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C=~! `1 1~ -HE ~ ; Al I ASTHMA AND INDOOR AIR EXPOSURES Committee on the Assessment of Asthma and Indoor Air Division of Health Promotion and Disease Prevention INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C.

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NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Gov- erning Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engi- neering, and the Institute of Medicine. The members of the committee respon- sible for the report were chosen for their special competences and with regard for appropriate balance. Support for this study was provided by the U.S. Environmental Protection Agency (contract no. X825863-01-3. The views presented in the book are those of the Institute of Medicine Committee on the Assessment of Asthma and Indoor Air and are not necessarily those of the funding organization. Library of Congress Cataloging-in-Publication Data Institute of Medicine (U.S.~. Committee on the Assessment of Asthma and Indoor Air. Clearing the air: asthma and indoor air exposures / Committee on the Assessment of Asthma and Indoor Air, Division of Health Promotion and Disease Prevention, Institute of Medicine. p. cm. Includes bibliographical references and index. ISBN 0-309-06496-1 (case) 1. Asthma. 2. Indoor air pollution. 3. Asthma Government policy United States. I. Title. RA645.A83 I55 2000 362.1'96238 dc21 00-025801 Clearing the Air: Asthma and Indoor Air Exposures is available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Box 285, Washington, DC 20055. Call 800-624-6242 (202-334-3313 in the Washington DC metropolitan area) or visit the NAP's on-line bookstore at www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at www.iom.edu. Copyright 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among al- most all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

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National Academy of Sciences National Academy of Engineering institute of Medicine National Research Council The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal govern- ment on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the char- ter of the National Academy of Sciences, as a parallel organization of outstand- ing engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and educa- tion. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engi- neering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.

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Clearing the Air: Asthma and Indoor Air Exposures 1~ 1 E:: 1\lt'\ l l () l\l 7-\1- :~(,~'~\[) r- 1\/\l r. :: National Academy of Sciences National Academy of Engineering institute of Medicine National Research Council Prepublication Copy The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences. and.the National Academy of Engineering ~ providing.services. to..the government, Me public, and the. scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council. iv

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COMMITTEE ON THE ASSESSMENT OF ASTHMA AND INDOOR AIR RICHARD B. JOHNSTON, Jr., M.D. (Chair), Professor, Department of Pediatrics, University of Colorado School of Medicine, and National Jewish Medical and Research Center, Denver HARRIET A. BURGE, Ph.D., Associate Professor of Environmental Health, Department of Environmental Health, Harvard School of Public Health WILLIAM J. FISK, M.S., P.E., Staff Scientist/Group Leader, Indoor Environment Department, Lawrence Berkeley National Laboratory, Berkeley, California DIANE R. GOLD, M.D., M.P.H., Assistant Professor of Medicine, Harvard Medical School, and Assistant Professor, Environmental Health, Harvard School of Public Health LEON GORDIS, M.D., Dr.P.H., Professor of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University MICHAEL M. GRUNSTEIN, M.D., Ph.D., Professor, Department of Pediatrics, Children's Hospital of Philadelphia PATRICK L. KINNEY, Sc.D., Associate Professor, Division of Environmental Health Sciences, Columbia School of Public Health HERMAN E. MITCHELL, Ph.D., Adjunct Professor of Biostatistics, University of North Carolina, School of Public Health, Senior Research Scientist, Rho Federal Systems Division, Chapel Hill, North Carolina DENNIS R. OWNBY, M.D., Professor of Pediatrics, Medical College of Georgia THOMAS A. E. PLATTS-MILLS, M.D., Ph.D., Professor, Department of Medicine and Microbiology, and Chief, Division of Allergy, Asthma, and Clinical Immunology, University of Virginia Health Sciences Center SAMPSON B. SARPONG, M.B.Ch.B., Assistant Professor of Pediatrics, The University of Chicago Children's Hospital SANDRA WILSON, Ph.D., Senior Staff Scientist and Chair, Department of Health Services Research, Palo Alto Medical Foundation, Palo Alto, California v

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Stan DAVID A. BALED Study D1~c~r JENNIFER A. COHEN, Research Assistant HOSE MARIE ~=INEZ, Director DK1~on of neatly Fromot10n and Disease Frevent10n (as of December 1999) KATHLEEN H. SlH~10` Director D1vis10n of neatly Fromobon and Disease Frevent10n Shroud November 1999) DONNA D. DONCAN, D1vis10n Assistant ANDREA COHEN, [1nanc1~1 Associate ~1

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PREFACE The tremendous burden of disease imparted by asthma, the alarming escalation of asthma prevalence, and the doubling of the asthma mortality rate in the United States since the 1970s have attracted increased attention from those concerned about the health of the American public, including Congress. Many agen- cies of the U.S. government have been charged to increase their efforts at addressing at least one facet of the problem, from re- search into pathogenesis by the National Institutes of Health to examination of environmental factors by the Environmental Pro- tection Agency (EPA). It is highly likely that such a rapid rise in asthma prevalence is due to a change in some factor or factors in the environment. Identifying these factors could allow remediation, and perhaps prevention. Within this context the EPA sought the guidance of the Institute of Medicine (IOM) in evaluating the quality and nature of the scientific data relating constituents of indoor air and the occurrence of asthma. The multidisciplinary committee convened by the IOM to re- spond to this charge, with considerable help from IOM staff, spent many hours in literature review and discussion. Our goal was to reach consensus about how strongly the research data implicated various components of indoor air as causes of asthma. A second goal was to evaluate the state of the scientific evidence concern- ing specific strategies for exposure mitigation and prevention. v''

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vIll PREFACE Common problems frustrated our efforts, starting with the imprecise and variable definition of asthma used in research stud- ies, and followed immediately by what it means to "cause" asthma. An unfortunate configuration of genes that influence the immune or inflammatory responses might be said to be the pri- mary "cause" of asthma. But even identical twins may differ as to whether they have asthma or not. Exposure to some environmen- tal factor or factors is required to elicit the clinical expression of asthma, i.e., cause the development of asthma. The same or other agents may then cause exacerbation of asthma symptoms in these individuals. Thus, the committee divided its analysis into whether an agent might cause asthma development or exacerba- tion of symptoms. Considering how the indoor environment might be modified to reduce the risk of asthma development or exacerbation pre- sented a particularly formidable challenge. It has been known for a long time that changing the environment of an asthmatic indi- vidual can reduce symptoms, at least temporarily. Mitigation is possible for individual patients. However, little data are available to allow firm conclusions about specific mitigation techniques applied as a public health measure. Although interventions that might reduce the severity of asthma in individual patients emerge from the committee's review, it is hard to escape the overwhelm- ing conclusion that more research is desperately needed to form the basis for public health interventions. Too much ignorance re- mains regarding the biologic changes that permit the disease to emerge and recur, the environmental "causes" that may underlie the increased prevalence, the socioeconomic differences in rates of morbidity and mortality, and the means of effective exposure mitigation and prevention. Although it will be essential to gain a better understanding of the relationship between particular agents and asthma, no single agent or factor has yet been identi- fied as a necessary or sufficient cause of asthma. Until a more fundamental understanding is available, multifaceted approaches will be needed to address the interrelationships among biologic, environmental, and socioeconomic factors that permit expression of this disease. The committee exercised final responsibility for all content of the report, but we were not its only contributors. In fact, we could

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PREFACE MIX not have completed our task satisfactorily without the substantial help of the individuals cited in the Acknowledgments section. We are especially indebted to Peter I. Gergen, Donald K. Milton, Wil- liam B. Rose, and Kathleen Kreiss, who furnished text and discus- sions that were essential to our deliberations on certain subjects. The committee has also recognized that the report could never have been developed without the work of the extraordinary staff assigned to us by the Institute of Medicine David Butler, lames Bowers, Jennifer Cohen, Donna Duncan, Andrea Cohen, and Kathleen Stratton. In particular, David Butler, Study Director, with intelligence, patience, persistence, and hard work, expedited and channeled our deliberations through a dismaying array of sub- jects, from exposure assessment to pathophysiology, to their final expression as the report. Richard B. Johnston, Ir., M.D. Chair

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ACKNOWLEDGMENTS Preparation of this report could not have happened without the guidance and expertise of numerous individuals. Although it is not possible to mention by name all of those who contributed to this committee's work, the committee wants to express its grati- tude to a number of individuals for their special contributions. Sincere thanks go to all of the participants at the workshops convened on January 18 and March 22, 1999. The intent of these workshops was to gather information regarding exposure to spe- cific indoor air allergens and irritants, and asthma pathogenesis, the triggering of asthma attacks, and the exacerbation of symp- toms in asthmatics. The speakers, who are listed in Appendix B. gave generously of their time and expertise to help inform and guide the committee's work. We are particularly appreciative of the efforts of four indi- viduals who contributed text that was used or formed the basis of discussions in this report: Peter I. Gergen, M.D., M.P.H.; Kathleen Kreiss, M.D.; Donald Milton, M.D., Dr.P.H.; and William B. Rose, M.Arch. Their contributions greatly aided the committee and had a significant positive impact. The Committee on the Assessment of Asthma and Indoor Air has, of course, final responsibility for all content in the report. The committee extends special thanks to the dedicated and hard working staff at the Institute of Medicine (IOM). The exper x'

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xI! ACKNOWLEDGMENTS tise and leadership of Kathleen Stratton, Director of the Division of Health Promotion and Disease Prevention, helped to ensure that this report met the highest standards for quality. This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Re- view Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institu- tion in making the published report as sound as possible and to ensure that the report meets institutional standards for objectiv- ity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Eula gingham, University of Cincinnati; Noreen Clark, University of Michigan School of Public Health; Peyton Eggleston, Johns Hopkins University School of Medicine; Leslie Grammer, Northwestern University Medical School; Jonathan Samet, Johns Hopkins University School of Hygiene and Public Health; Olli Seppanen, Helsinki University of Technology; and Scott Weiss, Harvard University School of Medicine. While the individuals listed above have provided constructive comments and suggestions, it must be emphasized that responsibility for the final content of this report rests entirely with the authoring committee and the institution. Finally, the committee would like to thank the chair, Richard Johnston, Ir., M.D., for his outstanding work, leadership, and dedication to this project.

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CONTENTS EXECUTIVE SUMMARY Organization and Framework, 2 Conclusions about the Relationship between Indoor Exposures and Asthma, 4 General Research Recommendations and Conclusions, 16 1 MAJOR ISSUES IN UNDERSTANDING ASTHMA Origin of the Study, 19 Summary of the Indoor Allergens Report, 20 Definitions of Asthma, 22 Clinical Presentation of Asthma 24 Risk Factors for Asthma, 28 Trends in the Prevalence of Asthma, 29 Mechanisms of Asthma, 31 Evaluating the Effectiveness of Interventions to Reduce Asthma, 33 2 METHODOLOGICAL CONSIDERATIONS IN EVALUATING THE EVIDENCE Evaluating the Evidence, 40 Summarizing Conclusions Regarding the Evidence, 48 Assessing Exposures to Agents in Indoor Air, 51 Other Considerations, 62 x''' 39

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xIv CONTENTS PATTERNS OF ASTHMA MORBIDITY AND MORTALITY The Burden of Asthma, 67 Mortality, 68 Utilization of Health Care Services, 69 Prevalence, 70 Severity, 75 Trends in Risk Factors, 77 Twin, Adoption, and Migrant Studies, 78 Socioeconomic Status Versus Race or Ethnicity, 79 Asthma Rates in Germany A Natural Experiment, 80 Reflections on the Trends, 81 67 4 PATHOPHYSIOLOGICAL BASIS OF ASTHMA 87 Airway Inflammation in Asthma, 88 The Airway Smooth Muscle in Asthma, 96 The Genetics of Asthma, 98 Conclusion, 99 INDOOR BIOLOGIC EXPOSURES Animals, 106 Cockroach, 124 House Dust Mites, 136 Endotoxins, 150 Fungi, 158 Infectious Agents, 175 Houseplants, 184 Pollen, 186 6 INDOOR CHEMICAL EXPOSURES Nitrogen Dioxide, 224 Pesticides, 234 Volatile Organic Compounds, 237 Formaldehyde, 243 Fragrances, 247 Plasticizers, 250 Other Chemical Exposures in the Indoor Environment, 251 105 223

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CONTENTS EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE Definition of Environmental Tobacco Smoke (ETS), 264 Factors Controlling Exposure to ETS, 265 Evidence of a Relationship between ETS and Asthma, 271 Conclusions Regarding the Health Impacts of ETS with Respect to Asthma, 280 Evidence Regarding Means of Source Mitigation or Prevention, 281 Conclusions Regarding ETS Source Control or Mitigation: Feasibility and Benefits, 288 Research Needs, 290 8 INDOOR DAMPNESS AND ASTHMA Indoor Water Sources and Removal Processes, 299 Indoor Dampness and Respiratory Disease, 307 Dampness Control, 310 Research Needs, 311 9 ASTHMA AND NONRESIDENTIAL INDOOR ENVIRONMENTS Building-Related Asthma, 316 Studies of Schools, 321 Conclusion, 324 Research Needs, 324 10 IMPACT OF VENTILATION AND AIR CLEANING ON ASTHMA Theoretical Background, 327 Building Ventilation, 331 Particle Air Cleaning: Introduction and Review of Conventional Practice, 360 11 SUMMARY OF RESEARCH RECOMMENDATIONS AND OVERALL CONCLUSIONS Pathophysiologic Basis of Asthma, 394 Animal Allergens, 394 Cockroach, 396 House Dust Mites, 396 xv 263 298 316 327 394

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xv! Endotoxin, 397 Fungi, 398 Infectious Agents, 398 Plants, 399 Nitrogen Dioxide (NO2), 399 Pesticides, 399 Plasticizers, 400 Volatile Organic Compounds, 400 Fragrances, 400 Environmental Tobacco Smoke (ETS), 401 Indoor Dampness, Moisture Problems and Moisture Control, 402 Nonresidential Indoor Environments, 402 Ventilation, 403 Air Cleaning, 404 Overall Conclusions, 405 APPENDIXES A Theoretical Considerations Relevant to the Influen of Ventilation and Air Cleaning on Exposures to Indoor-Generated Pollutants B Workshop Summaries C Committee and Staff Biographies INDEX CONTENTS 409 415 418 425

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CLEARI NO THE ~ j Al r

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