The Health Consequences of Involuntary Exposure to Tobacco Smoke A Report of the Surgeon General
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The Health Consequences of Involuntary Exposure to Tobacco Smoke A Report of the Surgeon General
Department of Health and Human Services
The Health Consequences of Involuntary Exposure to Tobacco Smoke
National Library of Medicine Cataloging in Publication The health consequences of involuntary exposure to tobacco smoke : a report of the Surgeon General. – [Atlanta, Ga.] : U.S. Dept. of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, [2006] Includes bibliographical references. 1.
Tobacco Smoke Pollution -- adverse effects. I. United States. Public Health Service. Office of the Surgeon General. II. United States. Office on Smoking and Health.
O2NLM: WA 754 H4325 2006
Centers for Disease Control and Prevention Coordinating Center for Health Promotion National Center for Chronic Disease Prevention and Health Promotion Office on Smoking and Health This publication is available on the World Wide Web at http://www.surgeongeneral.gov/library
Suggested Citation U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402. ISBN 0-16-076152-2 Use of trade names is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke A Report of the Surgeon General
2006 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Office of the Surgeon General Rockville, MD
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Message from Michael O. Leavitt Secretary of Health and Human Services
This Surgeon General’s report returns to the topic of the health effects of involuntary exposure to tobacco smoke. The last comprehensive review of this evidence by the Department of Health and Human Services (DHHS) was in the 1986 Surgeon General’s report, The Health Consequences of Involuntary Smoking, published 20 years ago this year. This new report updates the evidence of the harmful effects of involuntary exposure to tobacco smoke. This large body of research findings is captured in an accompanying dynamic database that profiles key epidemiologic findings, and allows the evidence on health effects of exposure to tobacco smoke to be synthesized and updated (following the format of the 2004 report, The Health Consequences of Smoking). The database enables users to explore the data and studies supporting the conclusions in the report. The database is available on the Web site of the Centers for Disease Control and Prevention (CDC) at http://www.cdc.gov/tobacco. I am grateful to the leadership of the Surgeon General, CDC’s Office on Smoking and Health, and all of the contributors for preparing this important report and bringing this topic to the forefront once again. Secondhand smoke, also known as environmental tobacco smoke, is a mixture of the smoke given off by the burning end of tobacco products (sidestream smoke) and the mainstream smoke exhaled by smokers. People are exposed to secondhand smoke at home, in the workplace, and in other public places such as bars, restaurants, and recreation venues. It is harmful and hazardous to the health of the general public and particularly dangerous to children. It increases the risk of serious respiratory problems in children, such as a greater number and severity of asthma attacks and lower respiratory tract infections, and increases the risk for middle ear infections. It is also a known human carcinogen (cancer-causing agent). Inhaling secondhand smoke causes lung cancer and coronary heart disease in nonsmoking adults. We have made great progress since the late 1980s in reducing the involuntary exposure of nonsmokers in this country to secondhand smoke. The proportion of nonsmokers aged 4 and older with a blood cotinine level (a metabolite of nicotine) indicating exposure has declined from 88 percent in 1988–1991 down to 43 percent in 2001–2002, a decline that exceeds the Healthy People 2010 objective for this measure. Despite the great progress that has been made, involuntary exposure to secondhand smoke remains a serious public health hazard that can be prevented by making homes, workplaces, and public places completely smoke-free. As of the year 2000, more than 126 million residents of the United States aged 3 or older still are estimated to be exposed to secondhand smoke. Smoke-free environments are the most effective method for reducing exposures. Healthy People 2010 objectives address this issue and seek optimal protection of nonsmokers through policies, regulations, and laws requiring smoke-free environments in all schools, workplaces, and public places.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Foreword This twenty-ninth report of the Surgeon General documents the serious and deadly health effects of involuntary exposure to tobacco smoke. Secondhand smoke is a major cause of disease, including lung cancer and coronary heart disease, in healthy nonsmokers. In 2005, it was estimated that exposure to secondhand smoke kills more than 3,000 adult nonsmokers from lung cancer, approximately 46,000 from coronary heart disease, and an estimated 430 newborns from sudden infant death syndrome. In addition, secondhand smoke causes other respiratory problems in nonsmokers such as coughing, phlegm, and reduced lung function. According to the CDC’s National Health Interview Survey in 2000, more than 80 percent of the respondents aged 18 years or older believe that secondhand smoke is harmful and nonsmokers should be protected in their workplaces. Components of chemical compounds in secondhand smoke, including nicotine, carbon monoxide, and tobacco-specific carcinogens, can be detected in body fluids of exposed nonsmokers. These exposures can be controlled. In 2005, CDC released the Third National Report on Human Exposure to Environmental Chemicals, which found that the median cotinine level (a metabolite of nicotine) in nonsmokers had decreased across the life stages: by 68 percent in children, 69 percent in adolescents, and 75 percent in adults, when samples collected between 1999 and 2002 were compared with samples collected a decade earlier. These dramatic declines are further evidence that smoking restrictions in public places and workplaces are helping to ensure a healthier life for all people in the United States. However, too many people continue to be exposed, especially children. The recent data indicate that median cotinine levels in children are more than twice those of adults, and non-Hispanic blacks have levels that are more than twice as high as those of Mexican Americans and non-Hispanic whites. These disparities need to be better understood and addressed. Research reviewed in this report indicates that smoke-free policies are the most economic and effective approach for providing protection from exposure to secondhand smoke. But do they provide the greatest health impact. Separating smokers and nonsmokers in the same airspace is not effective, nor is air cleaning or a greater exchange of indoor with outdoor air. Additionally, having separately ventilated areas for smoking may not offer a satisfactory solution to reducing workplace exposures. Policies prohibiting smoking in the workplace have multiple benefits. Besides reducing exposure of nonsmokers to secondhand smoke, these policies reduce tobacco use by smokers and change public attitudes about tobacco use from acceptable to unacceptable. Research indicates that the progressive restriction of smoking in the United States to protect nonsmokers has had the additional health impact of reducing active smoking. In November 2005, CDC’s Tobacco-Free Campus policy took full effect in all facilities owned by CDC in the Atlanta area. As the Director of the nation’s leading health promotion and disease prevention agency, I am proud to support this effort. With this commitment, CDC continues to protect the health and safety of all of its employees and serves as a role model for workplaces everywhere. Julie Louise Gerberding, M.D., M.P.H. Director Centers for Disease Control and Prevention and Administrator Agency for Toxic Substances and Disease Registry
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Preface
from the Surgeon General, U.S. Department of Health and Human Services Twenty years ago when Dr. C. Everett Koop released the Surgeon General’s report, The Health Consequences of Involuntary Smoking, it was the first Surgeon General’s report to conclude that involuntary exposure of nonsmokers to tobacco smoke causes disease. The topic of involuntary exposure of nonsmokers to secondhand smoke was first considered in Surgeon General Jesse Steinfeld’s 1972 report, and by 1986, the causal linkage between inhaling secondhand smoke and the risk for lung cancer was clear. By then, there was also abundant evidence of adverse effects of smoking by parents on their children. Today, massive and conclusive scientific evidence documents adverse effects of involuntary smoking on children and adults, including cancer and cardiovascular diseases in adults, and adverse respiratory effects in both children and adults. This 2006 report of the Surgeon General updates the 1986 report, The Health Consequences of Involuntary Smoking, and provides a detailed review of the epidemiologic evidence on the health effects of involuntary exposure to tobacco smoke. This new report also uses the revised standard language of causality that was applied in the 2004 Surgeon General’s report, The Health Consequences of Smoking. Secondhand smoke is similar to the mainstream smoke inhaled by the smoker in that it is a complex mixture containing many chemicals (including formaldehyde, cyanide, carbon monoxide, ammonia, and nicotine), many of which are known carcinogens. Exposure to secondhand smoke causes excess deaths in the U.S. population from lung cancer and cardiac related illnesses. Fortunately, exposures of adults are declining as smoking becomes increasingly restricted in workplaces and public places. Unfortunately, children continue to be exposed in their homes by the smoking of their parents and other adults. This exposure leads to unnecessary cases of bronchitis, pneumonia and worsened asthma. Among children younger than 18 years of age, an estimated 22 percent are exposed to secondhand smoke in their homes, with estimates ranging from 11.7 percent in Utah to 34.2 percent in Kentucky. As this report documents, exposure to secondhand smoke remains an alarming public health hazard. Approximately 60 percent of nonsmokers in the United States have biologic evidence of exposure to secondhand smoke. Yet compared with data reviewed in the 1986 report, I am encouraged by the progress that has been made in reducing involuntary exposure in many workplaces, restaurants, and other public places. These changes are most likely the major contributing factors to the more than 75 percent reduction in serum cotinine levels that researchers have observed from 1988 to 1991. However, more than 126 million nonsmokers are still exposed. We now have substantial evidence on the efficacy of different approaches to control exposure to secondhand smoke. Restrictions on smoking can control exposures effectively, but technical approaches involving air cleaning or a greater exchange of indoor with outdoor air cannot. Consequently, nonsmokers need protection through the restriction of smoking in public places and workplaces and by a voluntary adherence to policies at home, particularly to eliminate exposures of children. Since the release of the 1986 Surgeon General’s report, the public’s attitude and social norms toward secondhand smoke exposure have changed significantly—a direct result of the growing body of scientific evidence on the health effects of exposure to secondhand smoke that is summarized in this report.
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Finally, clinicians should routinely ask about secondhand smoke exposure, particularly in susceptible groups or when a child has had an illness caused by secondhand smoke, such as pneumonia. Because of the high levels of exposure among young children, their exposure should be considered a significant pediatric issue. Additionally, exposure to secondhand smoke poses significant risks for people with lung and heart disease. The large body of evidence documenting that secondhand smoke exposures produce substantial and immediate effects on the cardiovascular system indicates that even brief exposures could pose significant acute risks to older adults or to others at high risk for cardiovascular disease. Those caring for relatives with heart disease should be advised not to smoke in the presence of the sick relative. An environment free of involuntary exposure to secondhand smoke should remain an important national priority in order to reach the Healthy People 2010 objectives. Richard Carmona, M.D., M.P.H., F.A.C.S. Surgeon General
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Acknowledgments This report was prepared by the U.S. Department of Health and Human Services under the general direction of the Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.
Terry F. Pechacek, Ph.D., Associate Director for Science, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Richard H. Carmona, M.D., M.P.H., F.A.C.S., Surgeon General, United States Public Health Service, Office of the Surgeon General, Office of the Secretary, Washington, D.C.
The editors of the report were Jonathan M. Samet, M.D., M.S., Senior Scientific Editor, Professor and Chairman, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Kenneth P. Moritsugu, M.D., M.P.H., Deputy Surgeon General, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Leslie A. Norman, Managing Editor, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Robert C. Williams, P.E., DEE, Chief of Staff, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Caran Wilbanks, Technical Editor, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Karen A. Near, M.D., M.S., Senior Science Advisor, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Audrey Pinto, Technical Editor, Barrington, Rhode Island.
Ron Schoenfeld, Ph.D., Senior Science Advisor, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Contributing authors were
Julie Louise Gerberding, M.D., M.P.H., Director, Centers for Disease Control and Prevention, Atlanta, Georgia.
Stephen Babb, M.P.H., Health Education Specialist, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Janet Collins, Ph.D., Director, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
John T. Bernert, Ph.D., Supervisory Research Chemist, Emergency Response and Air Toxicants Branch, Division of Laboratory Sciences, National Center for Environmental Health, Coordinating Center for Environmental Health and Injury Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
Barbara Bowman, Ph.D., Associate Director for Science (acting), National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Derek G. Cook, Ph.D., Professor of Epidemiology, Division of Community Health Sciences, St. George’s, University of London, London, England.
Corinne G. Husten, M.D., M.P.H., Director (acting), Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
David B. Coultas, M.D., Professor and Chairman, Department of Internal Medicine, University of Texas Health Center at Tyler, Tyler, Texas.
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Dawn DeMeo, M.D., Associate Physician, Brigham and Women’s Hospital, Channing Laboratory, Instructor in Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts.
David M. Mannino, M.D., Associate Professor of Medicine, Pulmonary Epidemiology Research Laboratory, Division of Pulmonary, Critical Care and Sleep Medicine, University of Kentucky, Lexington, Kentucky.
Karen Emmons, Ph.D., Professor, Harvard School of Public Health, Deputy Director of Community-Based Research, Department of Medical Oncology, DanaFarber Cancer Institute, Boston, Massachusetts.
John F. McCarthy, Sc.D., C.I.H., President, Environmental Health and Engineering, Inc., Newton, Massachusetts. Murray A. Mittleman, M.D., Dr.P.H., Associate Professor of Medicine and Epidemiology, Harvard University at Beth Israel Deaconness Medical Center, Boston, Massachusetts.
Stanton Glantz, Ph.D., Professor of Medicine, Division of Cardiology, University of California, San Francisco, California. Steven N. Goodman, M.D., M.H.S., Ph.D., Associate Professor of Oncology, Pediatrics, Epidemiology, and Biostatistics, Department of Oncology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
Patricia J. O’Campo, Ph.D., Alma and Baxter Ricard Chair in Inner City Health, Director, Centre for Research on Inner City Health, St. Michael’s Hospital, Toronto, Ontario. William Parmley, M.D., The Seventy, Salt Lake City, Utah.
S. Katharine Hammond, Ph.D., C.I.H., Professor of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California.
Terry F. Pechacek, Ph.D., Associate Director for Science, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Stephen S. Hecht, Ph.D., Professor, University of Minnesota Cancer Center, Minneapolis, Minnesota. John R. Hoidal, M.D., The Clarence M. and Ruth N. Birrer Presidential Professor and Chairman of Medicine, School of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
Jonathan M. Samet, M.D., M.S., Professor and Chairman, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Jerelyn H. Jordan, Program Consultant, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Donald R. Shopland Sr., U.S. Public Health Service (retired), Ringgold, Georgia. John D. Spengler, Ph.D., Akira Yamaguchi Professor of Environmental Health and Human Habitation, Director, Environmental Health Department, School of Public Health, Harvard University, Boston, Massachusetts.
Ichiro Kawachi, M.D., Ph.D., Professor of Social Epidemiology, Harvard School of Public Health, Harvard University, and Associate Professor of Medicine, Channing Laboratory, Harvard Medical School, Harvard University, Boston, Massachusetts.
David P. Strachan, M.D., Professor of Epidemiology, Division of Community Health Sciences, St. George’s, University of London, London, England.
Nora L. Lee, Research Program Coordinator, Center for Autism and Developmental Disabilities Epidemiology, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Scott T. Weiss, M.D., M.S., Professor of Medicine, Harvard Medical School, and Director, Respiratory, Environmental, and Genetic Epidemiology, Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.
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Anna H. Wu, Ph.D., Professor, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Neal Benowitz, M.D., Professor of Medicine, Psychiatry, and Biopharmaceutical Sciences, and Chief, Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, California.
Reviewers were
Valerie Beral, F.R.C.P., Professor of Epidemiology, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.
Duane Alexander, M.D., Director, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Michele Bloch, M.D., Ph.D., Medical Officer, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
David L. Ashley, Ph.D., Chief, Emergency Response and Air Toxicants Branch, Division of Laboratory Sciences, National Center for Environmental Health, Coordinating Center for Environmental Health and Injury Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
William Blot, Ph.D., Chief Executive Officer, International Epidemiology Institute, Ltd., Rockville, Maryland, and Professor, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Edward L. Avol, M.S., Professor, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. Cathy L. Backinger, Ph.D., M.P.H., Acting Chief, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Paolo Boffetta, M.D., M.P.H., Coordinator, Genetics and Epidemiology Cluster, International Agency for Research on Cancer, Lyon, France. Michael B. Bracken, Ph.D., M.P.H., Susan Dwight Bliss Professor of Epidemiology, Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale University, New Haven, Connecticut.
Stephen W. Banspach, Ph.D., Associate Director for Science, Division of Adolescent and School Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Patrick Breysse, Ph.D., Professor, Division of Environmental Health Sciences, and Director, Division of Environmental Health Engineering, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
John Baron, M.D., Professor, Departments of Medicine and Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire.
John R. Britton, Professor of Epidemiology, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, England.
Rebecca Bascom, M.D., M.P.H., Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Arnold R. Brody, Ph.D., Professor and Vice Chairman, Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana.
Glen C. Bennett, M.P.H., Coordinator, Advanced Technologies Applications in Health Education, Office of Prevention, Education, and Control, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
David M. Burns, M.D., Professor of Family and Preventive Medicine, School of Medicine, University of California, San Diego, California.
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Carl J. Caspersen, Ph.D., M.P.H., Associate Director for Science, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Mirjana V. Djordevic, Ph.D., Bio-analytical Chemist, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland. Lucinda England, M.D., M.S.P.H., Medical Epidemiologist, Maternal and Infant Health Branch, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Terence L. Chorba, M.D., Associate Director for Science, National Center for HIV, STD, and TB Prevention, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia. Ralph J. Coates, Ph.D., Associate Director for Science, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Michael P. Eriksen, Sc.D., Professor and Director, Institute of Public Health, Georgia State University, Atlanta, Georgia. Brenda Eskenazi, Ph.D., Professor of Maternal and Child Health and Epidemiology, and Director, Center for Children’s Environmental Health Research, School of Public Health, University of California, Berkeley, California.
Graham Colditz, M.D., Dr.P.H., Professor of Medicine, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts.
Jing Fang, M.D., M.S., Epidemiologist, Epidemiology and Surveillance Team, Division of Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Adolfo Correa, M.D., Ph.D., M.P.H., Medical Epidemiologist, Division of Birth Defects and Developmental Disabilities, National Center for Birth Defects and Developmental Disabilities, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Elizabeth T.H. Fontham, Dr.P.H., Dean, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Daniel L. Costa, Sc.D., DABT, National Program Director for Air Research, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Alison Freeman, ETS Policy Specialist, Indoor Environments Division, U.S. Environmental Protection Agency, Washington, D.C.
David B. Coultas, M.D., Professor and Chairman, Department of Internal Medicine, University of Texas Health Center at Tyler, Tyler, Texas.
Deborah Galuska, Ph.D., M.P.H., Associate Director for Science, Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Linda S. Crossett, R.D.H., Health Scientist, Research Application Branch, Division of Adolescent and School Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Samuel S. Gidding, M.D., Professor of Pediatrics, Thomas Jefferson University, Nemours Cardiac Center, A.I. duPont Hospital for Children, Wilmington, Delaware.
Ronald M. Davis, M.D., Director, Center for Health Promotion and Disease Prevention, Henry Ford Health System, Detroit, Michigan.
Frank D. Gilliland, M.D., Ph.D., Professor, University of Southern California, Los Angeles, California.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Gary A. Giovino, Ph.D., M.S., Director, Tobacco Control Research Program, Roswell Park Cancer Institute, Buffalo, New York.
Jennifer Jinot, ETS Risk Assessment Scientist, Mathematical Statistician, Office of Research and Development, U.S. Environmental Protection Agency, Washington, D.C.
John Girman, Senior Science Advisor, Indoor Environments Division, U.S. Environmental Protection Agency, Washington, D.C.
Joel Kaufman, M.D., M.P.H., Associate Professor, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington.
Thomas J. Glynn, Ph.D., Director, Cancer Science and Trends, American Cancer Society, Washington, D.C.
Juliette Kendrick, M.D., Medical Officer, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Keith L. Goddard, D.Sc., P.E., Director, Directorate of Evaluation and Analysis, Occupational Safety and Health Administration, U.S. Department of Labor, Washington, D.C. Diane R. Gold, M.D., M.P.H., Channing Laboratory, Brigham and Women’s Hospital, Associate Professor of Medicine, Harvard Medical School, and Associate Professor of Environmental Health, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
Neil E. Klepeis, Ph.D., Post-Doctoral Researcher, Stanford University, and Exposure Science Consulting, Watsonville, California. William Kohn, D.D.S., CAPT, Deputy Associate Director for Science (acting), National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Allan Hackshaw, Deputy Director, Cancer Research UK and UCL Cancer Trials Centre, University College London, London, England.
Petros Koutrakis, Ph.D., Professor of Environmental Sciences, Department of Environmental Health, School of Public Health, Harvard University, Boston, Massachusetts.
Thomas P. Houston, M.D., Professor, Public Health and Family Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana. George Howard, Dr.P.H., Chairman, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
Darwin Labarthe, M.D., Ph.D., M.P.H., Director (acting), Division of Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Gary W. Hunninghake, M.D., Professor, Department of Internal Medicine, and Director, Pulmonary Program in Internal Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
John Lehnherr, Director (acting), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jouni Jaakkola, M.D, Ph.D., D.Sc., Professor and Director, Institute of Occupational and Environmental Medicine, The University of Birmingham, Edgbaston, Birmingham, England.
Youlian Liao, M.D., Epidemiologist, Deputy Associate Director for Science (acting), Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
David R. Jacobs Jr., Ph.D., Professor of Epidemiology, University of Minnesota, Minneapolis, Minnesota. Martin Jarvis, Professor, Cancer Research UK Health Behaviour Unit, Department of Epidemiology and Public Health, University College London, London, England.
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Catherine Lorraine, Director, Policy Development and Coordination Staff, Food and Drug Administration, Rockville, Maryland.
Mark Parascandola, Ph.D., M.P.H., Epidemiologist, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
William R. Maas, D.D.S., M.P.H., Director, Division of Oral Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Samuel F. Posner, Ph.D., Associate Director for Science, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jennifer H. Madans Ph.D., Associate Director for Science, National Center for Health Statistics, Coordinating Center for Health Information and Services, Centers for Disease Control and Prevention, Hyattsville, Maryland.
Bogdan Prokopczyk, Ph.D., Associate Professor of Pharmacology, Department of Pharmacology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Fernando D. Martinez, M.D., Director, Arizona Respiratory Center, and Swift-McNear Professor of Pediatrics, University of Arizona, Tucson, Arizona.
Scott Rogers, M.P.H., Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland.
Kenneth P. Moritsugu, M.D., M.P.H., Deputy Surgeon General, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Dale P. Sandler, Ph.D., Chief, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
Matthew L. Myers, President, Campaign for TobaccoFree Kids, Washington, D.C.
Laura A. Schieve, Ph.D., Epidemiologist, National Center on Birth Defects and Developmental Disabilities, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Elizabeth G. Nabel, M.D., Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. David Nelson, M.D., M.P.H., Senior Scientific Advisor, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Susan Schober, Ph.D., Senior Epidemiologist, National Health and Nutrition Examination Survey (NHANES) Program, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland.
F. Javier Nieto, M.D., Ph.D., Professor and Chair, Department of Population Health Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
Lawrence Schoen, M.S., President and Principal Engineer, Schoen Engineering, Inc., Columbia, Maryland. Ron Schoenfeld, Ph.D., Senior Science Advisor, Office of the Surgeon General, United States Public Health Service, Office of the Secretary, Washington, D.C.
Thomas E. Novotny, M.D., M.P.H., Education Coordinator, UCSF Global Health Sciences, and Professor, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
David Schwartz, M.D., M.P.H., Director, National Institute of Environmental Health Sciences; Director, National Toxicology Program; and Professor of Medicine, Duke University Medical Center, Durham, North Carolina.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Harold E. Seifried, Ph.D., DABT, Chemist, Toxicologist, Industrial Hygenist, Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Noel S. Weiss, M.D., Dr.P.H., Professor, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington.
Frank E. Speizer, M.D., Channing Laboratory, Brigham and Women’s Hospital; Edward H. Kass Professor of Medicine, Harvard Medical School; and Professor of Environmental Health, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
Scott T. Weiss, M.D., M.S., Professor of Medicine, Harvard Medical School, and Director, Respiratory, Environmental, and Genetic Epidemiology, Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts.
Margaret R. Spitz, M.D., M.P.H., Professor and Chair, Department of Epidemiology, M.D. Anderson Cancer Center, University of Texas, Houston, Texas.
Elizabeth M. Whelan, Sc.D., M.P.H., M.S., President, American Council on Science and Health, New York, New York.
Meir J. Stampfer, M.D., Dr.P.H., Department Chair of Epidemiology; Professor of Epidemiology and Nutrition, School of Public Health; and Professor of Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts.
Allen J. Wilcox, M.D., Ph.D., Senior Investigator, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina. Walter C. Willett, M.D., Dr.P.H., Professor of Epidemiology and Nutrition, and Chair, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
James W. Stephens, Ph.D., Associate Director for Science, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Washington, D.C. Gary D. Stoner, Ph.D., Professor, Division of Hematology and Oncology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio.
Gayle Windham, Ph.D., Research Scientist (Epidemiology), Division of Environmental and Occupational Disease Control, California Department of Health Services, Richmond, California.
Esther Sumartojo, Ph.D., M.Sc., Acting Associate Director for Science and Public Health, National Center on Birth Defects and Developmental Disabilities, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Deborah M. Winn, Ph.D., Chief, Clinical and Genetic Epidemiology Research Branch, Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Ira Tager, M.D., M.P.H., Professor of Epidemiology, Division of Epidemiology, School of Public Health, University of California, Berkeley, California.
Alistair Woodward, Ph.D., Head, School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Michael J. Thun, M.D., Vice President, Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia.
Other contributors were Nicole C. Ammerman, Sc.M., Ph.D. Candidate, Research Assistant, Institute for Global Tobacco Control, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Edward Trapido, Sc.D., Associate Director, Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Mary Bedford, Proofreader, Cygnus Corporation, Rockville, Maryland.
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Caroline M. Fichtenberg, M.S., Ph.D. Candidate, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Alyce Ortuzar, Copy Editor, Cygnus Corporation, Rockville, Maryland. Margot Raphael, Senior Editor, American Institutes for Research, Silver Spring, Maryland.
Charlotte Gerczak, M.L.A., Research Writer and Special Projects Coordinator, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Susan Schober, Ph.D., Senior Epidemiologist, National Health and Nutrition Examination Survey (NHANES) Program, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland.
Roberta B. Gray, Senior Administrative Assistant to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Angela Trosclair, M.S., Statistician, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Kat Jackson, Statistician, RTI International, Atlanta, Georgia. Mooim Kang, Graphics Specialist, Cygnus Corporation, Rockville, Maryland. Teresa Kelly, M.S., Project Director, Cygnus Corporation, Rockville, Maryland.
Glenda Vaughn, Public Health Analyst, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Elizabeth Khaykin, M.H.S., Sc.M., Ph.D. Candidate, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Deborah Williams, Desktop Publishing Specialist to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Nancy Leonard, Administrative Assistant II to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Peggy E. Williams, M.S., Writer-Editor, Quantell, Inc., Marietta, Georgia. Database contributors were
Allison MacNeil, M.P.H., Health Scientist, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Mahshid Amini, Health Education Specialist, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
William T. Marx, M.L.I.S., Health Communications Specialist, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Nicole C. Ammerman, Sc.M., Ph.D. Candidate, Research Assistant, Institute for Global Tobacco Control, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland. Erika Avila-Tang, Ph.D., M.H.S., Project Coordinator, Institute for Global Tobacco Control, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Linda McLaughlin, Word Processing Specialist, Cygnus Corporation, Rockville, Maryland. Laura Nelson, M.A., Senior Writer, Cygnus Corporation, Rockville, Maryland.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Jeffrey H. Chrismon, P.M.P., Project Manager, Northrup Grumman Mission Systems, Atlanta, Georgia.
Georgette Lavetsky, M.H.S., Epidemiologist, Office of Substance Abuse Services, Howard County Health Department, Columbia, Maryland.
Oyelola ‘Yomi Faparusi, M.D., Ph.D., Department of Mental Hygiene, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Maria Jose Lopez, B.Sc., Ph.D. Candidate, Evaluation and Intervention Methods Service, Public Health Agency, Barcelona, Spain.
Caroline M. Fichtenberg, M.S., Ph.D. Candidate, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Sharon Mc Aleer, Web Designer, Northrop Grumman Mission Systems, Atlanta, Georgia. Georgiana Onicescu, B.Sc., Master’s Candidate in Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Ola Gibson, Software Engineer, Northrup Grumman Mission Systems, Atlanta, Georgia.
Patti R. Seikus, M.P.H., Health Communications Specialist, Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Hope L. Johnson, M.P.H., Ph.D. Candidate, Department of International Health, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland. Bindu Kalesan, M.Sc., M.P.H., Biostatistician, Asthma and Allergy Center, The Johns Hopkins University, Baltimore, Maryland.
Stephen Strathdee, User Support Specialist, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Elizabeth Khaykin, M.H.S., Sc.M., Ph.D. Candidate, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
The Health Consequences of Involuntary Exposure to Tobacco Smoke Chapter 1.
Introduction, Summary, and Conclusions
1
Introduction 3 Definitions and Terminology 9 Evidence Evaluation 10 Major Conclusions 11 Chapter Conclusions 12 Methodologic Issues 17 Tobacco Industry Activities 23 References 24 Chapter 2.
Toxicology of Secondhand Smoke
27
Introduction 29 Evidence of Carcinogenic Effects from Secondhand Smoke Exposure 30 Mechanisms of Respiratory Tract Injury and Disease Caused by Secondhand Smoke Exposure Mechanisms of Secondhand Smoke Exposure and Heart Disease 52 Evidence Synthesis 64 Conclusions 65 Overall Implications 66 References 67 Chapter 3.
Assessment of Exposure to Secondhand Smoke
46
83
Introduction 85 Building Designs and Operations 86 Atmospheric Markers of Secondhand Smoke 93 Exposure Models 96 Biomarkers of Exposure to Secondhand Smoke 100 Conclusions 115 References 116 Chapter 4.
Prevalence of Exposure to Secondhand Smoke
Introduction 129 Methods 129 Metrics of Secondhand Smoke Exposure Estimates of Exposure 132 Conclusions 158 Overall Implications 158 References 159 Chapter 5.
127
130
Reproductive and Developmental Effects from Exposure to Secondhand Smoke
Introduction 167 Conclusions of Previous Surgeon General’s Reports and Other Relevant Reports Literature Search Methods 167
xv
167
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Critical Exposure Periods for Reproductive and Developmental Effects Fertility 171 Pregnancy (Spontaneous Abortion and Perinatal Death) 176 Infant Deaths 179 Sudden Infant Death Syndrome 180 Preterm Delivery 194 Low Birth Weight 198 Congenital Malformations 205 Cognitive, Behavioral, and Physical Development 210 Childhood Cancer 221 Conclusions 242 Overall Implications 244 References 245 Chapter 6.
Respiratory Effects in Children from Exposure to Secondhand Smoke
Introduction 261 Mechanisms of Health Effects from Secondhand Tobacco Smoke 262 Methods Used to Review the Evidence 266 Lower Respiratory Illnesses in Infancy and Early Childhood 267 Middle Ear Disease and Adenotonsillectomy 292 Respiratory Symptoms and Prevalent Asthma in School-Age Children Childhood Asthma Onset 355 Atopy 375 Lung Growth and Pulmonary Function 385 Conclusions 400 Overall Implications 401 References 402 Chapter 7.
310
Cancer Among Adults from Exposure to Secondhand Smoke
Introduction 423 Lung Cancer 423 Other Cancer Sites 446 Conclusions 484 Overall Implications 484 Appendix 7.1. Details of Recent Lung Cancer Studies References 498 Chapter 8.
169
421
485
Cardiovascular Diseases from Exposure to Secondhand Smoke
Introduction 509 Coronary Heart Disease 509 Stroke 527 Subclinical Vascular Disease 529 Evidence Synthesis 531 Conclusions 532 Overall Implications 532 References 533
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Chapter 9.
Respiratory Effects in Adults from Exposure to Secondhand Smoke
Introduction 539 Biologic Basis 542 Odor and Irritation 545 Respiratory Symptoms 547 Lung Function 553 Respiratory Diseases 555 Conclusions 562 Overall Implications 563 References 564 Chapter 10.
Control of Secondhand Smoke Exposure
Introduction 571 Historical Perspective 571 Attitudes and Beliefs About Secondhand Smoke Policy Approaches 598 Technical Approaches 635 Conclusions 649 Overall Implications 649 References 651 A Vision for the Future
Appendix
667
671
List of Abbreviations
675
List of Tables and Figures Index
588
679
685
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Chapter 1 Introduction, Summary, and Conclusions Introduction
3
Organization of the Report 8 Preparation of the Report 9 Definitions and Terminology Evidence Evaluation Major Conclusions Chapter Conclusions
9
10 11 12
Chapter 2. Toxicology of Secondhand Smoke 12 Evidence of Carcinogenic Effects from Secondhand Smoke Exposure 12 Mechanisms of Respiratory Tract Injury and Disease Caused by Secondhand Smoke Exposure Mechanisms of Secondhand Smoke Exposure and Heart Disease 12 Chapter 3. Assessment of Exposure to Secondhand Smoke 12 Building Designs and Operations 12 Exposure Models 12 Biomarkers of Exposure to Secondhand Smoke 12 Chapter 4. Prevalence of Exposure to Secondhand Smoke 13 Chapter 5. Reproductive and Developmental Effects from Exposure to Secondhand Smoke 13 Fertility 13 Pregnancy (Spontaneous Abortion and Perinatal Death) 13 Infant Deaths 13 Sudden Infant Death Syndrome 13 Preterm Delivery 13 Low Birth Weight 13 Congenital Malformations 13 Cognitive Development 13 Behavioral Development 13 Height/Growth 13 Childhood Cancer 13 Chapter 6. Respiratory Effects in Children from Exposure to Secondhand Smoke 14 Lower Respiratory Illnesses in Infancy and Early Childhood 14 Middle Ear Disease and Adenotonsillectomy 14 Respiratory Symptoms and Prevalent Asthma in School-Age Children 14 Childhood Asthma Onset 14 Atopy 14 Lung Growth and Pulmonary Function 14 Chapter 7. Cancer Among Adults from Exposure to Secondhand Smoke 14 Lung Cancer 14 Breast Cancer 15 Nasal Sinus Cavity and Nasopharyngeal Carcinoma 15 Cervical Cancer 15
12
Introduction, Summary, and Conclusions
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Surgeon General’s Report
Chapter 8. Cardiovascular Diseases from Exposure to Secondhand Smoke 15 Chapter 9. Respiratory Effects in Adults from Exposure to Secondhand Smoke 15 Odor and Irritation 15 Respiratory Symptoms 15 Lung Function 15 Asthma 16 Chronic Obstructive Pulmonary Disease 16 Chapter 10. Control of Secondhand Smoke Exposure 16 Methodologic Issues
17
Classification of Secondhand Smoke Exposure 17 Misclassification of Secondhand Smoke Exposure 19 Use of Meta-Analysis 21 Confounding 22 Tobacco Industry Activities References
2
Chapter 1
24
23
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Introduction
The topic of passive or involuntary smoking was first addressed in the 1972 U.S. Surgeon General’s report (The Health Consequences of Smoking, U.S. Department of Health, Education, and Welfare [USDHEW] 1972), only eight years after the first Surgeon General’s report on the health consequences of active smoking (USDHEW 1964). Surgeon General Dr. Jesse Steinfeld had raised concerns about this topic, leading to its inclusion in that report. According to the 1972 report, nonsmokers inhale the mixture of sidestream smoke given off by a smoldering cigarette and mainstream smoke exhaled by a smoker, a mixture now referred to as “secondhand smoke” or “environmental tobacco smoke.” Cited experimental studies showed that smoking in enclosed spaces could lead to high levels of cigarette smoke components in the air. For carbon monoxide (CO) specifically, levels in enclosed spaces could exceed levels then permitted in outdoor air. The studies supported a conclusion that “an atmosphere contaminated with tobacco smoke can contribute to the discomfort of many individuals” (USDHEW 1972, p. 7). The possibility that CO emitted from cigarettes could harm persons with chronic heart or lung disease was also mentioned. Secondhand tobacco smoke was then addressed in greater depth in Chapter 4 (Involuntary Smoking) of the 1975 Surgeon General’s report, The Health Consequences of Smoking (USDHEW 1975). The chapter noted that involuntary smoking takes place when nonsmokers inhale both sidestream and exhaled mainstream smoke and that this “smoking” is “involuntary” when “the exposure occurs as an unavoidable consequence of breathing in a smoke-filled environment” (p. 87). The report covered exposures and potential health consequences of involuntary smoking, and the researchers concluded that smoking on buses and airplanes was annoying to nonsmokers and that involuntary smoking had potentially adverse consequences for persons with heart and lung diseases. Two studies on nicotine concentrations in nonsmokers raised concerns about nicotine as a contributing factor to atherosclerotic cardiovascular disease in nonsmokers. The 1979 Surgeon General’s report, Smoking and Health: A Report of the Surgeon General (USDHEW 1979), also contained a chapter entitled “Involuntary Smoking.” The chapter stressed that “attention to involuntary smoking is of recent vintage, and only
limited information regarding the health effects of such exposure upon the nonsmoker is available” (p. 11–35). The chapter concluded with recommendations for research including epidemiologic and clinical studies. The 1982 Surgeon General’s report specifically addressed smoking and cancer (U.S. Department of Health and Human Services [USDHHS] 1982). By 1982, there were three published epidemiologic studies on involuntary smoking and lung cancer, and the 1982 Surgeon General’s report included a brief chapter on this topic. That chapter commented on the methodologic difficulties inherent in such studies, including exposure assessment, the lengthy interval during which exposures are likely to be relevant, and accounting for exposures to other carcinogens. Nonetheless, the report concluded that “Although the currently available evidence is not sufficient to conclude that passive or involuntary smoking causes lung cancer in nonsmokers, the evidence does raise concern about a possible serious public health problem” (p. 251). Involuntary smoking was also reviewed in the 1984 report, which focused on chronic obstructive pulmonary disease and smoking (USDHHS 1984). Chapter 7 (Passive Smoking) of that report included a comprehensive review of the mounting information on smoking by parents and the effects on respiratory health of their children, data on irritation of the eye, and the more limited evidence on pulmonary effects of involuntary smoking on adults. The chapter began with a compilation of measurements of tobacco smoke components in various indoor environments. The extent of the data had increased substantially since 1972. By 1984, the data included measurements of more specific indicators such as acrolein and nicotine, and less specific indicators such as particulate matter (PM), nitrogen oxides, and CO. The report reviewed new evidence on exposures of nonsmokers using biomarkers, with substantial information on levels of cotinine, a major nicotine metabolite. The report anticipated future conclusions with regard to respiratory effects of parental smoking on child respiratory health (Table 1.1). Involuntary smoking was the topic for the entire 1986 Surgeon General’s report, The Health Consequences of Involuntary Smoking (USDHHS 1986). In its 359 pages, the report covered the full breadth of the
Introduction, Summary, and Conclusions
3
Surgeon General’s Report
Table 1.1
Conclusions from previous Surgeon General’s reports on the health effects of secondhand smoke exposure
Disease and statement Coronary heart disease: “The presence of such levels” as found in cigarettes “indicates that the effect of exposure to carbon monoxide may on occasion, depending upon the length of exposure, be sufficient to be harmful to the health of an exposed person. This would be particularly significant for people who are already suffering from. . .coronary heart disease.”
Surgeon General’s report 1972
(p. 7)
4
Chronic respiratory symptoms (adults): “The presence of such levels” as found in cigarettes “indicates that the effect of exposure to carbon monoxide may on occasion, depending upon the length of exposure, be sufficient to be harmful to the health of an exposed person. This would be particularly significant for people who are already suffering from chronic bronchopulmonary disease. . . .” (p. 7)
1972
Pulmonary function: “Other components of tobacco smoke, such as particulate matter and the oxides of nitrogen, have been shown in various concentrations to affect adversely animal pulmonary. . .function. The extent of the contributions of these substances to illness in humans exposed to the concentrations present in an atmosphere contaminated with tobacco smoke is not presently known.” (pp. 7–8)
1972
Asthma: “The limited existing data yield conflicting results concerning the relationship between passive smoke exposure and pulmonary function changes in patients with asthma.” (p. 13)
1984
Bronchitis and pneumonia: “The children of smoking parents have an increased prevalence of reported respiratory symptoms, and have an increased frequency of bronchitis and pneumonia early in life.” (p. 13)
1984
Pulmonary function (children): “The children of smoking parents appear to have measurable but small differences in tests of pulmonary function when compared with children of nonsmoking parents. The significance of this finding to the future development of lung disease is unknown.” (p. 13)
1984
Pulmonary function (adults): “. . .some studies suggest that high levels of involuntary [tobacco] smoke exposure might produce small changes in pulmonary function in normal subjects. . . . Two studies have reported differences in measures of lung function in older populations between subjects chronically exposed to involuntary smoking and those who were not. This difference was not found in a younger and possibly less exposed population.” (p. 13)
1984
Acute respiratory infections: “The children of parents who smoke have an increased frequency 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 compared with the children of nonsmokers.” (p. 13)
1986
Bronchitis and pneumonia: “The children of parents who smoke have an increased frequency of hospitalization for bronchitis and pneumonia during the first year of life when compared with the children of nonsmokers.” (p. 13)
1986
Cancers other than lung: “The associations between cancers, other than cancer of the lung, and involuntary smoking require further investigation before a determination can be made about the relationship of involuntary smoking to these cancers.” (p. 14)
1986
Cardiovascular disease: “Further studies on the relationship between involuntary smoking and cardiovascular disease are needed in order to determine whether involuntary smoking increases the risk of cardiovascular disease.” (p. 14)
1986
Chapter 1
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Table 1.1
Continued Surgeon General’s report
Disease and statement Chronic cough and phlegm (children): “Chronic cough and phlegm are more frequent in children whose parents smoke compared with children of nonsmokers.” (p. 13)
1986
Chronic obstructive pulmonary disease (COPD): “Healthy adults exposed to environmental tobacco smoke may have small changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmonary function as a result of exposure to environmental tobacco smoke alone.” (pp. 13–14)
1986
“The implications of chronic respiratory symptoms for respiratory health as an adult are unknown and deserve further study.” (p. 13) Lung cancer: “Involuntary smoking can cause lung cancer in nonsmokers.” (p. 13)
1986
Middle ear effusions: “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.” (p. 14)
1986
Pulmonary function (children): “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 susceptibility to chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., [sic] active smoking or occupational exposures, needs investigation.” (p. 13)
1986
Other: “An atmosphere contaminated with tobacco smoke can contribute to the discomfort of many individuals.” (p. 7)
1972
“Cigarette smoke can make a significant, measurable contribution to the level of indoor air pollution at levels of smoking and ventilation that are common in the indoor environment.” (p. 13)
1984
“Cigarette smoke in the air can produce an increase in both subjective and objective measures of eye irritation.” (p. 13)
1984
“Nonsmokers who report exposure to environmental tobacco smoke have higher levels of urinary cotinine, a metabolite of nicotine, than those who do not report such exposure.” (p. 13)
1984
“The simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to environmental tobacco smoke.” (p. 13)
1986
“Validated questionnaires are needed for the assessment of recent and remote exposure to environmental tobacco smoke in the home, workplace, and other environments.” (p. 14)
1986
Sources: U.S. Department of Health, Education, and Welfare 1972; U.S. Department of Health and Human Services 1984, 1986.
Introduction, Summary, and Conclusions
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Surgeon General’s Report
topic, addressing toxicology and dosimetry of tobacco smoke; the relevant evidence on active smoking; patterns of exposure of nonsmokers to tobacco smoke; the epidemiologic evidence on involuntary smoking and disease risks for infants, children, and adults; and policies to control involuntary exposure to tobacco smoke. That report concluded that involuntary smoking caused lung cancer in lifetime nonsmoking adults and was associated with adverse effects on respiratory health in children. The report also stated that simply separating smokers and nonsmokers within the same airspace reduced but did not eliminate exposure to secondhand smoke. All of these findings are relevant to public health and public policy (Table 1.1). The lung cancer conclusion was based on extensive information already available on the carcinogenicity of active smoking, the qualitative similarities between secondhand and mainstream smoke, the uptake of tobacco smoke components by nonsmokers, and the epidemiologic data on involuntary smoking. The three major conclusions of the report (Table 1.2), led Dr. C. Everett Koop, Surgeon General at the time, to comment in his preface that “the right of smokers to smoke ends where their behavior affects the health and well-being of others; furthermore, it is the smokers’ responsibility to ensure that they do not expose nonsmokers to the potential [sic] harmful effects of tobacco smoke” (USDHHS 1986, p. xii). Two other reports published in 1986 also reached the conclusion that involuntary smoking increased the risk for lung cancer. The International Agency for Research on Cancer (IARC) of the World Health Organization concluded that “passive smoking gives rise to some risk of cancer” (IARC 1986, p. 314). In its monograph on tobacco smoking, the agency supported this conclusion on the basis of the characteristics of sidestream and mainstream smoke, the
Table 1.2
absorption of tobacco smoke materials during an involuntary exposure, and the nature of dose-response relationships for carcinogenesis. In the same year, the National Research Council (NRC) also concluded that involuntary smoking increases the incidence of lung cancer in nonsmokers (NRC 1986). In reaching this conclusion, the NRC report cited the biologic plausibility of the association between exposure to secondhand smoke and lung cancer and the supporting epidemiologic evidence. On the basis of a pooled analysis of the epidemiologic data adjusted for bias, the report concluded that the best estimate for the excess risk of lung cancer in nonsmokers married to smokers was 25 percent, compared with nonsmokers married to nonsmokers. With regard to the effects of involuntary smoking on children, the NRC report commented on the literature linking secondhand smoke exposures from parental smoking to increased risks for respiratory symptoms and infections and to a slightly diminished rate of lung growth. Since 1986, the conclusions with regard to both the carcinogenicity of secondhand smoke and the adverse effects of parental smoking on the health of children have been echoed and expanded (Table 1.3). In 1992, the U.S. Environmental Protection Agency (EPA) published its risk assessment of secondhand smoke as a carcinogen (USEPA 1992). The agency’s evaluation drew on toxicologic information on secondhand smoke and the extensive literature on active smoking. A comprehensive meta-analysis of the 31 epidemiologic studies of secondhand smoke and lung cancer published up to that time was central to the decision to classify secondhand smoke as a group A carcinogen—namely, a known human carcinogen. Estimates of approximately 3,000 U.S. lung cancer deaths per year in nonsmokers were attributed to secondhand smoke. The report also covered other respiratory health effects in
Major conclusions of the 1986 Surgeon General’s report, The Health Consequences of Involuntary Smoking
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. The simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to environmental tobacco smoke. Source: U.S. Department of Health and Human Services 1986, p. 7.
6
Chapter 1
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Table 1.3
Selected major reports, other than those of the U.S. Surgeon General, addressing adverse effects from exposure to tobacco smoke Place and date of publication
Agency
Publication
National Research Council
Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects
Washington, D.C. United States 1986
International Agency for Research on Cancer (IARC)
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Tobacco Smoking (IARC Monograph 38)
Lyon, France 1986
U.S. Environmental Protection Agency (EPA)
Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders
Washington, D.C. United States 1992
National Health and Medical Research Council
The Health Effects of Passive Smoking
Canberra, Australia 1997
California EPA (Cal/EPA), Office of Environmental Health Hazard Assessment
Health Effects of Exposure to Environmental Tobacco Smoke
Sacramento, California United States 1997
Scientific Committee on Tobacco and Health
Report of the Scientific Committee on Tobacco and Health
London, United Kingdom 1998
World Health Organization
International Consultation on Environmental Tobacco Smoke (ETS) and Child Health. Consultation Report
Geneva, Switzerland 1999
IARC
Tobacco Smoke and Involuntary Smoking (IARC Monograph 83)
Lyon, France 2004
Cal/EPA, Office of Environmental Health Hazard Assessment
Proposed Identification of Environmental Tobacco Smoke as a Toxic Air Contaminant
Sacramento, California United States 2005
children and adults and concluded that involuntary smoking is causally associated with several adverse respiratory effects in children. There was also a quantitative risk assessment for the impact of involuntary smoking on childhood asthma and lower respiratory tract infections in young children. In the decade since the 1992 EPA report, scientific panels continued to evaluate the mounting evidence linking involuntary smoking to adverse health effects (Table 1.3). The most recent was the 2005 report of the California EPA (Cal/EPA 2005). Over time, research has repeatedly affirmed the conclusions of the 1986 Surgeon General’s reports and studies have further identified causal associations of involuntary smoking with diseases and other health disorders. The epidemiologic evidence on involuntary smoking has
markedly expanded since 1986, as have the data on exposure to tobacco smoke in the many environments where people spend time. An understanding of the mechanisms by which involuntary smoking causes disease has also deepened. As part of the environmental health hazard assessment, Cal/EPA identified specific health effects causally associated with exposure to secondhand smoke. The agency estimated the annual excess deaths in the United States that are attributable to secondhand smoke exposure for specific disorders: sudden infant death syndrome (SIDS), cardiac-related illnesses (ischemic heart disease), and lung cancer (Cal/EPA 2005). For the excess incidence of other health outcomes, either new estimates were provided or estimates from the 1997 health hazard assessment were
Introduction, Summary, and Conclusions
7
Surgeon General’s Report
used without any revisions (Cal/EPA 1997). Overall, Cal/EPA estimated that about 50,000 excess deaths result annually from exposure to secondhand smoke (Cal/EPA 2005). Estimated annual excess deaths for the total U.S. population are about 3,400 (a range of 3,423 to 8,866) from lung cancer, 46,000 (a range of 22,700 to 69,600) from cardiac-related illnesses, and 430 from SIDS. The agency also estimated that between 24,300 and 71,900 low birth weight or preterm deliveries, about 202,300 episodes of childhood asthma (new cases and exacerbations), between 150,000 and 300,000 cases of lower respiratory illness in children, and about 789,700 cases of middle ear infections in children occur each year in the United States as a result of exposure to secondhand smoke. This new 2006 Surgeon General’s report returns to the topic of involuntary smoking. The health effects of involuntary smoking have not received comprehensive coverage in this series of reports since 1986. Reports since then have touched on selected aspects of the topic: the 1994 report on tobacco use among young people (USDHHS 1994), the 1998 report on tobacco use among U.S. racial and ethnic minorities (USDHHS 1998), and the 2001 report on women and smoking (USDHHS 2001). As involuntary smoking remains widespread in the United States and elsewhere, the preparation of this report was motivated by the persistence of involuntary smoking as a public health problem and the need to evaluate the substantial new evidence reported since 1986. This report substantially expands the list of topics that were included in the 1986 report. Additional topics include SIDS, developmental effects, and other reproductive effects; heart disease in adults; and cancer sites beyond the lung. For some associations of involuntary smoking with adverse health effects, only a few studies were reviewed in 1986 (e.g., ear disease in children); now, the relevant literature is substantial. Consequently, this report uses meta-analysis to quantitatively summarize evidence as appropriate. Following the approach used in the 2004 report (The Health Consequences of Smoking, USDHHS 2004), this 2006 report also systematically evaluates the evidence for causality, judging the extent of the evidence available and then making an inference as to the nature of the association.
Organization of the Report This twenty-ninth report of the Surgeon General examines the topics of toxicology of secondhand smoke, assessment and prevalence of exposure to
8
Chapter 1
secondhand smoke, reproductive and developmental health effects, respiratory effects of exposure to secondhand smoke in children and adults, cancer among adults, cardiovascular diseases, and the control of secondhand smoke exposure. This introductory chapter (Chapter 1) includes a discussion of the concept of causation and introduces concepts of causality that are used throughout this report; this chapter also summarizes the major conclusions of the report. Chapter 2 (Toxicology of Secondhand Smoke) sets out a foundation for interpreting the observational evidence that is the focus of most of the following chapters. The discussion details the mechanisms that enable tobacco smoke components to injure the respiratory tract and cause nonmalignant and malignant diseases and other adverse effects. Chapter 3 (Assessment of Exposure to Secondhand Smoke) provides a perspective on key factors that determine exposures of people to secondhand smoke in indoor environments, including building designs and operations, atmospheric markers of secondhand smoke, exposure models, and biomarkers of exposure to secondhand smoke. Chapter 4 (Prevalence of Exposure to Secondhand Smoke) summarizes findings that focus on nicotine measurements in the air and cotinine measurements in biologic materials. The chapter includes exposures in the home, workplace, public places, and special populations. Chapter 5 (Reproductive and Developmental Effects from Exposure to Secondhand Smoke) reviews the health effects on reproduction, on infants, and on child development. Chapter 6 (Respiratory Effects in Children from Exposure to Secondhand Smoke) examines the effects of parental smoking on the respiratory health of children. Chapter 7 (Cancer Among Adults from Exposure to Secondhand Smoke) summarizes the evidence on cancer of the lung, breast, nasal sinuses, and the cervix. Chapter 8 (Cardiovascular Diseases from Exposure to Secondhand Smoke) discusses coronary heart disease (CHD), stroke, and subclinical vascular disease. Chapter 9 (Respiratory Effects in Adults from Exposure to Secondhand Smoke) examines odor and irritation, respiratory symptoms, lung function, and respiratory diseases such as asthma and chronic obstructive pulmonary disease. Chapter 10 (Control of Secondhand Smoke Exposure) considers measures used to control exposure to secondhand smoke in public places, including legislation, education, and approaches based on building designs and operations. The report concludes with “A Vision for the Future.” Major conclusions of the report were distilled from the chapter conclusions and appear later in this chapter.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Preparation of the Report This report of the Surgeon General was prepared by the Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention (CDC), and U.S. DHHS. Initial chapters were written by 22 experts who were selected because of their knowledge of a particular topic. The contributions of the initial experts were consolidated into 10 major chapters that were then reviewed by more than 40 peer reviewers. The entire manuscript was then sent to more than 30 scientists and experts who reviewed it for its scientific integrity. After each review cycle, the drafts were revised by the scientific editors on the basis of the experts’ comments. Subsequently, the report was reviewed by various institutes and agencies
within U.S. DHHS. Publication lags, even short ones, prevent an up-to-the-minute inclusion of all recently published articles and data. Therefore, by the time the public reads this report, there may be additional published studies or data. To provide published information as current as possible, this report includes an Appendix of more recent studies that represent major additions to the literature. This report is also accompanied by a companion database of key evidence that is accessible through the Internet (http://www.cdc.gov/tobacco). The database includes a uniform description of the studies and results on the health effects of exposure to secondhand smoke that were presented in a format compatible with abstraction into standardized tables. Readers of the report may access these data for additional analyses, tables, or figures.
Definitions and Terminology
The inhalation of tobacco smoke by nonsmokers has been variably referred to as “passive smoking” or “involuntary smoking.” Smokers, of course, also inhale secondhand smoke. Cigarette smoke contains both particles and gases generated by the combustion at high temperatures of tobacco, paper, and additives. The smoke inhaled by nonsmokers that contaminates indoor spaces and outdoor environments has often been referred to as “secondhand smoke” or “environmental tobacco smoke.” This inhaled smoke is the mixture of sidestream smoke released by the smoldering cigarette and the mainstream smoke that is exhaled by a smoker. Sidestream smoke, generated at lower temperatures and under somewhat different combustion conditions than mainstream smoke, tends to have higher concentrations of many of the toxins found in cigarette smoke (USDHHS 1986). However, it is rapidly diluted as it travels away from the burning cigarette. Secondhand smoke is an inherently dynamic mixture that changes in characteristics and concentration with the time since it was formed and the
distance it has traveled. The smoke particles change in size and composition as gaseous components are volatilized and moisture content changes; gaseous elements of secondhand smoke may be adsorbed onto materials, and particle concentrations drop with both dilution in the air or environment and impaction on surfaces, including the lungs or on the body. Because of its dynamic nature, a specific quantitative definition of secondhand smoke cannot be offered. This report uses the term secondhand smoke in preference to environmental tobacco smoke, even though the latter may have been used more frequently in previous reports. The descriptor “secondhand” captures the involuntary nature of the exposure, while “environmental” does not. This report also refers to the inhalation of secondhand smoke as involuntary smoking, acknowledging that most nonsmokers do not want to inhale tobacco smoke. The exposure of the fetus to tobacco smoke, whether from active smoking by the mother or from her exposure to secondhand smoke, also constitutes involuntary smoking.
Introduction, Summary, and Conclusions
9
Surgeon General’s Report
Evidence Evaluation
Following the model of the 1964 report, the Surgeon General’s reports on smoking have included comprehensive compilations of the evidence on the health effects of smoking. The evidence is analyzed to identify causal associations between smoking and disease according to enunciated principles, sometimes referred to as the “Surgeon General’s criteria” or the “Hill” criteria (after Sir Austin Bradford Hill) for causality (USDHEW 1964; USDHHS 2004). Application of these criteria involves covering all relevant observational and experimental evidence. The criteria, offered in a brief chapter of the 1964 report entitled “Criteria for Judgment,” included (1) the consistency of the association, (2) the strength of the association, (3) the specificity of the association, (4) the temporal relationship of the association, and (5) the coherence of the association. Although these criteria have been criticized (e.g., Rothman and Greenland 1998), they have proved useful as a framework for interpreting evidence on smoking and other postulated causes of disease, and for judging whether causality can be inferred. In the 2004 report of the Surgeon General, The Health Consequences of Smoking, the framework for interpreting evidence on smoking and health was revisited in depth for the first time since the 1964 report (USDHHS 2004). The 2004 report provided a four-level hierarchy for interpreting evidence (Table 1.4). The categories acknowledge that evidence can be “suggestive” but not adequate to infer a causal relationship, and also allows for evidence that is “suggestive of no causal relationship.” Since the 2004 report, the individual chapter conclusions have consistently used this four-level hierarchy (Table 1.4), but
Table 1.4
evidence syntheses and other summary statements may use either the term “increased risk” or “cause” to describe instances in which there is sufficient evidence to conclude that active or involuntary smoking causes a disease or condition. This four-level framework also sharply and completely separates conclusions regarding causality from the implications of such conclusions. That same framework was used in this report on involuntary smoking and health. The criteria dating back to the 1964 Surgeon General’s report remain useful as guidelines for evaluating evidence (USDHEW 1964), but they were not intended to be applied strictly or as a “checklist” that needed to be met before the designation of “causal” could be applied to an association. In fact, for involuntary smoking and health, several of the criteria will not be met for some associations. Specificity, referring to a unique exposure-disease relationship (e.g., the association between thalidomide use during pregnancy and unusual birth defects), can be set aside as not relevant, as all of the health effects considered in this report have causes other than involuntary smoking. Associations are considered more likely to be causal as the strength of an association increases because competing explanations become less plausible alternatives. However, based on knowledge of dosimetry and mechanisms of injury and disease causation, the risk is anticipated to be only slightly or modestly increased for some associations of involuntary smoking with disease, such as lung cancer, particularly when the very strong relative risks found for active smokers are compared with those for lifetime nonsmokers. The finding of only a small elevation in risk, as in the
Four-level hierarchy for classifying the strength of causal inferences based on available evidence
Level 1
Evidence is sufficient to infer a causal relationship.
Level 2
Evidence is suggestive but not sufficient to infer a causal relationship.
Level 3
Evidence is inadequate to infer the presence or absence of a causal relationship (which encompasses evidence that is sparse, of poor quality, or conflicting).
Level 4
Evidence is suggestive of no causal relationship.
Source: U.S. Department of Health and Human Services 2004.
10
Chapter 1
The Health Consequences of Involuntary Exposure to Tobacco Smoke
example of spousal smoking and lung cancer risk in lifetime nonsmokers, does not weigh against a causal association; however, alternative explanations for a risk of a small magnitude need full exploration and cannot be so easily set aside as alternative explanations for a stronger association. Consistency, coherence, and the temporal relationship of involuntary smoking with disease are central to the interpretations in this report. To address coherence, the report draws not only on the evidence for involuntary smoking, but on the even more extensive literature on active smoking and disease. Although the evidence reviewed in this report comes largely from investigations of secondhand smoke specifically, the larger body of evidence on active smoking is also relevant to many of the associations that were evaluated. The 1986 report found secondhand smoke to be qualitatively similar to mainstream smoke inhaled by the smoker and concluded that secondhand smoke would be expected to have “a toxic and carcinogenic potential that would
not be expected to be qualitatively different from that of MS [mainstream smoke]” (USDHHS 1986, p. 23). The 2004 report of the Surgeon General revisited the health consequences of active smoking (USDHHS 2004), and the conclusions substantially expanded the list of diseases and conditions caused by smoking. Chapters in the present report consider the evidence on active smoking that is relevant to biologic plausibility for causal associations between involuntary smoking and disease. The reviews included in this report cover evidence identified through search strategies set out in each chapter. Of necessity, the evidence on mechanisms was selectively reviewed. However, an attempt was made to cover all health studies through specified target dates. Because of the substantial amount of time involved in preparing this report, lists of new key references published after these cut-off dates are included in an Appendix. Literature reviews were extended when new evidence was sufficient to possibly change the level of a causal conclusion.
Major Conclusions
This report returns to involuntary smoking, the topic of the 1986 Surgeon General’s report. Since then, there have been many advances in the research on secondhand smoke, and substantial evidence has been reported over the ensuing 20 years. This report uses the revised language for causal conclusions that was implemented in the 2004 Surgeon General’s report (USDHHS 2004). Each chapter provides a comprehensive review of the evidence, a quantitative synthesis of the evidence if appropriate, and a rigorous assessment of sources of bias that may affect interpretations of the findings. The reviews in this report reaffirm and strengthen the findings of the 1986 report. With regard to the involuntary exposure of nonsmokers to tobacco smoke, the scientific evidence now supports the following major conclusions: 1.
Secondhand smoke causes premature death and disease in children and in adults who do not smoke.
2.
Children exposed to secondhand smoke are at an increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems,
and more severe asthma. Smoking by parents causes respiratory symptoms and slows lung growth in their children. 3.
Exposure of adults to secondhand smoke has immediate adverse effects on the cardiovascular system and causes coronary heart disease and lung cancer.
4.
The scientific evidence indicates that there is no risk-free level of exposure to secondhand smoke.
5.
Many millions of Americans, both children and adults, are still exposed to secondhand smoke in their homes and workplaces despite substantial progress in tobacco control.
6.
Eliminating smoking in indoor spaces fully protects nonsmokers from exposure to secondhand smoke. Separating smokers from nonsmokers, cleaning the air, and ventilating buildings cannot eliminate exposures of nonsmokers to secondhand smoke.
Introduction, Summary, and Conclusions
11
Surgeon General’s Report
Chapter Conclusions
Chapter 2. Toxicology of Secondhand Smoke Evidence of Carcinogenic Effects from Secondhand Smoke Exposure 1.
More than 50 carcinogens have been identified in sidestream and secondhand smoke.
2.
The evidence is sufficient to infer a causal relationship between exposure to secondhand smoke and its condensates and tumors in laboratory animals.
3.
4.
6.
12
9.
The evidence is sufficient to infer that exposure to secondhand smoke causes atherosclerosis in animal models.
Chapter 3. Assessment of Exposure to Secondhand Smoke Building Designs and Operations 1.
Current heating, ventilating, and air conditioning systems alone cannot control exposure to secondhand smoke.
2.
The operation of a heating, ventilating, and air conditioning system can distribute secondhand smoke throughout a building.
The mechanisms by which secondhand smoke causes lung cancer are probably similar to those observed in smokers. The overall risk of secondhand smoke exposure, compared with active smoking, is diminished by a substantially lower carcinogenic dose.
3.
Atmospheric concentration of nicotine is a sensitive and specific indicator for secondhand smoke.
4.
Smoking increases indoor particle concentrations.
5.
Models can be used to estimate concentrations of secondhand smoke.
Exposure Models
The evidence indicates multiple mechanisms by which secondhand smoke exposure causes injury to the respiratory tract.
Biomarkers of Exposure to Secondhand Smoke 6.
Biomarkers suitable for assessing recent exposures to secondhand smoke are available.
The evidence indicates mechanisms by which secondhand smoke exposure could increase the risk for sudden infant death syndrome.
7.
At this time, cotinine, the primary proximate metabolite of nicotine, remains the biomarker of choice for assessing secondhand smoke exposure.
8.
Individual biomarkers of exposure to secondhand smoke represent only one component of a complex mixture, and measurements of one marker may not wholly reflect an exposure to other components of concern as a result of involuntary smoking.
Mechanisms of Secondhand Smoke Exposure and Heart Disease 7.
The evidence is sufficient to infer that exposure to secondhand smoke causes endothelial cell dysfunctions.
The evidence is sufficient to infer that exposure of nonsmokers to secondhand smoke causes a significant increase in urinary levels of metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The presence of these metabolites links exposure to secondhand smoke with an increased risk for lung cancer.
Mechanisms of Respiratory Tract Injury and Disease Caused by Secondhand Smoke Exposure 5.
8.
The evidence is sufficient to infer that exposure to secondhand smoke has a prothrombotic effect.
Chapter 1
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Chapter 4. Prevalence of Exposure to Secondhand Smoke 1.
The evidence is sufficient to infer that large numbers of nonsmokers are still exposed to secondhand smoke.
Sudden Infant Death Syndrome 4.
The evidence is sufficient to infer a causal relationship between exposure to secondhand smoke and sudden infant death syndrome.
Preterm Delivery
2.
Exposure of nonsmokers to secondhand smoke has declined in the United States since the 1986 Surgeon General’s report, The Health Consequences of Involuntary Smoking.
5.
3.
The evidence indicates that the extent of secondhand smoke exposure varies across the country.
Low Birth Weight
4.
Homes and workplaces are the predominant locations for exposure to secondhand smoke.
5.
Exposure to secondhand smoke tends to be greater for persons with lower incomes.
6.
Exposure to secondhand smoke continues in restaurants, bars, casinos, gaming halls, and vehicles.
6.
The evidence is suggestive but not sufficient to infer a causal relationship between maternal exposure to secondhand smoke during pregnancy and preterm delivery.
The evidence is sufficient to infer a causal relationship between maternal exposure to secondhand smoke during pregnancy and a small reduction in birth weight.
Congenital Malformations 7.
The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke and congenital malformations.
Cognitive Development
Chapter 5. Reproductive and Developmental Effects from Exposure to Secondhand Smoke Fertility 1.
The evidence is inadequate to infer the presence or absence of a causal relationship between maternal exposure to secondhand smoke and female fertility or fecundability. No data were found on paternal exposure to secondhand smoke and male fertility or fecundability.
Pregnancy (Spontaneous Abortion and Perinatal Death) 2.
The evidence is inadequate to infer the presence or absence of a causal relationship between maternal exposure to secondhand smoke during pregnancy and spontaneous abortion.
Infant Deaths 3.
The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke and neonatal mortality.
8.
The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke and cognitive functioning among children.
Behavioral Development 9.
The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke and behavioral problems among children.
Height/Growth 10. The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke and children’s height/growth. Childhood Cancer 11. The evidence is suggestive but not sufficient to infer a causal relationship between prenatal and postnatal exposure to secondhand smoke and childhood cancer.
Introduction, Summary, and Conclusions
13
Surgeon General’s Report
12. The evidence is inadequate to infer the presence or absence of a causal relationship between maternal exposure to secondhand smoke during pregnancy and childhood cancer.
4.
The evidence is suggestive but not sufficient to infer a causal relationship between parental smoking and the natural history of middle ear effusion.
13. The evidence is inadequate to infer the presence or absence of a causal relationship between exposure to secondhand smoke during infancy and childhood cancer.
5.
The evidence is inadequate to infer the presence or absence of a causal relationship between parental smoking and an increase in the risk of adenoidectomy or tonsillectomy among children.
14. The evidence is suggestive but not sufficient to infer a causal relationship between prenatal and postnatal exposure to secondhand smoke and childhood leukemias.
Respiratory Symptoms and Prevalent Asthma in School-Age Children
15. The evidence is suggestive but not sufficient to infer a causal relationship between prenatal and postnatal exposure to secondhand smoke and childhood lymphomas. 16. The evidence is suggestive but not sufficient to infer a causal relationship between prenatal and postnatal exposure to secondhand smoke and childhood brain tumors.
6.
The evidence is sufficient to infer a causal relationship between parental smoking and cough, phlegm, wheeze, and breathlessness among children of school age.
7.
The evidence is sufficient to infer a causal relationship between parental smoking and ever having asthma among children of school age.
Childhood Asthma Onset 8.
17. The evidence is inadequate to infer the presence or absence of a causal relationship between prenatal and postnatal exposure to secondhand smoke and other childhood cancer types.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure from parental smoking and the onset of wheeze illnesses in early childhood.
9.
Chapter 6. Respiratory Effects in Children from Exposure to Secondhand Smoke
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure from parental smoking and the onset of childhood asthma.
Atopy
Lower Respiratory Illnesses in Infancy and Early Childhood 1.
2.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure from parental smoking and lower respiratory illnesses in infants and children. The increased risk for lower respiratory illnesses is greatest from smoking by the mother.
Middle Ear Disease and Adenotonsillectomy 3.
14
The evidence is sufficient to infer a causal relationship between parental smoking and middle ear disease in children, including acute and recurrent otitis media and chronic middle ear effusion.
Chapter 1
10. The evidence is inadequate to infer the presence or absence of a causal relationship between parental smoking and the risk of immunoglobulin E-mediated allergy in their children. Lung Growth and Pulmonary Function 11. The evidence is sufficient to infer a causal relationship between maternal smoking during pregnancy and persistent adverse effects on lung function across childhood. 12. The evidence is sufficient to infer a causal relationship between exposure to secondhand smoke after birth and a lower level of lung function during childhood.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
heart disease from exposure to secondhand smoke.
Chapter 7. Cancer Among Adults from Exposure to Secondhand Smoke Lung Cancer 1.
2.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure and lung cancer among lifetime nonsmokers. This conclusion extends to all secondhand smoke exposure, regardless of location. The pooled evidence indicates a 20 to 30 percent increase in the risk of lung cancer from secondhand smoke exposure associated with living with a smoker.
3.
The evidence is suggestive but not sufficient to infer a causal relationship between exposure to secondhand smoke and an increased risk of stroke.
4.
Studies of secondhand smoke and subclinical vascular disease, particularly carotid arterial wall thickening, are suggestive but not sufficient to infer a causal relationship between exposure to secondhand smoke and atherosclerosis.
Breast Cancer
Chapter 9. Respiratory Effects in Adults from Exposure to Secondhand Smoke
3.
Odor and Irritation
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke and breast cancer.
1.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure and odor annoyance.
2.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure and nasal irritation.
3.
The evidence is suggestive but not sufficient to conclude that persons with nasal allergies or a history of respiratory illnesses are more susceptible to developing nasal irritation from secondhand smoke exposure.
Nasal Sinus Cavity and Nasopharyngeal Carcinoma 4.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and a risk of nasal sinus cancer among nonsmokers.
5.
The evidence is inadequate to infer the presence or absence of a causal relationship between secondhand smoke exposure and a risk of nasopharyngeal carcinoma among nonsmokers.
Cervical Cancer
Respiratory Symptoms
6.
4.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and acute respiratory symptoms including cough, wheeze, chest tightness, and difficulty breathing among persons with asthma.
5.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and acute respiratory symptoms including cough, wheeze, chest tightness, and difficulty breathing among healthy persons.
6.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and chronic respiratory symptoms.
The evidence is inadequate to infer the presence or absence of a causal relationship between secondhand smoke exposure and the risk of cervical cancer among lifetime nonsmokers.
Chapter 8. Cardiovascular Diseases from Exposure to Secondhand Smoke 1.
2.
The evidence is sufficient to infer a causal relationship between exposure to secondhand smoke and increased risks of coronary heart disease morbidity and mortality among both men and women. Pooled relative risks from meta-analyses indicate a 25 to 30 percent increase in the risk of coronary
Introduction, Summary, and Conclusions
15
Surgeon General’s Report
Lung Function 7.
8.
9.
The evidence is suggestive but not sufficient to infer a causal relationship between short-term secondhand smoke exposure and an acute decline in lung function in persons with asthma. The evidence is inadequate to infer the presence or absence of a causal relationship between shortterm secondhand smoke exposure and an acute decline in lung function in healthy persons. The evidence is suggestive but not sufficient to infer a causal relationship between chronic secondhand smoke exposure and a small decrement in lung function in the general population.
10. The evidence is inadequate to infer the presence or absence of a causal relationship between chronic secondhand smoke exposure and an accelerated decline in lung function.
Chapter 10. Control of Secondhand Smoke Exposure 1.
Workplace smoking restrictions are effective in reducing secondhand smoke exposure.
2.
Workplace smoking restrictions lead to less smoking among covered workers.
3.
Establishing smoke-free workplaces is the only effective way to ensure that secondhand smoke exposure does not occur in the workplace.
4.
The majority of workers in the United States are now covered by smoke-free policies.
5.
The extent to which workplaces are covered by smoke-free policies varies among worker groups, across states, and by sociodemographic factors. Workplaces related to the entertainment and hospitality industries have notably high potential for secondhand smoke exposure.
6.
Evidence from peer-reviewed studies shows that smoke-free policies and regulations do not have an adverse economic impact on the hospitality industry.
7.
Evidence suggests that exposure to secondhand smoke varies by ethnicity and gender.
8.
In the United States, the home is now becoming the predominant location for exposure of children and adults to secondhand smoke.
9.
Total bans on indoor smoking in hospitals, restaurants, bars, and offices substantially reduce secondhand smoke exposure, up to several orders of magnitude with incomplete compliance, and with full compliance, exposures are eliminated.
Asthma 11. The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and adult-onset asthma. 12. The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and a worsening of asthma control. Chronic Obstructive Pulmonary Disease 13. The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and risk for chronic obstructive pulmonary disease. 14. The evidence is inadequate to infer the presence or absence of a causal relationship between secondhand smoke exposure and morbidity in persons with chronic obstructive pulmonary disease.
16
Chapter 1
10. Exposures of nonsmokers to secondhand smoke cannot be controlled by air cleaning or mechanical air exchange.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Methodologic Issues
Much of the evidence on the health effects of involuntary smoking comes from observational epidemiologic studies that were carried out to test hypotheses related to secondhand smoke and risk for diseases and other adverse health effects. The challenges faced in carrying out these studies reflect those of observational research generally: assessment of the relevant exposures and outcomes with sufficient validity and precision, selection of an appropriate study design, identification of an appropriate and sufficiently large study population, and collection of information on other relevant factors that may confound or modify the association being studied. The challenge of accurately classifying secondhand smoke exposures confronts all studies of such exposures, and consequently the literature on approaches to and limitations of exposure classification is substantial. Sources of bias that can affect the findings of epidemiologic studies have been widely discussed (Rothman and Greenland 1998), both in general and in relation to studies of involuntary smoking. Concerns about bias apply to any study of an environmental agent and disease risk: misclassification of exposures or outcomes, confounding effect modification, and proper selection of study participants. In addition, the generalizability of findings from one population to another (external validity) further determines the value of evidence from a study. Another methodologic concern affecting secondhand smoke literature comes from the use of meta-analysis to combine the findings of epidemiologic studies; general concerns related to the use of meta-analysis for observational data and more specific concerns related to involuntary smoking have also been raised. This chapter considers these methodologic issues in anticipation of more specific treatment in the following chapters.
Classification of Secondhand Smoke Exposure For secondhand smoke, as for any environmental factor that may be a cause of disease, the exposure assessment might encompass the time and place of the exposure, cumulative exposures, exposure during a particular time, or a recent exposure (Jaakkola and Jaakkola 1997; Jaakkola and Samet 1999). For example, exposures to secondhand smoke across the full life
span may be of interest for lung cancer, while only more recent exposures may be relevant to the exacerbation of asthma. For CHD, both temporally remote and current exposures may affect risk. Assessments of exposures are further complicated by the multiplicity of environments where exposures take place and the difficulty of characterizing the exposure in some locations, such as public places or workplaces. Additionally, exposures probably vary qualitatively and quantitatively over time and across locations because of temporal changes and geographic differences in smoking patterns. Nonetheless, researchers have used a variety of approaches for exposure assessments in epidemiologic studies of adverse health effects from involuntary smoking. Several core concepts that are fundamental to these approaches are illustrated in Figure 1.1 (Samet and Jaakkola 1999). Cigarette smoking is, of course, the source of most secondhand smoke in the United States, followed by pipes, cigars, and other products. Epidemiologic studies generally focus on assessing the exposure, which is the contact with secondhand smoke. The concentrations of secondhand smoke components in a space depend on the number of smokers and the rate at which they are smoking, the volume into which the smoke is distributed, the rate at which the air in the space exchanges with uncontaminated air, and the rate at which the secondhand smoke is removed from the air. Concentration, exposure, and dose differ in their definitions, although the terms are sometimes used without sharp distinctions. However, surrogate indicators that generally describe a source of exposure may also be used to assess the exposure, such as marriage to a smoker or the number of cigarettes smoked in the home. Biomarkers can provide an indication of an exposure or possibly the dose, but for secondhand smoke they are used for recent exposure only. People are exposed to secondhand smoke in a number of different places, often referred to as “microenvironments” (NRC 1991). A microenvironment is a definable location that has a constant concentration of the contaminant of interest, such as secondhand smoke, during the time that a person is there. Some key microenvironments for secondhand smoke include the home, the workplace, public places, and transportation environments (Klepeis 1999). Based
Introduction, Summary, and Conclusions
17
Surgeon General’s Report
The determinants of exposure, dose, and biologically effective dose that underlie the development of health effects from smoking Environment
Microenvironmental (mj) concentrations over time (tj) ▲
m4
C11
C20 C30 C40
t3
C12
C13
C21
C22
C41
C42
C31
C32
C23 C33
Concentration =
C43
Exposure
Etot = ∑ cij * tij
Dose
▲
m3
C10
t2
▲
m2
t1
▲
▲
▲▲ ▲ ▲
Indoor sources
m1
t0
Metabolic elimination
Susceptible body surface
▲
▲
Outdoor sources
Type and rate of breathing
Individual time (tj) present in location (mj)
▲
Dispersion
Human body
▲
Figure 1.1
Biologically effective dose
Ventilation removal
Source: Samet and Jaakkola 1999. Reprinted with permission.
on the microenvironmental model, total exposure can be estimated as the weighted average of the concentrations of secondhand smoke or indicator compounds, such as nicotine, in the microenvironments where time is spent; the weights are the time spent in each microenvironment. Klepeis (1999) illustrates the application of the microenvironmental model with national data from the National Human Activity Pattern Survey conducted by the EPA. His calculations yield an overall estimate of exposure to airborne particles from smoking and of the contributions to this exposure from various microenvironments. Much of the epidemiologic evidence addresses the consequences of an exposure in a particular microenvironment, such as the home (spousal smoking and lung cancer risk or maternal smoking and risk for asthma exacerbation), or the workplace (exacerbation of asthma by the presence of smokers). Some studies have attempted to cover multiple microenvironments
18
Chapter 1
and to characterize exposures over time. For example, in the multicenter study of secondhand smoke exposure and lung cancer carried out in the United States, Fontham and colleagues (1994) assessed exposures during childhood, in workplaces, and at home during adulthood. Questionnaires that assess exposures have been the primary tool used in epidemiologic studies of secondhand smoke and disease. Measurement of biomarkers has been added in some studies, either as an additional and complementary exposure assessment approach or for validating questionnaire responses. Some studies have also measured components of secondhand smoke in the air. Questionnaires generally address sources of exposure in microenvironments and can be tailored to address the time period of interest. Questionnaires represent the only approach that can be used to assess exposures retrospectively over a life span, because available biomarkers only reflect exposures
The Health Consequences of Involuntary Exposure to Tobacco Smoke
over recent days or, at most, weeks. Questionnaires on secondhand smoke exposure have been assessed for their reliability and validity, generally based on comparisons with either biomarker or air monitoring data as the “gold” standard (Jaakkola and Jaakkola 1997). Two studies evaluated the reliability of questionnaires on lifetime exposures (Pron et al. 1988; Coultas et al. 1989). Both showed a high degree of repeatability for questions concerning whether a spouse had smoked, but a lower reliability for responses concerning the quantitative aspects of an exposure. Emerson and colleagues (1995) evaluated the repeatability of information from parents of children with asthma. They found a high reliability for parent-reported tobacco use and for the number of cigarettes to which the child was exposed in the home during the past week. To assess validity, questionnaire reports of current or recent exposures have been compared with levels of cotinine and other biomarkers. These studies tend to show a moderate correlation between levels of cotinine and questionnaire indicators of exposures (Kawachi and Colditz 1996; Cal/EPA 1997; Jaakkola and Jaakkola 1997). However, cotinine levels reflect not only exposure but metabolism and excretion (Benowitz 1999). Consequently, exposure is only one determinant of variation in cotinine levels among persons; there also are individual variations in metabolism and excretion rates. In spite of these sources of variability, mean levels of cotinine vary as anticipated across categories of self-reported exposures (Cal/EPA 1997; Jaakkola and Jaakkola 1997), and self-reported exposures are moderately associated with measured levels of markers (Cal/EPA 1997; Jaakkola and Jaakkola 1997). Biomarkers are also used for assessing exposures to secondhand smoke. A number of biomarkers are available, but they vary in their specificity and in the dynamics of the temporal relationship between the exposure and the marker level (Cal/EPA 1997; Benowitz 1999). These markers include specific tobacco smoke components (nicotine) or metabolites (cotinine and tobacco-specific nitrosamines), nonspecific biomarkers (thiocyanate and CO), adducts with tobacco smoke components or metabolites (4-aminobiphenyl–hemoglobin adducts, benzo[a]pyrene–DNA adducts, and polycyclic aromatic hydrocarbon– albumin adducts), and nonspecific assays (urinary mutagenicity). Cotinine has been the most widely used biomarker, primarily because of its specificity, half-life, and ease of measurement in body fluids (e.g., urine, blood, and saliva). Biomarkers are discussed
in detail in Chapter 3 (Assessment of Exposure to Secondhand Smoke). Some epidemiologic studies have also incorporated air monitoring, either direct personal sampling or the indirect approach based on the microenvironmental model. Nicotine, present in the gas phase of secondhand smoke, can be monitored passively with a special filter or actively using a pump and a sorbent. Hammond and Leaderer (1987) first described a diffusion monitor for the passive sampling of nicotine in 1987; this device has now been widely used to assess concentrations in different environments and to study health effects. Airborne particles have also been measured using active monitoring devices. Each of these approaches for assessing exposures has strengths and limitations, and preference for one over another will depend on the research question and its context (Jaakkola and Jaakkola 1997; Jaakkola and Samet 1999). Questionnaires can be used to characterize sources of exposures, such as smoking by parents. With air concentrations of markers and timeactivity information, estimates of secondhand smoke exposures can be made with the microenvironmental model. Biomarkers provide exposure measures that reflect the patterns of exposure and the kinetics of the marker; the cotinine level in body fluids, for example, reflects an exposure during several days. Air monitoring may be useful for validating measurements of exposure. Exposure assessment strategies are matched to the research question and often employ a mixture of approaches determined by feasibility and cost constraints.
Misclassification of Secondhand Smoke Exposure Misclassification may occur when classifying exposures, outcomes, confounding factors, or modifying factors. Misclassification may be differential on either exposure or outcome, or it may be random (Armstrong et al. 1992). Differential or nonrandom misclassification may either increase or decrease estimates of effect, while random misclassification tends to reduce the apparent effect and weaken the relationship of exposure with disease risk. In studies of secondhand smoke and disease risk, exposure misclassification has been a major consideration in the interpretation of the evidence, although misclassification of health outcome measures has not been a substantial issue in this research. The consequences for epidemiologic studies of misclassification in general are well established (Rothman and Greenland 1998).
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An extensive body of literature on the classification of exposures to secondhand smoke is reviewed in this and other chapters, as well as in some publications on the consequences of misclassification (Wu 1999). Two general patterns of exposure misclassification are of concern to secondhand smoke: (1) random misclassification that is not differential by the presence or absence of the health outcome and (2) systematic misclassification that is differential by the health outcome. In studying the health effects of secondhand smoke in adults, there is a further concern as to the classification of the active smoking status (never, current, or former smoking); in studies of children, the accuracy of secondhand smoke exposure classification is the primary methodologic issue around exposure assessment, but unreported active smoking by adolescents is also a concern. With regard to random misclassification of secondhand smoke exposures, there is an inherent degree of unavoidable measurement error in the exposure measures used in epidemiologic studies. Questionnaires generally assess contact with sources of an exposure (e.g., smoking in the home or workplace) and cannot capture all exposures nor the intensity of exposures; biomarkers provide an exposure index for a particular time window and have intrinsic variability. Some building-related factors that determine an exposure cannot be assessed accurately by a questionnaire, such as the rate of air exchange and the size of the microenvironment where time is spent, nor can concentrations be assessed accurately by subjective reports of the perceived level of tobacco smoke. In general, random misclassification of exposures tends to reduce the likelihood that studies of secondhand smoke exposure will find an effect. This type of misclassification lessens the contrast between exposure groups, because some truly exposed persons are placed in the unexposed group and some truly unexposed persons are placed in the exposed group. Differential misclassification, also a concern, may increase or decrease associations, depending on the pattern of misreporting. One particular form of misclassification has been raised with regard to secondhand smoke exposure and lung cancer: the classification of some current or former smokers as lifetime nonsmokers (USEPA 1992; Lee and Forey 1995; Hackshaw et al. 1997; Wu 1999). The resulting bias would tend to increase the apparent association of secondhand smoke with lung cancer, if the misclassified active smokers are also more likely to be classified as involuntary smokers. Most studies of lung cancer and secondhand smoke have used spousal smoking as a main exposure variable. As
20
Chapter 1
smoking tends to aggregate between spouses (smokers are more likely to marry smokers), misclassification of active smoking would tend to be differential on the basis of spousal smoking (the exposure under investigation). Because active smoking is strongly associated with increased disease risk, greater misclassification of an actively smoking spouse as a nonsmoker among spouses of smokers compared with spouses of nonsmokers would lead to risk estimates for spousal smoking that are biased upward by the effect of active smoking. This type of misclassification is also relevant to studies of spousal exposure and CHD risk or other diseases also caused by active smoking, although the potential for bias is less because the association of active smoking with CHD is not as strong as with lung cancer. There have been a number of publications on this form of misclassification. Wu (1999) provides a review, and Lee and colleagues (2001) offer an assessment of potential consequences. A number of models have been developed to assess the extent of bias resulting from the misclassification of active smokers as lifetime nonsmokers (USEPA 1992; Hackshaw et al. 1997). These models incorporate estimates of the rate of misclassification, the degree of aggregation of smokers by marriage, the prevalence of smoking in the population, and the risk of lung cancer in misclassified smokers (Wu 1999). Although debate about this issue continues, analyses show that estimates of upward bias from misclassifying active smokers as lifetime nonsmokers cannot fully explain the observed increase in risk for lung cancer among lifetime nonsmokers married to smokers (Hackshaw et al. 1997; Wu 1999). There is one additional issue related to exposure misclassification. During the time the epidemiologic studies of secondhand smoke have been carried out, exposure has been widespread and almost unavoidable. Therefore, the risk estimates may be biased downward because there are no truly unexposed persons. The 1986 Surgeon General’s report recognized this methodologic issue and noted the need for further data on population exposures to secondhand smoke (USDHHS 1986). This bias was also recognized in the 1986 report of the NRC, and an adjustment for this misclassification was made to the lung cancer estimate (NRC 1986). Similarly, the 1992 report of the EPA commented on background exposure and made an adjustment (USEPA 1992). Some later studies have attempted to address this issue; for example, in a casecontrol study of active and involuntary smoking and breast cancer in Switzerland, Morabia and colleagues (2000) used a questionnaire to assess exposure and
The Health Consequences of Involuntary Exposure to Tobacco Smoke
identified a small group of lifetime nonsmokers who also reported no exposure to secondhand smoke. With this subgroup of controls as the reference population, the risks of secondhand smoke exposure were substantially greater for active smoking than when the full control population was used. This Surgeon General’s report further addresses specific issues of exposure misclassification when they are relevant to the health outcome under consideration.
Use of Meta-Analysis Meta-analysis refers to the process of evaluating and combining a body of research literature that addresses a common question. Meta-analysis is composed of qualitative and quantitative components. The qualitative component involves the systematic identification of all relevant investigations, a systematic assessment of their characteristics and quality, and the decision to include or exclude studies based on predetermined criteria. Consideration can be directed toward sources of bias that might affect the findings. The quantitative component involves the calculation and display of study results on common scales and, if appropriate, the statistical combination of these results across studies and an exploration of the reasons for any heterogeneity of findings. Viewing the findings of all studies as a single plot provides insights into the consistency of results and the precision of the studies considered. Most meta-analyses are based on published summary results, although they are most powerful when applied to data at the level of individual participants. Meta-analysis is most widely used to synthesize evidence from randomized clinical trials, sometimes yielding findings that were not evident from the results of individual studies. Metaanalysis also has been used extensively to examine bodies of observational evidence. Beginning with the 1986 NRC report, metaanalysis has been used to summarize the evidence on involuntary smoking and health. Meta-analysis was central to the 1992 EPA risk assessment of secondhand smoke, and a series of meta-analyses supported the conclusions of the 1998 report of the Scientific Committee on Tobacco and Health in the United Kingdom. The central role of meta-analysis in interpreting and applying the evidence related to involuntary smoking and disease has led to focused criticisms of the use of meta-analysis in this context. Several papers that acknowledged support from the tobacco industry have addressed the epidemiologic findings for lung cancer, including the selection and quality of the
studies, the methods for meta-analysis, and doseresponse associations (Fleiss and Gross 1991; Tweedie and Mengersen 1995; Lee 1998, 1999). In a lawsuit brought by the tobacco industry against the EPA, the 1998 decision handed down by Judge William L. Osteen, Sr., in the North Carolina Federal District Court criticized the approach EPA had used to select studies for its meta-analysis and criticized the use of 90 percent rather than 95 percent confidence intervals for the summary estimates (Flue-Cured Tobacco Cooperative Stabilization Corp. v. United States Environmental Protection Agency, 857 F. Supp. 1137 [M.D.N.C. 1993]). In December 2002, the 4th U.S. Circuit Court of Appeals threw out the lawsuit on the basis that tobacco companies cannot sue the EPA over its secondhand smoke report because the report was not a final agency action and therefore not subject to court review (Flue-Cured Tobacco Cooperative Stabilization Corp. v. The United States Environmental Protection Agency, No. 98-2407 [4th Cir., December 11, 2002], cited in 17.7 TPLR 2.472 [2003]). Recognizing that there is still an active discussion around the use of meta-analysis to pool data from observational studies (versus clinical trials), the authors of this Surgeon General’s report used this methodology to summarize the available data when deemed appropriate and useful, even while recognizing that the uncertainty around the metaanalytic estimates may exceed the uncertainty indicated by conventional statistical indices, because of biases either within the observational studies or produced by the manner of their selection. However, a decision to not combine estimates might have produced conclusions that are far more uncertain than the data warrant because the review would have focused on individual study results without considering their overall pattern, and without allowing for a full accounting of different sample sizes and effect estimates. The possibility of publication bias has been raised as a potential limitation to the interpretation of evidence on involuntary smoking and disease in general, and on lung cancer and secondhand smoke exposure specifically. A 1988 paper by Vandenbroucke used a descriptive approach, called a “funnel plot,” to assess the possibility that publication bias affected the 13 studies considered in a review by Wald and colleagues (1986). This type of plot characterizes the relationship between the magnitude of estimates and their precision. Vandenbroucke suggested the possibility of publication bias only in reference to the studies of men. Bero and colleagues (1994) concluded that there
Introduction, Summary, and Conclusions
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Figure 1.2
Model for socioeconomic status (SES) and secondhand smoke (SHS) exposure Direct path
Lower SES
▲
Risk for adverse effect
Causal path ▲ Smoking active
▲ SHS
▲ ▲
Lower SES
▲
exposure
Risk for adverse effect
Confounding
▲ Lower SES
▲
SHS exposure ▲
▲▲
Chapter 1
Confounding, which refers in this context to the mixing of the effect of another factor with that of secondhand smoke, has been proposed as an explanation for associations of secondhand smoke with adverse health consequences. Confounding occurs when the factor of interest (secondhand smoke) is associated in the data under consideration with another factor (the confounder) that, by itself, increases the risk for the disease (Rothman and Greenland 1998). Correlates of secondhand smoke exposures are not confounding factors unless an exposure to them increases the risk of disease. A factor proposed as a potential confounder is not necessarily an actual confounder unless it fulfills the two elements of the definition. Although lengthy lists of potential confounding factors have been offered as alternatives to direct associations of secondhand smoke exposures with the risk for disease, the factors on these lists generally have not been shown to be confounding in the particular data of interest. The term confounding also conveys an implicit conceptualization as to the causal pathways that link secondhand smoke and the confounding factor to
▲
22
Confounding
▲
had not been a publication bias against studies with statistically significant findings, nor against the publication of studies with nonsignificant or mixed findings in the research literature. The researchers were able to identify only five unpublished “negative” studies, of which two were dissertations that tend to be delayed in publication. A subsequent study by Misakian and Bero (1998) did find a delay in the publication of studies with nonsignificant results in comparison with studies having significant results; whether this pattern has varied over the several decades of research on secondhand smoke was not addressed. More recently, Copas and Shi (2000) assessed the 37 studies considered in the meta-analysis by Hackshaw and colleagues (1997) for publication bias. Copas and Shi (2000) found a significant correlation between the estimated risk of exposure and sample size, such that smaller studies tended to have higher values. This pattern suggests the possibility of publication bias. However, using a funnel plot of the same studies, Lubin (1999) found little evidence for publication bias. On this issue of publication bias, it is critical to distinguish between indirect statistical arguments and arguments based on actual identification of previously unidentified research. The strongest case against substantive publication bias has been made by researchers who mounted intensive efforts to find the possibly missing studies; these efforts have yielded little— nothing that would alter published conclusions (Bero et al. 1994; Glantz 2000). Presumably because this exposure is a great public health concern, the findings of studies that do not have statistically significant outcomes continue to be published (Kawachi and Colditz 1996). The quantitative results of the meta-analyses, however, were not determinate in making causal inferences in this Surgeon General’s report. In particular, the level of statistical significance of estimates from the meta-analyses was not a predominant factor in making a causal conclusion. For that purpose, this report relied on the approach and criteria set out in the 1964 and 2004 reports of the Surgeon General, which involved judgments based on an array of quantitative and qualitative considerations that included the degree of heterogeneity in the designs of the studies that were examined. Sometimes this heterogeneity limits the inference from meta-analysis by weakening the rationale for pooling the study results. However, the availability of consistent evidence from heterogenous designs can strengthen the metaanalytic findings by making it unlikely that a common bias could persist across different study designs and populations.
Risk for adverse effect
Arrows indicate directionality of association.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
disease risk. Confounding implies that the confounding factor has an effect on risk that is independent of secondhand smoke exposure. Some factors considered as potential confounders may, however, be in the same causal pathway as a secondhand smoke exposure. Although socioeconomic status (SES) is often cited as a potential confounding factor, it may not have an independent effect but can affect disease risk through its association with secondhand smoke exposure (Figure 1.2). This figure shows general alternative relationships among SES, secondhand smoke exposure, and risk for an adverse effect. SES may have a direct effect, or it may indirectly exert its effect through an association with secondhand smoke exposure, or it may confound the relationship between secondhand smoke exposure and disease risk. To control for SES as a potential confounding factor without considering underlying relationships may lead to incorrect risk estimates. For example, controlling for SES would not be appropriate if it is a determinant of secondhand smoke exposure but has no direct effect. Nonetheless, because the health effects of involuntary smoking have other causes, the possibility of confounding needs careful exploration when assessing associations of secondhand smoke exposure with adverse health effects. In addition, survey data from
the last several decades show that secondhand smoke exposure is associated with correlates of lifestyle that may influence the risk for some health effects, thus increasing concerns for the possibility of confounding (Kawachi and Colditz 1996). Survey data from the United States (Matanoski et al. 1995) and the United Kingdom (Thornton et al. 1994) show that adults with secondhand smoke exposures generally tend to have less healthful lifestyles. However, the extent to which these patterns of association can be generalized, either to other countries or to the past, is uncertain. The potential bias from confounding varies with the association of the confounder to secondhand smoke exposures in a particular study and to the strength of the confounder as a risk factor. The importance of confounding to the interpretation of evidence depends further on the magnitude of the effect of secondhand smoke on disease. As the strength of an association lessens, confounding as an alternative explanation for an association becomes an increasing concern. In prior reviews, confounding has been addressed either quantitatively (Hackshaw et al. 1997) or qualitatively (Cal/EPA 1997; Thun et al. 1999). In the chapters in this report that focus on specific diseases, confounding is specifically addressed in the context of potential confounding factors for the particular diseases.
Tobacco Industry Activities
The evidence on secondhand smoke and disease risk, given the public health and public policy implications, has been reviewed extensively in the published peer-reviewed literature and in evaluations by a number of expert panels. In addition, the evidence has been criticized repeatedly by the tobacco industry and its consultants in venues that have included the peer-reviewed literature, public meetings and hearings, and scientific symposia that included symposia sponsored by the industry. Open criticism in the peerreviewed literature can strengthen the credibility of scientific evidence by challenging researchers to consider the arguments proposed by critics and to rebut them. Industry documents indicate that the tobacco industry has engaged in widespread activities, however, that have gone beyond the bounds of accepted scientific practice (Glantz 1996; Ong and Glantz 2000, 2001; Rampton and Stauber 2000; Yach and Bialous
2001; Hong and Bero 2002; Diethelm et al. 2004). Through a variety of organized tactics, the industry has attempted to undermine the credibility of the scientific evidence on secondhand smoke. The industry has funded or carried out research that has been judged to be biased, supported scientists to generate letters to editors that criticized research publications, attempted to undermine the findings of key studies, assisted in establishing a scientific society with a journal, and attempted to sustain controversy even as the scientific community reached consensus (Garne et al. 2005). These tactics are not a topic of this report, but to the extent that the scientific literature has been distorted, they are addressed as the evidence is reviewed. This report does not specifically identify tobacco industry sponsorship of publications unless that information is relevant to the interpretation of the findings and conclusions.
Introduction, Summary, and Conclusions
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References
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U.S. Department of Health, Education, and Welfare. The Health Consequences of Smoking. A Report of the Surgeon General: 1972. Washington: U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, 1972. DHEW Publication No. (HSM) 72-7516. U.S. Department of Health, Education, and Welfare. The Health Consequences of Smoking. A Report of the Surgeon General, 1975. Washington: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, 1975. DHEW Publication No. (CDC) 77-8704. U.S. Department of Health, Education, and Welfare. Smoking and Health. A Report of the Surgeon General. Washington: U.S. Department of Health, Education, and Welfare, Public Health Service, Office of the Assistant Secretary for Health, Office of Smoking and Health, 1979. DHEW Publication No. (PHS) 79-50066. U.S. Environmental Protection Agency. Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. Washington: U.S. Environmental Protection Agency, Office of Research and Development, Office of Air Radiation, 1992. Report No. EPA/600/6-90/0006F. Vandenbroucke JP. Passive smoking and lung cancer: a publication bias? British Medical Journal (Clinical Research Edition) 1988;296(6619):391–2. Wald NJ, Nanchahal K, Thompson SG, Cuckle HS. Does breathing other people’s tobacco smoke cause lung cancer? British Medical Journal (Clinical Research Edition) 1986;293(6556):1217–22. World Health Organization. International Consultation on Environmental Tobacco Smoke (ETS) and Child Health. Consultation Report. Geneva: World Health Organization, 1999. Wu AH. Exposure misclassification bias in studies of environmental tobacco smoke and lung cancer. Environmental Health Perspectives 1999;107(Suppl 6):873–7. Yach D, Bialous SA. Junking science to promote tobacco. American Journal of Public Health 2001;91(11):1745–8.
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Chapter 2 Toxicology of Secondhand Smoke
Introduction
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Composition of Tobacco Smoke
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Evidence of Carcinogenic Effects from Secondhand Smoke Exposure
30
Carcinogens in Sidestream Smoke and Secondhand Smoke 30 Carcinogenicity of Sidestream Smoke and Secondhand Smoke 33 Human Carcinogen Uptake from Secondhand Smoke 34 Mechanisms of Carcinogenesis of Secondhand Smoke 42 Summary 45 Conclusions 45 Mechanisms of Respiratory Tract Injury and Disease Caused by Secondhand Smoke Exposure Secondhand Smoke and Asthma 46 Secondhand Smoke and Infection 49 Secondhand Smoke and Chronic Obstructive Pulmonary Disease Secondhand Smoke and Sudden Infant Death Syndrome 50 Secondhand Smoke and Nasal or Sinus Disease 51 Summary 51 Conclusions 52
49
Mechanisms of Secondhand Smoke Exposure and Heart Disease Platelets 53 Endothelial Function and Vasodilation 54 Atherosclerosis 57 Effects on Children 57 Chemical Interactions with Low-Density Lipoprotein Cholesterol Experimental Atherosclerosis 58 Oxygen Delivery, Processing, and Exercise 59 Free Radicals and Ischemic Damage 59 Myocardial Infarction 63 Heart Rate Variability 63 Summary 63 Conclusions 64 Evidence Synthesis Conclusions
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Overall Implications References
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Chapter 2
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Introduction
A full range of scientific evidence, extending from the molecular level to whole populations, supports the conclusion that secondhand smoke causes disease. The scope of this evidence is enormous, and encompasses not only the literature on secondhand smoke but also relevant findings on active smoking and on the toxicity of individual tobacco smoke components. The 2004 report of the Surgeon General provides reviews on biologic considerations in relation to active smoking (U.S. Department of Health and Human Services [USDHHS] 2004). The guidelines for causal inference include coherence, which is defined as the extent to which all lines of scientific evidence converge in support of a causal conclusion. Beginning with the 1964 Surgeon General’s report on smoking and health (U.S. Department of Health, Education, and Welfare [USDHEW] 1964), reports in this series have comprehensively evaluated the full scope of evidence supporting causal inference with regard to particular associations of smoking with disease. This chapter reviews the evidence relevant to coherence, and includes the mechanisms relevant to the pathogenesis of diseases caused by secondhand smoke. Studies reviewed for this chapter were selected from Medline and SciFinder literature searches. Search terms included “carcinogens,” “environmental tobacco smoke,” “DNA adducts,” “protein adducts,” “urinary metabolites,” “tobacco smoke,” and the names of specific carcinogens and their metabolites. Recent reviews and cited references in recent papers provided additional sources for this chapter. This chapter sets out a foundation for interpreting the observational evidence that is the focus of most of the following chapters. The discussion that follows details the mechanisms that enable tobacco smoke components to injure the respiratory tract and
cardiovascular system and to cause nonmalignant and malignant diseases and other adverse effects.
Composition of Tobacco Smoke The chemical and physical properties of tobacco smoke from mainstream (drawn through the cigarette) and sidestream (released by the smoldering cigarette) smoke have been reviewed in a number of publications (Jenkins et al. 2000; Hoffmann et al. 2001; International Agency for Research on Cancer [IARC] 2004; California Environmental Protection Agency [Cal/ EPA] 2005). The IARC (2004) review indicates that some 4,000 mainstream tobacco smoke compounds have been identified (Roberts 1988), and the qualitative composition of the components is nearly identical in mainstream smoke, sidestream smoke, and secondhand smoke. An assessment by the National Research Council (1986) of differences in the composition of mainstream and sidestream smoke indicates that some compounds are emitted at levels up to more than 10 times greater in sidestream smoke compared with mainstream smoke (see also Table III-1 in Cal/EPA 2005). The Cal/EPA (2005) report identified 19 gas-phase and 21 particulate matter compounds in sidestream smoke with known carcinogenic and noncarcinogenic health effects (e.g., pulmonary edema, immune alterations, cardiac arrthythmias, and hepatotoxic and neurologic effects). The National Toxicology Program (USDHHS 2000) estimates that at least 250 chemicals in secondhand smoke are known to be toxic or carcinogenic. Other published reports have additional listings of specific chemical compounds in mainstream and secondhand smoke (Fowles and Dybing 2003; Cal/EPA 2005).
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Evidence of Carcinogenic Effects from Secondhand Smoke Exposure
Carcinogens in Sidestream Smoke and Secondhand Smoke As a result of advances in chemical analytical techniques and an expanded understanding of the mechanisms by which environmental agents are genotoxic, the number of known carcinogens in tobacco smoke increased to 69 in the year 2000 (IARC 2004). Table 2.1 summarizes representative levels of carcinogens found in sidestream and secondhand cigarette smoke, but includes only 30 compounds that have been evaluated by IARC and that have fulfilled certain other criteria: sufficient evidence of carcinogenicity in either laboratory animals or humans and published data on levels found in sidestream or secondhand smoke. Field studies on the carcinogenic composition of secondhand smoke cannot comprehensively evaluate all of the potential carcinogens in secondhand smoke. Some tobacco smoke carcinogens that IARC evaluated were not included in Table 2.1 because there were no published data on their levels in sidestream or secondhand cigarette smoke (Hoffmann et al. 2001). It is likely, however, that these carcinogens (which include some polycyclic aromatic hydrocarbons [PAHs], heterocycles, heterocyclic aromatic amines, nitro compounds, and other miscellaneous organic compounds) are also present in sidestream and secondhand smoke. In addition, there may be carcinogens present that IARC has not yet fully characterized or evaluated. PAHs are a diverse group of compounds formed in the incomplete combustion of organic material, and are potent, locally acting carcinogens in laboratory animals. PAHs induce tumors of the upper respiratory tract and lung when inhaled, instilled in the trachea, implanted in the lung, or administered by other routes (Shimkin and Stoner 1975), and are found in tobacco smoke, broiled foods, and polluted environments of various types. The best known member of this class of compounds is benzo[a]pyrene (B[a]P), which induces tumors of the upper respiratory tract and lung when inhaled, instilled in the trachea, implanted in the lung, or administered intraperitoneally, intravenously, subcutaneously, or by other routes (Shimkin and Stoner 1975). When administered systemically, B[a]P causes lung tumors in mice but not in rats (IARC 1973, 1983; Culp et al. 1998). Workers in iron and steel foundries and aluminum and coke production plants are
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exposed to PAHs. These exposures are considered to be a cause of excess cancers among workers in these settings (IARC 1983, 1984). N-Nitrosamines are a large group of carcinogens that induce cancer in a wide variety of species and tissues and are presumed to cause cancer in humans (Preussmann and Stewart 1984). These carcinogens can be formed endogenously from amines and nitrogen oxides and are found at low levels in foods (Bartsch and Spiegelhalder 1996). Tobacco smoke contains volatile N-nitrosamines such as N-nitrosodimethylamine and N-nitrosopyrrolidine, as well as tobacco-specific N-nitrosamines such as N’-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (Hoffmann and Hecht 1990). Tobaccospecific N-nitrosamines are chemically related to nicotine and other tobacco alkaloids and are therefore found only in tobacco products or related materials (Hecht and Hoffmann 1988). In laboratory animals, many N-nitrosamines are powerful carcinogens that display a striking organospecificity and affect particular tissues often independently of the route of administration (Preussmann and Stewart 1984). For example, NNN causes tumors of the esophagus and nasal cavity in rats, while the principal target of NNK in rodents is the lung; NNK is the only tobacco smoke carcinogen that induces lung tumors by systemic administration in all three commonly used rodent models—rat, mouse, and hamster (Hecht 1998). Among the aromatic amines first identified as carcinogens in dye industrial exposures, 2-naphthylamine and 4-aminobiphenyl are well-established human bladder carcinogens (IARC 1973, 1974). These carcinogens are also found in tobacco smoke. Aromatic amines cause tumors at a variety of sites in laboratory animals. Some members of this class, such as 2-toluidine, are only weakly carcinogenic (Garner et al. 1984). Formaldehyde and acetaldehyde, weaker carcinogens than PAHs, N-nitrosamines, and aromatic amines, have been measured in sidestream and secondhand smoke. When inhaled, formaldehyde and acetaldehyde induce respiratory tract tumors in rodents (Kerns et al. 1983; IARC 1999). Butadiene and benzene are volatile hydrocarbons that also occur in considerable quantities in sidestream and secondhand smoke. Butadiene is a multiorgan carcinogen that is particularly potent in mice; benzene causes leukemia
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Table 2.1
Levels of carcinogens in sidestream and secondhand cigarette smoke Representative amounts
Carcinogen
Sidestream (per cigarette)
Secondhand (per cubic meter [m3])
Study
Polycyclic aromatic hydrocarbons Benz[a]anthracene
201 nanograms (ng)
0.32–1.7 ng
Grimmer et al. 1987; Chuang et al. 1991
Benzo[a]pyrene
45–103 ng
0.37–1.7 ng
Adams et al. 1987; Grimmer et al. 1987; Chuang et al. 1991
Benzo[b]fluoranthene Benzo[j]fluoranthene Benzo[k]fluoranthene
196 ng
0.79–2.0 ng
Dibenz[a,h]anthracene
NR*
1 ng
Vu-Duc and Huynh 1989
Indeno[1,2,3-cd]pyrene
51 ng
0.35–1.1 ng
Grimmer et al. 1987; Chuang et al. 1991
5-Methylchrysene
NR
35.5 ng
Vu-Duc and Huynh 1989
Grimmer et al. 1987; Chuang et al. 1991
N-Nitrosamines N-Nitrosodiethanolamine
43 ng
NR
Brunnemann and Hoffmann 1981
N-Nitrosodiethylamine
8.2–73 ng
0–20 ng
Brunnemann et al. 1977; Hoffmann et al. 1987
N-Nitrosodimethylamine
143–1,040 ng
4–240 ng
Brunnemann et al. 1977; Hoffmann et al. 1987; Klus et al. 1992
N-Nitrosoethylmethylamine
3–35 ng
NR
Brunnemann et al. 1977; Hoffmann et al. 1987
N’-Nitrosonornicotine
110–857 ng
0.7–23 ng
Brunnemann et al. 1983, 1992; Adams et al. 1987; Klus et al. 1992
N-Nitrosopiperidine
4.8–19.8 ng
NR
Adams et al. 1987
N-Nitrosopyrrolidine
7–700 ng
3.5–27.0 ng
Brunnemann et al. 1977; Hoffmann et al. 1987; Klus et al. 1992; Mahanama and Daisey 1996
4-(Methylnitrosamino)-1(3-pyridyl)-1-butanone
201–1,440 ng
0.2–29.3 ng
Brunnemann et al. 1983, 1992; Adams et al. 1987; Klus et al. 1992
Aromatic amines 2-Naphthylamine
63.1–128 ng
NR
Government of British Columbia Ministry of Health Services 2001
2-Toluidine
3,030 ng
NR
Patrianakos and Hoffmann 1979
4-Aminobiphenyl
11.4–18.8 ng
NR
Government of British Columbia Ministry of Health Services 2001
Aldehydes Acetaldehyde
961–1,820 micrograms (µg)
268 µg
Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001
Formaldehyde
233–485 µg
143 µg
Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001
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Table 2.1
Continued Representative amounts
Carcinogen
Sidestream (per cigarette)
Secondhand (per cubic meter [m3])
Study
Miscellaneous organics Acrylonitrile
42–109 µg
NR
Government of British Columbia Ministry of Health Services 2001
Benzene
163–353 µg
4.2–63.7 µg
Scherer et al. 1995; Heavner et al. 1996; Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001; Kim et al. 2001
Catechol
98–292 µg
1.24 µg
Sakuma et al. 1983; Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001
Isoprene
668–1,260 µg
657 µg
Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001
1,3-Butadiene
98–205 µg
0.3–40 µg
Heavner et al. 1996; Martin et al. 1997; Government of British Columbia Ministry of Health Services 2001; Kim et al. 2001
Inorganic compounds Cadmium
330–689 ng
4–38 ng
Wu et al. 1995; Government of British Columbia Ministry of Health Services 2001
Chromium
57–79 ng
NR
Government of British Columbia Ministry of Health Services 2001
Hydrazine
94 ng
NR
Liu et al. 1974
Lead
28.9–46.6 ng
NR
Government of British Columbia Ministry of Health Services 2001
Nickel
51 ng
NR
Government of British Columbia Ministry of Health Services 2001
Polonium-210
0.091–0.139 picocurie
NR
Ferri and Baratta 1966
*NR = Data were not reported. Source: Adapted from Hoffmann et al. 2001.
in humans (IARC 1982, 1992, 1999). Metals such as nickel, chromium, and cadmium are human carcinogens that are also present in sidestream smoke (IARC 1990, 1994). Mainstream cigarette smoke consists of a gas phase and a particulate phase specifically composed of several million semiliquid particles per cubic
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centimeter (cm3) within a mixture of combustion gases (Ingebrethsen 1986; Guerin et al. 1992). Sidestream smoke contains free radicals in about the same concentrations as does mainstream smoke (Pryor et al. 1983). Pryor and colleagues (1998) detected reactive yet long-lived radicals in the gas phase; in the particulate phase, these investigators found a free
The Health Consequences of Involuntary Exposure to Tobacco Smoke
radical system that is a mixture of semiquinones, hydroquinones, and quinones (Pryor et al. 1998). Whether such agents can induce tumors in laboratory animals is not known.
Carcinogenicity of Sidestream Smoke and Secondhand Smoke Numerous studies have demonstrated that mainstream cigarette smoke condensate, the solid materials in the smoke, induces tumors on mouse skin and, by implantation, in rat lungs (IARC 1986, 2004). Inhalation experiments with mainstream smoke have demonstrated that cigarette smoke and its particulate phase induce preneoplastic lesions and benign and malignant tumors of the larynx in Syrian golden hamsters (IARC 1986). Studies with rats and mice documented less consistent results (IARC 1986, 2004; Hecht 1999). The carcinogenicity of sidestream smoke has been less extensively investigated. Sidestream smoke condensate was significantly more carcinogenic than mainstream smoke condensate when tested on mouse skin: mice treated with sidestream smoke developed two to six times more skin tumors than mice treated
Table 2.2
with mainstream smoke (Mohtashamipur et al. 1990). In a rat model using implanted sidestream smoke particles, a fraction containing PAHs with four or more rings produced tumors, while a fraction with semivolatiles and a PAH fraction with fewer rings had little effect (Grimmer et al. 1988). Limited histopathologic changes were observed in rats exposed to cigarette sidestream smoke aged in the chamber for 12 months (Haussmann et al. 1998). Researchers have carried out a series of investigations on the effects of secondhand smoke inhalation in A/J mice (Witschi et al. 1995, 1997a,b,c, 1998, 1999, 2000; Witschi 1998, 2000). Table 2.2 summarizes the data from these studies. Lung tumor multiplicity, the most sensitive indicator of response in this model, increased significantly in all experiments, and lung tumor incidence increased in several experiments. The protocol involved exposing mice to secondhand smoke (89 percent sidestream smoke and 11 percent mainstream smoke) for five months followed by a fourmonth recovery period in air. Other experiments have demonstrated that to observe an increase in lung tumor multiplicity, there must be a recovery period. These same experiments also showed that the response is due to a gas-phase component of secondhand smoke.
Inhalation studies of secondhand smoke (89% sidestream smoke and 11% mainstream smoke) in A/J mice
Study
Exposure (mg/m3* of total suspended particulates)
Lung tumor multiplicity†
Lung tumor incidence‡
Filtered air control
Smoke
Filtered air control (%)
Smoke (%)
Witschi et al. 1997a
79
0.5 ± 0.1 (24)
1.3 ± 0.3 (26)§
42
58
Witschi et al. 1997b
87
0.5 ± 0.2 (24)
1.4 ± 0.2 (24)§
38
83§
Witschi et al. 1998
83
0.9 ± 0.2 (29)
1.3 ± 0.2 (33)§
69
73
Witschi et al. 1999
132
0.6 ± 0.1 (30)
2.1 ± 0.3 (38)§
50
86∆
Witschi et al. 2000
137 137
0.9 ± 0.2 (30) 1.0 ± 0.1 (54)
2.8 ± 0.2 (38)§ 2.4 ± 0.3 (28)§
60 65
100∆ 89∆
Witschi et al., unpublished data
134
1.2 ± 0.2 (25)
2.3 ± 0.3 (26)§
60
88∆
*mg/m3 = Milligrams per cubic meter. † Mean ± standard error (number of animals is in parentheses). ‡ Percentage of all animals at risk that had tumors. § Significantly different (p 40 years Health insurance subscribers Korea 3.5 years
79 incident and prevalent cases
Questionnaires and medical exams of the husbands in 1992 and 1994; women completed questionnaires in 1993
Nishino et al. 2001
9,675 women aged >40 years Miyagi Prefecture, Japan 9 years
24 incident cases
Self-completed questionnaire by 31,345 (13,992 men and 17,353 women)
al. 1999; Nishino et al. 2001) and 13 case-control studies from around the world (Table 7.3) (Lei et al. 1996; Shen et al. 1996, 1998; Wang et al. 1996, 2000; Jöckel et al. 1998; Nyberg et al. 1998a; Zaridze et al. 1998; Rapiti et al. 1999; Zhong et al. 1999; Kreuzer et al. 2000; Lee et al. 2000; Zhou et al. 2000; Johnson et al. 2001; Seow et al. 2002). The case-control studies are organized by geographic areas because the relative importance of different sources of secondhand smoke exposure and the prevalence of other risk factors of lung cancer (such as occupational exposures, other sources of indoor air pollutants, and previous lung diseases) may differ from one country to another. Study design issues such as the reliance on pathologic confirmation and the proportion of surrogate respondents also differ by study area. Researchers have conducted several metaanalyses on secondhand smoke exposure and the risk of lung cancer (National Research Council [NRC] 1986; Dockery and Trichopoulos 1997; Hackshaw et al. 1997; Zhong et al. 2000). This chapter also contains a
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Data collection
meta-analysis that includes the more recent studies through 2002 in the pooled estimates, and in the estimates from the stratification of the studies by parameters such as gender and geographic area. Pooled estimates associated with secondhand smoke exposure from spouses, at the workplace, and during childhood are specifically presented (see “Pooled Analyses” later in this chapter).
Cohort Studies A total of eight cohort studies have evaluated secondhand smoke and the risk of lung cancer: three in the United States (Garfinkel 1981; Butler 1988; Cardenas et al. 1997), two in Japan (Hirayama 1981; Nishino et al. 2001), one in Scotland (Hole et al. 1989), one in Korea (Jee et al. 1999), and one in the Netherlands (de Waard et al. 1995). These cohort studies used questionnaires that asked about spousal smoking behaviors and used spousal smoking as the
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Relative risk (95% confidence interval)
Findings
Measure of secondhand smoke
• Urinary nicotine and cotinine levels were significantly associated with lung cancer risk • Risk increased with increasing urinary cotinine levels
Cotinine levels (nanograms/milligram): 30 years from 3 main local hospitals 2 controls per case Frequency matched for gender, age, and area of residence Sweden (Stockholm county) 1989–1995
124 (35 men, 89 women) 96% histologic confirmation Squamous cell carcinoma: 10% Small cell carcinoma: 2% Adenocarcinoma: 67%
235 (72 men, 163 women) selected from population register
In-person interview or by telephone Response rate Cases: 86% Controls: 83% 100% self-respondents
Zaridze et al. 1998
2 main cancer treatment hospitals Controls were from the same hospital as cases Russia (Local Moscow residents only)
189 women 100% histologic confirmation Squamous cell carcinoma: 22% Small cell carcinoma: 5% Adenocarcinoma: 56%
358 other cancer patients
In-person interview within 3 days of hospital admission Response rate was not reported 100% self-respondents
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Findings
Measure of secondhand smoke
Relative risk (95% confidence interval)
Comments (covariates considered, definition of lifetime nonsmokers)
Canada • Significant trend with smoker-years† of workplace and residential/workplace (i.e., total) secondhand smoke exposures
Any secondhand smoke exposure (childhood and adulthood): No Yes Total (smoker-years): None 1–36 37–77 ≥78
1.0 1.63 (0.8–3.5) 1.0 0.83 (0.3–2.1) 1.54 (0.7–3.5) 1.82 (0.8–4.2)
Controlled for age (10-year age group), education, province, fruit and vegetable intake; these results were based on 71 cases and 761 controls who had a more complete secondhand smoke exposure history; lifetime nonsmokers had smoked 10 years ago New Zealand
Incident stroke based on World Health Organization criteria
Secondhand smoke exposure in the home Men 2.10 (1.33–3.32) Women 1.66 (1.07–2.57) Combined 1.82 (1.34–2.49)
Age, gender, hypertension, diabetes, history of heart disease
You et al. 1999
Case-control Hospital cases and community controls
149 cases and 210 controls Lifetime nonsmoking men and women Australia
Incident stroke verified by CT scan
Spousal secondhand smoke 1.70 (0.98–2.92) Parental secondhand smoke 0.78 (0.48–1.26)
Age, gender, education, hypertension, diabetes mellitus, history of heart disease
Study
Design
Population
Case definition
Lee et al. 1986
Case-control Hospital-based
Men 4 cases 33 controls Women 8 cases 18 controls United Kingdom
Donnan et al. 1989
Case-control Hospital cases and community controls
Sandler et al. 1989
*Comparing the highest level of exposure with the lowest (see Lee et al. 1986, Table V, p. 102).
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
diabetes mellitus, dietary fat intake, leisure time physical activity, BMI, and alcohol intake. The investigators calculated an adjusted prevalence OR of 1.06 for SCI for those classified as exposed to secondhand smoke (95 percent CI, 0.64–1.75) compared with unexposed nonsmokers. There was no relationship between hours of exposure to secondhand smoke and SCI (Howard et al. 1998b). Bonita and colleagues (1999) carried out a population-based, case-control study of secondhand smoke and stroke in Auckland, New Zealand. Diagnostic criteria and methods for the 215 nonsmoking persons aged 35 through 74 years with first-ever acute stroke were defined according to WHO guidelines. The 1,336 nonsmoking controls were community-dwelling participants drawn from a 1993–1994 cross-sectional survey of cardiovascular risk factors carried out in the same city. The investigators determined exposures to secondhand smoke by asking patients and controls the same questions and characterized an exposure as a household member who regularly smoked cigarettes in their presence, or a coworker who smoked in the same indoor room in their presence for more than 1 year during the past 10 years. Risks were assessed among lifetime nonsmokers combined with long-term former smokers. Exposure to secondhand smoke was associated with an increased risk among men (crude OR = 2.10 [95 percent CI, 1.33–3.32]) and women (crude OR = 1.66 [95 percent CI, 1.07–2.57]). Overall, the risk of stroke was 1.82 (95 percent CI, 1.34–2.49)
for involuntary smokers with adjustment for several potential confounding factors. The nonsmokers in this study (both cases and controls) included former smokers who had stopped smoking for more than 10 years. No attempt was made in this study to distinguish secondhand smoke exposures at home, at work, or elsewhere (Bonita et al. 1999). One case-control study in Australia compared 452 hospitalized cases of first-ever ischemic stroke and 452 gender-matched neighborhood controls (You et al. 1999). Ischemic stroke was defined as the acute onset of a focal neurologic deficit that lasted more than 24 hours and that was verified by CT (excluding hemorrhage). Involuntary smoking was defined as living with a father, mother, or spouse who smoked at least one cigarette per day. To estimate the OR, You and colleagues (1999) controlled for educational attainment, history of CHD, hypertension, and diabetes mellitus, and then excluded current and former smokers. There were 154 participants who had suffered a stroke and 213 with no history of a stroke among the lifetime nonsmokers; missing values in either cases or controls bring the numbers to 149 cases and 210 controls used in the analysis. The adjusted OR of stroke for lifetime nonsmokers exposed to spousal smoking was 1.70 (95 percent CI, 0.98–2.92). No association was found for exposures to parental smoking (OR = 0.78 [95 percent CI, 0.48–1.26]) (Table 8.5). These studies were not pooled in this report because of their small number and the heterogeneity of their methods.
Subclinical Vascular Disease
A number of studies have been published linking secondhand smoke exposure to measures of subclinical vascular disease. These studies offer insights into the mechanisms underlying the relationship between exposures to secondhand smoke and the development of clinical coronary and cerebrovascular events (Howard and Wagenknecht 1999). Five different types of subclinical vascular outcomes that have been studied in humans in relation to secondhand smoke include the following: • assessing intimal-medial thickness (IMT) of the carotid artery using B-mode ultrasound as an
index of systemic atherosclerosis (Howard et al. 1994, 1998a; Diez-Roux et al. 1995); • assessing flow-mediated arterial endothelial function using B-mode ultrasound of the brachial artery as an index of vascular damage (Celermajer et al. 1996; Lekakis et al. 1997; Raitakari et al. 1999); • assessing coronary endothelial dysfunction using a quantitative coronary angiography to measure the extent of impairment of acetylcholineinduced coronary artery dilatation (Sumida et al. 1998);
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• assessing coronary flow velocity reserve using noninvasive transthoracic Doppler echocardiography (Otsuka et al. 2001); and • assessing aortic elastic properties before and after involuntary smoking with the aortic pressurediameter relation (Stefanadis et al. 1998, 1999). Published evidence suggests that exposure to secondhand smoke is damaging for each type of subclinical vascular outcome. This section reviews the evidence on secondhand smoke in relation to carotid arterial wall thickness.
Carotid Intimal-Medial Thickness Carotid IMT, assessed by B-mode ultrasound, is an established predictor of clinical events, including MI and stroke (Bots et al. 1997; Chambless et al. 1997; O’Leary et al. 1999). All three published studies linking secondhand smoke to an increased carotid IMT have used data from the ARIC Study (Howard et al. 1994, 1998a; Diez-Roux et al. 1995). In a cross-sectional analysis of data from the baseline ARIC assessment of 5,113 nonsmokers, Howard and colleagues (1994) found a difference of 11 micrometers (μm) in the average IMT of unexposed compared with exposed nonsmokers. This difference increased to 13 μm (p = 0.003) after adjusting for age, race, gender, education, hypertension, diabetes mellitus, low-density lipoprotein cholesterol level, fat intake, alcohol consumption, BMI, and leisure time physical activity. Among exposed male nonsmokers, there was a statistically significant dose-response relationship between the number of hours of the exposure and carotid IMT (p = 0.03). No dose-response relationship was observed among unexposed female nonsmokers. Diez-Roux and colleagues (1995) assessed IMT in relation to current and past exposures to secondhand smoke in a cohort of 2,073 persons who were included in the ARIC Study. The participants had information available on secondhand smoke exposure in 1975 and
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in 1987–1989. The authors defined four groups of lifetime nonsmokers: (1) those not exposed to secondhand smoke at either exam, (2) those exposed at the first but not at the second exam, (3) those exposed at the second but not at the first exam, and (4) those exposed at both exams. Exposure at one or both exams was associated with a nearly identical increase in IMT. This finding suggests that secondhand smoke has long-term harmful effects on atherosclerosis. The average IMT was 706 μm (±13 μm) for those not exposed in either period, 731 μm (±22 μm) for those exposed in the first period only, 738 μm (±11 μm) for those exposed in the second period only, and 734 μm (±12 μm) for those exposed in both periods (Diez-Roux et al. 1995). Finally, the ARIC Study examined the longitudinal association between secondhand smoke and the progression of IMT (Howard et al. 1998a). During a three-year follow-up period, the IMT progression rate was 31.6 μm for exposed lifetime nonsmokers and 25.9 μm for unexposed lifetime nonsmokers. The estimates of IMT progression were adjusted for the same demographic and coronary risk factors as in the crosssectional report by the same investigators (Howard et al. 1994). Among lifetime nonsmokers and former smokers combined, exposure to secondhand smoke was associated with an adjusted IMT progression rate of 5.9 μm over three years (±2.3 μm; p = 0.01). In proportional terms, this rate amounted to a 20 percent increase in IMT, which was nearly one-third of the size of the corresponding rate of progression among current smokers. No dose-response pattern was detected, however, between an increase in weekly hours of exposure and increased IMT progression rates. The evidence on CHD and stroke are considered separately in this section; however, the underlying pathogenetic mechanisms by which involuntary smoking increases risk are shared. For both outcomes, progression of atherosclerosis and increased risk for thrombosis are relevant. The finding that exposure to secondhand smoke increases IMT is supportive of a causal role for secondhand smoke exposure for both CHD and stroke.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Evidence Synthesis
Secondhand Smoke and Coronary Heart Disease Epidemiologic studies published since the 1986 Surgeon General’s report (USDHHS 1986) demonstrate convincingly that secondhand smoke is associated with an increased risk for CHD. The results of both case-control and cohort studies carried out in multiple populations consistently indicate about a 25 to 30 percent increase in risk of CHD from exposure to secondhand smoke. Additionally, cross-sectional and prospective studies convincingly demonstrate an association between exposure to secondhand smoke and the progression of carotid arterial IMT. The excess risk is unlikely to be explained by a measurement error with resulting exposure misclassification or uncontrolled confounding. One type of measurement error, the failure to correct for background secondhand smoke exposure, would lead to an underestimation of the association. Because exposures to secondhand smoke in different environments are presumed to be additive, studies that assess exposures in only one setting will underestimate the true, overall association. Although few studies have addressed CHD risk from secondhand smoke exposure in the workplace, there is no biologically plausible reason to suppose that the effect of secondhand smoke exposure at work differs from the effect of exposures in the home environment. When interpreting the epidemiologic data, researchers must also consider the possibility that the association reflects uncontrolled confounding. Several cross-sectional studies show differing profiles of cardiovascular risk factors in secondhand smokeexposed versus unexposed persons. However, an association has been consistently observed in multiple populations, and a number of studies have considered potential confounding factors in the analysis. Whereas some degree of residual confounding can never be fully excluded, the consistency of the association of secondhand smoke exposure with CHD risk and the persistence of an association with controls for confounding weigh heavily against residual confounding as the sole explanation. A substantial body of experimental evidence supports the biologic plausibility of an association of CHD risk with secondhand smoke exposure. Secondhand smoke exposure adversely affects platelet
function and endothelial function. In animal models, secondhand smoke exposure produces atherosclerosis in the coronary arteries. Current exposures to secondhand smoke appear to be more harmful than past exposures, and several studies suggest a higher risk of CHD from exposures of higher intensities. At least one study suggests that the risk declines as more time elapses since the last exposure. Compared with the effects of active smoking, the magnitude of the association between secondhand smoke and CHD seems large. This finding can be reconciled, however, with experimental data from both human and animal studies showing that acute effects of secondhand smoke on platelet aggregation as well as on endothelial dysfunction are nonlinear (Chapter 2, Toxicology of Secondhand Smoke).
Secondhand Smoke and Stroke The evidence is more limited for an association between secondhand smoke and stroke, although the biologic plausibility of an association with stroke risk is supported by the same evidence considered for CHD. The findings of the epidemiologic studies of CHD are complementary to those of stroke. Four case-control studies, one cross-sectional study, and one cohort study have addressed the association between secondhand smoke and the risk of stroke. In these studies, exposures to secondhand smoke were assessed either through self-reports (Lee et al. 1986; Donnan et al. 1989; Howard et al. 1998b; Bonita et al. 1999), or through the use of living in a household with other smokers as an indicator (Sandler et al. 1989; You et al. 1999). In addition to the possibility of measurement error, recall bias may be a problem in casecontrol studies that assess involuntary smoking with participant reports. Four of the six studies measured and adjusted for potential confounding variables such as hypertension and diabetes (Donnan et al. 1989; Howard et al. 1998b; Bonita et al. 1999; You et al. 1999). Measures of exposure differed across the studies. Of the six studies, two reported a statistically significant increase in the risk of stroke among involuntary smokers (Sandler et al. 1989; Bonita et al. 1999). Two other studies reported elevated risks of stroke from exposures to spousal
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smoking, but the lower 95 percent CI was below unity for both studies (Donnan et al. 1989; You et al. 1999). The six published studies also varied in their definition of stroke. Lee and colleagues (1986) did not define diagnostic criteria, whereas Donnan and colleagues (1989) included cases of TIA. Sandler and colleagues (1989) studied only stroke deaths based on death certificates; Howard and colleagues (1998b) examined SCI using MRI scans. The published studies of secondhand smoke exposure and stroke are still too
few and too heterogeneous in their methods and their exposure and outcome measures to warrant a pooled analysis. Given the established causal associations between active cigarette smoking and stroke and between involuntary smoking and CHD, an association between secondhand smoke and stroke is biologically plausible. There is a need for further research, especially more cohort studies, before a causal association can be inferred.
Conclusions
1.
The evidence is sufficient to infer a causal relationship between exposure to secondhand smoke and increased risks of coronary heart disease morbidity and mortality among both men and women.
2.
Pooled relative risks from meta-analyses indicate a 25 to 30 percent increase in the risk of coronary heart disease from exposure to secondhand smoke.
3.
The evidence is suggestive but not sufficient to infer a causal relationship between exposure to secondhand smoke and an increased risk of stroke.
4.
Studies of secondhand smoke and subclinical vascular disease, particularly carotid arterial wall thickening, are suggestive but not sufficient to infer a causal relationship between exposure to secondhand smoke and atherosclerosis.
Overall Implications
Cal/EPA has estimated that 46,000 (a range of 22,700 to 69,600) cardiac deaths in the United States each year are attributable to secondhand smoke exposures at home and in the workplace (Cal/EPA 2005). Thus, the estimated exposures in these two environments can potentially produce a substantial burden of avoidable deaths. Because researchers have identified workplaces as predominant sites for exposure to secondhand smoke (Chapter 4, Prevalence of Exposure to Secondhand Smoke), the estimated pooled RR for workplace exposures suggests that secondhand smoke represents a significant occupational hazard. Following a modified risk assessment approach adopted in 1994 by the U.S. Occupational Safety and Health Administration, Steenland (1999) estimated that as a
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result of secondhand smoke exposures in the workplace, the excess risk of death from heart disease by 70 years of age was 7 per 1,000 (95 percent CI, 1–13 per 1,000). On the basis of current estimates of exposures to secondhand smoke in U.S. workplaces, Steenland further estimated that these exposures had caused 1,710 excess deaths from CHD annually among nonsmoking workers aged 35 through 69 years. This review identified several areas for further research. Mechanistic studies that further refine the dose-response relationships and mechanisms of acute responses of the cardiovascular system to secondhand smoke exposure should be carried out. Additional epidemiologic studies of stroke are also needed.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
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Lee PN, Chamberlain J, Alderson MR. Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases. British Journal of Cancer 1986;54(1):97–105. Lekakis J, Papamichael C, Vemmos C, Nanas I, Kontoyannis D, Stamatelopoulos S, Moulopoulos S. Effect of acute cigarette smoking on endothelium-dependent brachial artery dilatation in healthy individuals. American Journal of Cardiology 1997;79(4):529–31. LeVois ME, Layard MW. Publication bias in the environmental tobacco smoke/coronary heart disease epidemiologic literature. Regulatory Toxicology and Pharmacology 1995;21(1):184–91. LeVois ME, Layard MW. Passive smoking and heart disease: authors need to analyse the data [letter]. British Medical Journal 1998;317(7154):344. Matanoski G, Kanchanaraska S, Lantry D, Chang Y. Characteristics of nonsmoking women in NHANES I and NHANES I Epidemiologic Follow-up Study with exposure to spouses who smoke. American Journal of Epidemiology 1995;142(2): 149–57. McElduff P, Dobson AJ, Jackson R, Beaglehole R, Heller RF, Lay-Yee R. Coronary events and exposure to environmental tobacco smoke: a case-control study from Australia and New Zealand. Tobacco Control 1998;7(1):41–6. Muscat JE, Wynder EL. Exposure to environmental tobacco smoke and the risk of heart attack. International Journal of Epidemiology 1995;24(4):715–9. National Cancer Institute. Health Effects of Exposure to Environmental Tobacco Smoke: The Report of the California Environmental Protection Agency. Smoking and Tobacco Monograph No. 10. Bethesda (MD): U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, 1999. NIH Publication No. 99-4645. National Health and Medical Research Council Working Party. The Health Effects of Passive Smoking: a Scientific Information Paper. Canberra (Australia): National Health and Medical Research Council, 1997. O’Leary DH, Polak JF, Kronmal RA, Maniolo TA, Burke GL, Wolfson SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults: Cardiovascular Health Study Collaborative Research Group. New England Journal of Medicine 1999;340(1): 14–22.
Ong EK, Glantz SA. Tobacco industry efforts subverting International Agency for Research on Cancer’s second-hand smoke study. Lancet 2000;355(9211):1253–9. Otsuka R, Watanabe H, Hirata K, Tokai K, Muro T, Yoshiyama M, Takeuchi K, Yoshikawa J. Acute effects of passive smoking on the coronary circulation in healthy young adults. Journal of the American Medical Association 2001;286(4):436–41. Raitakari OT, Adams MR, McCredie RJ, Griffiths KA, Celermajer DS. Arterial endothelial dysfunction related to passive smoking is potentially reversible in healthy young adults. Annals of Internal Medicine 1999;130(7):578–81. Rosenlund M, Berglind N, Gustavsson A, Reuterwall C, Hallqvist J, Nyberg F, Pershagen G. Environmental tobacco smoke and myocardial infarction among never-smokers in the Stockholm Heart Epidemiology Program (SHEEP). Epidemiology 2001; 12(5):558–64. Sandler DP, Comstock GW, Helsing KJ, Shore DL. Deaths from all causes in non-smokers who lived with smokers. American Journal of Public Health 1989; 79(2):163–7. Steenland K. Risk assessment for heart disease and workplace ETS exposure among nonsmokers. Environmental Health Perspectives 1999;107(Suppl 6): 859–63. Steenland K, Sieber K, Etzel RA, Pechacek T, Maurer K. Exposure to environmental tobacco smoke and risk factors for heart disease among never smokers in the Third National Health and Nutrition Examination Survey. American Journal of Epidemiology 1998;147(10):932–9. Steenland K, Thun M, Lally C, Heath C Jr. Environmental tobacco smoke and coronary heart disease in the American Cancer Society CPS-II cohort. Circulation 1996;94(4):622–8. Stefanadis C, Dernellis J, Toutouzas P. Mechanical properties of the aorta determined by the pressurediameter relation. Pathologie-Biologie 1999;47(7): 696–704. Stefanadis C, Vlachopoulos C, Tsiamis E, Diamantopoulos L, Toutouzas K, Giatrakos N, Vaina S, Tsekoura D, Toutouzas P. Unfavorable effects of passive smoking on aortic function in men. Annals of Internal Medicine 1998;128(6):426–34. Sumida H, Watanabe H, Kugiyama K, Ohgushi M, Matsumura T, Yasue H. Does passive smoking impair endothelium-dependent coronary artery dilation in women? Journal of the American College of Cardiology 1998;31(4):811–5.
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Sun Y, Zhu B, Browne AE, Sievers RE, Bekker JM, Chatterjee K, Parmley WW, Glantz SA. Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke. Circulation 2001;104(7):810–4. Svendsen KH, Kuller LH, Martin MJ, Ockene JK. Effects of passive smoking in the Multiple Risk Factor Intervention Trial. American Journal of Epidemiology 1987;126(5):783–95. Thornton A, Lee P, Fry J. Difference between smokers, ex-smokers, passive smokers and non-smokers. Journal of Clinical Epidemiology 1994;47(10):1143–62. Thun M, Henley J, Apicella L. Epidemiologic studies of fatal and nonfatal cardiovascular disease and ETS exposure from spousal smoking. Environmental Health Perspectives 1999;107(Suppl 6):841–6. Tunstall-Pedoe H, Brown CA, Woodward M, Tavendale R. Passive smoking by self-report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study. Journal of Epidemiology and Community Health 1995;49(2):139–43. U.S. Department of Health and Human Services. The Health Consequences of Smoking: Cardiovascular Disease. A Report of the Surgeon General. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service, Office on Smoking and Health, 1983. DHHS Publication No. (PHS) 84-50204. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Smoking. A Report of the Surgeon General. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Health Promotion and Education, Office on Smoking and Health, 1986. DHHS Publication No. (CDC) 87-8398.
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U.S. Department of Health and Human Services. Women and Smoking. A Report of the Surgeon General. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General, 2001. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Wagenknecht LE, Burke GL, Perkings LL, Haley NJ, Friedman GD. Misclassification of smoking status in the CARDIA Study: a comparison of self-report with serum cotinine levels. American Journal of Public Health 1992;82(1):33–8. Wells AJ. Passive smoking as a cause of heart disease. Journal of the American College of Cardiology 1994;24(2):546–54. Wells AJ. Heart disease from passive smoking in the workplace. Journal of the American College of Cardiology 1998;31(1):1–9. Whincup PH, Gilg JA, Emberson JR, Jarvis MJ, Feyerabend C, Bryant A, Walker M, Cook DG. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. British Medical Journal 2004;329(7459):200–5. World Health Organization. Seventh Revision of the International Classification of Diseases. Geneva: World Health Organization, 1957. You RX, Thrift AG, McNeil JJ, Davis SM, Donnan GA, and the Melbourne Stroke Risk Factor Study (MSRFS) Group. Ischemic stroke risk and passive exposure to spouses’ cigarette smoking. American Journal of Public Health 1999;89(4):572–5.
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Introduction
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Biologic Basis
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Odor and Irritation
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Evidence Synthesis Conclusions 546 Implications 546
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Respiratory Symptoms
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Experimental Studies 547 Observational Studies 547 Evidence Synthesis 552 Conclusions 553 Implications 553 Lung Function
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Asthma 555 Etiologic Studies 556 Morbidity Studies 557 Experimental Studies 557 Observational Studies 557 Evidence Synthesis 558 Conclusions 558 Implications 558 Chronic Obstructive Pulmonary Disease Etiologic Studies 559 Morbidity Studies 561 Evidence Synthesis 561 Conclusions 562 Implications 562 Conclusions
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Introduction
There have been far fewer studies of involuntary smoking and adverse respiratory effects on adults compared with the number of studies on children. In fact, the evidence for children has causally linked secondhand smoke exposure to a number of adverse respiratory effects (Chapter 6, Respiratory Effects in Children from Exposure to Secondhand Smoke). The more limited research on adults may partly reflect the methodologic challenges in designing studies of nonmalignant respiratory diseases in adults, who are exposed in multiple and often complex environments: the home, the workplace, transportation environments, and additional public and other places. The potential for misclassifying smoking status, with former or current smokers categorized as involuntary smokers, has been a concern in studies that rely on self-reports of former smoking. Measuring past secondhand smoke exposure presents a challenge in studies of chronic effects and diseases that may become clinically apparent only after 20 or more years of exposure. Bias in the reporting of symptoms attributed to involuntary smoking is increasingly possible as public awareness of involuntary smoking and its health consequences increases. It may also be difficult to measure exposures to potential confounding or modifying agents (e.g., infectious agents and dusty occupations) that may need to be considered in studies of involuntary smoking. Despite these challenges, the literature has been growing since the 1986 reports released by the Surgeon General (U.S. Department of Health and Human Services [USDHHS] 1986) and the National Research Council (NRC 1986). Subsequently, the literature has been summarized by federal and state agencies including the U.S. Environmental Protection Agency (USEPA 1992) and the California Environmental Protection Agency (Cal/EPA) (National Cancer Institute [NCI] 1999), and by several authors in peer-reviewed publications (Trédaniel et al. 1994; Coultas 1998; Weiss et al. 1999). Major reviews of the health effects of involuntary smoking in adults published between 1986
and 1999 examined respiratory health outcomes such as odor and irritation, respiratory symptoms, pulmonary function, and respiratory diseases (e.g., asthma and chronic obstructive pulmonary disease [COPD]) (Table 9.1). This table includes agency reviews as well as systematic reviews carried out by individual authors (Trédaniel et al. 1994; Coultas 1998). The evidence documented a strong link between secondhand smoke exposure and odor annoyance and irritation of mucous membranes of the eyes and nose. Weaker evidence suggested that involuntary smoking is associated with respiratory symptoms and small decrements in lung function among adults. Although experimental studies suggested that some persons with asthma may be susceptible to the effects of secondhand smoke exposure, only scant epidemiologic data consisting of a small number of studies on involuntary smoking and COPD were available on this issue at the time. This chapter reexamines the literature from these earlier reviews (Table 9.1), updates the literature with more recent publications, and evaluates the evidence supporting causal inferences. This discussion does not specifically review sinonasal disease because the evidence remains limited (Samet 2004). The research strategy for this chapter consisted of searching the Medline database to identify references between 1990 and 2001 using any of five terms for secondhand smoke: environmental tobacco smoke (ETS), tobacco smoke pollution, sidestream smoke, second hand smoke, or secondhand smoke. These terms were then linked to a series of terms: (1) respiratory symptoms (i.e., respiratory symptom, cough, coughing, wheeze, or dyspnea [difficulty breathing]); (2) lung function; (3) lung diseases (i.e., lung diseases, obstructive, asthma, emphysema, and bronchitis); (4) etiology (i.e., cause or risk factor) and morbidity; (5) irritation or irritating of eye or nose or throat; and (6) tobacco smoke sensitivity or odor. In addition, bibliographies from recent studies were reviewed for additional references (Trédaniel et al. 1994; Coultas 1998; NCI 1999; Weiss et al. 1999).
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Table 9.1
Major conclusions from reports on adverse respiratory effects of secondhand smoke exposure in adults
Odor and Irritation U.S. Department of Health and Human Services (USDHHS) 1986 “The main effects of the irritants present in ETS [environmental tobacco smoke] 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.” (p. 252) National Research Council (NRC) 1986 “ETS arouses odor responses. The objectionable odor generated by ETS greatly exceeds that generated by simple occupancy under comparable conditions of occupancy, density, temperature, and relative humidity, and is more persistent.” (p. 178) “Whereas odor will govern the reactions of visitors to a smoking space, irritation will largely govern the reactions of occupants. Over time, eye irritation grows to become the most important negative response of the occupant. Dissatisfaction observed in chamber studies is commensurate with that found in field studies.” (p. 178) Trédaniel et al. 1994 “The acute irritating effect of ETS on respiratory mucous membranes is well-established.” (p. 180) California Environmental Protection Agency (Cal/EPA) 1997 (National Cancer Institute [NCI] 1999) “Eye and nasal irritation are the most commonly reported symptoms among adult nonsmokers exposed to ETS; in addition, odor annoyance from indoor exposure to ETS has been shown in several studies.” (p. 253) Respiratory Symptoms USDHHS 1986 “The implications of chronic respiratory symptoms for respiratory health as an adult are unknown and deserve further study.” (p. 107) NRC 1986 “The extent to which normal and asthmatic adults are affected by short-term exposures to ETS needs to be studied further.” (p. 217) USEPA 1992 “. . .new evidence also has emerged suggesting that exposure to ETS may increase the frequency of respiratory symptoms in adults. These latter effects are estimated to be 30% to 60% higher in ETS-exposed nonsmokers compared to unexposed nonsmokers.” (pp. 7-68–7-69) Trédaniel et al. 1994 “. . .no definite conclusion can be drawn from the studies that have investigated chronic respiratory symptoms in relation to ETS exposure.” (p. 181) Cal/EPA 1997 (NCI 1999) “. . .regular ETS exposure in adults has been reported to increase the risk of occurrence of a variety of lower respiratory symptoms.” (p. 255) Pulmonary Function USDHHS 1986 “Healthy adults exposed to environmental tobacco smoke may have small changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmonary function as a result of exposure to environmental tobacco smoke alone.” (p. 107)
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Table 9.1
Continued
NRC 1986 “Future cross-sectional studies of ETS exposure and lung function in adults need to be designed to control for other factors that may affect lung function.” (p. 217) “Little information is available from long-term longitudinal studies of the effect of exposure to ETS by nonsmokers on lung function in either children or adults.” (p. 217) USEPA 1992 “Recent studies have confirmed the conclusion by the Surgeon General’s report (U.S. DHHS, 1986) that adult nonsmokers exposed to ETS may have small reductions in lung function (approximately 2.5% lower mean FEV1 [forced expiratory volume in 1 second]). . . .” (p. 7-68) Trédaniel et al. 1994 “It remains controversial whether acute passive smoking is associated with important pulmonary physiological hazards. . . . Most of the available studies are cross-sectional, and the relationship to long-term changes in lung function is not established.” (p. 181) Cal/EPA 1997 (NCI 1999) “The effect of chronic ETS exposure upon pulmonary function in otherwise healthy adults is likely to be small, and is unlikely by itself to result in clinically significant chronic disease.” (p. 255) Respiratory Diseases NRC 1986 “It is unlikely that exposure to ETS can cause much emphysema.” (p. 212) Trédaniel et al. 1994 “Conflicting evidence exists on the association in asthmatic patients between ETS exposure and appearance of symptoms and functional abnormalities (including change in bronchial responsiveness).” (p. 181) “Four out of five studies offer support to the hypothesis of an association between ETS exposure and risk of COPD [chronic obstructive pulmonary disease].” (p. 181) Coultas 1998 “While growing evidence suggests that passive smoking is a risk factor for adult onset asthma and COPD, the magnitude of the associations is small. However, additional evidence on the relationship between passive smoking and asthma and COPD is needed to fulfill the criteria for causality, particularly the criteria of temporality and doseresponse.” (p. 386) “Although the available literature is limited, it does show that exposure to ETS is associated. . .with worsening of respiratory symptoms and lung function in adult asthmatics.” (p. 383) “. . .little is known about the effects of ETS exposure on respiratory symptoms or lung function among patients with COPD.” (p. 385) Cal/EPA 1997 (NCI 1999) “There is suggestive evidence that ETS exposure may exacerbate adult asthma.” (p. 194) “. . .chamber studies. . .suggest that there is likely to be a subpopulation of asthmatics who are especially susceptible to ETS exposure.” (p. 203)
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Biologic Basis
Chapter 2 (Toxicology of Secondhand Smoke) reviews mechanisms by which secondhand smoke exposure may generally cause respiratory disease in populations. This section focuses more specifically on adults. Active cigarette smoking causes inflammatory injury throughout the respiratory tract, leading to chronic airway and alveolar injury and chronic respiratory symptoms and diseases (Floreani and Rennard 1999; Saetta et al. 2001; USDHHS 2004). Although the evidence on active smoking provides a strong basis of support for the plausibility of adverse respiratory effects from involuntary smoking, differences in the dose from involuntary versus active smoking limit direct inferences from active to involuntary smoking. Experimental studies in animals (Escolar et al. 1995; Joad et al. 1995; Seymour et al. 1997) and humans (Anderson et al. 1991; Yates et al. 1996, 2001; NCI 1999) provide relevant evidence of and insights into underlying mechanisms for the effects of involuntary smoking on the respiratory tract. The biologic outcomes examined in animal models of involuntary smoking have included antibody responses (Seymour et al. 1997), alterations of airway defense receptors (Joad et al. 1995), and pathologic changes of emphysema (Escolar et al. 1995). Using a mouse allergy model, Seymour and colleagues (1997) exposed the animals to secondhand smoke for 43 days (6 hours per day, 5 days per week, mean total suspended particulates at 1.04 milligrams per cubic meter [mg/m3], mean carbon monoxide [CO] at 6.1 parts per million [ppm]). Secondhand smoke exposure resulted in elevated levels of antibodies to allergens delivered by aerosol challenge, suggesting that such exposures enhance allergic inflammatory responses. Joad and colleagues (1995) exposed 29 developing guinea pigs aged 8 through 43 days to sidestream smoke (CO = 5.6 ± 0.7 ppm) for six hours per day, five days a week. Although lung morphology was unchanged, responsiveness of airway C-fiber receptors (a component of lung defense mechanisms) was reduced, which may facilitate further exposure and injury over time. Escolar and colleagues (1995) exposed 60 rats to secondhand smoke (mean CO at 35 ppm) for 90 minutes per day for three months. Morphometry showed changes in the alveoli consistent with emphysema, including the loss of elasticity in the lung tissue. Human experimental studies have involved short-term exposures of volunteers to known
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concentrations of sidestream smoke measured by CO and/or particulate levels in exposure chambers. The effects examined included eye and nasal irritation, nasal mucociliary clearance, respiratory symptoms, pulmonary function changes, and systemic inflammation. Although controlled human exposure studies have the advantages of accurate measurements and controlled levels of exposure, such studies have inherent limitations. Because the duration of exposure must be brief, only short-term effects can be measured. Exposure to sidestream smoke under controlled conditions may not accurately reflect exposure-response relationships associated with multiple exposures found in real-world conditions such as the workplace. These studies are necessarily restricted to a small number of volunteers, thus limiting the generalizability of the findings and the statistical power to detect effects. Moreover, variations in the duration of the exposures limit the comparability of the results. Controlled human exposures to sidestream smoke have been used to characterize effects on the nose such as odor detection, nasal symptoms, and physiologic changes (USDHHS 1986; Bascom et al. 1991, 1995, 1996; Cummings et al. 1991; Willes et al. 1992, 1998; Nowak et al. 1997a). In general, these exposures have been at the upper end of the range of measured secondhand smoke concentrations in various environments (Chapter 3, Assessment of Exposure to Secondhand Smoke, and Chapter 4, Prevalence of Exposure to Secondhand Smoke). Bascom and colleagues (1991, 1995, 1996) and Willes and colleagues (1992, 1998) conducted a series of chamber studies to characterize nasal responses to sidestream smoke. In an early investigation, Bascom and colleagues (1991) found that posterior nasal resistance (a measurement of nasal sensitivity in the bottom of the passageway) increased after 15 minutes of exposure to sidestream smoke (45 ppm of CO) among 10 healthy persons without asthma who reported nasal sensitivity to secondhand smoke (congestion, rhinorrhea, or sneezing), but not among 11 participants who did not report nasal sensitivity. However, assay of nasal secretions for histamine, kinin, esterase, or albumin provided no evidence for allergic inflammation or increased vascular permeability, indicating a nonallergic mechanism for the physiologic response. Nowak and colleagues (1997a) reported similar findings after examining nasal fluid for markers of inflammation 30 minutes
The Health Consequences of Involuntary Exposure to Tobacco Smoke
before and 30 minutes after exposing 10 persons with mild asthma to secondhand smoke at 22.4 ppm of CO. Bascom and colleagues (1996) examined exposure-response relationships among 13 persons with reported secondhand smoke sensitivity and 16 persons who were not sensitive; the experiment involved two hours of sidestream smoke exposure at 1 ppm, 5 ppm, and 15 ppm of CO. Nasal resistance increased significantly in both groups after exposure to the highest level of sidestream smoke (15 ppm of CO). Bascom and colleagues (1995) also assessed the effect of sidestream smoke exposure on nasal mucociliary clearance in 12 volunteers. The rate of clearance increased in some participants but slowed in three others; all three had a history of rhinitis associated with secondhand smoke exposure. Human volunteers, including healthy nonsmokers and persons with asthma, have been exposed to secondhand smoke under controlled conditions to examine symptoms, pulmonary function changes, inflammatory markers, and lung injury (Trédaniel et al. 1994; Yates et al. 1996, 2001; Nowak et al. 1997a,b; NCI 1999; Weiss et al. 1999). The 1997 Cal/EPA report reviewed results from 10 studies of persons with asthma and concluded that “although the design constraints of the chamber studies limit the interpretation of the results, they do suggest that there is likely to be a subpopulation of asthmatics who are especially susceptible to ETS exposure. The physiological responses observed in these investigations appear to be reproducible in both ‘reactors’ and ‘nonreactors.’ It is unlikely that the physiological and symptomatic responses reported are due exclusively to either stress or suggestion” (NCI 1999, p. 203). Nowak and colleagues (1997b) provided additional evidence for this conclusion by exposing 17 persons with mild asthma to secondhand smoke (20 ppm of CO) or ambient air (“sham”) for three hours. The investigators measured spirometry and bronchial responsiveness one hour, five hours, and nine hours after the exposure. The overall average decline in forced expiratory volume in one second (FEV1) levels was 9.1 percent after the secondhand smoke exposure and 5.9 percent after the sham exposure. However, the mean FEV1 decline largely reflected declines in three persons, and secondhand smoke-induced symptoms were not associated with the FEV1 decline. In a separate study of 10 persons with mild asthma who were exposed to secondhand smoke at 22.4 ppm of CO for three hours, the FEV1 level and the levels of markers of inflammation obtained by bronchoalveolar lavage were unchanged by the exposure (Nowak et al. 1997a).
Studies have associated nonspecific bronchial hyperresponsiveness with an accelerated decline in lung function, which may thus be a marker for susceptibility to the development of COPD (Kanner et al. 1994; Paoletti et al. 1995; Rijcken et al. 1995; Tracey et al. 1995). Menon and colleagues (1992) exposed 31 smoke-sensitive persons with asthma and 39 smoke-sensitive persons without asthma to secondhand smoke at relatively high levels (suspended particles >1,000 micrograms/m3) for four hours in a test chamber. Compared with pre-exposure bronchial reactivity among those without asthma, bronchial reactivity to methacholine increased in 18 percent of the participants 6 hours after exposure, in 10 percent of the participants 24 hours after exposure, and in 8 percent of the participants three weeks after exposure. These results suggest that secondhand smoke exposure may increase bronchial hyperreactivity even in asymptomatic persons who do not have asthma. In contrast to these results, a study of 17 secondhand smoke-exposed persons with mild asthma did not find an increase in airway responsiveness when measured by the methacholine challenge (Nowak et al. 1997b). Jindal and colleagues (1999) measured bronchial hyperresponsiveness in a sample of 50 women aged 20 through 40 years with asthma who were from a chest clinic in India. Exposure to secondhand smoke was assessed with a questionnaire that included questions on smoking by the husband, smoking by other family members, and smoking by coworkers. Women exposed to secondhand smoke had significantly greater bronchial hyperreactivity than did unexposed women; the mean provocative dose of histamine used to produce a 20 percent drop in FEV1 was 50 percent lower in the exposed group compared with the unexposed group. In active smokers, the uptake of inhaled technetium99m (labeled diethylenetriamine pentaacetate [99mTc-DTPA]) was increased, suggesting an increase in alveolar permeability (Jones et al. 1980). Yates and colleagues (1996) applied this technique to 20 healthy nonsmokers and assessed whether exposure to secondhand smoke for one hour in a chamber affected alveolar permeability. The exposure was followed by an increase in the time for 99mTc-DTPA clearance, from 69.1 to 77.4 minutes. In contrast to active smoking, these results imply a decrease in alveolar permeability following exposure. The findings do, however, provide evidence of a physiologic response to even a very brief exposure to secondhand smoke. Nowak and colleagues (1997a) also provided indirect evidence for a decrease in epithelial
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permeability associated with secondhand smoke exposure in a study of 10 persons with mild asthma. Albumin levels from nasal and bronchoalveolar lavage were lower after three hours in a chamber at 22.4 ppm CO compared with a sham exposure. An increase in permeability would be expected to increase albumin leakage into the alveoli. Nitric oxide (NO) regulates a number of airway and vascular functions and can be measured in exhaled air. Compared with nonsmokers, active smokers had lower exhaled NO levels, and intermediate decrements were found in exhaled NO levels from nonsmokers exposed to secondhand smoke (Yates et al. 2001). Fifteen healthy nonsmoking volunteers were exposed to secondhand smoke at 23 ppm CO in a chamber for one hour, and exhaled NO was measured before and every 15 minutes during the exposure (Yates et al. 2001). Secondhand smoke exposure was associated with a significant decline in exhaled NO (134 parts per billion [ppb] before and 99 ppb 60 minutes after the exposure). Only limited information is available on the systemic effects of secondhand smoke exposure (Anderson et al. 1991; Oryszczyn et al. 2000). Anderson and colleagues (1991) exposed 16 healthy nonsmokers (mean age 29 years) to cigarette smoke from 6 smokers in a poorly ventilated room for three hours with hourly respirable particulate levels averaging 2.3 to 2.6 mg/m3. This exposure was associated with significant increases in peripheral blood leukocyte counts, chemotaxis, and the release of reactive oxidants; these findings are consistent with the mechanisms of respiratory tract injury in active smokers (Saetta et al. 2001; USDHHS 2004). Oryszczyn and colleagues (2000) examined the relationship between self-reported secondhand smoke exposure (i.e., currently living with one or more smokers) and the total serum immunoglobulin E (IgE) level, which is higher in persons with asthma than in those without asthma. The study included 122 persons with asthma, 430 of their firstdegree relatives, and 190 controls. Among lifetime nonsmokers with and without asthma, involuntary smoking was associated with higher IgE levels. The
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highest levels were among those with asthma who had been exposed to secondhand smoke. However, significant differences in IgE levels were observed only in women after adjusting for asthma. In summary, compared with research on active smoking, the literature on respiratory tract injury from involuntary smoking is limited. There are only a few animal investigations, and they examined different outcomes (e.g., antibody response to allergens, responsiveness of C-fiber receptors, and morphologic signs of emphysema). Most human studies have examined inflammatory and physiologic effects of short-term secondhand smoke exposure in chambers. The few studies that investigated markers of local inflammation in the nose and lower respiratory tract did not find any evidence of an increased inflammatory response to brief secondhand smoke exposures. Exhaled NO, which has a number of physiologic functions including inflammatory regulation, decreased in persons exposed to secondhand smoke, an effect also found in active smokers. Two studies suggest that there may be an enhanced systemic inflammatory and antibody response to secondhand smoke exposure. Similarly, one human study and one animal study provide complementary evidence that secondhand smoke exposure may enhance antibody responses to allergens. Two other investigations provide evidence that short-term secondhand smoke exposure may actually result in a protective physiologic response based on a decrease in epithelial permeability in the nose and alveoli. Another study paired variable effects with nasal mucociliary clearance. The physiologic responses to secondhand smoke exposure were examined by measuring lung function in healthy persons and in patients with asthma. These studies documented inconsistent results, but the small number of participants and the types of exposures may not accurately reflect secondhand smoke exposure in the “real” world. Despite these limitations, available evidence suggests that some people, regardless of whether they are healthy or have asthma, experience a short-term decline in lung function from secondhand smoke exposures.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Odor and Irritation
Secondhand smoke contains compounds such as pyridine that produce unpleasant odors (NCI 1999), and other agents such as particles, nicotine, acrolein, and formaldehyde, which may cause mucosal irritation (Lee et al. 1993). The topics of odor, odor annoyance, and mucosal irritation from secondhand smoke were reviewed in the 1986 Surgeon General’s report (USDHHS 1986), in the 1986 NRC report (1986), and by Samet and colleagues (1991). Controlled chamber studies (USDHHS 1986; NCI 1999) and epidemiologic studies (USDHHS 1986) have assessed the association of these symptoms with secondhand smoke exposure. The 1986 Surgeon General’s report reviewed results of 13 experimental studies and 5 field studies. The conclusions from that review have remained consistent with subsequent reviews of the topic (Table 9.1). In addition to the level of secondhand smoke exposure, other factors that may determine an odor response to secondhand smoke include the age of the exposed person as it relates to olfactory acuity and visual contact with the smoker (Moschandreas and Relwani 1992), and individual traits such as annoyance thresholds and coping styles (Winneke and Neuf 1996). Limited data suggest that olfactory acuity decreases with age, and seeing a smoker increases the perceived odor intensity and annoyance of secondhand smoke (Moschandreas and Relwani 1992). Although these factors are relevant to designing and interpreting studies of odor responses to secondhand smoke, available studies provide little information on these factors. Both experimental (Bascom et al. 1991, 1996; Willes et al. 1992, 1998; Nowak et al. 1997a) and observational studies (Cummings et al. 1991; Norback and Edling 1991; Ng and Tan 1994) have assessed nasal symptoms (e.g., congestion, excessive secretions, or sneezing) as measures of upper respiratory tract irritation. In a survey of 77 healthy, nonsmoking adults 18 through 45 years of age, Bascom and colleagues (1991) found that 34 percent reported one or more nasal symptoms following secondhand smoke exposure. Allergen sensitivity, measured by skin-prick testing in 21 persons, was more frequent among secondhand smoke-sensitive persons (70 percent) compared with persons not sensitive to secondhand smoke (27 percent). Bascom and colleagues (1991) then exposed 10 sensitive and 11 persons not sensitive to secondhand smoke (45 ppm of CO for
15 minutes) in a chamber; significant increases in nasal secretions and nose-throat irritation were reported by both groups. Only the secondhand smoke-sensitive persons reported significant increases in nasal congestion, headache, and cough. In a subsequent investigation, Bascom and colleagues (1996) examined exposure-response relationships between secondhand smoke exposure and nasal symptoms among 13 persons with a history of secondhand smoke sensitivity and 16 persons without secondhand smoke sensitivity. Compared with no exposure, the lowest level of secondhand smoke exposure at 1 ppm of CO was associated with a significant increase in selected symptoms (eye irritation, nose irritation, and odor perception) reported by both groups. After the exposure, three of the nine symptoms (headache, eye irritation, and odor perception) increased significantly among persons sensitive to secondhand smoke compared with those who were not sensitive. Nasal congestion, increased nasal secretions, and cough increased significantly in both groups at 15 ppm of CO. Nowak and colleagues (1997a) exposed 10 persons with mild asthma to secondhand smoke (22.4 ± 1.2 ppm of CO) in a chamber and measured nose and mouth symptoms (dry nose, running nose, blocked nose, dry mouth, and mucus accumulation). Three hours of exposure produced increases in nose and mouth symptoms. The 1986 Surgeon General’s report reviewed five cross-sectional studies that described the prevalence of annoyance and symptoms of irritation associated with secondhand smoke exposure, but only one study included an unexposed comparison group (USDHHS 1986). The main indicators of annoyance and irritation were self-reported annoyances (e.g., disturbed by tobacco smoke, poor air quality, frustration, and hostility) and symptoms (e.g., eye, nose, and throat irritation; rhinorrhea; headache; fatigue; nausea; dizziness; and wheeze). Since that report, a limited number of new observational studies have specifically examined odor annoyance and nasal irritation associated with secondhand smoke exposure (Cummings et al. 1991; Ng and Tan 1994). A larger number of investigations with conflicting results examined the role of secondhand smoke in building-related illnesses that included irritation of the skin and mucous membranes of the eyes, nose, and throat; headache; fatigue; and difficulty concentrating (Norback and Edling 1991;
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Menzies and Bourbeau 1997). The inconsistent findings in these studies may be explained by several methodologic challenges (Menzies and Bourbeau 1997) that severely compromise the usefulness of examining the role of indoor secondhand smoke exposures at work, specifically in associations with odor annoyance and nasal irritation. These challenges include the multifactorial basis of building-related symptoms and illnesses, the potential for multiple pollutants to contribute to symptom risk, and limitations of the designs of many of the epidemiologic studies on this issue. Therefore, there is no further discussion of secondhand smoke and nonspecific building-related illnesses in this chapter. Cummings and colleagues (1991) conducted a cross-sectional survey of 723 volunteers aged 18 through 84 years who attended a free cancer screening at a cancer center in New York. Overall, a high proportion of lifetime nonsmokers reported being bothered by tobacco smoke, with the highest rates among people who were atopic (81 percent) or who had a history of a respiratory illness (82 percent), compared with all others (74 percent). A similar pattern was found for reports of nose irritation (54 percent among those who were atopic, 48 percent among those who had a history of respiratory illnesses, and 30 percent among all others) and sneezing (23 percent among those who were atopic, 17 percent among those who had a history of respiratory illnesses, and 12 percent among all others) associated with secondhand smoke exposure. To assess risk factors for allergic rhinitis in Singapore, Ng and Tan (1994) conducted a population-based cross-sectional study of 2,868 adults aged 20 through 74 years. Overall, 4.5 percent of the participants had allergic rhinitis defined by self-reports during the previous year of usual nasal blockage and discharge apart from colds or the flu, provoked by allergens, with or without conjunctivitis. Compared with having no household exposure to smokers, exposure to one or more light smokers was not associated with allergic rhinitis (odds ratio [OR] = 0.96 [95 percent confidence interval (CI), 0.6–1.53]), whereas exposure to one or more heavy smokers was weakly associated with allergic rhinitis (OR = 1.43 [95 percent CI, 0.94–2.18]).
Evidence Synthesis Prior reviews have led to the conclusion that secondhand smoke exposure causes odor
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annoyance (Table 9.1). Coherent and consistent results from experimental and observational studies provide a strong basis for inferring a causal link between secondhand smoke exposure and odor annoyance and symptoms of nasal irritation. Moreover, experimental studies established both the temporal and dose-response relationships of odor annoyance and nasal irritation with secondhand smoke exposure. The intensity of odor annoyance and nasal irritation increased with increased levels of secondhand smoke exposure. In addition, persons with nasal allergies or a history of respiratory illnesses may be more susceptible to nasal irritation from secondhand smoke exposure compared with persons without these conditions. However, because few observational studies have included unexposed comparison groups, the strength of the association is more difficult to evaluate. Moreover, methodologic limitations, including exposure misclassification and nonspecificity of symptoms, may result in underestimates of the strength of the association.
Conclusions 1.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure and odor annoyance.
2.
The evidence is sufficient to infer a causal relationship between secondhand smoke exposure and nasal irritation.
3.
The evidence is suggestive but not sufficient to conclude that persons with nasal allergies or a history of respiratory illnesses are more susceptible to developing nasal irritation from secondhand smoke exposure.
Implications Although the symptoms of odor annoyance and nasal irritation may appear to be minor adverse health consequences, they have the potential to negatively affect daily functioning and quality of life. For example, studies have documented for a long time the potential of secondhand smoke to cause annoyance and irritation. This acute and adverse response is possibly only avoidable in smoke-free environments.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Respiratory Symptoms
The 1986 Surgeon General’s report included only a few studies on secondhand smoke exposure and respiratory symptoms in adults (Table 9.1). Although a number of investigations since 1986 have studied this relationship, conclusions from major reviews of this topic (Table 9.1) have been inconsistent. The sources of information on respiratory symptoms include experimental studies of acute exposures and symptoms (Table 9.2) and observational studies of chronic symptoms (Table 9.3).
without asthma (Bascom et al. 1996) strengthens the argument for a causal link between secondhand smoke exposure and acute respiratory symptoms. However, the generalizability of these results may be questioned because of the small numbers in the studies and the use of volunteers. Persons who volunteer may do so because of a perceived sensitivity to secondhand smoke, and may thus overreport symptoms compared with persons randomly selected from the general population.
Experimental Studies
Observational Studies
Persons with and without asthma were exposed to secondhand smoke in exposure chambers in efforts to characterize physiologic responses (see “Biologic Basis” earlier in this chapter) and acute symptom responses to secondhand smoke (Table 9.2). Most of the studies are small and provide limited information as to how the participants were recruited. Some were recruited through hospital-based asthma and allergy clinics (Shephard et al. 1979; Danuser et al. 1993) and others through advertisements to students (Bascom et al. 1996). Out of 10 studies (Table 9.2), 5 were restricted to persons with asthma and did not have a control group (Knight and Breslin 1985; Wiedemann et al. 1986; Stankus et al. 1988; Magnussen et al. 1992; Nowak et al. 1997a), 3 included persons with asthma and a control group without asthma (Shephard et al. 1979; Dahms et al. 1981; Danuser et al. 1993), and 2 were limited to persons without asthma (Bascom et al. 1991, 1996). The investigations using only persons with asthma and no control group provided only limited information on the occurrence of respiratory symptoms with secondhand smoke exposure. In one of these investigations (Magnussen et al. 1992), there was no difference in respiratory symptom responses between the sham and the secondhand smoke exposures. In the three studies that included persons with asthma and controls without asthma, results suggest that acute respiratory symptoms occur with a similar or slightly increased frequency with secondhand smoke exposure among persons with mild to moderate asthma compared with healthy controls. Moreover, the doseresponse relationship that was found in persons with asthma (Danuser et al. 1993) and in healthy persons
Chronic respiratory symptoms of cough, phlegm, wheeze, and dyspnea (difficulty breathing) associated with secondhand smoke exposure have been investigated largely in cross-sectional studies; there have been only a few longitudinal investigations (Schwartz and Zeger 1990; Robbins et al. 1993; Jaakkola et al. 1996). Table 9.3 describes these studies and their results. The documented symptoms are heterogeneous in etiology and vary with gender, age, associated diseases (e.g., allergy or respiratory illness), and smoking status (e.g., never versus former) (Cummings et al. 1991). For example, cough may result from irritation or inflammation of the upper and lower respiratory tract, but it may also be caused by gastroesophageal reflux disease. Similarly, dyspnea is often attributed to a respiratory disease, but it may also result from a cardiovascular disease. It is not feasible in observational studies to separate respiratory from nonrespiratory causes of these symptoms. However, variations in the distribution of the determinants of these symptoms among populations may contribute in part to the inconsistent findings. Moreover, numerous other environmental factors such as outdoor and indoor air pollution, allergens, and occupational exposures may vary among populations and may cause respiratory symptoms. Studies evaluating the relationship between secondhand smoke exposure and respiratory symptoms have not consistently included some of these other environmental factors (Table 9.3). Although not all of the available observational studies have found significant associations of secondhand smoke exposure with cough (Table 9.3) (Schwartz and Zeger 1990; Jaakkola et al. 1996; Zhang et al. 1999), the point estimates of risk with exposure
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Table 9.2
Chamber studies of exposure to secondhand smoke and acute respiratory symptoms
Study
Population
Exposure
Shephard et al. 1979
14 patients with mild to moderate asthma Aged 19–65 years
Average CO* = 24 ppm†, 2 hours
10 persons with asthma (5 smokesensitive) Aged 18–26 years 10 healthy controls Aged 24–53 years
Comments
Persons with asthma (%) Wheeze Chest tightness Cough Dyspnea
No controls without asthma Dahms et al. 1981
Symptoms
36 43 36 21
Normal controls (%) Rest Exercise 10 0 5 0 45 58 15 17
Regular asthma medications were not withheld before the test in 13 out of 14 patients; 1 or more may have been smokers; normal controls were from another study
Estimated CO = 15– 20 ppm (based on carboxyhemoglobin levels), 1 hour
All had similar degrees of eye and nasal irritation
Exposure levels were not measured directly; no individual data were reported
Knight and Breslin 1985
6 patients with mild to moderate asthma
CO level was not determined, 1 hour
Wheeze was reported by 33% of participants; increase in chest tightness was reported by 50% of participants
Participants and methods were not well described
Wiedemann et al. 1986
9 asymptomatic persons with asthma Aged 19–30 years
CO = 40–50 ppm, 1 hour
Cough was reported by 33% of participants
None
Stankus et al. 1988
21 smokesensitive persons with asthma Aged 21–50 years
Average CO = 8.7 ppm, 2 hours; if no change occurred in lung function, exposure was then increased to average CO = 13.3 ppm, 2 hours
Cough, chest tightness, and dyspnea were reported by 7 participants who had a >20% decline in forced expiratory volume in 1 second
No information was provided on symptoms among those who did not have a decline in lung function
Bascom et al. 1991
21 healthy nonsmokers
45 ppm CO for 15 minutes
Cough and chest tightness were greater among sensitive participants
11 not sensitive and 10 sensitive participants by questionnaire
Magnussen et al. 1992
18 persons with mild to moderate asthma Aged 21–51 years
Average CO = 20.5 ppm, 1 hour
Cough and chest tightness symptom scores were not significantly different for the secondhand smoke exposure compared with the sham exposure
None
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The Health Consequences of Involuntary Exposure to Tobacco Smoke
Table 9.2
Continued
Study
Population
Exposure
Symptoms
Comments
Danuser et al. 1993
10 persons with hyperreactive airways (5 asthma, 3 suggestive of asthma) Aged 24–51 years
Average CO = 0, 2, 4, 8, 16, and 32 ppm; 2 minutes at each level
Over the entire exposure, 7 hyperreactive persons and 6 healthy controls reported cough, chest tightness, or dyspnea
Small likelihood of “suggestibility” because of the mode of secondhand smoke delivery; symptom severity was mild for both groups, even at the highest level of exposure; there was a dose-response relationship between symptom scores and CO levels
10 healthy controls Aged 24–52 years Bascom et al. 1996
29 healthy nonsmokers Aged 22–31 years
Average CO = 0, 1, 5, and 15 ppm; 2 hours at each level
Cough and chest tightness scores increased with increasing CO levels
None
Nowak et al. 1997a
10 persons with mild asthma Aged 22–29 years
Average CO = 22.4 ppm, 3 hours
Throat and chest symptom scores (breathing difficulty, chest tightness, dyspnea, and chest pain) significantly increased with exposure
Unable to determine an effect on chest symptoms alone because throat and chest symptoms were combined
*CO = Carbon monoxide. † ppm = Parts per million.
compared with no exposure have been greater than one (Schwartz and Zeger 1990; White et al. 1991; Pope and Xu 1993; Lam et al. 1995; Jaakkola et al. 1996; Zhang et al. 1999). The studies range in size and in the precision of their estimates; however, many did not consider other factors (e.g., other indoor and outdoor pollutants, allergy, asthma, and occupation) that may influence the occurrence of cough. Pope and Xu (1993) highlight the complexity of investigating the relationship between secondhand smoke exposure and respiratory symptoms. Among 973 Chinese women aged 20 through 40 years who had never smoked, there was a dose-response relationship between cough and the number of smokers at home (OR = 1.02 for 1 smoker and 1.87 for ≥2 smokers). In addition, the combination of heating with coal, a source of indoor smoke, and two or more smokers in the home was associated with a further increase in the occurrence of cough (OR = 3.07). This finding indicates the potential for a joint effect of secondhand smoke exposure with other environmental exposures. Similarly, the findings of Cummings and colleagues (1991) (Table 9.3) suggest that associated illnesses, such as allergy and respiratory illnesses, increase the
occurrence of cough with secondhand smoke exposure compared with persons without these conditions. Phlegm production is a symptom often associated with cough, and findings for this symptom are similar to those for cough (Table 9.3) (Schwartz and Zeger 1990; White et al. 1991; Pope and Xu 1993; Lam et al. 1995; Jaakkola et al. 1996; Zhang et al. 1999). The point estimates for the association between secondhand smoke exposure and phlegm production have ranged from 0.69 to 8.3 (Table 9.3). Out of five studies that examined the association between secondhand smoke exposure and wheeze, two found significant associations (Leuenberger et al. 1994; Baker and Henderson 1999) and three did not (Pope and Xu 1993; Jaakkola et al. 1996; Zhang et al. 1999). The point estimates ranged from 0.62 to 1.94 (Table 9.3). Although Leuenberger and colleagues (1994) found a dose-response relationship between wheeze and the amount of the exposure, Pope and Xu (1993) did not. Moreover, Pope and Xu (1993) did not find an interaction for wheeze between the number of smokers at home and the use of coal heat as they did find for cough and phlegm.
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Table 9.3
Observational studies of exposure to secondhand smoke and chronic respiratory symptoms Period of study
Study
Population
Findings
Comments
Schwartz and Zeger 1990
Approximately 100 nursing students Los Angeles
Follow-up for up to 3 years
Exposure Roommate smoked
Cummings et al. 1991
723 volunteers attending a free cancer screening, 56% women, 90% White Aged 18–84 years United States
1986
Lifetime nonsmokers Atopic Respiratory All Symptom (%) illness (%) Others (%) Bothered by tobacco 81 82 74 smoke Watery eyes 57 60 43 Nose irritation 54 48 30 Cough episodes 36 37 21 Sore throat 23 19 13 Sneezing 23 17 12
Phlegm OR* (95% CI†) 1.41 (1.08–1.85)
There was no association with an increased risk of cough None
Former smokers Atopic Respiratory All Symptom (%) illness (%) Others (%) Bothered by tobacco 68 77 65 smoke Watery eyes 48 39 35 Nose irritation 38 40 21 Cough episodes 32 25 17 Sore throat 24 14 12 Sneezing 14 17 10 Norback and Edling 1991
White et al. 1991
550
466 persons from the general population Aged 20–65 years Sweden
1989
40 persons exposed to secondhand smoke at work and 40 nonsmokers evaluated as part of a fitness profile Aged 38–65 years United States
1979–1985
Chapter 9
Symptom Eye irratation or swollen eyelids
Adjusted OR (95% CI) 1.3 (0.8–2.2)
Nasal catarrh, blockedup nose, dry/sore throat, irritative cough Symptom Cough Phlegm Breathlessness Colds
1.1 (0.7–1.8)
Secondhand smoke exposure at work (OR) 7.0 8.3 11.8 22.7
Secondhand smoke exposure at work
None
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Table 9.3
Continued
Study
Population
Pope and Xu 1993
973 lifetime nonsmoking women Aged 20–40 years China
Period of study 1992
Findings
Comments
Symptom Chest illness Cough Phlegm Dyspnea Wheeze
No coal heat 1 smoker in home ≥2 smokers in home 0.98 (0.50–1.94) NR‡ 1.02 (0.60–1.75) 1.87 (0.71–4.88) 1.43 (0.85–2.40) 2.07 (0.85–5.01) 1.17 (0.61–2.25) 1.46 (0.39–5.52) 0.93 (0.50–1.75) 1.00 (0.27–3.71)
Symptom Chest illness Cough Phlegm Dyspnea Wheeze
Coal heat 1 smoker in home ≥2 smokers in home 1.57 (0.74–1.39) 3.79 (1.28–11.2) 1.03 (0.97–1.10) 3.07 (1.23–7.65) 1.89 (1.07–3.35) 3.64 (1.56–8.52) 1.88 (0.93–3.81) 3.55 (1.2–10.5) 1.20 (0.60–2.41) 1.07 (0.29–4.00)
Adjusted for age, job title, and mill employment
Robbins et al. 1993
3,914 participants Aged ≥25 years at completion of baseline questionnaire United States
Baseline: 1977 Follow-up: 1987
Obstructive airway disease symptoms Age of participant at exposure OR (95% CI) Childhood only 1.09 (0.69–1.79) Adulthood only 1.28 (0.90–1.79) Childhood and adulthood 1.72 (1.31–2.23)
None
Leuenberger et al. 1994
4,197 lifetime nonsmokers Aged 18–60 years Switzerland
NR
Symptom Wheeze apart from colds Dyspnea on exertion Bronchitis
There was a positive dose-response relationship
Ng and Tan 1994
2,868 participants Aged 20–74 years Singapore
1989
Unadjusted OR (95% CI) Secondhand smoke exposure Allergic rhinitis ≥1 light smoker 0.96 (0.60–1.53) ≥1 heavy smoker 1.43 (0.94–2.18)
None
Lam et al. 1995
2,558 lifetime nonsmoking women Hong Kong
1989
Symptom Sore throat Cough, morning Cough, evening Phlegm, morning Phlegm, day or night Phlegm for 3 months Any symptom
Exposure to husband’s smoking; adjusted for area of residence, education, type of housing, others smoking at home, use of fuel, and use of incense/ mosquito coil
OR (95% CI) 1.94 (1.39–2.70) 1.45 (1.20–1.76) 1.59 (1.17–2.15)
Adjusted OR (95% CI) 1.20 (0.89–1.64) 1.72 (1.06–2.79) 1.61 (0.97–2.68) 1.43 (1.04–1.98) 1.67 (1.11–2.50) 1.27 (0.82–1.95) 1.26 (0.99–1.59)
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Table 9.3
Continued Period of study
Study
Population
Findings
Comments
Jaakkola et al. 1996
117 lifetime nonsmokers Aged 15–40 years Montreal, Canada
Baseline: 1980– 1981 Follow-up: 1988– 1989
Per 10 cigarettes of secondhand smoke exposure/day Symptom OR (95% CI) Wheeze 1.15 (0.64–2.06) Dyspnea 2.37 (1.25–4.51) Cough 1.55 (0.61–3.90) Phlegm 0.69 (0.21–2.26) Any symptom 1.48 (0.88–2.49)
None
Baker and Henderson 1999
1,954 randomly selected women who gave birth England
1991–1992
Wheeze Secondhand smoke OR (95% CI) exposure Partner smoked 1.73 (1.05–2.85)
None
Zhang et al. 1999
4,108 adults China
1988
Women exposed to secondhand smoke by ≥1 household member Symptom OR (95% CI) Cough 1.18 (0.95–1.46) Phlegm 0.96 (0.75–1.24) Wheeze 0.62 (0.44–0.87)
None
Trinder et al. 2000
2,996 randomly selected patients from two general practices Aged ≥16 years England
NR
Reported severe respiratory symptoms Smoking status OR (95% CI) Involuntary smokers 1.4 (1.0–1.8) Former smokers 1.5 (1.2–1.8) Current smokers 2.9 (2.3–3.6)
10 respiratory symptoms were reported during the previous month
*OR = Odds ratio. † CI = Confidence interval. ‡ NR = Data were not reported.
Although dyspnea is nonspecific with many causes, studies have consistently associated it with secondhand smoke exposure (White et al. 1991; Pope and Xu 1993; Leuenberger et al. 1994; Jaakkola et al. 1996). Leuenberger and colleagues (1994) also found a dose-response relationship between secondhand smoke exposure and dyspnea. In addition to specific respiratory symptoms, several investigators have examined the association between secondhand smoke exposure and the presence of any respiratory symptom (Robbins et al. 1993; Lam et al. 1995; Jaakkola et al. 1996), the severity of respiratory symptoms (Trinder et al. 2000), chest illness (Pope and Xu 1993), or colds (White et al. 1991). Although not statistically significant, the magnitudes of the associations between secondhand smoke exposure and having any respiratory symptom have been
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similar and the relative risk (RR) estimates are above one (Lam et al. 1995; Jaakkola et al. 1996). Among 2,996 randomly selected patients from general practices in England, Trinder and colleagues (2000) found an association between secondhand smoke exposure and reports of severe respiratory symptoms (OR = 1.4 [95 percent CI, 1.0–1.8]).
Evidence Synthesis Since the 1986 Surgeon General’s report (USDHHS 1986), there have been numerous experimental and observational studies on the relationship between secondhand smoke exposure and acute and chronic respiratory symptoms, respectively. Overall, the experimental studies provide consistent evidence
The Health Consequences of Involuntary Exposure to Tobacco Smoke
for a link between secondhand smoke exposure and acute respiratory symptoms. Furthermore, these studies document that secondhand smoke exposure produced symptoms that meet the criterion of temporality and weigh against the possibility that secondhand smoke exposure leads to a heightened perception of already present symptoms. A limited number of investigations have also documented dose-response relationships. However, the experimental studies are limited by the small number of participants and by the use of volunteers. Of the chronic respiratory symptoms, cough and dyspnea have been most consistently associated with secondhand smoke exposure in the observational studies. In contrast, this association has been less consistently observed for phlegm and wheeze. Partly because exposures and symptoms often are misclassified in observational studies, the magnitude of the association with chronic respiratory symptoms probably has been underestimated, with weak ORs generally less than 2.0. Little information is available on the temporal or dose-response relationships between chronic symptoms and secondhand smoke exposure.
Conclusions 1.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and acute respiratory symptoms including cough, wheeze, chest tightness, and difficulty breathing among persons with asthma.
2.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and acute respiratory symptoms including cough, wheeze, chest tightness, and difficulty breathing among healthy persons.
3.
The evidence is suggestive but not sufficient to infer a causal relationship between secondhand smoke exposure and chronic respiratory symptoms.
Implications These new conclusions strengthen prior statements with regard to respiratory symptoms and secondhand smoke exposure. Because respiratory symptoms are common and may adversely affect functional status, quality of life, and the use of health care resources, the relationship between respiratory symptoms and secondhand smoke exposure has substantial relevance to clinical care, to public health, and to the general comfort of nonsmokers. Eliminating or reducing secondhand smoke exposure will likely decrease the occurrence of acute respiratory symptoms. However, further research on the relationship between secondhand smoke exposure and chronic respiratory symptoms needs to overcome the methodologic limitations of the available observational studies. To overcome these limitations, future studies should be population-based, longitudinal, restricted to lifetime nonsmokers, and should have sufficient power to comprehensively address confounding factors.
Lung Function
Studies of volunteers exposed experimentally to secondhand smoke have examined short-term effects on lung function. Observational studies of real-world exposures have addressed the long-term effects. Acute effects of secondhand smoke exposure on lung function have been examined primarily in patients with mild asthma (see “Biologic Basis” earlier in this chapter). As stated previously, the Cal/EPA report reviewed results from 10 experimental studies of persons with asthma and concluded that despite constraints in interpreting the results of the chamber studies, “they do suggest that there is likely to
be a subpopulation of asthmatics who are especially susceptible to ETS exposure” (NCI 1999, p. 203). Nowak and colleagues (1997b) subsequently provided further support for this conclusion by finding greater average declines in FEV1 levels compared with baseline FEV1 levels after a secondhand smoke versus a sham exposure. Nowak and colleagues (1997a) found no changes in FEV1 levels, but the small number of participants severely limited the statistical power. Bascom and colleagues (1991) recruited 77 healthy nonsmoking adults and exposed 21 to sidestream smoke for 15 minutes at a CO concentration of 45 ppm. In the
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11 participants not sensitive to secondhand smoke, spirometric test results before and after exposure were unchanged; small, but statistically significant, effects were found in the 10 participants sensitive to secondhand smoke. In the only study of the dose-response relationship between secondhand smoke exposure and lung function, Danuser and colleagues (1993) exposed 10 persons with hyperreactive airways and 10 healthy persons matched for age and gender to five increasing levels of secondhand smoke at 2, 4, 8, 16, and 32 ppm of CO for two minutes each. Among participants with hyperreactive airways, the FEV1 fell an average of 6.5 percent after a 2 ppm exposure of CO, and fell further with higher levels of exposure (-5.6 percent at 4 ppm of CO, -7.1 percent at 8 ppm, -8.2 percent at 16 ppm, and -8.7 percent at 32 ppm). The FEV1 level did not drop among the healthy participants at any level of exposure. Chronic effects of secondhand smoke exposure on lung function have been examined primarily in cross-sectional studies (Trédaniel et al. 1994; Coultas 1998; Carey et al. 1999; Chen et al. 2001) and in a few cohort studies (Jaakkola et al. 1995; Abbey et al. 1998; Carey et al. 1999). Carey and colleagues (1999) published a meta-analysis of 15 cross-sectional studies and found a 1.7 percent mean deficit (95 percent CI, -2.8 to -0.6) in the FEV1 level associated with secondhand smoke exposure. In addition, they conducted a cross-sectional investigation of secondhand smoke exposure, classified by salivary cotinine and FEV1 levels, among 1,623 British adults aged 18 through 73 years (Carey et al. 1999). Comparing the top with the bottom quintiles of cotinine levels among lifetime nonsmokers, the researchers observed small decrements in FEV1 levels that were larger in men than in women, -90 milliliters (mL) (95 percent CI, -276–96) and -61 mL (95 percent CI, -154–32), respectively. Chen and colleagues (2001) examined the effects of secondhand smoke exposure among 301 Scottish lifetime nonsmokers and found an inverse dose-response relationship between self-reported levels of secondhand smoke exposure at work (“none, little, some, a lot”) and FEV1 levels. Compared with persons who were unexposed at work, “a lot” (Chen et al. 2001, p. 564 [the term was not defined by the authors]) of secondhand smoke exposure was significantly associated with a lower FEV1 (-254 mL [95 percent CI, -420 to -84]). Only three cohort studies have assessed secondhand smoke exposure and lung function (Jaakkola et al. 1995; Abbey et al. 1998; Carey et al. 1999). In 1980, Canadian researchers enrolled 117 lifetime nonsmokers from Montreal aged 15 through 40 years
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and followed them through 1989 (Jaakkola et al. 1995). The investigators assessed cumulative exposures at enrollment, exposures at follow-up, and exposures at home and at work during the three days before completing the questionnaire. During the eight years of follow-up, the researchers did not find a significant association between secondhand smoke exposure and the rates of decline of FEV1 and forced expiratory flow between 25 and 75 percent of the forced vital capacity (FVC). Researchers also did not find significant associations for cumulative secondhand smoke exposures up to the start of the study. In a study of the effects of ambient air pollution on lung function, Abbey and colleagues (1998) followed 1,391 lifetime nonsmokers and former smokers from California for 16 years who were 25 years of age and older at enrollment in 1977. Secondhand smoke exposure was assessed from self-reports of the number of years the participants had lived or worked with a smoker. Among women, a small but nonsignificant decline in the ratio of FEV1 to FVC (-0.2 percent [95 percent CI, -0.5–0.1]) was associated with living with a smoker for 10 years through 1993. A similar decline was observed for men who had worked with a smoker for 10 years through 1993 (-0.5 percent [95 percent CI, -1.2–0.1]). Moreover, although quantitative data were not reported, the authors stated that concomitant secondhand smoke exposures (≥1 hour per day for at least one year at work or at home in 1987, 1992, or 1993) resulted in stronger effects of particulate pollution on lung function in men but not in women. In a population-based sample from Britain in 1984 and 1985, Carey and colleagues (1999) enrolled 1,623 lifetime nonsmokers and former smokers aged 18 through 73 years and followed them for 7 years. Living with a smoker at enrollment and at follow-up was not associated with an accelerated FEV1 decline (25 mL [95 percent CI, -20–70]).
Evidence Synthesis The effects of acute and chronic secondhand smoke exposure on lung function have been examined in experimental and observational studies, respectively. In experimental studies, some persons with asthma consistently had a small decline in the FEV1 following secondhand smoke exposure. Small decrements in lung function are coherent with the far greater impairment of lung function observed with active smoking (USDHHS 2004). However, evidence for the dose-response relationship between secondhand smoke exposure and the FEV1 decline is
The Health Consequences of Involuntary Exposure to Tobacco Smoke
limited. In the only relevant study, a dose-response relationship was not found (Danuser et al. 1993). The available evidence from experimental studies on the relationship between acute exposure to secondhand smoke and a decline in the FEV1 suggests that the subgroup of persons with asthma is at risk from secondhand smoke. The cross-sectional studies documented an association between chronic secondhand smoke exposure and a small decrement in lung function (Carey et al. 1999). However, these findings provide limited support for a causal relationship because the temporality between exposure and lung function decrement cannot be established with this study design, and most of these studies lack information on dose-response relationships. Although the small effect in these observational studies is coherent with larger decrements in lung function level associated with active smoking (USDHHS 2004), the small overall effect may actually reflect a larger decrement in a susceptible subpopulation. However, this hypothesis has received limited attention (Chen et al. 2001). The lack of an effect of secondhand smoke exposure on lung function decline in a small number of longitudinal studies further suggests that chronic secondhand smoke exposure may have little or no effect on lung function in the general population, but the effect in possibly susceptible subgroups has not been examined.
Conclusions 1.
The evidence is suggestive but not sufficient to infer a causal relationship between short-term secondhand smoke exposure and an acute decline in lung function in persons with asthma.
2.
The evidence is inadequate to infer the presence or absence of a causal relationship between short-term secondhand smoke exposure and an acute decline in lung function in healthy persons.
3.
The evidence is suggestive but not sufficient to infer a causal relationship between chronic secondhand smoke exposure and a small decrement in lung function in the general population.
4.
The evidence is inadequate to infer the presence or absence of a causal relationship between chronic secondhand smoke exposure and an accelerated decline in lung function.
Implications Although acute secondhand smoke exposure is associated with small decrements in lung function among persons with asthma, the magnitude of the effect is, on average, small. Moreover, the characteristics of a one-time exposure in the experimental studies do not reflect a real-life exposure repeated over months and years. Future experimental studies of the effects of secondhand smoke exposure need to create better simulations of real-world situations, but these studies cannot address chronic effects on lung function, functional status, quality of life, and health care utilization. Experimental and observational studies document small decrements in lung function. These findings provide a rationale for conducting observational studies to examine the larger effects of secondhand smoke exposure on lung function in potentially susceptible subgroups, such as persons with asthma (see “Respiratory Diseases” in the next section).
Respiratory Diseases
Asthma Asthma is a heterogenous and complex disorder characterized by chronic airway inflammation and reversible airflow obstruction (National Heart, Lung, and Blood Institute 1997; Floreani and Rennard 1999). Since the 1992 U.S. EPA risk assessment report (USEPA 1992), a number of published studies have
examined the role of involuntary smoking in causing asthma (etiologic) and in exacerbating asthma (morbidity) among adults. These studies have been reviewed for this report (Coultas 1998; NCI 1999; Weiss et al. 1999). The aim of the etiologic studies has been to determine the association between involuntary smoking and the new diagnosis of asthma among adults. However, because asthma often begins during
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infancy or childhood (Chapter 6, Respiratory Effects in Children from Exposure to Secondhand Smoke), it may be difficult to truly establish adult-onset asthma and distinguish it from a failure to recall the onset of childhood asthma (see the next section). In contrast to studies of causation, morbidity studies have examined the role of involuntary smoking in causing symptoms, worsening lung function, causing or increasing the use of medication, increasing health care utilization, and worsening the quality of life in persons with asthma. Etiologic Studies Asthma is diagnosed by six years of age in approximately 80 percent of the cases (Yunginger et al. 1992), and available data suggest that by early adulthood, 30 to 50 percent of persons with childhood asthma become asymptomatic (Barbee and Murphy 1998). In etiologic investigations of adult-onset asthma, it may thus be difficult to differentiate adultonset asthma from childhood asthma that is recurrent in adulthood because of exposure to secondhand smoke or to another environmental agent (Weiss et al. 1999). Investigation of the relationship between secondhand smoke exposure and adult-onset asthma may be further complicated by the “healthy smoker effect” (Weiss et al. 1999, p. 891), that is, the selfselection of persons with better respiratory health to be active smokers compared with those who remain nonsmokers. This effect might explain the avoidance of exposure to secondhand smoke by some persons susceptible to the development of asthma. The resulting bias would tend to underestimate the association between secondhand smoke exposure and adult-onset asthma. Greer and colleagues (1993) examined the association between workplace exposure to secondhand smoke and a new onset of asthma among a nonsmoking population of 3,577 Seventh-Day Adventists from southern California followed between 1977 and 1987. The mean age at enrollment was 56.5 years. During the 10-year follow-up period 78 participants developed asthma, and workplace exposure to secondhand smoke was a significant risk factor (RR = 1.5 [95 percent CI, 1.2–1.8]) after controlling for gender, education, a history of obstructive airway disease before 16 years of age, and ambient ozone levels. In a cross-sectional study of 4,197 lifetime nonsmoking Swiss adults 18 through 60 years of age, Leuenberger and colleagues (1994) found that self-reports of physician-diagnosed asthma were
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associated with involuntary smoking (OR = 1.39 [95 percent CI, 1.04–1.86]), defined as any secondhand smoke exposure in the past 12 months. They also found a dose-response relationship between the total number of hours of secondhand smoke exposure per day and a risk of physician-diagnosed asthma. Flodin and colleagues (1995) conducted a population-based, case-control study in Sweden that included 79 persons with adult-onset asthma, defined as the onset of symptoms consistent with asthma after 20 years of age and bronchial reactivity measured by methacholine challenge or bronchodilator responsiveness. Secondhand smoke exposure at work was associated with an increase in the risk of asthma (OR = 1.5 [95 percent CI, 0.8–2.5]) similar in magnitude to the findings of Greer and colleagues (1993) and Leuenberger and colleagues (1994). Because active cigarette smoking has been associated with an increased risk of developing occupational asthma attributable to IgE-inducing agents (Venables and Chan-Yeung 1997), and secondhand smoke exposure has been associated with higher IgE levels (Oryszczyn et al. 2000), it is plausible to hypothesize that involuntary smoking may also contribute to the development of occupational asthma in nonsmokers. Although workplace exposures to secondhand smoke have been associated with asthma among adults (Greer et al. 1993; Flodin et al. 1995), no investigations have reported on the interaction of secondhand smoke exposure at the workplace with specific occupational agents. In 1993, Hu and colleagues (1997) surveyed 1,469 young adults aged 20 through 22 years from Los Angeles and San Diego (California) to determine the prevalence of asthma in this population. Parental reports obtained in 1986 as part of a school-based smoking prevention program were used to determine exposures to secondhand smoke. Maternal and paternal smoking were associated with the young adults ever having had physician-diagnosed asthma (OR = 1.6 [95 percent CI, 1.1–2.3] and 1.3 [95 percent CI, 0.9–1.8], respectively). Similar results were found for current asthma with maternal smoking (OR = 1.6 [95 percent CI, 1.0–2.1]). Hu and colleagues (1997) also found a dose-response relationship with the amount smoked and the number of parents who smoked. The highest risk of having a physician-diagnosed asthma (OR = 2.9 [95 percent CI, 1.6–5.6]) and current asthma (OR = 3.3 [95 percent CI, 1.7–6.4]) was associated with smoking by both parents compared with smoking by neither parent.
The Health Consequences of Involuntary Exposure to Tobacco Smoke
Morbidity Studies Trédaniel and colleagues (1994) summarized results of the effects of secondhand smoke exposure on respiratory symptoms and lung function from four observational studies of patients with respiratory allergies and from five experimental studies of patients with asthma. The authors concluded that “Conflicting evidence exists on the association in asthmatic patients between ETS exposure and appearance of symptoms and functional abnormalities (including change in bronchial responsiveness)” (p. 181). Weiss and colleagues (1999) reached similar conclusions in their review of 2 observational studies and 12 experimental studies of secondhand smoke exposure and an exacerbation of asthma. Experimental Studies Results of 10 chamber studies of secondhand smoke exposure in persons with asthma were extensively reviewed in the Cal/EPA report (NCI 1999) and summarized earlier in this chapter (see “Biologic Basis” and “Lung Function”). Methodologic limitations of experimental studies examining the relationship between secondhand smoke exposure and asthma morbidity reflect the inability to replicate reallife exposure conditions and the failure of health outcome measures (e.g., symptoms or lung function) to adequately assess asthma morbidity. Consequently, observational studies provide the best evidence for assessing asthma morbidity associated with secondhand smoke exposure. Observational Studies Study designs that have been used to examine secondhand smoke exposure and asthma morbidity include population-based, cross-sectional surveys (Mannino et al. 1997); clinic-based, cross-sectional studies (Jindal et al. 1999); case-control studies (Tarlo et al. 2000); and prospective cohort studies (Jindal et al. 1994; Ostro et al. 1994; Sippel et al. 1999). In a nationally representative sample of 43,732 U.S. adults who participated in the 1991 National Health Interview Survey (NHIS), Mannino and colleagues (1997) examined the relationship between any self-reported secondhand smoke exposure during the previous two weeks and the exacerbation of any chronic respiratory disease (asthma, chronic bronchitis, emphysema, and chronic sinusitis) in the two weeks before the survey. In a multiple logistic regression model that adjusted for age, gender, race, socioeconomic status (SES), living alone, season, and region of the country, exposure
to secondhand smoke was significantly associated with the exacerbation of any chronic respiratory condition among lifetime nonsmokers (OR = 1.44 [95 percent CI, 1.07–1.95]). Jindal and colleagues (1999) measured bronchial hyperresponsiveness and bronchodilator use in a sample of 50 women with asthma aged 20 through 40 years followed at a chest clinic in India. Exposure to secondhand smoke was assessed with questions on smoking by the husband, by other family members, and by coworkers. Compared with no exposure, secondhand smoke exposure was associated with significantly greater bronchial hyperreactivity and with continuous bronchodilator use (39 percent of exposed women and 26 percent of unexposed women [p