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This page intentionally left blank
 Fourth Edition

Edited by

Jean-Luc Malo
Department of Medicine, Université de Montréal and
Department of Chest Medicine, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada

Moira Chan-Yeung
Occupational and Environmental Lung Diseases Unit,
Respiratory Division, Department of Medicine,
University of British Columbia and Respiratory Division,
Department of Medicine, The University of Hong Kong

and

David I. Bernstein
Division of Allergy–Immunology, Department of Internal Medicine,
College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

Boca Raton London New York

CRC Press is an imprint of the

Taylor & Francis Group, an informa business
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 In memoriam

We dedicate this fourth edition of Asthma in the Workplace to the memory of our esteemed colleague and fellow co-editor, I. Leonard
Bernstein, who passed away on March 26, 2012, at the age of 88. Dr. Bernstein received his medical degree from the University of
Cincinnati in 1949, followed by training in internal medicine, pulmonology, and allergy. He rose to become a professor of medi-
cine and environmental health sciences at the University of Cincinnati, where he served as director of the Allergy Research Labora-
tory and Allergy Fellowship Training Program. For most of his career, he conducted NIH- and NIOSH-sponsored research in his
Allergy Laboratory in the Division of Immunology, University of Cincinnati, focused on allergens and occupational asthma. He
was a member of 14 professional organizations including the American Academy of Allergy Asthma and Immunology, for which
he served as its president in 1982. Throughout his long professional career, he was highly committed to the training and mentoring
of countless numbers of young physicians and graduate students. Among his many research contributions to the field of occupa-
tional lung disease, he defined allergic mechanisms of occupational asthma (e.g., acid anhydrides, platinum salts) and was the first
to identify cellular immune mechanisms associated with diisocyanate-induced asthma. Leonard viewed his active participation in
editing and writing the first three editions of Asthma in the Workplace as a labor of love. He was highly enthusiastic and assiduous
in editing and personally authored or coauthored many of the most important chapters. As the senior editor, he set the highest of
standards for content and accuracy. He loved interacting with his colleagues at meetings and forums devoted to occupational
disorders, where he was usually the first to pose an insightful question or initiate a stimulating discussion. He will be remembered
by his friends and colleagues for his wisdom, breadth of knowledge, and intellectual curiosity.

Sincerely,
Co-Editors
This page intentionally left blank
Contributors ix 12. Prevention and surveillance 150
Foreword xii Gary M. Liss, Susan M. Tarlo, Manon Labrecque,
Preface xiii Jean-Luc Malo
13A. Impairment and disability evaluations:
I. Psychosocial, economic,
and medicolegal aspects 163
1. Definition and classification of asthma Paul D. Blanc, Philip Harber, Kim L. Lavoie,
in the workplace 1 Olivier Vandenplas
I. Leonard Bernstein, David I. Bernstein, 13B. Impairment and disability evaluation:
Moira Chan-Yeung, Jean-Luc Malo II. Various legislations 182
2. Historical aspects 6 Mohamed F. Jeebhay, Philip Harber, Xaver Baur,
Jack Pepys, I. Leonard Bernstein, Jean-Luc Malo Marcos Ribeiro, Hae-Sim Park, Jean-Luc Malo
3. Disease occurrence and risk factors 18
Maritta S. Jaakkola, Denyse Gautrin, Jean-Luc Malo
4. Mechanisms, genetics, and pathophysiology 40
Piero Maestrelli, Berran Yucesoy, Hae-Sim Park,
Adam V. Wisnewski
14. High- and low-molecular weight agents 194
5. Animal models 57
Moira Chan-Yeung, Jean-Luc Malo,
Victor J. Johnson, Vanessa De Vooght,
David I. Bernstein
Jeroen A.J. Vanoirbeek
15. Enzymes 209
Jonathan A. Bernstein, Katherine Sarlo,
Carlos Rodriguez, Remko Houba
16. Occupational asthma in the baking industry 222
6. Assessment of the worker 73 Paul Cullinan, Torben Sigsgaard, Rolf Merget
André Cartier, Nathalie Bourdeau, 17. Asthma and allergy to animals 238
Pierre Phénix, Kenneth D. Rosenman Karin A. Pacheco, Denyse Gautrin,
7. Assessment of the workplace 85 Andreas L. Lopata, Mohamed F. Jeebhay
Dick Heederik, Lygia Budnik, 18. Polyisocyanates and their prepolymers 262
Brigitte Roberge, Nicole Goyer Adam V. Wisnewski, Carrie A. Redlich,
8. Immunological and inflammatory assessments 99 Cristina E. Mapp, David I. Bernstein
Catherine Lemière, David I. Bernstein, 19. Western red cedar and other wood dusts 276
Leslie C. Grammer, Meinir Jones, Hae-Sim Park Moira Chan-Yeung, Jean-Luc Malo,
9. Functional assessment 113 Torben Sigsgaard
Olivier Vandenplas, P. Sherwood Burge, 20. Metals 290
Gianna Moscato, Jean-Luc Malo Rolf Merget, Denyse Gautrin

10. Management of the worker 133

André Cartier, Paul K. Henneberger, 21. Irritant-induced asthma and reactive
Stuart M. Brooks airways dysfunction syndrome 305
11. Protecting the worker and modifying the Stuart M. Brooks, Jean-Luc Malo, Denyse Gautrin
work environment 138 22. Asthma exacerbated at work 325
Dick Heederik, Remko Houba, Gary M. Liss, Paul K. Henneberger, Gregory R. Wagner,
Melissa Millerick-May Catherine Lemière

vii
 contents
23. Eosinophilic bronchitis 336 27. Hypersensitivity pneumonitis and organic
Santiago Quirce, Catherine Lemière, dust toxic syndrome 392
Joaquín Sastre Yvon Cormier, Yves Lacasse
24. Occupational rhinitis 344 28. Building-related illnesses and
Gianna Moscato, Mark S. Dykewicz, mold-related conditions 406
Martin Desrosiers, Roberto Castano Dan Norbäck, J. David Miller
25. Airway diseases due to organic dust exposure 357 29. Occupational urticaria and allergic
Moira Chan-Yeung, I. Leonard Bernstein, contact dermatitis 418
Susanna Von Essen, Jill A. Poole D. Linn Holness, Victoria H. Arrandale,
26. Chronic obstructive airway disease due C.G. Toby Mathias
to occupational exposure 375
Paul D. Blanc, Eva Hnizdo, Index 435
Kathleen Kreiss, Kjell Toren

viii
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Division of Preventive Medicine, University of Alberta, Department of Surgery/Otolaryngology, Respiratory Division,
Edmonton, AB T6G 2T4, Canada Research Institute, Hôpital du Sacré-Coeur de Montréal,
Université de Montréal, Québec, Canada

Institute for Occupational and Maritime Medicine, Medical

Faculty, University of Hamburg, University Medical Center, Occupational and Environmental Lung Diseases Unit,
WHO Collaborating Centre for Health of Seafarers, Respiratory Division, Department of Medicine,
Hamburg, Germany University of British Columbia and Respiratory Division,
Department of Medicine, The University of Hong Kong,
Hong Kong
Division of Allergy–Immunology, Department of Internal
Medicine, College of Medicine, University of Cincinnati,
Cincinnati, Ohio, USA Centre de Pneumologie, Institut universitaire de cardiologie et
de pneumologie de Québec (Hôpital Laval), Québec, Canada

Department of Medicine, University of Cincinnati College of

Medicine, Cincinnati, Ohio, USA Occupational and Environmental Medicine,
Imperial College (NHLI), London, UK
Division of Allergy–Immunology,
Department of Internal Medicine, College of Medicine,
University of Cincinnati, Cincinnati, Ohio, USA Department of Public Health, Occupational, Environmental &
Insurance Medicine, KU Leuven, Belgium

Division of Occupational and Environmental Medicine,

Department of Medicine, University of Université de Montréal and Hôtel-Dieu de Montréal, Centre
California-San Francisco, USA hospitalier universitaire de l’Université de Montréal, Montréal,
Québec, Canada
Clinical nurse, Occupational Health Service,
CSSS Pointe-de-l’Île, Montréal, Qc, Canada
Allergy and Immunology Unit, Section on Pulmonary,
Critical Care, Allergy and Immunologic Diseases, Wake Forest
College of Public Health, University of South Florida, University School of Medicine, Center for Human Genomics
Tampa, Florida, USA and Personalized Medicine Research,
Winston-Salem, North Carolina, USA

Institute for Occupational and Maritime Medicine, Medical

Faculty, University of Hamburg, University Medical Center,
Department of Medicine, Université de Montréal and
WHO Collaborating Centre for Health of Seafarers,
Research Center, Hôpital du Sacré-Cœur de Montréal,
Hamburg, Germany
Montréal, Québec, Canada

Occupational Lung Disease Unit, Birmingham Heartlands

Hospital, Birmingham, UK Montréal, Québec, Canada

Department of Chest Medicine, Hôpital du Sacré-Coeur de Allergy-Immunology Division, Northwestern University

Montréal, Université de Montréal, Montréal, Québec, Canada Feinberg School of Medicine, Chicago, Illinois, USA

ix
 contributors

Mel and Enid Zuckerman College of Public Health, Centre de Pneumologie, Institut universitaire de cardiologie et
University of Arizona, Tucson, Arizona, USA; and de pneumologie de Québec (Hôpital Laval), Québec, Canada
Professor Emeritus, David Geffen School of Medicine at UCLA,
Los Angeles, California, USA
Montreal Behavioural Medicine Centre; Research Centre,
Hôpital du Sacré-Coeur de Montréal and
Division of Environmental Epidemiology, IRAS, Utrecht Institut de cardiologie de Montréal (both Université
University, Utrecht, the Netherlands de Montréal affiliated). Department of Psychology,
Université du Québec à Montréal,
Montréal, Québec, Canada
Division of Respiratory Disease Studies, National Institute for
Occupational Safety and Health, Centers for Disease Control
and Prevention, Morgantown, West Virginia, USA Pulmonology Department, Université de Montréal and
Hôpital du Sacré-Coeur Hospital, Montréal,
Québec, Canada
Surveillance Branch, Division of Respiratory Disease Studies,
NIOSH, Morgantown, West Virginia, USA
Gage Occupational and Environmental Health Unit, Dalla
Lana School of Public Health, University of Toronto,
University of Toronto, Toronto, Ontario, Canada, Toronto, Canada
St Michael’s Hospital, Toronto, Ontario, Canada

School of Pharmacy and Molecular Science; Molecular

Institute for Risk Assessment Sciences (IRAS) & Netherlands Immunology Group, Faculty of Medicine, Health & Molecular
Expertise Centre for Occupational Respiratory Disorders Sciences, James Cook University, Queensland, Australia
(NECORD), Utrecht, the Netherlands

Department of Cardiologic, Thoracic and Vascular Sciences,

Center for Environmental and Respiratory Health Research, University of Padova, Padova, Italy
University of Oulu, Oulu, Finland, and Respiratory Medicine
Unit, Institute of Clinical Sciences, University of Oulu, and
Oulu University Hospital, Oulu, Finland Department of Medicine, Université de Montréal and
Department of Chest Medicine, Hôpital du Sacré-Coeur de
Montréal, Montréal, Québec, Canada
Centre for Occupational and Environmental Health Research,
WHO Collaborating Centre in Occupational Health, School of
Public Health and Family Medicine, University of Cape Town,
Section of Hygiene and Occupational
Cape Town, South Africa
Medicine, Department of Clinical and
Experimental Medicine, University of Ferrara,
Padova, Italy
Burleson Research Technologies, Inc. Morrisville,
North Carolina, USA
Departments of Environmental Health and Dermatology,
Department of Occupational and Environmental Medicine, University of Cincinnati Medical Center and Group Health
Imperial College, London, UK Associates, Cincinnati, Ohio, USA

Surveillance Branch, Division of Respiratory Disease Studies, Institute for Prevention and Occupational Medicine
NIOSH, Morgantown, West Virginia, USA of the German Social Accident Insurance, Institute of
the Ruhr University (IPA), Bochum, Germany

Department of Medicine, Université de Montréal and

Department of Chest Medicine, Hôpital du Sacré-Coeur Department of Chemistry, Carleton University,
de Montréal, Montréal, Québec, Canada Ottawa, Ontario, Canada

x
 contributors

Division of Occupational and Environmental Medicine, Procter & Gamble Eurocor, Belgium
Michigan State University, East Lansing, Michigan, USA

Division of Occupational and Environmental Medicine,

Michigan State University, Michigan, USA
Allergy and Immunology Unit, Fondazione Salvatore Maugeri,
IRCCS, Scientific Institute of Pavia, Pavia, Italy
Procter & Gamble Company, Miami Valley Laboratories,
Cincinnati, Ohio, USA
Department of Medical Science, Occupational and Environ-
mental Medicine, Uppsala University and University Hospital,
Uppsala, Sweden Department of Allergy, Fundación Jiménez Díaz and CIBERES
(Carlos III National Institute of Health, Ministry of Economy
and Competitiveness), Madrid, Spain
Division of Environmental & Occupational Health Sciences,
National Jewish Health, Denver, Colorado, USA; and
Colorado School of Public Health, Aurora, Colorado, USA Department of Public Health, Section of Environmental &
Occupational Medicine, University of Aarhus, Aarhus, Denmark

Department of Allergy and Clinical Immunology, Ajou University

School of Medicine, Youngtongku, Suwon, South Korea Gage Occupational and Environmental Health Unit, Dalla Lana
School of Public Health University of Toronto, Toronto, Canada

Royal Postgraduate Medical School, London, UK

Section of Occupational and Environmental Medicine,
Institute of Medicine, Sahlgrenska Academy at University of
Occupational Health Service, Public Health Department, Gothenburg, University Hospital, Sahlgrenska Academy at
Agence de la santé et des services sociaux de Montréal, Göteborg University, Göteborg, Sweden
Montréal, Québec, Canada
Service de pneumologie, Centre Hospitalier Universitaire de
Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium
Division of Pulmonary, Critical Care, Sleep & Allergy
Medicine, Department of Medicine, University of Nebraska
Medical Center, Omaha, Nebraska, USA Department of Public Health, Occupational, Environmental &
Insurance Medicine, KU Leuven, Belgium

Department of Allergy, Hospital La Paz Institute for Health

Research (IdiPAZ) and CIBERES (Carlos III National Institute of Department of Internal Medicine, Pulmonary, Critical Care,
Health, Ministry of Economy and Competitiveness), Sleep and Allergy Division, University of Nebraska Medical
Madrid, Spain Center, Omaha, Nebraska, USA

Occupational and Environmental Medicine and Pulmonary National Institute for Occupational Safety and Health,
and Critical Care Medicine, Yale School of Medicine, Washington, D.C., and Department of Environmental Health,
New Haven, Connecticut, USA Harvard School of Public Health, Boston, Massachusetts, USA

Division of Respirology, Department of Medicine, University Department of Internal Medicine, Yale University School of
of Toronto, Toronto, Ontario, Canada; and Medicine, New Haven, Connecticut, USA
Toronto Western Hospital, Toronto, Ontario, Canada

Toxicology and Molecular Biology Branch, Health Effects

Institut de recherche Robert-Sauvé en santé et en sécurité du Laboratory Division, NIOSH/CDC, Morgantown,
travail, Montréal, Québec, Canada West Virginia, USA

xi
Asthma is a potentially reversible and treatable disease. Over are designed to have relevance to a broad group of readers. The
the past decades, the mechanisms of asthma pathogenesis sections are well organized to provide current information con-
have been increasingly examined and better understood. cerning workplace asthma, including clinical assessment and
The role of occupational exposure in the pathogenesis of patient management, specific causes, and disease entities.
asthma has also been recognized to be a common work- The new edition follows the tradition of previous editions in
related phenomenon. bringing in new topics. Examples in the new edition include
The textbook Asthma in the Workplace was initiated to pro- worker protection and work environment modification; dis-
vide up-to-date information concerning the causes and treat- ease management by the worker; and diseases such as occupa-
ment of work-related asthma. The incidence of asthma has tional eosinophilic bronchitis, bronchiolitis obliterans, and
increased markedly, and the frequency of asthma in the work- occupational contact dermatitis caused by agents that cause
place and occupational asthma has also increased. Each edition occupational asthma. Presenting accurate information pertain-
of this text has provided new strategies and new insights. This ing to occupational asthma continues to be an important chal-
is due in part to the fact that new causes occur and to the emer- lenge to this collaborative team of international experts who
gence of new ideas about persistent problems. In the new edi- continue to share successfully their expertise with the reader.
tion, roles of occupational exposures in chronic obstructive In summary, a worldwide group of experts contribute new
pulmonary disease are added. At the end of each chapter, the approaches and ideas to this excellent textbook.
authors consider where the issues explored in the chapter are
headed. Jay A. Nadel, MD
The new edition is also designed to provide appeal to a wider University of California, San Francisco
group of readers, including general physicians, occupational San Francisco, California
nurses, general industrial hygienists, and others. The chapters USA

xii
Although occupational asthma was recognized as early as updated and revised edition. In addition, coverage of several
the 18th century by Ramazzini, its importance as a signifi- specific areas of interest that had not yet clearly evolved prior to
cant hazard in the workplace was not widely appreciated publication of the first three editions has been either added or
until the spurt in industrial technology after World War II. expanded.
The literature concerning workplace asthma has steadily The fourth edition retains the international nature in the
increased since the great impetus given by Professor Jack coalition of editors and individual contributors. The common
Pepys, who can be considered the father of occupational goal of this cooperative effort was to prepare an authoritative,
asthma and to whom the first three editions of this book educational resource for primary care physicians, occupational
were dedicated. The frequency of asthma in the workplace health specialists, allergists, and pulmonologists.
and occupational asthma has increased with a recent plateau To make this reference book particularly germane for pri-
and is now one of the most prevalent occupational lung mary care providers to develop skills in the early recognition
diseases (chap. 3). In some industrialized countries, occupa- of the disease, this edition has a new feature at the beginning
tional asthma has even replaced pneumoconiosis as the most of relevant chapters: a clinical history or a workplace scenario
common work-related respiratory diseases. with referrals in the main part of the chapter. As the diagnosis
Asthma in the workplace is a complex entity that is not of occupational asthma is often difficult because of multiple
equivalent to new-onset occupational asthma as defined in the causalities in many occupational environments, the variability
first chapter of the first two editions of the book but has been of symptoms and patterns of late-phase asthmatic reactions,
revised in the third edition to account for the fact that approxi- the requirements for special diagnostic procedures, and the
mately 10% of asthmatic subjects have preexisting or concomi- unpredictability of onset and persistence of symptoms, spe-
tant nonoccupational asthma and to note that conditions at cial emphasis has been given to an algorithm of clinical diag-
work worsen their symptoms (i.e., work-exacerbated asthma). nosis, immunological evaluation, and physiological methods
Occupational asthma is a condition that has attracted the of evaluation (chaps. 6–9) as a practical guide for primary
interests of a wide variety of disciplines: allergists, immunolo- care physicians.
gists, pulmonologists, immunotoxicologists, occupational health New chapters on assessment and management of the work-
specialists, aerosol scientists, hygienists, and epidemiologists. place have been added for industrial hygienists. Expanded
Outbreaks of occupational asthma in specific work settings are chapters on medicolegal aspects, prevention, and surveillance
ideal, mini-epidemiological paradigms of nonoccupational asthma (chaps. 11–13) address the social outcomes of workers dis-
and provide excellent opportunities for investigating the source, abled by asthma and should serve as useful reference sources
the characteristics of the emission–dispersion cycles, and the for occupational health physicians, workers’ compensation
health impact of inciting agents. The ready access to such inte- administrators, private insurers, attorneys, adjudicators, and
grated data in a defined setting provides an ideal milieu and legislators.
investigational model for further advancement of knowledge The chapters concerning epidemiology and disease enti-
about the pathophysiological pathways and natural history of ties have been prepared to provide sufficient in-depth infor-
asthma by specialists from various disciplines. In addition, the mation for occupational health and other medical
economic and social hardships imposed on a worker with refrac- subspecialists primarily concerned with asthma in the work-
tory symptoms associated with occupational asthma may require place. Although occupational asthma represents the core of
consultation with a psychologist and a legal counsel. These inter- this book, this edition includes chapters on irritant-induced
actions have clearly established that the features of occupational asthma and reactive airways syndrome and asthma exacer-
asthma are unique and often at odds with medical dogma derived bated at work, with all conditions being grouped under the
from the surveillance, diagnosis, and prevention of mineral general theme of “asthma in the workplace.” Conditions that
dust–induced lung disorders. share clinical, functional, or immunological features to
The enthusiastic response to publication of the first, second, workplace asthma (eosinophilic bronchitis, airway diseases
and third editions of this book and the number of literature due to organic dust exposure, chronic obstructive pulmo-
citations attributed to it have more than justified preparation nary disease due to occupational exposure, hypersensitivity
of a fourth edition. pneumonitis, building-related illnesses) are covered in spe-
Discovery and research in workplace-related asthma have cific chapters 23 and 25 to 28. The relationship of conditions
continued at a rapid pace and have served as the impetus for this frequently associated with workplace asthma is reviewed

xiii
 preface
in chapters 24 (occupational rhinitis) and 29 (occupational question. As often occurs with meta-analyses, agreement at
urticaria and contact dermatitis). times is incomplete. Above all, the authors and editors have
The book is organized into five main parts: attempted to balance opposing views as objectively as possible.
Part I, “General Considerations,” contains chapters on defini- In most cases, this balancing process was successful in arriving
tions, historical background, epidemiology, genetics, patho- at editorial consensus. Where this was not possible, the data
physiology, and animal models. appear with the caveat that a controversy exists and resolution
Part II, “Assessment” includes chapters that delineate guide- is not possible, because definitive data are either not yet avail-
lines for assessing the worker and the workplace. able or under investigation. These critical assessments have
Part III, “Management” includes chapters that propose been rewarding educational experiences for the editors and
guidelines for the management of worker and the workplace, authors. We hope that this joint effort will not only provide
including compensation aspects. pragmatic information for current clinical applications but
Part IV, “Specific Agents Causing Immunological Occupa- also serve as a foundation for significant new research infor-
tional Asthma” provides detailed information about specific mation that will most assuredly advance the discipline during
agents (including a variety of high- and low-molecular weight this new millennium.
agents). The preparation of this fourth edition was sadly marked by
Part V, “Specific Disease Entities and Variants,” covers other the recent loss of one of our editors, Dr. I. Leonard Bernstein, a
types of work-related asthma conditions, for example, irritant- most renowned thought leader and authority in allergy and
induced asthma, asthma exacerbated at work, eosinophilic immunology and an attentive, stimulating, and cheerful col-
bronchitis as well as acute and chronic asthma-like syndromes. league. He had played a leading role in initiating, writing, and
Occupational rhinitis, urticaria and allergic contact dermatitis editing the first three editions of this textbook and had dedi-
are also covered in this section. cated enormous energy and effort toward its success. The edi-
Most of the chapters have been revised and new chapters tors wish to dedicate this fourth edition to the beloved memory
have been introduced without adding to the overall length of of Leonard, our dear friend and colleague.
the book. Some of the chapters have new or additional con-
tributors. The preparation of individual chapters by multiple
authors and the endeavor that the authors have put forth in Jean-Luc Malo
this edition are similar to meta-analyses that compare different Moira Chan-Yeung
published health-related data pertaining to a given research David I. Bernstein

xiv
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