such that physiological dead space increases and maximal voluntary ventilation decreases. As a result, carbon dioxide elimination becomes more critical than oxygen delivery when working hard at pressure. Apart from its direct toxic effects, which are well recognized in other clinical situations and are not listed here, high levels of carbon dioxide have other relevant consequences. Vasodilatation accelerates heat loss from superficial vessels in a cold environment and might accelerate delivery of inert gas to tissues. The carbon dioxide also potentiates the narcotic effects of inert gases such as nitrogen and lowers the threshold for cerebral oxygen toxicity. Management of hypercapnia Symptoms and signs are seldom sufficiently unique to make a diagnosis, although a persistent throbbing headache is traditionally associated with hypercapnia. Dependent on the precise cause, aim to reduce the inspired partial pressure of carbon dioxide, reduce its endogenous production and/or increase its elimination. Changing to a

372

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

non-contaminated gas (including fresh air at the surface), increasing ventilatory rate and tidal volume, reducing activity and moving to a shallower depth are options that will be appropriate, according to the circumstances. Preventive measures include ensuring that: 1. the breathing gas is not contaminated; 2. activity is limited to safe levels; 3. equipment complies with breathing standards; 4. absorbent is packed to avoid settling or formation of low-resistance ‘channels’; 5. equipment is functioning correctly. Less dense gas mixtures instead of air, such as heliox (oxygen in helium) or trimix (oxygen in a mixture of helium and nitrogen) can also minimize the density-related problems. A small population hypoventilates and develops hypercapnia even when diving in moderately raised pressures. Other than monitoring their physiological response while diving, it is difficult to identify these individuals. Although they often have a reduced ventilatory response to PICO2 or a raised end-breath-hold PACO2, these measurements lack sufficient specificity and sensitivity for effective screening. A smaller proportion of non-divers also have this tendency. Although these carbon dioxide retainers are economical with gas consumption and have little or no dyspnea, they are not protected from the indirect effects of hypercapnia mentioned above. Also, they are not immune to hypercapnic narcosis and will receive little dyspnoeic warning of rising PICO2 in the event of equipment malfunction. Use of a less dense mixture, such as oxygen-in-helium, also reduces the tendency to retain carbon dioxide in this group.

25.2.14 Central nervous system toxicity Symptoms that are commonly attributed to oxygen toxicity are visual disturbances, tinnitus, irritability and dizziness. Appearance of any of these symptoms often heralds a generalized seizure if the inspired partial pressure of oxygen is not reduced promptly. The seizure can also occur without warning. Management of central nervous system toxicity Details of management will depend on whether the symptoms occur in a dry environment or while diving. Reduce the inspired partial pressure of oxygen if at all possible and safe to do so. Avoid depressurization until the seizure has resolved as the glottis can be closed during the tonic phase, predisposing to pulmonary barotrauma. Keep the casualty safe from harm during the seizure, which is usually short-lived. The post-ictal phase can be prolonged. In a hyperbaric chamber, patients often breathe air between periods on high-oxygen therapeutic gas in order to reduce the risk of toxicity. While diving, the risk is reduced by keeping the inspired partial pressure within a safe range, typically below 140–160 kPa depending on circumstances and level of activity.

25.3

FURTHER INFORMATION

373

25.2.15 High pressure neurological syndrome Dives to great depths typically use mixtures which contain a large fraction of helium. Such dives are associated with a disorder characterized predominantly by dysfunction of the central nervous system, known as the high pressure neurological syndrome (HPNS). At depths in excess of 300 m divers complain of dyspnea which is worse on inspiration. The symptoms are lessened by the addition of nitrogen to the breathing mixture, despite the fact that this makes the gas denser and increases the work of breathing. Nitrogen can be used to counter some of the other effects of HPNS so the symptoms are probably due to neurological interference with the control of breathing rather than a direct effect upon the lungs. The effects resolve on depressurization.

25.2.16 Long-term pulmonary effects Divers tend to have larger lung volumes than expected. Suggested reasons for this include divers being a self-selecting fit population and respiratory muscle training from breathing dense gas against resistance in the diving equipment. Forced vital capacity (FVC) tends to be enlarged proportionately more than FEV1, which gives many divers a lower FEV1/FVC expiratory ratio. Mid and late expiratory flows have also been found to be lower in divers, with some evidence of a relationship with length of diving career, and this might be an indication of small airway changes. In addition, lung volumes appear to decline at a faster rate than expected in some longitudinal studies of divers. Diffusing capacity is impaired after a saturation dive, possibly due to low grade oxygen toxicity and bubble damage, but it is thought that this recovers gradually following the exposure. Despite these findings, no structural changes have been demonstrated on imaging and the no clinically relevant consequences have been found.

25.2.17 Respiratory aspects of fitness for hyperbaric exposure In general, normal pulmonary function is required for hyperbaric exposures. Impaired gas flow could predispose to barotraumatic injury. Depending on severity, deficient gas exchange will restrict the candidate’s ability to cope with the respiratory demands of the hyperbaric environment, the work routinely required within it or emergency actions that might arise. The British Thoracic Society has produced very useful Guidelines on Respiratory Aspects of Fitness for Diving.

25.3

Further information

Further information on activities involving hyperbaric exposures can be obtained from: Regulatory bodies .

UK Health and Safety Executive: http://www.hse.gov.uk/

.

Occupational Safety and Health Administration: www.osha.gov

374

CH 25 WORK IN HYPERBARIC ENVIRONMENTS

Advisory bodies .

Compressed Air Working Group: http://www.britishtunnelling.org.uk/groups_ safety.php

.

European Diving Technology Committee: http://www.edtc.org

.

European Committee for Hyperbaric Medicine: http://www.echm.org

.

International Maritime Contractors Association: www.imca-int.com

.

Diving Medical Advisory Committee: http://www.dmac-diving.org

Recreational diving organizations .

UK Sport Diving Medical Committee: http://www.uksdmc.co.uk/

.

British Sub-Aqua Club: http://www.bsac.com

.

Professional Association of Diving Instructors: http://www.padi.com

.

Divers Alert Network: http://www.diversalertnetwork.org

Diving and hyperbaric medicine societies .

European Underwater and Baromedical Society: http://www.eubs.org

.

British Hyperbaric Association: http://www.hyperbaric.org.uk

.

Undersea and Hyperbaric Medical Society: http://www.uhms.org

.

South Pacific Underwater Medicine Society: http://www.spums.org.au

Sources of scientific information .

Rubicon Research Repository: http://archive.rubicon-foundation.org/

Further reading Textbook specifically dedicated to the effects of hyperbaric exposure on the lung: Lundgren, C.E.G., Miller, J.N. (eds) (1999) The Lung at Depth. Marcel Dekker: New York.

General textbooks of diving medicine Brubakk, A., Neuman, T. (eds) (2003) Bennett and Elliott’s Physiology and Medicine of Diving, 5th edn. London: Saunders. Edmonds, C., Lowry, C., Pennefather, J., Walker, R. (eds) (2002) Diving and Subaquatic Medicine, 4th edn. Arnold: London.

Relevant studies and case reports Benton, P., Woodfine, J., Westwood, P. (1996) Arterial gas embolism following a 1-meter ascent during helicopter escape training: a case report. Aviat. Space Environ. Med. 67: 63–64.

FURTHER READING

375

Brooks, G.J., Pethybridge, R.J., Pearson, R.R. (1988) Lung function reference values for FEV1, FVC, FEV1/FVC ratio and FEF (75–85) derived from the results of screening 3,788 Royal Navy submariners and submarine candidates by spirometry. Paper 13 in Conference Papers of the XIVth Annual Meeting of the EUBS, Aberdeen, 5–9 September 1988. Slade, J.B., Hattori, T. et al. (2001) Pulmonary edema associated with scuba diving: case reports and review. Chest 120: 1686–1694. Wilmshurst, P.T., Nuri, M., Crowther, A. et al. (1989) Cold-induced pulmonary oedema in scuba divers and swimmers and subsequent development of hypertension. Lancet i: 62–65.

Medical standards British Thoracic Society (2003) Guidelines on respiratory aspects of fitness for diving. Thorax 58: 3–13.

Regulations Diving at Work Regulations (1997) Available from: http://www.opsi.gov.uk/SI/si1997/19972776.htm (accessed 4 December 2009). Work in Compressed Air Regulations (1996) Available from: http://www.opsi.gov.uk/SI/si1996/ Uksi_19961656_en_1.htm (accessed 4 December 2009).

Miscellaneous HSE Diving Health and Safety Strategy to 2010. UK Health and Safety Executive. Offshore Injury, Ill Health and Incident Statistics 2007/2008. HID Statistics Report. HSR 2008 – 1. Date of Issue: December 2008. Health and Safety Executive. United States Navy Diving Manual. Available from: http://www.supsalv.org/pdf/DiveMan_rev6.pdf (accessed 4 December 2009).

26 Effects of travel or work at high altitudes or low pressures Michael Bagshaw King’s College London and Cranfield University, UK

26.1 Introduction Exposure to high altitude implies exposure to low ambient pressure as a consequence of the physics of the atmosphere. The exposure can occur gradually, as in mountaineering or high hill walking, or relatively quickly, as in ascent by aeroplane or balloon. Exposure to gradual terrestrial ascent above about 3000 m puts the susceptible individual at risk of developing altitude illness, a collective term encompassing the major conditions caused directly by hypobaric hypoxia. These include acute mountain sickness and high-altitude pulmonary edema. Rapid ascent in the atmosphere above about 3000 m on the other hand, as may occur in an aeroplane, gives rise to hypoxic hypoxia (the term given to hypoxia due to insufficient oxygen reaching the blood and a low partial pressure of oxygen in arterial blood), to which all individuals are susceptible. The clinical features of the acute phases of altitude illness are different from those observed in aviation-related hypoxic hypoxia, with differences in diagnosis and treatment. A high incidence of acute mountain sickness has been reported in tourists flying to high-altitude cities such as Lhasa (3658 m), Leh (3514 m), La Paz (3625 m) and Cuzco (3415 m), so a simple distinction between mountain sickness and aviation hypoxia is not necessarily straightforward. Occupations exposed to high altitude include mountaineers and mountain guides, with their associated professions, and professional aircrew and frequent business flyers.

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

378

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

26.2 Physics of the high-altitude environment At sea level the atmosphere exerts a pressure of about 760 mmHg (101 kPa); it is variably moist, has a temperature that ranges from
60 to þ 60 C, and moves at wind speeds from 0 to 160 km/h. With increasing altitude, the temperature, pressure and water content of the atmosphere fall and wind speeds increase.

26.2.1 Atmospheric pressure Total gas pressure falls with altitude in a regular manner, halving every 18,000 ft (5500 m; it remains the convention in aviation to use ft for altitude). The oxygen percentage of the atmosphere (20.93%) is constant to very high altitudes, so the same curve can be used to obtain the ambient oxygen pressure by rescaling the ordinate. The oxygen pressure of physiological importance is that which exists in ambient air when it is warmed and wetted on entering the bronchial tree. This raises water vapor pressure to about 47 mmHg, regardless of the total gas pressure outside. The oxygen pressure in moist inspired gas (PiO2) fully saturated with water vapor at 37 C is given by the relationship: PiO2 ¼ FiO2 ðPB
47Þ

where PB is barometric pressure and FiO2, the fractional concentration of oxygen in the inspirate, is 0.2093.

26.2.2 Atmospheric temperature The atmospheric temperature falls at a rate of 1.98 C/1000 ft (300 m) from the standard sea level temperature of 15 C, to the tropopause [the border between the lower level, the troposphere, and the higher level or stratosphere; 40,000 ft (12,200 m)]. It remains stable at
56 C up to about 80,000 ft (24,400 m) and then rises to almost body temperature at about 150,000 ft (46,000 m), but by then air density is so low that its temperature is unimportant.

26.2.3 Atmospheric ozone Atmospheric ozone at high altitude is formed by ultraviolet irradiation of diatomic oxygen molecules which dissociate into atoms. At very high altitudes all oxygen exists in the monatomic form. Lower down, some of this monatomic oxygen combines with oxygen molecules to form the triatomic gas ozone, with concentrations up to 10 ppm. The ozonosphere normally exists between 40,000 and 140,000 ft (12,200 and 42,700 m). Below 40,000 ft (12,200 m) the irradiation is normally too weak for significant amounts of ozone to form in this manner (although it is formed by reactions between hydrocarbons and nitrogen oxides in the presence of sunlight and contributes to tropospheric air pollution). Concentrations of ozone of 1 ppm at sea level can cause

26.3

PHYSIOLOGY OF FLIGHT

379

lung irritation. However, modern passenger jet aircraft are fitted with catalytic converters in the environmental control system which break down the ozone before it enters the pressurized cabin.

26.2.4 Cosmic radiation Aircraft occupants are exposed to elevated levels of cosmic radiation of galactic and solar origin. At jet aircraft operating altitudes, galactic cosmic radiation is 2.5–5 times more intense in polar regions than near the equator. The Earth’s surface is shielded from cosmic radiation by the atmosphere, the ambient radiation increasing with altitude by approximately 15% for each increase of around 2000 ft (dependent on latitude). Cosmic radiation doses The effect of ionizing radiation depends not only on the dose absorbed, but also on the type and energy of the radiation and the tissues involved. These factors are taken into account in arriving at the dose equivalent, measured in Sieverts (Sv). However doses of cosmic radiation are so low that figures are usually quoted in microsieverts (mSv) or millisieverts (mSv). Calculated and measured doses for aircrew and frequent flyers are well within the occupational exposure limits recommended by the International Commission on Radiological Protection. Health risks of cosmic radiation Whilst it is accepted that there is no level of ionizing radiation exposure below which effects do not occur, current epidemiological evidence indicates that the probability of airline crew members or passengers suffering any abnormality or disease as a result of exposure to cosmic radiation is very low.

26.3

Physiology of flight

The physiological effects of flight are distinguished from those of terrestrial high altitude because exposures are relatively rapid, brief and not cumulative. Flyers do not adapt to the hypoxic environment, unlike inhabitants of terrestrial high altitudes. However, the aircraft can be a means of transporting an individual to a high-altitude destination.

26.3.1 Hypoxia Although ambient oxygen pressure is related exponentially to altitude, falling progressively with ascent from the surface of the Earth, the pressure of oxygen to be found in the lungs does not have the same relationship. That pressure is determined by two equations. The alveolar ventilation equation states that alveolar CO2 pressure (PaCO2) depends only on CO2 excretion (CO2) and alveolar ventilation (Va), so: PaCO2 ¼ kðCO2 =Va Þ

380

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

where k is a constant. The alveolar air equation states that, since at any one time there is a fixed trading ratio (R) between oxygen uptake and CO2 excretion (R ¼ CO2/O2), alveolar oxygen pressure (PaO2) can be calculated from the moist inspired oxygen pressure (PiO2 ) and alveolar PCO2, so: PaO2 ¼ PiO2 *
ðPaCO2 =RÞ

Progressive hypoxia leads to a mild hyperventilation (i.e. a rise in Va and fall in PaCO2). When arterialized blood leaves a healthy lung, the oxygen pressure is some 10 mmHg less than that in the alveoli, due to uneven matching of ventilation to perfusion, some anatomical shunting and an almost nominal obstacle to diffusion. In resting individuals, the alveolar–arterial oxygen gradient does not change much with altitude, although the relative importance of the factors contributing to it alter considerably as explained below, so subtracting a further 10–15 mmHg describes the relationship between arterial oxygen pressure and altitude. The most important change is the loss of pressure driving oxygen from the alveoli to blood, as the fall in alveolar PO2 is much greater than that in mixed venous PO2 (because of the shape of the oxygen dissociation curve, Figure 26.1). As a result the alveolar– venous gradient for oxygen diffusion is reduced and equilibration is slower than at ground level. When people ascend to altitude in a matter of minutes, rather than over several days, they react to hypoxia by an increase in blood flow and a modest hyperventilation, limiting the effects of hypoxia. Individuals abruptly exposed to altitudes of 10,000 ft (3000 m) and above suffer mental and physical effects, and this is the ceiling above which aviators are provided with oxygen. To allow a margin of safety, the maximum certified cabin altitude in civilian passenger aircraft is 8000 ft (2440 m), at which barometric pressure is 565 mmHg and arterial oxygen pressure is around 55 mmHg (Figure 26.1), and venous oxygen pressures have fallen by only by 1–2 mmHg. Even at this altitude, there is a decrease in performance. The latest generation passenger aircraft are manufactured from newer materials that are lighter and stronger, allowing a lower cabin altitude to be maintained at higher aircraft altitudes. Two physiological features of

Figure 26.1 The oxyhemoglobin dissociation curve

26.3

381

PHYSIOLOGY OF FLIGHT

Table 26.1 The time of useful consciousness following the sudden loss of oxygen supply for a healthy individual at rest and moderately active, both for a progressive decompression and a rapid decompression Altitude (ft)

20,000 25,000 30,000 35,000 40,000 43,000

Progressive decompression

Progressive decompression

Rapid decompression

Seated at rest

Moderately active

Seated at rest

20 min 5 min 1.5 min 45 s 25 s 18 s

10 min 3 min 45–60 s 30 s 18 s 12 s

5 min 2–2.5 min 60 s 25 s 12–15 s 12–15 s

altitude hypoxia are important for safety in aviation. The first is the total lack of awareness of cerebral impairment. The second is that there is a ‘time of useful consciousness’, which describes how rapidly consciousness is lost, thus dictating how quickly the condition must be recognized and corrective action taken. The time of useful consciousness is the interval after the onset of hypoxia during which an individual can carry out some purposeful activity. The general relationship between this time interval and the altitude of sudden exposure is shown in Table 26.1. This diminishes from about 4 min at 25,000 ft (7620 m) to a minimum of roughly 15 s, which is reached at around 40,000 ft (12,200 m). This represents the sum of the 7 s or so required for blood to travel from the lungs to the brain and the time needed for the brain to utilize the oxygen already dissolved in its substance. Loss of useful consciousness is sensitive to many other factors, such as the degree of hyperventilation and the acceleration to which the individual is exposed at the time. Hyperventilation causes cerebral vasoconstriction, and positive headwards acceleration opposes the upward flow of blood to the brain. Sometimes deterioration in consciousness is quickened by vasovagal syncope, but more often there is tachycardia as consciousness is lost. Exertion also quickens loss of consciousness, because blood transits quickly through the lungs, leaving insufficient time for oxygen equilibration. The minimum cabin pressure of 565 mmHg (75.1 kPa; 8000 ft, 2440 m) in commercial passenger aircraft, will bring a healthy individual’s arterial PO2 along the plateau of the oxyhemoglobin dissociation curve until just at the top of the steep part (Figure 26.1), still saturated. At ground level, people with respiratory disease may have an adequate arterial oxygen saturation with arterial oxygen pressures as low as 55–60 mmHg. As they ascend to 8000 ft (2440 m), their arterial PO2 will fall further and may result in respiratory failure. If their hypoxemia at ground level is due to a mismatch of ventilation to perfusion, as is usually the case, the drop in arterial PO2 will not be as extensive as in healthy people (about 40 mmHg), but if it is due to diffusion defect associated with desaturation on exertion, as in some fibrotic conditions, it may be greater.

26.3.2 Treatment of acute hypoxic hypoxia In either event, hypoxic hypoxia can be reversed completely by the administration of oxygen, 30% oxygen at 8000 ft (2440 m) being equivalent to breathing air at ground

382

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

level. Given prior notice, most airlines can provide a personal oxygen supply for any passenger, although there may be a charge. (The altitudes of the patient’s destination and transit points en route should also be considered.) The administration of oxygen to an acutely hypoxic individual almost invariably results in a rapid and complete recovery, as is also the case if environmental pressure is increased so that the alveolar oxygen tension is restored towards its normal level. The only persistent symptom tends to be a generalized headache, and only then if the exposure to hypoxia was prolonged. In some individuals, however, sudden restoration of the alveolar oxygen tension to normal may cause a transient worsening of the severity of symptoms and signs of hypoxia for up to a minute. This oxygen paradox is usually mild and is manifest only by flushing of the face and hands and perhaps deterioration in performance of complex tasks over the immediate period following restoration of the oxygen supply. Occasionally oxygen administration may produce a severe paradox, with the appearance of clonic spasms and even loss of consciousness. The mechanisms responsible for the phenomenon are unclear and it is a rare occurrence. It may be the result of generalized hypotension associated with marked hypocapnia.

26.3.3 Aircraft oxygen equipment and pressure cabins Aircraft operating below 10,000 ft (3000 m) do not require oxygen equipment. Many sophisticated light aircraft which can cruise above 10,000 ft do not have pressurized cabins, so oxygen equipment must be provided, usually consisting of a gas bottle, simple regulator, tubing and nasal speculae or a mask for each occupant. Other aircraft that fly higher usually have reinforced cabins capable of holding a high differential pressure between inside and out. These are the high-differential type, seen in passenger and transport aircraft generally, and the low-differential variety found in military high-performance aircraft. The former, holding a high transmural pressure, maintain cabin pressure above 565 mmHg (8000 ft, 2440 m). They provide an environment in which the occupants breathe cabin air. However, it is possible rarely that the pressurization system can fail, allowing the cabin pressure to fall to the external ambient value. Thus an emergency oxygen supply is available for passengers and crew. The aircraft environmental control system automatically manages the internal cabin environment, providing healthy and comfortable surroundings for all occupants. There are regulatory requirements for minimum cabin air pressure, maximum levels of carbon monoxide, carbon dioxide and ozone, and minimum ventilation flow rates. The cabin air must also be free from harmful or hazardous concentrations of gases or vapors. The cabin air supply is bled from the outside air entering the aircraft engine, or may be supplied from the outside air via electrically driven compressors. It is then passed through the air-conditioning packs and mixed with filtered recirculated air before distribution to the cabin. The system provides approximately 20 cubic feet (566 liters) of air per minute per passenger, of which about 50% is recirculated air (compared with up to 80% recirculated in buildings and other forms of public transport), giving a complete cabin air exchange every 2–3 min. These high ventilatory flow rates maintain normal pressurization, as well as temperature control and the removal of odours and carbon dioxide. The high flow

26.3

PHYSIOLOGY OF FLIGHT

383

Figure 26.2 Cabin air circulation and distribution

rates also ensure that the volume of oxygen far exceeds the requirements of the aircraft occupants (0.34 l/min at rest and 0.85 l/min when walking). The air is distributed to the cabin via overhead ducts and grills running the length of the cabin. The airflow circulates around the cabin rather than along the cabin and is continuously extracted through vents at floor level, as shown in Figure 26.2. The recirculated air is passed through high efficiency particulate air (HEPA) filters, giving 99.99% efficiency in the removal of physical contaminants such as microbial particles. Aircraft cabin air has been demonstrated to be bacteriologically cleaner than the air in buildings, trains or buses. Although clean, the aircraft cabin air remains dry. During the flight, moisture is derived from the metabolism and activities of the cabin occupants as well as from the galleys and washrooms, giving a maximum relative humidity in the order of 10–20%. These levels are associated with surface drying of skin, mucous membranes and cornea which may cause discomfort. Normal homeostatic mechanisms prevent dehydration and no harm to health has been demonstrated, although pharyngeal drying can stimulate the cough reflex. A high-differential cabin pressure limits the vehicle’s range and manoeuvrability and increases the risk of catastrophic damage if the fuselage is punctured. Thus military high-performance aircraft are fitted with low-differential cabins, which prevent cabin pressure falling below 280 mmHg (37.2 kPa) (equivalent to a pressure altitude of 25,000 ft, 7620 m). At this level decompression illness becomes a potential hazard (see below). In such aircraft, oxygen equipment is used routinely.

26.3.4 Mechanical effects of pressure change In civilian passenger and transport aircraft the climb to cruise altitude takes about 30 min and involves a maximum fall of about 200 mmHg (26.6 kPa) in cabin pressure

384

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

(to the equivalent of 8000 ft, 2440 m). Descent to land takes much the same time. Body fluids and tissues generally are virtually incompressible and do not alter shape to any important extent when such pressures changes are applied. The same is true of cavities such as the lungs, gut, middle ear and facial sinuses that contain air, provided that they can vent easily. Gas-containing spaces that cannot vent easily behave differently. The thoraco-abdominal wall can develop transmural pressures of þ100 mmHg or so briefly, but is normally flaccid and has a transmural pressure of a few millimeters of mercury. Gas within will usually be at a pressure very close to that outside, and must follow Boyle’s law. Ascent from ground level (760 mmHg) to 8000 ft (2440 m) (565 mmHg) will expand a given volume of trapped gas in a completely pliable container by about 35%. This may cause slightly uncomfortable gut distension in healthy people but it is not an important problem. Even very diseased lungs can vent themselves over a minute or so. In consequence, the risk of lung rupture in normal flight is extremely small. The cavity of the middle ear vents easily, but sometimes fails to fill because the lower part of the Eustachian tube behaves as a non-return valve, especially when it is inflamed. As a result, the cavity equilibrates quite easily on ascent but may not refill on descent, and the ear-drum bows inwards, causing pain that can be severe (otic barotrauma).

26.3.5 Altitude-induced decompression illness If ambient pressure falls quickly to less than half its original value, the gas dissolved in blood and tissue fluids may come out of solution precipitously, forming bubbles and obstructing flow in small blood vessels. The time symptoms take to develop varies widely between individuals and shortens markedly as the altitude of exposure rises. Symptoms usually resolve quickly after a descent of a few thousand feet and rarely persist after descent to ground level, breathing oxygen. Should they persist, treatment should involve recompression in a specialist unit (as discussed in the Chapter 25, Work in Hyperbaric Environments). Atmospheric pressure halves at 18,000 ft and decompression illness occurs rarely, if at all, below this altitude. It is very rare below 25,000 ft (7600m) and therefore is normally of no concern at normal passenger aircraft cabin altitudes, although the risk continues to be significant in some military flights. However, it does occasionally occur in those passengers who have been exposed to a hyperbaric environment prior to flight, such as divers and tunnel workers. Sub-aqua divers are advised to allow a minimum of 12 h to elapse between diving and flight, or 24 h if the dive required decompression stops.

26.3.6 Hyperventilation In the aviation environment it is generally recognized that hyperventilation is a common condition, often related to anxiety or emotional stress. Studies have shown that a large proportion of aircrew under training hyperventilate, as do experienced aircrew when confronted with an unusual event or in-flight emergency. A 2009 study raised concerns about the prevalence of unrecognized hyperventilation amongst airline pilots and the potential risk to flight safety. Symptoms can include light-headedness, headache, feelings

26.4

ALTITUDE ILLNESS

385

Figure 26.3 The hyperventilation syndrome

of unreality and anxiety, paresthesiae, visual disturbances, palpitations, cognitive impairment, loss of concentration and, in extreme cases, muscular tetany and paralysis. Whereas in general medicine, the hyperventilation syndrome may not always be readily recognized as a clinical entity, falling as it does between physiology, psychiatry, psychology and medicine, the condition of hyperventilation is readily accepted in aviation medicine. However, diagnosis can be difficult in the absence of a simple measurement. The physiological diagnosis of hyperventilation is breathing in excess of metabolic requirements, thus implying arterial hypocapnia and an abnormally high respiratory drive. However, in chronic cases PCO2 can be profoundly affected by the total physiological inputs to respiration and the conscious state of the individual. There can be a tendency to hyperventilate, even though the resting PCO2 is normal. There are a number of factors which may perpetuate hyperventilation (Figure 26.3). Apart from renal compensation, there appear to be physiological mechanisms resetting the PCO2 to a lower level independent of chemoreceptor setting. Habit may be a perpetuating mechanism, as may be misattribution of symptoms of hypocapnia (symptoms not dissimilar to those of carbon monoxide toxicity). The interaction of factors contributing to chronic hyperventilation remains uncertain.

26.4

Altitude illness

This is a collective term including the major conditions resulting directly from terrestrial hypobaric hypoxia, namely acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). It is thought that AMS and HACE probably represent different ends of a severity spectrum, sharing a common pathophysiology.

26.4.1 Acute mountain sickness Away from aviation, AMS is the commonest type of altitude illness. Although relatively benign, its presence indicates that acclimatization is incomplete and the traveler is at

386

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

risk of developing life-threatening altitude illness (HACE or HAPE) if ascent is continued with symptoms. Important risk factors include the altitude attained and the rate of ascent, as well as individual susceptibility. Some individuals readily develop AMS on ascent to high altitude while others are able to ascend rapidly without problems; approximately 25% of visitors who ascend rapidly to 3000–4000 m in Colorado experience AMS and 50% of trekkers in Nepal develop AMS when hiking above 4000 m over 5 days. Exertion may be a risk factor for AMS, but lack of physical fitness is not. There is no relationship with age, although females seem to have a higher incidence than males. Characteristic symptoms include the development of headache, accompanied by some or all of nausea, vomiting, anorexia, lassitude and dizziness, typically starting a few hours after arriving at altitude. Physical signs are non-specific, but often include an apathetic disinterested facial expression. Localized crackles may be heard in the lung fields and peripheral and periorbital edema may be observed. Vital signs are usually normal. Pathophysiology AMS is likely to be due to mild cerebral edema and is thus part of the spectrum of HACE. The symptoms and signs involve the central nervous system and neuroimaging studies have demonstrated brain swelling in AMS. However, brain swelling has also been demonstrated on ascent to high altitude in the absence of AMS, indicating individual susceptibility. Prevention The following guidelines are recommended for travelers ascending to high altitude:

1. Avoid abrupt ascent to greater than 3000 m, limiting the ascent rate to 300–400 m per day. 2. Spend at least one night at an intermediate elevation (1500–2500 m) to aid acclimatization. 3. If rapid ascent to greater than 3000 m is unavoidable (e.g. flying to La Paz or Lhasa), allow sufficient time for acclimatization before ascending higher. Consider drug prophylaxis. 4. Follow any recommended established safe itinerary for a given destination. 5. If previous experience indicates individual susceptibility to AMS, ascend at a rate slower than recommended in the itinerary. 6. Allow for unplanned rest days when planning the itinerary. 7. Be aware and watchful for symptoms of AMS and take immediate action. Drug prophylaxis Susceptible individuals may benefit from drug prophylaxis, but the use of drugs for other travelers remains controversial. Acetazolamide is the drug of choice for prevention of AMS, its effectiveness having been demonstrated in several placebo-controlled trials. The standard dosage is 250 mg twice daily, or a single daily dose of the 500 mg

26.4

ALTITUDE ILLNESS

387

slow-release formulation. For prophylaxis, acetazolamide should be started 1 day before ascent and continued until 2 days after the maximum altitude is reached. Side effects are mild and may include paresthesiae, diuresis, change in taste, nausea, drowsiness and headache. Should hypersensitivity occur, the less effective alternative of dexamethasone 4 mg 8-hourly may be used. Aspirin has been used prophylactically to prevent highaltitude headache. Treatment Unlike the hypoxic hypoxia encountered in aviation, where administration of oxygen is immediately effective, descent is the definitive treatment for all forms of terrestrial altitude illness. In the presence of symptoms of AMS, descent should be immediate if there is any suggestion of cerebral or pulmonary edema, as deterioration can occur rapidly. Oxygen relieves the symptoms of AMS, but the optimal therapy includes descent of 500–1000 m. Portable hyperbaric chambers made from fabric bags are carried on some high-altitude expeditions for emergency use.

26.4.2 High-altitude pulmonary edema HAPE is a potentially life-threatening form of non-cardiogenic pulmonary edema which may occur at altitudes above 2500 m. When compared with AMS it is relatively uncommon, although for susceptible individuals the recurrence rate is 60–70% at about the same altitude. In these individuals HAPE is precipitated by rapid ascent, strenuous exercise and cold. Recent inflammatory illness such as a viral infection increases the risk. HAPE is frequently preceded by symptoms of AMS, with the main symptoms being breathlessness and cough. Dyspnea on exertion progresses to orthopnea and breathlessness at rest. The initially dry cough may progress to the production of white then pink frothy sputum associated with gurgling in the chest and chest pain. Physical signs may include sinus tachycardia, low-grade pyrexia, tachypnea, central cyanosis and localized inspiratory crackles. Cerebral edema may also occur in severe cases. Where medical facilities are available, chest radiography may show patchy pulmonary edema and arterial blood gases confirm pronounced hypoxia. Untreated the mortality is up to 50%, emphasizing the importance of early recognition and treatment. Pathophysiology The mechanism of HAPE is uncertain, although it has been shown that pulmonary hypertension precedes the formation of pulmonary edema. It may result from uneven pulmonary vasoconstriction throughout the vascular bed, leading to pulmonary overperfusion in susceptible individuals. Another hypothesis suggests that inflammation in the presence of hypoxia may be the cause of pulmonary capillary leakage in some cases. Prevention Individuals with known susceptibility to HAPE should understand that it is a lifethreatening condition. They should avoid hasty ascent and gain altitude only slowly.

1. Above 2500 m, ascent up to 350 m per day in sleeping altitude may take place in the absence of symptoms of AMS.

388

CH 26 EFFECTS OF TRAVEL OR WORK AT HIGH ALTITUDES OR LOW PRESSURES

2. If symptoms of AMS persist for more than a day, descend. 3. Avoid vigorous exercise during acclimatization. Drug prophylaxis Drug prophylaxis is effective in individuals susceptible to HAPE. The drug of choice is nifedipine MR 20 mg orally 8-hourly and should be continued until the subject descends to an acclimatized altitude or below 3000 m. Nifedipine will not prevent AMS. Advice should be sought from a physician experienced in high-altitude medicine (not necessarily the same specialty as aviation medicine). Treatment The treatment of HAPE is urgent, with the aim of improving oxygenation and reducing pulmonary artery pressure. The patient should be sat up, kept warm and administered oxygen, with an immediate descent of at least 1000 m. Nifedipine can be given sublingually and a portable hyperbaric bag should be used to facilitate descent when available. If an oxygen saturation >90% can be achieved with no more than 4 liters oxygen per minute, then immediate descent may be avoided. Diuretics, nitrates, opiates and alcohol should be avoided.

26.4.3 Other altitude-related respiratory conditions Dry cough and sore throat are common occurrences at terrestrial high altitude, with 42% of trekkers to Mount Everest developing cough and 39% sore throat. This is likely to be the result of increased ventilation, breathing cold dry air, and increased cough receptor sensitivity. Occupants of pressurized aircraft cabins frequently report the development of coughs and colds. There is no evidence of an increased risk of respiratory infection during airline travel, the cabin air being microbiologically clean due to HEPA filtration. The cabin air is dry, which may lead to pharyngeal drying and stimulation of the cough reflex.

Further reading Aviation medicine Davis, J.R., Johnson, R., Stepanek, J., Fogarty, J.A. (eds) (2008) Fundamentals of Aerospace Medicine, 4th edn. Philadelphia, PA: Lippincott Williams & Wilkins. Rainford, D.J., Gradwell, D.P. (eds) (2006) Ernsting’s Aviation Medicine, 4th edn. London: Hodder Arnold.

Terrestrial altitude illness Murdoch, D.R., Pollard, A.J., Gibbs, J.S.R. (2001) Altitude and expedition medicine. In Principles and Practice of Travel Medicine, Zuckerman, J., Zuckerman, A.J. (ed.). Chichester: Wiley; 247–260.

Part IV The general environment

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

27 Natural sources – wildland fires and volcanoes Sverre Vedal University of Washington, Seattle, WA, USA

27.1 Introduction The distinction between natural sources of air pollution and other emission sources is not a clear one. We do not typically speak of ‘unnatural’ sources as distinct from ‘natural’ sources, but rather of anthropogenic (i.e. man-made) sources and natural sources. While most often ‘anthropogenic’ refers to pollution made up of products of combustion, crustal and other types of dust generated by human activities are also in a sense man-made and could be considered anthropogenic, although that is not common usage. It is important to understand that designating a source of air pollution as natural provides no assurance that these natural emissions are not harmful to health. Emissions from natural sources, as will be described in this chapter, contain components that are well known to be toxic. The following specific types of pollution from natural sources will be considered in this chapter: smoke from wildfires, including forest, bush and grass fires; smoke from agricultural burning; and volcanic emissions. Smoke from agricultural burning, while not strictly natural, is included here to the extent that it provides insight into wildfire emissions and their effects. Biomass smoke will be used here to refer to smoke from wildland (forest and bush) fires and agricultural burning. Inhalation burn injuries or effects due to carbon monoxide intoxication will not be covered here. Much is known about the health effects of individual components that make up biomass smoke and volcanic emissions. Much less is known about the effects of exposure to biomass smoke or volcanic emission in general, or about the contributions of the individual components in the respective pollutant mixes in producing these effects. Information from many sources will be used and integrated here in summarizing the health effects evidence. Some insight can be gained from knowing the individual Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

392

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

components and concentrations that are present in these emissions. Toxicological studies employing exposures to emissions can provide insights into pathophysiological mechanisms and can serve to shore up plausibility of suspected effects. Ultimately, findings from experimental and epidemiological (observational) human studies are needed to understand the effects that actually result from these exposures. The study designs employed in the human studies will be briefly identified as they are encountered in this chapter, as will some of their strengths and shortcomings that influence how we interpret findings based on them. This chapter begins with a review of biomass smoke exposure and its effects, followed by a review of volcanic emissions exposure and effects. Each review will conclude with a brief summary. A final section will address prevention of exposures and patient management. A small list of recommended readings is included at the end. Many of the studies referred to in this chapter review are referenced in those readings.

27.2 Biomass burning Exposure to smoke from wood and other biomass burning has been commonplace throughout human history. While smoke from forest wildfires is the most dramatic example of biomass smoke, bush and grass fires and controlled agricultural burns are also important outdoor sources of smoke exposure. The most prevalent source of biomass smoke exposure is indoor burning, with exposures resulting from personal wood burning for heating or biomass burning for cooking, or from neighborhood smoke resulting from residential burning. Effects of these more prevalent exposures will not be reviewed here, apart from brief mention in the context of extreme exposures below.

27.2.1 Extreme biomass smoke exposures Health effects resulting from extreme exposures can serve to suggest effects that might potentially occur with more commonplace exposures. It should be kept in mind, however, that more commonplace exposures may never in fact have such severe effects. Case reports involving intense exposures to products of wood combustion indoors have strongly indicated that these exposures have the potential to cause interstitial lung disease and asthma. ‘Hut lung’ has been used to describe cases of interstitial lung disease caused by chronic exposure to high levels of biomass smoke. Case–control studies of women in developing countries have provided good evidence that long-term exposure to the high concentrations of pollutants generated from burning biomass for cooking can produce chronic obstructive pulmonary disease (COPD) and associated pulmonary hypertension that can be as severe as those due to cigarette smoking. There is also evidence that these exposures in developing countries can cause lung cancer and increase the risk of active tuberculosis.

27.2.2 Forest fires Forest wildfires are either caused naturally, most often from lightning strikes, or are started by people either accidentally or intentionally. In the USA, from 15,000 to

27.2

BIOMASS BURNING

393

20,000 km2 (or 0.2% of the total land area) are burned each year. In Indonesia in 1997 and 1998, approximately 100,000 km2 burned. Smoke from forest fires often does not drift to areas where people will be exposed. When exposure does occur, it is most often on a small scale in small rural communities involving relatively few people. On occasion, especially with very large fires, smoke can drift over large urban areas exposing a large number of people to varying degrees and over varying periods of time. While the health impacts of smoke exposure on an individual are not obviously influenced by the size of the community affected, except perhaps through the potentially modifying effects of background urban air pollution, the ability to adequately study these impacts, and in particular the most adverse impacts such as mortality, is only possible when large numbers of people are exposed. Opportunities for studying these more severe effects are consequently limited. Population density is increasing in areas prone to forest fires, such as in southern California, which is increasing the likelihood of significant population exposures. The apparent increased occurrence of large forest fires, possibly related to global climate change, and certainly related to the practice of using burning to clear large areas of forest, is also enhancing prospects for increased exposure. Wood smoke constituents and exposures Forest fire smoke, as is typical of smoke from any combustion process, especially an inefficient one, is a complex mixture of particles and hundreds of chemical compounds. Most of the particles are in the inhalable size range (PM10), by both number and by mass, and most of those are in the fine inhalable (PM2.5) size fraction. By far the largest numbers of particles are in the submicrometer size range. Particles this small settle poorly and can be transported in the air over several hundreds of kilometers before depositing. The particles are carbonaceous and include both elemental carbon (essentially soot) and organic carbon compounds. Gaseous compounds in wood smoke include carbon monoxide (CO), nitrogen oxides and a host of hydrocarbons. Many of the hydrocarbons are potent respiratory irritants, such as acrolein, and many, including formaldehyde, benzene, and polycyclic aromatic hydrocarbons (PAHs), are either known or strongly suspected to be carcinogens. The relative proportions of the various compounds present in smoke both in the particulate and vapor phase is highly dependent on the type of wood burned and its water content, and the burning conditions such as whether a fire is smoldering or flaming. Less efficient burning, such as with a smoldering fire, produces less oxidized compounds. Exposures to wildfire smoke are extremely variable, as would be expected, with the primary determinant being proximity to the fire. Particulate concentrations measured in areas where people are exposed can vary by more than two orders of magnitude. In close proximity, PM10 concentrations can reach several milligrams per cubic meter (i.e. thousands of micrograms per cubic meter), while dispersed smoke in urban areas may result in increases above background concentrations of only a few micrograms per cubic meter. CO can reach lethal concentrations immediately next to a fire and in smoke-filled spaces, but elevations in CO concentrations can also be barely detectable when smoke is dispersed. Only a minority of forest fires result in significant nonoccupational (‘environmental’) smoke exposure, and a much smaller number result in large populations being

394

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

exposed. As a group, firefighters receive the highest concentrations and the longest durations of smoke exposure. Of the many constituents of wood smoke, personal concentrations of PM in firefighters when fighting fires are consistently the most elevated relative to occupational or ambient air standards. Personal peak concentrations over 1 mg/m3 are regularly measured in firefighters. Because of the intense physical activity entailed in fighting fires, lung doses for a given air concentration would be expected to be considerably higher in these workers than in the relatively sedentary. See the section on wildland firefighters on the next page. Wood smoke health effects In Table 27.1, health effects are listed that might be expected on the basis of the constituents present in wood smoke. Later, in Table 27.2, a summary of the evidence that these expected effects actually result from exposure to wood smoke is presented, ordered from least to most adverse effects. There is little controversy that exposure to wood smoke causes symptoms of irritation such as eye burning, throat soreness and cough. Anyone who has been exposed to wood smoke can personally relate experiencing these symptoms. It is reasonable to expect that individuals with underlying cardiopulmonary disorders, and even some without underlying illnesses, would be more sensitive to wood smoke effects and therefore experience more deleterious effects from wood smoke exposure than merely symptoms of irritation. Findings from properly conducted epidemiological and experimental health effects studies provide the basis for optimal recommendations for preventive measures and medical management. The 2003 wildfires in Southern California provided an opportunity to study effects in a large population. Recently, the effects on children already enrolled in a large cohort study were reported. Children in this cohort experienced more respiratory symptoms with smoke exposure. Asthmatic children were not singled out as being more likely to experience worsened symptoms than children without asthma. Doctor visits prompted by symptoms were increased in those who reported more smoke exposure, but not in those living in areas with higher concentrations of PM mostly from wood smoke. Increased doctor visits for respiratory complaints were also seen during the 2003 wildfires in southern British Columbia. The increase in doctor visits was limited to the one of the two cities studied that experienced the highest PM concentrations, suggesting that a certain level of exposure may be required to trigger doctor visits. Table 27.1

Constituents and potential health effects of wood smoke

Component

Health concerns

Particulate matter (PM)

Wide ranging effects from respiratory symptoms to cardiopulmonary morbidity and mortality; effects of both short- and long-term exposure Acute hypoxia; myocardial ischemia in coronary artery disease at low concentrations Pulmonary edema at high concentrations; possible airways effects at low concentrations Mucous membrane and respiratory irritant Carcinogen (leukemia) Probable lung carcinogens (e.g. benzo[a]pyrene)

Carbon monoxide (CO) Nitrogen oxides Acrolein Benzene Polycyclic aromatic hydrocarbons (PAHs)

27.2

BIOMASS BURNING

395

Table 27.2 Evidence for health effects of biomass smoke exposure Health outcome

State of evidence

Irritant symptoms Impaired lung function Increased hospital visits Lung cancer

Definite Suggestive in wildland firefighters Best evidence for asthma With indoor biomass burning in developing countries; possible from occupational exposure in the sugar cane industry Possible, but evidence for an acute effect is mixed

Increased mortality

Earlier studies in California and Florida identified increases in emergency room visits for respiratory conditions in relation to wildfires. Increased hospitalizations were also reported during the Southeast Asia wildfires of 1997 and 1998. Because of the wealth of evidence regarding short-term PM exposure effects on mortality, there would naturally be concern that wood smoke-related increases in PM have similar effects. Also, if hospitalizations are increased from smoke exposure, one might expect that some very susceptible persons would be even more severely affected. The evidence for mortality effects is mixed, however. Findings of studies of the Southeast Asia wildfires were inconsistent, but indicated that effects on mortality may have occurred. No effects on mortality were identified in a recent study of two episodes in which smoke from a wildfire drifted briefly over Denver, Colorado. There is little information on acute cardiovascular effects of wood smoke exposure, effects expected in light of the cardiovascular effects of PM. No increase in cardiovascular doctor visits was seen in the 2003 southern British Columbia fires. One controlled, human exposure study using wood smoke generated from a wood stove has been performed to date. The most compelling finding was an exposure-related increase in serum amyloid A, an acute-phase reactant that reflects increased systemic inflammation and is a risk factor for atherosclerosis. There were no meaningful effects in this experimental study on coagulation factors, exhaled nitric oxide or an indicator of oxidative stress. Wildland firefighters The dramatically higher exposures to wildfire smoke experienced by firefighters would indicate that studies of smoke-related health effects in wildland firefighters might be ideal for identifying worst case scenarios. Unfortunately, some challenges encountered in studying firefighters have limited their usefulness in this regard. The physical demands of firefighting require a relatively healthy workforce. Studies in which no effects are identified can therefore be generalized to only a subset of the exposed population. Effects that are identified might be expected to underestimate effects experienced in a less healthy general population in settings of comparable exposure, but these settings would be unusual. Finally, the locations and rough terrain where firefighting activities are often performed limit the ability to assess exposure. Use of respiratory protection (respirators) by wildfire firefighters to reduce exposure is variable. The most effective protection is provided by atmosphere-supplying respirators, such as self-contained breathing apparatuses, but these are largely impractical. The least effective is the bandana, which provides only minimal protection against particles and essentially no protection against gases, but is nevertheless commonly used. Air filter

396

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

masks that are more effective than bandanas against respirable particles are variably used. Powered air-purifying respirators are more effective than filter masks, but these are little used. Firefighter exposures to smoke occur both while fighting fires using some type of respiratory protection that is most often inadequate to protect against the many components of smoke, and while in the vicinity of fires when respiratory protection is not used. Study designs have therefore most often relied on indirect and crude measures of exposure such as a workshift in pre- and post-workshift studies, and a fire season in pre- and post-season studies. Cross-season studies have shown increased symptom reporting, lower level of lung function and increased bronchial responsiveness after a firefighting season compared with those before the season. The rare cross-shift study has shown mean decreases in level of lung function over a workshift. One cross-sectional study of wildland firefighters done before the fire season was aimed at identifying effects of long-term smoke exposure. Levels in measures of lung airway function in this study were lower than those in control workers. Workers with more years of exposure, surprisingly, were not more severely affected than those with less exposure. Assessing exposure–response relationships in cross-sectional studies such as this is hampered by the healthy worker effect in which the more healthy workers tend to preferentially continue working. This could make it appear that those who have worked the longest, and had the largest cumulative exposure, are actually healthier. In spite of the challenges in interpreting and applying findings from firefighter studies, evidence favors both short-term and long-term respiratory effects from the sometimes extreme exposures that this work entails. Evidence from toxicology Toxicological studies serve not only to investigate mechanisms underlying effects of smoke exposure, but to enhance the plausibility of epidemiological findings. Very high dose, acute inhalational studies, although relevant in indicating the types of effects that could occur with smoke inhalation, do not offer much insight into effects at the levels of exposure investigated in most epidemiological studies. Some lower dose studies have been done, however. Animal studies in which carboxyhemoglobin levels did not exceed 20% have demonstrated alterations in pulmonary immune defense mechanisms, specifically in macrophage function, and reduction in pulmonary clearance of bacteria. No pulmonary inflammation, as reflected by increased pulmonary inflammatory cell infiltration or increased lung cytokines, is typically observed at those levels of exposure. There is evidence for reduced lung antioxidant activity, however. There is also some evidence of smoke-induced exacerbation of allergen allergic responses, such as increased allergen-specific serum IgE and increased pulmonary eosinophils, which may be relevant to the epidemiological observations regarding smoke exposure and asthma. Forest fire smoke instilled in rat lungs produces little inflammation compared with other combustion sources. Little evidence for cardiac effects or lung tumors has been found in relevant toxicological studies of wood smoke exposure. Wood smoke is mutagenic, however. Although somewhat dependent on burning conditions and type of wood burned, the potency of wood smoke in initiating skin tumors, a test of general tumor producing potential, is less than gasoline or diesel exhaust, but greater than cigarette smoke, which is typically less potent than other combustion sources.

27.2

BIOMASS BURNING

397

27.2.3 Bush and grass fires and agricultural burning Bush and grass fires, and agricultural fires, most of which involve burning of agricultural straw and stubble, can be reasonably discussed together. Increases in PM, CO and volatile organic compounds have been measured in relation to these types of burning, as they have for forest fires. Unlike for forest fires, it is not unusual for smoke from these fires to drift over large urban areas, thereby providing an opportunity to investigate effects in population studies. A series of relatively small studies from Sydney, Australia largely showed no effects of bush fire smoke on respiratory emergency room visits or on level of lung function in asthmatic children. In contrast, in a larger time series study in Darwin, an association between PM concentration and asthma emergency visits was detected during a period of near-continuous bushfires. Time series studies, in which daily measures of smoke are related to daily counts of health events such as hospitalizations or deaths, are often used to study smoke effects. These studies are relatively easy to carry out as long as the relevant smoke data and counts of health endpoints are available. Interpretation of time series studies in assessing smoke effects relies on being able to identify burning-related pollutant concentrations or time periods. PM concentrations are often used as a measure of smoke exposure, which is reasonable if PM in the specific study setting is composed largely of wood smoke PM. Number of acres burned has been used as a surrogate measure of agricultural burning in some time series studies. Emergency room visits for asthma have been associated with burn acreage in California and eastern Washington State. In Winnipeg, Canada, most of a cohort of subjects with mild to moderate airways obstruction reported increased respiratory symptoms with exposure to smoke from straw and stubble burning in surrounding fields; over one-third of this presumably susceptible cohort noted no increase in symptoms. Recently, relatively low concentrations of smoke from agricultural stubble burning in eastern Washington State did not affect either level of lung function or exhaled nitric oxide in asthmatics. In rural Iran, however, rice stubble burning was associated with measures of worsened asthma control. Also, rice stubble burning in Japan has been associated with increased asthma emergency visits and hospitalization in children. One experimental human exposure study using controlled burning of rice stubble has been performed, and included only subjects with allergic rhinitis. No increase in inflammatory cells was seen in broncho-alveolar lavage fluid. Effects of sugar cane burning have also been studied. Time series studies have suggested effects on intensity of hospital emergency nebulizer use in Brazil and, more recently, on asthma hospitalizations. Asthma hospital visits in Louisiana are higher in the sugar cane burning season. There has been concern that occupational exposure in the sugar cane industry causes lung cancer and mesothelioma, specifically exposure to the amorphous silica fibers in sugar cane smoke. Evidence was determined to be inadequate for judging the carcinogenicity of sugar cane work in the IARC assessment on this in 1997, in spite of reports of increased lung cancer risk from several case–control studies. A subsequent case–control study from India also identified increased risk of lung cancer. Although anecdotal cases of mesothelioma have been reported in sugar cane workers, case–control studies have not supported this anecdotal impression.

398

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

27.2.4 Biomass burning summary There are many challenges to rigorously studying health effects associated with exposure to smoke from forest fires, bush fires and agricultural burning. One of the greatest challenges is adequately estimating exposure to smoke. Exposure misclassification is likely to be substantial when surrogate measures such as burning season and burn acreage are used. Even when concentrations of smoke pollutants such as PM are used, substantial spatial variability in concentrations is likely to be present, with attendant exposure misclassification. Also, when PM concentrations are not dramatically elevated during burning periods, PM may include significant contributions from nonburning sources. This limits the ability to attribute observed PM effects to burninggenerated PM specifically, especially in time series studies that attempt to relate shortterm concentration changes with changes in health. Use of PM measures that are specific for biomass burning would address this limitation, but specific measures have not been used in epidemiological studies. In one commonly used study design, a measure of morbidity over a specified time period, hospital visits for asthma in September or October, for example, is compared across other time periods of the year. This design is particularly prone to bias due to seasonal trends in disease morbidity that may coincide with the burning season. The near-universal increase of asthma morbidity in the fall of each year, for example, often coincides with periods of burning. If these short-term temporal trends in the data cannot be accounted for, the more credible comparisons may be with morbidity measures at the same time period from other years when no burning occurred, such as was done in studying the wildfire smoke effects from the 2003 southern British Columbia fires described above. In spite of these challenges in adequately estimating exposure and in using appropriate study designs, it is clear that exposure to smoke from biomass burning has health impacts. The types of impacts produced are known with varying degrees of certainty (Table 27.2). Some are known to occur only in specific exposure settings, but might be suspected in other settings as well. Regardless of the type of biomass burned, smoke produces symptoms of mucous membrane and airway irritation. There is good evidence that people exposed to smoke are more likely to seek medical attention manifested either as increased doctor visits, emergency room visits or hospitalizations; this evidence is particularly strong for asthmatics. It is not clear that effects on asthma are due to worsened airways inflammation; there is little suggestion from experimental studies that relevant exposures result in airways inflammation, although some data suggest enhancement of allergic responses. Whether smoke exposure increases mortality is controversial at this point. Clearly intense acute smoke inhalation can be lethal. Also, arguing from the example of PM and its effects on mortality, unless PM in smoke is considerably less toxic than other sources of PM, smoke-induced mortality would be expected. Based on studies to date of large populations exposed to smoke, however, no firm conclusion regarding mortality is possible. Similarly, there is yet little evidence for cardiovascular effects of wood smoke exposure. However, based on the burgeoning amount of information on the cardiovascular effects of PM, cardiovascular effects of smoke would be anticipated. The human experimental finding of smoke-induced increase in serum amyloid A, an inflammatory marker and risk factor for atherosclerosis, supports the possibility of vascular effects.

27.3

27.3

VOLCANOES

399

Volcanoes

Volcanic eruptions, exposures to volcanic emissions and their attendant health impacts have occurred repeatedly throughout human history. Reportedly, the most significant air pollution event related to a volcanic eruption in Europe in recent times was due to the eruption of Laki in Iceland in 1783. The resulting degradation in air quality in Europe during the summer months of 1783 was such that there was a distinct odor, visibility was reduced, effects on vegetation were apparent and human health impacts, consisting of irritation symptoms and respiratory illness, were reported. In North America, the Mt St Helens eruption in 1980 was important in focusing attention on the health effects of emissions from volcanic eruptions. Rather than producing discrete air pollution episodes, volcanic emissions sometimes contribute to further degradation of already poor air quality, such as the contributions of emissions from Popocatepetl or the Miyake Island volcano on Mexico City’s and Tokyo’s air quality, respectively. In some cases, concern is focused more on gaseous volcanic emissions vented from a relatively quiescent volcano or due to soil gas in the vicinity of a volcano (‘degassing’), rather than eruptive emissions.

27.3.1 Composition of volcanic emissions Emissions from volcanic eruptions contain pollutants in the particulate, vapor and gaseous phases. Emissions of air pollutants from volcanoes that occur between eruptions include similar pollutants. Gaseous pollutants include carbon monoxide, carbon dioxide, sulfur dioxide, hydrogen sulfide and radon. These can be present as gases in a volcanic eruption or produced in volcanic venting or degassing; degassing refers to the noneruptive emission of volatile compounds from volcanic magma in volcanic craters or through the ground. Acidic fumes (from condensed vapor) composed of hydrochloric acid, hydrofluoric acid and sulfuric acid can also be emitted primarily or formed secondarily from gaseous emissions. Volcanic ash consists of particles of varying size, ranging from larger particles that settle quickly and are not inhalable, to fine inhalable particles. Inhalable particles (PM10) typically make up the largest number of particles but less than half of the particle (PM) mass. Fine inhalable PM (PM2.5) in volcanic ash, as distinct from typical urban ambient PM2.5, usually makes up only a small proportion of the PM mass. Silica is a prominent component of ash, especially in the inhalable fraction, but its contribution to total mass varies according to the type of volcanic activity. Crystalline silica, the form of concern in relation to silicosis, makes up much less of the mass. Volcanic PM also includes secondary compounds such as sulfate and various acid aerosols that form in the atmosphere after being emitted, although these can also be part of the primary emission mix. Heavy metals such as lead and mercury are also common particle components. It is important to realize that not all volcanoes emit the same mix of pollutants in similar proportions, and that the same volcano may emit a different pollutant mix at different times. Health effects, to the extent that they are related to the composition of the emissions, would also be expected to be variable.

400

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

A large range of exposures to volcanic pollutants is expected based largely on marked differences in proximity of populations to volcanic emission plumes. It is estimated that at least 500 million people in the world today (8%) live in areas where they could be exposed to emissions from volcanoes known to have been active in human times. Volcanic emissions from the often long periods between eruptions affect a much smaller subset of this population.

27.3.2 Health effects Health effects due to exposure to volcanic ash have been investigated using both observational and experimental approaches. There was a flurry of interest in the health effects of volcanic ash following the Mt St Helens eruption in southern Washington State in 1980. Short-term effects included increased emergency and hospital visits for respiratory symptoms and asthma. Pre-existing respiratory disease was a risk factor for adverse effects. Short-term ocular symptoms were also common. In vitro toxicology studies generally found toxicity similar to that of ‘low-toxicity’ minerals. Inhalational animal studies showed conflicting results, but those done using more realistic, although still high, concentrations of ash showed little toxicity. The ash was clearly less toxic than crystalline silica. Other series of health studies have been carried out in relation to the Mt Sakurajima volcano in Japan and the Soufriere Hills volcano in Montserrat in the West Indies. Regular and frequent eruptions of the Mt Sakurajima volcano have chronically exposed the local population to volcanic emissions and ash since 1955. While no cases of silicosis have been detected, there is a slightly increased prevalence of respiratory symptoms related to exposure. Level of lung function in area loggers has not been associated with exposure. Eruptions of the Soufriere Hills volcano have resulted in frequent ash exposures of the resident population since 1995. Most of the crystalline silica in ash from this volcano is cristobalite, a particularly fibrogenic form. Prevalence of respiratory symptoms in children is higher in those from higher exposure areas of Montserrat. Inhalational studies using the Soufriere Hills ash in rats have shown more lung inflammation than with inert dust, but toxicity is considerably less than that of quartz. While no chest radiographic evidence of pneumoconiosis in island residents has been found, the latency period from onset of exposure is obviously short. Exposure to volcanic gases also has the potential to be harmful. CO2 from volcanoes may be concentrated in high enough concentrations to cause asphyxiation. This can occur as a result of the sudden release of a CO2 cloud or from accumulation of CO2 in low-elevation areas where air circulation is limited, even at times when a volcano is quiescent. The evidence for deaths due to CO2 asphyxiation is largely indirect, being typically based on reports of large numbers of deaths in a defined area not due to other apparent causes, such as occurred around Lake Nyos in the Cameroon in 1986, and on some case reports. These reports are nevertheless compelling. Hydrogen sulfide is another potential cause of asphyxiation from concentrated volcanic or geothermal releases. Like CO2, H2S can concentrate in low-elevation areas. If concentrations are high enough, the fraction of inspired oxygen could be critically reduced, leading to asphyxia. Unlike CO2, H2S in these situations probably causes its

27.3

VOLCANOES

401

effects not by asphyxiation but by blocking the mitochondrial cytochrome chain, much like cyanide. Also, because H2S is lipid-soluble, effects are often localized to the central nervous system with manifestations of loss of consciousness or respiratory arrest. In those who survive exposure to high H2S concentrations, the clinical presentation could be one of pulmonary edema, adult respiratory distress syndrome or pneumonia. While the pneumonia is probably a chemical pneumonitis, bacterial pneumonia should be suspected if pneumonia develops several days after the incident. At low concentrations, H2S is a potent irritant to mucous membranes and the respiratory tract. The sulfurous rotten egg odor of H2S is apparent at much lower concentrations than produce irritant symptoms. There has also been concern about effects of long-term exposure to much lower concentrations of H2S and other reduced sulfur compounds. The evidence is most convincing for neurological and psychological sequelae of long-term H2S exposure and for increased reported respiratory symptoms. As concerns other respiratory effects of H2S exposure, most evidence indicates no effect on level of lung function; evidence for increased respiratory hospitalizations and lung cancer is sporadic and inconsistent. An ecological study from Rotorua, New Zealand, a city affected by H2S emissions from a geothermal field, found evidence for neurological and respiratory hospitalization rates being increased in higher exposure areas, although there was also a suggestion that cardiovascular hospitalization rates were also increased. As in all ecological studies, because no data on individuals was available, there is concern that the observed associations could have other explanations than exposure to H2S. Sulfur dioxide exposure can also be harmful, especially at high concentrations, where it is well known to cause bronchoconstriction in asthmatics. The evidence that high concentrations of volcanic SO2 specifically have been harmful is limited. As with other gases and fumes, it is has been difficult to implicate SO2 as the harmful component of what is often a mix of gases and fumes. However, episodes of degassing of SO2 have reportedly caused a small number of deaths in asthmatics. Volcanic acid fumes and acid aerosols, some generated from SO2, could potentially also contribute to adverse health effects, but evidence implicating them specifically is lacking.

27.3.3 Volcanic emissions summary Both volcanic ash and gases from volcanic eruptions and degassing can cause effects on health. Exposure to ash most certainly causes ocular and respiratory symptoms and causes symptomatic individuals to seek medical care, especially those with pre-existing respiratory conditions such as asthma. Whether more severe effects of volcanic ash occur is controversial. Of particular concern is whether those chronically exposed to airborne ash are at risk of silicosis. While there have been no documented cases of silicosis caused by volcanic ash, silicosis is a theoretical possibility when risk is assessed on the basis of concentrations of crystalline silica and years of exposure. The health impacts of volcanic gases specifically appear to be due largely to the rare episodes in which very high concentrations cause death by asphyxiation, poisoning or severe exacerbation of asthma. While chronic exposure to gases is of concern, apart perhaps for neuropsychological sequelae of H2S exposure, the evidence for effects from long-term exposure to volcanic gases is weak (Table 27.3).

402 Table 27.3

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

Volcanic emissions and anticipated severity of respiratory health effects

Emission component

Respiratory health effect Respiratory symptoms

Reduced level of lung function

Respiratory hospitalization

Respiratory mortality

Ash

Good evidence

None

Good evidence, especially if preexisting lung disease From asphyxiation and its sequelae

Little evidence, but plausible

CO2

Little evidence as a result of long-term exposure None

H2S

Potent respiratory irritant; odor threshold much lower than irritant threshold In asthma

Unlikely

From asphyxiation or poisoning and sequelae

Acutely in asthma

Plausible in asthma

SO2

From asphyxiation and its sequelae From asphyxiation or poisoning and sequelae

Suspected in case reports of asthma

27.4 Management/prevention 27.4.1 Biomass smoke exposure There are many instances where a diagnosis of a respiratory disease in an individual, or even an exacerbation of underlying disease, cannot be unequivocally attributed to smoke exposure. Exceptions include dramatic cases where the temporal association firmly establishes the causal connection, or where a diagnostic procedure such as broncho-alveolar lavage detects evidence of high-level particle exposure in the context of clinical disease, such as interstitial lung disease. In the common situation where such certainty is not possible, it is prudent to keep an open mind about the likelihood that, failing other explanations, smoke exposure is responsible for symptoms or illness. Since there are no treatment approaches for respiratory conditions that are specific to the exposures described in this chapter, except possibly for the case of H2S intoxication (see below), general recommendations for management of these conditions should be followed. Preventive measures should be considered, especially if the underlying condition is sufficiently severe that worsening would cause distress or prompt clinical intervention. General preventive measures include pharmacologic measures; exposure specific preventive measures typically aim to reduce or eliminate exposure. In patients with asthma or COPD, it is important to encourage compliance with maintenance medications and to review action plans of incrementally more aggressive treatment and management based on symptoms or personally monitored level of lung function. In

27.4

MANAGEMENT/PREVENTION

403

fragile patients exposed to smoke, it may be prudent to increase medication dosage or frequency above the maintenance level before symptoms or lung function worsens. Because particles smaller that 1 mm in diameter gain ready access indoors, staying indoors will not provide much protection from these fine particles. When doors and windows are closed, larger particles, many of which still reach distal parts of the bronchial tree as well as the alveoli, do not gain ready access indoors. Irritant symptoms, to the extent they are caused by larger particles, can be lessened or prevented by keeping indoors. Running air conditioning or using the fan on home heating systems that have some filtration function can also be helpful. The effectiveness of portable air cleaners in lowering indoor concentrations of PM from wood smoke has been debated. The effectiveness of portable high efficiency particulate air (HEPA) cleaners and electrostatic precipitators was investigated recently in two studies, one in relation to forest fires in the Okanagan Valley in southern British Columbia in 2003, and the other in relation to the Hayman fire near Denver, Colorado in 2002. Somewhat surprisingly, in both studies use of air cleaners resulted in substantial reductions in indoor PM concentrations. In a California study, people who used portable HEPA filters longer had fewer symptoms. Air cleaning devices are therefore recommended. These should be appropriate for the size of the room in which they are used. Personal protective equipment, such as an N95 mask that has been fit tested, theoretically should also provide some degree of protection against fine PM. The effectiveness of such well-fitted masks in relevant exposure settings has not been formally tested, however. In the California study above, mask use was deemed ineffective, but fit testing was not performed. It is very difficult to determine whether and when to evacuate residents exposed to smoke for health reasons, particularly those with underlying cardiopulmonary disease. Health surveillance data are seldom timely or definitive enough to be helpful. Guidelines to assist in making evacuation decisions have been formulated, such as those contained in the Forest Fire Emergency Action Guidelines of the Manitoba Emergency Plan (http://www.gov.mb.ca/emo/index.html) from the Province of Manitoba in Canada.

27.4.2 Exposure to volcanic emissions Because of the temporal association, the diagnosis of respiratory conditions related to volcanic eruptions is relatively straightforward. Also, for the most part, management of these respiratory conditions is not dictated by the nature of the exposure. Exceptions include patients presenting with conditions potentially due to exposure to high concentrations of gases. In those who survive these exposures, the nature of the exposure may not be immediately apparent, thereby making the diagnosis difficult. Medical practitioners working in areas close to volcanic or geothermal activity should be familiar with situations in which exposure to gases occurs and to suspect exposure when presented with suggestive symptoms. For example, in these settings, SO2 exposure should be considered when faced with worsening asthma. Pulmonary edema may be the presenting picture following extreme CO2 or H2S exposure if asphyxiation or poisoning was not severe enough to be lethal. It is often suggested that patients exposed acutely to high concentrations of H2S should be treated with the cyanide antidote kit that uses

404

CH 27 NATURAL SOURCES – WILDLAND FIRES AND VOLCANOES

nitrites to produce methemoglobin to bind H2S, forming sulfhemoglobin. This treatment is controversial in H2S poisoning and has even been suggested to be potentially harmful as a result of sulfhemoglobinemia, further reducing blood oxygen-carrying capacity. In the aftermath of the Mt St Helens eruption, attention was given to the preparedness of medical facilities in adequately managing the sudden increase in patient load following volcanic eruptions in areas at risk. While outside the scope of this chapter, one of the lessons learned from Mt St Helens and other dramatic volcanic eruptions is that planners are well-advised to develop emergency plans to deal with the abruptly increased demand for appropriate care. Practicing physicians and other health care professionals in these areas can and should play important roles in the planning process.

Further reading Biomass fires Naeher, L.P., Brauer, M., Lipsett, M., Zelikoff, J.T., Simpson, C.D., Koenig, J.Q., Smith, K.R. (2007) Woodsmoke health effects: a review. Inhal. Toxicol. 19: 67–106.

Volcanoes Hansell, A., Oppenheimer, C. (2004) Health hazards from volcanic gases: a systematic literature review. Arch. Environ. Hlth 59: 628–639. Horwell C.J., Baxter P.J. (2006) The respiratory health hazards of volcanic ash: a review for volcanic risk mitigation. Bull. Volcanol. 69: 1–24.

28 Traditional urban pollution Sam Parsia1, Amee Patrawalla2 and William N. Rom1 1 2

New York University School of Medicine, New York, NY, USA New Jersey School of Medicine, Newark, NJ, USA

28.1 Introduction The twentieth century was marked by a rapid increase in industrial processes involving consumption of fossil fuels, particularly in the years following the Second World War. The pollutants generated by coal-fired power plants, steel mills, smelters and fertilizer plants became increasingly prevalent in the ambient air of developed regions of the world, particularly Europe and the USA. Even before the Second World War, air pollution was becoming an increasingly recognized reality. The first health crisis directly attributable to air pollution occurred in the Meuse Valley in Belgium in December 1930, where hundreds became ill and approximately 60 people (10 times the mortality rate) died during a 3 day period. The cause of this episode was a perfect combination of geography, weather and heavy industrial activity that resulted in a stagnant air mass containing high concentrations of toxic pollutants that settled over the towns of Huy and Liege. In the USA, a cloud of smog was visible over the Los Angeles skyline by the mid 1940s, and the coal-fueled Midwestern industrial boom filled the skies of the populous Eastern seaboard with airborne pollutants. A weather pattern similar to that seen in the Meuse valley occurred over the small town of Donora, Pennsylvania in 1948, once again concentrating the pollutants from nearby factories and causing widespread respiratory symptoms and 20 deaths (6 times the mortality rate). Although both the events in Liege and Donora received intense political and media attention in their respective countries at the time of each occurrence, the event that probably receives the most attention in environmental health literature is the London Fog of December 1952. During a four day period of December 1952, a dense, pollutantladen fog settled over the city and was blamed for about 3000 excessive deaths during the following weeks. Recent investigators have applied more contemporary modeling Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

406

CH 28 TRADITIONAL URBAN POLLUTION

techniques to public health records from the period and have raised the estimated death toll to as many as 12,000 excess deaths. Even taking the historical figure of 3000 deaths, the astounding number of deaths from this episode is considered by many to be the first major stimulus to the study and reduction of air pollution. Despite the many lessons learned from these historic environmental disasters, the rapidly developing countries of Asia, the Middle East and Latin America will probably suffer similar episodes given their large reliance on traditional energy sources and industrial practices to build their economies. In today’s global society, countries that have already learned from such disasters should help develop methods of industry that allow for sustainable growth, without a return to the smoggy days of London, Liege and Donora. The following will include a description of the major components of traditional sources of air pollution, a current understanding of the health effects of each component, and a brief summary of current policy issues. Common patient questions are addressed below (Table 28.1).

Table 28.1 Selected issues for patients with respiratory disease Question

Answer

When is the best time to exercise outdoors?

In cities, air pollution from ozone is generally lowest early mornings before rush-hour traffic, so exercise at that time, not close to a highway At a population level, by legislation to reduce air pollutants At a personal level, reduce use of gasoline or diesel, and limit outdoor activities during high pollution episodes By reducing outdoor exposure, by reducing exposure to relevant allergens and other asthma triggers and by optimizing asthma control with prescribed medications Ozone concentrations can also be high in rural areas with natural sources of NOx contributing to ozone in the summer months. No studies to date have shown overall improved outcomes among those who have moved to rural areas For patients with cardiovascular disease or COPD, there also is no current evidence to support a move to a more rural setting which may have less air pollution but also may have less availability of healthcare resources The generally relatively small risks of air pollution effects need to be balanced against the known beneficial effects of exercise for children, and there are currently no recommendations to restrict outdoor exercise for children except at times of extreme air pollution episodes The answer to this remains unclear but smoking, cooking with biomass fuel and occupational exposures remain the most important causes of COPD

How can exposure to air pollution be minimized?

How can the effects of air pollution on asthma exacerbations be prevented?

Should a patient with lung disease avoid living in a city?

Should outdoor play be restricted for children in cities?

How much COPD can be blamed on outdoor air pollution?

28.2

28.2

PARTICULATE MATTER

407

Particulate matter

28.2.1 Characteristics of PM Particulate matter (PM) includes air particles from many different sources and of various sizes. Total suspended particles are composed of particles up to 40 mm in diameter. PM10 refers to particles up to 10 mm in diameter and are those which can be inhaled past the upper airways. PM is further delineated into PM10-2.5 and PM2.5, the latter of which are fine particles up to 2.5 mm in diameter. Ultrafine particles are those which have a diameter less than 0.1 mm. Other important characteristics of PM are the contributing source and its various components. PM can be directly produced by combustive sources such as coal-fired power plants, or can be formed in the atmosphere as a result of the combination of gases from motor vehicles, industries and natural sources. Direct sources of PM in the traditional urban environment include coal- and oil-fired power plants and industry. The actual composition of PM2.5 varies tremendously based on both region and season. In a study of composition of PM2.5 over 187 counties in the USA, only seven of the 52 compounds analyzed accounted for 1% or more of the yearly or seasonal average of total PM2.5 mass. These included ammonium, elemental carbon, organic carbon matter, nitrate, sodium, silicon and sulfates and made up 79–85% of the total PM2.5 mass. PM and its effects vary based on source, region and season, which are also linked to particle size and composition.

28.2.2 Animal experiments Many efforts to develop a simple and consistent animal model of particle induced health effects have been made with variable success. The development of techniques to concentrate ambient particles at both New York University and Harvard School of Public Health in the 1990s has made standardized exposures easier to achieve, and have advanced this line of research immeasurably. These techniques allow investigators to collect ambient air and concentrate the particles without necessarily altering the distribution of sizes and chemical composition of the pollutants. Results of experiments employing materials obtained via these concentrators in closed chamber animal experiments follow. Effects on the respiratory system Early experiments compared normal rats with those exposed to 250 ppm SO2/day for 6 weeks as a method of inducing chronic bronchitis. The rats were then exposed to either concentrated ambient particles (CAPs) or filtered air 5 hours per day for three consecutive days and assessed for measures of pulmonary function and inflammation. The ambient air particle mass on each day was 7.1, 19.1 and 18.6 mg/m3 and after concentration via the Harvard/EPA Ambient Particle Concentrator levels of 205.5, 733.3 and 606.7 mg/m3 were achieved in the exposure chamber. After exposure, the chronic bronchitis rats interestingly had significant increases in both tidal volume and peak expiratory flow, whereas normal rats had increased tidal volume over baseline. Bronchoalveloar lavage showed no difference in total cell counts, but a shift in the

408

CH 28 TRADITIONAL URBAN POLLUTION

cellular differential towards neutrophilic inflammation and increased fluid protein content was observed. Similar experiments in normal dogs showed no statistically significant differences in bronchoalveloar lavage cellularity, but a nonsignificant trend towards increased neutrophils. Exposure to CAPs, collected from a community in southwestern Detroit with known high levels of air pollution showed no demonstrable airway inflammation in healthy rats; however, ovalbumin-sensitized rats did have significant, although variable inflammatory responses after five consecutive days of exposure. Finally, no differences were found in pulmonary immune responses in rats exposed to CAPs collected in New York City; however, there was a significant elevation in blood polymorphonuclear leukocytes. Effects on the cardiovascular system Acute exposure (4 weeks) to PM10 has been shown to enhance progression of atherosclerotic lesions in rabbits with inherited hyperlipidemia. A longer term (6 month) study of apolipoprotein E knockout mice (ApoE
/
) who were exposed to concentrated PM2.5 for 6 hours per day, 5 days per week also showed increased atherosclerosis, particularly when fed a high-fat diet. These mice were also found to have alterations in vasomotor tone, heart-rate fluctuation and vascular inflammation. These effects also seem to translate into worse clinical outcomes in models of myocardial infarction, as dogs exposed to CAPs developed a significantly greater degree of ST segment elevation after coronary artery occlusion.

28.2.3 Health effects of PM in humans Short-term health effects of PM The influence of particulate air pollution on short-term health effects has been largely examined through time-series studies, which generally relate daily PM levels to various indicators of disease. Several multi-city, time-series studies have been performed, including a 90-city study in the USA, the National Morbidity, Mortality and Air Pollution Study (NMMAPS). In this study, multiple pollutants were examined and PM10 levels were found to be associated with an increase in mortality, with the largest effect size seen in the northeast region. Nationally, for every 10 mg/m3 increase in PM10, a 0.2% increase in mortality with a 1-day lag was detected. In addition, there was a 0.3% increase in cardiopulmonary-specific mortality, for every 10 mg/m3 rise in PM10. Hospital admissions for cardiovascular disease and COPD among elderly in 14 cities from NMMAPS were also correlated with PM10 levels. The multi-city European project, APHEA (Air Pollution and Health: a European Approach), has also studied the short-term effects of particulate air pollution. In the initial study, black smoke (representing PM < 4 mm) and PM10 were correlated with daily mortality in 12 European cities. A 50 mm3 increase in black smoke and PM10 was associated with respective 3 and 2% rises in mortality in western European cities. A more comprehensive study, APHEA2, included 29 European cities and measured health outcome and particulate levels over 5 years, beginning in 1990. Similar to NMMAPS, APHEA2 correlated a 0.6% increase in daily mortality with a 10 mg/m3 rise in PM10 and black smoke. Larger effects sizes were noted among elderly, and in cities with higher NO2 and warmer climates.

28.2

PARTICULATE MATTER

409

Long-term health effects of PM Health effects of chronic air pollution in traditional urban areas were investigated in a study comparing three counties in Utah, each with a major city. Two of the counties, Utah and Cache Counties, were similar, in terms of demographics, religion and minimal tobacco use, until a steel mill was built in Provo (Utah County) in the 1940s. Salt Lake County, which included the third city, was notably more characteristic of a US city. Smoking, for example, was twice as common in Salt Lake County. Approximately 45% of PM10 levels in Utah County were produced by the Provo steel mill. From 1960 to 1970, respiratory cancer death rates doubled in Utah County, in contrast to Cache County, where they were relatively unchanged, and continued to increase in subsequent decades. Long-term air pollution, which increased substantially in Provo and was largely attributed to the steel mill, was associated with increased mortality and morbidity from both respiratory cancers and nonmalignant pulmonary disease. Temporary cessation of operations at the Utah County steel mill in 1986 led to decreased PM10 levels, and was associated with fewer county-wide hospital admissions for respiratory illnesses [1]. Fine particulate matter and mortality More specific health effects of fine particulate matter have also been studied. The effects of long-term air pollution and PM2.5 were studied in the cohort from the Harvard Six Cities Study, which included roughly 8100 adults from Watertown, MA, Harriman and Kingston, TN, St Louis, MO, Steubenville, OH, Portage, WI and Topeka, KS, areas with differing degrees of air pollution. Central air pollution and individual health data were collected from the mid-1970s to 1991. Overall mortality in this cohort study was most strongly linked with fine (PM2.5), inhalable particulate matter, especially sulfates, with relative rate ratios of 1.26–1.27 across the range of pollution found in these cities. Specific causes of death linked to air pollution in this study included lung cancer and cardio-respiratory illness [2]. An association between PM2.5 and mortality was also found as part of the Cancer Prevention Study II, where data on 1.2 million people across the USA was prospectively collected. Overall, PM2.5 levels decreased in the USA from 1979 to 2000, which was the span over which air pollution data was collected. Whether assessed at the start or end of the study, air pollution as reflected by PM2.5 levels was linked with all-cause, cardiorespiratory and lung cancer deaths. For a 10 mg/m3 increase in PM2.5, there was a relative risk of 1.06 (95% CI 1.02–1.11), 1.09 (95% CI 1.03–1.16) and 1.14 (95% CI 1.04–1.23) for all-cause, cardio-pulmonary and lung cancer mortality, respectively [3]. In a follow-up study of the Harvard Six Cities cohort, all-cause, cardiopulmonary and lung cancer mortality were again found to parallel PM2.5 levels [4]. As seen in CPSII, PM2.5 levels decreased in all six cities, with greatest reduction in the most polluted cities. For every 10 mg/m3 decrease in PM2.5 seen in the follow-up period, there was a reduction in all-cause mortality (RR ¼ 0.73; 95% CI 0.57–0.95). This was seen for cardio-respiratory mortality, but not for lung cancer deaths. This follow-up study reiterated the association between PM2.5 levels and mortality, and also suggests that health effects of air pollution can be attenuated [4]. Fine particulate matter and morbidity PM2.5 has also been studied in terms of morbidity among both adults and children. Hospital admissions in a Medicare population were recently reviewed in conjunction

410

CH 28 TRADITIONAL URBAN POLLUTION

with available PM2.5 levels in 204 US counties to examine the short-term effects of air pollution on cardiopulmonary morbidity. Daily variations in PM2.5 were linked to change in hospital admission rates for heart failure, COPD, respiratory tract infections, cerebrovascular disease, peripheral vascular disease, ischemic heart disease and heart rhythms. Hospitalization rates for up to 2 days of lag time after the measured PM2.5 level were examined. Cardiovascular hospitalizations were most likely on day 0 (except for ischemic heart disease), whereas there was more variability in timing of hospitalization for respiratory illnesses. For every 10 mg/m3 increase in PM2.5, there was a 1.28% higher risk of same-day hospitalization due to heart failure. The authors calculated that annual admissions for heart failure would drop by 3156, in these 204 counties, if PM2.5 was reduced by 10 mg/m3. Hospitalizations for respiratory tract infections and COPD would be reduced by 2085 and 990, respectively [5]. Some regional variation was also seen, with greater cardiovascular effect size seen in Eastern counties. Fine PM and cardiovascular morbidity Cardiovascular health effects include reduced heart rate variability as a risk factor for mortality, especially in elderly subjects. Diminished heart rate variability was linked with higher PM2.5 levels in a small, elderly population in Utah. More recently, a study of the cardiovascular effects of long-term air pollution in a large cohort of postmenopausal women without pre-existing heart disease was published (Women’s Health Initiative Observational Study). An adjusted hazard ratio of 1.24% (95% CI 1.09–1.41) for time to first cardiovascular event, including cerebrovascular events, was associated with a 10 mg/m3 increase in PM2.5. Other pollutants were measured, but were not significantly linked to cardiac morbidity. The strongest findings were for mortality endpoints, and especially for death due to definite coronary heart disease. Higher hazard ratios for mortality endpoints were found than in previous cohort studies which included men, which may reflect greater vulnerability of women in terms of air pollution or differences in methodology of the studies. Theories that have been offered to help explain the effect of air pollution on cardiovascular disease include accelerated atherosclerosis, change in autonomic control and increased inflammation. Fine PM and respiratory morbidity Clinical studies assessing the association of PM2.5 on respiratory morbidity have also been performed. Populations with pre-existing illnesses seem to be at greater risk of negative effects of air pollution. In APHEA2, a 10 mg/m3 rise in PM10 levels was correlated with an increase in respiratory admissions, including children and adults with acute asthma and COPD, by approximately 1%. In another study, children with asthma were given personal exposure monitors and followed for 2 week periods. FEV1 (percentage predicted) was found to be negatively associated with the level of personal, fine PM exposure. Nonmobile measurements of PM were also recorded and associated with pulmonary function, but more weakly than personal PM levels. In addition, personal PM had a larger effect in atopic boys with susceptibility to indoor allergens. Children with more severe asthma also seem to be more susceptible to effects of particulate air pollution, in a study of schoolchildren in Denver, Colorado. PM2.5 levels were found to be highest in the morning hours when children were traveling to school. Higher morning PM2.5 levels resulted in greater use of bronchodilators at school, also suggesting rapid onset of symptoms. This relationship was also more pronounced in

28.3

SULFUR OXIDES

411

children with severe asthma. In addition, urinary leukotriene E4 was measured during the school day and was associated with morning PM2.5 levels. Another personal monitor study in Seattle, Washington examined lung function effects of particulate air pollution in children with asthma and adults with COPD. Decrease in FEV1 was associated with PM2.5 measurement at a central location, after a 1-day lag, in patients with COPD, although it did not correlate with personal levels. In asthmatic children not on antiinflammatory medications, PM2.5 was associated with declines in MMEF, FEV1 and PEF. While some change in lung function was seen overall, the correlation was stronger in asthmatics not on anti-inflammatory medications, lending support to possible PM triggering of inflammatory mechanisms [6]. Elevated exhaled nitric oxide was associated with PM2.5 levels in these same children in an earlier report, further highlighting the potential inflammatory effects of air pollution. While further categorizing the respiratory effects of air pollution, these studies also point out that use of daily averages of PM levels may not be sufficient to fully understand the health effects of particulate air pollution. Associations between respiratory illness and particulate air pollution have been further strengthened by studies involving experimental exposures to PM in humans, which help define underlying mechanisms for disease causation. In one study, healthy volunteers were exposed to CAPS (concentrated ambient particles 0.1–2.5 mm in size) for 2 hours. Final exposure concentrations ranged from 23.1 to 311.1 mg/m3, and were dependent on variation in outside particulate levels. There were no differences in pulmonary function testing or symptoms between those exposed to CAPS versus filtered air controls. However, increases in cellularity and neutrophil counts of bronchoalveolar lavage fluid were seen after CAPS exposure as compared with filtered air. In addition, bronchoalveolar lavage fluid neutrophils appeared to increase in a dose-dependent manner, highlighting a possible inflammatory pathway of particulate air pollution induced illnesses. In recent literature, particulate air pollution has been increasingly associated with adverse health effects. As reviewed, there is evidence for both increased mortality and cardio-respiratory morbidity linked to PM exposure. While earlier studies focused on short-term mortality risk, the current body of research supports an increased chance of long-term consequences as well. There has also been focus on highly susceptible populations, such as those with chronic respiratory illnesses as well as the elderly. Work on elucidating the pathogenesis of PM-associated cardiovascular and respiratory morbidity has also progressed. In the USA, the National Ambient Air Quality Standards (NAAQS) for PM were slightly lowered in 2006 on the basis of growing evidence for adverse PM-related health effects. Adverse health outcomes have been seen even at low PM concentrations in recent time-series studies and many argue, in fact, that PM NAAQS are not stringent enough.

28.3

Sulfur oxides

28.3.1 Characteristics of sulfur oxides Sulfur is a major component of fossil fuel sources such as coal and oil, as well as several common metal ores such as iron, zinc, and copper. Combustion of these materials leads to the formation of the gas sulfur dioxide, which may dissolve in water vapor to form

412

CH 28 TRADITIONAL URBAN POLLUTION

acidic aerosols that eventually fall to the earth in the form of acid rain. These acidic byproducts of sulfur combustion primarily concentrate in lakes and streams, often resulting in a decrease in pH significant enough to reduce, or in some cases eliminate natural aquatic wildlife populations. Sulfur dioxide may also combine with other particles in the air to form sulfate particulate matter, which contributes to visual pollution, particularly in summer months when it forms a milky, white haze in the afternoon. While ambient SO2 concentrations are highest close to the source of production (coal-fired power plants, petroleum refineries, smelters), sulfate particles can have an impact relatively far away since their small size lends to long distance transport. Intercontinental transport of SO2 and other toxic emissions promises to be an important policy issue for years to come.

28.3.2 Acute health effects Sulfur dioxide is rapidly absorbed by mucosal surfaces of the nasopharynx and upper airway. It is readily soluble in epithelial lining fluid, forming acidic species that result in cellular damage. Although this rapid upper airway absorption protects the lower airways from the irritant effect, the increase in minute ventilation and tidal volume during exercise overcomes its absorptive capacity, often resulting in lower airway effects. Acute exposure to sulfur dioxide can result in a variety of symptoms, most commonly dyspnea, cough, and exacerbation of chronic cardio-pulmonary disease. Controlled chamber experiments, which allow for measurements of the specific effects of SO2, have demonstrated a spectrum of responses in healthy individuals, from no effect to marked bronchoconstriction. The asthmatic population is generally more susceptible, but in these controlled settings without the additive effects of other pollutants, the effects are generally reversible in minutes to hours. The minimum concentration required to demonstrate a decline in lung function in normal is approximately 1000 ppb (2860 mg/m3), whereas asthmatics may have significant reductions in lung function at as low as 400 ppb (1144 mg/m3). For reasons mentioned above, the effects of SO2 may be augmented by exercise, and in one study an interaction was found when SO2 was administered with cold dry air.

28.3.3 Effects of chronic exposure The effects of long-term exposures to SO2 are less clear, and there is controversy in the literature as to its negative effect independent of sulfate and nonsulfate PM. As part of the APHEA project, a 3% increase in daily mortality was shown with an increase in SO2 by 50 mg/m3 (95% CI 2–4%) that was independent of PM10. However, six other studies that resulted from APHEA data failed to replicate these findings. Several Chinese investigators have been able to demonstrate an effect of SO2 on morbidity and mortality independent of total suspended particles in a variety of locations in China, which may reflect a difference in population susceptibility or unique characteristics of industrial emissions in the region. Since PM2.5 may be the more specific causal agent in PMrelated disease, further data on SO2 effects independent of PM2.5 would be valuable in establishing an independent effect. One such analysis of data from Chongqinq, China

28.4

NITROGEN OXIDES

413

did show independent increases in relative risk of respiratory and cardiovascular mortality independent of PM2.5. Overall, SO2 should be viewed as an airway irritant with several demonstrated acute, negative effects on respiratory symptoms and physiology, while its long-term effects on morbidity and mortality remain a topic for investigation.

28.3.4 Regulatory actions Worldwide sulfur emissions peaked in 1989, and have declined since then, although they remain well above those at the beginning of last century. Initial efforts to decrease the local levels of SO2 involved mandating the construction of tall (in some cases 500 feet high) smokestacks so that SO2 would disperse over a greater area and reduce the effects on the local population. While this policy was successful in reducing the human impact of SO2, the generation of PM remained unabated until policy to decrease the total amount of sulfur emissions produced was enacted. The first Clean Air Act was passed by the UK during the 1950s after recognizing the health impacts of the London Smog, and the USA followed suit in 1963 with subsequent modifications, most notably in 1970 with the establishment of the Environmental Protection Agency (EPA). The most recent revision of the Clean Air Act in 1990 included a specific Acid Rain Program that implemented a ‘cap and trade’ system whereby individual power plants were given an allowance of emissions per unit of energy when compared with a historical standard. If this allowance is then exceeded, additional emissions ‘credits’ may be bought or traded for on the open market. This policy was hailed as an approach to air pollution control that allowed for some flexibility within the industry to reduce emissions without necessarily forcing the immediate closure of older plants that would be costly to update to cleaner technologies. As a result of the initial phase of the Acid Rain Program, SO2 emissions in the USA declined by 17% between 1990 and 1998, and Phase II of the program promises further reductions in years to come. As mentioned previously, concerns about industrialization in Asia and other parts of the developing world temper optimism about a true reduction in sulfur emissions globally, since many of the improvements made in developed countries could easily be nullified by increased emissions worldwide.

28.4

Nitrogen oxides

28.4.1 Characteristics of nitrogen oxides Although there are many known sources of nitrogen oxides in rural settings related to nitrogenous fertilizers and manure management, traditional urban sources (excluding vehicular) arise primarily from combustion of fossil fuels such as coal and oil for electricity production, with a lesser contribution by sewage treatment plants. Fossil fuelrelated power generation initially leads to release of nitrogen oxide, which can be further oxidized to nitrogen dioxide in the atmosphere. Nitrogen dioxode is a colorless, odorless gas, whereas nitrogen oxide has an odor and a reddish-brown color that contributes to visible pollution independent of associated particulates. The combination of these and other oxidized nitrogen species are typically referred to as NOx. As will

414

CH 28 TRADITIONAL URBAN POLLUTION

be described in subsequent sections, the primary health effects of NOx species are ozone formation via interactions with volatile organic compounds in the presence of sunlight. In addition, NOx contributes to acid rain along with sulfur oxides, and has effects on water systems independent of pH by upsetting the balance of nutrients required by aquatic plants and animals. This process of excess nitrogen deposition is termed eutrophication, and can result in algae overgrowth that eventually depletes oxygen from the body of water creating a ‘dead’ zone. Nitrous oxide (N2O), a lesser component of NOx, persists in the atmosphere for approximately 120 years and is thought to be a significant contributor to global warming.

28.4.2 Acute health effects In terms of direct health effects of nitrogen oxides, NO2 has widely recognized effects from known occupational exposures (silo-filler’s disease), during which a highly concentrated exposure leads to severe respiratory symptoms and adult respiratory distress syndrome. In the case of ambient pollution, however, studies vary in their ability to demonstrate or refute the specific role of NOx in human disease due to the large populations required and potential confounding from other pollutants. Controlled experiments that simulate levels commonly observed in the atmosphere have shown no effect in healthy subjects at NO2 concentrations up to 0.60 ppm, but asthmatics were demonstrated to have a decrease in FEV1 during exercise and cold air inhalation after exposure to NO2 at 0.30 ppm.

28.4.3 Effects of chronic exposure Large-scale population based studies are less conclusive, although several are suggestive. A retrospective analysis of hospital asthma admissions in Hong Kong found the relative risk of admission was 1.028 (95% CI 1.021–1.034) for every 10 mg/m3 rise in NO2 concentration. Similar findings were obtained in a study that included controls for four types of pollen, as well as the more usual PM, SO2 and ozone. Increases in viral respiratory tract infections have been observed in asthmatic children, and patients over the age of 65, and there is some in-vitro data to suggest altered host response to infection with respiratory syncytial virus. In terms of mortality, although some found no association with increased mortality from NO2 independent of PM, several others found positive associations with statistically significant increases in total mortality 0.30% (95% CI 0.25–0.35%), cardiovascular disease mortality 0.41% (95% CI 0.34–0.49%), and respiratory mortality 0.34% (95%CI 0.17–0.51%) for every 10 mg/m3 increase in NO2 in an analysis of APHEA-2 data [7]. A cohort study of 4800 German women living in North Rhine–Wesphalia found that both total and cardiopulmonary mortality correlated with a rise in the NO2 interquartile range by 16 mg/m3, when adjusted for smoking and socioeconomic status [8].

28.4.4 Regulatory actions As in the case of sulfur oxides, levels of nitrogen oxides have been decreasing in the USA and Europe as the result of legislation. Data from the UK National Atmospheric

28.5

OZONE

415

Emissions Inventory show energy generating emissions declined by approximately 45% between 1990 and 2003, and US EPA data show a 30% decline over a similar period. These data do not take into account reductions due to a decrease in industrial activity in developed countries, but also fail to note the impact of increased industrialization in Asia. In summary, nitrogen oxides in concentrations commonly observed in the atmosphere are likely contributors to cardiopulmonary morbidity in susceptible populations; however, definite mortality associations remain to be fully elucidated (Table 28.2).

28.5

Ozone

28.5.1 Characteristics of ozone Ozone is not a directly emitted pollutant, but rather is generated by the interaction of multiple pollutants in the atmosphere in the presence of sunlight. Volatile organic compounds emitted by industry, solvents and motor vehicles (gasoline), combine in the atmosphere with nitrogen oxides (NOx) generated by combustion of coal and other fossil fuels to form atmospheric ozone (O3). This interaction was first noted by A.J. HagenSmit, a Dutch chemist working at the California Institute of Technology in the 1940s, during a period of intense smog in the Los Angeles area. Although ozone serves as protection from UV radiation when it naturally forms high in the stratosphere (15–35 km above sea level), high concentrations near the Earth’s surface are associated with adverse health effects. Ozone levels typically peak during summer afternoons given the longer duration of sunlight, and susceptible individuals should be encouraged to stay indoors as much as possible during these periods.

28.5.2 Acute health effects Ozone has a potent oxidizing and direct toxic effect on cell membranes that leads to the generation of intracellular peroxides and free radicals. In vitro studies show that O3 is able to deactivate alpha1-antitrypsin, which could theoretically increase susceptibility to emphysema. In terms of acute effects in humans, as with other pollutants, the response is variable and largely depends on individual susceptibility. A heterogeneous sample of asthmatics and nonasthmatics will demonstrate a significant drop in FEV1 after controlled ozone exposure in only 10–20% of subjects, while others have mild or even no effect from the exposure. Contrary to these findings, an hourly decrease in lung function was shown in 10 healthy volunteers who were exposed to 120 ppb of O3 for 6.6 hours while performing 5 hours of moderate exertion (similar to outdoor labor). These findings were subsequently replicated using lower concentrations of ozone, with 80 ppb being the lowest concentration to show a significant effect. Studies of inflammatory mediators in bronchoalveolar lavage as well as nasal airway lavage, have shown increases in neutrophils, immunoglobulins, elastase and a variety of other markers of inflammation. Airway responses to allergen can also be enhanced by preceding ozone exposure.

Interaction of VOCs, nitrogen oxides and sunlight VOCs derived from vehicle exhaust, industry, solvents

Vehicle exhaust Combustion of fossil fuels Sewage treatment plants Fertilizers and manure in rural settings Coal burning plants and other fossil fuel use such as smelters Coal-fired power plants, diesel and other vehicle exhaust, industry, natural sources

Ozone

NOx

VOC, volatile organic compounds.

Carbon monoxide Traffic exhaust fumes

Particulate pollution

SO2

Main sources

Pollutant

Bronchoconstriction in asthmatics (with exercise) Possible increased mortality separate from particle effects Association with firing of defibrillators Cardiovacular and COPD hospitalization

Asthmatics Athletes Elderly Those with cardiovascular risk factors or cardiovascular disease Possibly women Asthmatics and those with COPD

Elderly Those with cardiovascular risk factors or cardiovascular disease

Cardiovascular mortality All-cause death, including lung cancer and cardiorespiratory deaths Asthma emergency visits Cardiac events

Chest tightness, difficulty in full inspiration, airflow limitation, asthma exacerbation, increased airway inflammation, increased response to allergen, increased emergency visits and hospitalization for asthma, possibly increased risk of onset of asthma Significant effect on mortality separate from particle effects Increased risk of respiratory viral illness in children Airflow limitation in asthmatics (with exercise) Unclear if increases in cardiorespiratory mortality separate from particle effects

Genetically susceptible individuals Asthmatics Children Endurance athletes

Children

Health effects

Susceptible populations

Table 28.2 Summary of health effects of outdoor air pollutants (dependent on exposure concentrations and susceptibility of population)

416 CH 28 TRADITIONAL URBAN POLLUTION

28.6

AIR TOXICS

417

28.5.3 Chronic health effects Studies correlating increases in environmental ozone and health indicators are numerous and fairly consistently demonstrate adverse effects. The Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society of 1996 included several statements regarding ambient ozone resulting in increases in respiratory symptoms, emergency room visits and hospitalizations for exacerbations of asthma and other respiratory diseases, as well as some of the physiological and molecular effects mentioned above. This statement was in part fueled by studies by multiple groups studying air pollution in general that found effects of ozone independent of particulates, SO2 and other pollutants. Despite these findings, policy makers in the USA at times cite ‘scientific uncertainty’ regarding the negative health effects of ozone when pressed to impose stricter standards on ambient ozone levels.

28.5.4 Effects on human mortality Many large-scale, population-based studies have attempted to show a relationship between ambient ozone levels and mortality. Recent data demonstrated a significant association between short-term changes in ozone and noninjury related mortality across 95 US urban centers utilizing databases developed for the National Morbidity, Mortality, and Air Pollution Study. A 10 ppb increase in ozone levels showed a 0.52% increase in daily mortality (95% posterior interval [PI] 0.27–0.77%), and a 0.64% increase in cardiovascular and respiratory mortality (95% PI 0.31–0.98%) in the subsequent week. Similar conclusions were drawn in a study of 23 European cities (APHEA), where increases of 0.45% of cardiovascular deaths and 1.13% of respiratory deaths were observed during summer months following increases in ozone concentrations. In addition, several meta-analyses support these hypotheses as well. As with sulfur oxides, the potential for confounding by PM is omnipresent; however, results indicate a robust effect independent of PM10 or PM2.5.

28.6

Air toxics

28.6.1 Benzene Potential sources of exposure include exhaust from vehicles, solvents used in manufacturing plants and hazardous waste areas. Health effects of benzene are probably the result of its metabolites, including benzoquinone, benzene oxide and muconaldehyde. While it has been recognized as a carcinogen for hematologic malignancy in occupational settings, correlation between exposure level and hematologic risk has also been variable. Several nonoccupational studies have linked childhood leukemia with residence near petroleum industries and gas stations, which may point to the effects of ambient benzene exposure. Little is known about other effects of benzene at the low exposure levels found in outdoor air.

418

CH 28 TRADITIONAL URBAN POLLUTION

28.6.2 Other exposures Outdoor air may also contain other pollutants that can affect the lung. Examples include chemicals from industrial sources in the area. Cases of sensitization have been reported from beryllium and diisocyanates in the neighborhood around companies using these. Asbestos fibers are in the air in urban settings at low levels, but in areas close to asbestos mines there have been increased risks of mesothelioma reported (although it may be difficult to separate the effects of outdoor exposure from second-hand indoor exposure from family members who worked in the mines).

References 1. Pope, C.A. (1991) Respiratory hospital admissions associated with PM10 pollution in Utah, Salt Lake, and Cache Valleys. Arch. Environ. Hlth 46: 90–97. 2. Dockery, D.W., Pope, C.A., Xu, X. et al. (1993) An association between air pollution and mortality in six U.S. cities. New Engl. J. Med. 329: 1753–1759. 3. Pope, C.A., Burnett, R.T., Thun, M.J. et al. (2002) Lung cancer, cardiopulmonary mortality and long-term exposure to fine particulate air pollution. J. Am. Med. Assoc. 287: 1132–1141. 4. Laden, F., Schwartz, J., Speizer, F.E., Dockery, D.W. (2006) Reduction in fine particulate air pollution and mortality. Am. J. Respir. Crit. Care Med. 173: 667–672. 5. Dominici, F., Peng, R.D., Bell, M.L. et al. (2006) Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. J. Am. Med. Assoc. 295: 1127–1134. 6. Trenga, C.A., Sullivan, J.H., Schildcrout, J.S. et al. (2006) Effect of particulate air pollution on lung function in adult and pediatric subjects in a Seattle panel study. Chest 129: 1614–1622. 7. Samoli, E., Aga, E., Touloumi, G. et al. (2006) Short-term effects of nitrogen dioxide on mortality: an analysis within the APHEA project. Eur. Respir. J. 27: 1129–1138. 8. Gehring, U., Heinrich, J., Kramer, U. et al. (2006) Long-term exposure to ambient air pollution and cardiopulmonary mortality in women. Epidemiology 17: 545–551.

Further reading Balmes, J.R., Fanucchi, M.V., Rom, W.N. (2007) Ozone, a malady for all ages. Am. J. Respir. Crit. Care Med. 176: 107–108. Bernstein, J.A., Alexis, N., Barnes, C., Bernstein, I.L., Bernstein, J.A., Nel, A., Peden, D., Diaz-Sanchez, D., Tarlo, S.M., Williams, P.B. (2004) Health effects of air pollution. J. Allergy Clin. Immunol. 114: 1116–1123. Chen, T.M., Shofer, S., Gokhale, J., Kuschner, W.G. (2007) Outdoor air pollution: overview and historical perspective. Am. J. Med. Sci. 333: 230–234. Committee of the Environmental Occupational Health Assembly of the American Thoracic Society (1996) Health effects of outdoor air pollution. Am. J. Respir. Crit. Care Med. 153: 3–50. Committee of the Environmental Occupational Health Assembly of the American Thoracic Society (1996) Health effects of outdoor air pollution Part 2. Am. J. Respir. Crit. Care Med. 153: 477–498. Delfino, R.J., Sioutas, C., Malik, S. (2005) Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ. Health Perspect. 113: 934–946. Gryparis, A., Forsberg, B., Katsouyanni, K. et al. (2004) Acute effects of ozone on mortality from the ‘Air Pollution and Health: A European Approach’ Project. Am. J. Respir. Crit. Care Med. 170: 1080–1087.

FURTHER READING

419

Schwartz, J., Zanobetti, A., Bateson, T. (2003) Morbidity and mortality among elderly residents of cities with daily PM measurements In Revised Analyses of Time-Series Studies of Air Pollution and Health. Special Report Health Effects Institute Boston, MA. Vedal, S. (2002) Update on the health effects of outdoor air pollution. Clin. Chest Med. 23: 763–775, vi. Viegi, G., Maio, S., Pistelli, F., Baldacci, S., Carrozzi, L. (2006) Epidemiology of chronic obstructive pulmonary disease: health effects of air pollution. Respirology 11: 523–532.

29 Traffic-related urban air pollution Steven M. Lee1 and Mark W. Frampton2 1 2

Kaiser Permanente Fontana Medical Center, Fontana, CA, USA University of Rochester Medical Center, Rochester, NY, USA

29.1 Introduction There is widespread recognition that pollution of the air we breathe, by cumulative products of human activity, adversely affects health. Studies of air pollution find evidence for health effects at ever-lower ambient concentrations, leading to continual tightening of air quality standards in developed countries. While these developed countries work to minimize emissions in order to improve air quality, many developing countries are experiencing massive increases in air pollution as a result of economic growth in the absence of emissions controls. Studies over the last two decades show that current pollution levels in cities around the world worsen the burden of lung and heart disease, increase mortality and may affect fetal and newborn growth and development. Traffic-related emissions represent a major contribution to the burden of ambient air pollution. The role that traffic pollution plays in air pollution health effects, relative to other emission sources such as industry and power generation, remains uncertain. However, the public health impact of traffic-related air pollution is not inconsequential. K€ unzli et al. [1] studied the overall public health impact of traffic-related air pollution in three European countries: Austria, France and Switzerland. While the individual risk for a significant health related impact of air pollution was small, the public health impact was significant. In the three countries, more than 40,000 deaths (6% of total mortality) were attributable to increases in particulate air pollution, with about 20,000 deaths attributable to traffic-related pollution. The costs associated with the increased mortality and morbidity amounted to 1.7% of the gross domestic product, a cost exceeding that for traffic accidents [2]. Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

422

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

Considerable effort is being expended to reduce engine emissions, with some notable success. However, the potential benefits of reduced emissions are often negated by the increased number of vehicles on the road, increased miles traveled by those vehicles, and the persistence of older, high-emitting vehicles. It is anticipated that traffic-related emissions, and their health effects, will increase most dramatically in developing countries. The growth of vehicle sales in Asia is likely to far outstrip that of the rest of the world in the coming decades. Emission and pollution controls have not received a major priority in many developing countries, and thus marked increases in trafficrelated emissions are expected. The goal of this chapter is to provide a perspective on our current understanding of the health hazards associated with exposure to traffic related air pollution. We will begin with a historical overview, describe the nature of traffic emissions, review current evidence that traffic emissions adversely affect health and finally identify key knowledge gaps and future approaches to the problem.

29.2 History of traffic-related air pollution Traffic-related air pollution started with the invention and widespread use of gasoline and diesel-powered motor vehicles. Automobiles were first developed in the nineteenth century, and were predominately powered by steam or electric engines. In 1876, Nicolaus Otto developed the first practical four-stroke internal combustion engine, and used it to power a motorcycle. Gottlieb Daimler constructed the first fourwheel automobile powered by a gasoline engine in 1886. Rudolf Diesel, who was born in Paris, discovered that fuel could be ignited in an engine without a spark. He was granted a patent in 1898 for the first diesel engine. Mass production of gasolinepowered automobiles was underway by the early 1900s, with Henry Ford pioneering assembly-line mass production, and making the automobile available to the masses. The increasing use of the automobile meant that people no longer had to live and work in the city. The past 50 years has seen a steady migration out of cities to the suburbs as improved roadways made this practical, especially in the USA. Commuting to work has contributed to an increased dependence on motor vehicle transport and marked increases in miles traveled. The numbers of cars on the road is increasing in many parts of the world. Automobile traffic in Europe is increasing much more rapidly than other modes of transportation (Figure 29.1). China is experiencing an explosion in the number of automobiles (Figure 29.2), with the number of registered vehicles increasing from about 600,000 in the year 2000, to 3.8 million in 2005. As the number of motor vehicles and the number of miles they travel increases around the world, vehicle emissions will be a growing international concern. The realization that traffic-related emissions have adverse health effects is a fairly recent phenomenon. Historical air pollution events in the Meuse Valley in Belgium in 1930, Donora, Pennsylvania in 1948, and London, UK in 1952 demonstrated unequivocally that air pollution can kill. The London Fog episode ranks as one of the worst natural disasters in history. During four days of stagnant air and temperature inversion over London, concentrations of particulate matter and sulfur dioxide soared, and more than 4000 people died. These episodes made it starkly clear that air pollution was more

29.2

HISTORY OF TRAFFIC-RELATED AIR POLLUTION

423

Figure 29.1 Volume of passenger transport in the 15 countries belonging to the EU before May 2004, in 1990, 1998 and 2010 (projection). From World Health Organization [34], reproduced by permission of World Health Organization

than just a nuisance, and spurred efforts to control emissions and establish air pollution standards, including the passage of the Clean Air Act by the US Congress in 1970. The pollution causing these historical air pollution episodes predominantly represented emissions from industrial processes and coal burning for home heating, not traffic. In developed nations, such ‘point source’ emissions have decreased, in part through improved emission control technology and air pollution regulation, but also as

Figure 29.2 New car registrations in China, 1998–2005. From: http://www1.eere.energy.gov/ vehiclesandfuels/facts/2006_fcvt_fotw438.html, accessed 2 April 2008

424

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

a consequence of outsourcing of industrial production and changing home heating from coal burning to natural gas and electric. In contrast, traffic emissions continue to increase. Today, in developed countries, most human exposure to outdoor air pollution comes from traffic. Traffic has long been acknowledged as a major contributor to air pollution in major US cities. Table 29.1 summarizes the efforts and milestones in controlling traffic related pollution in the USA. Deterioration of air quality in Los Angeles and other cities in the 1950s and 1960s, and the growing recognition of health risks associated with air pollution, spurred the US Congress to pass sweeping air pollution legislation in 1970. The Clean Air Act established the new US Environmental Protection Agency (EPA) and promulgated an aggressive plan to reduce automobile emissions. The subsequent story of efforts to reduce traffic related air pollution is one of success mixed with compromise and delay. For example, the Clean Air Act emissions standards targeted for 1975 were

Table 29.1

A brief history of US traffic air pollution control measures

Year

Action

1970

Congress passes Clean Air Act US Environmental Protection Agency (EPA) established EPA directed to set ‘National Ambient Air Quality Standards’ for six pollutants A 90% reduction in emissions from new automobiles required by 1975 Congress delays the hydrocarbon and carbon monoxide standards until 1978 Corporate Average Fuel Economy (CAFE) program: more stringent fuel economy standards Catalytic converters introduced Unleaded gasoline introduced Congress amends Clean Air Act Hydrocarbon, carbon monoxide and nitrogen oxides standards delayed again New cars meet amended Clean Air Act standards for the first time EPA lowers the amount of lead allowed in gasoline Inspection and Maintenance programs established EPA adopts stringent diesel emission standards Phase-out of leaded gasoline is completed EPA sets fuel volatility limits aimed at reducing evaporative emissions EPA limits diesel fuel sulfur content Congress amends Clean Air Act: further reductions in emissions, gives EPA authority to regulate nonroad vehicles Oxygenated gasoline introduced in cities with high carbon monoxide levels EPA regulations target marine engines Emission standards for diesel-powered locomotives Emission standards for nonroad diesel engines Reduced emission standards for new large marine diesel engines Reduced emission standards for SUVs and light-duty trucks Plans to reduce sulfur in on-road diesel fuel by 97% by mid-2006 EPA identifies 21 mobile source hazardous pollutants (air toxics) and regulates toxic emissions Japanese electric–gasoline hybrid cars hit market

1974

1975 1977 1981 1982 1983 1985 1986 1989 1990 1990 1992 1996 1997 1998 1999 2000

2001

Modified from: http://www.epa.gov/otaq/invntory/overview/solutions/milestones.htm.

29.3

ENGINES AND EMISSIONS

425

Table 29.2 Strategies for reducing motor vehicle emissions More stringent regulation of vehicle emissions Technological advances in engine design Inspection and maintenance of vehicles Reduced sulfur in fuels Increased fuel prices Reduction in miles traveled: Carpooling Increased use of public transport City planning

not actually met until 1981. Nevertheless, regulatory efforts overall have been successful in reducing vehicle emissions in the nearly 40 years since the passage of the Clean Air Act. However, much of the benefits related to reduced vehicle emissions have been negated by increased numbers of vehicles and miles traveled. Table 29.2 lists approaches to limiting vehicular travel and emissons.

29.3

Engines and emissions

29.3.1 Combustion engines In order to understand traffic emissions, we must first learn about the various types of combustion engines. Modern combustion engines are internal or external. Diesel and gasoline engines, the two major sources of traffic-related air pollution, are both internal combustion engines. External combustion engines include steam and Stirling engines. Since they do not contribute significantly to traffic-related air pollution, we will not discuss them further in this chapter. Internal combustion engines have been widely used to power modern vehicles, including almost all automobiles, trucks, motorcycles, boats and aircraft. Their advantages include high power-to-weight ratios and excellent fuel energy density. In internal combustion engines, the combustion of fuel and oxidizer occurs in a combustion chamber (a closed system). Thus, gases are generated at high temperature and pressure and are permitted to expand. This expansion of hot gases applies force to the solid parts of the engine, such as pistons and rotors. Figure 29.3 shows a representative design of an internal combustion engine. A commonly used internal combustion engine is the diesel engine. In this type of engine, combustion is initiated by the process of self-ignition of the fuel, which is injected after the air is compressed in the combustion chamber. A diesel engine is more efficient than a gasoline engine of equivalent power, resulting in lower fuel consumption. This greater efficiency leads to production of less carbon dioxide (CO2) and carbon monoxide (CO) per unit distance, compared with the gasoline engine. The second type of internal combustion engine is the gasoline (petrol) engine. In gasoline engines, the fuel and air are pre-mixed before the compression stroke, and combustion is ignited with a spark plug. Gasoline alone has a tendency to ignite early when used in high compression internal combustion engines, so additives are almost always used to retard ignition. Lead was historically used as an additive, but fell out of

426

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

Figure 29.3 Internal combustion engine. The cross section shows one cylinder of a four-stroke internal-combustion engine. In the first stroke (shown), a cam (left) compresses a valve spring, opening the intake valve to admit the fuel-air mixture to the cylinder. Both valves then close, the mixture is compressed by the piston, and current is sent to the spark plug. Ignited by the spark plug, the burning mixture forces the piston down, producing power to turn the crankshaft and run the car. Another cam (right) opens the exhaust valve and the burned exhaust gases exit. From MerriamWebster’s Collegiate Encyclopedia,
2000 by Merriam-Webster Inc. Reproduced by permission of Merriam-Webster. Available from: http://www.britannica.com/eb/art-66070/Cross-sectionshowing-one-cylinder-of-a-four-stroke-internal (accessed 28 April 2008)

favor and was removed in the 1980s, because of the discovery of its adverse environmental and health effects. Lead has been replaced by other additives, such as methylcyclopentadienyl manganese tricarbonyl (MMT), aromatic hydrocarbons, ethers and alcohol (ethanol or methanol).

29.3.2 Engine emissions In this section, we will discuss some of the potential environmental issues created by diesel and gasoline engines. Diesel engines can contribute to traffic air pollution, because the exhaust contains large numbers of ultrafine particles containing elemental and organic carbon – so-called ‘black soot’. This may increase the risk for asthma and cancer. Diesel exhaust also includes gaseous pollutants such as nitrogen oxides (NOx), which contribute to the photochemical production of ozone. Because of the potential health risks associated with diesel exhaust, the EPA has enforced the 2008 Locomotive and Marine Diesel Rule, which mandated that all new diesel engines sold in the USA, starting on 1 January 2007, must meet more stringent emission standards with

29.3

ENGINES AND EMISSIONS

Figure 29.4

427

Clean diesel technology.

particulate matter (PM) reductions of about 90% and NOx reductions of about 80%, compared with engines meeting the previous standards. As a result of this regulation, the newer diesel engines have been designed with addition of some of the following features: (1) a diesel particulate filter to filter out PM from the exhaust system; (2) diesel oxidation catalysts to break down pollutants into harmless gases; (3) exhaust gas recirculation, selective catalytic reduction, and NOx absorber technologies to reduce NOx emissions; (4) utilization of ultra-low sulfur diesel fuel; and (5) a new combustion chamber to maximize power output, fuel efficiency and reduce combustion emissions (Figure 29.4). However, because diesel engines generally have a long road life, years must pass for the new emission reductions to have a beneficial effect. Like diesel engines, gasoline engines are also important sources of air pollution. Lead additive in gasoline is an important example. Although leaded gasoline was eliminated in the USA in 1986, vehicles running on leaded gasoline prior to that time released a significant amount of lead into the atmosphere, with the potential for adverse health effects, including reduced cognitive abilities, lethargy, impaired hearing acuity, hyperactivity, hypertension, abdominal symptoms, impaired hemoglobin synthesis, male infertility and developmental delay in children. Combustion of unleaded gasoline can still lead to air pollution with the release of many compounds, such as CO, CO2, NOx, hydrocarbon (HC) and PM. Furthermore, gasoline vapors evaporating from the tank react in the sunlight to produce photochemical smog in the atmosphere.

29.3.3 Emission patterns The emissions from road transport can be categorized into four main classes: (1) hot emissions; (2) cold-start emissions; (3) emissions from fuel evaporation; and (4) nonexhaust PM emissions. In this section, we will discuss each of the four emission patterns in detail.

428

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

Hot exhaust emissions are those that occur when the engine has warmed up to its normal operating temperature. Parameters that affect hot emissions include: mean vehicle speed, driving dynamics, vehicle type, fuel and road type. For instance, high vehicle speed demands higher power output, which can in turn increase emissions. On the other hand, when automobiles travel at slow speeds in city traffic, the frequent stopand-go conditions, with increased frequency and intensity of vehicle acceleration and deceleration, can also enhance emissions. Cold-start emissions are pollutants generated immediately after engine start-up, before reaching normal operating temperature. A vehicle engine generally emits at a higher rate when it is cold than when it has warmed up to the designed operating temperature. For this reason, a decrease in ambient temperature will increase cold-start exhaust emissions. Other dependent parameters for cold-start emission include vehicle technology and distance traveled when the engine is cold. Cold-start emission of pollutants is concentrated mainly in urban areas, where the average trip distance is short, and car engines are turned on and off at high frequency. This leads to relatively high emissions per distance driven, compared with long-distance driving on roads outside of urban areas. Emissions also originate from evaporative losses, which consist of diurnal loss, hot soak loss and running loss. The diurnal rise in ambient temperature increases the volatility of the fuel and expansion of vapor in the tank. Hot soak loss is the evaporation of fuel when the hot engine is turned off, arising from the transfer of heat from the engine and hot exhaust to the fuel system where fuel is no longer flowing. Running loss occurs when the vehicle is in motion. Evaporative losses depend on the ambient temperature variation, fuel volatility, and mean trip distance. Emissions are also generated from nonexhaust sources through wear on vehicle components, such as tires, brakes and clutch, and through road abrasion. The above emissions often consist of PM with a diameter of 3–10 mm, with primary composition of metals, organic materials, rubber and silicon compounds. Some brake pads, linings and clutches may still contain asbestos, even though there has been significant international effort to ban the use of asbestos in all industries, including automobile manufacturing, due to the potential health hazards of asbestos exposure. Some countries, such as China, Russia, India, Kazakhstan, Ukraine, Thailand, Brazil and Iran, remain large consumers of asbestos, and produce asbestos-containing automobile parts. Asbestos is currently banned in the European Union, Japan and Australia. However, it has been reported that many Japanese automakers continued to use asbestos-containing components in new automobiles from 1996 to 2005. In the USA, the industrial use of asbestos has not been completely eliminated. In 1989, the EPA issued the Asbestos Ban and Phase Out Rule, but this was subsequently overturned in 1991. Asbestos use continues in the production of some automobile parts in the USA. In addition, some vehicles imported into the USA have asbestos-containing components.

29.4 Traffic-related air pollutants The main pollutants emitted from traffic include: PM, elemental carbon (EC), carbon monoxide (CO), carbon dioxide (CO2), nitrogen oxides (NOx), sulfur dioxide (SO2)

29.4

TRAFFIC-RELATED AIR POLLUTANTS

429

and polycyclic aromatic hydrocarbons (PAH). Carbon monoxide, nitrogen dioxide (NO2), benzene and black smoke are often used as indicators of traffic-related air pollution. We will discuss some of the above pollutants in detail.

29.4.1 Particulate matter Particulate matter is now recognized as one of the most important traffic air pollutants, because of its significant effects on human health. Ambient PM consists of a heterogeneous mixture of solid and liquid particles suspended in air, continually varying in size and chemical composition in space and time. Particulate matter can be characterized by source, size and chemical composition, and comes from both natural and anthropogenic sources. Natural sources include wind-borne soil, sea spray and emissions of organic compounds from vegetation. Anthropogenic sources include combustion of fuel, vehicle exhaust, mining, agriculture, industry and power generation. Figure 29.5 shows the particle size distribution of typical roadway aerosol. Particles smaller than 10 mm (PM10) are considered ‘respirable’, because they have a greater likelihood than larger particles to gain access to the lower respiratory tract. PM10 is further categorized as: (1) coarse particles diameter (between 2.5 and 10 mm); (2) fine particles (PM2.5, or diameter less than 2.5 mm); and (3) ultrafine particles (PM0.1, with diameter less than 0.1 mm). Larger (coarse and fine) particles dominate ambient particle mass concentrations, while smaller particles (ultrafine) dominate ambient particle number concentrations. Particles with diameter less than 1 mm usually have ambient particle concentrations ranging from 100 to 100,000 particles/cm3, while those larger than 1 mm may have concentration less than 10 particles/cm3. In other words, ultrafine particles have a high ambient particle number concentration, but low mass concentration.

Figure 29.5 Typical engine exhaust particle size distribution, showing weighting by both particle mass and number. From Kittelson D. (1998) Engines and nanoparticles: a review. J. Aerosol Sci. 29: 575–588. Reproduced by permission of Elsevier

430

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

Particulate matter from different sources has different chemical compositions. For example, tailpipe exhaust emissions of PM consist of a mixture of EC, organic compounds, sulfur and trace heavy metals. Nonexhaust PM from wearing of tires contains many carbonaceous compounds, while brake wear releases PM rich in heavy metals. In addition, PM can be formed in the atmosphere by conversion from gaseous precursors, such as NOx, SO2, ammonia (NH3) and volatile organic compounds.

29.4.2 Other traffic pollutants In addition to PM, gases also contribute to traffic-related air pollution. CO is produced from incomplete combustion of carbon-containing fuels, which occurs in the engine operation of motor vehicles. Given the current low ambient concentrations in the USA, CO serves more as an indicator of combustion-related pollution, rather than a direct toxicant. However, in certain circumstances (such as an insufficiently ventilated parking structure or on a busy highway), CO can attain concentrations sufficient to increase the risk for cardiac ischemia in persons with atherosclerotic coronary artery disease. Sulfur dioxide is primarily considered a point source emission, related to the burning of sulfur-containing coal in power plants and industry. However, the combustion of sulfur-containing fuels in diesel engines also produces SO2. Sulfur dioxide is a highly soluble gas. On contact with water, as in the respiratory tract lining fluid, it forms sulfurous acid, a strong irritant to eyes, mucous membranes and skin. People with asthma may experience acute reductions in lung function following even very brief exposures to SO2. In general, traffic is not considered a major contributor to ambient levels of SO2 in the USA. The formation of NOx results mainly from combustion of fossil fuels in motor vehicles. Most toxicological and epidemiological studies have focused on NO2 rather than other NOx chemical species, because it is the most abundant, stable and toxic form of NOx in the atmosphere, it is one of the air pollutants regulated by ambient air quality standards, and it plays a major role in the generation of ozone. Polycyclic aromatic hydrocarbons are a group of organic chemical compounds that contain two or more aromatic benzene rings fused together. Today, vehicle emissions are the primary sources of PAH in most urban areas, although wood burning may be an important source in some areas, such as Scandinavia and Eastern Europe. Some PAHs, such as benzene, are carcinogenic. The particulate fraction of PAH is usually of greater concern, since it contains the majority of the carcinogenic compounds and can be transported over long distances. A major review of mobile-source air toxics, which include PAHs, was recently published [3].

29.5 Health effects of traffic-related air pollution Many epidemiological studies have shown an association between human exposure to ambient air pollutions and increased mortality and morbidity. However, limited epidemiological studies have focused on the effects of traffic-related air pollution on human health. There are two reasons for this: (1) federal and state air monitoring

29.5

HEALTH EFFECTS OF TRAFFIC-RELATED AIR POLLUTION

431

programs are typically set up to measure pollutants at regional, but not local levels; and (2) regional monitoring stations typically do not measure all types of pollutants, such as ultrafine particles (UFP), that are increased near highways. However, it is important to investigate how near-highway exposure affects the health status of people living near busy roads. Several studies have demonstrated higher rates of respiratory symptoms, elevated risk for development of asthma, lung cancer, increased cardiopulmonary mortality and reduced lung function in people living near major roads. In the following sections, we will review some of the epidemiological studies examining the relationship between traffic-related air pollution and human health, by organ system.

29.5.1 Pulmonary diseases Pediatric pulmonary morbidity Evidence is fairly strong that near-highway exposures present increased risk for respiratory symptoms and diseases in pediatric populations. Studies that used larger geographic frames have generally found no association between traffic-related pollution and asthma prevalence. However, recent studies that have used narrower definitions of proximity to traffic and focused on major highways have found statistically significant association between the prevalence of asthma or wheezing and residence close to busy roadways [4]. In the following sections, we will discuss some of the recent studies of highway exposure and childhood respiratory morbidity. The risk for wheezing has been found to be elevated among children living near busy roads. In a case–control study of 6147 primary school children (aged 4–11 years) and a random cross-sectional sample of 3709 secondary school children (aged 11–16 years) in the UK, Venn et al. [5] found the following results: among children living within 150 m of a main road, the risk of wheezing per 30 m increment in road proximity increased by an odds ratio (OR) of 1.08 (95% confidence interval, CI, 1.00–1.16) in primary school children, and 1.16 (95% CI 1.02–1.32) in secondary school children. In addition to wheezing, morning cough has been found to be a common association with traffic-related pollution among children. In a cross sectional study between 1995 and 1996 of 5421 children (aged 5–11 years) living in a 1 km2 grid in Dresden, Germany, with monitoring of air pollution from streets, Hirsch et al. [6] showed that an increase in the exposure to benzene of 1 mg/m3 air was associated with an increased prevalence of morning cough (adjusted OR, aOR, 1.15; 95% CI 1.04–1.27) and bronchitis (based on physician’s clinical diagnosis) (OR 1.11; 95% CI 1.03–1.19). Similar associations were observed between cough and exposures to NO2 and CO. Studies have also investigated the association between traffic-related pollution and asthma. For example, English et al. [7] examined the locations of residences of 5996 children (age
14) who lived in San Diego county with the diagnosis of asthma in 1993, and compared them with a random control series of nonrespiratory diagnoses (n ¼ 2284). The investigators found that, among children with the diagnosis of asthma, there was an increase in the number of medical visits associated with higher traffic flow. Similarly, Morgenstern et al. [8] studied the association between individual exposure to traffic-related air pollutants and allergic diseases (including asthma) in a prospective birth cohort study on 2860 children at the age of 4 and 3061 at the age of 6 in Munich,

432

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

Germany in 2005. The study used individual estimated exposure levels derived from geographical information system (GIS) based modeling. The investigators found that the distance to the nearest main road and long-term exposure to particulate matter were positively associated with asthmatic bronchitis (OR 1.56; 95% CI 1.03–2.37), hay fever, eczema and allergic sensitization. In addition, it has been found that traffic-related air pollution is linked to diminished lung development in children. In a longitudinal study of 1759 children (average age of 10 years) in southern California beginning in 1993, Gauderman et al. [9] found that over the 8-year period of follow-up, deficits in the growth of FEV1 were associated with exposure to NO2 (p ¼ 0.005), acid vapor (p ¼ 0.004), PM2.5 (p ¼ 0.04) and elemental carbon (p ¼ 0.007). Traffic-related air pollution has also been found to cause short-term reductions in lung function. In a 2-week panel study of 19 children (aged 9–17 years) in southern California in the autumn of 1999 and spring of 2000, Delfino et al. [10] examined the relationship between temporal changes in subjects’ FEV1 and their continuous PM exposure (measured by nephelometer), as well as 24-hour average of gravimetric PM mass measured at home and central sites. The investigators found an inverse association between subjects’ FEV1 and their PM exposure. In sum, there is epidemiological evidence that traffic-related air pollution is associated with increased risk for wheezing, morning cough, prevalence or exacerbation of asthma, and diminished lung growth in children. Nonetheless, it should be noted that many of the epidemiological studies on pediatric populations used a cross-sectional design, which may not distinguish whether the traffic exposure precedes or follows the respiratory symptoms or diseases, since exposure and morbidity are measured at the same time. Such studies should be interpreted with caution. Adult pulmonary morbidity The majority of epidemiological studies on the relationship between traffic-related air pollution and pulmonary diseases have been conducted with children, and the data on adults are more limited and less consistent. While some studies have found an increased prevalence of asthma in adults exposed to traffic-related pollution, other studies did not find such positive associations. However, recent studies by McCreanor et al. [11] provide strong evidence for acute adverse effects of diesel exposure in people with asthma. A possible explanation for the inconsistency among studies on asthma prevalence is study methodology: cross-sectional studies vs case–control studies vs survey of respiratory symptoms and demographics. None of the methods used in the above studies is considered ideal for examining the causal relationship between traffic exposure and respiratory morbidity. Over the years, there has been growing interest in the association between asthma and exposure to diesel exhaust, which is one of the major contributors to traffic-related air pollution. Since it is difficult to isolate diesel exhaust from other components of traffic air pollution, many studies have used surrogates of diesel exhaust (such as elemental carbon, black smoke, ultrafine particles or proximity to roadway) to measure exposure to diesel. In general, the epidemiological data on the association of diesel exhaust (or its surrogates) with causation or worsening of asthma has been inconsistent [12]. However, two studies are worth mentioning and are described below.

29.5

HEALTH EFFECTS OF TRAFFIC-RELATED AIR POLLUTION

433

One published study suggested that diesel exhaust exposure caused asthma in three workers [13]. Three workers developed asthma following excessive exposure to diesel exhaust while riding immediately behind the lead engines of caboose-less trains. In this report, asthma was diagnosed by respiratory symptoms, pulmonary function tests and measurement of bronchial hyper-responsiveness. All three workers went on to develop persistent asthma. McCreanor et al. [11] probably provided the strongest evidence thus far to support the association of diesel exposure with worsening of asthma. They conducted a randomized, cross-over study in 2003–2005 to investigate the effects of short-term exposure to diesel traffic in adults with either mild or moderate asthma. In the study, each of the 60 participants walked for 2 hours on Oxford Street in the center of London (heavy diesel traffic with higher exposure to PM2.5, UFP, EC, and NO2) and in Hyde Park (away from major roadways, lower pollutant exposure). The investigators found that walking on Oxford Street significantly reduced subjects’ FEV1 (up to 6.1%; p ¼ 0.04) and FVC (up to 5.4%; p ¼ 0.01) in comparison with Hyde Park (Figure 29.6). In addition to allergic pulmonary disease, several adult studies have observed a link between nonallergic respiratory symptoms and near highway exposure. For example, Nitta et al. [14] used a standard questionnaire among approximately 5000 adult subjects in Japan in 1993 to investigate the effect of automobile exhaust on respiratory symptoms. The study showed that exposure to automobile exhaust may be associated with an increased risk of respiratory symptoms, such as chronic cough, chronic sputum production and chronic dyspnea. The ORs for the respiratory symptoms ranged from 0.76 to 2.75 [14]. More recently, in a cross-sectional study which investigated questionnaire-derived data on street type at home in relation to respiratory health in Germany in 1998, Heinrich et al.[15] found that living near busy roads was statistically significantly associated with chronic bronchitis (OR 1.36; 95% CI 1.01–1.83). Studies using exposure models have also sought an association between transportrelated pollution and nonallergic respiratory morbidity in adults. Buckeridge et al. [16] developed an exposure model using GIS to estimate the average daily exposure to PM2.5.

Figure 29.6 Mean percentage changes in FEV1 (A) and FVC (B) in asthmatics during and after exposure on Oxford Street and in Hyde Park. Asterisks denote p < 0.05 for the difference in values between Oxford Street and Hyde Park exposures. I bars represent 95% CI. From McCreanor et al. [11]. Reproduced by permission of Massachusetts Medical Society. Copyright
2007 Massachusetts Medical Society. All rights reserved

434

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

The modeled exposure to transport-related air pollution was associated with bronchitis, chronic obstructive pulmonary disease, pneumonia and hospital admission. In sum, the epidemiological data examining the association between asthma prevalence and traffic exposure has been limited and inconsistent. However, increasing evidence suggests that exposure to traffic-related air pollutants, especially diesel exhaust, worsens existing asthma. Studies also suggest that traffic-related air pollution is related to increased risks for respiratory symptoms in nonasthmatics, such as chronic cough, sputum production and dyspnea. Whether traffic exposure contributes to the causes of asthma, or increases allergen sensitization, has not been convincingly established.

29.5.2 Cardiovascular diseases Growing evidence has supported an association between exposure to traffic-related air pollution and increased risk for cardiovascular morbidity and mortality [4, 17]. Many epidemiological and controlled exposure studies have paid special attention to PM, although CO, SO2, NO2 and EC have also been studied. Although not particularly focused on near-highway pollution exposure, two large prospective cohort studies, namely the Six-Cities Study [18] and the American Cancer Society Study [19], provided the groundwork for subsequent research on the association between fine PM and cardiovascular diseases. Both studies found a strong correlation between increased levels of exposure to ambient PM and annual average mortality from cardiopulmonary causes. The epidemiology of other air pollutants has been studied as well. Although not specifically focused on traffic-related air pollution, several time-series studies showed that exposures to black smoke, NO2, CO and SO2 were associated with increased hospital admissions for cardiovascular diseases [20]. In addition, there has also been growing evidence that living close to high traffic roads is associated with increased prevalence of coronary heart disease (CHD). For example, in a population-based, prospective cohort study involving 3399 subjects, using data from the German Heinz Nixdorf Recall Study, Hoffmann et al. [21] showed that the OR for prevalence of CHD at high traffic exposure was significantly elevated at 1.62 (95% CI 1.12–2.34) and rose to 1.85 (95% CI 1.21–2.84) after adjusting for cardiovascular risk factors and background air pollution. With the same population data base from the German Heinz Nixdorf Recall Study, Hoffmann et al. [22] conducted another prospective cohort study from 2000 to 2003, involving 4494 participants (aged 45–74 years), to investigate the association of longterm residential traffic exposure with the degree of coronary artery calcification, which is an indirect measure of coronary atherosclerosis – the main mechanism of CHD. The investigators found that participants living 50, 51–100 and 101–200 m away from major roads had OR of 1.63 (95% CI 1.14–2.33), 1.34 (95% CI 1.00–1.79) and 1.08 (95% CI 0.85–1.39), respectively, for a high coronary artery calcification (above age- and genderspecific 75th percentile). The study indicated that long-term residential exposure to traffic-related air pollution is associated with increased coronary atherosclerosis. In recent years, there has been growing interest in scrutinizing the association between the onset of myocardial infarction and exposure to traffic-related pollution. In

29.5

HEALTH EFFECTS OF TRAFFIC-RELATED AIR POLLUTION

435

a case-crossover analysis of 772 subjects with myocardial infarction (MI) in the greater Boston area between 1995 and 1996 as part of Determinants of Myocardial Infarction Onset Study, Peters et al. [23] found that the risk of MI increased in association with elevated concentrations of PM2.5 both in the previous 2 hour period (OR 1.48; 95% CI 1.09–2.02) and the day before the onset of MI (OR 1.69; 95% CI 1.13–2.34). In a subsequent case-crossover study, Peters et al. [24] identified 691 subjects, from the Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry for the period from 1999 to 2001, who survived for at least 24 hours after the onset of MI and for whom the date and time of MI were known. An association was found between exposure to traffic and risk for onset of MI within 1 hour afterward (OR 2.92; 95% CI 2.22–3.83; p < 0.001; Figure 29.7). After adjusting for the levels of exertion, the risk for MI was slightly lower, but still significant (OR 2.73; 95% CI 2.06–3.61; p < 0.001). In addition, the study also showed that there was an association between the time spent on public transportation and the onset of MI 1 hour later. On the day of the MI, of all hours the subjects spent in traffic, 72% were spent in a car, 16% on a bicycle, 10% on public transportation and 2% on a motorcycle [24]. The Peters studies overall showed that increased traffic exposure is associated with higher risk of MI. The mechanisms by which traffic exposure induces cardiovascular events remain unclear. However, a growing body of evidence indicates that exposure to PM alters vascular endothelial function. Endothelial dysfunction is now considered to be an early marker of cardiovascular risk. In human clinical studies, 1 hour exposures to freshly generated diesel exhaust, with a PM concentration of 300 mg/m3, impaired vasodilatory responses in the forearm in healthy subjects [25]. In patients with previous myocardial infarction, 2 hour exposures to 300 mg/m3 diesel exhaust increased cardiac ischemia during exercise, and impaired acute endothelial release of plasminogen activator, a response that favors coagulation [26]. Pulmonary vascular function may also be affected by pollutant exposure. Inhalation of 50 mg/m3 carbon ultrafine particles for 2 hours, with intermittent exercise, altered peripheral blood leukocyte phenotype [27] and reduced the pulmonary diffusing capacity for carbon monoxide [28], findings which are consistent with effects on pulmonary vascular function. Inhalation of UFP also reduced forearm reactive hyperemia, a measure of systemic vascular

Figure 29.7 Time spent in traffic during 72 hours preceding the onset of myocardial infarction. Percentages are the proportions of subjects with exposure during the hour in question. From Peters et al. [24]. Reproduced by the permission of Massachusetts Medical Society. Copyright
2004 Massachusetts Medical Society. All rights reserved

436

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

responsiveness, and reduced plasma nitrate levels, findings consistent with reduced NO availability and subtle systemic vascular effects of UFP exposure [29]. In addition to endothelial dysfunction, reduced heart rate variability (HRV) has also been found to be a risk factor for cardiovascular events [30]. Adar et al. [31] were able to show that heart rate variability is reduced with exposure to traffic-related pollution. In the study, 44 nonsmoking seniors (aged 60 years; some with cardiac risk factors and coronary heart disease) were asked to participate in four 2 hour trips to downtown St Louis between March and June of 2002, aboard a diesel-powered bus. The investigators found that exposure to PM2.5 and black carbon was associated with reduced HRV. However, other studies [32] did not find reduced HRV in association with in-vehicle pollution (see below). Riediker et al. [32] showed that short-term exposure to PM2.5 among healthy young subjects can lead to elevated serum inflammatory makers, which are also risk factors for coronary heart disease [33]. In the Riediker et al. study, nine young (average age 27.3 years) healthy nonsmoking male North Carolina Highway Patrol troopers were monitored on four consecutive days while working a 3 p.m. to midnight shift and riding in gasoline-powered patrol cars. It was found that in-vehicle PM2.5 (average of 24 mg/m3) was associated with increased C-reactive protein (32%), von Willebrand factor (12%), neutrophils (6%) and red blood cell indices (1%). In addition, the investigators found increased HRV associated with in-vehicle PM2.5 exposure, a finding that differs from the negative association observed by Adar et al. [31]. The differing findings regarding HRV may be due to differences in age, cardiovascular fitness, or prevalence of heart diseases among the subjects in the two studies. In sum, epidemiological and clinical studies have increasingly demonstrated an association between traffic-related air pollution and increased risk for cardiovascular diseases and events. Several cohort and time series studies have shown that trafficrelated air pollutants, such as PM, CO, SO2, NO2 and EC, are linked to increased cardiovascular mortality and morbidity. In addition, recent evidence indicates that increased traffic exposure and concentration of traffic-related air pollutants are associated with increased risk for myocardial infarction. While the exact mechanism by which traffic exposure induces cardiovascular events remains unclear, some controlled exposure studies have found that traffic-related air pollution may increase markers of cardiovascular risk, such as reduced HRV and increased inflammatory markers. Human clinical studies have also indicated that exposures to diesel exhaust and ultrafine PM can alter vascular function – a potential mechanism by which traffic pollutants could induce cardiovascular effects. However, the specific pollutants or other traffic-related factors that are responsible for the epidemiological associations have not been conclusively identified.

29.5.3 Reproductive diseases Obstetric outcomes Epidemiological studies have indicated associations between ambient air pollution and adverse pregnancy outcomes, such as decreased fetal growth, congenital birth defects, low birth weight, preterm birth, stillbirth and post-neonatal infant mortality [34, 35].

29.5

HEALTH EFFECTS OF TRAFFIC-RELATED AIR POLLUTION

437

However, very few studies have specifically investigated the role of traffic-related air pollution in these effects. In addition, the currently available studies have inconsistent results. We will discuss some of the studies in the following sections. Wilhelm and Ritz [36] conducted an epidemiologic case–control study of 50,933 infants to examine whether maternal residential proximity to heavy-traffic roadways influenced the occurrence of low birth weight and preterm birth in Los Angeles County between 1994 and 1996. Traffic exposure was weakly associated with preterm birth (relative risk, RR 1.08; 95% CI 1.01–1.15), but not low birth weight. The study by Ha et al. [37], on the other hand, did find a positive, but weak, association between low birth weight and mothers’ exposure to CO and NO2 (markers of traffic-related air pollution) during pregnancy (gestational age 37–44 weeks) in South Korea from 1996 to 1997. The adjusted RR (aRR) for low birth weight was 1.08 (95% CI 1.04–1.12) for an interquartile increase in CO concentration during the first trimester. The aRR was 1.07 (95% CI 1.03–1.11) for NO2. There is limited evidence for associations between intrauterine growth retardation (IUGR) and traffic-related air pollution. However, several studies, not particularly focused on traffic exposure, did find positive relationships between PM and IUGR. For example, in the research project entitled ‘Teplice Program’, conducted in the Czech Republic to evaluate the impact of air pollution on all hospitalized pregnancies in two districts (Teplice and Prachatice), Sram et al. [35] found significant associations between intrauterine growth retardation and PM10 levels > 40 mg/m3 in the first trimester (OR for 40–50 mg/m3 ¼ 1.6; OR for >50 mg/m3 ¼ 1.9). Some data suggest that health consequences of traffic-related air pollution may persist beyond birth and infancy, and influence cognitive and intellectual development in children. For example, Suglia et al. [38] studied a prospective birth cohort of 202 children in Boston from 1986 to 2001 (mean age 9.7 years), to examine the association between cognitive development and exposure to black carbon (BC) (considered in this study to be a marker of traffic pollution). BC exposure was associated with decreases in matrices (4.0; 95% CI 7.6 to 0.5) and composite intelligence quotient (3.4; 95% CI 6.6 to 0.3) scores of the Kaufman Brief Intelligence Test, and with decreases on visual subscale (5.4; 95% CI 8.9 to 1.9) and general index (3.9; 95% CI 7.5 to 0.3) of the Wide Range Assessment of Memory and Learning. The exact mechanism by which BC and other traffic-related pollutants affect neurocognitive development in children is not clear at this point. Elder et al. [39] proposed that ultrafine and fine particles can translocate from the lungs to other organs such as the brain via the circulation, or directly from the nose to the brain via the olfactory nerve. This has been observed in animal studies [40]. Overall, the data on the association between traffic exposure and adverse pregnancy outcomes has been weak and inconsistent. Further research is needed in this area. Although limited, some data do suggest a possible association between traffic exposure and impaired cognitive and intellectual development among children. Male fertility Traffic-related air pollution may adversely affect male fertility, although the number of studies that have examined this relationship is small. De Rosa et al. [41] investigated the impact of traffic-related air pollution on semen quality. The study was conducted in Italy from 2000 to 2002, and involved 85 men employed at motorway tollgates and

438

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

85 age-matched men living in the same area. Sperm counts were within the normal range in both groups. However, sperm motility and function were significantly lower in the tollgate workers than the control subjects. In addition to traffic-related pollution, urban industrial air pollution has been found to be associated with male reproductive disorders. Selevan et al. [42] conducted a comparative study of sperm quality and quantity between young men living in Teplice, Czech Republic (a highly industrialized area with seasonally elevated levels of air pollutions) and those living in Prachatice (a rural district with relatively clean air). The sperm concentrations and total counts were not associated with district of residence or period of elevated air pollutions. However, periods of elevated air pollution in Teplice were strongly associated with decrease in sperm motility and fewer sperm with normal morphology and chromatin.

29.5.4 Cancer Epidemiological studies have long pointed out the association of cancer with exposure to ambient air pollution. Some of these studies have specifically focused on trafficrelated air pollution. Lung cancer is by far the most studied malignancy that has been found to be associated with air pollution. As part of the Cancer Prevention II Study, Pope et al. [19] collected vital status and causes of death for approximately 1.2 million adults in 1982. The results of the study showed that each 10 mg/m3 increase in fine particulate air pollution was associated with 8% increased risk of mortality due to lung cancer (aRR 1.08; 95% CI 1.01–1.16). Several Scandinavian studies, which used NO2 or benzene as indicators of transportrelated air pollution, showed increased risk for developing lung cancer with exposure to traffic-related pollution. For example, in a population-based case–control study among men aged 40–75 between 1950 and 1990 in Stockholm County, Sweden, Nyberg et al. [43] found that average traffic-related NO2 exposure over 30 years was associated with increased risk for lung cancer, with RR of 1.2 (95% CI 0.8–1.6), adjusted for tobacco smoking, socioeconomic status, residential radon and occupational exposures. In addition, many studies have found increased risks of developing lung cancer among professional drivers, such as truck, bus and taxi drivers. Hansen et al. [44] conducted a case–control study in Denmark between 1970 and 1989 on 2251 male professional drivers with primary lung cancer. The OR for lung cancer, adjusted for socioeconomic status, was 1.6 (95% CI 1.2–2.2) among taxi drivers (who were considered to be exposed to the highest concentrations of vehicle exhaust fumes); 1.3 (95% CI 1.2–1.5) among bus and truck drivers; and 1.4 (95% CI 1.3–1.5) for unspecified drivers. Professional drivers may be at risk of developing lung cancer because of their higher exposure to potential carcinogens, such as diesel exhaust. Steenland et al. [45] conducted an exposure–response analysis of diesel exhaust and lung cancers among workers in the trucking industry in the period 1949–1990. It was found that a male truck driver exposed to 5 mg/m3 of EC would have a lifetime (through age 75) excess risk of lung cancer of 1.6% (95% CI 0.4–3.1) above a background risk of 5%. Professional drivers may also have increased risk of developing malignancies other than lung cancer. In the National Bladder Cancer Study, a population-based,

29.6

CONCLUSIONS

439

case–control study conducted in 10 areas of the USA in 1977–1978, 1909 white male bladder cancer patients and 3569 controls were interviewed. The study indicated that male truck drivers have a statistically significant (50%) increase in risk of bladder cancer. In addition, a significant trend toward increasing risk of bladder cancer with increased duration of truck driving was observed [46]. Moreover, in a retrospective cohort study of 18,174 bus drivers or tramway employees in Copenhagen, Denmark in the period 1900–1994, bus drivers and tramway employees had an increased risk for all malignancies, compared with the expected cancer rates among general population (standardized incidence ratio 1.24; 95% CI 1.19–1.30). These malignancies included lung, laryngeal, pharyngeal, kidney, bladder cancer, rectal, liver and skin cancers [47]. While the association between traffic-related air pollution and risk of malignancy (especially lung cancer) has been better defined in adults, such association has been found to be less consistent among children. Raaschou-Nielsen and Reynolds [48] reviewed the epidemiological literature up to 2006 regarding association between traffic-related air pollution and childhood cancer. The authors found four case–control studies that provided positive evidence and three case–control studies with negative evidence. The four case–control studies that provided positive evidence were relatively small and had some methodological limitations. In conclusion, the evidence for an association between traffic-related air pollution and childhood cancer is weak and limited.

29.6

Conclusions

It is now well-established that combustion-related air pollution, especially PM, is associated with increased morbidity and mortality from pulmonary, cardiovascular and malignant disease. There is evidence that traffic-related emissions contribute to those relationships. In the USA and other developed countries, efforts to reduce motor vehicle emissions have been successful. However, public health benefits from those reductions have largely been negated by increases in numbers of vehicles and miles traveled. Traffic-related emissions include PM, NOx, CO and PAH. EC, CO and NOx may be markers of toxic traffic-related emissions, but may also contribute to health effects on their own. The most convincing relationship with health effects has been found for PM. However, other traffic-related emissions and stressors may contribute to traffic-related health effects. The complex mix of diesel exhaust deserves a special consideration, because growing evidence links diesel exposure with worsening of asthma, and possibly the causation of allergic-related disease. Considerable evidence suggests that exposure to diesel exhaust and particulate matter contribute to cardiovascular dysfunction and disease. There are persistent questions and issues related to the impact of traffic on health. For example, what are the components most responsible for traffic related health effects? What are the mechanisms involved? How do we most effectively minimize health impacts of traffic without stifling economic development and individual freedom? PM traffic emissions are perhaps at the top of the list of causative agents. However, PM is a complex mix, and there is no established consensus as to the components of PM most responsible. We may never completely understand the specific chemical species or characteristics that explain all traffic-related health effects. Smoking-related health

440

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

effects represent an example and precedent for this difficulty. The toxicology and health effects of smoking have been clearly and irrefutably established, and yet we still do not know what specific agents in cigarette smoke are most responsible. Traffic-related pollution is a major public health issue. The world is facing exponential growth in the number of vehicles and miles traveled, particularly in developing countries. This means more roads and more people living near roads, and thus increased exposure. In developed countries, technological and engineering advances are reducing vehicle emissions. We need to achieve the goal of zero emissions, which is a promise of fuel cell vehicles, and these advances need to be extended to developing countries. However, also needed are strategies to reduce the need for transport, increase the use of low-emitting public transport and replace older, polluting vehicles with newer and cleaner technology. Continued progress in understanding the mechanisms by which traffic affects health will allow us to target specific kinds of emissions or engines that are most responsible.

References 1. K€ unzli, N., Kaiser, R., Medina, S. et al. (2000) Public-health impact of outdoor and traffic-related air pollution: a European assessment. Lancet 356: 795–801. 2. London, S.J., Romieu, I. (2000) Health costs due to outdoor air pollution by traffic. Lancet 356 (9232): 782–783. 3. HEI. Air Toxics Review Panel (2007) Mobile-Source Air Toxics: A Critical Review of the Literature on Exposure and Hlth Effects. Health Effects Institute: Boston, MA. 4. Brugge, D., Durant, J.L., Rioux, C. (2007) Near-highway pollutants in motor vehicle exhaust: a review of epidemiologic evidence of cardiac and pulmonary health risks. Environ. Hlth: Global Access Sci. Source 6: 23. 5. Venn, A.J., Lewis, S.A., Cooper, M. et al. (2001) Living near a main road and the risk of wheezing illness in children. Am. J. Respir. Crit. Care Med. 164(12): 2177–2180. 6. Hirsch, T., Weiland, S.K., von Mutius, E. et al. (1999) Inner city air pollution and respiratory health and atopy in children. Eur. Respir. J. 14(3): 669–677. 7. English, P., Neutra, R., Scalf, R. et al. (1999) Examining associations between childhood asthma and traffic flow using a geographic information system. Environ. Hlth Perspect. 107(9): 761–767. 8. Morgenstern, V., Zutavern, A., Cyrys, J. et al. (2008) Atopic diseases, allergic sensitisation and exposure to traffic-related air pollution in children. Am. J. Respir. Crit. Care Med.; doi: 10.1164/ rccm.200701-036OC. 9. Gauderman, W.J., Avol, E., Gilliland, F. et al. (2004) The effect of air pollution on lung development from 10 to 18 years of age. New Engl. J. Med. 351(11): 1057–1067. 10. Delfino, R.J., Quintana, P.J., Floro, J. et al. (2004) Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter. Environ. Hlth Perspect. 112(8): 932–941. 11. McCreanor, J., Cullinan, P., Nieuwenhuijsen, M.J. et al. (2007) Respiratory effects of exposure to diesel traffic in persons with asthma. New Engl. J. Med. 357(23): 2348–2358. 12. Delfino, R.J. (2002) Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research. Environ. Hlth Perspect. 110(suppl. 4): 573–589. 13. Wade, J.F. III, Newman, L.S. (1993) Diesel asthma. Reactive airways disease following overexposure to locomotive exhaust. J. Occup. Med. 35(2): 149–154. 14. Nitta, H., Sato, T., Nakai, S. et al. (1993) Respiratory health associated with exposure to automobile exhaust. I. Results of cross-sectional studies in 1979, 1982, and 1983. Arch. Environ. Hlth 48(1): 53–58.

REFERENCES

441

15. Heinrich, J., Topp, R., Gehring, U. et al. (2005) Traffic at residential address, respiratory health, and atopy in adults: the National German Health Survey 1998. Environ. Res. 98(2): 240–249. 16. Buckeridge, D.L., Glazier, R., Harvey, B.J. et al. (2002) Effect of motor vehicle emissions on respiratory health in an urban area. Environ. Hlth Perspect. 110(3): 293–300. 17. Godleski, J.J. (2006) Responses of the heart to ambient particle inhalation. Clin. Occup. Environ. Med. 5(4): 849–864. 18. Dockery, D.W., Pope, C.A. III, Xu, X. et al. (1993) An association between air pollution and mortality in six US. cities. New Engl. J. Med. 329(24): 1753–1759. 19. Pope, C.A. III, Burnett, R.T., Thun, M.J. et al. (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287(9): 1132–1141. 20. Brunekreef, B. (2006) Traffic and the heart. Eur. Heart J. 27(22): 2621–2622. 21. Hoffmann, B., Moebus, S., Stang, A. et al. (2006) Residence close to high traffic and prevalence of coronary heart disease. Eur. Heart J. 27(22): 2696–2702. 22. Hoffmann, B., Moebus, S., Mohlenkamp, S. et al. (2007) Residential exposure to traffic is associated with coronary atherosclerosis. Circulation 116(5): 489–496. 23. Peters, A., Dockery, D.W., Muller, J.E. et al. (2001) Increased particulate air pollution and the triggering of myocardial infarction. Circulation 10(23): 2810–2815. 24. Peters, A., von Klot, S., Heier, M. et al. (2004) Exposure to traffic and the onset of myocardial infarction. New Engl. J. Med. 351(17): 1721–1730. 25. Mills, N.L., Tornqvist, H., Robinson, S.D. et al. (2005) Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation 112(25): 3930–3936. 26. Mills, N.L., T€ ornqvist, H., Gonzalez, M.C. et al. (2007) Ischemic and thrombotic effects of dilute diesel exhaust inhalation in men with coronary heart disease. New Engl. J. Med. 357: 1075–1082. 27. Frampton, M.W., Stewart, J.C., Oberd€ orster, G. et al. (2006) Inhalation of carbon ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environ. Hlth Perspect. 114: 51–58. 28. Pietropaoli, A.P., Frampton, M.W., Hyde, R.W. et al. (2004) Pulmonary function, diffusing capacity and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal. Toxicol. 16(suppl. 1): 59–72. 29. Shah, A.P., Pietropaoli, A.P., Frasier, L.M. et al. (2008) Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects. Environ. Hlth Perspect. 116: 375–380. 30. Godleski, J.J., Verrier, R.L., Koutrakis, P. et al. (2000) Mechanisms of morbidity and mortality from exposure to ambient air particles. Res. Rep. Hlth Effects Inst. 91: 5–88. 31. Adar, S.D., Gold, D.R., Coull, B.A. et al. (2007) Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology 18(1): 95–103. 32. Riediker, M., Cascio, W.E., Griggs, T.R. et al. (2004) Particulate matter exposure in cars is associated with cardiovascular effects in healthy young men. Am. J. Respir. Crit. Care Med. 169(8): 934–940. 33. Pai, J.K., Pischon, T., Ma, J. et al. (2004) Inflammatory markers and the risk of coronary heart disease in men and women. New Engl. J. Med. 351(25): 2599–2610. 34. World Health Organization Health Effects of Transport-related Air Pollution, Krzyzanowski, M., Kuna-Dibbert, B., Schneider, J., (2005) (eds). World Health Organization: Copenhagen. 35. Sram, R.J., Binkova, B., Rossner, P. et al. (1999) Adverse reproductive outcomes from exposure to environmental mutagens. Mutat. Res. 428(1–2): 203–215. 36. Wilhelm, M., Ritz, B. (2003) Residential proximity to traffic and adverse birth outcomes in Los Angeles county, California 1994–1996. Environ. Hlth Perspect. 111(2): 207–216. 37. Ha, E.H., Hong, Y.C., Lee, B.E. et al. (2001) Is air pollution a risk factor for low birth weight in Seoul? Epidemiology 12(6): 643–648. 38. Suglia, S.F., Gryparis, A., Wright, R.O. et al. (2008) Association of black carbon with cognition among children in a prospective birth cohort study. Am. J. Epidemiol. 167(3): 280–286. 39. Elder, A., Gelein, R., Silva, V. et al. (2006) Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ. Hlth Perspect. 114(8): 1172–1178.

442

CH 29 TRAFFIC-RELATED URBAN AIR POLLUTION

40. Oberdorster, G., Sharp, Z., Atudorei, V. et al. (2004) Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16(6–7): 437–445. 41. De Rosa, M., Zarrilli, S., Paesano, L. et al. (2003) Traffic pollutants affect fertility in men. Hum. Reprod. 18(5): 1055–1061. 42. Selevan, S.G., Borkovec, L., Slott, V.L. et al. (2000) Semen quality and reproductive health of young Czech men exposed to seasonal air pollution. Environ. Hlth Perspect. 108(9): 887–894. 43. Nyberg, F., Gustavsson, P., Jarup, L. et al. (2000) Urban air pollution and lung cancer in Stockholm. Epidemiology 11(5): 487–495. 44. Hansen, J., Raaschou-Nielsen, O., Olsen, J.H. (1998) Increased risk of lung cancer among different types of professional drivers in Denmark. Occup. Environ. Med. 55(2): 115–118. 45. Steenland, K., Deddens, J., Stayner, L. (1998) Diesel exhaust and lung cancer in the trucking industry: exposure–response analyses and risk assessment. Am. J. Ind. Med. 34(3): 220–228. 46. Silverman, D.T., Hoover, R.N., Mason, T.J. et al. (1986) Motor exhaust-related occupations and bladder cancer. Cancer Res. 46(4 Pt 2): 2113–2116. 47. Soll-Johanning, H., Bach, E., Olsen, J.H. et al. (1998) Cancer incidence in urban bus drivers and tramway employees: a retrospective cohort study. Occup. Environ. Med. 55(9): 594–598. 48. Raaschou-Nielsen, O., Reynolds, P. (2006) Air pollution and childhood cancer: a review of the epidemiological literature. Int. J. Cancer 118(12): 2920–2929.

Further reading [Anonymous] (2008) Automobile history – the history of cars and engines. [Homepage of Anonymous Ask.com] [Online]. Available from: http://inventors.about.com/od/cstartinventions/a/ Car_History.htm (accessed 3 July 2010). Brook, R.D., Franklin, B., Cascio, W. et al. (2004) Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 109(21): 2655–2671. Davis, D. (2004) When Smoke Ran Like Water: Tales of Environmental Deception and the Battle against Pollution. Basic Books: New York. Environmental Protection Agency (2002) Health Assessment Document for Diesel Engine Exhaust. Prepared by the National Center for Environmental Assessment. EPA/600/8-90/057F. Environmental Protection Agency (2007) Regulatory Announcement: EPA Proposal for More Stringent Emissions Standards for Locomotives and Marine Compression-ignition Engines. Available from: http://www.epa.gov (accessed 28 April 2008). Environmental Protection Agency (2007) An Introduction to Indoor Air Quality. Lead (Pb). Available from: http://www.epa.gov/iaq/lead.html (accessed 28 April 2008). Environmental Protection Agency (2007) Current Best Practices for Preventing Asbestos Exposure Among Brake and Clutch Repair Workers. Available from: http://www.epa.gov (accessed 28 April 2008). Environmental Protection Agency (2008) Asbestos Ban and Phase Out. Available from: http://www. epa.gov (accessed 29 April 2008). Jakobsson, R., Gustavsson, P., Lundberg, I., Increased risk of lung cancer among male professional drivers in urban but not rural areas of Sweden. Occup. Environ. Med. (1997) 54(3): 189–193. Janssen, N.A., Brunekreef, B., van Vliet, P. et al. (2003) The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ. Hlth Perspect. 111(12): 1512–1518. Jarvholm, B., Silverman, D. (2003) Lung cancer in heavy equipment operators and truck drivers with diesel exhaust exposure in the construction industry. Occup. Environ. Medicine. 60(7): 516–520. Joumard, R., S
eri
e, E (2008) Modelling of Cold Start Emissions for Passenger Cars. INRETS report, LTE 9931, Bron, France, 86. Available from: www.inrets.fr/infos/cost319/index.html (accessed 28 April 2008).

FURTHER READING

443

Kabir, Z., Bennett, K., Clancy, L. (2007) Lung cancer and urban air-pollution in Dublin: a temporal association? Irish Med. J. 100(2): 367–369. Kim, J.J., Smorodinsky, S., Lipsett, M. et al. (2004) Traffic-related air pollution near busy roads: the East Bay Children’s Respiratory Health Study. Am. J. Respir. Crit. Care Med. 170(5): 520–526. Langholz, B., Ebi, K.L., Thomas, D.C. et al. (2002) Traffic density and the risk of childhood leukemia in a Los Angeles case–control study. Ann. Epidemiol. 12(7): (2002) 482–487. Lanphear, B.P., Hornung, R., Khoury, J. et al. (2005) Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ. Hlth Perspect. 113(7): 894–899. Lanphear, B.P., Hornung, R., Khoury, J. et al. (2005) Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ. Hlth Perspect. 113(7): 894–899. Le Tertre, A., Quenel, P., Eilstein, D. et al. (2002) Short-term effects of air pollution on mortality in nine French cities: a quantitative summary. Archiv. Environ. Hlth 57(4): 311–319. Lin, M.C., Chiu, H.F., Yu, H.S. et al. (2001) Increased risk of preterm delivery in areas with air pollution from a petroleum refinery plant in Taiwan. J. Toxicol. Environ. Hlth Pt A 64(8): (2001) 637–644. Livingstone, A.E., Shaddick, G., Grundy, C. et al. (1996) Do people living near inner city main roads have more asthma needing treatment? Case control study. BMJ 312(7032): 676–677. UNECE/EMEP (2004) Task Force on Emissions Inventories and Projections. EMEP/CORINAIR Emission Inventory Guidebook, 3rd edn. European Environment Agency: Copenhagen. Wilkins, E.T. (1954) Air pollution aspects of the London fog of December 1952. Q. J. R. Meteorol. Soc. 80(344): 267–271.

30 Outdoor sports


Kai-Hakon Carlsen University of Oslo, Norwegian School of Sport Sciences and Oslo University Hospital, Rikshospitalet, Oslo, Norway

30.1 Introduction Exercise-induced asthma and exercise-related respiratory problems are important for both the asthmatic child and adolescent, as well as for actively competing athletes. For the asthmatic child it is important both for their self-perception and development that they undertake and enjoy physical activity; indeed it may even be a means of mastering their asthma. However, the present chapter will be limited to matters relevant to the competing athlete. Asthma and allergy represent increasing problems for the actively competing athlete with an increasing prevalence of exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB) reported, especially among elite endurance athletes [1–3]. Exercise-induced asthma and exercise-induced bronchoconstriction are terms used to describe the transient narrowing of the airways that follows vigorous exercise. The term EIA is used to describe symptoms and signs of asthma provoked by exercise and EIB for the reduction in lung function which may be demonstrated after an exercise test or a naturally occurring exercise. In 1989 it was reported for the first time that high-level endurance training by adolescent swimmers increased nonspecific bronchial hyper-responsiveness (BHR) to histamine depending on the intensity of the physical training. Nine years later the finding of inflammatory changes in bronchial biopsies from young skiers was reported from Trondheim. The effect of intensive physical activity may be enhanced by untoward environmental conditions during the activity, such as cold ambient temperatures for winter sports and organic chlorine products from indoor swimming pools in swimmers. It should also be emphasized that the present day heavy training and intense physical activity during competitions reached by elite athletes due to their extremely high level of physical fitness and maximum oxygen uptake (V’O2max), make it Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

446

CH 30 OUTDOOR SPORTS

increasingly difficult to discriminate between physiological and pathological limitations to maximum exercise.

30.2 Epidemiological context Sixty-seven of 597 American Olympic Athletes (who collectively won 41 medals) for the Los Angeles 1984 summer Olympic Games suffered from EIA or asthma. This was followed by reports of high prevalences of asthma from later Olympic Games; in 1996 an asthma prevalence of 45% was reported in cyclists and mountain bikers compared with none in divers and weightlifters. However, these reports were almost all questionnairebased without attempts objectively to verify the presence of EIB by exercise tests or other means. Later, the prevalence of BHR to metacholine (49%) in 100 competitive athletes of various sports was compared with that of sedentary subjects (28%). The prevalence of BHR varied in athletes performing their sports in cold air, dry air, humid air or combinations of these. Subsequently, reports on the use of inhaled drugs after applications for their use in the three latest Olympic Games suggested that 5.2% of all participating athletes used inhaled b2-agonists in the Winter Olympic Games in 2002 and 4.2% in the Summer Olympics in 2004. From data collected over the three latest Summer Olympic Games, in Atlanta 1996, Sydney 2000 and Athens 2004, it appears that the use of inhaled b2-agonists is highest in endurance sports, with cycling top (15.4% of all competitors), followed by the triathlon and by swimming.

30.2.1 Winter sports In 1993, it was reported that 23 of 42 elite cross country skiers had a combination of BHR and asthma symptoms compared with only one of 23 referents. This was followed by reports of high prevalences in Norwegian and Swedish skiers, in competitive figure skaters, in elite cold-weather athletes and among participants in the 1998 American Olympic National team for winter sports, including gold medalists.

30.2.2 Summer sports BHR to methacholine (PD20-methacholine < 16.3 mmol) was found in 35.5% of the Norwegian national female soccer team, and 56% of Canadian professional football players had a positive bronchodilator test (increase in FEV1  12%) to inhaled salbutamol [4]. Among American track and field athletes, 10% of men and 23% of women suffered from EIB after a national competitive event with higher incidences after long-distance events. Helenius and Haahtela in a series of studies on Finnish elite track and field athletes reported physician diagnosed asthma in 17% of long-distance runners, 8% of speed and power athletes and 3% of controls. They also reported total asthma (current asthma, physician diagnosed asthma or BHR) in 23% of the athletes compared with 4% of the controls, current asthma in 14% compared with 2% among controls and a positive skin prick test in 48% of the athletes compared with 36% among controls. Among swimmers

30.3

DEFINITION OF EXPOSURES RELATED TO ASTHMA AND RESPIRATORY DISORDERS IN ATHLETES 447

they found a high prevalence of BHR (48%) to histamine. Employing the objective criteria for diagnosing asthma and/or bronchial hyper-responsiveness as ruled by the IOC, Medical Comission, Dickinson reported prevalences among UK participants in the Olympic Games in 2000 and 2004 to be 21.2 and 20.7%, respectively, with a positive bronchoprovocation or bronchodilator test. Thus it can be concluded that elite athletes, especially active in endurance sports, have a high prevalence of asthma and bronchial hyper-responsiveness. We will enquire if this is due to type of physical activity in itself, or due to environmental exposures during the performance of sports. In relationship to individual sports, there is limited evidence and it is necessary to combine knowledge based upon different types of sports performed in different environments in order to reach an understanding about the relevant pathogenetic mechanisms.

30.3

Definition of exposures related to asthma and respiratory disorders in athletes – pathogenetic mechanisms

Exposures may be related to the environmental conditions under which the sport is performed, or to particular aspects of the type of sport itself. These exposures may have a direct relationship to the pathogenetic mechanisms at work in causing asthma and related problems in many athletes in particular types of sport. As above, asthma and bronchial responsiveness develop more frequently in endurance sports than in speed and power sports and sports related to esthetic performance. In particular these sports have in common prolonged and increased ventilation during training and competition. This was recently shown experimentally in an Italian study of training mice, with signs of wearing in the mucous membranes after exercising compared with nonexercising mice. Another animal study of competing Alaskan sled dogs participating in a 1100 mile endurance race demonstrated intraluminal debris by bronchoscopy 12–24 hours after completing the race with higher numbers of macrophages and neutrophils in bronchoalveolar lavage as compared with control, nonracing dogs. Table 30.1 shows which environmental exposures may be important for the different types of sports. Best described are the conditions for cross-country skiers, in which the environmental exposure factor is believed to be the repetitive inhalation of cold air, and swimmers with inhalation of chlorine and organic chlorine products like trichloramine. An increase in bronchial responsiveness correlating with exercise intensity in both asthmatic and healthy elite competitive adolescent swimmers after 3000 m swimming in an indoor swimming pool represents the first description of change in bronchial responsiveness related to sports. The exposure combined heavy endurance swimming with inhalation of chlorine and organic chlorine products. Subsequently, young competitive skiers were found to have lymphoid aggregates in their bronchial mucosa and signs of bronchial remodeling (tenascin) in bronchial biopsies in addition to increased responsiveness to cold air in contrast to healthy, somewhat older medical students who were not particularly physically active. A mixed type of eosinophilic and neutrophilic inflammation was found in elite swimmers, ice-hockey players and

448

CH 30 OUTDOOR SPORTS

Table 30.1 Environmental exposures important for the development of athma and bronchial hyperresponsiveness in some selected endurance sports Type of sports

Primary exposure

Secondary exposure

Cross country skiing; biathlon Swimming

Increased ventilation during training/competition Increased ventilation during training/competition Increased ventilation during training/competition Increased ventilation during training/competition Increased ventilation during training/competition

Cold air inhalation

Cycling Long-distance running; marathon Speed skating, figure skating, ice-hockey

Exposure to chlorine and organic chlorine products Environmental pollution, NOx Environmental pollution, NOx from accompanying cars Ultrafine particles from icing machines

cross-country skiers; the environmental exposures differed between these groups of athletes (Table 30.1). Swimmers with exercise-induced bronchial symptoms had significantly higher sputum eosinophil counts than symptom-free swimmers. The inflammation may be due to repeated thermal, mechanical or osmotic airway trauma resulting in a healing or remodeling process, and seems to be directly associated with heavy training since discontinuing high-level exercise was effective in reducing eosinophilic airway inflammation in a five-year follow-up study of competitive swimmers. There appears to be a relationship between neutrophilia in induced sputum and endurance training in swimmers, training and competing outdoors, and nonasthmatic middle-aged amateur marathon runners. In young competitive rowers an increased number of cells in sputum was found after an all-out rowing test with a change in cell dominance from neutrophils to bronchial epithelial cells. By use of induced sputum, comparing asthmatic subjects with and without EIB, it has been reported that injury to the airway epithelium, overexpression of cysteinyl leukotrienes, relative underproduction of prostaglandin E(2), and greater airway eosinophilia are distinctive immunopathologic features of asthma with EIB. The response may differ between different types of sports, being dependent upon the environment in which the sport takes place. Further research is needed in this field to fully understand these processes.

30.4 Diseases related to physical activity, training and competition in sports Physical activity may cause several different conditions in the respiratory tract. Exerciseinduced asthma is most important, occurring most often in asthmatics who are not taking inhaled steroids. EIA will typically occur shortly after exercise with bronchial obstruction occurring within a few minutes after exercise or after reducing the intensity of exercise. The dyspnoea will typically be expiratory and with audible wheeze on auscultation. Other respiratory conditions are also related to physical activity and sports, representing the important differential diagnoses to EIA and EIB in an athlete. Studies

30.4

DISEASES RELATED TO PHYSICAL ACTIVITY, TRAINING AND COMPETITION IN SPORTS 449

have demonstrated that most of the elite athletes referred for respiratory problems do not suffer from asthma or exercise-induced asthma, but rather from some of the differential diagnostic conditions. One frequent differential diagnosis is exercise-induced inspiratory stridor or exercise-induced vocal chord dysfunction. The symptoms consist of inspiratory stridor occurring during maximum exercise, and ceasing when exercise is terminated unless hyperventilation is maintained by the patient. In such cases, there are audible inspiratory sounds from the laryngeal area, and bronchodilators or other asthma medication will not help. This condition most often occurs in young well-trained athletic girls from approximately 15 years of age. Symptoms only occur during maximum exercise. The symptoms are probably due to the relatively small crosssectional area of the laryngeal orifice, which may be even further reduced by the negative pressure created by the strong inspiratory flow during heavy exercise. One possible differential diagnosis to this syndrome is paradoxical movement of the vocal chords with adduction during inspiration, sometimes occurring without exercise. The diagnosis of vocal chord dysfunction/exercise induced inspiratory stridor can be made clinically and confirmed and differentiated by direct fibreoptic laryngoscopy during exercise. Swimming-induced pulmonary edema is another differential diagnosis to EIA. Swimming-induced pulmonary edema occurs in well-trained swimmers after a heavy swimming session. The condition was reported in 70 previously healthy swimmers, who developed typical symptoms of pulmonary edema together with a restrictive pattern in pulmonary function, remaining for up to one week after the swimming incident. In addition, other chronic disorders including heart diseases as well as other chronic respiratory diseases may impact upon physical performance and represent a possible differential diagnosis to exercise-induced asthma. Over- and underweight may also influence the diagnosis, but rarely concerns athletes. Poor physical fitness or overtraining may represent other possible differential diagnoses to EIA. This is especially so when physical fitness and exercise performance are not up to the expectations of the athletes – or their trainers or parents. A lack of success in sports is often attributed to asthma even if this is not actually the case. Finally, exercise-induced arterial hypoxemia occurs in many athletes, especially in those who are highly trained. It is thought to be due to limitations in diffusion and ventilation–perfusion inequality during exercise. In the healthy lung, the former (limited diffusion) is thought to be due to a rapid red blood cell transit time through the pulmonary capillary bed. Physical training improves muscle strength and endurance, with increased ionotrophic and chronotrophic capacities of the cardiovascular system but no such effects occur in the respiratory tract. Ventilatory requirement rises with no alteration in the capacity of the airways and the lungs to produce higher flow rates or higher tidal volumes, and there is little or no change in the pressure-generating capability of inspiratory muscles. The result is exercise-induced arterial hypoxemia which may occur in up to 50% of highly trained athletes. This reduction in arterial oxygen saturation may be confused with EIA. Thus several differential diagnoses to EIA exist. Whatever the cause for the respiratory difficulties, it is important to make a thorough examination and rule out possible differential diagnoses as this has important implications for treatment.

450

CH 30 OUTDOOR SPORTS

30.5 Diagnostic considerations and medicolegal issues The following procedure is recommended in the examination of the athlete with respiratory problems. The diagnostic criteria are identical to those of the usual asthmatic patient. However, due to criteria set by the Medical Commission of the IOC, certain modifications must be made. The following diagnostic procedure is recommended. 1. Careful case history with a focus on exercise-related symptoms or other symptoms of asthma and possible allergic disease. 2. Clinical examination with a focus on possible signs of bronchial obstruction. 3. Lung function, in particular maximum expiratory flow volume loops with assessment of reversibility to an inhaled b2-agonist like salbutamol. 4. Assessment of bronchial responsiveness, either by direct or indirect methods: (a) bronchial provocation with metacholine (or histamine); (b) exercise test standardised for assessing EIB; (c) other tests of indirect bronchial responsiveness such as the eucapnic hyperventilation test, inhalation of cold dry air, AMP inhalation, mannitol inhalation or exercise field testing. 5. Exercise test with maximum intensity to diagnose possible exercise-induced vocal chord dysfunction. Other specific examinations may become necessary dependent on findings and symptoms. The choice of diagnostic procedure depends on laboratory facilities, on case history and the medical regulations in the different countries. More than one test may be necessary. To satisfy the criteria of the IOC Medical Commission and obtain permission to use inhaled b2-agonists in relationship to Olympics and other forms of competitive sports, a positive test related to point 3 or 4 above is necessary.

30.6 Treatment of asthma and exercise-induced bronchoconstriction in athletes The treatment of asthma is extensively covered in international guidelines. While they consider most aspects of asthma, few address the specific situation in the athlete, particularly regarding the use of reliever and controller treatment. When choosing treatment for athletes compared with the ordinary asthma patient, some additional factors should be considered. For the top athlete it is important not only to control symptoms of asthma and prevent progression, but it becomes equally important to stop disease processes to reduce their impact upon sports performance, often performed under extraordinary circumstances. Therefore, the prescribed treatment should have an optimal effect upon asthma, but the possibility of potential side effects should be carefully considered. Larsson et al. [4] have published a systematic review of the treatment of athletes and EIB, including only randomized double-blind placebocontrolled or drug-comparison studies with eight subjects or more.

30.7

INTERNATIONAL REGULATIONS FOR USE OF ASTHMA DRUGS IN SPORTS

451

Treatment of EIB has been extensively studied in asthmatic subjects over the last 30 years, but only occasionally in athletes with EIB. Thus, it is not fully known whether athletes with EIB or ‘sports-asthma’ respond similarly to subjects with classical allergic or nonallergic asthma; at present, however, there is no evidence supporting different treatment for EIB in asthmatic athletes and nonathletes. The same principles as for asthma management in general may be applicable to EIA, combining the judicious use of controller (anti inflammatory) and reliever (premedication before exercise and treatment of symptoms) therapies.

30.7

International regulations for use of asthma drugs in sports

In order to be allowed to use the most common asthma drugs in relationship to international competitive sports, it is necessary to obtain permission to do so from the World Anti-Doping Association (WADA) or IOC, Medical Commission (IOC-MC). For participation in Olympic Games IOC-MC gives the necessary permissions; WADA is responsible for other international competitive sports. Although IOC-MC set up restrictionsfortheuseofinhaledb2-agonistsasearlyas1993,thesehavesinceandrepeatedlybeen modified.Itisnecessarytomakeanapplication before acompetition; the asthmaticathlete in need of asthma medication such as inhaled steroids and inhaled b2-agonists may apply for a therapeutic use exemption (TUE). The latest update on the rules and application forms for a TUE can be found on the WADA website: http://www.wada-ama.org. Furthermore, WADA has published their own recommendation as regards athletes and asthma; this too which can be found on their website: http://www.wada-ama.org/ rtecontent/document/Asthma_en.pdf. Before each Olympic Games, the IOC-MC publishes the updated regulations for the coming Olympic Games. These can be found on the IOC-MC website: http://www .olympic.org/PageFiles/61597/Olympic_Movement_Medical_Code_eng.pdf. IOC-MC requires a positive bronchodilator test, a positive metacholine bronchial provocation test, with necessary results required specified on their website, or a positive exercise challenge test, a positive test of eucapnic voluntary hyperventilation or most recently a positive mannitol test. WADA has employed the following rules according to the latest 2009 update: .

Topical steroids – there are presently no restrictions for topical use on skin, nose and eye.

.

For the use of inhaled corticosteroids there is no longer a need for application for approval before competitions. Only a self-declaration about the use of inhaled steroids in case of doping control is required.

.

An application for a TUE is still needed for inhaled b2-agonists. Inhaled b2-agonists are also not permitted out-of competition. For the use of inhaled b2-agonists WADA has now declared: ‘It is preferred to leave to the professional judgment of the physician the medical conditions under which these drugs are to be prescribed’ (Explanatory Notes, 2006). The team manager and team doctor are also responsible when an athlete is caught in doping. A concentration of urinary salbutamol

452

CH 30 OUTDOOR SPORTS

1000 ng/l is considered an adverse analytical finding regardless of the granting of any form of TUE. The doping rules are usually modified every year, and the physician treating athletes with respiratory diseases should know these rules, keep updated and apply them to any prescribed medication in order not to cause problems for the competing athlete.

30.8 Controller treatment of EIA It should be emphasized that in general the ordinary international guidelines for asthma should be followed. However, specific concerns for the athlete have been mentioned above.

30.8.1 Inhaled corticosteroids Optimal treatment of asthma aiming at reducing BHR and maintaining control of disease activity is important for mastering EIA and enabling the athlete to participate freely in physical training, sports activity and competitions. Anti-inflammatory treatment by inhaled corticosteroids is currently the most important and effective management in these respects. Even after a week of regular treatment with inhaled budesonide in children, EIA improves significantly, but to obtain a significant reduction also in the fall of MEF25-75, further treatment of 3–4 weeks is necessary. Attenuation in exercise-induced decrease in FEV1 is also seen only after 1 week of therapy with inhaled ciclesonide at doses greater than 40 mg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 mg, even after 3 weeks of therapy. Inhaled corticosteroids improve EIA more rapidly than BHR, measured by methacholine bronchial provocation. After 2–3 months of treatment with inhaled corticosteroids in children, the anticipated improvement of EIA is reached [5], whereas ongoing improvement of methacholine-induced bronchial responsiveness can be observed for up to 22 months. In children with mild asthma, a low dose of inhaled corticosteroids significantly improved EIA over a 3 month treatment period. Few studies on the effect of inhaled corticosteroids on asthma and BHR have been performed in athletes, and no studies in top athletes. In a study of 25 young competitive skiers with asthma-like symptoms or bronchial hyper-responsiveness who were attending a specialist high-school, each was prescribed budesonide 400 mg twice daily or placebo over a period of 10–32 weeks in the competitive season. No effect upon cellular inflammation in the bronchial mucosa or tenascin expression in the mucosal basement membranes from bronchial biopsies nor any cellular differences in BAL fluid were found between those taking active or placebo treatments; moreover there was no differential effect on BHR. However, with few subjects in each group, and with only five subjects with reported BHR, the study may have been underpowered. Inhaled corticosteroids have both systemic and local side effects that should be taken into account in the relationship between sports and EIB. Of particular concern are

30.9

RELIEVER TREATMENT OF EIA

453

adrenal suppression, growth retardation in children and adolescents and reduction in bone density. Adrenal suppression is rare, but known to occur by use of high doses of inhaled corticosteroids. Because of adrenal suppression by high doses of inhaled steroids, hypoglycaemic convulsions have been reported in several patients being admitted to hospital. Reduction in bone mineral density has been noted as another possible systemic side effect of inhaled corticosteroids. Although rare, this possibility should be considered, especially when treating asthmatic women practising endurance sports since female marathon runners have been noted to be at particular risk for osteoporosis.

30.8.2 Leukotriene antagonists Leukotriene antagonists (LA) reduce EIA. In adults, a single dose of LA protects significantly better against EIA than placebo, and 2 days of treatment with a leukotriene synthesis inhibitor (zileuton) causes a 40% protection against EIA. Two days of use of montelukast, an alternative leukotriene receptor antagonist, significantly reduces EIA both in children and adults. Comparison studies with the long-acting inhaled b2-agonist, salmeterol, demonstrated that the protection against EIA obtained by montelukast after 3 days, remains unchanged after 8 weeks of treatment in adults, whereas tolerance to salmeterol develops after this time. In athletes there are few studies on the effect of montelukast on EIB. Whereas, in a randomized placebo-controlled cross over study of 16 ice-hockey players with EIB, no effects on asthma-like symptoms, BHR, exhaled nitric oxide and sputum cell parameters were found, in most, but not all of 11 physically active subjects with EIB, montelukast seemed to protect against EIB and lung function reduction after eucapnic hyperventilation. A Norwegian double-blind randomized crossover study in 16 adults with EIB demonstrated that montelukast improved their physical performance (running time, and Borg score for exhaustion), without altering gas exchange parameters. It may be concluded that montelukast has a protective effect upon most athletes with EIB, but not in all.

30.9

Reliever treatment of EIA

30.9.1 Treatment before exercise b2-Agonists The class of drugs most studied in this respect, and demonstrated to be effective against EIB, is the inhaled b2-agonists. By the 1970s it was established that orally administered b2-agonists offer poor protection against EIB compared with the same inhaled drug. Inhaled b2-agonists have an almost immediate effect upon EIB, with a maximum effect 20 minutes after inhalation. The effect may still be observed 3 hours after inhalation, but disappears after 4 hours. In a direct comparison of the shortacting inhaled b2-agonist salbutamol with the long-acting salmeterol, the latter appears to be to be active against EIB from 30 minutes to 6.5 hours after inhalation,

454

CH 30 OUTDOOR SPORTS

whereas salbutamol is as effective as salmeterol 30 minutes after, but less so from 2.5 to 6.5 hours after inhalation. Formoterol, another long-acting inhaled b2-agonist, has a similar long-lasting protective effect on EIB, but with the added benefit of an onset of protective effect as rapid as salbutamol or terbutaline. Even if the inhaled b2-agonists protect against EIB, they do not completely abolish it, as exemplified by one study with a maximum reduction in FEV1 after exercise of 18–19% after inhaled salmeterol compared with 30% after placebo. It has been observed that, after regular use of long-acting inhaled b2-agonists, the protective effect on EIB is somewhat reduced, a development referred to as tolerance. Tolerance develops after 4–8 weeks of regular treatment with salmeterol; whether it has any general clinical significance is uncertain, but this cannot be ruled out in athletes. However, use of the drugs three times a week or less does not seem to result in any tolerance. When prescribing asthma drugs for the athlete, the problem with the development of tolerance should be considered, but it is not widely recognized that it is not prevented by inhaled corticosteroids. Secondly, a systematic review suggested an increased risk of severe cardiovascular side effects in patients taking long-acting inhaled b2-agonists on a regular basis. Thirdly, the FDA issued in November 2005 an alert against the regular use of inhaled long-acting b2-agonists; it is recommended that long-acting b2-agonists should not be prescribed without simultaneously giving inhaled steroids. Ipratropium bromide Ipratropium bromide may be effective against EIA in some but seldom the majority of patients. An additional protective bronchodilator effect may be obtained when ipratropium bromide is added to an inhaled b2-agonist. Whereas ipratropium bromide improves lung function both before and after exercise in asthmatic men as compared with nonasthmatic men, it has no effect upon cardio-respiratory or cardiovascular parameters of performance after a step-wise cycle exercise test. No restrictions apply to ipratropium bromide in relationship to sports.

30.10 Recommendations for the treatment of exercise induced asthma in athletes Many of the above recommendations have been incoporated into a statement from the Joint Task Force of the European Respiratory Society and the European Academy of Allergy and Clinical Immunology for asthma, allergy and sports. Treatment of EIA should follow the general guidelines for treating asthma. Reports of symptoms of EIA and other chronic respiratory symptoms in athletes should be verified by objective diagnosis by standardized exercise test or other measures of direct or indirect BHR, as there are several important differential diagnoses to EIA. 1. EIA without other clinical manifestations of asthma may be best controlled by the use of short-acting inhaled b2-agonists taken 10–15 minutes before exercise.

REFERENCES

455

2.

EIA combined with other asthma symptoms may best be controlled by antiinflammatory treatment either alone or in combination with reliever treatment. Inhaled corticosteroids in low to moderate doses are the preferred treatment. It should be noted that, according to the latest modification of the rules given by WADA (from Januray 2009), it is not necessary to make an application for the use of inhaled steroids related to sports activity, but rather give a self-declaration about the use in case of a doping control.

3.

In certain circumstances leukotriene antagonists alone may be tried, but should be clearly followed up for assessment of treatment effect.

4.

Without full control with inhaled corticosteroids add either: (a) short-acting inhaled b2-agonists before exercise or (b)

long-acting inhaled b2-agonists may be tried;

(c)

a leukotriene antagonist can be tried in addition to inhaled corticosteroids.

Be aware of the possibility of developing tolerance to inhaled b2-agonists used on a regular basis, and the reports of nonresponse in some to patients to leukotriene antagonists. 5.

In some patients the combination of inhaled corticosteroids, long-acting inhaled b2-agonists and leukotriene antagonists may be needed to control exercise related symptoms.

6.

Sodium cromoglycate or nedocromil sodium or ipratropium bromide may be tried for EIA after individual assessment, either alone or in addition to other treatments.

To be noted: a lack of response to treatment may be due to misdiagnosis and require reassessment of the diagnosis of EIA. Another cause of lack of response is the possible lack of compliance with treatment. This should be taken into consideration as well as inhaler technique.

References 1. Larsson, K., Ohlsen, P., Larsson, L., Malmberg, P., Rydstrom, P.O., Ulriksen, H. (1993) High prevalence of asthma in cross country skiers. BMJ 307: 1326–1329. 2. Heir, T., Oseid, S. (1994) Self-reported asthma and exercise-induced asthma symptoms in highlevel competitive cross-country skiers. Scand. J. Med. Sci. Sports 4: 128–133. 3. Helenius, I.J., Tikkanen, H.O., Haahtela, T. (1998) Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy and exposure to cold air and pollen. Br. J. Sports Med. 32: 125–129. 4. Ross, R.G. (2000) The prevalence of reversible airway obstruction in professional football players. Med. Sci. Sports Exerc. 32: 1985–1989. 5. Waalkens, H.J., van Essen-Zandvliet, E.E., Gerritsen, J., Duiverman, E.J.K.K., Knol, K. (1993) The effect of an inhaled corticosteroid (budesonide) on exercise- induced asthma in children. Dutch CNSLD Study Group. Eur. Respir. J. 6: 652–656.

456

CH 30 OUTDOOR SPORTS

Further reading Anonymous (2006) Global Strategy for Asthma Mangement and Prevention. Available from: http:// www.ginasthma.com/Guidelineitem.asp??l1¼2&l2¼1&intId¼60. Bernard, A., Carbonnelle, S., Michel, O., Higuet, S., De Burbure, C., Buchet, J.P., Hermans, C., Dumont, X., Doyle, I. (2003) Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools. Occup. Environ. Med. 60(6): 385–394. Carlsen, K.H. (2005) Evidence-based recommendations for the diagnosis of exercise-induced asthma in athletes. In Diagnosis, Prevention and Treatment of Exercise-Related Asthma, Respiratory and allergic Disorders in Sports, Carlsen, K.H., Delgado, L., Del Giacco, S.,(eds). European Respiratory Journals: Sheffield; 102–104. Carlsen, K.H., Anderson, S.D., Bjermer, L., Bonini, S., Brusasco, V., Canonica, W., Cummiskey, J., Delgado, L., Giacco Del, S., Drobnic, F., Haahtela, T., Larsson, K., Palange, P., Popov, T., van Cauwenberge, P. (2008) Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN. Allergy 63(4): 387–403. Carlsen, K.H., Anderson, S.D., Bjermer, L., Bonini, S., Brusasco, V., Canonica, W., Cummiskey, J., Delgado, L., Giacco Del, S., Drobnic, F., Haahtela, T., Larsson, K., Palange, P., Popov, T., van Cauwenberge, P. (2008) Treatment of exercise induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN. Allergy 63(5): 492–505. Drobnic, F., Haahtela, T. (2005) The role of the environment and climate in relation to outdoor and indoor sports. In Diagnosis, Prevention and Treatment of Exercise-Related Asthma, Respiratory and allergic Disorders in Sports, Carlsen, K.H., Delgado, L., Del Giacco, S. (eds). European Respiratory Journals: Sheffield; 35–47. Drobnic, F., Freixa, A., Casan, P., Sanchis, J., Guardino, X. (1996) Assessment of chlorine exposure in swimmers during training. Med. Sci. Sports Exerc. 28(2): 271–274. Fitch, K.D. (2006) b2-Agonists at the Olympic Games. Clin. Rev. Allergy Immunol. 31(2–3): 259–268. Helenius, I., Haahtela, T. (2000) Allergy and asthma in elite summer sport athletes. J. Allergy Clin. Immunol. 106(3): 444–452. Lagerkvist, B.J., Bernard, A., Blomberg, A., Bergstrom, E., Forsberg, B., Holmstrom, K., Karp, K., Lundstrom, N.G., Segerstedt, B., Svensson, M., Nordberg, G. (2004) Pulmonary epithelial integrity in children: relationship to ambient ozone exposure and swimming pool attendance. Environ. Hlth Perspect. 112(17): 1768–1771. Larsson, K., Carlsen, K.H., Bonini, S. (2005) Anti-asthmatic drugs: treatment of athletes and exerciseinduced bronchoconstriction. In Diagnosis, Prevention and Treatment of Exercise-Related Asthma, Respiratory and allergic Disorders in Sports, Carlsen, K.H., Delgado, L., Del Giacco, S. (eds). European Respiratory Journals: Sheffield; 73–88. World Anti Doping Agency (2009) Medical Information to Support the Decisions of TUECs Asthma. Available from: www.wada-ama.org/rtecontent/document/Asthma_en.pdf

Index Numbers in italics refer to Figures Numbers in bold refer to Tables acarids, 81–2, 90 acrolein, 25, 293, 393, 394 firefighters, 266–7, 305 acrylates, 225, 243, 249, 250, 256 acrylics, 236 acrylonitrile, 236 acute eosinophilic pneumonia (AEP), 307, 308, 309 acute inhalational injury, 188, 241, 241–3 acute irritant symptoms, 33, 34–5 acute lower respiratory illness, 29, 29–30, 39 acute lung injury, 98, 102, 103, 104 acute mountain sickness (AMS), 377, 385–7, 388 acute pulmonary effects of immersion, 361 adult respiratory distress syndrome (ARDS), 63, 350, 401 agribusiness, 161–6, 169–70 agriculture, 161–75 burning, 391–2, 397, 398 non-allergen symptoms, 167–9 air-bag deployment, 129, 133 air conditioning in cars, 130–1, 134 air fresheners, 55, 60–5, 329 airways disease, 261–3 alcohols, 57, 58, 73, 426 Alternaria, 87–9, 225 altitude sickness, 377, 385–8 amines, 237, 243, 243, 252 ammonia, 16, 264, 293, 295, 305, 430 agriculture, 162, 167, 168 cleaning products, 56, 57, 58, 59, 62–3, 66–7, 269 research workers, 347, 349, 349, 353

ammonium chloride, 16, 248, 262 anhydrides, 236, 237, 241, 243, 243, 244, 250 animals, 82–5, 88, 90, 324–5, 331, 407–8 agriculture, 162, 162–4, 165, 166–8, 169, 170, 174 hobby pursuits, 99, 99–100 research workers, 337–8, 340, 340–3, 344–5, 345–6, 346, 347 veterinarians, 264–5, 270 see also cats; dogs; horses; rodents anthrax, 97, 98, 101, 102, 228, 230 biological weapons, 297, 298 anti-neutrophil cytoplasmic autoantibody (ANCA), 186 antenatal exposure see pregnancy ardystil syndrome, 241, 242 arsenic, 194, 195 arts and crafts, 96, 98–9 asbestos, 10, 182–3, 241, 244, 418, 428 automobile industry, 212, 213–5 automobile maintenance and repair, 204, 206, 209 construction, 274, 275, 279, 284, 286 firefighters, 306 hobby pursuits, 97, 98, 104 mining, 177–9, 182–3, 184–6 pulp and paper, 227, 227 asbestosis, 104, 179, 182–3, 206, 209 automobile industry, 212, 213 construction, 277, 287 Aspergillus, 87–8, 89, 225, 275, 283 asthma, 1–2, 91, 92, 243, 252 agriculture, 161, 163, 165, 167–8, 169, 170 attribution, 8, 9, 9

Occupational and Environmental Lung Diseases Edited by Susan M. Tarlo, Paul Cullinan and Benoit Nemery © 2010 John Wiley & Sons, Ltd. ISBN: 978-0-470-51594-5

458

INDEX

asthma (Continued ) automobile industry, 212, 213, 216–22 automobile maintenance and repair, 205–9 automobile pollution, 426, 430–3, 433, 434, 439 bakery, 14, 173 biomass smoke, 392, 394, 395, 396–8, 402 buildings and furnishing, 71–2, 72–3, 75–8 chemical weapons, 292, 295 chemicals and coatings, 236–40, 241, 241–5 children, 29, 31, 39 cleaning products, 16, 19, 61–3, 64, 65–7 cockroaches, 85–6 construction, 273, 276, 280–2, 282 cooking and heating emissions, 50, 51, 52, 53 cosmetics, 14–6, 17–21 day-care and schools, 109–10, 114–9 drugs allowed in sport, 451–5 electronics industry, 248–9, 250, 251–7 exercise-induced, 101, 101, 104, 445–6, 448–9, 451–5 firefighters, 266–8, 304, 305 food industry, 171, 172, 173–4 fungi and moulds, 86, 89 hairdressers, 17, 19 hobby pursuits, 96, 97, 98–105 horses, 152, 153–5 hospitality workers, 122, 124, 125, 127 indoor sports, 138, 142, 144, 147–9, 152–5 insects, 90 inside of automobiles, 130–3, 135 metal industry, 193, 194, 197, 199, 200 military, 307–8 mining, 179 mites, 82, 92 offices and schools, 314–5, 315, 320, 321, 323–4, 329–35 outdoor sports, 445–7, 448, 448–55 passive smoking, 28, 31, 33, 35–6, 38–40 pets, 84, 85, 99 police, 266, 302, 303 pulp and paper, 226, 227, 227 research workers, 338–9, 340–1, 342–8, 349, 351, 351–3 service industries, 261–5, 266–9 smoking in pregnancy, 28, 28 textile industry, 228, 228, 230

urban pollution, 406, 410–2, 414–5, 416, 417 volcanic emissions, 401, 403 wood industry, 224, 224–5 World Trade Centre disaster, 301–2 atelectasis, 363 atmospheric pressure, 378 atmospheric temperature, 378 athletes, 446–7, 448, 448–9, 450, 453–5 indoor meetings, 138, 155 attribution, 7–10 automobiles, 109, 129–30, 211–22 environment exposure inside, 129–35 maintenance and repair, 203–10 new car registrations in China, 423 urban pollution, 406, 407, 416, 417, 421–40 US traffic pollution controls, 424 volume of passenger transport, 423 avian influenza, 300, 301 aviation, 377–85, 387, 388 oxygen equipment, 382–3 physiology, 379–85 azobisformamide, 243 azodicarbonamide, 243 bagassosis, 164 bakery, 103, 103, 161, 165, 172–4, 268, 270 asthma, 14, 173 bars and restaurants 121–8, 268–9, 270 barium, 195 benzene, 64, 417 biomass smoke, 393, 394 inside automobiles, 130–1, 132, 133 second hand smoke 25, 122, 132 traffic pollution, 427, 430, 431, 438 benzopyrene, 212, 213, 215 beryllium, 192, 193, 194, 195–7, 199, 353 construction, 282–3, 286 electronics industry, 250, 253 mining, 183–4, 186 urban pollution, 418 see also chronic beryllium disease (CBD) beta-agonists, 18, 453–4, 455 biological hazards, 292, 296, 297, 298–9, 300 biomass fuels, 45, 46, 49, 53–4, 406 biomass smoke, 391–2, 394, 395, 396–8, 402–3 biomonitoring, 251 bird egg syndrome, 90 bird fancier’s lung, 99, 104

459

INDEX

birds, 90, 99, 99–100, 104, 164, 165, 168 blast injury to the lung (BLI), 307 blastomycosis, 103, 103 bone sarcomas, 284, 286 breast cancer, 33, 34, 122, 125 bromine, 145, 146 bromochlorodimethylhydantoin, 145, 146 bronchial hyper-responsiveness or hyperreactivity (BHR), 262, 433 animals, 82, 92, 116 buildings and furnishing, 71–2 cleaning products, 61, 62, 67, 269 cold air exacerbated, 144 firefighters, 267 hairdressers, 15 indoor water sports, 147 outdoor sports, 445–7, 448, 452, 454 research workers, 342, 343, 351, 351 bronchiectasis, 288, 295, 348 bronchiolitis, 5, 9, 29, 63, 188 bronchiolitis obliterans, 5, 241, 242, 295 food industry, 173–4 research workers, 338, 348, 350–1, 352–3 textile industry, 228, 228, 230 bronchiolitis obliterans organizing pneumonia (BOOP), 242 bronchitis, 77, 116, 200, 227, 230, 241 agriculture, 161, 163, 167, 169, 170, 174 automobile industry, 212, 213, 216 chemical weapons, 292, 296 cleaning products, 63 construction, 276, 279, 288 food industry, 171, 173 hobby pursuits, 96, 97 indoor equestrian sports, 138, 154 metal industry, 192, 193, 195, 199, 200 mining, 183, 184, 188 research workers, 348 second hand smoke, 29, 36, 37, 123, 124, 132 service industries, 262, 265 traffic pollution, 431–2, 433–4 urban pollution, 407 brucellosis, 297, 299, 300 buildings and furnishing, 69–78 agriculture, 162, 168 day-care and schools, 109–10, 113, 115, 117, 119 offices, 315, 316–30 buildings and grounds cleaning, 260, 269–70

bush and grass fires, 391, 397, 398 byssinosis, 228, 228–9, 229, 231 cadmium, 9, 10, 286, 347 metal industry, 194, 195, 199 mining, 178, 188 cadmium pneumonitis, 98 calcium carbonate, 138 Caplan’s syndrome, 183 carbamates, 60, 168 carbon dioxide, 110, 115, 162, 379–80 hyperbaric environment, 358, 359, 362, 366, 369, 371–2 traffic pollution, 425, 427, 428 volcanic emissions, 399, 400, 402, 403 carbon monoxide, 52, 53, 125, 188, 294 automobile maintenance and repair, 204, 205, 206 biomass smoke, 393, 394, 397 firefighters, 166–7, 305 indoor sports, 138, 138, 139–42, 143 inside automobiles, 129, 131, 132, 135 traffic pollution, 425, 427, 428–30, 434–5, 437, 439 volcanic emissions, 399 carbonless copy paper, 315, 317, 317, 318, 328–9, 330 cardiovascular disease, 38–9, 40, 132, 133–4, 135 particulate matter, 410, 413, 416 traffic pollution, 434–5, 435, 436, 439 carpeting for cars, 212, 218 cats, 82–4, 88, 89, 92 day-care and schools, 111, 112, 112, 116, 118 fleas, 91 offices, 324–5, 326–7, 330 research workers, 340, 340 central nervous system toxicity, 372 ceramics, 96, 97 cheese washer’s disease, 164 chemical industry, 233–45 components, 234, 235 potential hazards, 235 chemical weapons, 292, 293–4, 295–7, 309 chicken breeder’s disease, 164 children, 27–33, 84–5, 92, 394 buildings and furnishing, 70–2, 73–5 cancers, 29, 32 cleaning products, 61, 63–7 cooking and heating, 45, 50, 51

460

INDEX

children (Continued ) day-care and schools, 109–19 fungi and moulds, 86, 88, 89 green algae, 90–1 indoor sports, 145, 147–8, 153 inside automobiles, 131, 132, 134, 135 mites, 82, 92 outdoor sports, 445, 452 passive smoking, 23–4, 25–6, 27–33, 39–41 traffic pollution, 431–2, 437 urban pollution, 406, 410–1, 416 chloramines, 63 chlorine, 188, 226, 292, 293, 295, 297 cleaning products, 59, 63 research workers, 347, 349, 349 swimming, 145, 146, 147–8, 445, 447, 448 chlorine dioxide, 145, 146, 226, 227 chromium, 198, 200, 275, 276, 286 chronic beryllium disease (CBD), 183–4, 253, 353 construction, 280, 282–3 chronic obstructive lung disease, 96, 97 chronic obstructive pulmonary disease (COPD), 3–5, 194 agriculture, 167 attribution, 9, 10 automobile industry, 212, 213, 221 automobile maintenance and repair, 205, 206, 209 biomass smoke, 392, 402 chemical weapons, 295 chemicals and coatings, 243 construction, 276–7, 278, 279, 280 cooking and heating, 50–3 firefighters, 305, 309 food industry, 174 indoor equestrian sports, 152 inside of automobiles, 131, 133 mining, 183, 184, 188 second hand smoke, 33, 37, 39–40, 122, 124–5, 127 traffic police, 266 traffic pollution, 434 urban pollution, 406, 408, 410–1, 416 wood and textile industries, 231 circuit boards, 249 clean diesel technology, 427 cleaning products, 55–67, 168, 171, 172 day-care and schools, 117–8, 119 healthcare workers, 261–2 janitors, 269–70

offices, 315, 315, 317, 318, 323, 329, 330 research workers, 340, 351 swimming pools and hot tubs, 148, 150 coal, 53, 405, 407, 411–3, 415, 416, 423–4 coal mining, 9, 10, 177, 178, 183 coal worker’s pneumoconiosis (CWP), 179, 183, 185, 186 coatings, 233–40, 241, 241–5 cobalt, 192, 194, 197 coccidiomycosis, 103 cockroaches, 85–6, 92, 112, 340 offices, 317, 319, 324–5, 326–7, 330 cold-start emissions, 427, 428 colophony (rosin), 247–8, 249, 250, 249–57 combustion engines, 425–6, 426 compensation, 8, 40, 256, 335 firefighters and police, 309 hairdressers, 20–1 military, 309–10 mining, 182, 183, 184 research workers, 347, 352 connective tissue disease, 186, 214–5 cooking, 45–54, 91, 125, 392 food industry, 161, 170, 174 coronary heart disease, 122, 125–6, 128 cosmetics, 13–21, 234, 237, 265–6 cosmetology, 265–6 cosmic radiation, 379 cotinine, 27, 32, 113, 122, 125 cows, 164, 165, 166, 168 crowd control agents, 292, 293, 302 cyanoacrylate, 303, 303 cycling, 446, 448 damp, 49, 87–8, 111 buildings, 69, 71, 72–7 day-care and schools, 110–1, 115–6, 119 offices, 314–24, 330, 330–2, 336 decompression illness (DCI), 361, 362–3, 364, 364–8, 384 altitude induced, 383, 384 dental personnel, 264 diazonium salts, 240, 243 diffuse pneumonitis, 237 diisocyanates, 225, 239–40, 276, 418 disinfectants, 162, 264 cleaning products, 55, 56, 57, 58, 63 indoor water sports, 138, 145, 145–8 diving, 357–8, 359–60, 360–1, 362–3, 363–74, 384 saturation, 360, 360, 363–4

INDEX

dogs, 83–4, 88, 324, 408 day-care and schools, 111, 112, 116, 118 research workers, 340, 341, 347 drain cleansing agents, 60, 61 drug laboratories, 296 dyes and dyeing, 227, 228, 230, 240, 241, 243, 243 electroplating, 193 electronics industry, 247–57 elemental carbon (EC), 428, 430, 434, 439 emissions in buildings, 69, 70, 71–2, 72–6, 77–8 emissions from fuel evaporation, 427, 428 emphysema, 10, 37, 254, 296 construction, 276, 279 metal industry, 193, 194 endotoxins, 264 agriculture, 167, 170 offices, 320, 321, 322, 330 textile industry, 228, 229, 231 epoxies, 212, 222, 276 epoxy resins, 236, 237, 249, 250, 257 epistaxis, 237 equestrian sports, 138, 152–5 ethanolamines, 62 ethyl methacrylate, 20 ethylene, 238 ethylene oxide, 262 exercise-induced arterial hypoxemia, 449 exercise-induced bronchoconstriction (EIB), 445–6, 448, 450–4 extrinsic allergic alveolitis (EAA) see hypersensitivity pneumonitis (HP) farmer’s lung disease 100, 154, 164, 164–6 fertilizers, 162, 162 fire-eater’s lung, 101, 102 fibrous glass, 275 fire smoke, 266–8, 292, 293–4, 296, 304, 305, 305–6 from biomass, 391–2, 394, 395, 396–8, 402–3 research workers, 347, 351 firefighters, 266–8, 270, 291, 303–4, 305, 305–6, 309 biomass smoke, 394, 395, 395–6 first responders, 292, 296, 300–1 World Trade Center, 301–2 fishing, 99, 100, 103, 103, 161, 170–2 insect allergens, 90

461 flock worker’s lung, 230, 241, 242 floor cleaners, 57 fluorides, 198 fluoropolymers, 64, 238, 241 food allergens, 91, 113 food industry, 161, 164, 165, 170–5 food preparations, 260, 268–9 forest fires, 391, 392–6, 398 forging/stamping, 212, 217 formaldehyde, 25, 130, 172, 237–8, 244, 393 automobile industry, 215, 221 buildings and furnishing, 71, 70–2, 76 construction, 276, 286 cooking and heating, 46, 49 cosmetology, 265–6 electronics industry, 248, 252 firefighters, 266 offices, 323, 330 research workers, 347 wood industry, 224–5 formaldehyde–amino resins, 237–8 foundries, 213, 214, 214–15 fume fever, 97, 98 fungi and moulds, 49, 87–8, 225, 265, 319–20, 321, 322 agriculture, 162, 162, 164, 165, 166–7, 170, 174 buildings and furnishing, 69, 76 construction, 274, 275–6, 288 day-care and schools, 110, 111, 112, 115–16 hobby pursuits, 98, 103, 104 indoor equestrian sports, 152 indoor ice sports, 139 offices, 314–5, 317, 318, 319–23, 328, 330 pesticides, 60 research workers, 340 furniture makers, 223, 224 galvanization, 193 gas, 45, 46–50, 51–3 gastrophageal reflux disease (GERD), 301–2 giant cell interstitial pneumonitis, 197 glanders, 297, 299, 300 glass cleaners, 56, 57, 61, 63, 66 glass making, 97, 98 glutaraldehyde, 261–2, 264, 266 glycophosphate, 168 grass pollen, 89 green algae (chlorella), 90–1

462

INDEX

greenhouse lung, 164 gymnastics, 138, 155 hairdressing, 13–21, 265–6 hairspray lung, 13 halogenated acids, 293, 305 hard metal pulmonary disease, 197 hay fever, 18, 71, 340, 341, 432 hazardous materials, 292, 293–4, 295, 296–7 health diagnosing and treating occupations, 260, 260–5, 270 healthcare workers, 260, 260–3, 264, 269–70 heating, 45–54, 69, 77–8, 87 hemoptysis, 142, 143, 151 hemothorax, 189 henna, 16, 17, 265 HERA, 58, 60 herbicide, 168 hexamethyldiisocyanate (HDI), 219, 221, 240, 243 high altitude, 377–8, 379 high altitude cerebral edema (HACE), 385, 386, 387 high altitude pulmonary edema (HAPE), 377, 385–8 high density lipoprotein cholesterol (HDL), 33, 39 high pressure neurological syndrome (HPNS), 373 Histoplasma from bird and bat droppings, 315, 317, 328, 333 histoplasmosis, 103, 103, 328, 333, 333 horses, 138, 152–5, 164 hospitality workers, 121–8, 268–9, 270 hot emissions, 427, 428 hut lung, 392 hydrocarbon pneumonitis, 102, 104 hydrocarbons, 64, 131, 141, 393, 426, 427 buildings and furnishing, 70, 72, 73 polycyclic aromatic, 286, 393, 394, 429, 430, 439 hydrochloric acid, 63 hydrofluoric acid, 63, 98 hydrogen chloride, 293, 305, 349, 349 hydrogen cyanide, 294 hydrogen peroxide, 16 hydrogen sulphide 162, 168, 402 volcanic emissions, 399, 400–1, 402, 403–4 hygiene, 118, 161 hypercapnia, 362–3, 364, 371–2

hypersensitivity pneumonitis (HP; aka extrinsic allergic alveolitis (EAA)), 3 agriculture, 163, 164, 164, 166, 170, 174 automobile industry, 212, 213, 216–7, 219 automobile maintenance and repair, 205, 206, 206–7 chemicals and coatings, 237, 240, 241, 243, 244 construction, 280, 283 electronics industry, 250, 253 food industry, 171, 174 hobby pursuits, 98, 99, 99, 100, 102, 104–5 indoor equestrian sports, 154 indoor water sports, 138, 147, 149–51 mining, 179 offices, 314, 315, 331–2, 333 research workers, 339 schools, 114 welding, 199 wood industry, 224, 225, 231 hyperventilation, 380–1, 384–5, 385 hypocapnia, 148 hypoxemia, 148, 150 hypoxia hyperbaric, 359, 362, 364, 369–70 hypobaric, 377–81, 385–8 hypoxic, 377, 387, 379–82 ice sports, 447, 448, 453 indoor, 138, 139–44 toxicant syndromes, 140–3 idiopathic environmental intolerance (IEI), 15 immersion pulmonary edema, 362, 364, 370 indoor humidity, 110–1, 115–6 see also damp indium, 250, 253 indium alveolitis, 249 infections, 115, 131, 135, 151, 287–8 cooking and heating, 51, 52 military, 307–8, 309, 309 office workers and teachers, 315, 315, 333, 333–4 passive smoking, 29, 33, 38 police, 303, 309 research workers, 350, 353, 354 upper respiratory tract, 151, 300–1 inhalation fever, 228, 229, 231 inhaled corticosteroids for asthma, 452–3, 455

INDEX

463

insects, 90, 91, 163, 165, 340 see also cockroaches insulation, 276, 279, 281, 282, 282, 286 interstitial fibrosis, 212, 295 interstitial lung disease, 200, 241, 244, 230 automobile maintenance and repair, 205, 206, 209 biomass smoke, 392, 402 electronics industry, 249, 250, 253 research workers, 349, 351, 352 ipratropium bromide, 454, 455 iron oxide, 197, 198, 199, 200 ischaemic heart disease (IHD), 33, 38–9, 40 isocyanates, 252–4, 282, 294 automobile industry, 212, 213, 218–9, 221–2 automobile maintenance and repair, 204–9 chemicals and coatings, 239–40, 241, 243, 243–4 construction, 281, 282, 283 electronics industry, 248–51, 255, 256–7, 257

military, 307, 308, 309 mining, 182–3, 185–6, 187 police, 303, 303 pulp and paper, 227, 227 radon in schools, 110 research workers, 339, 353 second hand smoke, 26, 33, 33–4, 39, 122, 125, 127 smoking in automobiles, 132, 133, 135 textile industry, 231 urban pollution, 409 volcanic emissions, 401 welding, 199, 200–1 lung and pulmonary fibrosis, 103, 114, 225, 228 agriculture 165, 168 automobile maintenance and repair, 209 chemical weapons, 295, 297 hairdressers, 265 metal industry, 193, 194, 195 military, 307 mining, 177, 180, 182, 186 lung injury from sports, 142

jewelry, 97, 98

magicians, 99, 101, 102 magnesium carbonate, 138 male fertility, 437–8 mainstream smoke, 24, 25, 132 malt worker’s disease, 164 manganese, 195, 198, 199 manure, 162, 162, 168, 170 maple bark disease, 164 meat processing, 170, 172 meat wrapper’s asthma, 172, 239 mercury, 191, 195, 399 mesothelioma, 6–7, 9, 9, 186, 397, 418 brake linings, 204, 205, 206, 209 construction, 286, 287 military, 309, 309 pulp and paper, 227, 227 textile industry, 231 metal fume fever, 199, 199, 220, 238, 242 automobile maintenance and repair, 206, 209 metal machining, 212, 215–17 metal working, 97, 98, 191–201 metal-working fluids, 191, 193, 213, 215, 216, 216–17 methacrylates, 264, 266, 276 methane, 162 methyl colophony, 253

laryngocele, 101, 102 latex, 261, 264, 265 research workers, 337, 340, 342 laundry products, 55, 60 lead, 195, 199, 306, 425–6, 427 automobile maintenance and repair, 204, 206, 210 volcanic emissions, 399 legionella, 315, 317, 325, 328, 333, 333 Legionnaire’s disease, 333 leptospirosis, 102, 179 leukotriene antagonists, 453, 455 limonene, 62, 70, 72, 73 low birth weight, 28, 28, 436–7 lumberjacks, 224 lung cancer, 6–7, 10, 133–4, 244 automobile industry, 212, 213 automobile maintenance and repair, 204–5, 206, 209 automobile pollution, 426, 431, 438–9 biomass smoke, 392, 395, 396, 397 construction, 283, 284–5, 286–7 cooking and heating, 53 firefighters, 306, 309 metal industry, 193, 194

464

INDEX

methyl isocyanate, 240 methyl methacrylates, 266, 276 methylene diisocyanate (MDI), 240, 243, 282 automobile industry, 213–4, 218, 218–9 microbes and microorganisms, 115, 320, 321 agriculture, 162, 162–4, 165 automobile industry, 216–7 buildings and furnishing, 69, 71, 72–3, 75–7 indoor water sports, 146, 147, 149 offices, 316, 316–23, 325, 328, 330 textile industry, 228, 229 wood industry, 224 military, 291, 306–9, 310, 384 first responders, 292, 296, 300–1 mites, 81–2, 86, 90, 92 agriculture, 162, 162, 164, 165, 170 day-care and schools, 111, 112, 115 offices, 317, 319, 324–5, 326–7, 330 morbidity, 279, 409–13 traffic pollution, 430, 431–4, 436, 439 mortality, 409, 412–3, 414, 417, 421 construction, 277, 278, 279 traffic pollution, 430–1, 434, 436, 439 moulds see fungi and moulds mountaineering, 377 mushroom picker’s disease, 164 mycotoxicosis, 166 mycotoxins, 170 nasal sinus cancer, 34, 122, 125 nasal septal perforation, 193, 194 nasopharyngeal cancer, 34, 238, 283 near-drowning, 362, 364, 371 nerve agents, 292, 294, 296 neurobehavioral disorders, 29, 32–3 nickel, 25, 198, 200, 276, 286 nicotine, 113, 132 second hand smoke, 26, 27, 28, 32, 122 nitric oxide exhalation, 124 nitrogen chloride, 147 nitrogen dioxide, 188, 198, 241, 242, 266 agriculture, 162 cooking and heating, 46–8, 49–51 hobby pursuits, 103 ice-skating, 102, 138, 139–41, 142–3 inside automobiles, 131, 135 traffic pollution, 429, 434, 437–9 urban pollution, 408, 413, 414 nitrogen oxides, 25, 212, 266, 276, 448 automobile pollution, 426–7, 428, 430

biomass smoke, 393, 394 fire smoke, 294, 305 inside automobiles, 131 research workers, 349, 349, 351 urban pollution, 406, 413–5, 416 welding, 198, 198, 199 nonexhaust emissions, 427, 428 nontuberculosis mycobacterial (NTM) disease, 179, 185, 320 indoor water sports, 147, 151 numismatist’s lung, 103, 103 nylon flock disease, 212, 213, 218, 348 obstructive pulmonary disease (OPD), 184 organic dust toxic syndrome (ODTS), 154, 283 agriculture, 163, 166, 167, 169, 170 organophosphates, 60, 168 organizing pneumonia, 348, 351, 352 otitis, 29, 30, 39, 168 out-gassing from new cars, 132–3, 135 oxygen toxicity, 362, 363–4, 364, 365 oxyhemoglobin dissociation curve, 380, 380 ozone, 72, 212, 276, 426, 430 atmospheric, 378–9 indoor water sports, 145, 146, 148 inside automobiles, 131, 135 pulp and paper, 226, 227, 227 research workers, 349, 349 traffic police, 266 urban pollution, 406, 414, 415, 416, 417 welding 198, 198, 199 Paget–Schroetter syndrome, 101, 102 paints, 233, 234, 235–6, 241, 243, 243–4 agriculture, 162 automobiles, 14, 203–5, 206, 207–8, 211, 212, 221–2 buildings and furnishing, 70–2, 71, 77–8 construction, 276, 279, 281, 282, 288 electronics industry, 257 hobby pursuits, 96, 97 offices, 318, 330 wood industry, 224, 225 para-phenylamine diamine, 15 paraquat, 168 particleboard, 70, 71, 76 particulate matter (PM), 48–9, 152–3, 274–6, 407–11, 416, 429 agriculture, 161

INDEX

automobile industry, 49, 212, 215 automobile maintenance and repair, 204, 206 biomass smoke, 393–4, 394, 395–8, 402–3 buildings and furnishing, 74, 76 construction, 274–6, 280, 282 cooking and heating, 46, 48, 53 firefighters, 266–7 indoor sports, 139–40, 152–3, 154 inside automobiles, 129–30, 131–4, 135 offices, 315, 316–7, 318, 330, 331 research workers, 349, 353–4 traffic police, 266 traffic pollution, 422, 426–9, 429, 430–1, 434–6, 439 urban pollution, 407–11, 412–4, 416, 417 volcanic emissions, 399, 402 World Trade Center, 301 passive smoking see second hand smoke peat moss lung, 164 pediatric pulmonary morbidity, 431–2 performing arts, 100, 101, 101–2, 104 perfumes, 13, 16, 18–9 cleaning products, 58, 60, 62 personal care and service, 260, 265–6 persulfates, 15–7, 19–20, 249, 265 pesticides, 55, 60, 63–4, 100, 103 agriculture, 162, 162, 163, 168 hazardous materials, 294, 296 offices, 314, 315, 318, 329, 330 pets, 82–5, 88, 99, 99–100 day-care and schools, 110–1, 118–9, 318 phosgene, 98, 188, 199, 305, 349 chemical weapons, 292, 294, 295–7 phosphine, 199 photography, 96, 97 phthalates, 17–8, 239, 323–4, 330 buildings and furnishing, 71, 74–5, 77 pigeon breeder’s disease, 164 pinene, 62 plague, 297, 298 plant allergens, 91, 165 plastics, 96, 98–9, 233–45 automobile industry, 212, 221 platinum, 194 pleural plaques, 9, 104, 182, 186, 187 pneumoconiosis, 5–6, 179–84, 192, 339 attribution, 9, 9 construction, 276–7 hobby pursuits, 96, 104

465 mining, 177, 178, 179–84 PVC, 239 pneumomediastinum, 368 pneumonia, 151, 154, 296, 325, 401, 434 agriculture, 166 automobile industry, 216–7 passive smoking, 29, 38, 132 welding, 199, 199–200 pneumonitis, 13, 101, 215, 238, 307, 401 agriculture, 161, 163, 168 cleaning products, 63, 64 hobby pursuits, 103, 103 indoor sports, 138, 141, 143, 147 pneumothorax, 172, 189, 250, 368 water sports, 138, 147, 152 police, 291, 302–3, 303, 304, 309 first responders, 292, 296, 300–1 traffic duty, 266, 270, 302, 303 pollen, 162, 163, 164, 340 polycyclic aromatic hydrocarbons (PAHs), 286, 393, 394 traffic pollution, 429, 430, 439 polyethylene, 212, 238, 239 polymer fume fever, 64, 220, 238, 241, 242 polypropylene, 238–9 polystyrene, 239 polytetrafluoroethylene (PTFE), 238, 242 polyurethane, 212, 218–9, 239–40, 243, 282 electronics industry, 248, 249, 251, 255 polyvinyl chloride (PVC), 29, 212, 239, 241, 244 buildings and furnishing, 71, 72–7 food industry, 172 offices, 323 Pontiac fever, 328 pregnancy, 28, 421, 436–7 cleaning products, 61, 63 passive smoking, 25, 27–9, 30–2, 39–41 preterm delivery, 28, 28–9, 436–7 protective services, 260, 266–8 psittacosis, 99, 100, 168 public health, 21, 257, 405–18 cleaning products, 67 indoor ice arenas, 143–4 offices, 331, 334, 335–6 smoke-free workplaces, 126–7 pulmonary barotrauma, 362–3, 364, 368–9, 372 pulmonary contusion, 138, 147 pulmonary disease–anemia syndrome, 237

466

INDEX

pulmonary edema, 238, 240, 241–2, 295 agriculture, 168, 169 firefighters, 267 military, 307 research workers, 338, 348 sports, 101, 102, 138, 147, 151, 449 volcanic emissions, 401, 403 pulmonary embolus, 101, 102, 104 pulmonary fibrosis see lung fibrosis pulmonary hypertension, 392 pulp and paper industry, 223, 226–7, 227, 231 Q fever, 168, 297, 298, 300, 309 radiographers, 262 radon, 110, 113–4, 117, 119, 399 mining, 178, 185, 186 REACH, 59–60 reactive airway dysfunction syndrome (RADS), 241, 242, 262 agriculture, 163, 168 airbag deployment, 133 chemical weapons, 295–6 cleaning products, 62–3, 67 firefighters, 267, 306 research workers, 338, 351, 351 World Trade Center, 301 rebreathers, 358, 359, 360, 362, 369–70 renal diseases, 186 reproduction, 24, 64, 436–8 rhinitis, 82, 86, 89, 91, 171, 261, 265 agriculture, 161, 163, 164, 169, 169, 170 automobile maintenance and repair, 205, 206 bakery, 172 buildings and furnishing, 71–2, 75, 77–8 coatings and plastics, 237, 243 day-care and schools, 109, 116 electronics industry, 250, 251 hairdressers, 14, 16 hobby pursuits, 96, 98, 100, 103, 104 indoor sports, 138, 152, 153, 154 office workers and teachers, 323, 332, 333 pesticides, 64 pets, 82, 85, 100 pulp and paper, 227 research workers, 338, 338, 340–1, 343, 345, 347 wood industry, 224 rhinorrhea, 147, 153, 163 rhinosinusitis, 193, 194, 314, 332, 333

rock wall climbing, 138, 155 rodents, 84–5, 112, 324, 407–8 research workers, 340, 341, 343, 344–5, 347 saltwater aspiration syndrome, 362, 364, 370–1 sarcoidosis, 253, 268, 301–2, 304, 305 office workers and teachers, 314–5, 332 sawmills, 223, 224 SCUBA diving, 358, 358, 360, 362 seafood, 161, 164, 165, 170–2 second hand smoke, 23–41, 139 automobiles, 132, 134, 135, 135 children, 23–4, 25–6, 27–33, 39–41 day-care and schools, 110, 113, 116–7, 119 hobby pursuits, 103, 103 hospitality workers, 121–8 workplace smoking bans, 123–4 sensory irritation symptoms, 122, 123–4 sequoisis, 164 severe acute respiratory syndrome (SARS), 300, 301 shell lung, 164 ship building and breaking, 193 shoe care products, 60, 64 siderosis, 200 sidestream smoke, 24, 25, 132 silica, 192, 193, 195, 306 automobile industry, 212, 213, 214, 215 automobile maintenance and repair, 204, 209 construction, 274, 275, 279, 285, 286 mining, 177–80, 182–6, 188 volcanic emissions, 399, 400, 401 silicates, 274–5 silicosis, 97, 192, 230 automobile industry, 212, 213, 215 construction, 277, 287, 288 mining, 177, 179, 180, 181, 182, 183–6 volcanic emissions, 399, 400, 401 silver fish, 90 sino-nasal cancer, 224, 226, 285 sinusitis, 332, 333 skiing, 446, 447, 448, 448 smelting, 193 smoking 14, 23–41, 132, 268–9, 439–40 automobile industry, 213 construction workers, 277, 278, 279–80, 283, 287 COPD, 4, 5, 10

467

INDEX

firefighters, 306 indoor equestrian sports, 153–4 inside automobiles, 129–30, 132–5, 135 military, 308, 309 miners, 182–3, 184, 185, 187–8 police, 303 urban pollution, 406 welders, 200–1 workplace bans, 123–4 see also second hand smoke sodium azide, 133 soldering, 247–8, 249–56, 276 spices, 173 spinning and weaving, 96, 97, 227, 228 steel, 193 stings and bites, 91 stone sculpting, 97, 98 stroke, 33, 39 styrene, 212, 220, 239 suberosis, 164 sudden infant death syndrome (SIDS), 29, 32 sulphates, 409, 412 sulfite mills, 226, 227 sulfonates, 55, 62 sulfur dioxide, 46, 49, 227, 241, 242, 262 firefighters, 266, 305 research workers, 349, 349 traffic pollution, 428, 430, 434 urban pollution, 412–3, 414, 416, 417 volcanic emissions, 399, 401, 402, 403 sulfur mustard (SM), 292, 293, 295, 297 sulfur oxides, 266, 293, 411–3, 414, 417 swimming, 145, 146, 147–8, 445–7, 448, 448–9 swimming-induced pulmonary edema (SIPE) 151 talcosis, 101, 102 taxidermy, 99, 100 teargas, 292, 293 Teflon coating, 238, 242 temperature, 115–6, 378 terpenes, 224, 224, 227 textiles, 96, 97, 98, 227–31 thesaurosis, 13 thiocyanates, 236 thioglycolic acid, 16 ticks, 91 time of useful consciousness, 381, 381 tobacco worker’s disease, 164 toluene, 64, 130–1

toluene diisocyanate (TDI), 219, 240, 243, 281 toxic pneumonitis, 9, 166, 194 automobile maintenance and repair, 205, 206, 209 chemicals and coatings, 240, 241, 241–2 research workers, 338, 349, 350 welding, 199, 199–200, 209 trauma, 178, 179, 189, 287 trihalomethanes (THMs), 146–7 truck-bed liners, 205, 206 tuberculosis, 53, 214, 288, 333, 392 agriculture, 168 healthcare workers, 263 military, 300, 301, 309, 309 mining, 177–8, 180, 181, 182, 185, 188 police, 300, 301, 303, 303, 309 tularaemia, 297, 298 underground workers, 357–8, 360, 361 upper respiratory tract infections (URTI), 151, 300–1 urban pollution, 405–18, 421–40 vehicle assembly, 211–2, 212, 221, 222 velopharyngeal incompetence, 101, 102 ventilation, 137, 265, 448 automobile industry, 213, 217, 221 automobile maintenance and repair, 204–5, 208 barns, 164 buildings, 69, 77–8 cleaning products, 59, 66 cooking and heating, 45–9, 51, 52, 53 day-care and schools, 110, 111, 115, 118, 119 electronics industry, 252 fungi and moulds, 87–8 hairdressers, 16–7 ice sports, 139–40 inside automobiles, 130 mining, 178–9 offices, 313–6, 317, 325, 328, 331, 333, 333–4 second hand smoke, 126 water sports, 144, 146, 148, 149, 151 welding, 199 wood and textile industries, 231 veterinarians, 264–5, 270

468 vocal cord dysfunction (VCD), 101, 101–2, 351 military, 307–8 outdoor sports, 449, 450 volatile organic compounds (VOCs), 72–4, 87 biomass smoke, 397 buildings and furnishing, 69, 70, 72–4, 77, 115 cleaning products, 64 day-care and schools, 111, 115 indoor ice sports, 139–40 inside automobiles, 129, 130–1, 132–3, 134, 135 offices, 317, 318, 320, 321, 322–3 traffic, 266, 430 urban pollution, 415, 416 volcanic emissions, 391–2, 399–401, 402, 403–4 weaving and spinning, 96, 97, 227, 228 weightlifting, 138, 155 welding, 197, 198, 199–201, 221, 257

INDEX

automobile industry, 211, 212, 213, 221 automobile maintenance, 204–5, 206, 207, 209 construction, 275, 276, 279, 282 wine grower’s lung, 164 wood, 223, 224, 224–6, 231 construction, 274, 276, 282, 285, 286 forest fires, 391, 392–6, 398 hobby pursuits, 97, 98 wood pulp worker’s disease, 164 woodwork teachers, 223, 224, 226 wool, 228 woolsorter’s disease, 230 World Trade Center, 267–8, 270, 301–2, 304, 305 cough, 301–2 zinc, 199, 220, 248, 347 zinc chloride (smoke bombs), 207 zinc oxide, 347, 349 zoonoses, 162, 168, 174 zoonotic pneumonia, 99, 104, 105