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C=~! `1 1~
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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.
OCR for page R2
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
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OCR for page R3
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institute of Medicine
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sponsors engineering programs aimed at meeting national needs, encourages
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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
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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
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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.
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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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