THE HEALTH . 1 I CONSEQUENCES OF INVOLUNTARY SMOKING a report of the Surgeon General U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES P&k Health Smvke `.rtStCstlAs"Or*t.LI*.ND*"UI1ot.",(t~ ".s*l*GI"* DL mie, MC I 5 1986 The mnorable George Bush President of the Senetc W..hington. D.C. 20510 Desr Mr. President: It is my pleasure to transmit to the Congress the 1986 Surgeon Gener.1'. Report on the halt? consequence. of smking, . . mandated by Section g(s) of the Public Re.lth Cxgsrette S-king Act of 1969. me "e.lth Consequence* of involunt.ry Smking The current volume, entitled , exuine. the scientific evidence on the he.lth effect. re."lttng from mn.mker exposure to envirollaenr.1 tob.cc" snake. The issue of whether or mt tob.cco slake is c.rcinogeaic for humans was conclusively resolved mre thss 20 ye.=. *go when the first report on *staking *ad heslth w.. issued in 1964. Eased on the c"rrent report, the judgment c.n 11)y be tude that exposure to envim-nt.1 tob.cco s-kc csn E.".c disesse, including lung cancer, in mnstmkers. It is *la clear th.t simple .ep.r.cioa of smkers snd mns~ker. within the ..Y sirspsce uy reduce but canmt elimin.te mnsmker exposure to envirorucnt.1 tobacco slake. Ihe report .lw review. *II extensive body of evidence which e.t.bli.he. .O incressed risk of reapir.tory illness snd reduced lung function in infsnt. .nd very y~"ng children of p.rent. rbD .oke. Ihi. effect is ~)re pmmuaced if both pxent. sake than if only one p.rent sakes. A. . phy.ici.n. I believe th.t p.reot. should refr.in from -king *round s-11 children both s. . r.n. of protecting their children'. heslth and to set . pd o rqle for the child. Today, only 30 percent of the adult populstion in the United gt.te. .re *mker.-the 1are.C level of soking in the country since World Ysr II, reflecting th.t the grest msjority of the populstion h.. never mked or hr. *"cce**f"lly quit. Accompsnying this decline in over.11 prevslence of cigsrette smking h.. been sn Lcrersed cancera for protecting the he.lth .nd well being of mnsmxker., s. evidenced by the number of lr. and reyl.tion. restricting soking in public plsces. Todsy, 40 gtste. snd the District of Dlubi. hsve enacted some fotn of legislstion to restrict swking in public. Increasingly, these lr. pertsin to protecting mnswkcrs in uny different setting., including the varkplsce. B..ed on the evidence presented in this report. the choice to slake .hD"ld n"t interfere with the mn.aDker'. choice for sn environment free of tob.cco .aDke. Sincerely, . &gwhNtQ m% Otis B. gown, M.D. secretary enc1o.ure DEL 5 The ibnorable Thomas P. O'Neill, or. Speaker of the H3u.e of Representatives Washington, D.C. 20515 Oear Hr. Speaker: It is my pleasure co rransmit to the Congress the 1986 Surgeon General's Report an the health consequences of sroking, . . mandated by Section B(a) of the Public Health Cigarette Smklng Act of 1969. The current volume. entitled The Health Consequences of Involuntary Swking, examines the ocieotific evidence on the health effects resulting from nonsmoker exposure to environmental tobacco smoke. The issue of whether or mt tobscco awke is csrcimgenic for humans ~88 conclusively resolved m)re thsn 20 yesrs .go when the first report on smking and heslth YBB issued in 1964. Based on the current report. the judgment c.n now be made chat exposure to environmental tobscco sswke csn cause disease. including lung cancer, in mnsmkers. It is also c1e.r that simple separation of smkers and nonsrmkers within the s.me airap.ce msy reduce but csnnot eliminate mnsmDker exposure to environment.1 tobscco amke. The report also reviews sn extensive body of evidence which establishes .n incressed risk of respiratory illness and reduced lung function in infants .nd very young children of psrenta who smoke. This effect ia mire pmmunced if both p.rents anote th.n if only one parent amkes. As . physician, I believe that parents should refrsin from smoking emend sm.11 children both as . means of protecting their children's heslth and to set . pod ersmple for the child. Today, only 30 percent of the adult popul.tion in the United St.Ces are srtokers-the lovest level of waking in the country since YDrld Usr II, reflecting thst the great mjority of the populscion h.. never smked or has successfully quit. Accompanying this decline in overall prevalence of cigarette swking h.s been an incre.sed concern for protecting the health snd well being of nonsmokers, as evidenced by the number of lens snd regulstians restricting smking in public places. Today, 40 St.tea .nd the District of Columbia have enacted some form of legislation to restrict smoking in public. Increasingly, these 1~s pertain to protecting nonawkers in m.ny different setting., including the workplace. Based on the evidence presented in this report, the choice to srmke should mt interfere with the mnslmker's choice for an environment free of tobacco woke. Sincerely, W fl,a. Otis R. Bowen, M.D. secretary FOREWORD The data reviewed in 17 previous U.S. Public Health Service reports on the health consequences of smoking have conclusively established cigarette smoking as the largest single preventable cause of premature death and disability in the United States. The question whether tobacco smoke is harmful to smokers was answered more than 20 years ago. As a result, many scientists began to question whether the low levels of exposure to environmental tobacco smoke (ETS) received by nonsmokers could also be harmful. The current Report, The Health Consequences of Involuntary Smoking, examines the evidence that even the lower exposure to smoke received by the nonsmoker carries with it a health risk. Use of the term "involuntary smoking" denotes that for many nonsmokers, exposure to ETS is the result of an unavoidable consequence of being in proximity to smokers. It is the first Report in the health consequences of smoking series to establish a health risk due to tobacco smoke exposure for individuals other than the smoker, and represents the work of more than 60 distinguished physicians and scientists, both in this country and abroad. After careful examin ation of the available evidence, the following overall conclusions can be reached: 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2. The children of parents who smoke, compared with the children of nonsmoking parents, have an increased frequency of respiratory infections, increased respiratory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. Simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, exposure of nonsmokers to environmental tobacco smoke. Exposure to environmental tobacco smoke occurs at home, at the worksite, in public, and in other places where smoking is permitted. vii The quality of the indoor environment must be a concern of all who control and occupy that environment. Protection of individuals from exposure to environmental tobacco smoke is therefore a responsibili- ty shared by all: As parents and adults we must protect the health of our children by not exposing them to environmental tobacco smoke. As employers and employees we must ensure that the act of smoking does not expose the nonsmoker to tobacco smoke. For smokers, it is their responsibility to assure that their behavior does not jeopardize the health of others. For nonsmokers, it is their responsibility to provide a supportr ive environment for smokers who are attempting to stop. Actions taken by individuals, employers, and employee organixa- tions reflect the growing concern for protecting nonsmokers. The number of laws and regulations enacted at the national, State, and local level governing smoking in public has increased substantially over the past 10 years, and surveys conducted by numerous organizations show strong public support for these actions among both smokers and nonsmokers. As a Nation, we have made substantial progress in addressing the enormous toll inflicted by active smoking. Efforts to improve and protect individual health must be not only continued but strength- ened. On the basis of the evidence presented in this Report, it is clear that actions to protect nonsmokers from ETS exposure not only are warranted but are essential to protect public health. Robert E. Windom, M.D. Assistant Secretary for Health . . . vlll PREFACE This, the 1986 Report of the Surgeon General, is the U.S. Public Health Service's 18th in the health consequences of smoking series and the 5th issued during my tenure as Surgeon General. Previous Reports have documented the tremendous health burden to society from smoking, particularly cigarette smoking. The evi- dence establishing cigarette smoking as the single largest preventa- ble cause of premature death and disability in the United States is overwhelming-totaling more than 50,000 studies from dozens of cultures. Smoking is now known to be causally related to a variety of cancers in addition to lung cancer; it is a cause of cardiovascular disease, particularly coronary heart disease, and is the major cause of chronic obstructive lung disease. It is estimated that smoking is responsible for well over 800,000 deaths annually in the United States, representing approximately 15 percent of all mortality. Thirty years ago, however, the scientific evidence linking smoking with early death and disability was more limited. By 1964, the year the Advisory Committee to the Surgeon General issued the first report on smoking and health, a substantial body of evidence had accumulated upon which a judgment could be made that smoking was a cause of disease in active smokers. Subsequent reports over the last 20 years have expanded our understanding and knowledge about smoking behavior, the toxicity and carcinogenicity of tobacco smoke, and the specific disease risks resulting from exposure to this agent. This Report is the first issued since 1964 that identifies a chronic disease risk resulting from exposure to tobacco smoke for individuals other than smokers. It is now clear that disease risk due to the inhalation of tobacco smoke is not limited to the individual who is smoking, but can extend to those who inhale tobacco smoke emitted into the air. This Report represents a detailed review of the health effects resulting from nonsmoker exposure to environmental tobacco smoke (ETS). ETS is the combination of smoke emitted from a burning tobacco product between puffs (sidestream smoke) and the smoke exhaled by the smoker. The 1986 Report, The Health Consequences of Involuntary Smoking, is a critical review of all the available scientific evidence pertaining to the health effects of ETS exposure on nonsmokers. The term "involuntary smoking" is used to ix note that such exposures often occur as an unavoidable consequence of being in close proximity to smokers. Lung Cancer and Environmental Tobacco Smoke The appropriate framework for an examination of the lung cancer risk from involuntary smoking is that of a lowdose exposure to a known human carcinogen. Over 30 years of research have conclu- sively established cigarette smoke as a carcinogen. This Report presents evidence that the chemical composition of side&earn smoke is qualitatively similar to the mainstream smoke inhaled by the active smoker, and that both mainstream and sidestream smoke act as carcinogens in bioassay systems. Data related to environmen- tal levels of tobacco smoke constituents and from measures of nicotine absorption in nonsmokers suggest that nonsmokers are exposed to levels of environmental tobacco smoke that would be expected to generate a lung cancer risk, epidemiological studies of populations exposed to ETS have documented an increased risk for lung cancer in those nonsmokers with increased exposure. It is rare to have such detailed exposure data or human epidemic logic studies on disease occurrence when attempting to evaluate the risk of low-dose exposure to an agent with established toxicity at higher levels of exposure. The relative abundance of data reviewed in this Report, their cohesiveness, and their biologic plausibility allow a judgment that involuntary smoking can cause lung cancer in nonsmokers. Although the number of lung cancers due to involun- tary smoking is smaller than that due to active smoking, it still represents a number sufficiently large to generate substantial public health concern. It is certain that a substantial proportion of the lung cancers that occur in nonsmokers are due to EXS exposure; however, more complete data on the dose and variability of smoke exposure in the nonsmoking U.S. population will be needed before a quantitative estimate of the number of such cancers can be made. Children and Infants This Report also documents a relationship between parental smoking and the respiratory health of infants and children (under 2 years of age). Infants of parents who smoke have an increased risk of hospitalization for bronchitis and pneumonia when compared with infants of nonsmoking parents. There is a relationship between parental smoking and an increased frequency of respiratory symp tams in children. A slower rate of growth in lung function has been observed in children of smoking parents. In many studies, if both X parents smoke, a stronger relationship exists than if only one parent smokes. What future respiratory burden these findings may represent for these children later in life is not known. As a former pediatric surgeon, I strongly urge parents to refrain from smoking in the presence of children as a means of protecting not only their children's current health status but also their own. Diseases Other Than Lung Cancer Several studies have provided data on the relationship between ETS and cancers other than lung cancer and on ETS exposure and cardiovascular disease. However, further research in these areas will be required to determine whether an association exists between ETS exposure and an increased risk of developing these diseases. Policies Restricting Smoking in Public Places The growth in our understanding of the disease risk associated with involuntary smoking has been accompanied by a change in the social acceptability of smoking and by a growing body of legislation, regulation, and voluntary action that addresses where smoking may occur in public. Forty States and the District of Columbia now have some form of legislation controlling or restricting smoking in various public settings. Some States limit smoking to only a few designated areas; however, States are increasingly developing and implement- ing comprehensive legislation that restricts smoking in many public settings, including the workplace. Nine States have restrictions that cover smoking not only by public employees but also by employees in the private sector. No systematic evaluation of the effects these measures may have on smoking behavior has been conducted, but there is little doubt that strong public sentiment exists for implementing such restric- tions. A number of national surveys conducted by voluntary health organizations, government agencies, and even the tobacco industry have documented that an overwhelming majority of both smokers and nonsmokers support restricting smoking in public. Public Health Policy and Involuntary Smoking The 1986 Surgeon General's Report on the Health Consequences of Involuntary Smoking clearly documents that nonsmokers are placed at increased risk for developing disease as the result of exposure to environmental tobacco smoke. Critics often express that more research is required, that certain studies are flawed, or that we should delay action until more conclusive proof is produced, As both a physician and a public health xi official, it is my judgment that the time for delay is past; measures to protect the public health are required now. The scientific case against involuntary smoking as a health risk is more than sufficient to justify appropriate remedial action, and the goal of any remedial action must be to protect the nonsmoker from environmental tobacco smoke. The data contained in this Report on the rapid diffusion of tobacco smoke throughout an enclosed environment suggest that separation of smokers and nonsmokers in the same room or in different rooms that share the same ventilation system may reduce KTS exposure but will not eliminate exposure. The responsibility to protect the safety of the indoor environment is shared by all who occupy or control that environment. Changes in smoking policies regarding the workplace and other environments necessitated by the data presented in this Report should not be designed to punish the smoker. Successful implementa- tion of protection for the nonsmoker requires the support and cooperation of smokers, nonsmokers, management, and employees and should be developed through a cooperative effort of all groups affected. In addition, changes are often more effective when support and assistance is provided for the smoker who wants to quit. Cigarette smoking is an addictive behavior, and the individual smoker must decide whether or not to continue that behavior; however, it is evident from the data presented in this volume that the choice to smoke cannot interfere with the nonsmokers' right to breathe air free of tobacco smoke. The right of smokers to smoke ends where their behavior affects the health and wellbeing of others; furthermore, it is the smokers' responsibility to ensure that they do not expose nonsmokers to the potential harmful effects of tobacco smoke. C. Everett Koop, M.D. Surgeon General xii ACKNOWLEDGMENTS This Report was prepared by the Department of Health and Human Services under the general editorship of the Gffice on Smoking and Health, Donald R. Shopland, Acting Director. Manag- ing Editor was William R. Lynn, Acting Technical Information Officer, office on Smoking and Health. Senior scientific editor was David M. Burns, M.D., Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Medical Center, San Diego, San Diego, California. Consulting scientific editors were Ellen R. Grits, Ph.D., Director, Division of Cancer Control, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, John H. Holbrook, M.D., Associate Professor of Internal Medicine, Department of Internal Medicine, University Hospital, Salt Lake City, Utah, and Jonathan M. Same& M.D., Professor of Medicine, Department of Medicine, The University of New Mexico School of Medicine, Albuquerque, New Mexico. The following individuals prepared draft chapters or portions of the Report. Neal Benowitz, M.D., San Francisco General Medical Center, San Francisco, California A. Sonia Buist, M.D., Professor of Medicine, Department of Physiolo gy, Gregon Health Sciences University, Portland, Oregon Charles Hiller, M.D., Pulmonary Division, University Hospital, Little Rock, Arkansas Dietrich Hoffmann, Ph.D., Associate Director, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York Ilse Hoffmann, Research Coordinator, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York John R. Hoidal, M.D., Director of Pulmonary Medicine, University of Tennessee Center for Health Sciences, Memphis, Tennessee John McCarthy, M.P.H., Harvard School of Public Health, Boston, Massachusetts . . . xlll Nancy A. Rigotti, M.D., Institute for the Study of Smoking Behavior and Policy, John F. Kennedy School of Government, Harvard University, Cambridge, Massachusetts Jonathan M. &met, M.D., Professor of Medicine, Department of Medicine, The University of New Mexico School of Medicine, Albuquerque, New Mexico John Spengler, Ph.D., Harvard School of Public Health, Boston, Massachusetts Annetta Weber, Ph.D., Federal Institute of Technology, Zurich, Switzerland Scott T. Weiss, M.D., M.S., Associate Professor of Medicine, Chan- ning Laboratories, Harvard Medical School, Boston, Massachu- setts Anna H. Wu, Ph.D., Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, Califor- nia The editors acknowledge with gratitude the following distin- guished scientists, physicians, and others who lent their support in the development of this Report by coordinating manuscript prepara- tion, contributing critical reviews of the manuscript, or assisting in other ways. Elvin E. Adams, M.D., M.P.H., Director, Health and Temperance Department, General Conference of Seventh-Day Adventists, Washington, D.C. Stephen M. Ayres, M.D., Dean, School of Medicine, Medical College of Virginia, Richmond, Virginia David V. Bates, M.D., Professor of Medicine and Physiology, Department of Medicine, Acute Care Hospital, University of British Columbia, Vancouver; British Columbia William J. Blot, Ph.D., Chief, Biostatistics Branch, Epidemiology and Biostatistics Program, Division of Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Benjamin Burrows, M.D., Professor of Internal Medicine, and Director, Division of Respiratory Sciences,. The University of Arizona College of Medicine, Tucson, Arizona D. M. DeMarini, Ph.D., Genetic Toxicology Division, U.S. Environ- mental Protection Agency, Research Triangle Park, North Caro- lina Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Louis Diamond, Ph.D., College of Pharmacy, University of Kentucky, Lexington, Kentucky Richard Doll, Cancer Epidemiology and Clinical Trials Unit, Imperi- al Cancer Research Fund, The Radcliffe Infirmary, University of Oxford, Oxford, England, United Kingdom XiV Manning Feinleib, M.D., Dr.P.H., Director, National Center for Health Statistics, Office of the Assistant Secretary for Health, Hyattsville, Maryland Edwin B. Fisher, Jr., Ph.D., Associate Professor, Department of Psychology, Washington University, St. Louis, Missouri William H. Foege, M.D., Executive Director, Task Force for Child Survival, Carter Presidential Center, Atlanta, Georgia Joseph F. Fraumeni, Jr., M.D., Associate Director for Epidemiology and Biostatistics, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Lawrence Garfinkel, M.A., Vice President for Epidemiology and Statistics, and Director of Cancer Prevention, American Cancer Society, New York, New York R.A. Griesemer, D.V.M., Ph.D., Director, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee Michael R. Guerin, Ph.D., Organic Chemistry Section, Analytical Chemistry, Oak Ridge National Laboratory, Oak Ridge, Tennessee Jeffery E. Harris, M.D., Ph.D., Associate Professor, Department of Economics, Massachusetts Institute of Technology, Cambridge, Massachusetts Millicent Higgins, M.D., Associate Director, Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Takeshi Hirayama, M.D., Director, Institute of Preventive Oncology, Shinjuku-ku, Tokyo, Japan Dwight Janerich, D.D.S., M.P.H., Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut Martin Jarvis, M.P.H., Senior Clinical Psychologist, Addiction Research Unit, Institute of Psychiatry, London, England, United Kingdom Brian P. Leaderer, Ph.D., M.P.H., Associate Fellow, John B. Pierce Foundation Laboratory, Associate Professor, Department of Epide- miology and Public Health, Yale University School of Medicine, New Haven, Connecticut Charles L. LeMaistre, M.D., President, University of Texas Systems Cancer Center, Houston, Texas Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Donald Ian Macdonald, M.D., Administrator, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland James S. Marks, M.D., M.P.H., Assistant Director for Science, Center for Health Promotion and Education, Centers for Disease Control, Atlanta, Georgia James 0. Mason, M.D., Dr.P.H., Director, Centers for Disease Control, Atlanta, Georgia xv J. Michael McGinnis, M.D., Deputy Assistant Secretary for Health (Disease Prevention and Health Promotion), Office of the Assistant Secretary for Health, Washington, D.C. A. J. McMichael, M.D., M.B.B.S., Ph.D., Chairman and Senior Principal Research Scientist, CSIRO Division of Human Nutrition, Adelaide, South Australia D. J. Moschandreas, Ph.D., Research Director, ITT Research Insti- tute, Chicago, Illinois David Muir, M.D., Director, Occupational Health Program, Health Sciences Center, McMaster University, Hamilton, Ontario, Cana- da C. Tracy Orleans, Ph.D., Research Associate, Health Services RX+ search Center, University of North Carolina, Chapel Hill, North Carolina Richard Pete, M.A., MSc., I.C.R.F., Regius Assessor of Medicine, The Radcliffe Infirmary, University of Oxford, Oxford, England, Unit- ed Kingdom Otto Raabe, M.D., Laboratory for Energy Related Health Research, University of California, Davis, Davis, California James L. Repace, Chief of Technical Services, Indoor Air Quality Program, U.S. Environmental Protection Agency, Washington, D.C. M.A.H. Russell, F.R.C.P., Addiction Research Unit, Institute of Psychiatry, University of London, London, England, United King- dom Roy J. Shephard, M.D., Ph.D., Director, School of Physical and Health Education, University of Toronto, Toronto, Canada Frank E. Speixer, M.D., Charming Laboratories, Harvard Medical School, Boston, Massachusetts Jesse L. Steinfeld, M.D., President, Medical College of Georgia, Augusta, Georgia David N. Sundwall, M.D., Administrator, Health Resources and Services Administration, Rockville, Maryland Gregory W. Traynor, Staff Scientist, Lawrence Berkeley Laboratory, Berkeley, California Dimitrios Trichopoulos, Director, Department of Hygiene and Epide- miology, School of Medicine, University of Athens, Athens, Greece Kenneth E. Warner, Ph.D., Professor, and Chairman, Department of Public Health Policy and Administration, School of Public Health, The University of Michigan, Ann Arbor, Michigan Ernst L. Wynder, M.D., President, American Health Foundation, New York, New York James B. Wyngaarden, M.D., Director, National Institutes of Health, Bethesda, Maryland Frank E. Young, M.D., Commissioner, Food and Drug Administra- tion, Rockville, Maryland xvi The editors also acknowledge the contributions of the following staff members and others who assisted in the preparation of this Report. Erica W. Adams, Chief Copy Editor and Assistant Production Manager, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Richard H. Amacher, Director, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Margaret L. Anglin, Secretary, Gffice on Smoking and Health, Rockville, Maryland John L. Bagrosky, Associate Director for Program Operations, Office on Smoking and Health, Rockville, Maryland Charles A. Brown, Programmer, Automation and Technical Services Department, Sterling Software, Inc., Rockville, Maryland Clarice D. Brown, Statistician, Office on Smoking and Health, Rockville, Maryland Richard C. Brubaker, Information Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Catherine E. Burckhardt, Secretary, Office on Smoking and Health, Rockville, Maryland Joanna B. Crichton, Copy Editor, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Stephanie D. DeVoe, Programmer, Automation and Technical Services Department, Sterling Software, Inc., Rockville, Maryland Danny A. Goodman, Information Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary land Patricia E. Healy, Technical Information Specialist, Office on Smoking and Health, Rockville, Maryland Terri L. Henry, Clerk-Typist, Office on Smoking and Health, Rockville, Maryland Timothy K. Hensley, Technical Publications Writer, Office on Smoking and Health, Rockville, Maryland Shirley K. Hickman, Data Entry Operator, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary land Robert S. Hutchings, Associate Director for Information and Pro- gram Development, Office on Smoking and Health, Rockville, Maryland Maureen Illar, Editorial Assistant, Office on Smoking and Health, Rockville, Maryland Julie Kurt, Graphic Artist, Information Center Management De- partment, Sterling Software, Inc., Rockville, Maryland Ruth C. Palmer, Secretary, Office on Smoking and Health, Rockville, Maryland xvii Jerome A. Paulson, M.D., Medical Officer, Office on Smoking and Health, Rockville, Maryland Russell D. Peek, Library Acquisitions Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Margaret E. Pickerel, Public Information and Publications Special- ist, Office on Smoking and Health, Rockville, Maryland Raymond K. Poole, Production Coordinator, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Linda R. Spiegelman, Administrative Officer, office on Smoking and Health, Rockville, Maryland Evelyn L. Swarr, Administrative Secretary, Automation and Techni- cal Services Department, Sterling Software, Inc., Rockville, Mary- land Debra C. Tate, Publications Systems Specialist, Publishing Systems Division, Sterling Software, Inc., Riverdale, Maryland Jerry W. Vaughn, Programmer, University of California, San Diego, San Diego, California Mary I. Walz, Computer Systems Analyst, Office on Smoking and Health, Rockville, Maryland Louise G. Wiseman, Technical Information Specialist, Gffice on Smoking and Health, Rockville, Maryland Pamela Zuniga, Secretary, University of California, San Diego, San Diego, California . . . XVlll TABLE OF CONTENTS Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Acknowledgments . . . . . . . . . . . . . . . . . . ..*................................ Xl11 1. Introduction, Overview, and Summary and Conclusions . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Health Effects of Environmental Tobacco Smoke Ex- posure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3. Environmental Tobacco Smoke Chemistry and Expo sures of Nonsmokers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 4. Deposition and Absorption of Tobacco Smoke Constit- uents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 5. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke . . . . . . . . . . . . . . . . . . . . . . .225 6. Policies Restricting Smoking in Public Places and the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 xix CHAPTER 1 INTRODUCTION, OVERVIEW, AND SUMMARY AND CONCLUSIONS CONTENTS Introduction Development and Organization of the 1986 Report Overview Environmental Tobacco Smoke Constitutents Extent of Exposure Lung Cancer Respiratory Disease Cardiovascular Disease Irritation Determinants of Exposure Policies Restricting Smoking Summary and Conclusions of the 1986 Report Health Effects of Environmental Tobacco Smoke Exposure Environmental Tobacco Smoke Chemistry and Exposures of Nonsmokers Deposition and Absorption of Tobacco Smoke Constit- uents Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke Policies Restricting Smoking in Public Places and the Workplace htroductlon Development and Organization of the 1886 Report The 1966 Report was developed by the Off&e on Smoking and Health of the U.S. Department of Health and Human Services as part of the Department's responsibility, under Public Law 91-222, to report new and current information on smoking and health to the unitedstatescongress. The scientific content of this Report reflects the contributions of more than 66 scientists representing a variety of disciplines. Individual manuscripts were written by experts known for their understanding of and work in specific content areas. These manu- scripts were refined through a series of meetings attended by the authors, Office on Smoking Health staff and consultants, and the Surgeon General. Upon receipt of the final manuscripts from the authors, the O&e and its consultants edited and consolidated the individual manu- scripts into appropriate chapters. These- draft chapters were subjeo ted to an extensive outside peer review (see Acknowledgments for individuals and their affiliations) whereby each was reviewed by up to seven experts. Their comments were integrated and the entire volume was assembled. This revised edition of the Report was resubjected to review by 17 distinguished scientists outside the Federal Government, both in this country and abroad. Parallel to this review, the entire Report was also submitted to various institutes and agencies within the U.S. Public Health Service for review and comment. The 1966 Report contains a Foreword by the Assistant Secretary for Health, a Preface by the Surgeon General of the U.S. Public Health Service, and the following chapters: Chapter 1. Introduction, Overview, and Summary and Conclu- SiOM Chapter 2. Health Effects of Environmental Tobacco Smoke Exposure Chapter 3. Environmental Tobacco Smoke Chemistry and Expo sures of Nonsmokers Chapter 4. Deposition and Absorption of Tobacco Smoke Con&it+ uenta Chapter 5. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke Chapter 6. Policies Restricting Smoking in Public Places and the Workplace Overview Inhalation of tobacco smoke during active cigarette smoking remains the largest single preventable cause of death and disability 5 for the US. population. The health consequences of cigarette smoking and of the use of other tobacco products have been extensively documented in the 17 previous Reports in the health consequences of smoking series issued by the U.S. Public Health Service. cSgare* smoking is a major cause of cancer; it is most strongly associated with cancers of the lung and respiratory tract, but also causes cancers at other sites, including the pancreas and urinary bladder. It is the single greatest cause of chronic obstructive lung dka~3. It c8uf4f33 cardiovascular diseases, including coronary heart disease, aortic aneurysm, and atherosclerotic peripheral vascular disease. ~atermd cigarette smoking endangers fetal and neonatal health, it contributes to perinatal mortality, low birth weight, and complications during pregnancy. More than 3CQofl premature deaths occur in the United States each year that are directly attributable to tobacco use, particularly cigarette smoking. `Ihis Eteport examines in detail the scientific evidence on involun- tary smoking as a potential cause of disease in nonsmokers. Nonsmokers' exposure to environmental tobacco smoke is termed involuntary smoking in this Fteport because the expcsure generally occurs as an unavoidable consequence of being in proximity to smokers, particularly in enclosed indoor environments. The term "passive smoking" is also used throughout the scientific literature to describe this exposure. The magnitude of the disease risks for active smokers secondary to their "high dose" exposure to tobacco smoke suggests that the "lower dose" exposure to tobacco smoke received by involuntary smokers may also have risks. Although the risks of involuntary smoking are smaller than the risks of active smoking, the number of individuals injured by involuntary smoking is large both in absolute terms and in comparison with the number injured by some other agents in the general environment that are regulated to curtail their potential to cause human illness. This Report reviews the evidence on the characteristics of main- stream tobacco smoke and of environmental tobacco smoke, on the levels of exposure to environmental tobacco smoke that occur, and on the health effects of involuntary exposure to tobacco smoke. me composition of the tobacco smoke inhaled by active smokers and by involuntary smokers is examin ed for similarities and differences, and the concentrations of tobacco smoke components that can b immured in a variety of settings are explored, as is smoke deposition and absorption in the respiratory tract. The studies that &crib the risks of environmental tobacco smoke exposure for humans are carefully reviewed for their fmdings and their validity. `I'he evidence on the health effects of involuntary smoking is reviewed for biologic plausibility, and compared with extrapolations of the risks of active 6 smoking to the lower dose of exposure to tobacco smoke found in nonsmokers. This review leads to three major conclusions: 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2. The children of parents who smoke compared with the children of nonsmoking parents have an increased frequency of respiratoryinfections, increased respira- tory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. The simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to environmen- tal tobacco smoke. The subsequent chapters of this volume describe in detail the evidence that supports these conclusions; the evidence is briefly summarized here. Environmental Tobacco Smoke Constituents Important considerations in e xamining the risks of involuntary smoking are the composition of environmental tobacco smoke (ETS) and its toxicity and carcinogenicity relative to the tobacco smoke inhaled by active smokers. Mainstream cigarette smoke is the smoke drawn through the tobacco into the smoker's mouth. Sidestream smoke is the smoke emitted by the burning tobacco between puffs. Environmental tobacco smoke results from the combination of sidestream smoke and the fraction of exhaled mainstream smoke not retained by the smoker. In contrast with mainstream smoke, ETS is diluted into a larger volume of air, and it ages prior to inhalation. The comparison of the chemical composition of the smoke inhaled by active smokers with that inhaled by invohmtary smokers suggests that the toxic and carcinogenic effects are qualitatively similar, a similarity that is not too surprising because both mainstream smoke and environmental tobacco smoke result from the combustion of tobacco. Individual mainstream smoke constituents, with appropri- ate testing, have usually been found in sidestream smoke as well. However, differences between sidestream smoke and mainstream smoke have been well documented. The temperature of combustion during side&ream smoke formation is lower than during main- stream smoke formation. As a result, greater amounts of many of the organic constituents of smoke, including some carcinogens, are generated when tobacco burns and forms side&ream smoke than when mainstream smoke is produced. For example, in contrast with mainstream smoke, side&ream smoke contains greater amounts of ammonia, benzene, carbon monoxide, nicotine, and the carcinogens 7 %napthylamine, 4aminobipheny1, N-nitrosamine, ~=I+ anthracene, and benzo-pyrene per milligram of tobacco burned. Although only limited bioassay data comparing mainstream smoke and sidestream smoke are available, one study has suggested that sidestream smoke may be more carcinogenic. Extent of Exposure ~though siclestream smoke and mainstream smoke differ some- what qualitatively, the differing quantitative doses of smoke compo- nents inhaled by the active smoker and by the involuntary smoker are of greater importance in considering the risks of the two exposures. A number of different markers for tobacco smoke exposure and absorption have been identified for both active and involuntary smoking. No single marker quantifies, with precision, the exposure to each of the smoke constituents over the wide range of environmental settings in which involuntary smoking occurs. However, in environments without other significant sources of dust, respirable suspended particulate levels can be used as a marker of smoke exposure. Levels of nicotine and its metabolite cotinine in body fluids provide a sensitive and specific indication of recent whole smoke exposure under most conditions. Widely varying levels of environmental tobacco smoke can be measured in the home and other environments using markers. The time-activity patterns of nonsmokers, which indicate the time spent in environments containing EI'S, also vary widely. Thus, the extent of exposure to ETS is probably highly variable among individuals at a given point in time, and little is known about the variation in exposure of the same individual at different points in time. Llmg cancer The American Cancer Society estimates that there will be more than 135,000 deaths from lung cancer in the United States in 1986, and 85 percent of these lung cancer deaths are directly attributable to active cigarette smoking. Therefore, even if the number of lung cancer deaths caused by invohmtary smoking were much smaller than the number of lung cancer deaths caused by active smoking, the number of lung cancer deaths attributable to involuntary exposure would still represent a problem of sufficient magnitude to warrant substantial public health concern. Exposure to environmental tobacco smoke has been examined in numerous recent epidemiological studies as a risk factor for lung cancer in nonsmokers. These studies have compared the risks for subjects exposed to MS at home or at work with the risks for people not reported to be exposed in these environments. Because exposure to EIS is an almost universal experience in the more developed ~~fhs, theee studies involve comparison of more expased and less 8 exposed people rather than comparison of exposed and unexposed people. Thus, the studies are inherently conservative in assessing the consequences of exposure to ETS. Interpretation of these studies must consider the extent to which populations with different E'JJS exposures have been identified, the gradient in EXS exposure from the low-er exposure to the higher exposure groups, and the magni- tude of the increased lung cancer risk that results from the gradient in ETS exposure. To date, questionnaires have been used to classify ETS exposure. Quantification of exposure by questionnaire, particularly lifetime exposure, is difficult and has not been validated. However, spousal and parental smoking status identify individuals 6th different levels of exposure to ETS. Therefore, investigation has focused on the children and nonsmoking spouses of smokers, groups for whom greater ETS exposure would be expected and for whom increased nicotine absorption has been documented relative to the children and nonsmoking spouses of nonsmokers. Of the epidemiologic studies reviewed in this Report that have examined the question of involuntary smoking's association with lung cancer, most (11 of 13) have shown a positive association with exposure, and in 6 the association reached statistical significance. Given the difficulty in identifying groups with differing ET'S exposure, the low-dose range of exposure examined, and the small numbers of subjects in some series, it is not surprising that some studies have found no association and that in others the association did not reach a conventional level of statistical significance. The question is not whether cigarette smoke can cause lung cancer; that question has been answered unequivocally by examining the evi- dence for active smoking. The question is, rather, can tobacco smoke at a lower dose and through a different mode of exposure cause lung cancer in nonsmokers? The answer must be sought in the coherence and trends of the epidemiologic evidence available on this lowdose exposure to a known human carcinogen. In general, those studies with larger population sizes, more carefully validated diagnosis of lung cancer, and more careful assessment of M`s exposure status have shown statistically significant associations. A number of these studies have demonstrated a dose-response relationship between the level of M`S exposure and lung cancer risk. By using data on nicotine absorption by the nonsmoker, the nonsmoker's risk of developing lung cancer observed in human epidemiologic studies can be compared with the level of risk expected from an extrapolation of the d-response data for the active smoker. This extrapolation yields estimates of an expected lung cancer risk that approximate the observed lung cancer risk in epidemiologic studies of involud~ smoking. 9 Cigarette smoke is well established as a human carcinogen. The chemical composition of ETS is qualitatively similar to mainstream smoke and sidestream smoke and also acts as a carcinogen in bioassay systems. For many nonsmokers, the quantitative exposure to ETS is large enough to expect an increased risk of lung cancer to occur, and epidemiologic studies have demonstrated an increased lung cancer risk with involuntary smoking. In examining a low-dose exposure to a known carcinogen, it is rare to have such an abundance of evidence on which to make a judgment, and given this abundance of evidence, a clear judgment can now be made: exposure to ETS is a cause of lung cancer. The data presented in this Report establish that a substantial number of the lung cancer deaths that occur among nonsmokers can be attributed to involuntary smoking. However, better data on the extent and variability of E!lS exposure are needed to estimate the number of deaths with confidence. Respiratory Disease Acute and chronic respiratory diseases have ah30 been linked to hvol~ntary exposure to tobacco smoke; the evidence is strongest in infants. htig the first 2 years of life, infants of parents who smoke me more Likely than infants of nonsmoking parents to be hospital- ized for bronchitis and pneumonia. Children whose parents smoke aho develop respiratory symptoms more frequently, and they show small, but measurable, differences on tests of lung function when compared with children of nonsmoking parents. Respiratory infections in young children represent a direct health burden for the children and their parents; moreover, these infec- tions, and the reductions in pulmonary function found in the school- age children of smokers, may increase susceptibility to develop lung disease as an adult. Several studies have reported small decrements in the average level of lung function in nonsmoking adults exposed to ETS. These differences may represent a response of the lung to chronic exposure to the irritants in ETS, but it seems unlikely that ETS exposure, by itself, is responsible for a substantial number of cases of clinically significant chronic obstructive lung disease. The small magnitude of the changes associated with EX'S exposure suggesta that only Miti~uals with unusual susceptibility would be at risk of develop kg ClinicallY adent disease from E'I% exposure alone. However, ETS exposure IMY be a factor that contributes to the development of clinical disease in individuals with other causes of lug mjury. cardiovascular Disease A few studies have examined the relationship hebeen invohrn~ tarY smoking and cardiovascular disease, but no firm conclusion on 10 the relationship can be made owing to the limited number of deaths in the studies. Perhaps the most common effect of tobacco smoke exposure is tissue irrit&.ion. The eyes appear to be especially sensitive to irritation by EX'S, but the nose, throat, and airway may also be af%cted by smoke exposure. Irritation has been demonstrated to occur at levels that are similar to those found in real-life situations. The level of irritation increases with an increasing concentration of smoke and duration of exposure. In addition, participants in surveys report irritation and annoyance due to smoke in the environment under real-life conditions. Determinante of Espoi3ure &pc++ure to EX'S has been documented to be common in the United States, but additional data on the extent and determi,nanta of exposure are needed to identify individu& within the population who have the highest exposure and are at greatest risk. Studies with biological markers and measurements of EXS components in indoor air confirm that measurable exposure to l3TS is widespread. How- ever, within exposed populations, levels of cotinine excretion and presumably El% exposure vary greatly. In a room or other indoor area, the size of the space, the number of smokers, the amount of ventilation, and other factors determine the concentration of tobacco smoke in the air. The technology for the cost-effective atration of tobacco smoke from the air is not currently available, and because of their small size, the smoke particles remain suspended in the air for long periods of time; thus, the only way to remove smoke from indoor air is to increase the exchange of indoor air with clean outdoor air. The number of air changea per hour required to maintain acceptable indoor air quality is much higher when smoking is allowed than when smoking is prohibited. Environmental tobacco smoke originates at the lighted tip of the cigarette, and exposure to M`s is greatest in proximity to the smoker. However, the smoke rapidly disseminates throughout any airspace contiguous with the space in which the smoking is taking place. Dissemination of smoke is not uniform, and substantial gradienti in ETS levels have been demonstrated in different parta of the same airspace. The time course of tobacco smoke dissemination is rapid enough to ensure the spread of smoke throughout an airspace within an S-hour workday. In the home, the presence of even one smoker can GgnEcantly increase levels of respirable suspended particulates. These data lead to the conclusion that the simple separation of smokers and nonsmokers within the same airspace will reduce, but 11 not eliminate, exposure to El%, particularly in those settings where exposure is prolonged, such as the working environment. The exposure of an individual nonsmoker to ETS is also deter- m&xl by that person's time-activity pattern; that is, the amount of he spent in various locations. For adults, the duration of the spent in smoke-contaminated environments at work or at home is the principal dete rminant of E!!`8 exposure, along with the levels of smoke in those environments. For infants and very young children, the smoking habit of the primary caretaker, as well as that person's time-activity pattern, is likely to play a major role in de&mining ETS exposure. Policies Restricting Smoking Pohcies regulating cigarette smoking with the objective of reduc- ing e~l~ion or fire risk, or of safeguarding the quality of manufac- tured products, have been in force in a number of States since the late 1800s. More recently, and with steadily increasing frequency, pohcies regulating smoking on the basis of the health risk or the irritation of involuntary smoking have been promulgated. State and local governments have enacted laws and regulations restricting smoking in public places. These policies have been implemented with few problems and at little cost to the respective governments. !I'he public awareness of these policies that results from the media coverage surrounding their implementation proba- bly facilitates their selfenforcement. Public awareness may best be fostered by encouraging the establishment of these changes at the local level. Policies limiting smoking in the worksite have also become increasingly widespread and more restrictive. However, changes in worksite policies have evolved largely through voluntary rather than governmental action. In a steadily increasing number of worksites, smoking has been prohibited completely or limited to relatively few areas within the worksite. The creation of a smoke- free workplace has proceeded successfully when the policy has been jointly developed by employees, employee organizations, and man- agement; instituted in phases; and accompanied by support and assistarm for the smokers to quit smoking. This trend to protect nonsmokers from ETS exposure may have an added public health benefithelping those smokers who are at- tempting to quit to be more successful and not encouraging smoking by people entering the workforce. Summary and Conclusions of the 1988 Report The three major conclusions of this report are the following: 12 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2. The children of parents who smoke compared with the children of nonsmoking parente have an iucreased frequency of respiratory iufectiouq iucreased respira- tory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. The simple separation of smokers and nousmokers withiu the same air space may reduce, but doea not eliminate, the exposure of nonsmokers to enviroumen- tal tobacco smoke. ,Individual chapter summaries and conclusions follow. Health Effects of Euviroumental Tobacco Smoke Exposure 1. Involuntary smoking can cause lung cancer in nonsmokers. 2. Although a substantial number of the lung cancers that occur in nonsmokers can be attributed to involuntary smoking, more data on the dose and distribution of ETS exposure in the population are needed in order to accurately estimate the magnitude of risk in the U.S. population. 3. The children of parents who smoke have an increased frequen- cy of hospitalization for bronchitis and pneumonia during the first year of life when compared with the children of nonsmok- ers. 4. The children of parents who smoke have an increased frequen cy of a variety of acute respiratory illnesses and infections, including chest illnesses before 2 years of age and physician- diagnosed bronchitis, tracheitis, and laryngitis, when com- pared with the children of nonsmokers. 5. Chronic cough and phlegm are more frequent in children whose parents smoke compared with children of nonsmokers. The implications of chronic respiratory symptoms for respira- tory health as an adult are unknown and deserve further study. 6. The children of parents who smoke have small differences in tests of pulmonary function when compared with the children of nonsmokers. Although this decrement is insufficient to cause symptoms, the possibility that it may increase suscepti- bility to chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., active smoking or cccupation- al exposures, needs investigation. 7. Healthy adults exposed to environmental tobacco smoke may have small changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmo- 13 nary function as a result of exposure to environmental tobacco smoke alone. 8. A number of studies report that chronic middle ear effusions are more common in young children whose parents smoke than in children of nonsmoking parents. 9. Validated questionnaires are needed for the assessment of recent and remote exposure to environmental tobacco smoke in the home, workplace, and other environments. 10. The associations between cancers, other than cancer of the lung, and involuntary smoking require further investigation before a determina tion can be made about the relationship of involuntary smoking to these cancers. 11. Further studies on the relationship between involuntary smoking and cardiovascular disease are needed in order to determine whether involuntary smoking increases the risk of cardiovaaculardisease. Environmental Tobacco Smoke Chemistry and Expcwwes of Nonsmokera 1. Undiluted sidestream smoke is characterixed by significantly higher concentrations of many of the toxic and carcinogenic compounds found in mainstream smoke, including ammonia, volatile amines, volatile nitr osamines, certain nicotine decom- position products, and aromatic amines. 2. Environmental tobacco smoke can be a substantial contributor to the level of indoor air pollution concentrations of respirable particles, benzene, acrolein, N-nitrosamine, pyrene, and carbon monoxide. E!l'S is the only source of nicotine and some N- nitrosamine compounds in the general environment. 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to environmental tobacco smoke. Exposures to ETS occur widely .in the non- smoking population. 4. The small particle size of environmental tobacco smoke places it in the diffusioncontrolled regime of movement in air for deposition and removal mechanisms. Because these submicron particles will follow air streams, convective currents will dominate and the distribution of ETS will occur rapidly through the volume of a room. As a result, the simple separation of smokers and nonsmokers within the same airspace may reduce, but will not eliminate, exposure to ETS. 5. It has been demonstrated that ETS has resulted in elevated respirable suspended particulate levels in enclosed places. 14 Deposition and Absorption of Tobacco Smoke Constituenta 1. Absorption of tobacco-speciSc smoke constituents (i.e., nicotine) from environmental tobacco smoke exposures has been docu- mented in a number of samples of the general population of developed countries, suggesting that measurable exposure tc environmental tobacco smoke is common. 2. Mean levels of nicotine and cotinine in body fluids increase with self-reported EX'S exposure. 3. Because of the stability of cotinine levels measured at different times during exposure and the availability of noninvasive sampling techniques, cotinine appears to be the shortcterm marker of choice in epidemiological studies. 4. Both mathematical modeling techniques and experimental data suggest that 10 to 20 percent of the particulate fraction of side&ream smoke would be deposited in the airway. 5. The development of specific chemical assays for human expo sure to the components of cigarette tar is an important research goal. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke 1. The main effects of the irritants present in ETS occur in the conjunctiva of the eyes and the mucous membranes of the nose, throat, and lower respiratory tract These irritant effects are a frequent cause of complaints about poor air quality due to environmental tobacco smoke. 2. Active cigarette smoking is associated with prominent changes in the number, type, and function of respiratory epithelial and inflammatory cells; the potential for environmental tobacco smoke exposure to produce similar changes should be investi- gated. 3. Animal models have demonstrated the carcinogencity of ciga- rette smoke, and the limited data that exist suggest that more carcinogenic activity per milligram of cigarette smoke concen- trate may be contained in sidestream smoke than in main- stream cigarette smoke. Policies Restricting Smoking in Public Places and the Workplace 1. Beginning in the 19708, an increasing number of public and private sector institutions have adopted policies to protect individuals from environmental tobacco smoke exposure by restricting the circumstances in which smoking is permitted. 2. Smoking in public places has been regulated primarily by government actions, which have occurred at Federal, State, 15 and local levels. All but nine States have enacted laws regulating smoking in at least one public place. Since the mid- 19706, there has been an increase in the rate of enactment and in the comprehensiveness of State legislation. Local govern- ments have enacted smoking ordinances at an increasing rate since 1980, more than SO cities and counties have smoking laws in effect. 9. Smoking at the workplace is regulated by a combination of government action and private initiative. Legislation in 12 States regulates smoking by government employees, and 9 St&s and more than 70 communities regulate smoking in the private sector workplace. Approximately 96 percent of busi- nesses have adopted smoking policies. The increase in work- place smoking policies has been a trend of the 1980s. 4. Smoking policies may have multiple effects. In addition to reducing environmental tobacco smoke exposure, they may alter smoking behavior and public attitudes about tobacco use. Over time, this may contribute to a reduction in smoking in the United States. To the present, there has been relatively little systematic evaluation of policies restricting smoking in public places or at the workplace. 5. On the basis of case reports and a small number of systematic studies, it appears that workplace smoking policies improve air quality, are met with good compliance, and are well accepted by both smokers and nonsmokers. Policies appear to be followed by a decrease in smokers' cigarette consumption at work and an increase in enrollment in company-sponsored smoking cessation programs. 6. Laws restricting smoking in public places have been imple- mented with few problems and at little cost to State and local government. Their impact on smoking behavior and attitudes has not yet been evaluated. 7. Public opinion polls document strong and growing support for restricting or banning smoking in a wide range of public places. Changes in attitudes about smoking in public appear to have preceded legislation, but the interrelationship of smoking attitudes, behavior, and legislation are complex. 16 CHAPTER 2 HEALTH EFFECTS OF ENVIRONMENTAL TOBACCO SMOKE EXPOSURE CONTENTS Introduction Evaluation of Low-Dose Tobacco Smoke Exposures Extrapolation of Active Smoking Data to Environ- mental Tobacco Smoke Exposure Comparison of Mainstream Smoke and Side- stream Smoke Deposition of Mainstream Smoke and Side stream Smoke and Environmental Tobacco Smoke Dose Estimates Dose-Response Relationships and Threshold for Risk Pathophysiologic Considerations Cancer Lung Disease Methodological Considerations ip Epidemiologic Studies Measurement of Exposure Atmospheric Markers Personal Monitoring Questionnaires Measurements of Absorption Potentially Confounding Variables Statistical Issues Respiratory System Effeds of Involuntary Cigarette smoke Exposure Infants and Children Acute Respiratory Illness Longitudinal stud&3 Cross-Sectional Studies Case-Control Studies Cough, Phlegm, and Wheezing Pulmonary Function Bronchoconstriction Ear, Nose, and Throat Adults Acute Respiratory Illness Cough, Phlegm, and Wheezing 19 Pd.~~onary Function Bronchoconstriction Normal Subjects Asthmatics Ear, Nose, and Throat Lung Cancer Observed Risk General Methodological Issues &msal Exposure: Prospective Studies Tbe Japanese Cohort Study The American Cancer Society Cohort Study The Scottish Study Spousal Exposure: Cas&!ontrol Studies The Greek Study The Louisiana Study The Hong Kong Studies An Ongoing Study of Tobacc&elated Cancers The Ios Angeles County Study The Four Hospitals Study A United Kingdom Study The Japanese Case-Control Study The Swedish Study The German Study Other Sources of Tobacco Smoke Exposure Parental Smoking Coworker's Smoking Dose-Response Relationship Expected Lung Cancer Risk S- Other Cancers cardiovascular Diseases ~ ~- Conclusions Referencef4 20 Introduction In 1964, the fmt Report of the Surgeon General on smoking and health (TJS PHS 1964) determined that cigarette smoking was a cause of lung cancer in men and probably a cause of lung cancer in women. That Report also noted causal relationships between smok- ing and other cancers, as well as chronic lung disease. Subsequent Reports have described associations, both causal and noncausal, between tobacco smoking and a wide range of acute and chronic d&eases. Epidemiological investigations have documented the effects of tobacco smoking in humans; complementary laboratory investiga- tions have elucidated some of the mechanisms through which tobacco smoke causes disease. More recently, the effects of the inhalation of environmental tobacco smoke by nonsmokers have become a pressing public health concern. Nonsmokers, as well as active smokers, inhale environmen- tal tobacco smoke, the mixture of sidestream smoke and exhaled mainstream smoke. Various terms have been applied to the inhala- tion of environmental tobacco smoke by nonsmokers; the terms "involuntary smoking" and "passive smoking" are the most preva- lent and are often used interchangeably by researchers and the public. Many of the known toxic and carcinogenic agents found in mainstream cigarette smoke have also been demonstrated to be present in sidestream smoke. Furthermore, the combustion condi- tions under which sidestream smoke is produced result in the generation of larger amounts of many of these toxic and carcinogenic agents per gram of tobacco burned than the conditions under which mainstream smoke is generated (see Chapter 3). The characteristics of environmental tobacco smoke also differ from those of main- stream smoke because the sidestream smoke ages before it is inhaled and the mainstream smoke exhaled by the active smoker is modified during its residence in the lung. There is no evidence to suggest that environmental tobacco smoke has a qualitatively lower toxicity or carcinogenicity than mainstream smoke per milligram of smoke inhaled. In fact, the available evidence suggests that sidestream smoke contains higher concentrations of many known toxic and carcinogenic agents per milligram of smoke and is more tumorgenic than mainstream smoke in animal testing (Wynder and Hoff'mann 1967). As a result, involuntary smoking should not be viewed as a qualitatively different exposure from active smoking, but rather as a lowdose exposure to a known hazardous agent-cigarette smoke. Evaluation of Low-Dose Tobacco Smoke Exposures Assessment of the health effects of any environmental exposure poses methodological problems, particularly when exposure levels 21 are low and therefore the magnitude of the expected effect is small. me ev&ation of an effect due to a low-dose exposure such as environment& tobacco smoke requires the investigation of popula- tions with differences in exposure large enough so that an effect could be anticipated. The population studied must also be of sufficient size to quantitate the effects in the range of interest with pr&&n. Failure to fulfill these requirements may produce a false- negative result in a study of a low-dose exposure. Exposure to environmental tobacco smoke is a nearly universal experience in the more developed countries, so the identification of a truly unexposed population is very difficult. Epidemiological studies of involuntary smoking have attempted to identify populations with lower exposure and higher exposure to environmental tobacco smoke, most notably by examining nonsmokers exposed to tobacco smoke generated by the smokers of their family. The effects of environmental tobacco smoke have been investigated in a number of populations throughout the world. The diversity of these populations is likely to be accompanied by a similar diversity of their exposure to envircnmental tobacco smoke. Thus, the gradient in exposure to environmental tobacco smoke between the "exposed" and %onex- posed" groups is likely to vary widely among the reported studies. For example, the husband's smoking status may be a strong predictor of total exposure to ETS in traditional societies, such as Japan and Greece, where the wife's exposure outside the home is limited. In contrast, the husband's smoking status in the United States, where substantial exposure may occur outside the home, may not be as predictive. Sample size considerations are of particular concern for the epidemiological studies of lung cancer and involuntary smoking. Because the frequency of lung cancer in nonsmokers is low, many of these studies often included small numbers of nonsmokers and lacked the statistical power necessary to fmd the modest effect expected from this lowdose exposure. Given the constraints of sample size and the varying gradients of exposure, it would be expected that some studies would fmd no association between involuntary smoking and lung cancer, and that other studies would find associations that lacked statistical significance. Nonunifomity of the data, however, does not imply a lack of effect; rather, it is the coherence and trends of the evidence that must be judged. Thus, this Rep0l-t examines the entire body of evidence on the health effects of involuntary smoking, as the basis for its conclusions. In evaluating the hazards posed by an air pollutant such as environmental tobacco smoke, laboratory, toxicological, human exposure, and epidemiological investigations provide relevant data. Each approach has limitations, but the insights each prov&s Me Complementary. Epidemiological investigations describe the effects 22 in human populations, but their results must be interpreted in the context of the other types of investigations. Risk assessment techniques have also been used to characterize the potential adverse health effects of human exposures to environ- mental pollutants, particularly those at low levels. The four steps of risk assessment have been described by the National Academy of Sciences as hazard identification, dose-response assessment, expo- sure assessment, and risk characterization (NAS 1983). Risk assess+ ment has also been used to describe the consequences of exposure to ETS. However, unlike many environmental exposures for which risk assessment represents the only approach for estimating human risk, the health effects of ETS exposure can be examined directly using epidemiological methods. Although this Report reviews several risk assessmenta done by individual researchers on ETS, its conclusions are based on the laboratory, toxicological, and epidemiological evidence. Extrapolation of Active Smoking Data to Environmental Tobacco Smoke Exposure Comparison of Mainstream Smoke and Sidestream Smoke A detailed comparison of mainstream and side&ream smoke can be found in Chapter 3. Mainstream smoke (MS) is the term applied to the complex mixture that is inhaled by the smoker from the mouthpiece of a cigarette, cigar, or pipe with each puff. Side&ream smoke (SS) is the aerosol that comes from the burning end of the cigarette, pipe, or cigar between puffs. Environmental tobacco smoke (ETS) is the term applied to the combination of SS and exhaled MS, which is diluted and aged in an area where smoking has taken place. Most of the existing data on mainstream and sidestream smoke characteristics relate to cigarette smoking and relatively little information is available pertaining to cigar and pipe smoking. &cause both MS and SS are generated from the tip of the burning tobacco product, it is not surprising that their compositions are similar. Of the thousands of compounds identified in tobacco smoke, many have been identified as present in both MS and SS. Among these are carcinogens, gases such as carbon monoxide and the oxides of nitrogen, and nicotine. Since there is a wealth of information relating to the toxicity and carcinogenicity of MS, it should be emphasized again that ETS cannot be treated as a new environmen- tal agent for the purpose of assessing health risks. The presence of the same agents in MS and SS leads to the conclusion that ETS has a toxic and carcinogenic potential that would not be expected to be qualitatively different from that of MS. Quantitative differences between the active smoker's exposure to MS and the involuntary smoker's exposure to ETS are likely to be. the more important 23 determjnant of the differing magnitudes of risks associated with them3 two exposures. werences in the composition of MS and SS primarily reflect their generation at different temperatures in different oxygen environments. also, SS is diluted very rapidly, under most circum- ww, and has the opportunity to age before inhalation. The h~luntary smoker usually inhales E'IS, not SS, the aerosol that comes from the tip of a burning cigarette. In considering the &u&e&tics of SS, it must be emphasii that much of the existing data about the composition of MS and SS is derived from studies carried out in special chambers rather than by sampling MS and SS generated by smokers. In these chamber studies, SS has been sampled by a probe located close to the burning tip. This experimen- tal situation clearly differs from that of a room with one or more smokers freely smoking. In that situation, SS is mixed with exhaled MS, diluted and aged. Nevertheless, these &amber studies provide very useful information about the compounds present in the SS. These studies have established that SS in comparison with MS has a higher PHI, smaller particle size, and more carbon monoxide, benzene, toluene, acrolein, acetone, pyridine, ammonia, methyl- amine, nicotine, aniline, cadmium, radon daughters, beru@ajpyrene and benzIa]anthracene. Comparison of the relative concentrations of the various compo- nents of SS and MS smoke prcvides limited insights concerning the toxicological potential of ETS in comparison with active smoking. As described above, SS characteristics, as measured in a &amber, do not represent those of E!I'S, as inhaled by the nonsmoker under nonexperimental conditions. Further, the dose-response relation- sbips between specific tobacco smoke components and specific diseases are not sufficiently established for the necesssq extrapola- tions from active smoking to environmental tobacco smoke exposure for individual agents. For that reason the extrapolations in this section are confined to the doseresponse relationships of whole smoke for those diseases with established dose-response relation- ships. With regard to the potential of EX'S to cause lung cancer, UdilUted SS has 20 to 100 times greater concentrations of. highly carcinogenic volatile. N-nitrosamin es than MS (Brunnemam et al. 1978) as well as higher concentrations of benxopyrenes and benzCa]anthracenes. For mum&want effecta on airways and the lung parenchyma, the agents responsible for the development of acute and chronic respiratory disease have not been identified, although many tobacco smoke components have been shown tc cause lung injury (US DHHS 19&Q). Presumably, both vapor phase (gaseous) and particulate phase kW components of MS are involved. Both airways disease and 24 parenchymal disease are probably a response to the total burden of respiratory insults, some of which, like active smoking, may be sufficient by themselves to cause physiologic impairment and ultimately, clinical disease. Others, such as ETS, may contribute to the total burden but be insufficient, individually, to cause clinical disease. Deposition of Mainstream Smoke and Side&ream Smoke and Environmental Tobacco Smoke Dose Estimutes The dose of tobacco smoke delivered to the airways and alveoli depends, among other factors, on the volume of MS, SS, or E'I'S inhaled, on the rate and depth of inhalation, and on the sixe, shape, and density of the individual particles or droplets. Patterns of deposition of MS in the lungs have been described, but similar information about deposition patterns for ETS is not yet available. Without such data, it is necessary to extrapolate from the informa- tion on MS. The major factors that affect the pattern of deposition and retention for particles are particle size distriiution and breathing pattern. The particle sire range and mean aerodynamic diameter for particulates in sidestream smoke are similar to those of mainstream smoke (particle sire range of 0.01 to 0.8 pm for sidestream smoke and 0.1 to 1.0 v for mainstream smoke, and mean aerodynamic diameter 0.32 p for sidestream smoke and 0.4 pm for mainstream smoke) (see Cbapters 3 and 4). `l'he deposition site is determined largely by the size of the particles, with large particles being deposited preferentially in the nasopbarynx and large conducting airways. Smaller particles are deposited more peripherally, and very small particles tend to be exhaled and to have a very low deposition fraction. The particulates of ETS, because of their size range, are likely to be deposited peripherally. The breathing patterns for the inhalation of MS and EYI'S are also different; MS is inbaled intermittently by the smoker with an intense inhalation, often followed by a breathhold that resulta in a more equal distribution. Environmental tobacco smoke, on the other hand, is inhaled continuously with tidal breaths when the passive smoker is at rest and with deeper inhalations when the passive smoker is physically active. Breatbholding does not normally occur with tidal breathing. Estimates of the equivalent exposure, in terms of cigarettes per day, resulting from ETS, as compared with MS, vary quite widely and depend on the way in which the estimates were made. Bepace and Lowrey (1985) estimated that nonsmokers in the United States are exposed to from 0 to 14 mg of tobacco tar (average 1.4 rag) per day. Vutuc (1984) estimated that the exposure to environmental cigarette smoke is equivalent to 0.1 to 1 cigarette per day actively 25 smoked. Estimates of ETS exposure, based on cotinine measure- ments, suggest that involuntary smokers absorb about 0.5 to 1 percent of the nicotine that active smokers absorb (Jarvis et al. 1984, Haley and Hoffmann 1965; Wald et al. 1984; Russell et al. 1966). Dose-Response Ret!ationships and Threshold for Risk -response relationships for active smoking can provide in- sights into the expected magnitude of disease resulting from the exposure of nonsmokers to ETS. These data are reviewed to de&mine whether disease can be expected in association with E'I'S. Data from cohort and cas+control studies demonstrate dose- response relationships for lung cancer, which extend to the lowest levels of reported active smoking. The dose-response relationship of active smoking with lung cancer risk has been described by several investigators in several different date sets (Whittemore and Altshu- ler 1976; Doll and Pet0 1978; Pathak et al. 1986). Although the mathematical forms of these models vary, none have included a threshold level of active smoking that must be passed for lung cancer tc develop. The dose-response relationship for active smoking and lung cancer has been used to project the lung cancer risk for nonsmokers (Vutuc 1964). Such projections yield risk estimates of 1.03 to 1.36 for exposures, considered to be reasonable estimates of involuntary smoking exposures, i.e., 0.1 t.c 1.0 cigarettes per day. The reference population for these risk estimates is the risk for nonsmokers as a group, including those with higher and those with lower exposures to environmental tobacco smoke. In contrast, the reference population for the risk estimates in studies of involuntary smoking is the lung cancer risk in only that group of nonsmokers who have lower exposure to EITS. Comparisons of lung cancer risk estimates from active smoking studies with those from involuntary smoking studies require reference to the same exposure group for proper mterpreta- tion. In general, the lung cancer experience .of all nonsmokers (i.e., those with higher and lower involuntary smoking exposure com- bined) has been used to establish the reference rate of lung cancer occurrence (i.e., set as a risk of 1) in studies of active smoking. The use of all nonsmokers as the reference group averages the lower risks of nonsmokers with less ETS exposure with the higher risks of those with more ETS exposure. Thus, with the relative risk for the entire group of nonsmokers set to unity, the relative risk for nonsmokers with lower exposure is below 1 and that for the group with higher exposure is above 1. As a consequence, relative risk estimates from studies of involuntary exposure cannot be directly compared with risk estimates extrapolated from active smoking, unh c(qm%on to a single level of exposure is possible. Failure to 26 consider the differences between the reference populations explains the apparent discrepancy noted by Vutuc. Consider, for example, the mortality study reported by Hirayama (1981a). In this study, the relative risk of lung cancer for nonsmoking wives of smoking husbands (current and former) compared with nonsmoking wives of nonsmoking husbands (as calculated from Figure 1 in Hirayama 1981a) was 1.78. If the relative risk for nonsmoking wives of nonsmoking husbands were expressed in relation to the combined group of nonsmoking women, then a value of 0.63 is obtained, while with a similar calculation, that for nonsmoking wives of smoking husbands (both current and former), yields a value of 1.12. Thus, when the appropriate comparison is made, the risk estimates developed by extrapolation of the active smoking data (1.03 to 1.36) closely approximate those actually found in a study of lung cancer risk due to involuntary smoking. Dose-response relationships between active smoking and the level of lung function, the rate of decline of lung function in adult life, and the development of chronic airflow obstruction are well established (US DHHS 1984). Different measures of dose have provided the strongest correlation with functional decline in different studies. Pack-years, a cumulative dose measure, was the strongest predictor of the level of forced expiratory volume in 1 second (FEVI) in the Tucson epidemiologic study (Burrows, Knudson, Cline et al. 1977). Duration of smoking and the amount smoked were found to be the best predictors in male subjects in a study of three U.S. communities (Reck et al. 1981), and pack-years was the best predictor in female subjects. In both of these studies, however, the estimated dose accounted for only about 15 percent of the variation of age- and height-adjusted FEW1 levels. The relatively low predictive capability of cigarette smoking variables in these studies most likely reflects a lack of information on the dete rminants of individual susceptibility to tobacco smoke. Further, exposure variables obtained by question- naire, such as the number of cigarettes smoked daily, may only roughly approximate the dose delivered to target sites in the respiratory tract. Many factors, such as puff volume, lung volume at which inhalation starts, and airways geometry will influence the smoke dose and its distribution within the lungs. Extrapolation from the results of these studies to the pulmonary effects of exposure to ETS is, therefore, likely to be inaccurate. Another approach for assessing lowdose exposures is to consider the information available from studies involving children and teenagers who have recently taken up smoking. Even with brief smoking experience, cross-set tional studies of active cigarette smok- ing by children and adolescents have demonstrated an increased frequency of respiratory symptoms (Rawbone et al. 1978; Rush 1974; Bewley et al. 1973; Seely et al. 1971) and small but statistically 27 significant reductions in lung function (Seely et al. 1971; Peters and Ferris 1967; Lim 1973; Walter et al. 1974; &&house 1975; Woolcock et aL 1984). Longitudinal studies involving children and adolescents have demonstrated that a physiologic impairment attributable to smoking may be found in some children by age 14 and may be present after only 1 year of smoking 10 or more cigarettes per week in children with previously normal airways (woolcock et al. 1934), and that relatively small amounts of cigarette use may lead to significant effects on FEVl and on the growth of lung function in adolescents (Figure 1) (`l'ager et al. 1935). When considering the risk of lowdose exposures for the develop ment of chronic respiratory disease, the existence of a spectrum of risk and a distribution of dose within the population should be taken into consideration. The characteristics of the part of the population most susceptible to involuntary smoke exposure is still being clarified. Evidence is accumulating that airways hyperrespon- siveness, atopy, childhood respiratory illness, and occupational exposures may all influence response to ETS. Current understanding of lung injury suggests that individuals with one or more of these characteristics that place them at the most sensitive end of the susceptibility curve may be the most likely to develop symptoms or functional changes es a result of ETS exposure. Dose of ETS also varies in the population, and the coincidence of high dose and increased susceptibility may convey a particularly high risk. Fur- thermore, ET3 exposure may damage lungs that are also affected by other insults. Pathophysiologic Cbsiderations Cancer Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell with uncontrolled replication. Carcinogenesis has been conceptualixed as a multistage process involving a sequence of alterations in cellular DNA that terminate with the development of a malignant cell. Agents acting early in this sequence are referred tc as initiators; those actii later are referred to as promoters. Compounds with both initiating activity and promoting activity have been identified in tobacco smoke. Carcinogenesis reflects DNA damage; although some repair may take place, biological models have not suggested that there is a threshold of damage that must be exceeded. Rather, carcinogenesis has been considered to involve a series of changes, each occurring at a rate dependent on the dose of a damaging agent. Higher doses increase the probability that the entire sequence will be completed, but lower doses may also lead to mahgnancy. o 0 10,ooo 20300 30,ooo 4o.wo 50,ooo 60,ooo 70,Doo 30,ooo Number of cigamtes consumed 150 d o ? ? o o ? ? ? o o ? o o o o o o o o s + 25 0 lO,ooa 2a.ooo 30,ooo 40,ow 5o.ooo ewoo 70,ooo 3o.ooo Number of cigarettes consumed FIGURE l.-Relationship between levels of predicted for FEW, (A) and FEFSWIJ (B) at examination 8 and cumulative number of cigareti smoked during examinations 4 through 8 NOTEzMenandwome.nmmbined@J-44). SOURCE: Tagor et al. (1936). 29 with the PiZZ or other phenotypes, are modest particulate exposures likely to increase the risk for disease to an appreciable extent. The development of acute and chronic airzoay disease or symptoms of cough, phlegm production, and wheeze may require a considerably smaller exposure than changes in the lung parenchyma, and it is not unreasonable to hypothesize that these symptoms may be related to repeated and continuous exposure to EYES in the susceptible individu- al. Strong evidence that lowdose active smoking causes increased rates of respiratory symptoms and functional impairment comes from the studies of children and adolescents discussed earlier (Woolcock et al. 1984; Tager et al. 1985). Because of the length of exposure, it is likely that these reflect airway rather than parenchy- mal effects. Another pathophysiological mechanism by which exposure to EX'S may increase an individual's risk for the development of chronic airflow obstruction is through respiratory viral infections. Mounting evidence indicates that the very young child (under 2 years of age) exposed to ETS is at increased risk for lower respiratory tract viral infections (Harlap and Davies 1974; Colley 1974; Colley et al. 1974; Leeder et al. 1976a; Fergusson et al. 1981; Dutau et al. 1979; Pedreira et al. 1985). There is also increasing, though still inconclusive, epidemiologic evidence that respiratory viral infections in early life may be associated with an accelerated decline in F'EVl and, therefore, an increased risk for the development of chronic airflow obstruction in adult life in smokers (Burrows, Knudson, Lebowitz 1977; Samet et al. 1983). By increasing the occurrence of viral infections of the lower respiratory tract in early life, exposure to ETS in childhood may have an appreciable, but indirect, effect on the risk for the development of chronic airflow obstruction in adult life. The structural basis for this increased susceptibility has not yet been elucidated, however. Furthermore, the child whose parents smoke is also more likely to take up smoking than is the child of nonsmoking parents. Thus, the child made susceptible to the effecta of active smoking by prior PITS exposure is also more likely to become an active smoker. The possibility that exposure to constituents of tobacco smoke in utero may exert a prenatal effect must also be considered. This exposure is clearly not the same as ETS exposure, since the lungs of the fetus are not being exposed to ETS; rather, the developing fetal lung is exposed to compounds absorbed by the mother and delivered to the fetus transplacentally. Evidence of an in utero effect in pregnant rats has been reported by Collins and coworkers (1985). These investigators reported that pregnant rats exposed to smoke from day 5 to day 20 of gestation, in comparison with control rats, showed reduced lung volume at term and saccules that were reduced in number and increased in size as a result of the reduced formation 31 Lung Disease The noncarcinogenic pathophysiologic effects of active smoking on the respiratory tract can be separated into (1) effects on the airways and (2) effects on the lung parenchyma. In the airways, the structural changes include inflammation in the small airways and mucous gland hypertrophy and hyperplasia. In the parenchyma, the main structural change is alveolar wall destruction. Both the airways and the parenchymal changes are caused by active smoking, but the interrelationships of these changes are not clear. They may be independent pathophysiologic pi, linked only by their joint association with tobacco smoking. As discussed earlier, there is evidence showing an approximately linear d-response relationship between F'EWl level and amount smoked; however, the d-response relationships have not been as well described for the underlying pathophysiologic changes in the airways or in the lung parenchyma. Host factors and other environ- mental factors presumably interact with active smoking to affect an individual's risk for the development of disease. In this regard, present evidence would suggest that only 10 to 15 percent of smokers develop clinically significant airflow obstruction, although parenchy- mal and airways changes can be demonstrated in a substantially higher percentage at autopsy (US DHHS 1984). Extrapolation from the evidence on active smoking to the likely effect of exposure to environmental tobacco smoke on the airways and parenchyma suggests that pathophysiologic effeds on both the airways and the lung parenchyma might be expected. Because the dose of smoke components from ETS exposure is small in comparison with the dose from active smoking, the extent of lung injury would most likely also be much smaller than that found in active smokers. Small changes in the lung may be below the threshold for detection on pulmonary function testing. If clinically significant chronic airflow obstruction occurs in nonsmokers exposed to EYES, the risk is likely to be concentrated among those individuals highly susceptible to the airway or parenchymal effects of cigarette smoke. This susceptible group may include individuals with bronchial hyperre sponsiveness and with other, as yet unidentified, genetic and familial risk factors. Identifying the risk factors for susceptibility to the airway and parenchymal effects of both mainstream smoke and EL'S is an important priority. The dose of environmental tobacco smoke received by the nonsmoker is unlikely, by itself, to he sufficient to cause a clinically significant degree of purmchymul disease (em- physema) unless an individual is at the extreme end of the susceptibility distribution. Any particulate load is likely to increase the elaatase burden in the lungs by causing an influx of neutrophils. However, only in the individual with very inadequate lung defenses, specificaIly severe deficiency of protease inhibitor (pi) associated 30 of saccule partitions. These hypoplastic lungs showed an internal surface area that was decreased. Whether this study in rats has any relevance to humans is not yet clear, but this issue deserves further investigation. Whether continued exposure to EX'S during childhood, while the lung is remodeling and growing, affects the process of growth and remodeling is not yet clear. In general, rapidly dividing cells and immature organs are more susceptible to the effects of enviromnen- tal toxins than are cells undergoing a normal rate of division and mature organs. Apart from the evidence, cited above, linking lower respiratory tract viral infections in very early life to an accelerated decline of F'EVl in adult life, there is no information yet to link the rate of growth of lung function during childhood to the rate of decline of hmg function in adult life hecause the nw longitudi- nal studies have not heen done. More information is needed to describe the relationship of exposure to ETS at various times during childhood to the maximal level of lung function achieved at full lung growth. Mefiod~logical Considerations in Epidemiologic Studies Measumnent of Expure h mamsing the health effects of EX'S exposure, as with other enknmental pollutant8, accurate assessment of exposure is critical for obtaining estimates of this agent's effects. Both random and systematic misclassification of the exposures of subjects in an investigation are of concern. Random misclassification refers to errors that occur at random; the consequence of such random misclassification is to bias toward fmding no effect. Systematic misclassification refers to nonrandom errors in exposure assessment; the consequence maybe to bias toward a greater or lesser effect than is actually present. Biased answers in response to a questionnaire may introduce systematic misclsssification. Some misclassification occurs in most observational (nonexperi- mental) epidemiological studies, and is inherent in all epidemiologi- cal studies of ETS. Tobacco smoking is ubiquitous in nearly all environments; few people escape being exposed to EX'S. Thus, the exposure variables for ETS in epidemiological studies do not separate nonexposed subjects from exposed subjects, rather, they identify groups with more or less exposure, or with a qualitative or semiquantitative gradient of exposure. In assessing exposure to ETS, the information should cover the biologically appropriate time period for the health effkct of interest and be collected in a form that permita the construction of biologically appropriate exposure measures. However, the collection of a full lifetime history of IZTS exposure, as in a study of malignancy, may not he feasible, and the accuracy of the informa- 32 tion may he limited. In evaluating the effects of ETS exposure, cumulative exposure, duration of exposure, and intensity of exposure may each influence the magnitude of effects, as may the timing of exposure in relation to age and level of development. Because of the difficulties inherent in assessing exposures through questio maims, increased emphasis has been placed on meamuing exposure through the use of molecular or biochemical markers. With available markers, this approach is limited to providing an indica- tion of recent (within 48 hours) exposure, which may not necessarily correlate with past exposure. A marker has not yet been devised for total integrated dose. Nevertheless, biological markers provide another method for classification of current exposure, and a stan- dard for validating questionnaires. The strengths and weaknesses of the existing methods of measur- ing exposure are further discussed below. Atmospheric Markers A number of different markers of atmospheric contamination by tobacco combustion products can be feasibly measured. Ideally, the atmospheric levels of the air contaminant or class of contaminants that are implicated in producing the adverse health effects would be measured. A variety of contaminants have been measured as indicators of ETS, but no single measure can adequately index all of its myriad components. Further, some contaminanta are produced by sources of environmental contamination other than tobacco smoke. Nicotine is ahsorbed only from tobacco and tobacco combustion products. Some of the pollutants that have heen measured include (1) carbon monoxide, (2) respirahle suspended particulates CRSP), (3) nicotine, (4) a number of aromatic hydrocarbons, such as benzene, toluene, benxopyrene, and phenols, and (5) acrolein. Some of these are in the vapor phase and some in the particulate phase. Some, such as nicotine, may exist in one phase (particulate) in MS and in the other (gas) phase in SS. Until more is learned about the contaminants and their physical state in ETS, the results of monitoring for a particular ETS component will be difficult to relate to ita diseasecausing potential. At a practical level, the technology for measuring nicotine levels and RSP levels is available and accurate. Personal Monitoring Both active and passive personal monitors can be used to measure an individual's total exposure to an air contaminant at the breathing xone. Active personal monitoring systems .employ pumps to concen- trate the air contaminants on a collection medium for laboratory analysis or to deliver the air to a continuous monitor. Passive 33 personal monitoring systems use diffusion and permeation to concentrate gases on a collection medium for laboratory analysis. Personal monitoring should provide a more accurate estimate of the dose of a contaminant than area mOnitoring, because the actual air in the breathing zone is sampled and the subject's time-activity pattern is inherently considered. As with area monitoring, the results for a particular component of ETS may not adequately characterize exposure to other components responsible for a particular disease or effect. Respirable suspended particulates can be measured with accuracy and give a reasonably accurate measurement of current exposure. Questionnaires me que&ionnaire has heen the most frequently used means of estimating exposures for epidemiological investigations. Question- naires typic&y have obtained information about the smoking habits of parents, spouses, or other family members and often about exposure outside the home. From this information, the subject is classified as exposed or not exposed to Errs, and the extent of exposure may be estimated. The questionnaire approach for exposure estimation has several potential limitations. First, the information obtained cannot exhaus- tively cover lifetime exposure to ETS; therefore, a completely accurate reconstruction of integrated dose over the years cannot be achieved. Second, in evaluating El% exposure in the home, the usual daily smoking of the smokers has often been used as a measure of exposure intensity at home. This assumption may not be correct, since smoking does not occur only in the home. For example, a one- pack-a-day smoker may smoke only five cigarettes a day in the home environment and smoke the rest at work or elsewhere outside the home. Third, quantitation of exposure in the workplace is inherently Sfficult because of changes in jobs and the varying exposure in any particular workplace. Despite these shortcomings, the information obtained by question- taires does discriminate between more exposed and less exposed ubjects. The evidence validating the questionnaire method is trongest for domestic exposure. In several studies, levels of cotinine m body fluids have varied with reported exposure to tobacco smoke at home (Greenberg et al. 1984; Wald and Ritchie 1984; Matsukura et al. 1984; Jarvis et al. 1984). In fact, residence with a smoker may identify a population that is more tolerant of ETS, and therefore more likely to be exposed outside the home. Evidence in support of this speculation is provided by a study of urinary cotinine levels in nonsmoking men in the United Kingdom (`Wald and Ritchie 1984). In this study, the men married to women who smoked reported a 34 greater duration of exposure outside the home than men married to women who did not smoke. Until accurate and inexpensive exposure markers are available for cumulative ETS exposure, the questionnaire approach will remain the simplest means of obtaining exposure information. It is, there fore, important to consider the misclassification that can be intro duced by using this indirect measure of exposure, In studies of the effect of ETS exposure, two types of misclassification are of concern: misclassification of current or former smokers as never smokers and misclassification of the extent of ETS exposure. Because active smoking has a greater effect on the lungs than exposure to ETS? the inclusion of active smokers within a larger group of nonsmokers may lead to the fmding of a significant effect on lung function, which is actually attributable to active smoking rather than to involuntary smoking. Misclassification of undeclared active smoking is a particularly important source of error in studies involving teenagers. Misclassification of smoking status is also of concern in casecontrol studies of the association between exposure to M`S and lung cancer. Information about smoking habits for these studies often comes from interviews with a surviving spouse or surrogate, who may have been a close family member, neighbor, or friend, or from a review of medical records. The smoking habits of the subject may he incorrectly reported. Classification of individuals who are current or former smokers as never smokers would lead to a spurious increase in the relative risk for lung cancer in nonsmokers exposed to ETS, because the smoking habits of spouses tend to be correlated. The extent of this bias in the case-control studies is uncertain. The proportion of people reported as never smokers, but who in fact did smoke in the past, is unknown. The proportion of current smokers who report themselves as nonsmokers can be estimated from studies using markers to validate questionnaires. Using biochemical markers of tobacco smoke ahsorption, the propor- tion would appear to he about 0.5 to 3 percent, depending on the population studied and the questionnaire used (Wald et al. 1981; Saloojee et al. 1982). Misclassification of the extent of ETS exposure can also occur, and may reduce the observed risk if a nonsmoking spouse of a smoker is not exposed to smoke at home. Friedman and colleagues (19831, reporting on a survey of 38,000 subjects, noted that 47 percent of nonsmoking women married to smokers reported that they were not exposed to tobacco smoke at home. Measurements of Absorption The difficulties inherent in estimating exposure and dose have provided the impetus for the development of biological markers for exposure to both MS and ETS. The marker that at present holds the 36 highest promise is cdhine, the mqjor metabolite of nicotine. Cotinine may he measured in saliva, blood, or urine. Numerous studies have demonstrated that there is good correlation between these measures of cotinine and the estimated exposure to tobacco smoke under laboratory conditions (Russell and Feyerabend 1975; HofEnann et al. 1984) and under conditions of daily life (Russell and Feyerabend 1975; Feyerabend et al. 1982; Foliart et al. 1983; Wald et al. 1984; Wald and Ritchie 1984; Jarvis et al. 1984; Matsukura et al. 1984; Greenberg et al. 1984). Cotinine is probably the best marker for tobacco smoke intake because it is highly sensitive and specitlc for t&acc~ smoke and because it can be detected both in active smokers and in individuals exposed to EX'S. Further details about cotinine and other markem are to be found in Chapter 4. Pohntiully Gmfounding Variables In any epidemiological study, the confounding factors must be considered and their effects controlled. Confounding refers to the bii effect of a factor that independently influences the risk for the disease of concern and is also associated with the exposure under evaluation. Confounding is of particular concern when the effects of the exposure of interest are expe&d to be small. The potential confounding variables depend on the health outcome of interest. For lung cancer, occupational exposures, diet, and exposure to other combustion products are of concern. For acute and chronic pulmonary effects, potential confounders include airways hyperresponsiveness, other indoor air pollutants, outdoor air pollu- tion, respiratory tract infections, occupational exposure, and socio economic status, which may potentially influence disease risk through its environmental correlau23. While this list is extensive, it may not be inclusive; in any single investigation it may not be possible to meesure and control all potentially confounding vti- able& In general, the evidence on active smoking in combination with the dosimetrp of involuntary smoking leads to the conclusion that the effecta of ETS on a population will be substantially less than the effecta of active smoking. The effects of E!R3 on infants and young children are an important exception. The association of E'IS with an adverse effect in an individual study may reflect bias, chance, or a causal relationship. Statistical signiticance testing is used to quantitate the role of chance; by convention, a p (probability) value less than 0.05 is deemed statisti- cally significant. A p value less than 0.05 means that the observed results would occur by chance less than 5 times out of 100, if there is 36 truly no association between ETS and the effect. The choice of 0.05 is arbitrary, and as the significance level declines, the probability that the observation could have occurred by chance lessens. For effects of small magnitude, as may he anticipated for some consequences of exposure to ETS, a large study population may be necessary to demonstrate statistical significance. The absence of statistical significance for an association may refled an inadequate sample sixe and is not always indicative of the absence of an association. In this regard, reports describing the absence of effects of ETS should provide the calculations needed to demonstrate the study's statistical power (ability to detect effects of the magnitude expected) or a confidence interval for the estimate of effect. An additional statistical issue is the directionality of statistical significance testing. Either one-sided or two-sided tests may he used, in the fmt, only effects in one direction are considered a possibility, whereas twosided tests consider the possibility of effects in opposing directions, i.e., increase or decrease of risk Given the strength of the evidence on active smoking and disease risk, one-sided testing in the direction of an adverse effect seems appropriate for most potential consequences of ETS. However, one-sided tests have not been performed in all investigations of ETS; the use of two-sided tests makes these studies conservative, as statistical significance will less often be attained. Respiratory System Effects of Involuntary Cigarette Smoke Exposure This section reviews the evidence on involuntary smoking and the adverse physiologic effects, respiratory symptoms, and respiratory diseases in nonsmoking adults and children. Health effects related to fetal exposure in utero from active smoking by the mother are not discussed. Lung growth and development may he influenced by in utero exposure, and the effects of such exposures have not been separated from those of exposure after birth. More complete treatments of this issue have heen published (US DHEW 1979; US DHHS 1980, Abel 1980; Weinberger and Weiss 1981). This section begins with a review of the data on infants and children who are exposed primarily through parental smoking. The health effects examin ed are increased respiratory illnesses, of both the upper and the lower respiratory tracts, increased chronic respiratory symptoms and illnesses, and alterations in lung growth and development. Studies of adults, whose exposures to environmen- tal tobacco smoke occur in a variety of settings, are examined with regard to symptoms and changes in measures of lung function. The potential for J3TS to produce bronchoconstriction in asthmatic and nonasthmatic subjects is also examined. 37 InfantsandChildren Acute Respimtory Illness Longitudinal Studies A number of studies, based on a variety of different designs, have examined the effects of involuntary smoking on the acute respira- tory illness experience of children (Table 1). Several different end points have been ev&&ed in these investigations: hospitalization for bronchitis or pneumonia as 888e88ed by hospital records (Harlap and Davies 1974; Rantakallio 1978); questionnaire assessment of hospitalization for bronchitis or pneumonia or of doctor's visits (Colley 1971; Leeder et al. 1976a) or both G'ergusson et al. 1981; Fergusson and Horwood 1985); questionnaire assessment of reapira- tory illness within the last year (Cameron et al. 1969; Schenker et al. 1983; Ware et al. 1984); chest illness before age 2 (Schenker et al. 1983); hospitalization for respiratory syncytial virus 0 infection (Sims et al. 1978; pullan and Hey 1982); physiciandiagnosed bronchitis, tracheitis, or laryngitis (Pedreira et al. 1985); and tonsillectomy as an indication of recurrent respiratory infection (Said et al. 1978). These diverse end points range from illnesses associated with a specific etiologic agent, e.g., RSV bronchiolitis, to clinician&agnosed syndromes, e.g., bronchitis of undetermined etiology. The possibility of reporting bias must be considered for the studies that have used questionnaires to measure iUness experience. In most of these studies, parents, usually the mother, have responded for the child and reported on the child's illness experience. Some investiga- tors have suggested that mothers with respiratory symptoms are more likely to report symptoms for their children and that stratifica- tion of subjects by the symptom status of their parents removes this element of recall bias (Lebowitz and Burrows 1976). Removal of symptomatic parents, however, may result in overcorrection for recall bias because cigarette smoking is associated with symptoms in the adult. This analytical strategy would not be expected to adjust for biased parental recall of early life events. Additionally, in all studies in which potential reporting bias was examined, control for parents' status reduced, but did not eliminate, associations of involuntary smoking with health -outcomes (Colley et al. 1974; Leeder et al. 1976a,,b; Schenker et al. 1983; Ware et al. 198.4). Further, the consistency of these studies, in spite of differing study populations and methods, weighs against bias as the sole explanation for the effect of involuntary smoke exposure. Harlap and Davies (1974) studied 10,672 births in Israel between 1965 ad 1968 and observed that infants, whose mothers, at a prenatal visit, reported that they smoked, had a 27.5 percent greater hospital admission rate for pneumonia and bronchitis than children 38 TABLE 1.-E&y childhood reepiratory illnew and involuntary c@arette smoking 0 l-10 11-m m+ C-Y' 2$4x birth& 1963-1966, fJt&hdm bItmdLiti/ 7.6 10.4 11.1 153 (1971) prhemo&tIrrtyeuoflifo 10.3 16.1 14.6 292 Fa=1.78 for a?m pumt maker RR=280 fbr two puwlt mllokam numberaEm&rwx l&d-rhdr TABLE ~-continued Study Saidetal. w78) 8ohenkeretalal. mfw Eht&b fihP Dlneu~ rata per 100 ckllnumb 3,920 children, ajpd lo-!20, -w ondhr 28.2 41.4 60.9 ~&~notobu France edem, geaiemlly before pmultmmkiDghmldt~rspac age6,Milldi&orof~ueult timediredb-~ mepimtoly tact infedion r wP== lo+ Y=- 4,071 children, eged 6-14, che6tiuaembeforeage2 6.7 7.9 11.6 Trend#forbothsirmrhMt united stata ChdUblW>SdQ%3iDptlCt 8.8 11.8 13.6 Ye= Parent- NOMIlWkGI chrmlt- camerolJ et al. w60) Leederetal US?Bp, b) am8 et al. (1978) 168 children, agmi M; Reepimtory iuners, rertricted 1.33 1.4 lllneumportednot~ parenta t&phone activity sad/or medical notclearhoymportbgbdult quationnaire, united stata conmllhllwhlutyeu ml&dtoohud -ludy 2J4!3 infant& born l96s- RR - 2.0 for Wants with two Not provided Puew mlponu bin unlikely, 1986, EngLand amokhg per&a el&cte-Torinfmltod -P-P-e- Rp&wIul~~not invutigatod Lcmgiw Btlldy 36 children, hcapitakad, Bonierline eipifhlt in- in Not pmided R8vblvndlioli~36 Noh6niCant&ctfor matelnalmlloking,6lwtye8rof colltro~ E&end ?? ???o?*?? o ? life emountemokedorabrfw RR=266 IYLm~ofMthncul~ c---M* TABLE l.-Continued lZd&dliO (1Qw Pullan and Hey ww l&t21 children of amoking sienifieant incream in Not `& FlUBpdiV8fOllOUUpddda motbera hapMid for rupiratory vidt4hoapi~dmtba l&322 children of ilhemduringfimt6yeamoflih uPbrsas&- n-king mothem RRz1.74 alldingwal~ FWmd Iaaei-w 190 children hooPitaliced, 8ignis~teffe!ctofmatemal Not prwidd c---M-b B8vinfectioQfh%tywIrof (Rk1.96) and ~&msJ (RR-1.62) life; 111 nonhonPi~ smoking at time of rtudo; -hb FwNd Eignaant maternal lrmobhg effectduringiintyenroflife (RR=l.M) F&&a et al. ww Nommokex hoker -- 1,144 infanta in prdintric 8ignibntincreer,inrupiratory Brolrchitis 71 109 l%dia~nothlimkdb pi-act& united 8tatu ibUDESunonp~O~ 21 40 eqmuwmaffactmfa childrcm 4 7 LV" tia of nonsmoking mothers. In addition, they demonstrated a dose- response relationship between the amount of maternal smoking and the number of hospital admissions for these conditions. The infants were classified by the mothers' prenatal smoking behavior and not by the mothers' smoking behavior during the first year of the child's life. Maternal smoking habits would probably have remained relatively stable across the short observation period. British. investigators (Colley et al. 1974) followed children born between 1963 and 1985 in London and also observed an increased frequency of bronchitis and pneumonia during the first year of life in the children of parents who smoked. This difference did not persist at 2 to 5 years of age. Tbis effect was independent of the parents' personal reports of winter morning phlegm and increased with the amount of smoking by parents. The annual incidence of bronchitis and pneumonia during the first year of life also increased with a greater number of siblings. This variable was not controlled in the original analysis, however, Leeder and colleagues (1976b) subse quently reported that, in this same cohort, a dose-response relation- ship with parental smoking persisted for bronchitis and pneumonia in the first year of life, after control for parental respiratory symptoms, the sex of the child, the number of siblings, and a history of respiratory illness in the siblings. Fergusson and colleagues (1981) studied 1,265 New Zealand children from birth to age 3. They demonstrated an increase in bronchitis and pneumonia and in lower respiratory illness during the first 2 years of life in children whose mothers smoked compared with child.ren whose mothers did not smoke. Correction for maternal age, family size, and socioeconomic status did not affect the relationship between the amount of maternal smoking and the rate of respiratory illness. The effect of maternal smoking declined with increasing age of the child. In a second report (Fergusson and Horwood 1985) the followup was extended to include the first 6 years of life. The results conf%rmed the initial fmdings. Maternal, but not paternal, smoking was associated with a statistically significant increase in lower respiratory illnesses during the first 2 years of life. However, after age 2 there was no signif?cant effect of maternal smoking on respiratory illness occur- rence. Rmbkdlio (1978) followed more than 3,696 children during the first 5 years of life; half of the children had mothers who smoked cigarettes during pregnancy and half did not. The children of mothers who smoked had a 70 percent greater chance of hmpi&- tion for a respiratory illness than the children of nonsmoking mothers. Pedreira and associates (1985) prospsctively studied 1,144 infants and their families in the greater Washington, DC., area. Mate& 42 smoking was associated with an excess frequency of acute bronchitis, tracheitis, and lary&tis, as diagnosed by the pediatricians caring for these families. Episodes of croup, pneumonia, and bronchiolitis were not increased by maternal smoking. A family history of chronic respiratory symptoms ~88 also associated with excess respiratory illness. Ware and coworkers (1984) studied more than 10,009 children in six American cities. Maternal cigarette smoking was associated with increased parental reporting of a doctordiagnosed respiratory illness before the age of 2 years and of an acute respiratory illness within the past year. The prevalence of positive questionnaire responses increased consistently with the current daily cigarette consumption of the mother; the d-response relationships were unchanged by adjustment for maternal symptoms and educational status. Cross-Sectional Studies Schenker and coworkers (1983) studied 4,071 children between the ages of 5 and 14 years in a cross-sectional study in Pennsylvania. Both chest illness in the past year and severe chest illness before age 2 were more frequently reported in nonsmoking children of parents who smoked. These investigators found that symptom and illness rates were higher in children of parents with respiratory symptoms. However, a significant effect of maternal smoking on these illness variables remained after adjustment for the parents' own respira- tory symptom history. In a study of 1,355 children between 6 and 12 years of age in the Iowa public schools, Ekwo and coworkers (1983) found that the presence in the home of at least one parent who smoked was significantly associated with reported hospitalization of the child for a respiratory illness during the first 2 years of life. As in other studies, the effect was stronger for maternal smoking than for paternal smoking. Case-Control Studies In England, Sims and colleagues (1978) examined 35 children at 8 years of age who had been hospitalized during infancy for RSV bronchiolitis and compared them with 35 control children of similar age. Maternal smoking was associated with a relative risk of 2.65 for hospitalization due to bronchiolitis. The sample size was small, and this effect of maternal smoking was not statistically significant. Pullan and Hey (1982) studied children who had been hospitalized with documented RSV infection in infancy. They found significantly greater smoking by their mothers at the time of the infection, compared with children hospitalized for other illnesses, including respiratory disease for which RSV infection was not documented. At 43 age 10, the children previously ill with RSV infection had an excess reported occurrence of wheeze and asthma and had lower levels of pulmonary function in comparison with the controls. The research- ers could not determine whether the RSV infection had caused persistent damage that affected the maturation of the lung or whether these children were already more susceptible to severe RSV infection because of pulmonary problems that antedated the RN infection. In summary, the results of these studies show excess acute respiratory illness in the children of parents who smoke, particularly in children under 2 years of age. This pattern is evident in studies conducted with different methodologies and in different locales. The increased risk of hospitalization for severe bronchitis or pneumonia associated with parental smoking ranges from 20 to 40 percent during the first year of life. Young children appear to represent a more susceptible population for the adverse effects of involuntary smoking than older children or adults. The timeactivity patterns of infants, which generally place them in proximity to their mothers, may lead to particularly high exposures to environmental tobacco smoke if the mother smokes. Acute respiratory illnesses during childhood may have long-term effects on lung growth and development, and might increase the susceptibility of the lung to the effects of active smoking and to the development of chronic obstructive lung disease (Samet et al. 1983; US DHHS 1984). Cough, Phlegm, and Wheezing A number of crossse&onal studies from different countries (Table 2) have shown a positive association between parental cigarette smoking and the prevalence of chronic cough and chronic phlegm ,in children; some studies have shown a relationship for persistent wheeze. However, not all studies have shown a positive relationship for all symptoms. The results of some of these studies may have been confounded by the child's own smoking habits (Colley et al. 1974, Bland et al. 1978; Kasuga et al. 1979). The association with parental smoking was not statistically &i&ant for all symptoms in all studies (Lebowits and Burrows 1976; Schilling et al. 1977; Schenker et al. 1983). However, the majority of studies showed an increase in symptom prevalence with an increase in the number of smoking parents in the home. A recent report (Charlton 1984) provides crosssectional data on parent-reported cough for 15,000 children, 8 to 19 years of age, in northern England. Chronic cough in the children was related to their age and to their own cigarette smoking status. However, with control of these factors by stratification, the number of parental smokers in the home was positively associated with the occurrence of chronic 44 TABLE Z.-Chronic respiratory symptoma in children in relation to involuntary smoke exposure Bates per 100 by numb8r of amoking parents Study SUhjfXbJ Beapiitory eymptonu or illness 0 1 2 c!ammellte Wley et al. (1974) 2,426 children, agfd 614, Chronic cough; quentionnaire blend completed by parent 16.6 17.1 22.2 Trend eignifican~ reportiog bina -pcmible result of parent symptoma or ecth smoking in children, ldikdYtOC!IpL3blflIU&CtOf trend Bland et al. W378) 3.106 children, awl 12-13, did not admit-te-ever emoking cigarettes., England Couah durina day or at nkht - . Morning oough 16.4 19.0 29.6 1.6 2.8 2.9 Croewectional study children's self-reported symphme end emoking hietory a&&d aimul~ual~ morning end daytime-&e&- different dimeen, could be difference in expoeure (expomre more likely awnke than deep) Crowaxtionel study, adju&d for cbild'e own smoking habita Wek et al. 8E4 children, aged 6-9, wm United States Chronic wugh end phlegm 1.7 2.1 3.4 Per&tent wheeze 1.8 6.8 11.8 Tread not rign&ant Tend significant Cmm-wtional study, edjueted for parental symptoms and child% ~WII SmOkiIlg Charkon aw 16,ooO children, eged S-19 yeara, E&and 40.0 46.0 66.0 TABLE 2.4htinued Study Subject.3 Wee per 100 by number of smoking parent-g Respiratory 6ymptoms or illness 0 1 2 Comment8 Dodge (1982) 628 children, grades 3-4, twwparent households; parent questionnaire response, United States Any wheeze 27.6 27.9 40.0 Phlegm 6.4 10.9 12.0 Cwxh 14.6 23.0 27.8 Au trends tdgnlfiwn~ some aFect might relate to po.renM Wm@moa but no trend influence !ik.ely &os-e&onal study Schenker et al. u9w Lehowitz and Burrowx (1976) SchiIllng et al. (1977) Kaeuga et al. (1979) 4,071 children, aged 6-14, United States 1,625 children, <16 yenm old, United States 816 children, age 7+, United States 1,937 children, aged 6-11, Jaw Chronic cough chronic phlegm Persistent wheeze Pereietent cough Pen&tent phlegm whesre couph, phMm, wheeze wheeze. asthma Trend not significant not austed for parental eymptome, although parental symptom effect dyr-ed Croeee&ional study Hiiher rates in symptomatic parent .houeebol&, trends persisted for asymptomatic households; no adjustment for child`e own smoking Cros+e&ional etudy Specific data not provided -ional study Adjust.4 for distance of home from main tratl-ic, highway cmee-sectional study Ekwo et al. (1983) 1,366 children, eged 6-12, United States Coughs with adds Wheeeing apart from c&3 6.2 1.0 8.3 4.1 4.8 4.0 1.2 7.7 6.4 Never Parent smoker . smoker 3.7 7.2 10.0 12.8 23.4 94.1 No swcant effect Increased prevalence in heavy smoker (>21 &/day) family less clear effect in light smoker (~21 c&z