THE HEALTH
CONSEQUENCES
OF' SMOKING

CANCER AND
CHRONIC LUNG DISEASE
IN THE WORKPLACE

a report of the Surgeon General

1985

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Serwce
Offlce on Smokrtg and Health
RockwIle, Maryland 20857


The Honorable Thanas P. O'Neill, Jr.
Speaker of the Haxx of Representatives
Washington, D.C. 20515

Dear Mr. Speaker:

  It is a pleasure to transmit to the Congress the final edition of the Surgeon
General's Report on the Health Consequences of -king, as mandated by Section 8(a)
of the Public Health Cigarette Swkinq Act of 1969. This is the Public Health
Service's 17th Repsrt cn this topic and, like earlier Reports. identifies cigarette
smoking as one of this Nation's rmst seriws public health problems.

  This Reprt, tiicb provides a detailed review of the relationship between
snaking and hazardous substances in the workplace, is particularly disturbing
because of the added health burden that mny workers carry if they smke
cigarettes.  As this Report makes clear, for sane mrkers this added burden is
substantial.  No better example exists to illustrate this interaction than the case
of asbestos wxkers.  Current scientific evidence indicates that heavily exposed
asbestos insulation rorkers who did not snake may expxienne a S-fold increase in
lung cancer caped to making, nmexpsed uxkers. Hcw?ver, if this sanrz
worker also srraked, his lurq cxcw risk is increased rrore than 5C-fold.

  Also disturbi- is the mntinued high rate of current cigarette use anrxq blue
collar wrkers cmpred to their white collar counterparts. These wxkers are mm
apt to he eqosed to dusts and other harmful substances in their wrkplace
envir-nts.  Prqfan-s to reduce wxkplace hazardous eqx~~res are helping to
offset these risks.  For the majority of rorkers who make, cigarette smking poses
a greater risk to health than does cnxpaticnal exposure. Thus, elimination of
cigarette smking zum!q such mrkers can have a profound effect on iiqxoving their
health.

  This Department has a strong commitment to prevention and health pranticn.  It
is essential that wxkplxe health prcnnticn prcqrams have a strong fans on
reducing cigarette smking mm-g enplopes to the extent possible. These efforts
can not only have an effect cn the health of the individual, but may also have a
substantial impact by reducing absenteeism on the job, thereby improving
prcductivity ant! reduciq health care costs.

  Cigarette inking is associated with an estimated $23 billion in health care
costs annually and wer $30 billiar in lost productivity and wages.  To a certain
degree we all share these cxts whether we mke or not. Prqrams that reduce
smoking, therefore, can have a benefit to all cur society.

Sincerely,

Otis R. Bcwen, M.D.
secretary

Enclosure


              w1 1%
The Honorable George Bush
President of the Senate
Washington, D.C.  20510

Gear Mz. President:

   It is a pleasure to transnit to the Congress the final edition of the Surgecm
General's Report cm the Health Cmsequems of Smkirq, as rmrdated by Section 8(a)
of the Public Health Cigarette Smking Act of 1969. This is the Public Health
Service's 17th Reprt cm this tqic and, like earlier Reports, identifies cigarette
smking as me of this Nation's mst sericus @lit health problems.

   This Repxt, which provides a detailed review of the relationship between
smking and hazardcas substames in the wxkplace, is particularly disturbing
because of the added health burden that mny workers carry if they snake
cigarettes.  As this Report ekes clear, for xme workers this added burden is
substantial.  No better example exists to illustrate this interaction than the case
of asbestos hot-kers.  Current scientific evidence indicates that heavily exposed
asbestos insulation workers who did not m&e may experiexe a 5-fold iirrease in
luq cancer canpared to ncmsmking. ncnexpxed workers. Hmever, if this same
vorker also smoked. his lung cancer risk is increased mre than SC-fold.

   Also disturbing is the nntinued high rate of current cigarette use amrg blue
collar wxkers rrrrpared to their white collar canterparts.  These wxkers are rmre
apt to be exposed to dusts and other harmful substances I" their wxkplace
envirmuwnts.  Prqram to reduce workplace hazardous exposures are helpirq to
offset these risks.  For the majority of mrkers who mke, cigarette srckirq poses
a greater risk to health than dces occupational exposure.  Thus, eliminatim of
cigarette samking amng such wxkers can have a profound effect cn improving their
health.

  This Ehzpartment has a struq mitment to prevention and health pramtim. It
is essential that workplace health prmticn prqrams have a strong focus on
reducing cigarette making amxq qloyees to the extent possible. These efforts
can not only have an effect on the health of the individual, but my also have a
substantial impact by reducing absenteeism on the job, thereby improving
productivity and reducing health care costs.

   Cigarette sawking is assoziated with an estimated $23 billion in health care
costs annually and cwer $30 billim in lost productivity and wages.  To a certain
degree we all share these costs &ether we mke or not.  Prqram.5 that reduce
mking, therefore, can have a benefit tc all cur society.

                    Sincerely,





                     Otis R. Sam, M.D.
                      secretary


FOREWORD

Over the past generation, the actions of labor unions, manage-
ment, insurers, and Government have made substantial progress in
reducing exposure to hazardous substances in the workplace. This
Report acknowledges this progress, and demonstrates clearly that
these efforts to protect the American worker must continue. There
can be no relaxation in our efforts to continue the safeguards already
in place or to seek new safeguards as new hazards are identified.

This Report also establishes that for these efforts to protect the
worker to fully succeed, these same forces of labor, management,
insurers, and Government must become equally engaged in attempts
to reduce the prevalence of cigarette smoking, particularly among
those working populations most at risk. For the majority of workers
who smoke, cigarette smoking poses a greater risk to health than
does occupational exposure.

This 1985 Report of the Surgeon General examines in greater
depth than ever before the relationships between cigarette smoking
and occupational exposures; it is a document of singular importance.
As with previous Reports, a large number of experts and scientists
recruited from both within and outside the Federal service have
participated in developing and reviewing the content of this Report. I
express here my respect and gratitude for their efforts.

Donald Ian Macdonald, M.D.
Acting Assistant Secretary
for Health

vii


PREFACE

The 1985 Report on the Health Consequences of Smoking presents
a comprehensive review of the interaction of cigarette smoking with
occupational exposures in the production of cancer and chronic lung
disease.

Cigarette smoking and its relationship to cancer and chronic
obstructive lung disease (COLD) were extensively reviewed in the
1982 and 1984 Surgeon General's Reports, respectively. In the 1982
Report, cigarette smoking was judged to be the leading cause of
cancer mortality in the United States; a causal association was found
between smoking and cancer of the lung, larynx, oral cavity, and
esophagus, and smoking was identified as a contributory factor in
the development of cancer of the bladder, kidney, and pancreas. In
1984, cigarette smoking was identified as the major cause of COLD,
which includes chronic bronchitis and emphysema, among both men
and women in the United States. The contribution of other factors in
COLD morbidity and mortality was found to be far less important
than that of cigarette smoking.

This Report examines the evidence available on the role played by
cigarette smoking and occupational exposure in the development of
cancer and chronic lung disease. Cancer and chronic lung disease are
major causes of death in the United States, accounting for well over
25 percent of all deaths annually. Cancer mortality rates have shown
a steady increase, unlike rates for the major cardiovascular diseases,
which have declined over the last two decades. Chronic lung disease,
now the fifth leading cause of mortality, has been increasing more
rapidly than other major causes of death. It is estimated that more
than 10 million Americans report suffering from these diseases.

Findings of the 1985 Report

The major overall conclusions of this Report are these:

For the majority of American workers who smoke, cigarette
smoking represents a greater cause of death and disability than
their workplace environment.

In those worksites where well-established disease outcomes
occur, smoking control and reduction in exposure to hazardous
agents are effective, compatible, and occasionally synergistic

ix


approaches to the reduction of disease risk for the individual
worker.

Smoking and occupational exposures can interact synergistically
to create more disease than the sum of the separate exposures. This
kind of interaction is exemplified by the relationship between
asbestos exposure and smoking. A study of heavily exposed asbestos
insulation workers, more than 20 years after onset of exposure,
demonstrated a fivefold increased risk for lung cancer among
nonsmoking asbestos workers compared with nonsmokers without
asbestos exposure. We know that in non-asbestos-exposed popula-
tions, smoking increases the lung cancer risk approximately tenfold.
The risk is increased more than fiftyfold if the asbestos workers also
smoke. This risk in cigarette-smoking asbestos workers is greater
than the sum of the risk of the independent exposures, .and is
approximated by multiplying the risks of the two separate expo-
sures. In other words, for those workers who both smoke and are
exposed to asbestos, the risk of developing and dying from lung
cancer is 5,000 percent greater than the risk for individuals who
neither smoke nor are exposed. Thus, the interaction of cigarette
smoking and asbestos exposure is multiplicative. For asbestos
workers, the risk of developing and dying of lung cancer increases
with an increasing number of cigarettes smoked per day and with an
increasing asbestos exposure. For example, the risk is 87 times
greater for those workers who smoke more than one pack per day.
The risk declines among workers who are able to stop smoking,
compared with the risk for those who continue to smoke. An
interaction for the production of lung cancer also exists between
cigarette smoking and the radon daughters exposure of miners,
although the exact nature of this interaction is not clear.

Both cigarette smoking and exposure to certain occupational
hazards increase the risk for chronic lung disease. These risks can
occur independently or may combine to produce a greater degree of
lung injury than would have occurred from either exposure separate-
ly. While many exposures are capable of producing chronic lung
injury, either independently or in combination, smoking appears to
be the more important exposure for the majority of U.S. workers.

Differences in Smoking Behavior Between White-Collar
Workers and Blue-Collar Workers

This Report also presents detailed findings with regard to differ-
ences in smoking prevalence between blue-collar workers and white-
collar workers. Blue-collar workers are more likely to be exposed to
workplace agents, which, in combination with their higher smoking
rates, may place these workers at considerable excess risk for cancer

X


and chronic lung disease. Although these differences exist among
both men and women, they are more pronounced among men.

The differences in the prevalence of smoking between blue-collar
workers and white-collar workers may underestimate the differences
found among specific populations of occupationally exposed workers.
As noted in this Report, individual studies among certain workers
report current smoking rates well in excess of 50 percent. In
addition, in one of the largest studies of asbestos workers, more than
80 percent of the men in the cohort had been regular cigarette
smokers during their lifetime and only 11 percent were classified as
never having smoked regularly. These differences in smoking
behavior make the control for smoking behavior an important part
of the design of studies of the relationship of occupational exposures
and cancer or chronic lung disease.

On the average, blue-collar men initiate smoking approximately
14 months earlier than white-collar men. We know from existing
studies that an earlier age of initiation is strongly correlated with
increased mortality for lung cancer and chronic lung disease as well
as for most other smoking-related diseases. Even with this earlier
age of initiation, a substantial fraction of blue-collar workers begin
smoking coincident with their entry into the workforce, and blue-
collar workers are less likely than white-collar workers to be able to
successfully quit smoking.

Smoking Control in the Workplace

The potential role of the workplace in promoting initiation and
fostering the continuation of smoking behavior represents a kind of
interaction between smoking and the workplace that may affect
large numbers of U.S. workers. It seems clear that the responsibility
for health in the workplace includes at minimum a work environ-
ment that does not promote smoking or interfere with cessation.

The worksite offers an opportunity for implementation of smoking
cessation programs. A number of studies cited in this Report found
worksite-based programs to be more successful than clinic-based
programs, probably owing to their more intensive nature and
because many employer-sponsored programs offer economic and
other incentives, thus enhancing their success.

The goal in public health, both in the worksite and outside it, is the
reduction and elimination of disease and the promotion of healthy
behavior. The content of this Report makes it clear that the
elimination of chronic lung disease and cancer from the workplace
cannot succeed without a companion effort to alter the smoking
behavior of workers. It is precisely those occupations in which the
greatest occupational hazards have existed that smoking cessation
also yields the greatest return for individual worker's health. It

xi


should be obvious that smoking cessation efforts are an adjunct to,
and not a substitute for, occupational environmental controls.
Correspondingly, a concern about workers' health that limits itself to
the control of environmental exposure levels disregards the major
health benefits of smoking cessation.

C. Everett Koop, M.D.
Surgeon General

xii


ACKNOWLEDGMENTS

This Report was prepared by the U.S. Department of Health and
Human Services under the general editorship of the Office on
Smoking and Health, Donald R. Shopland, Acting Director. Manag-
ing Editor was William R. Lynn, Acting Technical Information
Officer, Office on Smoking and Health.
Senior scientific editor was David M. Burns, M.D., Associate
Professor of Medicine, Division of Pulmonary and Critical Care
Medicine, University of California at San Diego, San Diego, Califor-
nia. Consulting scientific editors were Ellen R. Gritz, Ph.D., Asso-
ciate Director for Research, Division of Cancer Control, Jonsson
Comprehensive Cancer Center, University of California at Los
Angeles, Los Angeles, California; John H. Holbrook, M.D., Associate
Professor of Internal Medicine, University of Utah Medical Center,
Salt Lake City, Utah; and Jonathan M. Samet, M.D., Associate
Professor of Medicine, Department of Medicine, The University of
New Mexico School of Medicine, Albuquerque, New Mexico.

The following individuals prepared draft chapters or portions of
the Report.

Victor E. Archer, M.D., Clinical Professor, Rocky Mountain Center
for Occupational and Environmental Health, The University of
Utah Medical Center, Salt Lake City, Utah
Michael E. Baser, M.S., Chief, Occupational Health, Bureau of
Environmental Epidemiology and Occupational Health, New York
State Health Department, Albany, New York
David M. Burns, M.D., Associate Professor of Medicine, Divisicn of
Pulmonary and Critical Care Medicine, University of California at
San Diego, San Diego, California

David B. Coultas, M.D., Instructor of Medicine, Department of
Medicine and the New Mexico Tumor Registry, The University of
New Mexico School of Medicine, Albuquerque, New Mexico
John E. Craighead, M.D., Professor and Chairman, Department of
Pathology, The University of Vermont College of Medicine,
Burlington, Vermont

Lori A. Crane, M.P.H., Staff Research Associate, Division of Cancer
Control, Jonsson Comprehensive Cancer Center, University of
California at Los Angeles, Los Angeles, California


Philip E. Enterline, Ph.D., Department of Biostatistics, University of
Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsyl-
vania

Russell E. Glasgow, Ph.D., Research Scientist, Oregon Research
Institute, Eugene, Oregon

David F. Goldsmith, Ph.D., Visiting Assistant Professor, Department
of Internal Medicine, School of Medicine, University of California
at Davis, Davis, California

Robert C. Klesges, Ph.D., Associate Professor, Center for Applied
Psychological Research, Department of Psychology, Memphis
State University, Memphis, Tennessee
Alfred C. Marcus, Ph.D., Program Director for Evaluation, Division
of Cancer Control, Jonsson Comprehensive Cancer Center, Univer-
sity of California at Los Angeles, Los Angeles, California
Steven Markowitz, M.D., Environmental Sciences Laboratory, De-
partment of Community Medicine, The Mount Sinai Medical
Center, The Mount Sinai School of Medicine of the City University
of New York, New York, New York

James A. Merchant, M.D., Dr.P.H., Professor of Preventive and
Internal Medicine, and Director, Institute of Agricultural Medi-
cine and Occupational Health, The University of Iowa College of
Medicine, Iowa City, Iowa

Albert Miller, M.D., Clinical Professor of Medicine (Pulmonary),
Clinical Professor of Community Medicine (Environmental), and
Director, Pulmonary Function Laboratory, Division of Pulmonary
Medicine, Department of Internal Medicine, The Mount Sinai
Medical Center, The Mount Sinai School of Medicine of the City
University of New York, New York, New York
Donald P. Morgan, M.D., Ph.D., Professor, Department of Preventive
Medicine and Environmental Health, The University of Iowa
College of Medicine, Iowa City, Iowa

W.K.C. Morgan, M.D., F.R.C.P.(Edl, F.R.C.P.(C), F.A.C.P., Chest
Diseases Unit, University Hospital, London, Ontario, Canada
Brooke T. Mossman, Ph.D., Associate Professor of Pathology, and
Chairman, Cell Biology Program, Department of Pathology, The
University of Vermont College of Medicine, Burlington, Vermont
Paul R. Pomrehn, Jr., M.D., Assistant Professor, Department of
Preventive Medicine and Environmental Health, and Director,
University Occupational Health Service, The University of Iowa
College of Medicine, Iowa City, Iowa

Howard E. Rockette, Ph.D., Professor of Biostatistics, Department of
Biostatistics, University of Pittsburgh Graduate School of Public
Health, Pittsburgh, Pennsylvania

Jonathan M. Samet, M.D., M.S., Associate Professor of Medicine,
Department of Medicine, The University of New Mexico School of
Medicine, Albuquerque, New Mexico

xiv


Cecilia M. Smith, M.D., Assistant Professor of Medicine, Division of
Pulmonary and Critical Care Medicine, University of California at
San Diego, San Diego, California

Melvyn S. Tockman, M.D., Ph.D., Associate Professor of Environ-
mental Health Sciences, with joint appointments in Respiratory
Medicine and Epidemiology, Center for Occupational and Environ-
mental Health, The Johns Hopkins University, Baltimore, Mary-
land

Pamela H. Wolf, Dr.P.H., Biostatistician, Contraceptive Evaluation
Branch, Center for Population Research, National Institute of
Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland

The editors acknowledge with gratitude the following distin-
guished scientists, physicians, and others who lent their support in
the development of this Report by coordinating manuscript prepara-
tion, contributing critical reviews of the manuscript, or assisting in
other ways.

Charles A. Althafer, Assistant Director for Health Promotion and
Risk Appraisal, Office of Program Planning and Evaluation,
National Institute for Occupational Safety and Health, Centers for
Disease Control, Atlanta, Georgia

Harlan E. Amandus, Ph.D., Statistician, Division of Respiratory
Disease Studies, National Institute for Occupational Safety and
Health, Centers for Disease Control, Morgantown, West Virginia
Stephen M. Ayres, M.D., Dean, School of Medicine, Medical College
of Virginia, Richmond, Virginia

Mary A. Ballew, MS., Epidemiologist, Document Development
Branch, Division of Standards Development and Technology
Transfer, National Institute for Occupational Safety and Health,
Centers for Disease Control, Cincinnati, Ohio

Margaret R. Becklake, M.D., Professor, Departments of Medicine,
Epidemiology, and Biostatistics, McGill University, Montreal,
Quebec, Canada, on sabbatical, and Career Investigator, Medical
Research Council of Canada, Montreal, Quebec, Canada, on leave;
Professor (Honorary), Department of Community Health, Univer-
sity of the Witwatersrand, and Principal Medical Officer, National
Centre for Occupational Health, Department of Health and
Welfare, Johannesburg, South Africa

Kenneth R. Berger, M.D., Ph.D., Adjunct Assistant Professor,
Epidemiology and Preventive Medicine, University of Maryland
School of Medicine, Baltimore, Maryland
Robert Bernstein, Senior Reviewer, Document Development Branch,
Division of Standards Development and Technology Transfer,
National Institute for Occupational Safety and Health, Centers for
Disease Control, Cincinnati, Ohio

xv


Donald B. Bishop, Ph.D., Research Associate, Department of Psychol-
ogy, Washington University in St. Louis, St. Louis, Missouri
Brian A. Boehlecke, M.D., M.P.H., Associate Professor of Medicine,
Division of Pulmonary Diseases, Critical Care and Occupational
Medicine, Department of Medicine, School of Medicine, The
University of North Carolina at Chapel Hill, Chapel Hill, North
Carolina

Lester Breslow, M.D., M.P.H., Co-Director, Division of Cancer
Control, Jonsson Comprehensive Cancer Center, University of
California at Los Angeles, Los Angeles, California
Benjamin Burrows, M.D., Professor of Internal Medicine, and
Director, Division of Respiratory Sciences, The University of
Arizona College of Medicine, Tucson, Arizona
Robert M. Castellan, M.D., Chief, Clinical Section, Clinical Investiga-
tions Branch, Division of Respiratory Disease Studies, National
Institute for Occupational Safety and Health, Centers for Disease
Control, Morgantown, West Virginia
John E. Davies, M.D., M.P.H., Professor and Chairman, Department
of Epidemiology and Public Health, University of Miami School of
Medicine, Miami, Florida

Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland
John E. Diem, Ph.D., Professor of Statistics, Tulane University, New
Orleans, Louisiana

Manning Feinleib, M.D., Dr.P.H., Director, National Center for
Health Statistics, Office of the Assistant Secretary for Health,
Hyattsville, Maryland

Edwin B. Fisher, Jr., Ph.D., Associate Professor of Psychology and
Preventive Medicine, Department of Psychology, Washington
University in St. Louis, St. Louis, Missouri
Lawrence Garfinkel, M.A., Vice President for Epidemiology and
Statistics, and Director of Cancer Prevention, American Cancer
Society, Incorporated, New York, New York
J.C. Gilson, M.D., Hembury Hill Farm, Honiton, Devon, England,
United Kingdom

William E. Halperin, M.D., M.P.H., Chief, Industrywide Studies
Branch, Division of Surveillance Hazard Evaluations and Field
Studies, National Institute for Occupational Safety and Health,
Centers for Disease Control, Cincinnati, Ohio
Peter V.V. Hamill, M.D., M.P.H., Adjunct Professor, Epidemiology
and Preventive Medicine, University of Maryland School of
Medicine, Baltimore, Maryland

John L. Hankinson, Ph.D., Chief, Clinical Investigations Branch,
Division of Respiratory Disease Studies, National Institute for
Occupational Safety and Health, Centers for Disease Control,
Morgantown, West Virginia

xvi


Naomi Harley, Ph.D., Professor, Institute of Environmental Medi-
cine, New York University Medical Center, New York, New York
Wayland J. Hayes, Jr., M.D., Ph.D., Professor Emeritus of Biochemis-
try (Toxicology), School of Medicine, Vanderbilt University, Nash-
ville, Tennessee

Ian T.T. Higgins, M.D., Professor Emeritus of Epidemiology and of
Environmental and Industrial Health, School of Public Health,
The University of Michigan, Ann Arbor, Michigan, and Acting
Chief of Epidemiology, American Health Foundation, New York,
New York

Thomas K. Hodous, M.D., Medical Officer, Clinical Investigations
Branch, Division of Respiratory Disease Studies, National Insti-
tute for Occupational Safety and Health, Centers for Disease
Control, and Adjunct Associate Professor, West Virginia Universi-
ty School of Medicine, Morgantown, West Virginia
Michael Jacobsen, Ph.D., Deputy Director, Institute for Occupational
Medicine, Edinburgh, Scotland, United Kingdom
Robert N. Jones, M.D., Professor of Medicine, Pulmonary Diseases
Section, Department of Medicine, Tulane University School of
Medicine, New Orleans, Louisiana

Marcus M. Key, M.D., Professor of Occupational Medicine, Program
in Occupational Safety and Health, School of Public Health,
University of Texas Health Science Center at Houston, Houston,
Texas

Kaye H. Kilburn, M.D., Ralph Edgington Professor of Medicine,
Laboratory for Environmental Sciences, University of Southern
California School of Medicine, Los Angeles, California
Arthur M. Langer, Ph.D., Associate Professor of Mineralogy, The
Mount Sinai School of Medicine of the City University of New
York, New York, New York

N. LeRoy Lapp, M.D., Professor of Medicine, Pulmonary Disease
Section, West Virginia University Medical Center, Morgantown,
West Virginia

Richard A. Lemen, Director, Division of Standards Development and
Technology Transfer, National Institute for Occupational Safety
and Health, Centers for Disease Control, Cincinnati, Ohio
Claude Lenfant, M.D., Director, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland
Trent R. Lewis, Ph.D., Chief, Experimental Toxicology Branch,
Division of Biomedical and Behavioral Science, National Institute
for Occupational Safety and Health, Centers for Disease Control,
Cincinnati, Ohio

Edward Lichtenstein, Ph.D., Professor of Psychology, University of
Oregon, and Research Scientist, Oregon Research Institute, Eu-
gene, Oregon

xvii


Ruth Lilis, M.D., Professor, Division of Environmental and Occupa-
tional Medicine, Department of Community Medicine, The Mount
Sinai School of Medicine of the City University of New York, New
York, New York

Jay H. Lubin, Ph.D., Health Statistician, Biostatistics Branch,
Division of Cancer Etiology, National Cancer Institute, National
Institutes of Health, Bethesda, Maryland
James 0. Mason, M.D., former Acting Assistant Secretary for
Health, Washington, D.C., and Director, Centers for Disease
Control, Atlanta, Georgia

J. Corbett McDonald, M.D., F.R.C.P., Professor, School of Occupa-
tional Health, McGill University, Montreal, Quebec, Canada
J. Michael McGinnis, M.D., Deputy Assistant Secretary for Health
(Disease Prevention and Health Promotion), Office of the Assistant
Secretary for Health, Washington, D.C.
J. Donald Millar, M.D., Assistant Surgeon General and Director,
National Institute for Occupational Safety and Health, Centers for
Disease Control, Atlanta, Georgia

Anthony B. Miller, M.B., F.R.C.P.(C), Director, Epidemiology Unit,
National Cancer Institute of Canada, and Professor of Preventive
Medicine and Biostatistics, University of Toronto, Toronto, Ontar-
io, Canada

Kenneth M. Moser, M.D., Professor of Medicine, School of Medicine,
University of California at San Diego, La Jolla, California, and
Director, Division of Pulmonary and Critical Care Medicine,
University of California Medical Center, San Diego, California
Robert J. Mullan, M.D., Medical Officer, Surveillance Branch,
Division of Surveillance Hazard Evaluations and Field Studies,
National Institute for Occupational Safety and Health, Centers for
Disease Control, Cincinnati, Ohio

Muriel Newhouse, M.D., F.R.C.P., Department of Occupational
Health and Applied Physiology, London School of Hygiene and
Tropical Medicine, University of London, London, England, Unit-
ed Kingdom

William J. Nicholson, Ph.D., Associate Professor, Division of Envi-
ronmental and Occupational Medicine, Department of Community
Medicine, The Mount Sinai School of Medicine of the City
University of New York, New York, New York
Judith K. Ockene, Ph.D., Associate Professor of Medicine, and
Director, Division of Preventive and Behavioral Medicine, Depart-
ment of Medicine, University of Massachusetts Medical School,
Worcester, Massachusetts

C. Tracy Orleans, Ph.D., Clinical Assistant Professor, University of
Pennsylvania Medical School, Philadelphia, Pennsylvania; Smok-
ing and Health Consultants, Incorporated, Princeton, New Jersey

. . .
xv111


Carl E. Ortmeyer, Ph.D., Public Health Statistician (Retired),
National Institute for Occupational Safety and Health, Centers for
Disease Control, Morgantown, West Virginia
John M. Peters, M.D., Professor, and Director, Division of Occupa-
tional Health, Department of Preventive Medicine, University of
Southern California School of Medicine, Los Angeles, California
Richard Peto, M.A., MSc., I.C.R.S., Requis Assessor of Medicine,
Radcliffe Infirmary, University of Oxford, Oxford, England, Unit-
ed Kingdom
Philip C. Pratt, M.D., Professor of Pathology, Department of
Pathology, Duke University Medical Center, Durham, North
Carolina
Edward P. Radford, M.D., Visiting Professor, University of Occupa-
tional and Environmental Health, School of Medicine, Yahata
Nishi-Ku, Kitakyushu, Japan
Robert B. Reger, Ph.D., Chief, Epidemiological Investigations
Branch, Division of Respiratory Disease Studies, National Insti-
tute for Occupational Safety and Health, Centers for Disease
Control, Morgantown, West Virginia
Attilio D. Renzetti, Jr., M.D., Professor of Medicine, and Chief,
Division of Respiratory, Critical Care, and Occupational Pulmo-
nary Medicine, University of Utah Health Sciences Center, Salt
Lake City, Utah
E. Neil Schachter, M.D., Professor of Medicine and Community
Medicine, The Mount Sinai School of Medicine, and Director,
Respiratory Therapy, The Mount Sinai Medical Center, The
Mount Sinai School of Medicine of the City University of New
York, New York, New York
Richard S. Schilling, M.D., Department of Occupational Health and
Applied Physiology, London School of Hygiene and Tropical
Medicine, University of London, London, England, United King-
dom
Irving J. Selikoff, M.D., Professor Emeritus, The Mount Sinai School
of Medicine of the City University of New York, New York, New
York
Kyle N. Steenland, Ph.D., Epidemiologist, Industrywide Studies
Branch, Division of Surveillance Hazard Evaluations and Field
Studies, National Institute for Occupational Safety and Health,
Centers for Disease Control, Cincinnati, Ohio
Jesse L. Steinfeld, M.D., President, Medical College of Georgia,
Augusta, Georgia
Arthur C. Upton, M.D., Professor, and Chairman, Institute of
Environmental Medicine, New York University Medical Center,
New York, New York


John Christopher Wagoner, M.D., F.R.C.(Path), Medical Research
Council Pneumoconiosis Unit, Llandough Hospital, Penarth,
South Glamorgan, Wales, United Kingdom
Kenneth E. Warner, Ph.D., Professor, and Chairman, Department of
Health Planning and Administration, School of Public Health, The
University of Michigan, Ann Arbor, Michigan
David H. Wegman, M.D., M.S., Professor, Environmental and
Occupational Health Sciences, School of Public Health, University
of California at Los Angeles, Los Angeles, California
Hans Weill, M.D., Schlieder Foundation Professor of Pulmonary
Medicine, Tulane University School of Medicine, New Orleans,
Louisiana

William Weiss, M.D., Professor Emeritus of Medicine, Hahnemann
University, Philadelphia, Pennsylvania
*R. Keith Wilson, M.D., Associate Professor of Medicine, Pulmonary
Section, Baylor College of Medicine and The Methodist Hospital,
  Houston, Texas

*Ronald W. Wilson, M.A., Director, Division of Epidemiology and
  Health Promotion, National Center for Health Statistics, Office of
  the Assistant Secretary for Health, Hyattsville, Maryland
James B. Wyngaarden, M.D., Director, National Institutes of Health,
  Bethesda, Maryland

Frank E. Young, M.D., Commissioner, Food and Drug Administra-
tion, Rockville, Maryland

The editors also acknowledge the contributions of the following
staff members and others who assisted in the preparation of this
Report.

Erica W. Adams, Chief Copy Editor and Assistant Production
Manager, Health and Natural Resources Department, Informatics
General Corporation, Rockville, Maryland
Richard H. Amacher, Director, Health and Natural Resources
Department, Informatics General Corporation, Rockville, Mary-
land

John L. Bagrosky, Associate Director for Program Operations, Office
on Smoking and Health, Rockville, Maryland
Charles A. Brown, Programmer, Automation and Technical Services
Department, Informatics General Corporation, Rockville, Mary-
land

Clarice D. Brown, Statistician, Office on Smoking and Health,
Rockville, Maryland

Richard C. Brubaker, Information Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Catherine E. Burckhardt, Secretary, Office on Smoking and Health,
Rockville, Maryland

xx


Joanna B. Crichton, Copy Editor, Health and Natural Resources
Department, Informatics General Corporation, Rockville, Mary-
land

Stephanie D. DeVoe, Programmer, Automation and Technical
Services Department, Informatics General Corporation, Rockville,
Maryland

Terri L. Ecker, Clerk-Typist, Office on Smoking and Health, Rock-
ville, Maryland

Felisa F. Enriquez, Information Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

James N. Ferguson, Reproduction Technician, Office Services De-
partment, Informatics General Corporation, Rockville, Maryland
Danny A. Goodman, Information Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Karen Harris, Clerk-Typist, Office on Smoking and Health, Rock-
ville, Maryland

Leslie J. Headlee, Information Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Patricia E. Healy, Technical Information Specialist, Office on
Smoking and Health, Rockville, Maryland
Timothy K. Hensley, Technical Publications Writer, Office on
Smoking and Health, Rockville, Maryland
Shirley K. Hickman, Data Entry Operator, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Ayse N. Hisim, Secretary, Health and Natural Resources Depart-
ment, Informatics General Corporation, Rockville, Maryland
Robert S. Hutchings, Associate Director for Information and Pro-
gram Development, Office on Smoking and Health, Rockville,
Maryland

Leena Kang, Data Entry Operator, Health and Natural Resources
Department, Informatics General Corporation, Rockville, Mary-
land

Carl M. Koch, Jr., Information Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Julie Kurz, Graphic Artist, Information Center Management De-
partment, Informatics General Corporation, Rockville, Maryland
Maureen Mann, Editorial Assistant, Office on Smoking and Health,
Rockville, Maryland

James G. Oakley, Library Acquisitions Clerk, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

xxi


Ruth C. Palmer, Secretary, Office on Smoking and Health, Rockville,
Maryland

Russell D. Peek, Library Acquisitions Specialist, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Roberta L. Phucas, Secretary, Office on Smoking and Health,
Rockville, Maryland

Margaret E. Pickerel, Public Information and Publications Special-
ist, Office on Smoking and Health, Rockville, Maryland
Raymond K. Poole, Production Coordinator, Health and Natural
Resources Department, Informatics General Corporation, Rock-
ville, Maryland

Linda R. Sexton, Information Specialist, Health and Natural Re-
sources Department, Informatics General Corporation, Rockville,
Maryland

Linda R. Spiegelman, Administrative Officer, Office on Smoking and
Health, Rockville, Maryland

Evelyn L. Swarr, Administrative Secretary, Automation and Techni-
cal Services Department, Informatics General Corporation, Rock-
ville, Maryland

Debra C. Tate, Publications Systems Specialist, Publishing Systems
Division, Informatics General Corporation, Riverdale, Maryland
Jerry W. Vaughn, Development Technician, University of California
at San Diego, San Diego, California
Mary I. Walz, Computer Systems Analyst, Office on Smoking and
Health, Rockville, Maryland

Louise G. Wiseman, Technical Information Specialist, Office on
Smoking and Health, Rockville, Maryland
Pamela Zuniga, Secretary, University of California at San Diego,
San Diego, California

xxii


TABLE OF CONTENTS

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

Preface.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

Acknowledgments ....................
                           ................................. x111

1. Introduction, Overview, and Summary and
Conclusions ........................................................ 1

2. Occupation and Smoking Behavior in the United
States: Current Estimates and Recent Trends . . . . . . . . 19

3. Evaluation of Smoking-Related Cancers in the
Workplace.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

4. Evaluation of Chronic Lung Disease in the
Workplace.. . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

5. Chronic Bronchitis: Interaction of Smoking and
Occupation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

6. Asbestos-Exposed Workers ................................. 195

7. Respiratory Disease in Coal Miners .................... 285

8. Silica-Exposed Workers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319

9. Occupational Exposures to Petrochemicals, Aromatic
Amines, and Pesticides . . . . . , . . . . . . . . . . . . . . . . . . . . . . . 355

10. Cotton Dust Exposure and Cigarette Smoking ....... 399

11. Ionizing Radiation and Lung Cancer ................... 441

12. Smoking Intervention Programs in the
Workplace.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517


xx111


CHAPTER 1

INTRODUCTION, OVERVIEW,
          AND
SUMMARY AND CONCLUSIONS


CONTENTS

Introduction

Development and Organization of the 1985 Report
Historical Perspective

Overview

Summary and Conclusions of the 1985 Report

3


Introduction

Development and Organization of the 1985 Report
The 1985 Report was prepared by the Office on Smoking and
Health of the U.S. Department of Health and Human Services as
part of the Department's responsibility, under Public Law 91-222, to
report new and current information on smoking and health to the
United States Congress. The scientific content of this Report is the
collective work of 100 scientists in the fields of both smoking and
occupational health. Individual manuscripts were written by experts
who are recognized for their understanding of specific content areas.
Each chapter was subjected to an intensive peer review, whereby
comments were solicited from four to six individuals knowledgeable
in that particular area. After these comments were incorporated, the
entire Report was submitted to distinguished experts representing a
balance of opinion in occupational disease and smoking and health.
Concurrent with this latter review, the manuscript was also submit-
ted to various U.S. Public Health Service agencies for review.
Throughout the entire report compilation process the Office on
Smoking and Health had the advice and consultation of four
internationally known scientists. These individuals represent exper-
tise in the fields of both smoking and occupation. They are Dr. Lester
Breslow, University of California at Los Angeles, Dr. Marcus Key,
University of Texas Health Science Center, Dr. Irving Selikoff, the
Mount Sinai Medical Center, and Dr. Jesse Steinfeld, Medical
College of Georgia. From the outset, this panel of experts was
instrumental in recommending the Report content and outline,
suggesting individual authors and reviewers, and providing overall
guidance during each stage of the compilation process. Each also
served as an overall reviewer of the completed manuscript.
The 1985 Report contains a Foreword by the Acting Assistant
Secretary for Health, a Preface by the Surgeon General of the U.S.
Public Health Service, and the following chapters:

o Chapter 1. Introduction, Overview, and Summary and Con-
          clusions
o Chapter 2.  Occupation and Smoking Behavior in the United
          States

o Chapter 3. Evaluation of Smoking-Related Cancers in the
        Workplace

o Chapter 4. Evaluation of Chronic Lung Disease in the
         Workplace

o Chapter 5. Chronic Bronchitis: Interaction of Smoking and

Occupation

o Chapter 6. Asbestos-Exposed Workers
o Chapter 7. Respiratory Disease in Coal Miners
o Chapter 8. Silica-Exposed Workers

5


a Chapter 9. Occupational Exposures to Petrochemicals,
          Aromatic Amines, and Pesticides
o Chapter 10.  Cotton Dust Exposure and Cigarette Smoking
o Chapter 11.  Ionizing Radiation and Lung Cancer
o Chapter 12. Smoking Intervention Programs in the Work-
          place

Historical Perspective
More than two centuries ago, the relationship between occupation-
al exposure and health outcome was presented by a noted English
practitioner of surgery. Dr. Percival1 Pott (1733-1788), in his
Chirugical Observation-s (17751, described this first scientific observa-
tion as a "superficial, painful ragged, ill-looking sore with hard and
rising edges" that appeared in chimney sweeps, who almost always
began working when they were very young and small enough to fit
down a chimney. This malady was appropriately tagged "chimney
sweep's cancer." Soon after the turn of the 19th century, additional
reports confirmed Dr. Pott's observations.
Only shortly before Dr. Pott's description was published, Dr. John
Hill (1716?-17751, in his Cautions Against the Immoderate Use of
Snuff; described an association between tobacco use and cancer. Hill
reported on two case histories and observed that "snuff is able to
produce . . . swellings and excrescences" in the nose, and he believed
them to be cancerous.
Although Dr. Pott's startling report and description of the
deplorable use of children as chimney sweeps was published in 1775,
it was not until nearly a century and a half later, in 1914, that
Yamagawa and Ichikawa were able to demonstrate the carcinogenic
nature of the hydrocarbons in soot and tar. Almost 20 years later, in
1933, the proximate carcinogen 3,4-benzypyrene was isolated from
coal tar by Cook, Hewett, and Hieger.
Also in the 1920s and 1930s scientists began investigating the
possible association between cigarette smoking and cancer, and near
the end of World War II, several scientists had noted the higher
percentages of cigarette smokers among cancer patients, particular-
ly those with lung cancer. In 1962, when the Surgeon General's
Advisory Committee on Smoking and Health began weighing the
scientific evidence for its 1964 Report, the causal significance of the
association of cigarette smoking and disease was evaluated by strict
criteria, none of which taken alone was sufficient for a causal
judgment. These criteria today form the basis for the continued
judgment that cigarette smoking is causally related to a number of
disease processes.


Overview

Cigarette smoking is clearly the major cause of lung cancer and
chronic lung disease identified for the U.S. population. The role that
cigarette smoking plays in the development of cancer was extensive-
ly reviewed in 1982 Report of the Surgeon General and chronic
obstructive lung disease was reviewed in 1984. However, cigarette
smoking is not the only cause of lung cancer or chronic lung disease
in the U.S. population. A number of occupational exposures are well
established as causes of cancer and chronic lung disease, and it is
reasonable to expect that ongoing investigation of workplace expo-
sures will continue to expand our understanding of the hazards of
specific exposures and increase our ability to protect U.S. workers.

This Report examines the contributions of cigarette smoking and a
number of workplace exposures to lung cancer and chronic lung
disease among occupations in which specific hazardous exposures are
known to occur. It is possible from the data presented to identify a
causal role for both smoking and certain workplace exposures in
lung cancer and disability from chronic lung disease. It is also known
that the occupational hazards reviewed in this Report frequently
occur on a substrate of risk and injury produced by cigarette
smoking. The combination of exposures may influence the nature or
extent of the disease produced by the isolated exposures (interact);
both may act to produce the same disease, or may produce separate
injuries to the lung that in combination result in more severe
disability than would be expected from the isolated injuries. In
addition, the worksite may represent a setting in which a substantial
number of workers begin to smoke, and may provide an environment
that either supports or discourages the efforts of individual workers
to stop smoking. The ability to alter the adverse health outcomes of
workers exposed to occupational hazards requires both an under-
standing of the disease risks that result from individual and
combined exposure and a knowledge of how changes in the worksite
can alter the pattern of disease occurrence.

Many of the major improvements in public health during the last
century and the first part of this century were produced through the
control of infectious diseases. The key to this success frequently was
the identification of the causal agent, with the subsequent elimina-
tion of exposure to the agent or immunization against the agent. The
criteria for establishing the causality of an infectious agent were
expressed by Robert Koch in 1877 and are commonly referred to as
Koch's postulates. They are the following:

1. The agent must be shown to be present in every case of the
disease by isolation in pure culture.
2. The agent must not be found in cases of other disease.

7


3. Once isolated, the agent must be capable of reproducing the
   disease in animal experiments.
4. The agent must be recovered from the experimental disease
   produced.
These postulates served well in identifying the causal agents in
acute infectious processes; frequently their identification was a
critical part of their successful control.
The major diseases responsible for death and disability in the
latter half of the 20th century are chronic heart and lung disease
and cancer. These diseases, which now account for over half of all
deaths in the United States annually, are commonly the result of
chronic exposures to noninfectious occupational and lifestyle influ-
ences, may be caused by a number of agents acting independently,
and may also result from more than one agent contributing to the
disease process in any given individual. For these reasons, Koch's
postulates have little relevance for establishing causality in lifestyle
and occupational exposures, and new criteria for causality have been
developed. These criteria rely heavily on epidemiologic data and
include an examination of the consistency, strength, specificity,
coherence, and temporal relationship of the association between the
agent and the disease as well as the evidence of the biologic
mechanisms by which the agent produced the disease.
The multifactorial etiology and chronic exposures that character-
ize cancer and chronic lung disease also have implications for control
of these diseases in the worksite. One of the important public health
achievements of this century has been the identification of hazard-
ous agents in the workplace, with subsequent reductions in these
exposures through changes in environmental levels of the agent,
modification of work practices, and alteration of manufacturing
practices. These changes were the result of regulation and voluntary
agreement, and they reflect the action and concern of labor,
management, Government, and the insurance industry. The result,
in some industries, has been a dramatic reduction in the exposure to
hazardous agents in the worksite and in the disease that would have
been produced by these exposures.
As this Report clearly documents, however, cigarette smoking may
alter the amount of disease or level of disability produced by
hazardous occupational exposures. For cancer, this alteration may
come in the form of adding an additional number of cancer cases, or
of the combined exposure synergistically increasing the number of
cancers. On an individual level, our understanding of the process of
carcinogenesis suggests that both agents may contribute to individu-
al cancer rather than some cases being caused exclusively by an
occupation exposure and other cases being caused exclusively by
cigarette smoking.


For lung disease, the combination of cigarette smoking and
exposure to a hazardous workplace agent may combine to produce
similar injuries or may produce independent disease processes in the
same lung that result in greater disability than with either exposure
separately.

The public health importance of interaction between smoking and
an occupational exposure is typified by the relationship between
cigarette smoking and asbestos exposure among asbestos workers. A
number of studies published in this country and abroad have
demonstrated an approximately fivefold excess risk for lung cancer
among nonsmoking asbestos insulation workers. Smoking in non-
asbestos-exposed populations increases the lung cancer risk by
approximately tenfold. However, the risk is more than fiftyfold
greater if the asbestos worker also smokes. The risk in cigarette-
smoking asbestos workers is greater than the sum of the risk of the
independent exposures, and is approximated by multiplying the
risks of the two separate exposures. Thus, the interaction of cigarette
smoking and asbestos exposure is multiplicative in nature. To state
this in another way, for those workers who both smoke and are
exposed to asbestos, the risk of developing and dying from lung
cancer is 5,000 percent greater than the risk for individuals who
neither smoke nor are exposed. Among these asbestos workers, the
extent of disease produced by asbestos is conditioned by the smoking
habits of the asbestos-exposed population. As is also evident,
attempts to control asbestos-related lung cancer can have a maximal
impact only if they include successful programs to change smoking
behavior as well as efforts aimed at reducing levels of asbestos dust
exposure.

Elimination of the contribution made by smoking to disease and
disability in the worksite is beneficial, even in the absence of
synergistic interaction between smoking and workplace exposures.
Even with an additive risk for an exposed population, both agents
probably contribute to the cancer that develops in an individual, and
removing that contribution is an important benefit to that individu-
al. In addition, a given degree of impairment produced by an
occupational agent will result in less disability in an individual
without concomitant lung injury due to smoking than in a worker
who has chronic obstructive lung disease due to smoking.

The focus on individuals rather than on populations when
considering strategies to control occupationally related diseases also
helps clarify the concept of a "safe" worksite. The same number of
lung cancers may occur in a population with a high smoking
prevalence and a low asbestos exposure and ;i population with a low
smoking prevalence and a high asbestos exposure. This similarity of
population risks does not suggest that the level of acceptable or
"safe" dust exposure l:an be adjusted on the basis of the smoking

9


prevalence in the population. It may be reasonable to select
nonsmokers for jobs in which smokers would be at much greater
risk, but this approach should never be used as a justification for
accepting occupational exposure levels that result in risk for those
exposed. The goal should always be the elimination of as much of the
disease as possible in the working population rather than the
lowering of the disease rate to the population norm.

Factors in the worksite may also influence smoking initiation and
smoking cessation. Chapter 2 of this Report updates the previously
reported increased smoking prevalence among blue-collar workers
compared with white-collar workers. It also reports two analyses
that suggest the workplace may play an important role in smoking
behavior. The mean age of initiation reported confirms that the
majority of smokers begin smoking prior to or during high school.
However, a substantial fraction also begin to smoke after high
school. Little is known about the influences that may predispose
individuals to become smokers at this age. One of the major life
experiences occurring at the same time is entry into the workforce,
particularly for blue-collar and clerical workers, and the work
environment may be a major factor capable of predisposing an
individual toward or away from becoming a smoker.

A second important consideration that emerges from chapter 2 is
the markedly lower prevalence of successful smoking cessation
among blue-collar workers compared with white-collar workers. This
difference in cessation is not explained by differences in rates of
initiation, and almost equal percentages of current smokers have
made a serious attempt to quit and failed. This suggests that the
majority of both groups of workers have attempted to become
nonsmokers, but blue-collar workers have been less successful. Once
again, a potential role for the workplace environment in reinforcing
or inhibiting successful cessation may help to explain these differ-
ences in the prevalence of former smokers.

If a workplace is to be considered "safe," one very important
criterion is the absence of exposures to agents that can cause disease.
Equally important, however, is that safety should include a work-
place that neither encourages initiation nor discourages cessation of
cigarette smoking. As demonstrated in the final chapter of this
Report, the worksite may provide a focus for the promotion of
healthy behavioral change in the workforce, but at a minimum,
should not be a focus that encourages behaviors that compromise a
worker's health.

Summary and Conclusions of the 1985 Report
The major conclusions of this Report are clear. They are the
following:

10


For the majority of American workers who smoke, cigarette
smoking represents a greater cause of death and disability than
their workplace environment.

In those worksites where well-established disease outcomes
occur, smoking control and reduction in exposure to hazardous
agents are effective, compatible, and occasionally synergistic
approaches to the reduction of disease risk for the individual
worker.

Individual chapter summaries and conclusions follow.

Occupation and Smoking Behavior in the United States:
Current Estimates and Recent Trends

1. Among men, a substantially higher percentage of blue-collar
workers than white-collar workers currently smoke cigarettes.
Operatives and kindred workers have the highest rate of
current smoking (approaching 50 percent), with professional,
technical, and kindred workers having the lowest rates of
current smoking (approximately 26 percent).

2. Among women, blue-collar versus white-collar differences are
less pronounced, but still show a higher percentage of current
smokers among blue-collar workers. Occupational categories
with the highest rates of current smoking include craftsmen
and kindred workers (approximately 45 percent current smok-
ers) and managers and administrators (38 percent), with the
lowest rate of current smoking occurring among women
employed in professional, technical, and kindred occupations
(26 percent).

3. Occupational differences in daily cigarette consumption are
generally modest. For both men and women, the highest daily
consumption of cigarettes occurs among managers and admin-
istrators and craftsmen and kindred workers.

4. Blue-collar workers (both men and women) report an earlier
onset of smoking than white-collar workers. A substantial
fraction of smokers report initiation of smoking at ages
coincident with their entry into the workforce.

5. Blue-collar occupations have a lower percentage of former
smokers than white-collar occupations; this difference is most
pronounced among men. Among women, the pattern for
homemakers closely parallels that of white-collar women.
6. Black workers have higher smoking rates than white workers,
with black male blue-collar workers exhibiting the highest
smoking rate. Black workers also have lower quit rates than
white workers. In contrast, white workers of both sexes are
more likely to be heavy smokers regardless of occupational
category.

11


Evaluation of Smoking-Related Cancers in the Workplace
1. Cigarette smoking and occupational exposures may interact
  biologically, within a given statistical model and in their public
  health consequences. The demonstration of an interaction at
  one of these levels does not always characterize the nature of
   the interaction at the other levels.
2. Information on smoking behaviors should be collected as part
  of the health screening of all workers and made a part of their
  permanent exposure record.

3. Examination of the smoking behavior of an exposed population
should include measures of smoking prevalence, smoking dose,
and duration of smoking.

4. Differences in age of onset of exposure to cigarette smoke and
occupational exposures should be considered when evaluating
studies of occupational exposure, particularly when the ex-
posed population is relatively young or the exposure is of
relatively recent onset.

Evaluation of Chronic Lung Disease in the Workplace
1. Existing resources for monitoring the occurrence of occupation-
  al lung diseases are not comprehensive and do not include
  information on cigarette smoking. Other approaches, such as
  registries, might offer more accurate data and facilitate
  research related to occupational lung diseases. Because of the
  variability in diagnostic criteria for chronic lung disease, in I
  studies on occupational lung diseases emphasis should be
  placed on measures of physiological change, roentgenographic
  abnormality, and other objective measures.
2. Further studies that correlate lung function with histopatholo-
  gy should be carried out in occupationally exposed smokers and
   nonsmokers.

3. The effects of cigarette smoking on the chest x ray should be
clarified. In particular, the sensitivity of the IL0 classification
to smoking-related changes should be further evaluated in
healthy populations.

4. To determine if smoking is reported with bias by occupational-
ly exposed workers, self-reported histories should be compared
with biological markers of smoking in appropriate populations.
5. Mechanisms through which specific occupational agents and
cigarette smoking might interact should be systematically
considered. Both laboratory and epidemiological approaches
should be used to evaluate such interactions.
6. Statistical methods for evaluating interaction require further
development. In particular, the biological implications of
conventional modeling approaches should be explored. Fur-
ther, the limitations posed by sample size for examining

12


independent and interactive effects should be evaluated. The
consequences of misclassification by exposure estimates and of
the colinearity of exposure variables should also be addressed.
7. The role of cigarette smoking in the "healthy worker effect"
requires further evaluation.

8. Approaches for apportioning the impairment in a specific
individual between occupational causes and cigarette smoking
should be developed and validated.

Chronic Bronchitis: Interaction of Smoking and Occupation
1. Chronic simple bronchitis has been associated with occupation-
  al exposures in both nonsmoking exposed workers and popula-
  tions of exposed smokers in excess of rates predicted from the
  smoking habit alone. Among these exposures are coal, grain,
  silica, the welding environment, and to a lesser extent, sulfur
   dioxide and cement.

2. The evidence indicates that the effects of smoking and those
occupational agents that cause bronchitis are frequently addi-
tive in producing symptoms of chronic cough and expectora-
tion. Smoking has commonly been demonstrated to be the more
important factor in producing these symptoms.

Asbestos-Exposed Workers

1. Asbestos exposure can increase the risk of developing lung
cancer in both cigarette smokers and nonsmokers. The risk in
cigarette-smoking asbestos workers is greater than the sum of
the risks of the independent exposures, and is approximated by
multiplying the risks of the separate exposures.

2. The risk of developing lung cancer in asbestos workers
increases with increasing number of cigarettes smoked per day
and increasing cumulative asbestos exposure.

3. The risk of developing lung cancer declines in asbestos workers
who stop smoking when compared with asbestos workers who
continue to smoke. Cessation of asbestos exposure may result
in a lower risk of developing lung cancer than continued
exposure, but the risk of developing lung cancer appears to
remain significantly elevated even 25 years after cessation of
exposure.

4. Cigarette smoking and asbestos exposure appear to have an
independent and additive effect on lung function decline.
Nonsmoking asbestos workers have decreased total lung capac-
ities (restrictive disease). Cigarette-smoking asbestos workers
develop both restrictive lung disease and chronic obstructive
lung disease (as defined by an abnormal FEV,/FVC), but the
evidence does not suggest that cigarette-smoking asbestos

13


workers have a lower FEV,/FVC than would be expected from
their smoking habits alone.

5. Both cigarette smoking and asbestos exposure result in an
increased resistance to airflow in the small airways. In the
absence of cigarette smoking, this increased resistance in the
small airways does not appear to result in obstruction on
standard spirometry as measured by FEV,/FVC.

6. Asbestos exposure is the predominant cause of interstitial
fibrosis in populations with substantial asbestos exposure.
Cigarette smokers do have a slightly higher prevalence of chest
radiographs interpreted as interstitial fibrosis than nonsmok-
ers, but neither the frequency of these changes nor the severity
of the changes approach levels found in populations with
substantial asbestos exposure.

7. The promotion of smoking cessation should be an intrinsic part
of efforts to control asbestos-related death and disability.

Respiratory Disease in Coal Miners
1. Coal dust exposure is clearly the major etiologic factor in the
  production of the radiologic changes of coal workers' pneumo-
  coniosis (CWP). Cigarette smoking probably increases the
  prevalence of irregular opacities on the chest roentgenograms
  of smoking coal miners, but appears to have little effect on the
  prevalence of small rounded opacities or complicated CWP.
2. Increasing category of simple radiologic CWP is not associated
  with increasing airflow obstruction, but increasing coal dust
  exposure is associated with increasing airflow obstruction in
   both smokers and nonsmokers.

3. Since the introduction of more effective controls to reduce the
level of coal dust exposure at the worksite, cigarette smoking
has become the more significant contributor to reported cases
of disabling airflow obstruction among coal miners.
4. Cigarette smoking and coal dust exposure appear to have an
independent and additive effect on the prevalence of chronic
cough and phlegm.

5. Increasing coal dust exposure is associated with a form of
emphysema known as focal dust emphysema, but there is no
definite evidence that extensive centrilobular emphysema
occurs in the absence of cigarette smoking.
6. The majority of studies have shown that coal dust exposure is
not associated with an increased risk for lung cancer.
7. Reduction in the levels of coal dust exposure is the only method
available to reduce the prevalence of simple or complicated
CWP. However, the prevalence of ventilatory disabilities in
coal miners could be substantially reduced by reducing the
prevalence of cigarette smoking, and efforts aimed at reducing

14


ventilatory disability should include efforts to enhance success-
ful smoking cessation.

Silica-Exposed Workers

1. Silicosis, acute silicosis, mixed-dust silicosis, silicotuberculosis,
and diatomaceous earth pneumoconiosis are causally related to
silica exposure as a sole or principal etiological agent.

2. Epidemiological evidence, based on both cross-sectional and
prospective studies, demonstrates that silica dust is associated
with chronic bronchitis and chronic airways obstruction. Silica
dust and smoking are major risk factors and appear to be
additive in producing chronic bronchitis and chronic airways
obstruction. Most studies indicate that the smoking effect is
stronger than the silica dust effect.

3. Pathological studies describe mineral dust airways disease,
which is morphologically similar to the small airways lesions
caused by cigarette smoking.

4. A number of studies have demonstrated an increased risk of
lung cancer in workers exposed to silica, but few of these
studies have adequately controlled for smoking. Therefore,
while the increased standardized mortality ratios for lung
cancer in these populations suggest the need for further
investigation of a potential carcinogenic effect of silica expo-
sure (particularly in a combined exposure with other possible
carcinogens), the evidence does not currently establish whether
silica exposure increases the risk of developing lung cancer in
man.

5. Smoking control efforts should be an important concomitant of
efforts to reduce the burden of silica-related illness in working
populations.

Occupational Exposures to Petrochemicals, Aromatic
Amines, and Pesticides

1. The biotransformation of industrial toxicants can be modified
at least to some extent by the constituents of tobacco smoke
through enzyme induction or possibly inhibition. Both tobacco
smoke and some industrial pollutants contain substances
capable of initiating and promoting cancer and damaging the
airways and lung parenchyma. There is, therefore, an ample
biologic basis for suspecting that important interactive effects
between some workplace pollutants and tobacco smoke exist.
2. In mortality studies of coke oven workers and gas workers,
convincing evidence has indicated that work exposures to oven
effluents are causing an excess risk of lung cancer in spite of
the lack of adequate information on smoking. Other mortality
studies that suggest small increases in smoking-related dis-

15


eases, such as pancreatic cancer in refinery workers, cannot be
interpreted without more information on smoking.
3. For bladder cancer, the interactions between smoking and
occupational exposure are unclear, with both additive and
antagonistic interactions having been demonstrated.
4. The risk of pulmonary disability in rubber workers was
increased when smoking and occupational exposure to particu-
lates were combined. There are few empirical animal experi-
ments that demonstrate interactive effects between cigarette
smoking and various industrial chemicals for lung disease.

Cotton Dust Exposure and Cigarette Smoking

1. Byssinosis prevalence and severity is increased in cotton textile
workers who smoke in comparison with workers who do not
smoke.

2. Cigarette smoking seems to facilitate the development of
byssinosis in smokers exposed to cotton dust, perhaps by the
prior induction of bronchitis. Cotton mill workers of both sexes
who smoke have a consistently greater prevalence of bronchitis
than nonsmokers.

3. The importance of cigarette smoking to byssinosis prevalence
seems to grow with rising dust levels (a smoking-cotton dust
interaction). At the highest dust levels, cigarette smoke was
found to interact with cotton dust exposure to substantially
increase the acute symptom prevalence.

4. Nonsmokers with byssinosis have lower preshift lung function
and a greater cross-shift decline in lung function than asymp-
tomatic workers, and those workers with bronchitis generally
have lower preshift lung function than those without bronchi-
tis. In general, smokers have lower lung function than non-
smokers among cotton workers, both in those with bronchitis
and in those with byssinosis.

5. Although the average forced expiration values measured at the
start of a shift are reduced among smokers, the cross-shift
decline in function does not seem to be affected by smoking
status.

6. The contribution of the acute byssinotic symptoms (grades l/2
and 1) to the subsequent development of what have been
termed the chronic forms (grade 3) of byssinosis (which include
airways obstruction) is not well documented; however, chronic
airflow obstruction has been found more frequently in cotton
textile workers than in control populations, and this lung
function loss appears to be additive to that caused by cigarette
smoking.

7. Cotton dust exposure is significantly associated with mucous
gland volume and peripheral goblet cell metaplasia in non-

16


smokers, a pathology consistent with bronchitis. Among ciga-
rette smokers, the interaction of cotton textile exposure and
smoking is demonstrable for goblet cell hyperplasia. Centrilo-
bular emphysema is found only in association with cigarette
smoking and pipe smoking. There is no emphysema association
found with cotton dust exposure.

8. The evidence does not currently suggest an excess risk of lung
cancer among cotton textile workers.

Ionizing Radiation and Lung Cancer

1. There is an interaction between radon daughters and cigarette
smoke exposures in the production of lung cancer in both man
and animals. The nature of this interaction is not entirely clear
because of the conflicting results in both epidemiological and
animal studies.

2. The interaction between radon daughters and cigarette smoke
exposures may consist of two parts. The first is an additive
effect on the number of cancers induced by the two agents. The
second is the hastening effect of the tumor promoters in
cigarette smoke on the appearance of cancers induced by
radiation, so that the induction-latent period is shorter among
smokers than nonsmokers and the resultant cancers are
distributed in time differently between smokers and nonsmok-
ers, appearing earlier in smokers.

Smoking Intervention Programs in the Workplace
1. Smoking modification and maintenance of nonsmoking status
  among initial quitters has the promise of being more successful
  in worksite programs than in clinic-based programs. Higher
  cessation rates in worksite programs are achieved with more
  intensive programs.

2. Incentives for nonsmoking appear to be associated with higher
participation and better success rates. Further research is
needed to specify the optimal types of incentive procedures.
3. Success of a worksite smoking program depends upon three
primary factors: the characteristics of the intervention pro-
gram, the characteristics of the organization in which the
program is offered, and the interaction between these factors.
4. Research is needed on recruitment strategies and participation
rates in worksite smoking programs and on Ihe impact of
interventions on the entire workforce of a compa :y.
5. More investigations are needed on worksite c:-~arr~~!eristics
associated with the success of occupational programs and on
comprehensive programs including components such as quit-
smoking contests, no-smoking policies, physician messages. and
self-help materials in addition to smoking cessation clinics.


6. The implementation of broadly based health promotion efforts
in the workplace should be encouraged, with smoking interven-
tions representing a major component of the larger effort to
improve health through a worksite focus.

18


CHAPTER 2

  OCCUPATION AND
SMOKING BEHAVIOR
IN THE UNITED STATES:
CURRENT ESTIMATES
AND RECENT TRENDS


CONTENTS

Introduction

Patterns of Employment

Smoking Prevalence

Daily Cigarette Consumption

Age of Initiation

Quitting Behavior

Recent Changes in Smoking Behavior

Birth Cohorts

Race

Summary and Conclusions

Technical Addendum: National Health Interview Survey
Estimates

References

Appendices

21


Introduction

Estimates of current smoking behavior reported in this section of
the Surgeon General's Report were obtained from the 1978, 1979,
and 1980 National Health Interview Surveys (NHIS). A data tape
was prepared by the National Center for Health Statistics to allow
linkages across surveys, thereby permitting analyses of the com-
bined 1978-1980 NHIS (n=49,715). The majority of the analysis
presented in this chapter were conducted on the population aged 20
to 64 (n =38,527). Given the large samples and exceptionally high
response rates of NHIS, these estimates are generally regarded as
the best available estimates of national smoking patterns. To
examine recent lo-year changes in smoking behavior by occupation-
al category, the 1978-1980 NHIS estimates have also been compared
with the 1970 NHIS estimates for selected smoking variables. A
more detailed description of the NHIS data base is provided in the
Technical Addendum to this section.

Patterns of Employment

Before characterizing the smoking behavior of the U.S. adult
workforce, it will be useful to describe the patterns of employment
for men and women. As is shown in Table 1, men are more likely to
be employed in professional and technical, management, and blue-
collar occupations. Women are more likely to be employed in
professional and technical and clerical and service occupations or to
be homemakers. Although there was an increase in participation by
women in white-collar occupations between 1970 and 1980, the
ranking of occupational categories by their relative frequency for
both sexes remained about the same in 1980 as it did in 1970.
Because of their low relative frequency, farm, sales, and clerical
workers, laborers, and service workers have less impact on the
smoking behavior of the total male workforce, and female farm
workers, laborers, craftsmen and kindred workers, sales workers,
and managers and administrators have a modest impact on the
smoking behavior of the total female workforce.

Smoking Prevalence

Surveys have repeatedly shown that blue-collar workers are more
likely than white-collar workers to smoke cigarettes (US DHEW
1979). Recent estimates from NHIS continue to substantiate this
fimding (Table 2). Overall, smoking rates for blue-collar men (47.1
percent) exceed that of white-collar men (33.0 percent). The same
pattern holds for women, but is less pronounced, with smoking rates
among blue-collar women (38.1 percent) exceeding that of white-
collar women (31.9 percent). Among women, this white-collar-blue-

23


TABLE I.-Estimates of the occupational distribution of
     men and women, aged 20 to 64 years, United
      States, 1970-1980

0ccupat10n

      Men                    Women

1970        1978-80          1970       197-o

Currently employed        87.8         85.1            47 9        57.3


Whitecollar total         39.2         39.2            31.1        40.5

Professional.
technical. and
kmdred workers

Managers and
admmistrators.
except farm

Sales workers

Clerical and
kmdred workers

14.2          14.9            7.9        11.4




13.3          13 5            2.6         4.9

50          5.3            3.4         3.6


6.8          5.5            17.1        20.6

Blue-collar total


Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers. except
farm


Serwce

43.1         40.8            9.0         93



19.9         20 7            0.8         1.5


18.1          14.6            8.0         7.2



5.1          5.5            0.2         0.6


5.4          6.1            10.3        IO.8

Farm                 37          2.9            0.5         0.6

Unemployed

Usual actwty.
homemaking

36          4.1            3.2         4.3



-                       52.5        41.7

SOTE The whitecollar. bluecollar. Service. and farm occupational categorres are mutually exclusive. however.
those class,fied as "Howmak:ng" or "Unrmployed" may also be classified ,n an occupat,onal group on the baxs of
a rrcent or part-tune Job. resulting in a small degree ofoveriap between cate~urles
SOURCE Nar~onal Center fur Health Srat~stics. Nat~anal Health Inrenww Surveys. 1970 and 197G1980
`combInedI ,See TechnIcal .4ddendum )

collar difference exists only for the younger age group (aged 20 to
441; for older women (aged 45 to 64) there is virtually no difference in
smoking prevalence between these two categories of workers.

For men, the highest rates of current smoking occur among
craftsmen and kindred workers, operatives and kindred workers,
laborers, service workers, and the unemployed. The lowest smoking
rates for men occur among professional, technical, and kindred
workers, managers and administrators, clerical and kindred work-
ers, and farm workers.

24


TABLE 2.-Estimates of the percentage of current smokers
     by sex, age, and occupation, aged 20 to 64
     years, United States, 1978-1980

Occupation

       Women                    Men

; otal     20-44     4wz4     Total     z&44     45-64

Total              332      34.2      314      409      414      39.8

Currently employed

33.3

34.0

31 a

39 9

409

37 7

Whmz-collar total       319      31.9      319      33 0      33 5      32.2

Professmnal,
technical, and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kmdred workers

26.5      26.1      27 9      257      253      26.6

38.3      37.8      39.2      36 3      38.9      32.2

33.3      33.2      33.5      40.6      42.0      38.0

33.2      33.9      31.4      37.7      36.4      40.4

Blue-collar total       38.1      41.3      31.9      47 1      48.7      43.6

Craftsmen and
kmdred workers

Operatwes and
kindred workers

Laborers, except
farm

44.6      45.4      43.0'     46.1      47.8      42.6

37.0      40.2      30.8      48.6      50.4      44.5

36.2      43.0'      14.1 o      46.8      47.3      45.1

Service             37.4      39.8      32.7

48.3      46.0

Farm              22.6

28.9      34.5

Unemployed          39.6

33.0

31.3 '


41.7



351

7.1'


30.4



30.4

47.5


31.5


53.1

Usual actwity.
homemakmg

53.9



-

50.8

' -- 1W cases m the denominator ~unweighted sample8
SOURCE: National Center for Health Statistics. National Health Intenxw Surveys, 1978-1980 icombine&
~See Technical Addendum.1

For women 20 to 64 years of age, the highest smoking rates are
found among craftsmen and kindred workers and managers and
administrators. Among women 20 to 44 years of age, there are also
relatively high smoking rates among operatives and kindred work-
ers, service workers, and the unemployed. The lowest rates of
current smoking occur among professional, technical, and kindred
workers, regardless of age. For homemakers, the category represent-
ing nearly 42 percent of all women aged 20 to 64, the prevalence of
smoking among those aged 20 to 44 is midway between the

25


prevalence rates for white-collar and blue-collar occupations. How-
ever, among women 45 to 64 years of age, smoking rates vary little
by occupational group (with the single exception of managers and
administrators), with white collar-workers, blue-collar workers, and
homemakers all having approximately the same smoking preva-
lence.

Among men, a more detailed breakdown of smoking by occupation
(Table 3) shows that painters, truck drivers, construction workers,
carpenters, auto mechanics, and guards and watchmen have the
highest rates of current smoking (among occupations having 100 or
more cases in the 1978-1980 NHIS), each exceeding 50 percent. In
contrast, electrical and electronic engineers, lawyers, and secondary
school teachers have the lowest rates of current smoking, all under
25 percent.

Among women, waitresses have a noticeably higher rate of current
smoking than other groups (Table 4), followed by cashiers, assem-
blers, nurses aides, machine operators, practical nurses, and packers
and wrappers-all of whom have rates of current smoking that equal
or surpass 40 percent. The lowest rates of smoking occur among
women employed as elementary school teachers, food service work-
ers, bank tellers, and sewers and stitchers.

Because of the exemplar role of physicians and nurses in regard to
health, their smoking rates are of special interest. Although the
sample is relatively small, physicians have among the lowest rates of
current smoking (18.1 percent). Among nurses, the pattern of
smoking reflects the white-collar-service worker distinction; regis-
tered nurses have among the lowest rates of current smoking, but
practical nurses have among the highest rates (Table 4).

Daily Cigarette Consumption

For men, occupational differences in cigarette consumption do not
follow the same patterns observed for prevalence. On the average,
adult male white-collar smokers consume 24 cigarettes per day,
essentially the same as the number of cigarettes consumed by blue-
collar smokers (23.3) (Table 5). In virtually all occupational sub-
groups, adult men report an average daily consumption exceeding 20
cigarettes. Consumption levels are highest among managers and
administrators and sales workers. These numbers represent daily
cigarette consumption and need to be interpreted with some caution,
as there may be a substantial underreporting of cigarette consump-
tion, and the tendency to underreport may not be constant across
occupational categories.

For women, no difference in consumption is found between white-
collar and blue-collar smokers. On the average, white-collar female
smokers consume 19.5 cigarettes per day, compared with 19.8

26


`FABLE 3.-Specific occupations with highest and lowest
     estimates of current smoking, men, aged 20 to
     64 years, United States, 1978-1980

Occupatio"

Highest rates

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Painters. construction and maintenance (5101

Truck drivers (715)
Construction laborers. except carpenters' helpers (7511
Carpenters (4151

Auto mechamcs 14731

Guards and watchmen (9621

Janitors and sextons (903)

Assemblers WIZI

Electricians 14301
Sales representatives. wholesale trade (282)

Lowest rates

1.   Electrical and electronic engineers 10121                        16.2

2.  Lawyers (031)                                      21.9

3. Secondary school teachers (144)                            24.9

4.  Accountants (001)                                    26.8

5.  Real estate agents and brokers (270)                         27.8

6  Farmers N301)                                       28.1

55.1

53.6

53.0

50.8

50.5

505

49.8

48.7

48.3

48.1

NOTE: Adapted from Table 22 in Technical Addendum Only thme occupatmns with at least 100 men (aged 20
to 641 in the 197%1980 NHIS are Included Numbers in parentheses denote code values from the U.S. Bureau of
the Census 1970 classlticatmn of occupations.

SOURCE: National Center for Health Statistics, Natmnal Health Interview Surveys. 197t%1980 (combmed).
(See Technical Addendum.)

cigarettes for blue-collar smokers, 19.4 cigarettes for homemakers,
and 19.0 cigarettes for service workers. Female smokers employed as
managers or administrators or as craftsmen or kindred workers
report the highest consumption levels, averaging more than 20
cigarettes per day; women employed in professional, technical, or
kindred occupations report lower average daily consumption. How-
ever, like the men, these differences are not large, averaging fewer
than two to four cigarettes per day.

The higher the average daily consumption of cigarettes within an
occupational group, the more likely it is that this group will also
contain a higher percentage of heavy smokers (more than 20 or more
than 40 cigarettes a day). Overall, 72 percent of the male smokers
employed in white-collar occupations reported smoking more than 20

27


TABLE 4.-Specific occupations with highest and lowest
      estimates of current smoking, women, aged 20
      to 64 years, United States, 1978-1980

OccupatKm

Current smokers
IpercentageJ

Highest rates

1   Wamesses 19151

2   Cashiers 13101

3   Assemblers 1602

4   Nurses aides. orderhes. and attendants ,925)

5  .Machine operatives 16901

6   Practxal nurses 19261

i  Packers and wrappers, excluding meat:produce 16431

8  Checkers, exammers. and inspectors; manufacturmg (6101

9  Managers and administrators n e.c. ' 12451

10  Hairdressers and cosmetologtsts 49441


Lowest rates

51.1

44.2

42.9

41.0

41.0

40.3

40.0

39.3

38.0

37.5

I   Elementary school teachers (1421                            19.8

2.   Food service workers 89161                               24.6

3  Secondary school teachers 11441                            24.8

4   Bank tellers 13011                                     25.7

5   Sewers and stlrchers 1663:                                25.8

6  Regtstered nurses 0751                                 27.2

7  Child care workers, excludmg prwate households (9421               28.9

SOTE Adapted from Table Z m Technical Addendum Only those occupatmns with at least 1W women (aged
20 to 64 m the lY7&1YR(l SHIS are mciuded Numb+vs m parentheses denote code values from the U S. Bureau of
the (`ensus 1970 ciass,ficat~un 01 occupations
  Sot elsewhere ciawfied
SOURCE Satmnal Center for Health Srat,st,cs. National Health Inrerwew Surveys. 1978-1880 ~combmedl
See Technical Addendum

cigarettes a day, and over 21 percent reported smoking 40 or more
cigarettes a day (Table 6). Comparable figures for blue-collar
smokers are 72 percent and 18 percent, respectively.

Among adult women (Table 71, the percentage of heavy smokers is
generally lower than for men, with women employed as craftsmen or
kindred workers reporting higher percentages of heavy smoking
than other female occupational groups. The pattern for homemakers
closely parallels that of white-collar workers, but service workers
have slightly lower rates of heavy smoking than white-collar
workers. For both men and women, and across virtually all
occupational groups, smokers 45 years of age or older are more likely

28


TABLE B.-Estimates of average daily cigarette
      consumption among current smokers by sex,
      age, and occupation, aged 20 to 64 years,
      United States, 1978-1980

Occupatuxl

       women                    .Men

TOtal     2&44     4%64     Total     2M4     45-a

Total              19.3      19.1      19.6      23.2      22.2      25 1

Currently employed     19 2      19 0      19 a      23 4      22 4      25.6

White-collar total       19 5      19 1      20 4      24 0      "2 6      26.9

Professional.
technical, and
kindred workers

Managers and
administrators.
except farm

Sales workers

Clerical and
kindred workers

18 3

17 9

19 3

215

19 8

25 4

21 1      206      22.0      26 2      25.2      28.1

19.1      18.0      21.0      25.1      22.7      30.3

19.6      19.4      20.1      22.3      21.8      23.2

Blue-collar total       19.8      19.9      19.4      23.3      22.6     25.1

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

22.4      22.3      22.5      24.4      23.7      26.1

18.4      22.4      21.7      24.2

25.6      21.5

23.6

service

18.9      21.5

24.7

Farm

19.2



18.9


19.0


18.0


21.2



19.4

19.5



18.1


19.0


18.0


21.2



19.4

18.0

Unemployed

Usual activity,
homemaking

20.9


215



-

20.9


19.9


20.2


20.1



-

21.7

21.3

26 0

19.4

SOURCE: Natmnal Center for Health Statistln, ?iational Health Internew Surveys. 1978-1980 icomblnedl.
(See Technical Addendum.1

to report a higher percentage of heavy smokers than their 20- to 44-
year-old counterparts.

Age of Initiation

Men employed as blue-collar workers initiate smoking approxi-
mately 14 months earlier, on the average, than men employed in
white-collar occupations (Table 8). The earliest ages of initiation are

29


TABLE 6.-Estimates of the percentage of current smokers
       who smoke more than 20 or more than 40
      cigarettes daily, by age and occupation, men,
      aged 20 to 64 years, United States, 1978-1980

                   Total             20.44            45-64

Occupation         220      >a     220     240     220     240

Total              70.6      18.8      66.5      15.7      74.8      24.5

Currently employed     71.4      19.1      69.3      16.1      76.0      25.7

Whit&collar total       72.1      21.1      69.5      16.9      77.6      29.5

Professional,
technical, and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

66.5      17.3      61.9      12.9      76.7      26.8

79.1      24.5      77.7      20.0      81.6      33.3

74.2      23.7      70.0      17.8      83.0      36.1

64.2      17.2      64.1      16.2      64.6      19.0

Blue-collar total       11.8      18.3      70.1      16.1      76.3      24.1

Craftsmen and
kindred workers

Operatives and
kindred workers

Lalmers. except
farm

75.3      21.2      73.6      18.7      79.6      27.2

694      15.6      68.3      13.5      72.1      21.4

65.7      15.1      63.1      14.2      74.6      17.9

Service             66.6      16.0      63.0      11.5      73.6      24.7

Farm

62.1

16.5

56.3 '

16.6 '

16.4 '

Unemployed          65.9      16.3      61.3      12.9

68.0 '


81.1 '



-

27.6 '

Usual actwlty.
homemakmg

-

-

-

-

' i 1W cases in the denominator lunwelghted sample).
SOURCE Natmnal Center for Health Statistics. Natmnal Health lnterv~ew Surveys. 197&1980 icombined
&e Techmcal Addendum 1

reported by men employed as laborers (16.5 years), operatives or
kindred workers (16.6 years), or craftsmen or kindred workers (16.8
years). Men employed in professional, technical, or kindred occupa-
tions, or as managers or administrators, sales workers, or clerical or
kindred workers report later onset of smoking, ranging between 17.7
and 18.1 years of age.

For women, blue-collar and service workers report a somewhat
earlier onset of smoking than white-collar workers or homemakers

30


TABLE `I.-Estimates of the percentage of current smokers
       who smoke more than 20 or more than 40
      cigarettes daily, by age and occupation, women,
      aged 20 to 64 years, United States, 1978-1980



                   Total             20-44            45-64

Occupation         2 20      _> 40      > 20      140     120 240

Total              58.6     114       57.1      10.8      61.3      12.4

Currently employed     58.5     113       57.2      10.9      61.7      12.3

White-collar total       59.4     118       57.8      11.0      63.2      13.8

Professional.
technical, and
kindred workers

Managers and
administrators.
except farm

Sales workers

Clerical and
kindred workers

52 8     10 8       52.0       9.8      55.0      1B.8

63.4     15.6       59.0      14.6      71.8      17.5

56.8      99       55.0       6.5      59.9 *     16.0 o

61.6

11.5

60.6

11.3


11.5



18.2 *



10.5



50'


11.9


5.5 '


14.4



10.9

643

12.0

Blue-collar total       62.0     11.2       61.2

64.0      10.6

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

70.0     18 2       67.4 *

75.5 *

18.1'

60.4

99

60.3

60.7

8.4

56.7 '     6.0 *       55.2 '

70.9 *     15.6 o

Service


FarIll

54.6

11.6

53.6

57 1

65.4 '

4.9 '


14.8



113

63.5 '

802'

Unemployed

62.1

61.7

64 4 *

Usual activity.
homemaking

59.1

58.4

60.0

11.0


0.0 *


17.0 o



11.8

* s: 100 cases in the denommator iunweighti samplel
SOURCE. National Center far Health Statmtics Natmnal Health Inrerwew Surveys. 197%1980 lcombmedi
(See Technical Addendum 1

(about 6 months). The earliest age of initiation occurs among women
employed as laborers (17.4 years of age) or operatives or kindred
workers (18.5 years of age), and the latest age of initiation occurs
among women employed in professional, technical, or kindred
occupations (19.4 years of age). Across all occupational categories,
men report an earlier age of initiation than women; this difference is
most pronounced within the 45 to 64 age group.

31


TABLE %-Estimates of average age of initiation of
      smoking among current and former smokers by
      sex, age, and occupation, aged 20 to 64 years,
      United States, 1978-1980

0ccupat10n

       Women                    Men

Total     2M4     45-64     Total     2b44     45-64

Total

Currently employed

White-collar total

Professional.
technical, and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

Blue-collar total

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

Service

Farm

Unemployed

Usual act1wty.
homemaking

i9.0

18.6

18.5

18 2

18.1

18.0

18.2

17.6

17.6

21.2

21 .o

20.9

21.2

20.7

21.2

20.9

21.3

22.9

21.1

16.5

21.4

18.4

21.1

21.3

17.2

17.3

17.9

18.1

17.8

17.8

17.7

16.7

16.8

16.6

16.5

17.2

17.0

169

16.9

17.0

17.6

17.6

17.5

16.5

16.5

16.4

16.4

169

16.4

16 4

17 6

18.7

18.0

18.4

18.2

SOURCE Natmnal Center for Health Statistics. Natmnal Health Interview Surveys. 197&1980 tcombinedl.
<See Technail Addendum I

An important inference of the age of initiation reported in Table 8
is that a substantial fraction of smokers report beginning to smoke at
ages when they would be first entering the workforce. This suggests
that a set of influences that promote initiation may be present in the
initial socialization into the workforce.

32


Quitting Behavior

Because cigarette smoking usually begins between the ages of 12
and 25 (US DHEW 1979; US PHS 1973, 1976) the prevalence of
smoking among people 25 years of age or older is determined in large
part by the rate at which they st,op smoking (or die). The percentage
of former smokers (as a portion of "ever smoked") by occupational
group is reported in Table 9. For men, relatively higher percentages
of former smokers are found among professional, technical, and
kindred workers (55.2 percent) and managers and administrators
(47.7 percent)--the same occupational groups reporting lower rates
of current smoking (Table 2). The striking feature for women is the
uniformly lower percentage of former smokers when compared with
men. However, even here the same general pattern can be found;
occupations that have lower rates of current smoking also tend to
have a higher percentage of former smokers. In general, there are
substantial differences by occupational category, with white-collar
workers of both sexes having a higher percentage of former smokers
than blue-collar workers. This white-collar-blue-collar difference is
most pronounced among men. Among women, homemakers tend to
mirror the pattern of white-collar women.

It does not appear that the lower percentage of former smokers in
blue-collar occupations occurs simply because blue-collar workers
are less likely than white-collar workers to attempt to quit. Among
men, white-collar current smokers are more likely to report "a
serious attempt" to quit smoking (Table lo), but these differences are
typically only half as large as the white-collar-blue-collar differences
in the proportion of former smokers. Among women, the white-
collar-blue-collar differences are relatively small and show a mixed
pattern.

Recent Changes in Smoking Behavior

A comparison of smoking estimates for the period 1970-1980
reveals several interesting changes by occupational group and sex
(Table 11). Among men, there was a 19 percent proportionate decline
in smoking prevalence between 1970 and 1980 for white-collar
workers (40.8 vs. 33.0 percent), compared with a 14 percent decline
for blue-collar workers (55.0 vs. 47.1 percent). Occupations with the
largest decline in male smoking include professional, technical, and
kindred occupations (21 percent decline) and farm workers (20.7
percent decline); the unemployed (3.6 percent) and service workers
(10.9 percent1 had the smallest proportionate declines in smoking
prevalence.

Among white-collar women, there was a proportionate reduction
in smoking prevalence of 11.6 percent between 1970 and 1980 (36.1

33


TABLE 9.-Estimates of the percentage of former smokers
      by sex, age, and occupation, aged 20 to 64
      years, United States, 1978-1980

Occupation          Total

Women                    Men

20-44     4S64     Total     2cL44     4S64

Total              33.2      30.2      35.7      40.0      34.2      48.7

Currently employed

31.4

30.1

34.2

40.8

35.1

50.5

Whitecollar total       33.8      32.7      36.4      48.1      42.7      56.4

Professional,
technical, and
kindred workers

Managers and
administrators.
except farm

Sales workers

Clerical and
kindred workers

41.1      40.1      43.8      55.2      51.8      61.3

30.2      30.9      28.6      47.7      39.9     57.9

32.0      30.9      34.1      39.1      32.8     49.1

31.3      29.4      35.9      40.9      36.4      47.8

Blue-collar total

24.9

22.8

29.8

34.8

29.5

45.4

Craftsmen and
kindred workers

Operatwes and
kindred workers

Laborers. except
farm

238      24.9      21.4'     36.7      31.1      46.8

24.6      21.8      30.9      33.8      28.8      44.1

307'

270'

53.5'

29.7

25.0

41.9

sen~lce             26.2      24.2      62.2      32.0      27.0     40.0

Farm

325'

25.7

25.0'


22.7



30.9

30.5'

Unemployed

39.7

45.7


30.0

38.3      51.5

26.0      40.6

Usual activity,
homemakmg

33.5

37.2

-

-

SOURCE Sarnnal Center for Health Statistics. Natmnal Health Interview Surveys, 1978-1980 Icombinedl.
See Technral Addendum I

vs. 31.9 percent), but blue-collar women showed virtually no change
in smoking prevalance (1.0 percent proportionate increase).

The greater rate of decline in smoking prevalence for men has
produced two fundamental changes in the occupational smoking
patterns in this country. In 1970, men employed in professional,
technical, or kindred occupations or as managers or administrators
had a higher rate of smoking than their female counterparts. By the
end of the decade, this pattern had been reversed; a slightly higher
percentage of women in these two occupational groups now smoke

34


TABLE lO.-Estimates of the percentage of current smokers
      who have ever seriously attempted to quit by
      sex, age, and occupation, aged 20 to 64 years,
       United States, 1978-1980

Occupation

       Women                   Men

TOtal     2M4     4s64     Total     2@44     4s

1 otal              59 3      60.6      56.8      602      59 1      62.4

Currently employed     58.4      60.3      54 1      601      59.2      62.0

Wh6z-collar total       59.7      61.7      54 a      636      627      65.3

Pr&SSiO"al.
techmcal, and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

62.2      622      62 1      688      666      73.8

61.0      644      54.8      60.2      59.5      61.5

59.3      63.4      520      609      59.2      64.5

58.3      60.6      525      648      66.6      613

Bluesollar total       58.7      588      584      586      577      61.0

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

57.1      52.2'     679'     59 4      569      60.7

58.8      60.1      55.6      57 9      567      61.1

62.6'     619'

57.4


77.5'


66.4



60.8

58.9


77.3 *


649



60.9

689'


540


78.9 o


74.8'



60.7

57 4      56.0      62.2

Service

55.1

53.7

57.9

Farm

610      613'     60.7'

Unemployed

609

Usual activity,
homemaking

585



-

69 1 o

* c 100 cases I" the denommator lunweqhti sample1
SOURCE: National Center for Health StatMxs. National Health Intervww Surveys, 197%1980 rcombinedl
t&e Technical Addendum /

cigarettes. If the previous lo-year trends prevail, by the end of this
decade women are likely to reach parity with men in the prevalence
of smoking among blue-collar workers (as an aggregate) and clerical
and kindred workers, and to surpass men in smoking prevalence in
two additional occupational categories: craftsmen and kindred
workers and laborers.

As is shown in Table 12, only one specific occupational group for
men showed a net gain in smoking prevalence between 1970 and

35


TABLE Il.-Estimates of the percentage of current smokers
      by sex and occupation, aged 20 to 64 years,
       United States, 1970-1980

Occupation

   1970            19761980        Net change

M       w       M       W       M       W

Total              48.1      36.0      40.9      33.2      -1.2      -2.8

Currently employed     47.9      36.5      39.9      33.3      -8.0      -3.2

White-2oliar total       40.8      36.1      330      31.9      -7.8      4.2

Professional.
technical, and
kmdred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

32.5      29.0      25.7      26.5      4.8      -2.5

443      42.8      36.3      38.3

48.5      378      40.6      33.3

4.5

4.5

45.4      37.9      37.7      33.2

4.7

Blue-collar total       55.0      37.7      47.1      38.1

-8.0

-7.9



-7.7


-7.9



-7.1



-7.8



-10.4


-5.8


-8.2


-2.0

+a.4

Craftsmen and
kindred workers

Operatives and
kmdred workers

Laborers. except
farm

53.2      40.1      46.1      44.6

+4.5

56.4      37.7      48.6      37.0

-0.7

57.2      28.2'     46.8      36.2

t8.0

Service

533


39.7


55.9

39.4

20.8

47.5


315


53.9

37.4

-2.0

Farm

22.6

Unemplqwi

42.3

39.6

+ 1.8


-2.7

Usual actwity.
homemaking

35.3              33.0              -2.3

*  1W cases m the denominator lunwelghted sample1
SOURCE Satmnal Center for Health Statistics. Sational Health lnterwew Surveys. 1970 and 197E1980
icombmedr <See Technical Addendum.,

1980 (i.e., electricians), but painters, farm laborers, stock clerks and
storekeepers, and deliverymen and routemen had net reductions in
excess of 10 percentage points. Among women (Table 13), three
occupational groups showed a net increase in smoking prevalence
between 1970 and 1980 (practical nurses, cashiers, and packers and
wrappers), but relatively large net declines in smoking prevalence
occurred among receptionists, waitresses, bank tellers, secretaries,
and hairdressers and cosmetologists.

36


TABLE 12.-Specific occupations with largest estimated net
      changes in smoking prevalence between 1970
      and 1980, men, aged 20 to 64 years, United
        States

Occupation

Net change U97C-1980'1
in current smoking

Largest "et gains

1. Electricians (4301~4211                                 + 3.9

Largest net reductions

1.  Painters. constructmn and maintenance r51011~4951

2.  Farm laborers, wage workers G322)/19021

3. Stockclerks and storekeepers 1381Vr3501

4.  Dehverymen and routemen (7051it650

5. Foremen n.e.c ' 14411/(430)

6. Machinists 14611/(465)

7. Checkers. examiners. and mspectors;

-17.1

-14 5

-12 0

-11.6

43.9

a.7

  manufacturing (6101:(6431

8.  Managers and admmistratcrs n.e.c. ' t245V(2901

9. Assemblers 1602~0631 I

10. Accountants @01~/@00l

437

4.1

-7.0

-6.8

NOTE: Adapted from Table 23 m Techmcal Addendum Only those c-xupatmns with at least 1M men (aged 20
to 641 in the 197&1980 NHIS are included Numbers in parentheses represent the occupatvxxtl codes used in the
1970-1980 HIS and the 1970 HIS.
' Not elsewhere classified.
SOURCE: National Center for Health Statistics. National Health Interweu Surveys. 1970 and 1978-1980
kombmedr tSeeTechmca1 Addendum.1

The lo-year changes in daily consumption patterns show that
among white-collar men, there was a 1.8 percent proportionate
increase in the percentage of smokers who averaged 20 or more
cigarettes a day, compared with a 3.3 percent increase for blue-collar
men (Table 14). Professional, technical, and kindred workers, clerical
and kindred workers, and the unemployed showed a net decrease in
the percentage of smokers of 20 or more cigarettes a day. The overall
pattern is one of modest differences.

For women, the proportionate increase in number of smokers of 20
or more cigarettes a day was 7.4 percent for white-collar workers
(55.3 vs. 59.4 percent) and 4.8 percent for homemakers (56.4 vs. 59.1
percent). Service workers showed virtually no change between 1970
and 1980. Among blue-collar women however, the proportionate
increase in smokers of 20 or more cigarettes a day was a much larger
20.4 percent (51.5 vs. 62.0 percent). High proportionate increases in
20-plus smokers occurred among women employed as operatives or

37


TABLE 13.-Specific occupations with largest estimated net
      changes in smoking prevalence between 1970
       and 1980, women, aged 20 to 64 years, United
        States

Occupation

Net change (197C-1980,
in current smoking

Largest net gains


1. Practical nurses 19261/@42)

2. Cashiers t310V1312)

3  Packers and wrappers, except meat and produce (643Vf693)

Largest net reductions

14.3

+3.7

+2.6

1  Receptionists l364Vt3411                                 -10.6

2   Wamesses (915vt8751                                   -9.0

3.  Bank tellers 13011/(305)                                  -9.0

4.  Secretaries n.e c. I (372)/(342)                              a.1

5.  Hairdressers and cosmetologists (944)/(843)                      -7.4

6.  Cooks. except private household 1912W325)                      -5.5

7.  Typists ~391)1(360)                                     -4.9

8.  Managers and administrators n.e.c. ' L`245VG90)                   -4.2

9.  Bookkeepers (305Vf3101                                 -4.2

NOTE Adapted from Table 23 in Techmcal Addendum. Only those occupations wtb at least 100 women (aged
20 to 64) m the 197b1980 NHIS are included Numbers in parentheses represent the occupational codes used m
the 197G1980 HIS and the 1970 HIS
`Sot elsewhere cla.wfied
SOURCE. National Center for Health Statistics. National Health Interview Surveys. 1970 and 197b1980
Icombmedl. l&e Technical Addendum.1

kindred workers (37.8 percent) or craftsmen or kindred workers (33.2
percent). If these lo-year trends continue, by the end of this decade
female blue-collar smokers may surpass their male counterparts in
the percentage classified as moderate to heavy smokers (i.e., smoking
more than 20 cigarettes a day).

Among men, the net change in smokers averaging more than 40
cigarettes a day generally parallels that of 20-plus smokers (Table
15). Only the unemployed show a net decrease in the percentage of
current smokers averaging 40 or more cigarettes a day. Among
women, the net changes in heavy smoking between 1970 and 1980
are relatively modest.

Birth Cohorts

Although there has been a lo-year decline in smoking prevalence
for male blue-collar and white-collar workers and for female white-

38


TABLE 14.-Estimates of percentage of current smokers
     who smoke 20 or more cigarettes daily, by sex
      and occupation, aged 20 to 64 years, United
       States, 1970-1980

   1970            197bl980        Net change

M       W       M       W       M       W

Total              685

69 5

White-collar total

70.9

Pr0fess10nal.
technical, and
kmdred workers

Managers and
administrators,
except farm

Sales workers

Clerd and
kindred workers

69.0

75.5      58.1      79.1      63.4      -3.6     -5.3

69.8      52.2      74.2      56.8      -4.4     -4.6

66.0

Blue-collar total

69.5

Craftsmen and
kindred workers

Operatives and
kmdred workers

Laborers. except
farm

72.0

68.3

64.2

Service

65.2

Farm

60.5

Unemployed

67.5

Usual activity.
homemaking

55 1

54 4

55 3

47 5

58.2

51.5

52.7 '

51.1

66.6 *

53.2

50.1 *


49.7



56 4

70 6

714

72.2

665

64.2

71 a

75.3

69.4

65.7

66.6

62.1

65.9

58 6

58 5

59.4

52.8

616

62.0

70.0

60.4

56.7 *

54.6

64.4 *

62.1

59.1

-21

-19

+ 1.3

-2 5

-1.8

t2.3

1-3.3

+l.l

+I.5

il.4

+1.6


-1.6

-

-35

-4.1

-4.1

+5.3

t3.4

+ 10.5

+ 17.3

+ 19.3

-9.9

+ 1.4

+ 15.3


- 12.4

+ 2.7

* <_ 100 cases I" the denommator (unuwghted sample;
SOURCE National Center for Health Statlstlcs. National Health lnterwew Surveys. 197&19m (combinedr
(See Technical Addendum.1

collar workers, service workers, and homemakers, this does not
necessarily indicate that rates of lung cancer (and other cigarette-
linked diseases) will decline in the near future. What transpires
during the next 10 to 20 years with regard to lung cancer incidence
and mortality will be determined by those birth cohorts now
entering the ages at which substantial numbers of lung cancer
deaths occur. Figures 1 through 6, based on data from the combined
1978-1980 NHIS, present the prevalence of smoking among succes-

39


TABLE 15.-Estimates of percentage of current smokers
      who smoke 40 or more cigarettes daily, by sex
      and occupation, aged 20 to 64 years, United
       States, 1970-1980

Occupation

   1970            19761980        Net change

M       W       M       W       M       W

Total

15.7

8.0

18.8

11.4

-3.1

-3.4

Currently employed     15.9       7.8      19 1      113      t3.2     +3.0

White-collar total

18 4

8.1

21.1

11.8

-2.8

-3.7

Professional,
technical, and
kmdred workers

Managers and
administrators.
except farm

Sales workers

Clerical and
kmdred workers

14.9       4.9      17.3      10.8      -2.4     + 5.9

22 8       9.8      24.5      15.6      - 1.7     +5.8

18.4       7.2      23.7       99      r5.3     +2.7

is.0       9.2      17.2      11.5      t2.2

Bluesollar total

15.0

70

18.3

11.2

c3.3

~2.3


+4.2

Craftsmen and
kmdred workers

Operatwes and
kindred workers

Laborers, except
farm

16.1       96'     21.2      18.2      t5.1     18.6

14.8       6.6      15.6       9.0      7 0.8     +2.4

118

???? o


8.5


10.1 *


10 9



81

15.1       6.0 *     73.3      -4.1

Service

145

16.0

116


4.9 '


148



11.3

f1.5

t3.1

Farm

10 3

16.5

t6.2      -5.2

Unemployed          184

16.3

Usual actwxg.
homemaking

-2.1



-

T3.9

-

~3.2

' 1W cases m rhe denominator funwelghted samplel
SOURCE Natuxml Center ior Health Statistics. Natmnal Health Interview Surveys. 1970 and 1978-1980
~combmed~ t.See Technical Addendum I

sive cohorts born during each decade of the first half of this century.
The prevalence of smoking for each cohort is presented from 1900 to
1978 for men and women and for whites and blacks of both sexes.
Men who are 50 to 60 years of age, the 1921-1930 birth cohort, are at
the age at which the incidence of lung cancer increases rapidly.

Among white-collar workers (Figure 71, this cohort of men is
currently smoking at a higher rate than the cohort they are
replacing (1911-1920). The 1921-1930 cohort exhibits an exceptional-


----

1900    1910   1920    1930    1940    1950    1960    1970    1990

                      Yeer

FIGURE I.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       U.S. men, 1900-1978

SOURCE Data from National Center for Health Statistics, National Health Interview Surveys, 197S-1980
(combined).

ly high peak prevalence of 74.6 percent-which has since declined to
36.3 percent-but is still higher than the current 28.3 percent
prevalence estimate for the 1911-1920 cohort. However, one encour-
aging note is that the 1921-1930 cohort is currently smoking less
frequently at age 50 to 60 than the 1911-1920 cohort did when they
were 50 to 60 years of age (36.3 vs. 40.1 percent). If the 1921-1930
cohort of white-collar men achieves the same proportionate reduc-
tion in smoking during the next 10 years as the 1911-1920 cohort did
during the previous 10 years, by 1990 the 1921-1930 birth cohort will
be smoking at a lower rate than the 1911-1920 cohort did in 1978. In
a continuation of this general trend, all cohorts of white-collar men

41


751  i   /      / i

70 4      !            I      I


6%                 1911-1920 "
       d
60'                     /I    I I

I i     I      I

30                           1     I '
                                  I i

25                     1

1900    1910    1920    1930    1940    1950    1960    1970    1960

                       YW

FIGURE 2.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       white U.S. men, MOO-1978
SOURCE: Data from National Center for He&h Statistics. National Health Intemiew Surveys, 197M980
b3mbinedL

after the 1921-1930 cohort have lower rates of smoking than
previous cohorts at comparable ages, and also have successively
lower rates of peak prevalence.

The same general pattern in evidence for white-collar men also
applies to blue-collar men (Figure 8). The 1921-1930 birth cohort has
a higher current and peak smoking prevalence than the 1911-1920
cohort they are replacing. However, the 1921-1930 cohort is current-
ly smoking at a lower rate than the previous cohort (1911-1920) was
at the same age (10 years ago). Similarly, the 1931-1940 cohort is
currently smoking at a higher rate than the 1921-1930 cohort, but
less frequently when compared with the 1921-1930 cohort 10 years

42


If
$ 35


  30


  25

20


15


10


5


0

1900    1910    1920    1930    1940    1950    1960    1970    1080
                        Ye&II

FIGURE S.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
      black U.S. men, 1900-1978
SOURCE: Data from National Center for Health Statistica, National Health Interview Surveys. 1978-1980
Icombined)

earlier. After the 1921-1930 cohort, each successive birth cohort has
a lower peak prevalence, suggesting less total cigarette exposure
than for the previous cohort.

If present trends in male smoking continue, successive birth
cohorts of white-collar and blue-collar workers will arrive at the ages
of increasing lung cancer incidence with a lower rate of current
smoking and lifetime exposure than the previous birth cohorts. For
white-collar men, this pattern began with the 1911-1920 cohort, but
blue-collar men exhibit this pattern beginning with the 1921-1930
cohort. This same pattern of decreasing smoking prevalence across
successive birth cohorts also characterizes each main subcategory

43


65 -   I i

  55


  60


  45
$40
i 35
Il.

30


  25


  20


  15


  10


  5


  0

1900    1910    1920    1930    1940    1950    1960    1970    1960
                       YW

FIGURE 4.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       U.S. women, NO&1978
SOURCE Data from Sationai Center for Health Statistics, National Health Interview Surveys, 197&19EKl
lcombinedl

within the white-collar and blue-collar categories, including profes-
sional, technical, and kindred workers, managers and administra-
tors, craftsmen and kindred workers, and operatives and kindred
workers (See Technical Addendum, Figures 13 through 16).

Among white-collar women the same general pattern is found as is
in evidence for men (Figure 9). The peak prevalence of smoking is
highest in the 1931-1940 cohort; however, beginning with the 1921-
1930 cohort, each successive birth cohort of women employed in
white-collar occupations has a lower rate of smoking in 1978 than
the previous cohort did 10 years earlier. This pattern is especially
pronounced for the 1941-1950 and 1951-1960 cohorts, and is similar

44


65


60

30


25


20

0

1900    1910    1920    1930    1940    1950 1960    1970 1960
                       Yew

FIGURE B.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       white U.S. women, 1900-1978
SOURCE: Data from National Center for Health Statistics, Natmnal Health Interview Surveya. 197b1980
eombinedl.

to that found among professional, technical, and kindred workers
and clerical and kindred workers (Technical Addendum, Figures 17
and 18). Among homemakers, the largest category of women aged 20
to 64, this same general pattern is also found (Figure 10).
Although the overall birth cohort patterns for white-collar women
and homemakers are similar to those of men in regard to current
smoking, one important difference should be noted. For men, the
birth cohort with the highest peak prevalence is the 1921-1930
cohort, but for female white-collar workers and homemakers this
occurs with the 1931-1940 cohort.

45


70

65

60,

55-
504

45
,
40                                                 1941-1950
                                                  1931-1940
35                                                 1951-1960
30                                                 1921-1930

25                                                 1911-1920
20

15


10                                                 1901-1910
5


0

1900    1910    1920    1930 1940    1060   l&O   1970 1960

FIGURE B.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       black U.S. women, 1966-1978
SOURCE, Data from Netlord Center for Health Statistics, National Health Interview Surveys, 1978-1980
(combine8

In contrast with white-collar women and homemakers, the 1941-
1950 cohort of blue-collar women has the highest peak prevalence
(Figure 11). The 1931-1940 and 1941-1950 cohorts each exhibit
approximately the same smoking rates in 1978 as did the previous
cohort 10 years earlier. Only the 1951-1960 cohort of blue-collar
women has significant potential to redirect this trend of increasing
prevalence downward, and this will depend on whether this cohort
can sustain its current downward trend in smoking prevalence.

Service workers represent another important category of em-
ployed women, and their birth cohort smoking patterns resemble
white-collar workers in some ways and blue-collar workers in other

46


60

55

50

45

240
6
2 36

30

25

20


15


10


5

0

-t-
1901-1910

                                             -G
4       I  I  I   I   I        hx
      I  /?f
                    I L


                                   /
                                   I
     I   d      I    I L-

             I      i      1'
           / /    1
                             `I
                 A        I! I
                1 i    -. 1951-19ia
    ,/J I        I

+.-G. ..T ..,. ,..T T 7 ,.., r....q . ..y<.?.-,,~~.. ,.....  i

1901-1910

1960   rno   I!& 1930 l&o 1950 19&J    1970 lee0

                       YeU

FIGURE `I.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
      U.S. men employed in white+oIIar occupations,
        BOO-1978

SOURCE: Data from National Center for Health Statistics, National Health Interview Surveys. 197ElW0
(combined).

ways (Figure 12). Like white-collar women, female service workers
reached their highest peak prevalence with the 1931-1940 birth
cohort, and subsequent cohorts have experienced much lower peaks.
However, like blue-collar women, the 1921-1930 cohort of female
service workers continued to smoke at a higher rate in 1978 than the
previous cohort at the same age. This pattern becomes more
pronounced with the 1931-1940 cohort, but then reverses, with the
1941-1950 cohort reporting a lower smoking prevalence in 1978 than
the previous cohort 10 years ago.

47


T

1911-1920

o\          j                  `, ,r
    -  !  4 (-~,,~--c-,.e,-$-h I/ - /  A--
1900    1910   1920 1930 1940 1950 1960    1970    1960
                       YecU

FIGURE &-Changes in the prevalence of cigarette
     smoking among successive birth cohorts of
     U.S. men employed in blue-collar occupations,
        1900-1978

SOURCE: Data from Natmnd Center for Health Stati?.tics. Natmnal Health Interview Surveys. 1978-1980
(combmed).

Race

Among black men there are almost twice as many blue-collar
workers as white-collar workers (Table 16). This contrasts with white
men, who fall about equally into the white-collar and blue-collar
categories. Additionally, blacks of both sexes are more heavily
concentrated in the service category of workers, making this
category an important one to consider when examining occupational
differences in smoking by race. Black men are also almost twice as

48


1900    1910    1920    1930    1940    1950    1960    1970    lB60

                      YBU

FIGURE S.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
      U.S. women employed in white-collar
      occupations, 1900-1978
SOURCE. Data from National Center for Health Statistics, National Health Interview Surveys. 1978-1980
Icombined).

likely as white men to fall into the "Not Employed" category, which
includes both unemployed people and those "not in the labor force."

The differences in smoking prevalence between black men and
white men parallel the differences between blue-collar and white-
collar workers (Table 171, with black men having a considerably
higher smoking prevalence (47.7 percent) than white men (40.2
percent). Among men, blue-collar workers have considerably higher
smoking rates than white-collar workers within each racial group,
with black male blue-collar workers having the highest smoking
prevalence (52.1 percent).

49


25

1900    1910    1wO    1939    '940    1950    1960    1970    1990

                      YecV

FIGURE lO.-Changes in the prevalence of cigarette
     smoking among successive birth cohorts of
      U.S. women classified as homemakers, 1!IOO-

1978

SOURCE: Data from National Center for Health Statistica. National Health Interview Surveya, 197b1990
(combined).

Among black women, there is little difference in smoking preva-
lence between occupations, although homemakers have a somewhat
higher smoking rate (Table 17). However, among white women, the
expected white-collar, blue-collar, service worker differences prevail,
with blue-collar and service workers having a higher smoking
prevalence (39.6 and 38.7 percent, respectively) than white collar
workers (32.0 percent).

As shown in Table 17, black workers are considerably less likely
than their white counterparts to be heavy smokers (smoking 20 or
more cigarettes daily). This holds true for all categories of workers

50


1900    1910    1920    1930    1940    1950    1960    1970    1990
                       YW

FIGURE Il.-Changes in the prevalence of cigarette
       smoking among successive birth cohorts of
       U.S. women employed in blue-collar
       occupations, 1900-1978
SOURCE, Data from National Center for Health St&sties. National Health Interview Surveys, 1978-1990
(combined).

and for men and women. Among white women and biack men, blue-
collar workers are somewhat more likely than others to be heavy
smokers. The consumption differences between white workers and
black workers are even more pronounced when the percentage of
smokers smoking 40 or more cigarettes daily is examined. White
men are about four times more likely than black men to smoke 40 or
more cigarettes daily, regardless of occupation. Similarly, white
women are about three times more likely than black women to
smoke more than 40 cigarettes daily, regardless of occupational
group.

51


leo0    1910    1920    1930    1940    1950    1960    1970    1930

                       YW

FIGURE 12.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
      U.S. women employed in service occupations,
         1900-1978

SOURCE: Data from National Center for Health Statistics, National Health Interview Surveys, 197&1960
kombmedL

Among women, there are minimal racial or occupational differ-
ences in the proportion of current smokers who have attempted to
quit smoking. However, blue-collar, service, and not employed black
men are somewhat less likely than all other groups to have
attempted to quit. Among those who have ever smoked, white-collar
male workers are the most likely to have quit smoking. Blue-collar
and service workers generally have lower quit rates than white-
collar workers, and this pattern holds true for white men and black
men and white women. Black women have low quit rates regardless
of occupational category. Additionally, black male blue-collar work-

52


TABLE l&-Estimates of occupational distribution by sex
     and race, aged 20 to 64 years, United States,

1978-1980

                 Men (percentage)          Women (percentage1

Classification           while        Black           white       Black



White-collar            40.8         23.0            41.8        31.1


BlU~Ollar             40.6         45.2            9.0        11.0


Service                5.5         11.6            9.4        22.8

Homemaking                                    42.6        34.7

Not employed           10.0         18.8                      -

SOURCES National Center for Health Statistics, Natnxml Health lnterv~ew Surveys. 1970 and 197~1980
icombmed) (See Technical Addendum.1

ers have a considerably lower quit rate (24.9 percent) than white
male blue-collar workers (36.0 percent).

In summary, black workers are more likely than white workers to
be cigarette smokers, with black male blue-collar workers having the
highest smoking rate. In contrast, white workers are much more
likely than black workers to be heavy smokers, regardless of
occupational category. White workers are more likely to have quit
smoking, with the exception of white female blue-collar workers.
Black male blue-collar workers and all black female workers have
low quit rates. Among black men and white men and white women,
white-collar workers have both lower rates of current smoking and
higher proportions of former smokers than blue-collar or service
workers. The one group that deviates from this pattern is black
women; white-collar workers have a higher rate of current smoking
and a somewhat lower proportion of former smokers than blue-collar
or service workers, and homemakers have a relatively high rate of
current smoking.

Summary and Conclusions

1. Among men, a substantially higher percentage of blue-collar
workers than white-collar workers currently smoke cigarettes.
Operatives and kindred workers have the highest rate of
current smoking (approaching 50 percent), with professional,
technical, and kindred workers having the lowest rates of
current smoking (approximately 26 percent).

2. Among women, blue-collar versus white-collar differences are
less pronounced, but still show a higher percentage of current
smokers among blue-collar workers. Occupational categories

53


TABLE 17.-Estimates (percentages) of smoking prevalence,
      heavy smoking, and quitting behavior by race,
      sex, and occupation, aged 20 to 64 years,
        United States 1978-1980

Occupation

    White              Black

Men      Women      Men     Women

Current smokers

Total            40.1       33.3
White-collar        32.8       32.0
Blue-collar         46.5       39.6
servia?           47 0        38.7
Homemaking         -        32.9
Not employed        43.6        -

Smoke 220 daily

Total            74.5        62.8
White-collar         74.9        62.5
Bluecollar         75.4        66.0
service           72.1        60.9
Homemaking         -        63.2
Not employed        73.4        -

Smoke 240 daily
  Total
  White-collar
  Bluecollar
  SWViC%?
  Homemaking
  Not employed

20.7        12.4
22.5        12.6
20.0       12.0
19.0        13.9
-        12.2
19.9        -

Current smokers who have made a serious attempt to quit

Total            61.2        59.4
White-callar         63.6        59.1
Blue-collar         59.1       58.5
Service           57.2        57.5
Homemaking         -        60.5
Not employed        64.6        -

Ever smoked who are former smokers

Total            41.4        33.1
White-collar        48.8        34.6
Blue-collar         36.0        24.6
Service           32.6       26.6
Homemaking         -        34.3
Not employed       35.2        -

47.1
38.4
52.1
48.8

-
47.6

43.1
40.0
45.9
42.5'

-
42.1

5.4
3.3
6.0
2.3'

-
8.4

53.6
62.1
53.3
50.0 '

-
49.5

28.6
34.4
24.9
30.8

-
29.7

' < 100 cases m the denommator lunweighted sample).
SOURCE National Center for Health Statistics. Natvmal Health Interview Surveys. 197f?-1980 (combined).
rSee Techmcal Addendum.)

with the highest rates of current smoking include craftsmen
and kindred workers (approximately 45 percent current smok-
ers) and managers and administrators (38 percent), with the

34.6
35.2
33.4
33.5
37.1
-

27.6
29.5
31.8 *
31.4
23.5
-

4.0
4.2
5.2 *
3.5
4.0
-

60.0
60.0
59.9 '
58.1
64.2
-

24.6
23.6
24.8
25.3
24.4

-

54


lowest rate of current smoking occurring among women
employed in professional, technical, and kindred occupations
(26 percent).

3. Occupational differences in daily cigarette consumption are
generally modest. For both men and women, the highest daily
consumption of cigarettes occurs among managers and admin-
istrators and craftsmen and kindred workers.

4. Blue-collar workers (both men and women) report an earlier
onset of smoking than white-collar workers. A substantial
fraction of smokers report initiation of smoking at ages
coincident with their entry into the workforce.

5. Blue-collar occupations have a lower percentage of former
smokers than white-collar occupations; this difference is most
pronounced among men. Among women, the pattern for
homemakers closely parallels that of white-collar women.
6. Black workers have higher smoking rates than white workers,
with black male blue-collar workers exhibiting the highest
smoking rate. Black workers also have lower quit rates than
white workers. In contrast, white workers of both sexes are
more likely to be heavy smokers regardless of occupational
category.

55


Technical Addendum: National Health Interview Survey
Estimates

Estimates of current smoking reported in this chapter were
obtained from the 1978, 1979, and 1980 National Health Interview
Surveys (NHIS). A special data tape was prepared by the National
Center for Health Statistics to allow linkages across surveys, thereby
permitting analyses of the combined 1978-1980 NHIS. This increase
in sample size provides greater statistical reliability in the estimates
of population subgroups of interest to this Report.

The smoking items were completed by 12,105 respondents in 1978,
24,727 in 1979, and 10,649 in 1980, resulting in a combined sample of
47,481. Standard NHIS protocols were followed in each survey,
including a random probability sample design of the noninstitution-
alized adult U.S. population, and face-to-face interviews using U.S.
Bureau of the Census interviewers. Response rates routinely exceed-
ed 95 percent.

Given the large samples and exceptionally high response rates, the
NHIS estimates are generally regarded as the best available
estimates of national smoking patterns. Because the focus of this
Report is on occupational differences in smoking, analysis of the
197&1980 NHIS was restricted to respondents 20 to 64 years of age
(n = 36,745).

The definition of a current smoker was obtained from the
following question asked in the surveys: "DO you smoke cigarettes
now?" This includes both regular and occasional smokers who are
currently smoking. For estimates of average age of initiation and
quitting behavior, the denominator includes both current and former
smokers who describe themselves as having ever smoked "fairly
regularly."
The 1978-1980 National Health Interview Surveys utilized the
occupational coding scheme used in the 1970 U.S. Census. The
occupational subgroups examined in this Report, along with their
respective code numbers, are listed in Table 18.

Accompanying each NHIS public use data tape is an algorithm
that weights the sample to the 1970 U.S. population. All estimates of
smoking behavior reported here use this algorithm.

Data from the 1970 NHIS (reported in Tables 1, 11-15) were
obtained from the 1970 NHIS public use tape, which contains data
from 76,239 respondents who completed questions on their smoking
behavior. Of these, 59,557 respondents were between the ages of 20
and 64. Because the occupational classifications were revised be-
tween the 1970 and the 1978-1980 NHIS, changes in smoking
behavior could be reported only for the specific occupations whose
classification did not change.

As a preliminary step in the analysis of the 1978-1980 NHIS, the
equivalency of the three NHIS samples within occupational groups


TABLE l&-Occupational codes and categories used in the
      1978-1980 National Health Interview Surveys

occupation category       Occupations included    U.S. Census Bureau occupation codes'

Professional, technical,
and kindred

Managers, admin.,
except farm

201-245

Sales workers                             260-280

Clerical and kindred
workers

Bookkeepers
Office machine operators
Mail handlers, postal clerks
telegraph messengers
Secretaries, stenographers,
typists. receptionists
All other clerical workers

305
341-355

331. 332, 361. 383

Craftsmen and kindred   Carpenters
workers           Other construction craftsmen

Operatives and kindred   Operatives, except transport    601-695
workers          Transport equipment operatives  701-715

Laborers, except farm                        740-785

Service workers

Cleaning service           901-903
Food service             91C-916
Health and personal service    921-954
Protective service          960-965
Private household workers     9fs9ed

Engineers and architects      002, cQ6-023
Screntists               034-054.091-096
Health workers            061-085
Teachers, including college     102-145
Enmneerinrr. science technicians lW162
All-other &essional,       001, c03-m5. 024-033, 05540. 0%
technical, kindred workers   090, 097-101, 146149, 16199

Mechanics and repairmen
Metal craftsmen. except
mechanics
All ether craftsmen

Farmers and farm managers    801.802
Farm laborers and foremen    821-824

364-372, 276, 391

301-304, 306-330, 333-340, 35&360,
362, 363, 373-375. 377-382, 384-390,
392-399

41S416

410-412. 421. 430. 431, 436, 440,
51CL.512, 520-523, 534. 550, 560
470-495

403, 404, 442, 446, 454, 461. 462,
502-504. 514, 533, 53s0, 561, 562
401-402. 405-409, 413. 414, 417-421,
422-429, 43243.5. 437-439, 441, 443-
445, 447453. 455-480, 46.3469, 4%
501, 50.5-509, 513, 515-519, 524-532,
541-549, 551659. ?&L560

' Whitecollar occupations are designated by code values 001-399; blue-collar occupatmns are designated by code
valss 400785

was examined in regard to smoking prevalence and heavy smoking.
These results showed a high degree of statistical equivalency across

57


TABLE 19.~Estimates of the percentage of current smokers
      by sex, occupation, and NHIS sample (1978,
       1979, 1980), aged 20 to 84 years


                      Men                      Women

                                P                        P
Occupation         197.8    1979    1980   value       1978    1979    1980  value

White-collar total    32.5    33.4    33.1     NS'       32.9    32.4    30.8    NS

Professional,
technical and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

28.1    24.6    24.3    NS       26.3    26.8    26.6    NS

36.1    37.9    34.6

36.8    39.0    45.9

36.3    34.1     .a3

34.4    31.2    NS

37.6

38.5

37.4

34.3    32.3

Blue-collar total     46.8    46.8    47.6

NS       44.8

NS       35.1



NS       33.1


NS       41.9



NS       49.2



NS       41.1



NS       36.0


005       39.9


NS        .1

36.2    36.2

NS


NS

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

45.7    45.3    47.2

39.0    45.6    NS

48.6    48.8    48.6

35.5    33.9    NS

46.4

47.0


41.9


32.0

46.4

39.4

33.3

SetiCe

Farm

45.1


33.1



-

54.8

36.0    36.2

28.7

-        33.9

.




33.4

.

NS


NS

.

Usual activity,
homemaking

-

31.6    NS

/ Not statistxally slgmficant (p>O.O51

samples. As is reported in Table 19, among men one difference was
detected for smoking prevalence, but this difference showed an
inconsistent pattern across samples. Among women employed as
managers or administrators, there was a remarkable 10.7 percentage
point decline in smoking prevalence between 1978 and 1980, which is
over twice as large as the lo-year net decline between 1970 and 1980
(see Table 11).

One possible explanation for this large 3-year decline in smoking
prevalence is random fluctuation in the survey estimate. However, if
this short-term time trend for female managers and administrators
is valid, it would be of considerable interest. Given that the 197C
1978 comparisons already show female managers and administrators
to be quitting at a relatively high rate (when compared with other

58


TABLE 20.-Estimates of the percentage of current smokers
      who smoke 40 or more cigarettes daily by sex,
       occupation, and NHIS sample (1978, 1979, 19801,
      aged 20 to 64 years

                      Men                      Women

                               P                        P
Occupation        1978    1979    1980    value      1978    1979    1980   value

Whitecollar total    23.6    21.0    19.3     NS'       10.1    11.4    14.0     NS

Professional,
technical and
kindred workers

Managers and
administrators,
except farm

Sales workers

Clerical and
kindred workers

20.9    17.0    14.2     NS        90     8.6    14.1     NS

25.8    23.9    246

31.0    21.2    2u.5

16.0    15.2     NS

9.4    17.3     .05

16.0    20.5    15.4

11.8

NS

Blue-collar total

18.7

11.7

NS

Craftsmen and
kindred workers

Operatives and
kindred workers

Laborers, except
farm

19.4



22.7



16.9



13.9


13.4


20.5

174



19.1



16.6



13.6


15.9


11.5



-

22.2

NS       15 7

NS        3.4



NS        98


NS       11.3



NS       16.1



NS       11.0



NS        .2


NS       11.1


NS        .

13.0

13.1


10.5



22.9



7.1


.


11.4

,




12.9

NS

13.8

11.1

NS

18.9

o

.

Service

18.9

10.5

NS

Farm

17.2

.

o

Usual activity,
homemaking

-     -        10.4    10.6

??

' Nor statistically significant (p>O.O5)

`Not enough cases for valid chisquare test (the expected cell frequency for one or more cells wa8 less than five).

female occupational groups), it would seem prudent to closely
monitor the smoking patterns of this occupational cohort of women.

In regard to heavy smoking (see Table 20), no sample differences
were found for men. Among female salesworkers, there was a
striking 500 percent proportionate increase between 1978 and 1980
in the percentage of smokers of 40-plus cigarettes a day, which again
must be interpreted with caution. Overall, 50 separate chi-square
tests were examined, and 3 were statistically significant at p 5 0.05-
which would be expected solely on the basis of chance.
Detailed presentations of NHIS estimates of smoking prevalence
are provided in Table 21 (1978-1980) and Table 22 (1970-1980 net
change) for all occupational codes with 100 or more cases in the

59


combined 1978-1980 NHIS (unweighted sample). In Table 23 are
provided a comprehensive list of all occupational codes with 100 or
more cases in the 1978-1980 NHIS and the estimated percentage of
men and women, aged 20 to 64 years, who are employed in each
occupation. Figures 13 through 18 depict results from birth cohort
analyses that were briefly summarized in the text, including male
professional, technical, and kindred workers (Figure 13), managers
and administrators (Figure 141, craftsman and kindred workers
(Figure 151, and operatives and kindred workers (Figure 161, and
female professional, technical, and kindred workers (Figure 17), and
clerical and kindred workers (Figure 18).

60


TABLE 21.~Estimates of the percentage of current smokers
      by selected occupations, aged 20 to 64 years,
       united states, 197S1980

Occupation                             Men       Women      Total

WHITEXDLLAR

Professional, technical, and kindred workers

Accountants (001)
Electrical and electronic engineers (012)
Law-j-era (031)
Personnel and labor relationa workers (056)
Physicians, medical and arteopathic #X6)
Regard nu- (076)
Social workers WO)
Elementary school teachers (142)
Secondary school teachers (144)

Managers and administrators. except farm

Bank offxers and fmancial managers (202)
office managers n.e.c.' (220)
Of?kiels and administrators, public
administrators n.e.c. ' (222)
Restaurant. cafeteria, and bar managers (230)
Sales managers and department heads, retail
trade (231)

Managers and administrators n.e.c. (246)

Sake workers

lnsuranw agents, brokers, and underwriters

(265)

Real estate agents and brokers (270)
Sales representatives, manufacturing

industries (281)

Sales representatives, wholesale trade (282)
Sales clerks, retail trade (283)
Salesmen, retail trade (284)

Clerical and kindred workers

Bank tellers (301)
Bookkeepemao5)
Cashiers (310)

Estimators and investigators n.e.c. (321)
Expediters and production controllers (323)
Computer and peripheral equipment operators

(34.3

Postal clerks (361)
Receptionists (364)
Secretaries n.e.c. (372)
Stock clerks and storekeepers (381)
Typists (391)
Clerical workers, miscellaneous (394)
Clerical workers, not specified (395)

26.8        30.4        28.2
16.2        33.0 '        16.4
21.9        21.4'        21.8
30.9 '        37.9 '        34.1
18.1'        18.2'        18.1
46.4 '        27.2        28.0
42.6'        37.3'        39.0
18.8 '        19.8        19.6
24.9        24.8        24.9

35.9
43.9 '

28.1 '
25.4'

32.9
45.0

22.2'        20.3'        21.6
53.9 '        52.4'        53.3

28.7 '        33.8'        30.5
36.2        38.0        36.6

41.1'
21.8

41.0'
48.1'

41.1
36.4

43.2        32.9 '        41.2
48.1        45.8 1        47.9
39.6        30.5        33.7
42.6'        39.3'        42.4

0.0 '
42.9 '
43.4 '
28.4'
44.9 1


31.3'
38.2'
56.5'
61.7 '
38.1
10.3 '
34.9 '
33.5'

25.7
36.5
44.2
35.9 '
43.1'

24.7
37.1
44.1
33.1
44.3

44.7 '        38.5
24.9'        33.9
31.0        31.8
30.9        31.2
31.2'        35.3
33.0        31.7
33.3        33.6
28.4'        29.1

61


TABLE 21.-Continued

Occupation                            Men       WOlIX?tl      TOtal

BLUE-COLLAR

Craftamen and kindred workers

carpenters (415)

Electricians (430)
Foremen n.e.c. (441)
Machinists (461)

Automobile mechanics (473)
Heavy equipment mechanics. incl. diesel (481)
Painters, cmet~ction and maintenance (510)
Plumbers and pipe fitters (522)

Operatives, except transport

Aeeemblera (602)
Checkers, examiners, and inepectore;
manufacturing (610)
Packers and wrappers. except meat end
produce (643)
Sewers and stitchers (663)
Welders end flamecutters V%O)
Machine operatives, miecellaneoua,
specified @90)
Machine operatives, not specified (692)
hGcellaneoue operatives (694)

Tramport operatives

Bus drivers (703)
Deliverymen and routemen (705)
Fork lift and tow motor operatives (706)
Truck drivers (715)

50.8        70.4 '
46.3        100.0'
42.7
43.4        53.0 '
50.5        54.7 L
47.4        49.5 '
55.1        61.4'
47.1        39.1'

48.7        42.9


45.8        39.3

47.2 1        40.0        42.3
26.9 '        25.8        25.9
47.8        28.9 '        46.8

43.7        41.0        42.7
42.9 '        50.3 '        44.7
43.3        40.1'        42.4

50.3 '       35.2 L        42.7
42.4        46.1'        42.7
49.3 '        35.4 '       48.7
53.6        62.7 '        53.7

Workers, except farm
Construction laborers, except carpenters'
  helpers (751)                        53.0        52.8 '
Freight and material handlers (753)            42.5        34.6 '
Gardeners end groundskeepers, except farm (755)     46.1        43.7 1
Stock handlers (762)                     37.4 '        34.5 I
Laborers, not specitied (785)                 38.0        46.3 '

Farm workers

Farmers @Ol)
Farm laborers, wage workers (822)

28.1        29.9'        28.3
39.0        25.6 '        34.9

50.9
48.5
44.2
43.7
50.5
47.7
54.0
47.1

45.3

42.3

53.0
41.6
45.9
36.6
39.0

62


TABLE 2l.--Continued

Occupation

Men       women       Total

Service workers

Cleaners and charwomen K102)
Janitors and sextons (903)
Cooks, except private household (912)
waiters (915)
Food service workers n.e.c.`, except private

household (9161

Nursing aides, orderlies, and attendants (925)
Practical numes (926)
Child care workers, except private

household (942)

Hairdressm and cmmetilcgista KM)
Guards and watchmen (962)
Policemen and detectivea (964)
Maids and servants, private household (934)

49.8 '
49.8
45.0 '
44.7 '

42.1'        24.6        27.0
46.2 '        41.0        42.0
55.3 '        40.3        41.2

0.0 '        28.9
63.2 '        37.5
50.5        35.7 '
44.5        51.5 '
55.0 '        32.1

30.5
39.0 '
31.1
51.1

38.0
47.1
35.9
50.4

28.4
39.0
47.3
45.1
33.1

' < 100 caea in the denominator (unweighted sample).
`Not elsewhere claarified.

SOURCE: National Center for Health Statistics Health Interview Surveya. 1979-1980 kombined).

63


TABLE 22.~Estimates of the net change in smoking
      prevalence by sex and selected occupations,
      age 20 to 64 years, United States, 1970-1980

Occupation

Men

Women

Total

WHfITrcoLLAR

Professional, technical, and kindred workers

Accountants @01NOO)
Electrical and electronic engineen, @12)~
Personnel and labor relations workers

KJ56M154)
Physicians, medical and osteopathic
@65M153,162)
Regietered nuraea (075M150)
Social workers (lOOM171)
Elementary school teachers (142M182)
Secondary school teachera (144)/(163)

           -6.8
W83)         4.0

Managers and adminiatratars, except farm

OtXcinla and administrators, public
  admhiatrators n.e.c.' (222M270)
Managers and administratoza n.e.c. @45M2SO)

Sales workers

Insurance agents, brokers, and underwriters

ww(385)
Real estate agents and brokers (27OM393)

Clerical end kindred workers

Bank tellers (301)/(3051
BaAkeepers @05v(3101
Cashiers (310)/(312)
Postal clerks 061M340)
lleceptionti 064K?41)
Secretaries n.e.c. (372M342)
Stock clerks and storekeepers 031M350~
Typists @91v060)

BLUECOLLAR

-8.9

-8.5 '
+ 10.2 '
+3.8 1
-10.5 '
-3.5

16.3 '
-8.1

-9.8 '
14.6

-45.7'
-1.3'
+2.6 '
-1.0 '

-
-0.8 '
-12.0
-52.8 I

Craftsmen end kindred workers

Carpenters (415)/(411)                       -4.1
Electricians (43OM421)                    +3.9
Foremen n.e.c. M41V(4301                    -8.9
Machiniste (46M465)                       4.7
Automobile mechanics (473M472)                4.5
Painters. construction and maintenance (510)/(495)     -17.1
Plumbers and pipe tittera (522M510)              4.1

-0.4
-18.0 '

-9.2

-29.3 '     -10.0
-12.3      -11.4
+ 11.0 '     +7.7
-1.2      -2.6
-1.3      -2.4

A.6
-4.1

-2.0

7.3 '     -15.4
-4.2       -7.3

-22.6 '     -11.3
+3.8'      4.8

-9.0      -11.3
4.2      -3.9
+3.7      +3.5
-15.7'      -5.7
-10.6      -9.8
-6.1       -8.0
8.2 '     -12.2
4.9      -7.1

+50.3'      -3.7
+33.4 '      -3.9
-       -8.9
-7.3 '      -6.5
+22.3'      -4.3
+ 17.7 '     -17.3
-       -4.1

64


TABLE 22.-Continued

Occupation                              Men       Women     Total

Operatives, except transport
Assemblers @02)/(631)
Checkers, examiners, and inspectors,
manufacturing (61OM643)
Packera and wrappers, except meat and
produce (643)/(693)
Sewers and stitchers @63)/(7&V
Welders and flame-cutters S8OM721)

-7.0

-2.0

-4.6

-8.7

-0.3

-4.4

-8.0 '
-18.8'
-3.5

+2.6
-0.5
-12.7'

-0.7
-0.8
-3.9

Transport operatives

Bus drivers (703N641)
Deliverymen and routemen (705V(650)

+6.6'      +11.2'     +4.0
-11.6       f 10.0 '     -10.9

Farm workers

Farmers @Ol)/@O)                        -44       +9.3'      3.4
Farm laborers, wage workers (822M902)           -14.5        -6.2 '     -14.8

Service workers

Cleaners and charwomen @02V@24)
Cooks, except private household (912M825)
Janitors and sextona (903)/@34)
WaiterE (915)/@75)
Practical nursea (926)/(&2)
Hairdressers and ccemetolcgiste (944MJ343)
Guards and watchmen (962M851)
Policemen and detectives G64M853)

-14.3'
-19.2 '
-1.9
-2.9 '
-31.1'
-5.4'
5.5
-3.2

-2.3       -1.6
-5.5       -9.4
+10.4'      -0.4
-9.0       -8.7
i4.3      +3.7
-7.4       -8.0
+17.6'      -6.9
+24.4'      -2.0

' < 100 - in the denominator (unweighted sample).
`Not elsewhere classified.

SOURcE: National Center for Health Statistica Health Interview Surveys. 1978-1980 (combined).

65


TABLE 23.~Estimates of percentage of U.S. population,
      aged 20 to 64 years, in selected occupations,
        1978-1980

Occupation                            Men        Women     Total

Professional, technical, and kindred workers

Accountants (001)
Electrical and electronic engineers (012)
Lawyers (031)
Personnel and labor relations workers (058)
Physicians, medical and osteopathic (065)
Registemd nurse4 (075)
Social workers (100)
Elementary echo01 teachera (142)
Secondmy school teachers (144)

Managers and adminiatratora, except farm

Bank officers and financial managers (202)
G&e managers n.e.c.' (220)
Gflkide and administrators; public
administratora n.e.c. (222)
Restaurant, cafeteria, and bar managem (230)
Sales managers and department heads, retail

trade (231)

Managers and adminintratora n.e.c. (245)

S&a workers

Insurance age&, brokers, and underwritera

w5)

Real estate agents and brokers (270)
Sale9 representatives, manufacturing

industries (281)

Sales representatives. wholesale trade (282)
S&a clerks, retail trade (283)
Salesmen, retail trade (284)

Clerical and kindred workers

Bank tellers 001)
Bcdkeepem 005)
Caahiera (310)

Estimator, and investigatora n.e.c. (321)
Expediters and production controllers (323)
Computer and peripheral equipment operatora

@43)

Postal clerks (361)
Receptionist8 (364)
Secretark n.e.c. (372)
Stock clerks and storekeepers (381)
Typll (391)
Clerical workers, miscellaneous (394)
Clerical workers, not specified (395)

1.2          0.7       1.0
0.6          0.0       0.3
0.7          0.1       0.4
0.5          0.4       0.4
0.5          0.1       0.3
0.1          2.0       1.1
0.2          0.4       0.3
0.5          2.1       1.3
1.0          1.0       1.0

0.7
0.1

0.4
0.3

0.5
0.2

0.4
0.5

0.2
0.3

0.3
0.4

0.4          0.2       0.3
9.4          2.4       5.8

0.6          0.2       0.4
0.6          0.4       0.5

0.9          0.2       0.5
0.9          0.1       0.5
0.5          1.0       1.6
0.5          0.1       0.3

0.0          0.6       0.3
0.3          2.7       1.5
0.2          1.5       0.9
0.3          0.4       0.4
0.4          0.2       0.3

0.4          0.4       0.4
0.4          0.2       0.3
0.0          0.6       0.3
0.1          5.5       2.9
0.6          0.4       0.5
0.1          1.1       0.6
0.3          1.1       0.7
0.1          0.7       0.8

66


TABLE 23.4ntinued

Occupation                            Men        Women     Total

BLUJZ-COLLAR

Craftsmen end kindred workers

carpenters (415)                         2.4          0.0       1.2
Electriciana (430)                        1.0          0.0       0.5
Foremen n.e.c. (441)                      3.0          0.4       1.7
Machininta (461)                         1.1          0.0       0.5
Automobile me&mica (473)                  1.7          0.0       0.8
Heavy equipment mechanics, incl. diesel (481)       1.2          0.0       0.6
Paintew, construction and maintenance (510)        0.7          0.1       0.4
Plumbers and pipe fitters (522)                0.8          0.0       0.4

Operativea, except transport

Assemblers (602)
Checkers, examiners, end inspectors,
  manufacturing (610)
Packers and wrappers, except meat and
  produce w.3

0.8          1.1       0.9

0.7

0.7

0.7

Sewers and stitchers (663)
Welders and flamecutters (680)
Machine operatives. mieceIlaneou8.
specified SQO)

0.3
0.1
1.0


1.7
0.4
0.7

0.6
1.3
0.1

Machine operatives, not specified (692)
Miacellaneoua operatives (694)

0.9
0.1
0.3

0.5
0.7
0.5


1.3
0.2
0.5

Transport operativea

Bus drivers (703)
Deliverymen and mutemen (705)
Fork IiR and tow motor operatives (706)
Truck drivers (715)

0.3          0.3       0.3
0.7          0.1       0.4
0.6          0.0       0.3
3.0          0.0       1.5

Workers, except farm

Con&uction laborers, except carpenters'
  helpera (751)

Freiiht and material handlers (753)
Gardeners and groundskeepers, except farm
(756)

Stock handlers (762)
Not specifd labotera (786)

1.2          0.0       0.6
0.8          0.1       0.4


0.7          0.0       0.4
0.5          0.2       0.3
0.7          0.1       0.4

Farm workers

Farmers (801)
Farm laborers, wage workers (822)

2.0
0.7

0.2       1.1
0.3       0.5

67


TABLE 23.-Continued

Occupation

Men        Women

Total

Service workers

Cleaners and charwomen @02)                0.5          0.7       0.6
Janitors end sextons WW                  1.3          0.4       0.8
Cooke, except private household (912)            0.6          1.0       0.8
waiters (915)                         0.2          1.4       0.8

Food service workera n.e.c.. except private

household (916)

Nursing aides. orderlies, and attendante (925)
Practical nurses (926)
Child care workers, except private

0.1          0.6       0.4
0.2          1.3       0.8
0.1          0.7       0.4

household (942)

Hairdressera and comnetologiste (944)
Guards and watchmen (962)
Policemen and detectives (964)
Maids and servants, private household (984)

0.0          0.6       0.3
0.1          0.8       0.4
0.7          0.2       0.5
0.9          0.1       0.4
0.0          0.7       0.4

All other occupations                      30.2          15.9       22.7


Not in labor force                        10.9          38.6       25.3

NOTE Includes all occupational codes with at lea& 100 ce&?a (aged 20 to 641 in the 1978-1980 HIS (unweighted
aample).
`Not ekwhere cla.ktied
SOURCE. National Center for Health Statistics Health Interview Surveys, 197B1980 (combined).

68


Year

FIGURE 13.-Changes in the prevalence of cigarette
     smoking among successive birth cohorts of
     U.S. men employed in professional, technical,
      and kindred occupations, 1909-1978
SOURCE. Data from Natmnal Center for Health Statistics. National Health Interview Surveys, 1978-1980
lcombinedl

69


3                / L d
                                    1,
0 `&  G ~I//> - ! - f - -.LiLz!zzX-
       -                     2.
1900   1910 19x) 1930 1940 1950 1960    1970    1960

FIGURE 14.-Changes in the prevalence of cigarette
     smoking among successive birth cohorts of
     U.S. men employed as managers and
       administrators, 1900-1978
SOURCE. Data from Nat,onal Center for Health Statistxs. National Health Inter-&w Surveys, 197b1980
icombmed)

70


53                                     ,            i
                   I
                         I

                                            I

                                      1931-1940

lso0    1910    1920    1930    1940    1950    1960    1970    1980

FIGURE 15.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
      U.S. men employed as craftsmen or in
      kindred occupations, 190&1978
SOURCE: Data from National Center for Health Statistics. National Health Interview Surveys. 19761980
(combined).

71


.e1901-1910

1  /   I / / J j         ;

1900    1910    1920    1930    1940    1950    1960    1970    1990

(   j :,I !I    I    i
                        1.
     I   ,r--r- `,     \lT

FIGURE 16.-Changes in the prevalence of cigarette
    smoking among successive birth cohorts of
     U.S. men employed as operatives or in
     kindred occupations, 1900-1978
SOURCE. Data from National Center far Health Stathtice, National Health fntetiew Surveys. 197b1980
Icombined)

72


1931-1940
-I

FIGURE 17.-Changes in the prevalence of cigarette
    smoking among successive birth cohorts of
     U.S. women employed in professional,
     technical, or kindred occupations, 1900-1978
SOURCE: Data from National Center for Health Statistics. National Health Interview Surveys, 1978-1980
(combmed).

157-964 0 - 86 - 4

73


25

20


15


10


5


0

H-19401 '

--;,,;i
4
   /      ~1901-1910
A      I
          I

FIGURE l&-Changes in the prevalence of cigarette
     smoking among successive birth cohorts of
     U.S. women employed in clerical or kindred
      occupations, 1909-1978

SOURCE: Data from National Center for Health Statistics. National Health Interview Surveys. 19751980
bmhind).


References

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Smoking and
Health: A Report of the Surgeon General. U.S. Department of Health, Education,
and Welfare, Public Health Service, Office of the Assistant Secretary for Health,
Office on Smoking and Health. DHEW Pub. No. (PHS)79-50066,1979.
U.S. PUBLIC HEALTH SERVICE. Adult Use of Tobacco, 1970. U.S. Department of
Health, Education, and Welfare, Public Health Service, Centers for Disease
Control, National Clearinghouse for Smoking and Health, DHEW Pub. No.
(HSMl73-8727, June 1973.

U.S. PUBLIC HEALTH SERVICE. Adult Use of Tobacco, 1975. U.S. Department of
Health, Education, and Welfare, Public Health Service, Centers for Disease
Control, National Clearinghouse for Smoking and Health, June 1976.

75


APPENDICES


Appendix A

The two tables in appendix A describe the smoking habits of more
than 18,000 employees from 16 components of the General Electric
Company in various parts of the United States (personal communica-
tion, T. R. Casey and H. R. Richards, General Electric Company,
June 1985). The data are presented to demonstrate the differences
that can exist by payment category within the same workforce. The
employees categorized as exempt are managers and specialists in
various professions who are not bound by the provisions of the wage
and hours law. Nonexempt personnel are generally clerical and
secretarial workers, and hourly personnel are skilled and semi-
skilled people who work in manufacturing. It is clear that substan-
tial differences in smoking habits exist between men and women,
between older and younger workers, and among employees in the
three payment classifications.

78


TABLE Al.-Sample of smoking habits of employees of 16 workforce components of the General
      Electric Company, May 1985

category

     Nonsmokers                      Smokers                         Examokers

Women         MelI           Women              Men            Women            Mel-l     -
145    145    545   >45     545     >45      545      >45      545     >45     545     145      Total

5 20 c&/day

No. of employees
Years of smoking
Average years

>20 cigs/day

No of employees
Years of smoking
Average years

264     29    1.208    404        53       15       320      286       33       9      252      266    3.139
                         721      485      5,172     9,979      232     205     2.050    5.106
                          13.6      32.3       16.2      349       7.0     22.8       6.1      19.2



                           9        4        122      140        6       3       75      163     522
                         154      135      2,175     4,363       56      66      820    3,527
                          17.1      33.8       17.8      31.2       9.3     22.0      10.9     21.6

2 20 eigslday

No. of employees
Years of smoking
Average years

>20 cigslday

370    135     528    94        188       79       273       83       75      29      131       91    2,076
                      2,441     2,376      3,631     2,810      555     518     1,111     1,919
                         13.0      30.1       13.3      33.9       7.4     17.9       a.5      21.1

No. of employees                              47       20       130       35       11       9       57       40     349
Years of smoking                             863      666      2.021     1,220      161     226      761     1,092
Average years                               18.4      33.3       15.5      34.9      14.6     25.1      13.4      27.3


(x1
0   TABLE Al.-Continued


                      Nonsmokers                       Smokers                         Ex-smoken

                  WCllllen         Men           Women              Men             Women            Men

    category       545 .45     5 45    -145     545      -,45      145      .45      545     >45      < 45     .45      TVtal

Hourly

< 20 c&/day

No of employees   1.521   1,153    1.779    582      1,211      674      1,556      716      219     168      501      507    10.5x9
Years of smoking                         17,247    21,786     22,287    25,942     2,036    3.662     4.579    11.986
Average years                               14.2      32.3       14.3      36.2       9.3     21.9       9.1      23.6

:a 20 cigsiday

No. of employees                             155       91       405      259       35      34      144      233    1,3.x
Years of smoking                         2,714     3,083      7,520     9,716      482     870     1,706     6,265
Average years                               17.5      33.9       113.6      37.5      13.8     25.6      11.8     26.9

Total employees   2,155   1,317    3,515   1.080      1,663

SOURCE: General Electric Campany Corporate Medical Operation (1985)

883      2,608     1,519      379     252      1.160     1,300   18.031


TABLE AL.-Smoking habits of General Electric employees in various employment categories

                               Men                                        Women

              545 years old           >45 years old             <45 years old           i45 years old
category         Never   Current   Former     Never   Current   Former       Never   Current   Former     Never   Current Former


Exempt


Total            61.1     22.4      16.5       32.1     35.1     34.1         72.3    17.0     10.7       48.3    31.7    20

< 20 cigarettes/day          12.4      77.1             67.1     62.0               85.5     84.6             78.9    75

) 20 ciaarettes/dav          27.6     22.9             32.9     38.0               14.5     15.4             21.1    25

Nonexempt


Total

5 20 cigarettes/day

> 20 clgaretteslday

Hourly


Total

<' 20 cigarettes/day

`,, 20 cigarettes/day

47.2    36.0      16.8       27.4    344     38.2         53.6    34.0     12.4       496    36.4    14.0

      67.7     69.7             70.3     69.5               80.0     87.2             79.8    763

      32.3     30.3             297     30.5               200     12.8             20.2    23.7




40.6    44.7      14.7       25.7    42.4     32.2         48.4    43.5      8.1       54.4    361     9.5

      79.4      77.7             73.4     685               687     862             881     83.2

      20.6     22.3             26.6     31.5               11.3     13.8             11.9     168


Appendix B

The data in appendix B, portrayed in bar graph format (personal
communication, L. Garfinkel, October 19851, represent smoking
characteristics by age, occupation, and sex of the more than 1.2
million men and women studied in the American Cancer Society's
Cancer Prevention Study II. This study, initiated in 1982, is the
largest known prospective study of its kind. The data on smoking
and occupation were collected at the time of enrollment. Occupation-
al categories were determined from answers to open-ended questions
and, therefore, may not correspond to U.S. Department of Labor
categories.

These data provide comparative information on smoking habits
within occupational categories to demonstrate the variability that
exists between the estimates derived from individual research
designs and the national probability estimates derived from surveys.
The number above each bar represents the total population for each
age and occupational category. The first graph presents the percent-
ages for all occupations; the occupational categories compared are

the following.
Aide
Architect
Assembler
$$Im$ve
pr~e;yan
~l~rlgyService
Construction
iii%gry
Disabled
Doctor
Education
Electrician
Engineer
Executive
Factory Worker

Farmer
Fire Fighter
I??myYparation
Heavy Equipment
Hospital Worker
Housewife
Law Enforcement
Lawyer
l&&me Operator
Ea&itetrance
Military
Miner
Nursing
Office Worker
Painter

Pharmacy
gmE&yd Printing
Postal Service
Printing
kurogtiorker
Sales
Social Worker
Steel Mill
Technician
zEFttkne Operator
Truck Driver
Unemployed
gEVfe;/ WElltESS
Woodworker

82


00             ALL OCCUPATIONS

00.                       AIDE
M-

10 -

B  00

50

40

JO

20

  !O

  0

Do                   ARCHITECT

I, 

 /
/
/
I
/

`8 ,*

r
I-.

I
I

/
I
I/

   j I'
llil

ASSEMBLER


AUTOMOTIVE

I--
  -

            Mm     W-
too

BARBER/BEAUTICIAN

1


             un     W-
tm

90               CIVIL SERVKX

            Mm     W-
too

91)               CONSTRUCTION

so                   CLERGY

so                  DATA ENTRY
80


  -'

L3 Pmudaw        rm

               90                  EDUCATION


90                 ELECTRICIAN I

K!                   ENGINEER

m                   EXECUTIVE

._

m               FACTORY WORKER
a0

70


1

                                    i:.i Ppdagu        IM
a3                                                    00
90                FIRE FIGHTER                                       FOREMAN
                                                       Jb "--' ,i,Y


so             HEAW EQUIPMENT
bl

70

J

I--
  -

tm                                    r'.l WDmdaor
00              HOSPITAL WORKER

90     I I:        LAW ENFORCEMENT
  *,* ( I.`-' I  "


W
0

LAWYER  I

      MACHINE OPERATOR


90              MAINTENANCE


            un     W-
rm

MANAGER

./ :,

      I iiT
/- 1

,- . .


ml 557         MILITARY 1

w                        MINER

80

a0                     NURSING


w
N

h     -

Do               OFFICE WORKER
co

70

00

00

4

30

20

10

0
lblsSWO-Iccn

PAINTER

            yn     -
tm

90

PHARMACY

PHOTO AND PRINTtNG 1


I--
  -

40-e x-60 oo-00 m-m

00               POSTAL SERVICE

ml-                   PRINTING

6.2              RAILROAD WORKER


            Mm     W-
tm

00                 REAL ESTATE

100                                   E3 plpmdaor

Do                     SALES

            Mm     W-
`ml                  I

SOCIAL WORKER (

100

00  176                STEEL MILL


             Mm     W-
Ial

RI                   TECHNICIAN

            Men     W-
Irn

w      , ,,I                TEXTILE

TELEPHONE OPERATOR

90      881           TRUCK DRIVER


m                   UNEMPLOYED

O"i      WAITER/WAITRESS 1

1

WOOD WORKER


CHAPTER 3

    EVALUATION OF
SMOKING-RELATED CANCERS
   IN THE WORKPLACE


CONTENTS

Introduction

Lung Cancer Death Rates and Smoking

Interactions Between Cigarette Smoking and Occupational
Exposures

Biologic Interactions
Statistical Interaction
Public Health Interactions

Confounding of Occupational Exposures by Smoking
Behavior

Sources of Confounding
  Smoking Status

  Measures of Smoking Intensity
  Duration of Exposure
Control of Confounding
  Comparisons Using External Control Populations
  Comparisons Using Internal Control Populations

Examination of Occupational Exposures When Smoking
Habits Are Not Known

Summary and Conclusions

References

99


Introduction

Cigarette smoking is a major cause of cancer of the lung, larynx,
oral cavity, and esophagus and is a contributory factor for cancer of
the kidney, urinary bladder, and pancreas (US DHHS 1982). These
cancers will cause 278,700 of the estimated 910,000 new cancer cases
in the United States during 1985 (ACS 1985), or 30.6 percent of the
cancers occurring in the United States other than skin cancer.
Exposures to agents in the workplace other than cigarette smoke
will also cause some of these new cancers, and a number of cancers
will result from the combined effects of cigarette smoking and
carcinogenic exposures in the workplace.

The role that cigarette smoking plays in causing these cancers is
well established and extensively documented (US DHHS 1982). The
role that occupational agents play in the development of these same
cancers continues to emerge as the effects of more agents are
examined both in the laboratory and in the workplace. However,
cigarette smoking by exposed workers makes it difficult to separate
the effects of smoking from the effects of occupational agents for
cancers of sites causally linked to cigarette smoking. For some
agents, such as asbestos, both the large numbers of people exposed
and the magnitude of the increased cancer risk have allowed a
careful examination of the relative contributions of cigarette smok-
ing and the workplace exposure. For most agents, the data are more
limited. Nevertheless, protection of workers requires that regulatory
decisions be made about individual workplace exposures, even in the
face of limited data. In assessing the effects of workplace exposures,
consideration must be given to the interactions of smoking with
agents that increase risk and to the bias introduced into studies of
occupational groups by confounding effects of cigarette smoking.
This chapter discusses the nature and measurement of interactions
between smoking and occupational exposures and the sources and
&ntrol of confounding of smoking and occupational exposures. It is
not intended to be a comprehensive discussion of the epidemiologic
methods used to evaluate workplace exposures, but rather a discus-
sion of how smoking behavior in the workforce can effect the
evaluation of occupational exposures. The data on smoking and
specific occupational exposures are presented in later chapters of
this Report. The discussion of these issues is intended to aid in the
design and interpretation of studies of occupational exposure and not
to criticize those studies in which smoking could not be completely
addressed.

Lung Cancer Death Rates and Smoking
A detailed discussion of the causal relationship between cigarette
smoking and the cancers is provided in an earlier Report in this

101


series (US DHHS 1982) and is not repeated here. However, the
relationship between smoking and lung cancer is briefly described,
as a framework for the discussion of interaction and confounding in
subsequent sections of this chapter. Lung cancer was chosen as an
example because of its strong link to smoking and because it is the
greatest cause of cancer death in both men and women (ACS 1985).

Lung cancer will cause an estimated 125,600 deaths in 1985 (ACS
1985): 87,000 men and 38,600 women. For men, this represents more
than 8 percent of all deaths. Current U.S. age-specific lung cancer
death rates increase with age into the late seventies age range and
then decline. However, when death rates for any given birth cohort
of men are examined (Figure l), there is no decline in death rates at
the older ages. This difference between the cross-sectional mortality
statistics and the cohort data is generally attributed to differences in
the smoking habits of successive birth cohorts of men (and women)
during this century. This Report's chapter on smoking patterns in
the U.S. population also carefully documents that cigarette smoking
is not uniformly distributed in the U.S. population, but rather varies
considerably with both age and occupation. This nonuniform distri-
bution of smoking patterns introduces much of the difficulty in
controlling for smoking in occupational studies.

The relationships among age, lung cancer death rates, and number
of cigarettes smoked per day, derived from the mortality study of
U.S. veterans (Kahn 1966), are presented in Figure 2. The risk
associated with smoking is a function of both the intensity of
smoking, as measured by number of cigarettes smoked per day and
depth of inhalation, and the duration of smoking as measured by age
and age of initiation.

The lung cancer mortality ratios derived from the American
Cancer Society (ACS) study of 1 million men and women (Hammond
1966) for smokers compared with nonsmokers, stratified by age and
by number of cigarettes smoked per day, depth of inhalation, and age
of initiation are presented in Table 1. In general, the mortality ratios
are greater in the older age groups and increase with increasing
dosage measure within each age strata. The data demonstrate that
within the broader category of smokers a substantial variation in
risk (up to fivefold) occurs between the different levels of dose and
duration of smoking. The variation in mortality ratios for each
isolated measure in Table 1 almost certainly overestimates the
independent contribution of that measure to the actual risk, owing to
correlation among the measures of number of cigarettes smoked per
day, depth of inhalation, and age of initiation. For example, those
who begin to smoke at a young age also smoke more cigarettes per
day (Shopland and Brown 1985). However, it is unlikely that this
correlation among dosage and duration measures explains all of the
variation in mortality ratios with the isolated measures; therefore, it

102


1885


1880


1875

FIGURE I.-Age-specific mortality rates for cancer of the
      bronchus and lung, by birth cohort and age at
      death, men, United States, 1959-1975
SOURCE: Data derived from McKay et al. W82).

is reasonable to expect that the accuracy of lung cancer risk
estimates for a population would improve with the inclusion of a

103


FIGURE 2.-Death rates from cancer of the lung and
       bronchus in nonsmokers and smokers of
      various numbers of cigarettes per day
SOURCES Kahn (1966).

measure of smoking prevalence, a measure of smoking intensity, a
measure of smoking duration, and a measure of the duration of
cessation for former smokers.

Interactions Between Cigarette Smoking and Occupational
Exposures

Interactions between cigarette smoking and occupational expo-
sures may be examined in the context of a biological process, as a
statistical phenomenon, or as a problem in public health and
individual decisionmaking (Rothman et al. 1980; Saracci 1980;
Siemiatycki and Thomas 1981). In each of these contexts the

104


E   TABLE l.-Number of lung cancer deaths (men), age-standardized death rates, and mortality ratios, by
;'         current number of cigarettes smoked per day, degree of inhalation, and age began
if         smoking, by age at start of study
0
I                         Age35-54             Age 55.69             Age 7cH34           All ages, 35-E-4
g                       Number                 NUdX?r                 Number                 Number
I     SllKking               of     Death   Mortality     of     Death   Mortality     of     Death   Mortality     of     Death   Mortality
cn     characteristics           deaths rate     ration     deatha    rate     ratios     deaths    rate     ratios     deaths    rate     ratios

Current number of cigarettes a day

l-9                   9
lo-19                 15
20-39                138
240                  26

Degree of inhalation

None or slight            19
Moderate               114
D=P                  56

Age began cigarette .3moking

2%                   5
20-24                 31
15-19                 112
< 15                  36

Never smoked regularly        11

38       6.17       12      68    3.53        5      134      5.32      26      66      4.60
24       3.90      57     168    8.77        10      243      9.62      82      90      7.48
58       9.37      216     264    13.82        27      446     17.62      381     169     13.14
47       7.67      60     334    17.47        6      754     29.84      82     201      16.61

29       4.75      97     203    10.60        14      193      7.66      120     102      8.42
62       8.48      177     224    11.72        20      401      15.88      311     138     11.45
65       9.00      73     266    13.93        13      638     25.26      141     173     14.31

17       2.77      12
36       6.83      72
54       8.71      176
79      12.80      57

6               27

65
212
250
302

19

3.39
11.11
13.06
15.81

3
7
27
9

11

85      3.38      20      39      3.21
306     12.11      110     118      9.72
490     19.37      315     155     12.81
424     16.76      101     183     15.10

25              49      12

NCYI'E: Mortality ration are baeed on death rates carried cut to one more significant fmre than shown
SOURCE Hammond (1966).


concepts are applied somewhat differently, and confusion results
when a move from one context to another is attempted without
consideration of these differences in application. Biological interac-
tion refers to the presence of one agent influencing the form,
availability, or effect of a second agent, and includes physical
interaction such as the adsorption of carcinogens to particulates in
inspired air, process interactions such as the induction by one agent
of an enzyme system capable of converting a second agent into a
carcinogenic metabolite, and outcome interactions such as the
number of tumors produced by separate and combined exposures in
an animal exposure system. Statistical interaction refers to a
departure from the mathematical model used to assess the effects of
the exposure variables. The model being tested may be additive,
multiplicative, or some other form; the outcome of interest may be
death rates, relative risks, or other outcome measures; the indepen-
dent variables may be intensity of exposure, duration of exposure, a
combination of intensity and duration (e.g., pack-years), or a
logarithmic or other transformation of these measures. Public health
interaction usually refers to the presence or level of one agent
influencing the incidence, prevalence, or extent of disease produced
by a second agent. An exposure to two agents that resulted in a
multiplicative effect on lung cancer death rates might show no
interaction using a multiplicative statistical model, but might show a
profound interaction in terms of public health and a variety of
interactions within the biologic system under consideration (i.e.,
human carcinogenesis).

Biologic Interactions

The transformation of normal lung tissue into a clinically mani-
fest lung cancer is a complex, incompletely understood process that
is generally assumed to require multiple inheritable changes within
the cell (Armitage and Doll 1961; Day and Brown 1980). Although
cellular changes are assumed to be requisite for carcinogenesis,
phenomena taking place outside the cell may influence carcinogene-
sis. Cigarette smoke and occupational agents may potentially
interact by influencing the fraction of inhaled carcinogen deposited
and retained in the lung, the rate of metabolic activation of a
procarcinogen into a carcinogenic metabolite, the transfer of agents
across mucosal and cellular boundaries, the vulnerability of the cell
to carcinogenic change (by increasing the rate of cell replication), or
the transformation of the cellular DNA. In addition, cellular DNA
repair, humoral or metabolic factors influencing tumor growth, and
immunologic recognition or destruction of tumor cells are processes
that may influence tumor manifestation and may be affected by
occupational exposures and cigarette smoke. A detailed discussion of
chemical carcinogenesis is beyond the scope of this chapter and is

106


provided elsewhere (Weinstein 1985; Farber 1982); however, this
chapter explores some potential sites of biological interaction
between occupational exposure and cigarette smoke to illustrate the
biologic interactions that may take place.

Cigarette smoking and occupational exposures may interact
through effects of smoking on the dose of the carcinogen that reaches
the cell. Long-term exposure to cigarette smoke impairs mucociliary
clearance (US DHHS 1982) and could alter the dose of an occupation-
al agent retained. Carcinogens may adsorb to particulates in smoke
or to environmental dusts (Natusch et al. 1974; Mossman et al. 19831,
resulting in a higher fractional retention or different distribution in
the lung. The adsorption to dust may also facilitate or inhibit
transport of carcinogens through th, mucus layer. Cigarette smoke
has been shown to increase epithelial permeability in the tracheo-
bronchial tree (Simani et al. 1974); the effect may increase the
exposure of the underlying cell to an occupational agent.

Another potential site of biologic interaction is the metabolic
activation of a carcinogen. A number of agents, including the
polycyclic aromatic hydrocarbons in cigarette smoke, undergo chem-
ical transformation within the body to met,abolites that are consid-
ered to be active carcinogens (Gelboin and Tso 1978a, b). The
majority of known conversions occur through the mixed function
oxygenase system predominately located in the microsomal fraction
of the cell. A number of constituents of cigarette smoke have been
shown to induce this enzyme system (US DHEW 19791, and its
activation may increase the rate of biologic activation of procarcino-
gens in the worksite. Cigarette smoking also alters the cellular
composition of the lung, increasing the number of neutrophils and
activated macrophages in the lung (US DHHS 1984); these cells may
also play a role in the metabolic transformation of occupational
agents.

Much of the consideration of interactions between smoking and
occupational exposures has centered on interactions that might
influence the response of the cell rather than the "dose" of
carcinogen (Siemiatycki and Thomas 1981; Rothman et al. 1980;
Rothman 1974, 1978; Walter and Holford 1978). In a widely accepted
conceptual model, the process of malignant transformation of a cell
into a cancer is considered to be a multistage process requiring
multiple inheritable changes (Armitage and Doll 1961; Day and
Brown 1980). Individual agents may initiate or promote the process
of carcinogenesis. Initiation is thought to be at least a two-stage
process that requires cell division before becoming irreversible
(Farber 1982). Promotion describes the process by which an agent
encourages an initiated tissue to develop focal proliferation. A tumor
initiator may exert its effect through a brief exposure, whereas a
tumor promoter usually requires repetitive contact with initiated

107


tissue to exert its effect. Cigarette smoke is known to contain a
number of compounds that act as tumor initiators and promoters
(US DHHS 1982); occupational exposures reflect a similar range of
agents. Tumor promoters in smoke may influence the effects of
exposure to tumor initiators in the workplace and thus increase the
number of cancers that occur, and the presence of tumor initiators in
smoke may allow the expression of a tumor promoter in the
worksite.

The process of carcinogenesis is frequently modeled as a multistep
process in which each succeeding step can occur only in those cells
that have undergone the preceding step (Armitage and Doll 1961;
Day and Brown 1980). In this model, agents may influence one (or
more) of these steps, and therefore may have an effect early or late
in the carcinogenic transition. Because the later steps in the process
can occur only in cells that have undergone the changes of earlier
steps, agents that act at separate steps may have multiplicative
effects. For example, an agent that results in a fourfold increase in
the rate of transition from a hypothetical step 1 to step 2 in the
carcinogenic process would result in a fourfold increase in the
number of malignant transformations by increasing the number of
cells available for step 2 and subsequent steps. Similarly an agent
that tripled the rate of transition from step 2 to step 3 would triple
the number of malignant transformations. However, exposure to
both agents would provide a fourfold (300 percent) increase in the
number of cells available for transition from step 2 to step 3 as well
as a threefold (200 percent) increase of the rate of transition from
step 2 to step 3, with a resultant twelvefold (1,100 percent) increase
in the number of malignant transformations. Therefore, the effect of
the combined exposure on number of malignant transformations
(1,100 percent) would be greater than the sum of the effects of
independent exposures (300 percent plus 200 percent).

A similar phenomenon may occur with cigarette smoke and an
agent that has an independent and additive effect as an initiator of
carcinogenesis. The additive effects on tumor initiation may appear
as a multiplicative effect on tumor occurrence because of the action
of the tumor promoters in cigarette smoke. The tumor promoters in
smoke may act on the cells initiated by an occupational agent, as
well as on the cells initiated by smoke, to increase the number of the
cells that become cancers. The number of tumors produced by a
combined exposure could then be greater than the sum of the
numbers of tumors produced by the individual exp<osures separately.

Two additional mechanisms by which cigarette smoking and
occupational exposures may interact are by alterations in the
immunologic surveillance for cancers and by increasing the frequen-
cy of cell division. Differences in the number, type, and function of
cellular components of the immune system have been demonstrated

108


between smokers and nonsmokers (US DHHS 1984) and among
workers exposed to occupational agents (see other chapters of this
Report). The potential for these differences to influence the rates of
clinically manifest cancers (either positively or negatively) is an
issue of considerable interest. The increase in cell turnover in the
respiratory tract in response to the acute toxic and inflammatory
effects of cigarette smoke, or of occupational exposures, may also
influence cancer rates, as it is believed that cells are more
vulnerable to carcinogenic changes during periods of replication.

This discussion is intended to illustrate the kinds of biologic
interactions that might occur between smoking and occupational
agents and not to be a complete description of either the carcinogenic
process or the sites of potential interaction.

Statistical Interaction

Statistical interaction refers to departure from a mathematical
model in assessing the main effects of independent variables; its
presence is often evaluated by the addition of an interaction term to
the independent variables (Siemiatycki and Thomas 1981; Blot and
Day 1979; Saracci 1980). With this approach, the presence of
interaction is dependent on the model being used (Rothman 1974;
Kupper and Hogan 1978). For example, a multiplicative effect can be
adequately modeled without an interaction term on a log scale, but
requires an interaction term on an additive scale. In this section, an
additive model for the effects of two exposures assumes that the
combined exposure produces an effect equal to the background rate
plus the sum of the increases from the background rate of the two
exposures experienced separately. In a multiplicative model, com-
bined exposure results in an effect equal to the product of the effects
produced by the separate exposures.

The following example illustrates this terminology and demon-
strates the dependence of statistical interaction on the selected
model. Assuming that two agents independently increase the risk of
lung cancer and that the separate exposures result in a fivefold and
tenfold increase in risk, respectively, if exposure to both agents
produces an eightfold increase in risk, there is negative interaction
(protective effect) in the additive and the multiplicative models. A
combined risk of 14 indicates no interaction in an additive model, but
a negative interaction in a multiplicative model; a risk of 30 is a
positive interaction with an additive model and negative with a
multiplicative model; a risk of 50 is a positive interaction with an
additive model and no interaction with a multiplicative model; and a
risk of 60 is a positive interaction with both models.

This example illustrates the critical dependence of tests for
interaction on the mathematical model that is selected. Ideally, the
choice of a model is based on biological considerations and not on

109


statistical convenience. For example, if the potential interaction of
two initiators is being examined, an additive model should be used.
The use of a multiplicative model may result in the demonstration of
a negative interaction.

When applied to the multistage biologic model of carcinogenesis,
independent actions at the same step would yield additive effects and
actions at separate steps would yield multiplicative effects (Siemia-
tycki and Thomas 1981; Walter and Holford 1978). This progression
from the biologic model to the statistical effect is easily defended;
however, it is less clear that the reverse progression is valid,
particularly in epidemiologic studies. The demonstration of an
additive effect on lung cancer death rates does not necessarily imply
that the two agents are acting at the same point in the carcinogenic
process, nor does a multiplicative effect guarantee action at separate
steps. As should be evident from the discussion of biologic interac-
tion, cigarette smoke may interact with occupational agents at
points external to the cell, and smoke consists of a variety of agents
with different carcinogenic effects. The complex biologic processes
that underlie the exposure-disease relationships evaluated in epide-
miological studies limit the inference from the results of statistical
modeling to biological mechanisms.

Rothman (1974) and Hogan and colleagues (19781 described
methods of quantifying the magnitude of statistical interaction, and
Kupper and Hogan (1978) described the detection of interaction in
cohort and case-control studies. This Report's chapter on the
evaluation of chronic lung disease also discusses the concepts of
interaction and its measurement in studies of outcomes that are
continuous (i.e., lung function measures) rather than binary (i.e.,
presence or absence of lung cancer).

In the simplest analytical problem, departure from additivity can
be readily assessed when a population has two exposures, the rates
in the presence of each individual exposure are known, and the rates
in the presence and absence of both are known. If the relative risk
(RR) in the absence of exposure is set equal to 1, then the ratio of the
rate in the population with only one of the exposures to the rate in
the population with neither exposure is the RR associated with the
exposure. Correspondingly, the ratio of the rate in the population
with both exposures over the rate in the population with neither
exposure is the RR associated with combined exposure. The magni-
tude of the interaction can then be estimated by the ratio of the
increase in rate with combined exposure (the RR of combined
exposure minus 1) over the sum of the increases from the unexposed
rate produced by the single exposures ((RR,-l)+(RR~11). The
confidence interval around this estimate of interaction can also be
estimated (Rothman 1974) as a measure of its statistical significance.
More complicated estimates of the magnitude of interaction are

110


necessary when the rate in the unexposed population is unknown,
when the rate of the disease being measured is high in the general
population, and when case-control analyses are being performed
(Rothman 1974; Hogan et al. 1978). In general, the size of the
population needed to test for interaction between two exposures is
considerably larger than the size of the population needed to
establish statistically significant effects for the separate exposures.

Both case-control and cohort data can be analyzed with ap
proaches that involve stratification (Kleinbaum et al. 1982; Rothman
and Boice 1979). The data are separated into strata defined by levels
of the occupational exposure and of cigarette smoking. By combining
the information within the separate strata, summary measures can
then be calculated that estimate the independent effects of the
variables and describe their interaction. Although stratified analysis
can be readily performed, its application is frequently limited by the
number of available subjects, both in the entire study and within
specific strata. For example, if an investigator designates four levels
of exposure to an occupational agent and classifies smokers as
currently smoking, previously smoking, or never smoking, twelve
separate exposure categories are created. If age, sex, and race must
also be considered, stratified analysis may be feasible only if the
number of subjects is extremely large.

Statistical modeling represents an alternative that is less compro-
mised by smaller sample sizes and that provides greater flexibility
for controlling confounding and for testing for interaction. Modeling
refers to the specification of a particular mathematical relationship
between the outcome variable, e.g., the occurrence of lung cancer,
and the variables representing the exposures of interest, e.g.,
cigarette smoking and an occupational agent. Statistical methods
describe the adequacy of the model for the data and provide
estimates of the effects of the exposure variables. Modeling can be
performed with the programs available in most conventional statisti-
cal packages, but some special applications may require customized
software.

In analyzing data on the effects of occupational exposures in
populations with a high prevalence of smoking, modeling facilitates
the control of confounding by smoking; multiple variables that
characterize smoking, such as duration, daily amount, and depth of
inhalation, can be entered simultaneously into the model. Further, if
the cumulative exposures to the occupational agent and to cigarette
smoke are temporally correlated, modeling may more satisfactorily
separate their effects, in comparison with stratified analysis.

A recent report by Whittemore and McMillan (1983) illustrates the
application of modeling to occupational data. These investigators
analyzed data collected in the U.S. Public Health Service study of
Colorado Plateau uranium miners, a prospective cohort study of

111


mortality in relationship to exposure to radon daughters in the
mines. Their analysis assessed exposure to radon daughters and
cigarette smoking as risk factors for lung cancer. To assess the joint
effects of smoking and radiation, they developed and contrasted
additive and multiplicative models. They found that the multiplica-
tive model fit the data better than the additive. Of the alternative
multiplicative models, giving the highest likelihood of the data was a
linear function of the variables for smoking and radon daughter
exposure. Whittemore and McMillan then used this multiplicative
model to assess the effects of age and birth cohort. This analysis
complemented the conventional cohort methods that had been
applied previously to the data (Lundin et al. 1971; Archer et al.
1976).

Most conventional forms of modeling assume either an additive or
a multiplicative relationship between the independent effects of the
variables representing the exposures. Case-control data are most
often analyzed with the multiple logistic model (Breslow and Day
1980; Schlesselman and Stolley 19821, although alternatives have
been described (Walker and Rothman 1982; Breslow and Storer
1985). The multiple logistic model is multiplicative; the risk of
disease from multiple exposures is obtained as the product of the
risks from the individual exposures, in the absence of interaction
among the exposures. A variety of approaches have been described
for the modeling of data from cohort studies (Breslow et al. 1983;
Breslow 1985). These models may be developed as additive or as
multiplicative or on other scales.

In developing a model, confounding is controlled by introducing
variables for the potentially confounding exposures. Statistical
interaction among the variables is tested by entering terms formed
as their product or by running the model within groups of subjects
separated by their classification on one of the exposure variables.
When a product term is entered into a model to test for interaction,
the presence and extent of interaction is indicated by the coefficient
calculated for the product term. Most modeling techniques also
supply a test of statistical significance for the coefficient, under the
null hypothesis that its value is zero. Such a test of statistical
significance may not be very powerful (Greenland 19831, and the
coefficient may suggest an interaction of potentially important
magnitude, although it does not reach statistical significance at
conventional levels.

The presence of statistical interaction between two variables
demonstrates that their effects are interdependent, as assessed by
the specific statistical model (Rothman et al. 1980). Statistical
interaction does not necessarily imply biological interaction. In fact,
the interpretation of interaction hinges on the scale on which it is
measured; the choice of the statistical model may determine whether

112


interaction is present or absent, synergestic or antagonistic (Green-
land 1979; Rothman et al. 1980). If possible, the choice of model
should be based on biological considerations. For malignancy, the
results of modeling may be interpretable within the conceptual
framework supplied by the theory that carcinogenesis is a multistep
process (Armitage and Doll 1961; Day and Brown 1980).

Public Health Interactions

From a public health perspective, an interaction occurs when the
number of individuals injured, or the extent of the injury, with
combined exposure exceeds that expected from the sum of the
background rate and the differences between the background rate
and the rates with the individual exposures. Public health interac-
tions can be considered a case of statistical interaction in which both
the model being tested and the outcome measurement scale being
used are defined by their ability to assess the contribution of a given
agent to the disease burden in society. When a positive interaction
occurs in this definition, the term "synergism" should be used. The
model used to examine interactions is often further specified by the
importance of considering the intensity and duration of exposure in
the risk model being examined. Establishing a dose-response rela-
tionship for an exposure supports a causal association, and the slope
of the exposure-response relationship allows an estimation of the
reduction in disease burden that might occur with a reduction in the
workplace exposure. Both of these issues are important in establish-
ing safe levels of exposure in the working environment.

Estimation of the reduction in disease burden due to an occupa-
tional exposure with the lowering of exposure levels has three
components: How much disease will be prevented in those workers
who begin their work exposure at the new levels? How much disease
will be prevented by reducing the exposure of workers previously
exposed to higher levels to these levels? and How much disease can
be prevented by altering the smoking habits of the exposed workers?
For those exposures for which synergism between smoking and an
occupational exposure exists, the sum of these three estimates may
exceed the total amount of disease that occurs in the population
(Samet and Lerchen 1984; Doll and Peto 1981). If a group of asbestos
workers have a fiftyfold increased risk with combined exposure and
a fivefold risk with exposure only to asbestos and a tenfold risk with
exposure only to cigarettes, then elimination of smoking would
eliminate 90 percent of the risk (from 50 to 5) and elimination of
asbestos would eliminate 80 percent of the risk (from 50 to 10). The
sum of these reductions is greater than 100 percent, and points out
that for prevention efforts, the synergistic effect works to potentiate
the effect of the intervention.

113


Confounding of Occupational Exposures by Smoking Behavior

By the nature of the employing industries, most occupational
exposures occur to a limited number of individuals who are often
geographically clustered and who are not representative of the U.S.
population. Prospective studies of cancer rates in populations that
are representative of the U.S. population generally contain too few
individuals with specific occupational exposures to allow analysis by
occupational exposure. Therefore, most studies of occupational
exposures involve populations selected on the basis of a specific
exposure. Then either these selected populations of exposed workers
are compared with a control group or individuals with high dose
exposures are compared with individuals with low dose exposures.
Validity depends upon the comparability of the groups being
examined for variables that may influence cancer risk. other than
occupational exposure. Age is one such variable, as rates of most
cancers increase with increasing age. For those cancers linked to
smoking, the comparability of the smoking habits of the various
exposed subjects is a second such variable. This variation may
potentially confound an association between an occupational expo-
sure and a cancer known to be associated with smoking, and control
for this potential confounding may be critical for an unbiased
evaluation of such an association.

Sources of Confounding

Confounding is the distortion of the apparent effect of an exposure
on risk brought about by the association with other factors that can
influence the outcome (Last 1983). Cigarette smoking can be a
confounding factor in occupational studies through an association
(either positive or negative) with the exposure in question. As
described earlier in this chapter, the major determinants of smoking-
related risk in a population include smoking prevalence, intensity of
exposure, and duration of exposure. Each of these measures can
potentially confound an occupational exposure.

Smoking Status

In occupational studies, cancer mortality in the occupational
group is often compared with that in the entire population of a given
geographic area. Age-specific death rates are available for the U.S.
population on an annual basis and can be used to develop an age- and
calendar-year-adjusted overall expected number of deaths, or a
cause-specific expected number of deaths, for the population of
workers being examined. The ratio of the actual number of deaths in
the exposed population compared with the expected number in the
general population, multiplied by 100, is referred to as a standard-
ized mortality ratio (SMR) for the exposed population. The SMR may

114


be based on national mortality data or on data from the geographic
location of the exposure group. In addition to providing a control
population, the use of SMRs also adjusts for differences in age
distribution between the exposed population and the population on
which the SMR is based.

Cigarette smoking behavior is not uniformly distributed through-
out the U.S. population. As demonstrated in the preceding chapter,
there are substantial differences in smoking behavior among men
and women, blacks and whites, different age groups, and different
occupations. It is not surprising, therefore, that the smoking
behavior of selected populations of exposed workers might differ
markedly from the average for the U.S. population, and these
differences would be expected to influence the SMR for smoking-
related cancers,

Axelson (1978) has suggested that the effect on the SMR of
differences in smoking habits could be estimated by dividing the
population being examined into various smoking categories, multi-
plying the proportion of the population in that smoking category by
the relative risk of developing disease produced by that smoking
category, and summing the resultant numbers. The ratio of this
number, calculated for the exposed population and compared with
the number for the population on which the SMR is based, is then a
multiplier that can be used to evaluate the effect on the SMR of the
smoking habits of the exposed population.

In its simplest form this calculation would use only the proportion
of smokers and nonsmokers in the population and a single relative
risk number for the smokers. The effect that differences in smoking
habits might have on the SMR for three different relative risks due
to smoking is shown in Table 2. These different relative risks
correspond approximately to the different relative risks for different
sites of cancer associated with smoking (US DHHS 1982). Blair and
colleagues (1985) have compared the crude and smoking-adjusted
SMRs for different job categories in the population of the U.S.
veterans study. They used four categories: smoker, never smoked, ex-
smoker, and other. In general, adjustment for smoking did not
substantially alter the SMRs for lung cancer (R 0.881, and the
differences were small for most job categories (the largest difference
between crude and adjusted SMR, 68.0).

Measures of Smoking Intensity

The risks due to smoking increase with increasing number of
cigarettes smoked per day and depth of inhalation (Table 1) (US
DHHS 1982). A calculation, similar to the one in the preceding
section, can be performed using separate risk estimates for light
smokers and heavy smokers and for ex-smokers. The magnitude of
the effect on the SMR for lung cancer of a range of different smoking

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TABLE 2.-Effect of differences in smoking prevalence on
      the relative risk of an occupational group
      compared with a control group

                       Proportion of smokers in exposed group
Assumed risk   Proportion of smokers
due to smoking    in control group      .l       .3       .5       .I        .9

.3
.5
.I
.9

.3

.I
.9

.5

9

1.00     1.18     1.36      1.55     1.73
.85      1.00      1.15      1.31      1.46
.73      .87      1.00      1.13     1.27
.65      .76      .8a      1.00      1.12
.58      6f3      .79      .89      1.00

1.00      1.57      2.14      2.71     3.29
64      1.00      1.36      1.73     2.09
.47      .I3      1.00      1.27     1.53
.37      .58      .79      1.00     1.21
30      48      .65      .83     1.00

1.00      1.95      2.89      3.64     4.79
.51      1.00      1.49      1.97     2.46
.35      .67      1.00      1.33      1.65
.26      .51      .75      1.00      1.25
21      .41      .60      .80      1.00

prevalences and dosages is shown in Table 3, calculated using a
relative risk of 7 for smokers of less than one pack per day, 20 for
smokers of over one pack per day, and 4 for ex-smokers. These
relative risks were drawn from the major prospective mortality
studies on smoking (US DHHS 1982). The proportions of smokers
and ex-smokers in the population and the percentage of smokers who
smoke more than 20 cigarettes per day were drawn from the data
presented in the preceding chapter for the U.S. population between
the ages of 20 and 64. On the basis of the data, the current
differences in smoking patterns between blue-collar men and the
total male population might be expected to result in a 10.2 percent
elevation in the SMR for lung cancer. A hypothetical population
with a prevalence of current smoking of 80 percent might have a 59.9
percent increase in the lung cancer SMR. Correspondingly, a
population with a low smoking prevalence might have a 45.1 percent
reduction in the SMR. These numbers are similar to those calculated
for the Swedish population by Axelson (1978) as outer limits of the
adjustment that might need to be made in lung cancer SMRs,
secondary to differences in smoking patterns in an occupationally
exposed population.

One of the basic assumptions made in the risk adjustment
calculations described is that differences in smoking behavior (and
the resultant risk) can be described by simple prevalence numbers
(percentage of smokers, never smokers, and ex-smokers) or by using

116


TABLE S.-Effect of differences in smoking prevalence on
      the standardized mortality ratio for lung cancer

Smoking status

Group         Total

  Current                         SMR
c 20      220      Former     Never   multiplier

u s.
population


White collar


Blue collar

Hypothetd
1OW

40 9       29.4       70 6       40 0       19.1      1.0



39.9       27.8       72.2       40 8       19.7      0.994


47 1       28 2       71.8       34 8       18.1      1.102


20 0       29 4       70.6       20.0       600      0.549

Hypothetical
high

800       294       70.6       10.0       10 0      1.599

a division of current smoking prevalence into heavy smokers or light
smokers. Other characteristics of smoking behavior have also been
shown to influence lung cancer risk, including depth of inhalation,
age of initiation (duration), and tar and nicotine yield of the cigarette
smoked (US DHHS 1981, 1982). The differences in lung cancer
relative risks among male smokers in the ACS study of 1 million
men and women resulting from differences in depth of inhalation
and age of initiation are presented in Table 1. It is apparent that
substantial differences in lung cancer mortality ratios (up to fivefold)
can occur within the broad category of smokers because of differ-
ences in the various dosage measures. It also appears that, in
general, the difference in mortality ratios between the highest and
lowest exposure categories was greater in the older age group than in
the younger age group.

When the SMR is based on the general population, in which
smoking behavior is in the middle range of the dosage measures in
Table 1, it is unlikely that differences in behaviors between an
exposed population and the general population would equal the
differences between the highest and lowest dosage categories.
However, sizable differences may occur, and the values shown in
Table 1 can be used to estimate the impact of these differences. If the
lowest age of initiation (under 15 years) were used as the risk for the
exposed population, and the risk for an age of initiation of age 20 to
24 were used for the control population, there would be a 30 percent
increase (using one risk value for all current smokers) in the SMRs
listed in Table 3. This would increase the SMR for the hypothetical
high smoking prevalence population to 207.4. A corresponding
adjustment for a difference in depth of inhalation could increase

117


hese numbers even further. However, because there is almost
:ertainly some correlation among the various dosage measures
smokers of higher numbers of cigarettes per day are more likely to
nhale and to have begun smoking at an earlier age), it is not valid to
rest these numbers as independent measures of risk. It does seem
:lear, however, that substantial variations can occur in the "expect-
?d SMR" for a population, based on differences in smoking preva-
lence, differences in number of cigarettes smoked per day, and
probably differences in age of initiation. These adjustments suggest
that SMRs in excess of 200 may occur owing to differences in
smoking patterns and differences in depth of inhalation. The use of
high tar and nicotine cigarettes might increase the SMR even
further.

In the description of differences in smoking patterns by occupation
presented in the preceding chapter, only modest differences between
blue-collar workers and white-collar workers were found for age of
initiation and number of cigarettes smoked per day. However, larger
differences in these dosage measures are present among some of the
subcategories of blue-collar and white-collar workers. Substantial
variation from national norms in the various dosage measures may
also occur because of sampling and selection bias in the small
population samples that are often a real limitation in occupational
studies. Even in larger studies, such as the study of 17,800 asbestos
insulation workers (Hammond et al. 1979), substantial differences
between the asbestos-exposed workers and the general population in
number of cigarettes smoked per day are demonstrable (82.8 percent
of the asbestos workers smoked more than 20 cigarettes per day in
contrast with 68.5 percent of the men in the general population).

Failure to control for differences in smoking behavior may lead to
a spurious impression of interaction. A spurious interaction pro-
duced by differences in smoke dose has a greater public health
significance when the outcome is an apparent antagonism rather
than a synergism. If the workers who smoke and are exposed to a
given agent smoke fewer cigarettes per day, or began smoking later
in life than the control population, an apparent protective effect (i.e.,
a less than additive effect) of the occupational exposure may result.
In this setting, if the population of nonsmokers is too small to
evaluate the effects of the occupational agent, only the biased
estimate of the agent's effect on smokers will be available; the
spurious antagonism may mask the effect of an occupational
carcinogen by lowering the rate of lung cancer in the workers with
combined exposure. A lower number of cigarettes smoked per day
may be a relatively frequent confounder in worksites where smoking
is not allowed during working hours, and a later age of initiation
may exist in workforces with higher education levels. Thus, lack of
information on smoking may lead to biased estimates of the effect of

118


an occupational agent, and even to the impression that the agent has
no effect. This potential for missing the effects of an occupational
carcinogen makes the incorporation of dosage data a critical part of
the consideration of statistical interactions.

This discussion has used examples in which differences in smoking
dosage measures resulted in spurious interactions between smoking
and occupational exposures. However, the same potential exists for
differences in occupational exposure dose between smokers and
nonsmokers in the exposed population. If the smokers in the exposed
population have a greater exposure to an occupational carcinogen
than the nonsmokers, then the effect of combined exposure might be
expected to appear to be greater than additive.

A companion question of "dosage" measurement among the
smokers in occupational studies is how to classify pipe and cigar
smokers and former smokers. Pipe and cigar smokers have a lower
risk of developing lung cancer (but not oral cancer) than cigarette
smokers and are distributed differently by age, reflecting the greater
use of pipes and cigars by older men (US DHEW 1979). To the extent
that differences in the use of pipes and cigars exist among exposed
groups and control populations, the effects of smoking may be
confounded if pipe and cigar smokers are classified in the study as
smokers. Pipe and cigar smokers should be either analyzed as a
separate category, or if the number of subjects is too small for
separate analysis, they may be combined with light smokers as part
of a dose-response relationship. A similar problem arises with
former smokers. The lung cancer risk in former smokers declines
with the increasing duration of cessation. Few people begin to smoke
after age 25, and the percentage of the population who have quit
smoking increases with increasing age. Many occupational settings
have been the focus of intensive cessation efforts, particularly those
worksites where an increased lung cancer risk has been established
or suspected. These efforts, as well as the other previously described
reasons for differences in smoking patterns, may make the preva-
lence and age distribution of former smokers in an occupationally
exposed population different from that in a control population;
therefore, former smokers should not be included with current
smokers in an analysis of occupational exposures but should be
treated as a separate category.

One of the methods that has been used to control for the
differences in smoking between control groups and exposed popula-
tions, or between cases and controls (Liddell et al. 1984), is to
examine the dose-response relationships of smoking and occupation-
al exposure for lung cancer. An example of such an analysis
performed on a group of asbestos miners using a case-control
approach is presented in Table 4. The risk of developing lung cancer
is shown to increase with increasing cumulative asbestos exposure in

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TABLE 4.-Risks of lung cancer, by cigarette smoking and
      asbestos exposure, relative to all 223 cases and
      715 referents for whom smoking histories were
      reliable; unmatched analysis

Exposure accumulated up to 9 years before death of case!
            (f/mL)q

Pack-years `

Law       Medium
(<loo)     (< um

High and
very high
(2 1,ooo)

All

0       Number of cases            6          7          10        23
      Number of referents         103         61          37        201
      Relative risk             0.19        0.37         0.87       0.37

1, 140   Number of cases            29         27          34        90
      Number of referents         123         93          63       279
      Relative risk             0.76        0.93         1.73       1.03

240     Number of cases            40         35          35        110
      Number of referents         117         79          39       235
      Relative risk             1.10        1.42         2.88       1.50


All     Number of cases            75         69          79       223
      Number of referents         343        233         139       715
      Relative risk             0.70        0.95         1.82       1.00

s Sumber ofcqprettes a day:20 x duration in year6
SOURCE LIddell et al r19@4)

all three categories of smoking dose. Stratification is useful for
examining exposure-response relationships, an important element
in establishing a causal association between a given exposure and
lung cancer.

If stratification is used to control the confounding between
smoking and an occupational exposure, careful consideration must
be given to the relative magnitudes of the effects of smoking and
occupational exposure on lung cancer risks when determining the
number of smoking dose categories compared with the number of
occupational exposure dose categories. As discussed elsewhere in this
Report, the prevalence of smoking has been higher among men born
between 1910 and 1930 than among men born in later decades. This
cohort of men represents the older workers in many occupationally
exposed populations, and it is these same workers who were
previously exposed to levels of occupational agents that substantially
exceeded the levels currently experienced. Thus, populations of older
workers have had higher cumulative exposures to occupational
agents than their younger peers at the same age, and have also had
higher cumulative exposure to cigarette smoke than their younger
peers at the same age. The result may be a residual confounding
between cumulative occupational exposure and cumulative smoke
exposure in assessing the effects of these two exposures. If bhe

120


magnitude of the effect of smoking is large compared with the
magnitude of the effect of the occupational exposure, and few broad
categories of smoking status are used with a greater number of
categories of occupational exposure, then higher levels of smoking
dose may occur with increasing occupational exposure dose category,
generating a spurious dose-response relationship. Correspondingly,
too few occupational exposure categories may result in a spurious
strengthening of the dose-response relationship present for smoking.
The total number of categories that can be used in this kind of
analysis is usually limited by the number of lung cancer patients
available for analysis; therefore, the distribution of the dosage
categories to smoking and to the occupational exposure should
reflect the relative magnitude of the effects of the separate expo-
sures on lung cancer risk.

Duration of Exposure

In models of lung cancer risk due to smoking behavior, separate
terms for intensity of smoking and duration are commonly included.
In a risk model developed by Doll and Peto (19781 for the study of
British physicians, the term for intensity of exposure was raised to
the second power and the term for duration of exposure was raised to
the power of 4.5.

Confounding may arise because of correlation between age and
duration of exposure. Because of the importance of duration of
exposure (and its covariate age) on lung cancer risk, the majority of
the lung cancer cases will develop in the older members of a
population. Correspondingly it is the smoking prevalence and dosage
among these older workers that will largely determine the lung
cancer risk for the population. The mean prevalence or mean dosage
measures for the population do not take into account the effect of
duration of exposure on the lung cancer risk. In a comparison of
populations with different age distributions of smoking prevalence,
or of the prevalence of heavy smokers, the population with the
higher prevalence in the older age ranges will have the higher risk.

A final source of concern in examining the relationship between
occupational exposure and lung cancer in cigarette smokers is
generated by the lag time between the exposure to a carcinogen and
the clinical manifestation of lung cancer. This lag time is a
combination of the induction period (the time from exposure to
disease initiation) and the latent period (the time from disease
initiation to clinical manifestation) (Rothman 1981). This lag period
is not fixed, but rather has a broad distribution over perhaps 50 or
more years (Nicholson et al. 1982).

Epidemiologically, the shortest lag times are identified by the
interval between the age of onset of exposure and the age when an
increased relative risk can first be demonstrated secondary to the

121


exposure. For some exposures, once the exposure period has exceed-
ed the shortest lag time, the relative risk often increases rapidly
with increasing duration of exposure (Nicholson et al. 1982),
resulting in a dramatic increase in disease rates with increasing age.
It appears that the shortest lag period for smoking-induced lung
cancers is in the range of 15 to 20 years, as demonstrated by the rise
in lung cancer death rates that begins after age 30 to 35. The lag
period for occupational carcinogens in lung cancer is not well
characterized, but some agents have lag times similar to that found
with smoking (Nicholson et al.  1982; Selikoff and Lee 1978).
However, the onset of exposure to cigarettes and occupational
carcinogens may occur at substantially different ages. Any such
difference needs to be considered when examining the interactions of
occupational exposures and smoking.

Ideally, the study of an occupationally exposed cohort would follow
the entire cohort until the last survivor had died, so that late effects
of exposures would not be missed. The reality of examining working
populations and the need for timely assessment of existing risks
makes the examination of workers at a variety of ages the norm in
epidemiologic studies. In this setting, careful consideration of the
differences in age of onset of smoking and of occupational exposures
is necessary if the effects of occupational exposure are not to be
missed or underestimated. For example, assuming that the average
age of onset of smoking is 15 and the average age of onset of a
particular occupational exposure is 25, the combined exposure effect
is one of equal and additive risks of lung cancer and the lag time for
both agents is 20 years. The lung cancer risk due to smoking would
begin to increase at age 35, but because of the lo-year difference in
age of onset of exposure, the risk due to the occupational exposure
would not begin to be expressed until age 45, and even then would
appear to be much smaller than the risk due to smoking because of
the effects of the longer duration of exposure to cigarettes. If the
cohort of workers with these two exposures is relatively young, with
few older workers, then the effect of an occupational exposure may
be missed or substantially underestimated. A similar concern exists
when examining an agent that was introduced into the workplace 20
to 30 years ago. The cohort of exposed workers would represent a
cross-section of ages, and therefore a cross-section of smoking habit
durations. An additive risk effect of the occupational exposure would
be small in comparison with the cumulative risk secondary to
smoking in the older workers, and the number of cases of lung
cancer in young workers (where the risk effects might be more equal)
would be small. Again, the effect of an occupational carcinogen could
easily be missed in this setting.

This discussion uses a simple statistical model of independent
additive effects in concert with a biological concept of lag time.

122


Interpretation based on this kind of biologic extrapolation of
statistical concepts is hazardous at best; nevertheless, some consider-
ation of the differences in the age of onset of exposure should be part
of both the biologic and the statistical considerations of the
interactions between smoking and occupational exposures.

Control of Confounding

The examination of the risk associated with an occupational
exposure generally requires a comparison group. Prospective mortal-
ity studies of the general population generally have too few
individuals with the exposures of interest to allow analysis. There-
fore, cohort and case-control formats have commonly been used. The
control groups in either of these formats may be external (i.e.,
separate population) or internal (i.e., workers with high exposure
compared with workers with lower exposure). A variety of methods
have been used to deal with the confounding of occupational
exposure by cigarette smoking.

Comparisons Using External Control Populations

Common external control populations are the national or regional
populations. Death rates in these populations can be used to
generate age- and time-adjusted expected numbers of deaths for the
exposed population, with the ratio of actual deaths to expected
deaths as the SMR. The large numbers of deaths in these large
control populations results in relatively stable death rates over time
for the common causes of death, and the smoking habits of these
populations are often available from national or regional survey
data. However, the smoking habits of the population are not known
in relation to the cause of death, which limits the use of this data to
control the confounding of occupational exposure by smoking in
occupational cohorts. If the smoking habits of the workforce are also
known, then the magnitude of the effect that the differences in
smoking habits might have on the SMR can be estimated by
assigning risk values to the proportions of the populations in
different smoking categories (as described in the section on sources of
confounding) (Axelson 1978). This adjustment for differences in
smoking prevalence ignores trends over time as well as a variety of
other potential sources of confounding. However, when this ap-
proach is used, the smoking-adjusted SMR alters the expected value
of the SMR from the value of 100 that was expected prior to
adjustment for smoking.

An alternative approach is to use an external control population
for whom the smoking habits are known in relation to the causes of
death. The use of a control population with known smoking habits
allows the direct comparison of populations of smokers and non-

123


smokers with and without the exposure being investigated. These
direct comparisons allow an examination of the risk of the occupa-
tional exposure in the absence of smoking (i.e., in never smokers) and
also the examination of potential interactions between smoking and
occupational exposures. A study may be constructed to prospectively
or retrospectively examine the lung cancer death rates in a cohort of
occupationally exposed workers compared with a control population,
or a group of patients with lung cancer may be identified and
matched with a set of controls without lung cancer in order to
examine the frequency of a given occupational exposure in the two
groups. In examining lung cancer risk, it is important that the
control population be similar to the exposed population in age,
ethnicity, socioeconomic status, and geographic location.

In general, studies are designed to be able to identify levels of lung
cancer risk due to occupational carcinogens that are lower than the
level of risk due to smoking. This potential difference in magnitude
of effect needs to be assessed carefully when considering the level of
detail with which the smoking data are obtained and examined.

The selection of a control group for an occupational study is often
influenced by the ease with which data can be collected as well as by
the comparability of the control group with the exposed workers.
Control groups can be selected from unexposed workers in the same
plant, from workers in different plants where no exposure occurred,
from populations selected from the same geographic locations as the
workers, and from populations being followed as part of other
epidemiologic investigations. Some of these control groups may have
substantial differences in smoking behavior from the exposed group.
For example, if management and administrative employees are
included in the control group, the prevalence of smoking in the
control population or in comparison with a blue-collar exposed group
may be reduced. Similarly, controls selected from different worksites
may have different smoking patterns owing to differences in work
rules, age of employees, or other demographic factors, or simply by
chance. Populations drawn from other epidemiologic studies may
also have different smoking patterns, and the mode of determination
and definition of smoking status may be different from that used in
the exposed group.

A common method of controlling for the confounding due to
smoking is to separately examine smokers, nonsmokers, and former
smokers. This allows examination of the independent effects as well
as of the interactions; however, the examination of smoking patterns
represents slightly different challenges in each of these groups.

Lung cancer risks may be examined in nonsmoking populations of
occupationally exposed and nonexposed individuals for two separate
reasons. First, such analyses can establish whether a risk due to
occupational exposure occurs in the absence of cigarette smoking or

124


whether exposure only modifies the effect of smoking. Second,
nonsmokers represent the lowest dosage category in examining the
dose-response relationship for smoking. The demonstration of an
effect of an occupational exposure in the absence of cigarette
smoking requires a population of lifelong nonsmokers who have
neither smoked cigarettes or cigars or used a pipe. In contrast, when
a dose-response relationship is being examined, it would not be
unreasonable to combine never smokers with pipe and cigar smok-
ers, or even with light smokers, as a low dose group for lung cancer
risk (pipe and cigar smokers should not be included in the low dose
group for oral cancer risk). For exposures with modest increases in
lung cancer risk, the low prevalence of never smoking status,
coupled with the low expected risk of lung cancer in this group,
means that large populations of workers must be examined in order
to define the risk of exposure in the absence of smoking. Most
occupational studies are limited by the size of the workforce being
examined, and therefore, it is often necessary to combine never
smokers with low smoking risk groups in order to have an adequate
sample size. Once this combination has taken place, the study can
examine only the effect of low smoke exposure coupled with
occupational exposure, rather than the effects of occupational
exposure in the absence of smoke exposure.
The low prevalence in many current workforces of people who
have never smoked and the low risk of lung cancer in this group
generally means that only a very few lung cancer deaths occur in
this group, limiting the number of deaths for which to perform an
analysis of the effects of an occupational exposure in the absence of
smoking. For example, in the large study of asbestos insulation
workers (Hammond et al. 1979), only 5 lung cancer deaths were
recorded in nonsmokers out of more than 8,000 asbestos-exposed
workers (smokers and nonsmokers included) whose smoking habits
were known. Drawing inferences from small numbers of lung cancer
cases is necessary in occupational studies, but two important caveats
should be considered. First, it is essential that lung cancer patients
placed in the never smoking category are actually individuals who
have never smoked. The inclusion of even modest numbers of
misclassified smokers or light smokers may increase the number of
lung cancers over that expected on the basis of the risks in the never
smoker, nonexposed control population. For this reason it is critical
that the data on smoking habits be accurate and obtained in the
same way in the exposed population as in the control population.
When the level of monetary compensation for occupational disability
may be influenced by smoking status, workers may be motivated to
define themselves as never having smoked, regardless of their actual
smoking status. In many studies the determination of smoking
status is made for the living subjects by questionnaire or interview

125


TABLE &-Comparison of smoking habit data obtained
      during life and after death

Smoking habit data obtained at death

Smokmg habit data obtained
dunng life, 1971

Number

NW?r   Formerly
smoked    smoked

Smoked

Smoked at
some time

Never smoker

12       8        2        2        0

Ex-smoker                 26       2        1.5        2        7


Smoker                   76       1        12        33       30


SOURCE Berry et al. (19851.

and for those who have died (which would include most individuals
with lung cancer> by questioning next of kin or checking hospital
records. Berry and colleagues (1985) examined the comparability of
these data sources in a prospective evaluation of asbestos workers in
which smoking data were accumulated both at the start of the study
period (i.e., prospectively) and at the time of death from lung cancer
(i.e., retrospectively). A comparison of the smoking status obtained
by the two methods for the same individuals is shown in Table 5. In
general, there was good agreement between the two methods, but
both methods identified as never smokers individuals who were
classified as smokers by the other method. No data were presented to
allow determination of which method was more accurate.

The random misclassification of smoking status, of itself, should
not introduce spurious associations for the population as a whole, or
for the smokers in the population (Greenland 19801. However, when
the question being asked is whether a risk exists in the absence of
smoking and synergism between smoking and the occupational
exposure is present, the misclassification of even small numbers of
exposed smokers as nonsmokers can lead to the conclusion of
increased risk of lung cancer due to an occupational exposure in the
absence of cigarette smoking. The potential for misclassification
exists and is of greatest concern when decisions are being made on
small numbers of cases.

The second caveat that may need to be applied in the examination
of the effects of occupational exposure among people who have never
smoked is the potential effect of involuntary exposure to cigarette
smoke. A number of studies have shown increased lung cancer risks
in the nonsmoking wives of smokers, raising the question of a
carcinogenic risk due to environmental tobacco smoke exposure
(IARC, in press). If these studies can be extrapolated to the
workplace, then the potential exists for environmental tobacco
smoke in the worksite to act as an occupational carcinogen,

126


particularly in those occupations in which there is a high prevalence
of active smoking among workers.

The considerations raised by examination of smokers with work-
place exposures are somewhat different from those raised by
examination of nonsmokers. Comparisons of smokers with and
without an occupational exposure r. `I-
                      pnqiire careful attention to the
correlations among age, duration of exposure, and smoking dose. Age
adjustment of the death rates in the exposed group and the control
population is generally accepted as more useful than simply compar-
ing the mean age of the two populations, because of the rapid rise in
lung cancer death rates in the older age groups. It is less widely
understood that age adjustment does not eliminate the effects of
differences in the age distributions of smokers between the two
populations. The smoking-related risk of developing lung cancer
occurs disproportionately in older smokers compared with younger
smokers. Therefore, in two populations with similar prevalences of
smoking, but with different age distributions of that smoking
prevalence, the population with the higher prevalence of smoking in
the older age group will have the higher number of lung cancer
deaths. This difference in number of lung cancers will persist after
an age adjustment using the age distributions of the entire popula-
tion (smoker and nonsmoker). Therefore, in considering the differ-
ences between occupationally exposed smokers and smokers who are
not exposed, the lung cancer deaths should be adjusted for age on the
basis of the age distribution of the smokers in the two populations
rather than the age distribution of the entire population.

Several attempts have been made to combine the strengths of
large population-based measurements with the detailed measure-
ments of smoking status available in cohort studies. Hammond and
colleagues (1979) used the American Cancer Society (ACS) study of 1
million men and women to develop a control group for a study of
asbestos insulation workers. From the ACS study population, they
extracted a group of more than 73,000 men who were white, not a
farmer, had no more than high school education; did have a history
of occupational exposure to dust, fumes, vapors, gases, chemicals, or
radiation; and were alive at the time of the initiation of followup of
the insulators. From this control group, they were able to develop
age-specific and smoking-specific expected lung cancer death rates
for comparison with the observed death rates in the insulation
workers. There was a difference in the time period of followup
between these two studies; therefore, the expected lung cancer death
rates were adjusted upward on the basis of differences in the
national lung cancer death rates during the years of differential
followup. This approach allowed the expected rates to be calculated
from a large enough population to provide stable rates in a number
of separate age and smoking categories. The control group and the

127


exposed populations were also matched for a number of those
characteristics that raise questions about the comparability of
national death rate data to populations of employed workers.

A somewhat different approach to the same problem was taken by
Berry and colleagues (1985). They used data from a prospective
mortality study of British physicians by smoking status (Doll and
Peto 1978, 1981) to develop factors that related the risks of smokers,
nonsmokers, and ex-smokers separately to the risk in the entire
population of physicians. They calculated the expected number of
deaths for the exposed workers in each smoking category, using
national death rate data, and multiplied this expected number of
deaths by the smoking factor to get a smoking-specific expected
number of deaths for each category of exposed workers. They also
adjusted the number of expected deaths for differences in g-graphic
location by multiplying the expected deaths by the ratio of the local
lung cancer SMR to the national lung cancer SMR. This approach is
obviously quite sensitive to the method by which the smoking-
specific factors are developed, and it is not clear that one set of
factors can be applied to all ages.

When an explicit control population is being used, the differences
in smoking behavior can be controlled through the use of a statistical
model for lung cancer risk in the population. Models may include a
variety of measures of cigarette smoking dosage and duration, and
the mortality experienced by the exposed population can be exam-
ined by using the risk model developed in the control population.
This approach allows the confounding due to smoking to be adjusted
through the use of terms for intensity and duration of exposure.

Comparisons Using Internal Control Populations

The use of an internal control group drawn from the same
workforce as the exposed population, but not exposed to the agent of
interest, may produce a control group that is more closely matched
to the exposed population than the total US. population would be
(Breslow et al. 1983; Pasternack and Shore 1976; Redmond and
Breslin 1975). Working populations tend to have a lower overall
mortality than the U.S. population of the same ages (McMichael
1976; Enterline 1975; Fox and Collier 1976; Shindell et al. 1978;
Vinni and Hakama 19801, at least in part because workers with
illness tend to drop out of the working population. This lower
mortality has been called the healthy worker effect and is one of the
reasons the selection of an internal control population may be more
appropriate than using SMRs for evaluating occupational exposure
risks. External control groups, selected from populations geographi-
cally or demographically similar to the exposed population, may also
provide a population more similar to the exposed workers than the
general U.S. population.

128


That the smoking behaviors of the exposed group and the control
population are comparable must still be established. The selection of
a control population based on its similarity in one variable (such as
worksite) does not allow the assumption of comparability on other
variables (such as smoking behaviors). It is possible for a control
population to deviate from national measures of smoking behavior in
one direction and for the exposed population to deviate in the
opposite direction; thus it is important to actually examine the
comparability of the smoking behaviors in the exposed group and the
control population even when an internal control population is used.

The absence of an external control group means that the entire
population has some exposure. Potential confounding of cumulative
occupational exposure by cumulative smoking exposure can be
reduced by stratification of the two exposures in question. The risk
with increasing exposure to an occupational agent can then be
examined within each strata of smoking exposure. Stratification of
smoking by intensity only (cigarettes per day) would lead to a
residual confounding of smoking and cumulative dust exposure,
owing to the importance of duration of smoking for lung cancer risk
and the association of age with both duration of smoking and
cumulative dust exposure.

The reduction of residual confounding should also guide the
selection of the number of strata selected for smoking and the
occupational exposure. The larger the risk due to smoking in
relation to the risk due to the occupational exposure, the larger the
number of smoking strata needed to control the confounding. The
use of too few strata may result in the residual confounding
producing the appearance of a dose-response relationship with the
occupational exposure.

A second method of controlling the confounding of occupational
exposure by smoking behaviors is through the use of modeling
techniques. By using a multiple logistic regression, a model of the
smoking variables that contribute to lung cancer risk can be
developed. The model should include measures of intensity and
duration as well as a factor for cessation. Other factors that may
contribute to the model are type of cigarette smoked, use of pipes or
cigars, and age of initiation (as separate from duration). Once the
model is established for smoking variables, a term or terms for the
occupational exposure can be added to the risk prediction equation
and tested to see whether the term improves the fit of the model to
the observed data.

Case-control analyses can also be applied in the absence of an
external control group by examining the distribution of exposures in
cases of lung cancer and in a control group selected from the sample
population of workers, but who have not died of lung cancer.
Confounding due to cigarette smoking can then be controlled by

129


stratification (Liddell et al. 1984) or by modeling (Whittemore and
McMillan 1983; Pathak et al., in press). This approach is particularly
useful when a case-control analysis can be nested within an ongoing
study of a cohort of workers. In this setting, the smoking habits of
the workforce are often known prior to the development of lung
cancer, eliminating the potential for biased recall of smoking habits
by the lung cancer patients (or their survivors) compared with the
controls.

Examination of Occupational Exposures When Smoking Habits
Are Not Known

In many occupational settings the smoking habits of the workforce
are either unavailable or incompletely ascertained. In these cases,
the death rates for these workers are compared with rates for a
control population or with national mortality data (to generate an
SMR). The potential for smoking pattern differences to influence the
SMR is then evaluated by calculating the maximal distortion that
would be produced, assuming that the exposed population had a very
high smoking prevalence. The calculations used are similar to those
used in generating Tables 2 and 3. As discussed earlier, extremes of
differences in smoking prevalence and dosage could be expected to
generate SMRs in excess of 200, and differences in age distribution
and type of cigarette smoked may increase this number even more.
Once an outer limit for smoking-related distortions of the SMR is
estimated, it becomes the value that must be below (outside) the
confidence interval surrounding the actual SMR for the exposed
population in order to exclude a potential smoking effect. This
approach may be useful in settings where smoking data are
unobtainable, but should not be used as a substitute for collecting
smoking information.

When the mortality in a control population is compared with the
mortality of an exposed population in the absence of smoking data,
the potential for differences between the smoking habits of the two
populations may be larger than the differences when using SMRs.
The control group and the exposed population may deviate in
opposite directions from the mean smoking behaviors represented in
the SMR, and correspondingly, the differences in cancer outcome
may also be magnified.

One method of adjusting for differences in smoking patterns
between populations when smoking data are not available, or would
be too costly to obtain, is to survey a random sample of the two
populations for smoking behavior. The limitation of this technique is
that the sample size needed to obtain estimates of usable precision is
large and may approximate the size of the two populations com-
bined.

130


An additional method of examining the effects of unknown
differences in smoking habits on the rates of one smoking-related
cancer is to look at the rates of other smoking-related cancers in the
same population. The various smoking-associated cancers do not all
have the same incidence rates, rate of change in incidence with time,
ethnic distribution, cure rate, or age distribution. These differences
make cross-comparison between rates of these cancers as a measure
of differences in smoking patterns between populations a complex
and uncertain exercise at best. This kind of comparison may be
useful as a point of discussion, but probably offers little in the way of
an estimate of the differences between populations in their smoking
behavior.

Summary and Conclusions

1. Cigarette smoking and occupational exposures may interact
biologically, within a given statistical model and in their public
health consequences. The demonstration of an interaction at
one of these levels does not always characterize the nature of
the interaction at the other levels.
2. Information on smoking behaviors should be collected as part
of the health screening of all workers and made a part of their
permanent exposure record.

3. Examination of the smoking behavior of an exposed population
should include measures of smoking prevalence, smoking dose,
and duration of smoking.

4. Differences in age of onset of exposure to cigarette smoke and
occupational exposures should be considered when evaluating
studies of occupational exposure, particularly when the ex-
posed population is relatively young or the exposure is of
relatively recent onset.

131


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135


CHAPTER 4

  EVALUATION OF
CHRONIC LUNG DISEASE
IN THE WORKPLACE

157-964 0 - 86 - c


CONTENTS

Introduction

Chronic Lung Diseases
  Sources of Information
  Occurrence of Chronic Lung Diseases

Patterns of Lung Injury
  Injury From Cigarette Smoke
  Injury From Occupational Exposures

Methods for Evaluating the Effects of Occupational Expo-
sures on the Lungs
  History of Respiratory Symptoms
  Chest X Ray

Physiological Assessment

Quantification of Effects of Smoking and Occupation in
Populations
  Concepts of Interaction
  Study Design
  Assessment of Exposures
    Cigarette Smoking
    Occupational Exposures
  Data Analysis
  Specific Investigation Issues
    Population Selection
    External Control Populations
    Colinearity of Aging, Cigarette Smoking, and Oc-
     cupational Exposure Effects

Quantification of Effects in Individuals

Summary and Conclusions

References

139


Introduction

Exposure to harmful agents in the workplace is, and will probably
continue to be, an important and avoidable cause of both acute and
chronic lung diseases. The major chronic lung diseases associated
with workplace exposures can be classified as the pneumoconioses
(fibrotic diseases of the lung parenchyma secondary to dust inhala-
tion), industrial bronchitis and other processes involving the lung's
airways, and occupational asthma. Some of these diseases were
recognized long before cigarette smoking became prevalent. During
the 16th century, Agricola and Paracelsus described diseases of
miners (Hunter 1978); early in the 18th century, Ramazzini (1940)
reported further on the respiratory problems of miners and noted
that the lungs of stonecutters were full of sand. Occupational lung
disease in coal miners was recognized during the 1800s (Morgan
1984a).

In the 20th century, many chronic lung diseases caused by
workplace exposures have been studied intensively using epidemio-
logical, physiological, and clinical approaches. The resulting data
have been essential for developing the standards that govern
workplace exposures and for evaluating worker safety. In this
century, however, assessment of the effects of occupational agents on
the lung has been made difficult by the widespread smoking of
cigarettes. This behavior has been particularly prevalent among
those at high risk for occupational lung diseases-men employed in
blue-collar jobs (US DHEW 1979b).

The degree of pulmonary impairment in any individual represents
the summation of the effects of all harmful environmental factors,
including cigarette smoking, occupational agents, and other expo-
sures. Cigarette smoking, in the absence of other exposures, causes
chronic bronchitis (cough and mucous hypersecretion), airway abnor-
malities, and emphysema (abnormal dilation of the distal airspaces
with destruction of alveolar walls); together, the last two disease
processes underlie the expiratory flow limitation found in chronic
obstructive lung disease (COLD) (US DHHS 1984). Cigarette smoking
may potentiate the effects of some occupational agents on the lung.
This potentiation may occur through an effect of cigarette smoke on
the mechanism of lung injury that results from a given occupational
exposure, or it may result from a mechanism of lung injury due to
cigarette smoke that is independent of the mechanism of occupation-
al injury but produces a level of combined lung damage capable of
potentiating the level of disability or the level of abnormality
detected by pulmonary function tests, x rays, or symptoms. The term
"synergism" is used in this chapter to refer to an effect of combined
exposure to cigarette smoke and occupational agents that results in a
level of abnormality (by whatever measure being used) that is
significantly greater than the sum of the levels of abnormality

141


produced by the agents separately. Such interactions are of impor-
tance not only for researchers but also for the exposed workers and
their employers. Synergism between cigarette smoking and occupa-
tional agents may, at the individual level, markedly raise the risk of
developing disease and, at the group level, greatly increase the
burden of occupational disease in the workforce. Thus, in evaluating
the effects of workplace exposures on the lung, consideration must be
given not only to the independent effects of cigarette smoking and of
the agent of interest but also to the possible interaction of these
factors.

This chapter describes the techniques used to evaluate chronic
lung disease in the workplace and addresses the methodological
issues raised by cigarette smoking. The focus of the chapter is largely
confined to the chronic, fixed lung injuries that result from these
exposures rather than the acute reversible responses that character-
ize occupational asthma. This focus was adopted in the interest of
clarity and brevity and does not suggest that the issues related to the
evaluation of occupational asthma are either unimportant or
unrelated to cigarette smoking. Emphasis is placed on methodologi-
cal problems; specific exposures are reviewed in other chapters of
this Report.

Chronic Lung Diseases

Sources of Information

Although cigarette smoking is the predominant cause of preventa-
ble morbidity and mortality from respiratory diseases in the United
States (US DHHS 1984), occupational exposures also produce sub-
stantial disease. Because the occurrence of nonmalignant respiratory
diseases is not directly monitored, its frequency must be estimated
from diverse information sources such as the National Center for
Health Statistics, the U.S. Bureau of Labor Statistics, the Social
Security Administration, and epidemiologic surveys. The extent to
which chronic lung diseases are ascertained by these sources is
difficult to establish, but coverage is probably not comprehensive.

Vital statistics enumerate the numbers of deaths from specific
causes. Chronic conditions, such as respiratory diseases, may be
listed on the death certificate, but remain uncoded unless they led
directly to death. For example, Rank and Bal (1984) reviewed death
certificates and found that in comparison with its frequency as an
underlying cause of death, emphysema was listed nearly twice as
often as an uncoded "other" condition. Vital statistics data cannot
readily be used for addressing questions related to the pulmonary
effects of cigarette smoking and occupational exposures. Cigarette
smoking is not included on the death certificate, and only usual

142


TABLE l.-Number of deaths in selected categories of the
     International Classification of Diseases (ICD),
     for three time periods, United States

Year (classification)

Cause of death           1960 (ICDI        1970 (ICDI         1980 (ICDI

COLD

Chronic bronchitis       2.287  15021        5,014  (491)        3,269  (491)

Emphysema           9.253  (527.11       22,721  (4921       13.677  (4921

Chronic airways
obstruction n.e.c. '          -            4,444  1519.31      34,743  (496)

Occupational disorders

Coal workers'
pneumoconiosls           810  1523.1)       1,160  (515.1)        982  mlo)

Asbestosis              21  1523.2)         26  (515.2~         101  will

Silicosis               550  1523.01        355  (515.0)         207  (502)

Other inorganic dusts                      13  (516.01          8  (5031

Other dusts             62  (524)          7  (516.1)          3  (504)

Unspecified             210  (523.3)                       281  (505)

Conditions due to
chemical fumes/vapors                      5  !516.21         43  (506)


Chronic interstitial
pneumonia            3,973  (525)        3,351  (517)         202  (516.31

' Not elsewhere claasifwzd
SOURCE, US DHEW (19631; National Center for Health Statista (1974), unpublished data (1980).

occupation and industry are noted. Further, the occupational
information is not routinely coded by States (Kaminski et al. 1981).

Cause of death is coded according to the International Classifica-
tion of Diseases, currently in its ninth revision (WHO 1977). For the
chronic respiratory diseases, separate categories cover the obstruc-
tive disorders, major pneumoconioses, and other interstitial diseases
(Table 1). As the International Classification of Diseases has been
modified from the seventh through the ninth revisions, major
changes in the coding of chronic respiratory diseases have been
made. The categories for occupational lung diseases have been
expanded and their titles have been made more specific. With the
eighth revision (US DHEW 1968), a category (519.3) was added for
the diagnosis of chronic obstructive lung disease (COLD). These
changes must be considered in examining time trends of mortality.
For example, after the introduction of a category for COLD, the
number of deaths assigned to this code increased and deaths
attributed to emphysema decreased (Table 11.

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Estimates of disease occurrence based on vital statistics must be
interpreted with caution. Some causes of death may be underreport-
ed, and mortality rates may not directly reflect incidence. The
mortality rate for a particular disease approximates the incidence
rate as the case-fatality rate approaches unity (Kleinbaum et al.
1982). Competing causes of death will also influence the relationship
between incidence and mortality (Kleinbaum et al. 1982). For
example, Berry (1981a) examined the mortality of 665 men certified
as having asbestosis by medical boards in England and Wales. Of the
283 deaths, 39 percent were from lung cancer, 9 percent were from
mesothelioma, and only 20 percent were from asbestosis. The
distribution of competing causes of death should be different in
smokers and nonsmokers; thus, even for non-smoking-related occu-
pational lung diseases the relationship between incidence and
mortality may vary with smoking practices.

For several respiratory diseases, vital statistics underestimate
mortality. For COLD, Mitchell and colleagues (1971) compared cause
of death, as reported on the death certificate, with clinical and
autopsy-derived diagnoses. In 211 subjects who died of COLD, as
determined by autopsy, another cause of death was listed on the
death certificate for 51. For asbestosis, Hammond and colleagues
(1979) used "the best available medical information" and identified
160 deaths from this pneumoconiosis in a cohort study of asbestos
workers. Only 76 were similarly classified by the death certificate
statement of cause of death.

State workmen's compensation claims are another source of
information about the occurrence of occupational lung diseases.
However, most workmen's compensation claims involve acute prob-
lems (Whorton 1983) and may more accurately measure conditions
associated with irritant gas or vapor inhalation than with the
pneumoconioses.

Under the Occupational Safety and Health Act, selected employ-
ers are required to maintain records of occupational injury and
illness (US House of Representatives 1984). In an annual survey, the
Bureau of Labor Statistics collects and reports the injury and illness
data. During 1982, 2,000 reports for dust diseases of the lungs and
8,800 for respiratory conditions due to toxic agents were filed, but
more specific diagnoses were unavailable (US DOL 1984). In the
introduction to the 1982 survey, it was acknowledged that "to the
extent that occupational illnesses are unrecognized and therefore
unreported, the survey estimates understate their occurrence" (US
DOL 1984, p. 3).

On a national level, the Social Security Administration operates a
compensation program for people who have been disabled for at least
5 months (US DHHS 1983). People receiving compensation for
chronic lung diseases must meet this criterion as well as stringent

144


requirements for the extent of impairment on lung function testing
(US DHEW 1979a). Data from the Social Security Administration
probably underestimate the prevalence of most chronic lung dis-
eases. For example, Epler and colleagues (1980) showed that
approximately 9 percent of a series of clinically diagnosed patients
with pneumoconiosis met the Social Security disability criteria.

Epidemiological surveys offer the most accurate estimates of
disease frequency, though the surveyed populations are generally
limited to employed workers and disease frequency may therefore be
underestimated. Estimates of disease frequency from a particular
survey should be generalized cautiously. Nonrandom selection of
occupational groups for study as well as the nonrandom enrollment
of workers within a particular workforce may introduce bias.

Occurrence of Chronic Lung Diseases

Although the available data sources have limitations, they can be
used to document the relative frequencies of cigarette-related and
occupation-related chronic lung diseases. Most indicate that the
diseases associated with cigarette smoking are much more common
in the general population than those resulting from occupational
exposures.

In recent years, mortality from COLD has steadily increased; the
number of deaths rose from 32,179 in 1970 to 51,889 in 1980 (Table
1). The 1984 Surgeon General's Report, The Health Consequences of
Smoking: Chronic ObstructiveLung Disease (US DHHS 19841, offered
the estimate that 60,000 people would die from COLD during that
year. Examination of COLD mortality rates for smokers and
nonsmokers suggests that 85 to 90 percent of COLD deaths in the
United States can be attributed to cigarette smoking (US DHHS
1984).

As described in the 1984 Surgeon General's Report, numerous
surveys provide estimates of the prevalence of COLD (US DHHS
1984). Representative recent data have been collected in Tucson,
Arizona, in six other U.S. cities, and nationwide in the National
Health Interview Survey (NHIS). Lebowitz and colleagues (1975)
sampled 3,805 subjects in Tucson from 1972 through 1974. In men
over 44 years of age, physician-diagnosed chronic bronchitis and
emphysema were reported to be 10.2 and 13.3 percent, respectively.
In women over 44 years of age, the percentage with chronic
bronchitis was 9.0 percent and with emphysema, 4.3 percent. From
1974 through 1977, Ferris and colleagues (1978) surveyed 7,909 men
and women in six U.S. cities; 5 percent of the men and 1.9 percent of
the women had airway obstruction, defined as a ratio of forced
expiratory volume in 1 second (FEV,) to forced vital capacity (FVC)
less than or equal to 60 percent. The 1970 NHIS included about
116,000 persons in a nationwide sample (NCHS 1974). Individuals 19

145


years of age and older were asked whether they or other family
members not present at the time of the interview had bronchitis or
emphysema during the previous 12 months. On the basis of this
survey, 3.4 million Americans over 45 years of age were projected as
having chronic bronchitis or emphysema. In contrast, data from the
Social Security Administration, not included in the 1984 Surgeon
General's Report, showed only 20,246 new claimants for COLD
receiving disability benefits in 1979 (US DHHS 1983).

The available data sources also probably do not comprehensively
document the nationwide occurrence of occupational lung diseases.
The number of deaths recorded as due to several occupational lung
diseases was stable from 1960 to 1980 (Table l), but it is unlikely that
these death certificate data provide accurate estimates of the actual
prevalence or severity of these disease processes in the U.S.
population, owing to the inaccurate reporting of these diseases as
cause of death. The Social Security Administration is also an ongoing
source of information. In 1977, 820 persons were granted disability
for pneumoconiosis; in 1979, the number had decreased to 389 (US
DHHS 1983). Data from the 1970 NHIS provide an estimate of the
prevalence of work-related chronic lung diseases across the Nation
(NCHS 1974). Participants were queried concerning dust in the
lungs, silicosis, or pneumoconiosis during the previous 12 months;
their responses were used to estimate that 126,000 people nationwide
had these conditions.

Numerous workforces in the United States and elsewhere have
been surveyed to establish the prevalence of occupational and
nonoccupational lung diseases. Representative recent surveys of
workers in the United States are presented in Table 2, showing the
prevalence of disease and of cigarette smoking. Various disease
indicators were considered in these studies. Chronic bronchitis was
diagnosed on the basis of persistent cough and phlegm as ascertained
by questionnaire. For the pneumoconioses, the presence of disease
was based on the presence of radiographic abnormality. Of note is
the high prevalence of coal workers' pneumoconiosis reported by
Morgan and colleagues (1973). A different group of readers subse-
quently reinterpreted the chest films reported in the Morgan and
colleagues study and found a prevalence of only 12 percent; this
lower prevalence suggests overinterpretation on the initial reading
(Morring and Attfield 1984).

Regardless of the occupational group, cigarette smoking is com-
mon, even in workforces exposed to acknowledged respiratory
hazards (Tabit: 2). At the time the selected surveys of these workers
were conducted, 1966 to 1977 for the asbestos workers (Weiss and
Theodos 1978; Samet et al. 1979) and 1981 for the uranium miners
(Samet et al. 19841, knowledge of the hazards of these occupations
was widely disseminated and information concerning interaction

146


TABLE 2.-Prevalence of cigarette smoking and
     occupational lung disease in selected survey
      populations

Study, location.
years of study

Study population

Prevalence of smokmg   Prevalence of disease
   Iper 100)         cper 1M)l

Kibelstis et al
119731, c s..
1969

Morgan et al
119731, U.S..
1969

Weiss and Theodos
(19781, U.S..
1975

Samet et al
11979J. U.S..
196G1977

Theriault et al
(19741, U.S.,
1971

&met et al
11984), U.S..
1981

Merchant et al.
(1973), U.S.,
197M971

Do Pica et al.
(19771. U.S.,
1974

Gruchow et al.
I1981 I, U.S.

8.555 coal miners

9,076 coal m,ners

88 workers from two
asbestos manufacturing
phIItS

409 workers from two
asbestos manufacturing
plants and two shtpyards

792 granite shed
workers

192 uranium miners

787 male, 473

Smokers 51
Ex-smokers 24
Nonsmokers 25

Smokers 56
Ex-smokers 23
Nonsmokers 21

Smokers 4666
Ex-smokers 27-42
Nonsmokers 10-18

Exposed workers
Smokers 61
Ex-smokers 25
Nonsmokers 13

Smokers    43
Exsmokers 39
Nonsmokers 19

M W

female cotton textile    Smokers    63   44
mill workers         Ex-smokers  16   6
               Nonsmokers 21   50

300 grain workers

Smokers 59      Chronic bronchitis
Ex-smokers 22       Smokers 42
Nonsmokers 19       Nonsmokers 30

1,510 farm workers

Smokers 15
Ex-smokers 27
Nonsmokers 57

Chronic bronchitis
Smokers 3~3
Ex-smokers 30
Nonsmokers 25

Airway obstruction '
Smokers 18
Ex-smokers 14
Nonsmokers 6

Coal workers'
pneumoconiosis
Simple     30.0
Complicated   2.5

X-ray profusion
   >l/O 20

X-ray profusion
2110 12-31
2211   513

X-ray profusion
  l/O 21
  210 7
  3/o 2

X-ray profusion
2110 8.0

Chronic cough/phlegm
< 10 years mining 52
10-19 years mining 46
220 years mining 59

   Byssinosls
          M W
Current smokers 25 19
Never smokers 18 15

Farmers lung disease
         0.5

147


with cigarette smoking was accumulating. Nevertheless, a large
proportion of the participants in these surveys smoked cigarettes.
The findings from these surveys with regard to the prevalence of
smoking are supported by larger data sets collected from population
samples (Friedman et al. 1973; Sterling and Weinkam 1976).
Friedman and colleagues (1973) questioned 70,289 participants in
the Kaiser-Permanente Multiphasic Health Checkups program and
found a higher proportion of smokers in those reporting occupational
exposure to asbestos, silica, or fumes. Similarly, Sterling and
Weinkam (1976) examined smoking patterns by employment status
in data from the 1970 NHIS and found the prevalence of smoking to
be highest among blue-collar workers. Association between occupa-
tional group and cigarette smoking practices is addressed in detail
elsewhere in this Report.

Thus, in research and clinical care related to chronic occupational
lung diseases, consideration must be given not only to occupational
exposures but also to cigarette smoking. The remainder of this
chapter describes the general patterns of lung injury by cigarette
smoking and occupational exposures and the methods used for
evaluating workers who are exposed to both.

Patterns of Lung Injury

The sites of lung injury caused by cigarette smoke and occupation-
al agents may be broadly categorized as the large airways, the small
airways, and the parenchyma. The effects of cigarette smoke on
these sites are summarized in Table 3. A comparison of injury
patterns from cigarette smoke and from selected, but representative,
occupational exposures follows.

Injury From Cigarette Smoke

The pattern of lung injury associated with cigarette smoking has
been comprehensively described elsewhere (US DHHS 1984). In the
large airways, cigarette smoke causes an increase in mucous gland
size and in goblet cell number. These changes result in increased
mucus production and the associated symptom of chronic bronchitis.
Large airway injury may contribute to airflow obstruction, but the
peripheral airways are the predominant site of the increased airflow
resistance in COLD (US DHHS 1984).

Changes in the small airways are one of the earliest manifesta-
tions of cigarette smoking. Niewoehner and colleagues (1974) exam-
ined the lungs of 20 smokers and 19 nonsmokers who died suddenly
at a mean age of 25 years. A pattern of small airways injury, termed
"respiratory bronchiolitis," was readily identified, even in these
young smokers. Clusters of brown pigmented macrophages were
found in the respiratory bronchioles, which also displayed increased

148


TABLE 3.-Pathologic changes and manifestations of lung
      injury by cigarette smoke

Large airways

Small airways

Parenchyma

Pathologic changes






Manifestations

Mucous gland hyper-   Goblet cell metaplasia. Emphysema,
plasia. inflammation    inflammation and     minimal
and edema, ' bronchial  fibrosis of the       interstital
smooth muscle      respiratory bronchiole   fibrosis

Symptoms      Cough, phlegm

Physical signs     None

Cough, phlegm


Crackles

Dyspnea


Diminished breath
SOUdS

X ray          None

Pulmonary function ? j FEV,
testing

? Linear opacities    ? Linear opacities

FEV,, 1 FEV,%,    i FEV,, 1 FEV,%,
: TLC, 1 RV. J DLCO  `TLC, TRV. LDLCO


Accelerated annual    Accelerated annual
decline of FEV,      decline of FEV,

numbers of inflammatory cells and denuded epithelium. To charac-
terize the physiological consequences of small airways injury associ-
ated with smoking cigarettes, Cosio and colleagues (1978) correlated
small airways morphology with lung function in 36 patients under-
going thoracotomy for a localized lesion. With increasing cumulative
consumption, both inflammation and fibrosis of the respiratory
bronchioles increased. Furthermore, airflow obstruction, as mea-
sured by the ratio of FEV, to FVC or by the maximum midexpirato-
ry flow rate (FEFzMNI, progressively decreased and residual volume
increased with the amount smoked. Physiological measures of
airflow obstruction correlated with the severity of small airways
abnormalities.

The major parenchymal injury associated with cigarette smoking
is emphysema: "abnormal dilation of air spaces distal to the
terminal bronchioles accompanied by destruction of air space walls"
(US DHHS 1984, p. 119). Emphysema and small airways injury
contribute to the physiological impairment found in COLD; in
individual patients with COLD, either may be predominant, but both
are probably important in most (US DHHS 1984). By itself, emphyse-
ma is accompanied by spirometric evidence of airflow obstruction,
increased lung compliance, and increased total lung capacity (TLC)
and residual volume (RV). The diffusing capacity for carbon monox-
ide varies inversely with the extent of emphysema (Park et al. 1970;
Cotes 1979). Emphysema is also associated with abnormalities of gas
exchange.

149


Cigarette smoking, through its effects on the small airways and
lung parenchyma, produces the clinical syndrome of expiratory flow
limitation with dyspnea. The chronic airflow obstruction found in
COLD develops progressively and insidiously in most cases through a
sustained excessive decline of ventilatory function (US DHHS 1984).
In COLD, spirometry shows reduced FEV, and a reduced FEV, to
FVC ratio; FVC may also be diminished. The airflow obstruction is
accompanied by increases in RV and TLC (Boushy et al. 1971; Cotes
1979).

Injury From Occupational Exposures

For occupational exposures in the absence of cigarette smoking,
the patterns of lung injury vary among the agents, presumably on
the basis of differences in their physical and chemical properties.
Although the clinical and physiological manifestations of occupa-
tional lung injury may be distinct from those of cigarette smoking,
overlap occurs for some exposures.

As with cigarette smoke, chronic irritation of the large airways by
dusts and gases is associated with mucous gland enlargement and
mucus hypersecretion (Morgan 1978, 1984b). This pattern of injury
has been well documented clinically and pathologically for coal and
cotton dust (Douglas et al. 1982; Edwards et al. 1975; Kibelstis et al.
1973; Merchant et al. 1972). Gold miners and grain workers also
develop chronic bronchitis attributable to occupational dust expo-
sure (Irwig and Rocks 1978; Dosman et al. 1980).

Industrial bronchitis may be associated with airflow obstruction.
Hankinson and colleagues (1977) studied approximately 9,000 coal
miners from 1973 to 1974. Among the nonsmoking miners with dust-
induced bronchitis, decreased airflow at high lung volumes was
demonstrated, a finding suggestive of changes in the larger airways.

Abnormalities of the small airways seem to be one of the earliest
responses to mineral dust exposure (Churg et al. 1985). In a recent
study of hard-rock miners and people employed in the asbestos,
construction, and shipyard industries, Churg and colleagues (1985)
showed that the abnormalities of the respiratory bronchioles associ-
ated with mineral dust are accompanied by airflow abnormalities.
The lesions consisted of fibrosis and pigmentation in the small
airways and were considered by these researchers to represent a
nonspecific response to dust.

Involvement of the small airways has also been demonstrated in
workers with specific exposures. For example, the coal macule is
characterized by the deposition of alveolar macrophages loaded with
coal dust in the respiratory bronchioles (Morgan 1984a). Subsequent-
ly, the involved respiratory bronchioles dilate, a change termed
"focal emphysema" (Morgan 1984a). At this stage, individuals
usually are asymptomatic and have no physical findings. The chest x

150


ray may be normal, or rounded nodules, less than 10 mm in
diameter, may be present, predominantly in the upper lobes. These
findings characterize the simple form of coal workers' pneumoco-
niosis. In spite of the presence of roentgenographic and pathologic
abnormalities, only subtle abnormalities of small airways function
are demonstrable in simple coal workers' pneumoconiosis (Morgan
1984a).

In certain chronic occupational lung diseases, parenchymal lung
injury may be accompanied by evidence of restriction alone; in
others, variable combinations of restriction and obstruction may
occur. Relevant examples of these two types of processes are
asbestosis (Seaton 1984a) and the complicated forms of coal workers'
pneumoconiosis and silicosis (Morgan 1984a; Seaton 1984b).

Although asbestos exposure is associated with fibrosis of the
respiratory bronchioles, the injury often progresses and involves the
alveolar interstitium with the development of parenchymal fibrosis
Seaton 1984a). The clinical consequences of this parenchymal injury
are cough and dyspnea. Other changes found in asbestosis include
crackles, clubbing, and basilar, irregular, linear opacities on chest x
ray. Pulmonary function testing shows only a restrictive pattern
with reduced FVC, normal FEV/FVC%, and decreased TLC.

In contrast, the complicated forms of silicosis and coal workers'
pneumoconiosis may be accompanied by obstruction in addition to
restriction. In both disorders, large masses of dust and fibrosis
replace the normal lung parenchyma and reduce FVC and TLC.
Obstruction may also be present, presumably because of increased
airways resistance and parenchymal abnormalities. Dyspnea is
generally a prominent symptom.

Thus, for some occupational agents, the associated lung injury at
specific anatomic loci resembles that from cigarette smoking. Large
airway irritation, regardless of the exposure, is accompanied by
abnormalities of the mucous glands and mucus hypersecretion.
Small airways may be affected by occupational agents, and a pattern
of injury distinct from that found in cigarette smokers has been
described (Churg et al. 1985). However, the parenchymal abnormali-
ties of advanced pneumoconiosis can be readily distinguished from
emphysema associated with cigarette smoking.

Methods for Evaluating the Effects of Occupational Exposures
on the Lungs

Workers exposed to occupational agents that cause chronic lung
disease may be examined for diagnostic reasons, for surveillance, or
for research. Regardless of the purpose of the evaluation, the same
assessment techniques are generally used: history of respiratory
symptoms, physical examination of the chest and extremities,

151


spirometry and other physiological tests, and chest x ray (American
Thoracic Society 1982b; Boehlecke 1984; Townsend and Belk 1984).
These techniques and their sensitivity to the effects of cigarette
smoking are described below.

History of Respiratory Symptoms

Symptoms of lung disease are nonspecific; the most prevalent are
cough, phlegm production, wheezing, and breathlessness or dyspnea
(Gandevia 1981). Although a physician may take a conventional
history to evaluate these symptoms, standardized questionnaires are
generally used for surveillance and research purposes.

In the 195Os, the British Medical Research Council developed a
standardized respiratory symptoms questionnaire for studies of the
epidemiology of chronic bronchitis and chronic obstructive lung
disease (Samet 1978; Florey and Leeder 1982). In 1968, this question-
naire was adopted for use in the United States by a committee of the
American Thoracic Society (1969). Three years later, the National
Heart and Lung Institute made available a version that had been
modified to improve its suitability for the United States (US DHEW
1971). In 1978, the American Thoracic Society published a further
revised respiratory symptoms questionnaire (Ferris 1978). The
Medical Research Council questionnaire or one of these modified
versions has been used in most studies of chronic lung disease in the
workplace. All include a series of questions related to cough, phlegm,
wheezing, and dyspnea.

The Medical Research Council questionnaire was originally devel-
oped for investigating the etiology of chronic bronchitis and airflow
obstruction (Fletcher et al. 1959; Samet 1978). The questionnaire was
designed, in part, to test one of the prevailing hypotheses about
airflow obstruction: that mucus hypersecretion predisposed repeated
lower respiratory tract infections and consequent airflow obstruction
(Fletcher et al. 1959, 1976). Accordingly, the cough and phlegm
questions were worded to be sensitive to the earliest phases of mucus
hypersecretion, a condition largely attributable to cigarette smoking
(US DHHS 1984). The questions may be less satisfactory for cough
and sputum associated with other exposures, particularly if those
other exposures produce a pattern of symptoms different from those
due to cigarette smoking, such as nocturnal cough or episodic cough.
Further, their sensitivity to cigarette-associated mucus hypersecre-
tion may hinder separation of an occupational exposure's effect on
the occurrence of cough and phlegm from that of cigarette smoking.
The dyspnea and wheeze questions probably do not share this
sensitivity.

In population surveys, cigarette smoking is the major determinant
of the prevalence of cough and phlegm (US DHHS 1984). This
association has been confirmed in occupational groups as well as in

152


population samples (Gandevia 1981; US DHHS 1984; Petersen and
Castellan 1984). Wheezing is also associated with cigarette smoking
(Mueller et al. 1971; Samet et al. 1982; Schenker et al. 1982).
Dyspnea has multiple determinants that interact in a complex
fashion; cigarette smoking and smoking-related impairment of lung
function contribub,: to the occurrence of dyspnea (Wasserman and
Whipp 1975; Cotes 1979; Killian and Jones 1984).

Chest X Ray

The pneumoconioses are associated with characteristic radio-
graphic abnormalities, although the chest film may be normal in the
presence of biopsy-proven disease (Epler, McLoud et al. 1978). A
conventional clinical interpretation is usually sufficient for estab-
lishing the presence of pneumoconiosis. Preferably, however, the
chest x ray should be coded according to the classification estab-
lished by the International Labour Office (ILO) (1980). This system,
originally published in 1950, categorizes the types of abnormalities
on the chest x ray by shape and size, and provides a grading (the
profusion) for describing the density of small opacities. The opacities
classified as small are grouped as rounded or irregular. If the
opacities are less than 1 cm in diameter, they are called small; if
equal to or greater than 1 cm, they are called large.

The effects of cigarette smoking on chest x-ray findings have been
examined, using both conventional interpretations and readings in
the IL0 system. Human autopsy evidence and animal exposure
studies show that cigarette smoking leads to abnormalities in the
airways and parenchyma that might produce radiographic abnor-
malities (US DHEW 1979b; Weiss 1984). However, these changes are
subtle in comparison with the pathological findings in the pneumo-
conioses. Cigarette smoking is associated with modest amounts of
interstitial fibrosis in the lungs, in addition to airways abnormalities
and emphysema (US DHEW 1979b; Weiss 1984). For example,
Auerbach and colleagues (1974) examined lung sections from 1,443
men and 388 women deceased between 1963 and 1970, and found
more fibrosis in smokers than in nonsmokers and a dose-response
relationship between the degree of fibrosis and the amount smoked.
The small airways of cigarette smokers, even at young ages, display
inflammation with edema of the bronchiolar walls, smooth muscle
hypertrophy, and goblet cell metaplasia (US DHHS 1984). These
changes may underlie, at least in part, the pattern of increased lung
markings in smokers described anecdotally by clinicians, but are
unlikely to be confused with the more extensive fibrosis found in
moderate or advanced pneumoconiotic lung disease.

Comparisons of chest x-ray findings generally show a higher
frequency of abnormalities, interpreted as representing interstitial
fibrosis, in smokers than in nonsmokers. These investigations have

153


been based on chest films from both the general population and
specific occupational groups. Weiss (1967, 1969) reviewed chest films
from two samples of adults-participants in a tuberculosis screening
program and hospital employees. In both groups, he identified a
pattern of increased lung markings, termed diffuse pulmonary
fibrosis, more often in smokers, and showed that the prevalence of
this finding increased with the amount and duration of smoking.
These studies have been criticized because the films were 70 mm
photofluorograms taken for screening purposes and not full sized
(Kilburn 1981). Further, the films were not read directly according to
the IL0 classification. In another study that did not use the IL0
system, Carilli and colleagues (1973) showed that radiologists could
generally distinguish smoking women from nonsmoking women by
the presence of linear and nodular fibrotic changes in the smokers.
Epstein and colleagues (1984) read the chest x rays of 200 hospital-
ized patients according to the IL0 classification. Twenty-two patients
with at least category l/O profusion and no documented dust
exposure or other explanation for nodular densities were identified,
10 of whom had not smoked cigarettes. Because this study included
only hospitalized people, the results may not be generalizable to
working populations.

The results of investigations involving occupational groups do not
show strong effects of cigarette smoking on the profusion of small
opacities. Glover and colleagues (19801 read the chest films of slate
workers and a nonexposed control group according to the 1971 IL0
classification. In the controls, small irregular opacities were not seen
in nonsmokers, but were present in 2 percent of current and former
smokers. Investigators from the National Institute for Occupational
Safety and Health interpreted chest x rays of 1,422 blue-collar
workers whose present and past employment should not have
involved exposure to respiratory hazards (Castellan et al. 1984). Only
three workers had at least category l/O profusion, two with small
rounded opacities and one with small irregular opacities. Sixty-one
percent of the subjects were current or former smokers. However,
the mean age of subjects in this study was only 33.9 years,
substantially lower than the age at which pneumoconiosis or
significant cigarette-related airflow obstruction would generally be
manifest if exposure began at about age 20. In a much smaller study
of similar design, Cordier and colleagues (1984) identified small
opacities in only 1 person in a control group of 48 office workers, 31
percent of whom smoked.

Studies of workers exposed to hazardous agents show that
cigarette smoking may modify the pattern of radiographic abnormal-
ity. In coal workers, small rounded opacities predominate in the
simple phase of coal workers' pneumoconiosis, but irregular opaci-
ties may also be present (Amandus et al. 1976; Cockcroft et al. 1982,

154


1983). The irregular opacities are associated with cigarette smoking
and with reductions of FEV1, FVC, and diffusing capacity (Cockcroft
et al. 1982). In autopsy specimens obtained from coal workers in the
United Kingdom, Ruckley and colleagues (1984) demonstrated that
emphysema was present in 90 percent of the lungs with small
irregular opacities, but in only 60 percent with small rounded
opacities alone. Dick and colleagues (1983) examined the radiographs
of a stratified random sample of miners from 10 British coal mines
and concluded that smoking did not influence the prevalence of
rounded opacities. Smokers had a greater prevalence of irregular
opacities, but after adjusting for the effects of differences in age and
dust exposure, these results were not statistically significant.

Studies of other occupationally exposed groups also demonstrate
that cigarette smoking may affect the pattern and extent of
radiographic abnormality. In granite workers, Theriault and col-
leagues (1974) found that rounded opacities were related to an
estimate of lifetime dust exposure, whereas small irregular opacities
were more strongly related to smoking. In workers exposed to
manmade vitreous fibers, the prevalence of small opacities was
determined not only by estimated exposure but also by smoking
habits (Weill et al. 1983). Using multiple logistic regression, Peters
and colleagues (1984) showed that cigarette smoking, but not
particulate exposure, predicted the occurrence of linear opacities in
silicon carbide workers. In asbestos workers, the predominance of
evidence indicates that cigarette smoking acts independently and
additively with asbestos to create radiographic abnormalities (Weiss
1984).

The findings of these studies of occupationally exposed and
nonexposed individuals indicate that cigarette smoking may affect
chest x-ray readings. Cigarette smoking alone is occasionally associ-
ated with definite abnormalities classified in the IL0 system.
Smoking may also affect the radiographic pattern and independently
increase the prevalence of abnormality. In addition, the threshold
for detection of an abnormality on chest x ray may be exceeded more
frequently or at an earlier age in workers who smoke than in
workers who do not smoke.

Physiological Assessment

An evaluation of workers for diagnosis and surveillance may
include auscultation of the chest, for breath sound quality and
intensity and for the presence of adventitious sounds including
crackles, and examination of the fingernails for evidence of clubbing.
Crackles, also referred to as rales or crepitations, are discontinuous,
interrupted sounds thought to arise from the sudden opening of
small airways or from the bubbling of air through secretions in
larger airways (Loudon and Murphy 1984). Fine crackles may be

155


heard in people with diffuse interstitial fibrosis. For example, Epler,
Carrington, and colleagues (1978) reported that fine crackles were
present in 60 and 65 percent of subjects with biopsy-proven and
clinically diagnosed asbestosis, respectively. Some definitions of
asbestosis incorporate the presence of crackles as a diagnostic
criterion (Murphy et al. 1978). Because crackles may be heard in
asbestosis and other occupational lung diseases, auscultation has
been advocated as a surveillance technique for monitoring workers
exposed to asbestos and other agents (Loudon and Murphy 1984;
Murphy et al. 19841.

Few studies have addressed the effects of cigarette smoking on
auscultatory findings, however. Epler, Carrington, and colleagues
(1978) reported the results of a conventional clinical auscultation of
patients with various interstitial disorders or with chronic obstruc-
tive lung disease, which is largely attributable to cigarette smoking.
Fine crackles, characteristic of asbestosis, were heard in only 10 to
12 percent of the latter group, though coarse crackles were more
common in those with chronic bronchitis. Two studies of asbestos
workers suggest that cigarette smoking may independently increase
the frequency of crackles. To quantify the separate effects of asbestos
exposure and cigarette smoking on the prevalence of bilateral fine
crackles, Samet and colleagues (1979) analyzed data from 409 survey
subjects, using multiple logistic regression. Statistically significant
effects of both smoking and asbestos exposure were found. In the
other study (Murphy et al. 19841, a technician examined each subject
with a standardized approach and a summary crackles score was
calculated. Multivariate analysis suggested that cigarette smoking
was associated with the lower abnormality levels of this score. The
consistent findings of these two investigations seem plausible in view
of the effects of cigarette smoking on the small airways, the site
where fine crackles are presumed to originate (Loudon and Murphy
1984). In 590 employed men not exposed to respiratory hazards,
crackles were heard predominantly in the older smokers (Gandevia
1981). This finding further supports a relationship between cigarette
smoking and the presence of crackles.

Clubbing refers to a change in the configuration of the nail beds,
which can be best quantitated by the hyponychial angle (Regan et al.
1967). It has many causes and is a nonspecific manifestation of
advanced chronic respiratory diseases, lung cancer, and other
disorders (Shneerson 1981). Because clubbing may be occasionally
found with COLD, its presence may be related to cigarette smoking
as well as to occupational lung disease. Samet and colleagues (1979)
found that cigarette smoking and occupational exposure to asbestos
were independent determinants of the prevalence of clubbing in four
different populations of asbestos workers.

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Findings on clinical examination, like respiratory symptoms, are
nonspecific, and a conventional physical examination alone is an
insensitive method for diagnosing chronic occupational lung dis-
eases. However, the presence of fine crackles, in the setting of an
appropriate exposure, should alert the clinician to the possibility of
pneumoconiosis, even if the chest x ray is unremarkable. Clubbing,
when attributable to a chronic pulmonary process, is generally a
marker for more advanced disease. Diseases associated with ciga-
rette smoking may be accompanied by crackles or clubbing.

Evaluation of pulmonary function in occupationally exposed
individuals, whether for diagnostic or research purposes, should
include spirometry, which measures FVC, FEV1, and maximal
expiratory flow rates (Ferris 1978; American Thoracic Society
1982b). The effects of smoking on spirometric parameters are
discussed elsewhere in this chapter. The diffusing capacity for
carbon monoxide may also be measured; it is a sensitive test that
may detect early abnormalities in chronic occupational lung diseases
(Weinberger et al. 1980). As with FVC, FEVI, and other spirometric
measures, cigarette smoking habits must be considered in interpret-
ing the level of diffusing capacity, which is reduced by smoking-
related lung disease (particularly emphysema) as well as by occupa-
tional lung disease (Make et al. 1982; Miller et al. 19831. FVC can be
reduced either by restrictive lung diseases, such as asbestosis, or by
COLD; therefore, TLC should be measured with a physiological or
radiological method in order to establish the presence of a restrictive
disorder. In evaluating subjects for occupational asthma, nonspecific
bronchial reactivity may be assessed with pharmacologic agents,
such as methacholine, or with cold air inhalation (Brooks 1982).
Some studies indicate that nonspecific bronchial reactivity is in-
creased in cigarette smokers (Kabiraj et al. 1982; Gerrard et al.
1980), though others do not (Kennedy et al. 1984; Wanner et al.
1985).

Exercise testing is one of the methods used to assess the degree of
impairment resulting from a chronic occupational lung disease
(American Thoracic Society 1982a). Exercise testing has been used to
characterize the pathophysiology of chronic occupational lung
diseases, but is rarely used for establishing clinical diagnoses or for
epidemiological studies (Wiedemann et al. 1984) and is not discussed
further in this chapter. Cigarette smoking can impair exercise
performance through a variety of mechanisms (Cotes 1979).

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Quantification of Effects of Smoking and Occupation in
Populations

Concepts of Interaction

Interaction has been defined as "the interdependent operation of
two or more causes to produce an effect" (Last 1983, p. 51).
Epidemiclogists may also apply the term "effect modification" to
variation in the magnitude of an exposure's effect as the level of
another exposure changes (Last 1983). Synergism refers to an
increased effect of the exposures when both are present, and
antagonism refers to a reduced effect (Last 1983). Statistical model-
ing techniques are generally used to test for the presence and
direction of interaction. The most widely applied statistical tech-
niques measure interaction on either an additive or a multiplicative
scale (Rothman et al. 1980; Kleinbaum et al. 1982). Ideally, the
choice of a model should be based on a specific biological formulation
of disease pathogenesis; most often, however, the underlying biologi-
cal mechanisms are not well established and largely statistical
considerations govern the selection of an analytical model.

The results of such models must be interpreted not only statistical-
ly but also in biological and public health contexts (Rothman et al.
1980). Rothman and colleagues (1980) argued that biological models
should be explicitly described; in their view, the labeling of mecha-
nisms as synergistic or independent does not advance the under-
standing of disease etiology. They broadly described two categories of
mechanisms: those with the multiple etiological factors acting
interchangeably at the same step and those with the factors acting at
different steps. The corresponding statistical models are the additive
and the multiplicative, respectively. These authors and others (Blot
and Day 1979; Saracci 1980; Kleinbaum et al. 1982) have concluded
that, from the public health viewpoint, departure from additivity
represents interaction.

Both advancing the understanding of disease etiology and the need
for protecting public health provide a compelling rationale for
assessing interaction between cigarette smoking and workplace
exposures. Cigarette smoking may interact with a particular expo-
sure through diverse mechanisms that range from behavioral to
molecular levels (Table 4). The 1979 Report of the Surgeon General
(US DHEW 1979131 partially addressed different forms of interaction
between smoking and occupational exposures; other plausible hy-
potheses concerning interaction between cigarette smoking and
occupational agents can also be postulated. The interactions listed in
Table 4 are intended to be illustrative and not exhaustive.

Some consequences of cigarette smoking might lead to a reduction
of the dose of an inhaled agent. In comparison with nonsmokers,
current and former smokers have higher rates of absenteeism from

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TABLE 4.Come potential interactions between cigarette
      smoking and occupational exposures in the
      pathogenesis of chronic occupational lung
       diseases

Source of interactmn

Potential consequence

Increased absenteeism by smokers from work

Reduced mhaled dose in
smokers

Selection of more fit nonsmokers into
aerobically demandmg jobs

Contaminated cigarettes act as a vector

Reduced inhaled dose in
smokers

Increased exposure of smokers

Workplace chemicals are metabolized
to toxic or more toxic agents by
cigarettes

Increased exposure of smokers

Increased tracheobronchial depwtion of
particulates m smokers and people
with chronic bronchitis

Differing regional lung doses
in smokers and nonsmoken

Reduced mucociliary transport in smokers       Increased dose in smokers

Reduced alveolar clearance of
particulates in smokers

Increased dose in smokers

Increased numbers of polymorphonuclear
leukocytes and other inflammatory
cells in lungs of smokers

Increased lung injury in smokers

work (US DHEW 1979b). Because cigarette smoking and cigarette-
related cardiorespiratory diseases are associated with reduced aero-
bic capacity, nonsmokers may tend to perform the more strenuous
tasks in the workplace. The higher ventilatory requirements of such
jobs might increase the amount of dust or other agents inhaled;
smokers would be spared to the extent that they are selected for
more sedentary jobs. The excess mucus production of chronic
bronchitis might protect against soluble agents through the in-
creased absorptive capacity of the mucus.

Tobacco products might serve as vectors for the transformation of
workplace chemicals into more harmful agents. For example,
smokers are placed at increased risk for polymer fume fever through
contamination of their cigarettes by fluorocarbons; toxic products
are generated by the cigarette's heat and are inhaled by the smokers.
Reduced pulmonary defenses in smokers might also increase the
effects of occupational agents. The mucociliary apparatus of the
airways removes particles and absorbed gases by physical transport
(Wanner 1977; Lippmann et al. 1980). Both cilia and mucus are
affected by tobacco smoke, and direct measurements of mucociliary

159


transport in animals and in humans confirm that long-term smoking
impairs particle clearance (Wanner 1977; Lippmann et al. 1980; US
DHHS 19841. Cohen and colleagues (1979) have demonstrated
impaired alveolar clearance of particulates in smokers, as well. A
plausible, though not established, consequence of reduced clearance
is the increased pulmonary residence time of harmful agents and an
increased dust burden in the lungs. Finally, alterations of lung cell
populations and the presence of inflammation in smokers might
amplify the effects of inhaled occupational agents. Inflammatory
cells are thought to have a central role in lung injury caused by
occupational agents (Campbell and Senior 1981; Bitterman et al.
1981). The lungs of smokers yield markedly increased numbers of
macrophages and neutrophils in bronchoalveolar lavage fluid in
comparison with the lungs of nonsmokers (US DHHS 1984). Thus,
synergism between cigarette smoking and an occupational agent
could reflect a greater release of enzymes and other toxic products
from the large numbers of inflammatory cells that have been
recruited into the lung by cigarette smoke.

Study Design

Several epidemiological study designs are used to assess the
independent and interactive effects of smoking and occupational
exposures in human populations. The cross-sectional study, or
survey, is the most widely used approach, primarily because of its
feasibility and low cost. Most surveys involve data collection from
samples defined by employment status or union membership. In a
cohort study, exposed and nonexposed people are followed over time
and monitored for the development of disease. Large-scale cohort
investigations of workers exposed to asbestos, silica, and coal dust
have been carried out. The case-control design involves the identifi-
cation of cases with the disease of interest and a control series of
people without the disease who would be potentially selected as cases
if they were to develop the disease. The exposure histories of the
cases and controls are ascertained and compared. This design has
been used infrequently for studying chronic occupational lung
diseases.

As a minimum, when cigarette smoking and a single occupational
agent are of interest, the study should provide estimates of their
independent effects and of the combined effect. This minimum is
suggested because the impairment observed in a particular popula-
tion reflects the consequences not only of the occupational agent but
also of all other damaging environmental exposures. Of these,
cigarette smoking is by far the most important and the most readily
assessed. Cross-sectional, case-control, and cohort designs meet this
requirement if the cigarette smoking practices and exposure histo-
ries of the subjects can be accurately determined.

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Assessment of Exposures
Cigarette Smoking

The American Thoracic Society (Ferris 1978) has recommended
that a cigarette smoking questionnaire include smoking status
(never, current, or previous), age started smoking, age stopped
smoking (for former smokers), current and usual amount smoked,
and depth of inhalation. Questions concerned with brand and extent
of filter cigarette smoking are optional, but should be used when
possible to address research questions related to types of cigarettes
smoked. The recommended items provide several measures of
exposure to cigarette smoke for data analysis: usual amount smoked,
duration of smoking, and cumulative consumption. The items
related to cigarette smoking status can be used to stratify a study
population into current, former, and never smokers.

These simple measures of exposure to cigarette smoking strongly
predict the risk of both age-specific overall mortality and COLD
mortality (US DHEW 1979b; US DHHS 1984). In the major
prospective cohort studies, dose-response relationships between
amount smoked and age-specific mortality have been demonstrated;
the findings have been similar for duration of smoking (US DHEW
1979b). Associations with self-reported depth of inhalation have been
less consistent. Indices of pulmonary morbidity also vary with
measures of cigarette smoke exposure (US DHHS 1984). The
consistency of these findings for morbidity and mortality emphasizes
the importance of collecting information on the parameters of
cigarette smoking in epidemiological investigations.

Self-reported data may underestimate true cigarette consumption;
however, the degree of bias has not been shown to vary with
occupational status. For the United States and other countries,
estimates of nationwide consumption based on survey data are
generally lower than consumption figures calculated with informa-
tion from manufacturers and government agencies (Todd 1978;
Warner 1978). In the Multiple Risk Factor Intervention Trial
(MRFIT), validation of smoking with serum thiocyanate measure-
ments documented underreporting of smoking, which was greater in
the group randomized to special intervention (Neaton et al. 1981;
Ockene et al. 1982). This finding implies that bias in reported
smoking may vary with the context in which the information is
collected. Workers exposed to agents associated with lung disease
might report their smoking habits differently from unexposed
workers; both more and less accurate reporting by the exposed
population can be postulated.

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Occupational Exposures

For clinical and research purposes, exposure to occupational
agents should be documented and both duration and concentration
estimated, when possible. The techniques used to establish exposure,
duration, and concentration are diverse, and are not considered in
detail here. Comprehensive reviews and books about them have been
published (Hammad et al. 1981; Dodgson 1984; Cralley and Cralley
1979). The methods include self-report, use of industry, occupation,
or job title as a surrogate for exposure, area sampling, personal
dosimetry, and biological markers.

Data Analysis

In an epidemiological investigation of a population at risk for
chronic occupational lung disease, information concerning work-
place exposures and cigarette smoking is collected and appropriate
health outcome measures, such as the chest radiograph and spirome-
try, are assessed. Data analysis is directed at characterizing associa-
tions between risk factors and disease and at the modifiers of these
associations; in studies of chronic occupational lung disease, ciga-
rette smoking and exposure to the occupational agent are the
primary risk factors to be considered. Data analysis with epidemio-
logical methods can provide estimates of the independent effects of
smoking and the occupational agent and test for interaction between
them (Kleinbaum et al. 1982). These techniques, some quite complex,
are not described here, but approaches for assessing interaction are
considered.

Analysis of data related to a chronic occupational lung disease,
regardless of the study design, must address the potential confound-
ing and effect modification, or interaction, resulting from cigarette
smoking. Confounding refers to the bias introduced when the effects
of one factor are not separated from those of another. In studies of
chronic occupational lung diseases, confounding may occur when
estimates of exposure to the occupational agent are associated with
cigarette smoking. For example, in a study of asbestos workers,
confounding would be present if the more heavily exposed individu-
als were also heavy smokers. Comparisons of blue-collar workers
with white-collar employees may be confounded because the former
are more often smokers.

Confounding can be controlled at the design phase or at analysis
by either stratified or multivariate techniques (Kleinbaum et al.
1982). Options in study design include restriction of participants to
smokers or to nonsmokers alone and matching of occupationally
exposed and nonexposed subjects for smoking habits. At analysis,
whether stratified or multivariate, biologically appropriate and valid
measures of cigarette smoking are needed. More simplistic variables,

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such as categorical indicators designating never and ever smokers,
may not be satisfactory, and their use may only partially control
confounding. In particular, measures of cumulative consumption
seem most appropriate for the lung function changes of COLD
(Burrows et al. 1977; US DHHS 1984). However, errors in the
measurement of smoking may reintroduce confounding and appar-
ent effect modification (Kleinbaum et al. 1982).
Simple generalizations cannot be offered concerning the potential
magnitude of bias that uncontrolled confounding by cigarette
smoking can produce. The bias will depend on the strength of the
association between the occupational exposure and cigarette smok-
ing and on the magnitude of smoking's effects in the population.
However, because there is a high prevalence of smoking in the
workforce and smoking has a strong association with lung function
impairment, it should not be dismissed as a confounder merely
because some particular level of effect is found for an occupational
exposure. Further, the attainment of statistical significance for the
effect of an occupational exposure does not exclude confounding.
Either stratified or multivariate statistical techniques can be used
to test for interaction. In the first approach, variation in the effects
of one factor (e.g., an occupational agent) is examined across strata
defined by the second factor (e.g., cigarette smoking). More often,
multivariate regression models, either linear or logistic, are used to
test for interaction (Kleinbaum et al. 1982). In linear regression
models, the dependent variable is a continuous measure, such as
FEV,; in the logistic model, the dependent variable is the occurrence
or nonoccurrence of a discrete outcome, such as the presence of
crackles. In both types of models, the independent variables may
include terms for the individual exposures and cross-product terms
to test for interaction. The regression coefficients estimate the
effects of the exposures on the dependent variables. For example,
models developed for an asbestos-exposed study population might
include a variable for cumulative asbestos exposure, a variable for
cumulative cigarette consumption, and a variable created by multi-
plying the two. Statistically, the null hypothesis of no interaction is
tested by the cross-product term. Failure to reject this null hypothe-
sis indicates that the data are consistent with the two factors acting
independently. However, interpretation of such analyses must
consider the scale on which interaction is measured; linear models
assess departure from additivity, whereas logistic models test
departure from a multiplicative interaction (Kleinbaum et al. 1982).
The coefficient for the cross-product term specifies the direction and
magnitude of the effect of interaction, at various levels of the two
interacting factors.
The limitations posed by sample size must also be considered in
interpreting the results of modeling. In studies of occupational


groups, the number of subjects is most often determined by the size
of the workforce and by feasibility considerations, and rarely on the
basis of more formal sample size calculations with statistical
methods. The statistical power of tests for interaction tends to be low
(Greenland 19831, and potentially important interactions may not
attain conventional levels of statistical significance without a
sufficiently large population.

Analysis of epidemiological data can also provide estimates of the
effects of exposure at the individual level and at the group level
(Kleinbaum et al. 1982). Measures of association between exposure
and disease estimate the excess risk incurred by exposed individuals.
Measures of impact combine measures of association with the
prevalence of exposure and estimate the contribution of specific
exposures to the disease burden in a population. The most widely
used is the population attributable risk or etiologic fraction. These
measures can be used to gauge the relative importance of cigarette
smoking and occupational agents.

Specific Investigation Issues
Population Selection

The most widely employed design for investigating occupational
lung disease, the cross-sectional study or survey, may be biased when
subjects are selected from the active workforce. The individuals
examined at any particular time in a cross-sectional study may be
regarded as survivors from the entire population that entered the
particular workplace. Individuals with illness tend to leave the
workforce, whereas healthy individuals tend to remain. This bias,
often called the healthy worker effect, must be considered in both
longitudinal and cross-sectional designs (Fox and Collier 1976; Wen
et al. 1983). The implications for surveys of occupational lung disease
are evident and have been widely discussed (McDonald 1981; Field
1981; Lebowitz 1981). If only employed workers are considered and
individuals with occupational lung disease leave the workforce, the
measures of association will underestimate the true effect of
exposure. In fact, the leaving of employment by people who are ill
has been demonstrated in several industries (Fox and Collier 1976;
Musk et al. 1977; McDonald 1981; Soutar and Maclaren 1982; Eisen
et al. 1983). The resulting bias should be evaluated by examining
retirees and others who have left.

The role of cigarette smoking in determining the magnitude of the
healthy worker effect has not been fully evaluated. Overall mortality
ratios for cigarette smokers are greater below age 65 (US DHEW
1979b), and cardiovascular diseases, respiratory diseases, and lung
cancer generally contribute prominently to the reduced all-cause
mortality of the healthy worker effect (Fox and Collier 1976; Wen et
al. 19831. Thus, cigarette smokers would be anticipated to leave the

164


workforce prematurely more often than nonsmokers. A recent study
of Vermont granite workers provides data that conflict with this
hypothesis, however. Eisen and colleagues (1983) compared men who
remained in the industry during a 5-year followup period with those
who terminated. The rate of FEV, loss was greater in those who left
the industry, but their cumulative cigarette consumption was not
significantly greater than that of those who stayed. These data do
illustrate the selection bias that results from differential termina-
tion of employment, contingent on the development of disease.

Eisen and colleagues (1983, 19841 have explored other sources of
bias in respiratory disease surveys. In the granite workers' study,
men whose spirometric testing repeatedly failed to meet criteria for
acceptability had a more rapid decline of FEV, than those with a
better performance. This finding suggests that the exclusion of
subjects whose lung function testing is judged unacceptable may
introduce bias toward the null.

External Control Populations

When subjects are selected for an epidemiological investigation, a
population, not exposed to the agent of interest but similar in other
respects to those who are, may not be available for comparison
purposes. In this circumstance, an investigator may consider only
the exposed subjects and evaluate the dose-response relationships if
the necessary data are available, or identify an external population
as controls. If the latter approach is used, the control population
must be comparable to the exposed group on potential confounding
factors such as age, sex, race, and cigarette smoking. At times,
appropriate external populations may not be readily identified.

Nevertheless, external control populations are frequently used. In
mortality studies, the use of general population rates for calculation
of "expected" deaths assumes that the general public is the control
group. Frequently, lung function levels in exposed people are
compared with those predicted from tests performed on "normal"
populations, most often asymptomatic nonsmokers without respira-
tory disease (Clausen 1982). Recently, Peterson and Castellan (1984)
reported the prevalence of chest symptoms, as measured with a
modified Medical Research Council questionnaire, in 1,372 blue-
collar workers employed in plants considered to be free of respira-
tory hazards. The data are illustrative of the effects of smoking on
the prevalence of major respiratory symptoms; even in this young,
employed population, all of the symptoms examined were more
common in current and former smokers. The authors provided
smoking-specific prediction equations and suggested that these data
can be used for comparative purposes.

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Coiinearity of Aging, Cigarette Smoking, and Occupational
Exposure Effects

From approximately age 25, measures of ventilatory function
gradually and progressively decline. In nonsmokers, the rate of loss
is approximately 20 to 30 mL annually for FEV, and FVC (US
DHHS 1984). The decline in FEV, with age may not be a linear
function with a constant decline each year, but rather, the absolute
rate of annual decline may vary with age. In addition, the rate of
decline in lung function with age derived from cross-sectional studies
may be an overestimate of the actual rate of decline because of
possible differences in lung function among different birth cohorts in
cross-sectional studies. Some cigarette smokers lose function at much
more rapid rates and ultimately develop COLD, unless they stop
smoking (US DHHS 1984). Presumably, a similar insidious excess
loss of function antedates the appearance of clinically evident
chronic occupational lung disease.

This simultaneous contribution of aging, smoking, and occupation-
al exposure to lung function loss represents a formidable analytical
problem. Further complicating its solution is the temporal colineari-
ty or correlation of these three independent factors; age, cumulative
smoking, and cumulative exposure all increase with the passage of
time. Failure to address this colinearity may lead to confounding and
to an incorrect assessment of the effect of exposure.

This problem is most often addressed by using external standard
populations to control for aging and, at times, cigarette smoking, or
by multiple regression modeling (Berry 1981b). In the first approach,
expected lung function levels in the exposed workers are calculated
with prediction equations developed in other populations; sex, age,
race, and cigarette smoking habits may all be considered in the
calculations. For example, Beck and colleagues (1984) conducted a
cross-sectional survey of cotton textile workers in Columbia, South
Carolina. Spirometric test results for the cotton workers were
compared with the expected values calculated from survey data
collected in two towns in Connecticut and one town in South
Carolina. For each cotton worker, an expected value was predicted
on the basis of sex, age, height, and weight, with regression
equations derived from asymptomatic nonsmokers in the control
communities. Deviations from the expected value were then exam-
ined within the strata defined by smoking. This approach is effective
when appropriate external populations are available. Prediction
equations developed for clinical purposes are frequently used,
primarily owing to availability; investigators should, however,
consider the comparability of the exposed workers with the "nor-
mal" population from which the prediction equations were derived.

Multiple regression techniques permit a simultaneous examina-
tion of the effects of age, exposure, and smoking, as well as their

166


interactions, on lung function measures. Comprehensive treatments
of these methods have been published (Draper and Smith 1966;
Kleinbaum and Kupper 1978), and only their use for lung function
data is considered here. With this approach, the lung function
measures are the dependent variables, and age, smoking, and
exposure are the independent variables in a model of this form:
Y=a+B,X,+B,X,+BB,X,+ . . . BiX, + E; where Y is a lung function
parameter, a is a constant term, X, through X, are the independent
variables and B, through B, are their regression coefficients, and E is
a term for error. The regression coefficients describe the change in Y
per unit change in a particular X,, with all other independent
variables held constant. An estimated regression equation is general-
ly obtained by the least squares criterion.

Most standard statistical packages for computers include this
technique, and it can be readily applied to a data set. However, the
results of such modeling may be misleading, and the plausibility of
such models should be assessed by careful examination of the raw
data and residuals and by other formal means. In addition, model
development should be guided by biological rather than primarily
statistical considerations; that is, the investigator should specify the
regression model in the most appropriate fashion biologically, rather
than rely on statistical procedures for variable selection. Colinearity
of the age, smoking, and exposure effects may limit the multiple
regression approach. High correlation in a data set between any two
of these factors may prevent assessment of their independent effects.

Quantification of Effects in Individuals

Properly designed epidemiological investigations can provide
essential information about the occurrence of chronic occupational
lung diseases in populations. They can establish that an occupational
exposure is hazardous, quantify the risk associated with exposure,
describe the agent's contribution to the disease burden in the
population, and document the consequences of reducing the expo-
sures. For an individual, epidemiologically derived estimates of
relative risk generally indicate the excess risk incurred by virtue of
exposure to a particular agent, as compared with nonexposure. But
such a measure of relative risk cannot be interpreted directly as a
quantitative indicator of the chance that a particular individual's
exposure to the agent was responsible for the occurrence of the
disease concerned. Statements concerning causality in an individual
case are particularly difficult when the disease of interest has
multiple causes and interactions among them are of potential
importance.

Judgments concerning the causation of disease in specific individu-
als are frequently necessary, however, for deciding claims made

167


through workmen's compensation, the courts, or other mechanisms
(Hoffman 1984; Hadler 1984). Legal proof of causation hinges on a
finding that the exposure more likely than not caused the disease
(Danner and Saga11 1977; Hoffman 1984). Allocation of probability of
causation when multiple agents interact is particularly problematic
(Cox 19841, but frequently necessary. In particular, the evaluation of
impairment in cigarette smokers exposed to harmful occupational
agents requires judgment concerning the independent and combined
effects of all exposures.

Accepted methods for accomplishing this quantification have not
yet been developed. Enterline (1983) considered the problem for two
agents that interact in a multiplicative fashion. Cox (1984) has
suggested an approach that covers the situation of joint and
interacting causes. Algorithms have been proposed for specific
diseases, such as asbestosis (Mitchell et al. 19851, and for specific
agents, such as radiation (NRC 1984). However, these approaches
have only recently been proposed and their applicability remains to
be established.

Some guidance can be found, however, in the pattern of physiologi-
cal abnormality. For example, the impairment in a smoker with
asbestosis, but with no evidence of airflow obstruction, can be
attributed mostly to the pneumoconiosis. Correspondingly, the
presence of airflow obstruction and an increased TLC in an asbestos
worker who smokes and who has a normal chest x ray suggests that
the impairment is largely attributable to cigarette smoking. The
problem is more complicated in those situations where reduced
expiratory airflow is present and TLC is decreased or in those
pneumoconioses where reductions in the rate of expiratory airflow
are part of the pattern of the pneumoconiosis. For example,
reductions of FEV1, FVC, and FEV,/FVC may all be found in
complicated silicosis and coal workers' pneumoconiosis, and these
patterns are similar to those found in cigarette smokers. Emphyse-
ma decreases lung elastic recoil, whereas some pneumoconioses, such
as asbestosis, increase it. These competing effects may result in a
TLC that is increased, normal, or reduced in a smoker with COLD
and pneumoconiosis, depending on which effect predominates. Thus,
smokers with COLD and pneumoconiosis display diverse patterns of
lung function abnormality. Evidence of airflow obstruction on
spirometry may be accompanied by a reduced, normal, or increased
TLC, and the diffusing capacity for carbon monoxide will generally
be reduced regardless of the cause of the injury. In this setting, the
diagnosis of pneumoconiosis can often be established from the chest
x ray findings, but responsibility for impairment cannot readily be
divided between COLD and pneumoconiosis. For chronic occupation-
al lung diseases associated with airflow obstruction, even diagnosis
may be difficult in an individual cigarette smoker.

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A second method of separating the relative effects of two agents in
a combined exposure is to use the known dose-response relationships
for the agents. This approach is most useful when exposure to one
agent has been slight in comparison with the exposure to the second
agent. Difficulty arises when an individual has been exposed to
biologically equivalent doses of both agents or when exposure to one
of the agents cannot accurately be assessed.

Summary and Conclusions

During the 20th century, cigarette smoking has become prevalent
among workers at risk for occupational lung disease. By itself,
smoking causes pulmonary impairment; among people exposed to
harmful occupational agents, the interactive effects of smoking may
increase the number of individuals developing clinically significant
impairment. For both clinicians and researchers, cigarette smoking
by workers poses difficult and important challenges.
1. Existing resources for monitoring the occurrence of occupation-
  al lung diseases are not comprehensive and do not include
  information on cigarette smoking. Other approaches, such as
  registries, might offer more accurate data and facilitate
  research related to occupational lung diseases. Because of the
  variability in diagnostic criteria for chronic lung disease, in
  studies on occupational lung diseases emphasis should be
  placed on measures of physiological change, roentgenographic
  abnormality, and other objective measures.
2. Further studies that correlate lung function with histopatholo-
  gy should be carried out in occupationally exposed smokers and
   nonsmokers.

3. The effects of cigarette smoking on the chest x ray should be
clarified. In particular, the sensitivity of the IL0 classification
to smoking-related changes should be further evaluated in
healthy populations.

4. To determine if smoking is reported with bias by occupational-
ly exposed workers, self-reported histories should be compared
with biological markers of smoking in appropriate populations.
5. Mechanisms through which specific occupational agents and
cigarette smoking might interact should be systematically
considered. Both laboratory and epidemiological approaches
should be used to evaluate such interactions.
6. Statistical methods for evaluating interaction require further
development. In particular, the biological implications of
conventional modeling approaches should be explored. Fur-
ther, the limitations posed by sample size for examining
independent and interactive effects should be evaluated. The

169

157-964 3 - 86 - 7


consequences of misclassification by exposure estimates and of
the colinearity of exposure variables should also be addressed.
7. The role of cigarette smoking in the "healthy worker effect"
requires further evaluation.

8. Approaches for apportioning the impairment in a specific
individual between occupational causes and cigarette smoking
should be developed and validated.

170


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CHAPTER 5

CHRONIC BRONCHITIS:
INTERACTION OF SMOKING
   AND OCCUPATION


CONTENTS

Introduction

Coal

Silica

Cement

Grain

Polyvinyl Chloride and Vinyl Chloride

Welding

Sulfur Dioxide

Other Exposures

Summary and Conclusions

References


Introduction

Occupational bronchitis is defined as the occurrence of bronchitis
caused by worksite chemical or physical agents, whether encoun-
tered as gases, fumes, vapors, or dusts. Having derived from a
crowded field of overlapping and confusing terms, the term "occupa-
tional bronchitis" has inherited a certain inexactitude and has been
applied with ambiguity. To complicate the issues further, some
industrial substances that cause bronchitis also frequently cause
other lung diseases, especially the pneumoconioses and asthma, the
symptoms of which may mimic those of occupational bronchitis.
Studies of these occupational lung diseases have not always differen-
tiated clearly between the development of bronchitis and the
development of other lung disorders. Hence, this review begins by
briefly applying the customary distinctions in terminology to the
area of occupationally derived bronchitis.

Whether caused by cigarette smoking, industrial agents, or
otherwise, "chronic simple bronchitis" denotes the presence of
persistent cough with phlegm production not attributable to a
specific pulmonary disease such as bronchiectasis or tuberculosis
(Ciba 1959; American Thoracic Society 1962). The operational defini-
tion of this form of bronchitis provided by consensus groups of
American and British investigators 20 years ago has been widely
used in industrial and nonindustrial studies: cough and sputum
production on most days for at least 3 months annually for 2
consecutive years (Ciba 1959). Fletcher and coworkers (1976) subse-
quently demonstrated that this hypersecretory disorder among
cigarette smokers can occur independent of airway obstruction and
does not of itself lead to an obstructive disorder. Brinkman and
colleagues (1972) confirmed these findings in an occupational setting
in a more abbreviated study. Mucus production causes morbidity in
that it may lead to increased pulmonary infections, but it does not
cause significant dyspnea or potentially disabling obstructive dis-
ease.

"Chronic obstructive bronchitis" often included in the generic
term "chronic obstructive pulmonary disease" (COPD), is defined by
the presence of airflow obstruction as measured in most occupational
studies by the reduction in the ratio of forced expiratory volume in 1
second to forced vital capacity (FEV,/FVC). More recently, flow
rates at low lung volumes obtained from the same forced expiratory
maneuver have been used to detect dysfunction of the small airways.
In contrast to the mere production of cough and phlegm, the
presence of obstruction may have important impact on morbidity
and mortality (Fletcher et al. 1976). This subject is reviewed more
fully elsewhere in this Report.

The term "occupational bronchitis" has been used more often to
refer to simple bronchitis than to the airflow obstructive disorder

183


because of the widespread notion that many airborne occupational
contaminants produce chronic cough and phlegm, but relatively few
agents have been found to lead to measurable airflow obstruction or
to clinically significant COPD (Parkes 1982; Casey 1983; Kilburn
1980; Morgan and Seaton 1984).
Two related criteria have commonly been used to demonstrate the
existence of occupational bronchitis in the presence of a specific
exposure or in a specific workplace. First, occupational bronchitis is
favored if excessive rates of respiratory symptoms are found in
workers who have never smoked. The obvious advantage of such a
criterion is the elimination of cigarette smoking, which is a major
confounding variable in bronchitis. Unfortunately, this approach
could fail to incriminate an occupational agent that produces no
respiratory effects by itself but causes higher rates of bronchitis
among workers who smoke than are attributable to cigarette
smoking alone. Second, the entire exposed population-smokers,
former smokers, and nonsmokers-may experience higher rates of
chronic cough and phlegm production than a similarly constituted
unexposed control population. If the population of exposed nonsmok-
ers is small, however, only the interactive effects of smoking and the
occupational agent of interest may be evaluated.

This chapter describes the impact of smoking and occupational
exposures on the prevalence of simple bronchitis. Examining the
interaction between smoking and hazardous substances, however,
requires documenting the ability of industrial agents alone to
produce chronic respiratory disease. The additional or multiplicative
effects of cigarette smoking can then be described. Emphasis is
placed on evaluating the nature and quality of data rather than on
compiling a complete list of agents putatively associated with
bronchitis.

Coal

The role of coal dust in the development of chronic simple
bronchitis has been examined (Morgan and Seaton 1984; Parkes
19821, and respiratory disease in coal miners is discussed more fully
in a separate chapter of this Report. The specific issue of bronchitis
and occupational exposure to coal is reviewed briefly in this section.

Evidence supports an independent causal relationship for both
cigarette smoking and coal dust in chronic cough and phlegm
production (Higgins et al. 1959; Saric and Palaic 1971; Higgins 1972;
Lowe and Khosla 1972; Kibelstis et al. 19731. In a series of
community-based studies in England and in the United States
during the 1950s and 1960s Higgins and colleagues (Higgins et al.
1959; Higgins 1972) found an increased prevalence of chronic simple

184


bronchitis in miners and ex-miners, ranging from 1.2 to 6.4 times the
rates in nonminer controls.

Lowe and Khosla (19721 studied chronic bronchitis among more
than 12,000 Welsh steelworkers, about one-fourth of whom were
former coal miners. In the absence of cigarette smoking, previous
exposure to coal dust increased the rate of chronic cough and phlegm
production from 5.7 percent in nonsmoking nonminers to 13.6
percent in nonsmoking ex-miners. Cigarette smoking was somewhat
more important than previous exposure to coal in producing chronic
simple bronchitis; 16.6 percent of the nonminers who smoked and
25.5 percent of the ex-miners who smoked had chronic bronchitis.
Differences in age among the various subgroups did not account for
the varying prevalence of symptoms, which appeared to be additive.

Saric and Palaic (1971) compared 904 Yugoslav coal miners with
342 control workers of similar socioeconomic status without occupa-
tional exposure to dusts, and found that cigarette smoking and coal
dust exposure were multiplicative in the production of chronic
simple bronchitis. Of the miners who smoked, 32 percent reported
chronic cough and phlegm production, compared with 10 percent of
the controls who smoked, 8 percent of the nonsmoking miners, and 2
percent of the nonsmoking controls. However, the rates of chronic
simple bronchitis for each exposure subgroup, except the workers
who smoked, were below other published rates.

Increasing coal dust exposure increased the prevalence of chronic
simple bronchitis in both smokers and nonsmokers in the studies by
Kibelstis and colleagues (1973) and Rae and colleagues (1971).
Neither study included groups not exposed to coal dust. Both studies
reported a larger effect of cigarette smoking than of coal dust
exposure in causing chronic simple bronchitis, but did demonstrate a
substantial coal dust exposure effect. One-third to one-half of the
nonsmoking American coal miners over the age of 50 reported
chronic cough and phlegm production (Kibelstis et al. 1973). Some-
what lower proportions (20 to 40 percent) of the nonsmoking British
coal miners with tht highest levels of dust exposure suffered
symptoms of chronic cough and phlegm production (Rae et al. 1971).

In summary, coal dust exposure causes chronic simple bronchitis
independent of cigarette smoking. Although the effects are additive,
the effect of smoking is somewhat greater than the effect of coal dust
exposure in producing symptoms of chronic bronchitis.

Silica

Early studies showed no relationship between silica exposure and
chronic cough and phlegm production. In 1959, Higgins and col-
leagues (19593 found no increase in chronic simple bronchitis in
British foundry workers and former foundry workers, regardless of

185


duration of employment, compared with community controls with-
out dust exposure. In a cross-sectional study, Brinkman and Coates
(1962) found no difference in cough and phlegm production in long-
term American foundry workers with normal chest roentgenograms
and control workers with no dust exposures. More recently, Glover
and colleagues (1980) examined 725 Welsh slate workers and former
workers and noted no relation between duration of exposure to slate
and presence of chronic simple bronchitis independent of pneumoco-
niosis.

On the other hand, studies of South African gold miners showed
an association between silica and simple bronchitis among smoking
miners. White miners were compared with age-matched white
nonminers in an area where gold mines had a 50 to 70 percent free
silica content (Sluis-Cremer et al. 1967). Nonsmoking miners report-
ed an 8.2 percent rate of chronic simple bronchitis, which did not
differ from the 6.7 percent rate found among nonsmoking nonmin-
ers. However, 50.5 percent of the miners who smoked had chronic
cough and phelgm production, almost twice the 28.0 percent found
among the nonminers who smoked. Hence, silica dust alone ap-
peared not to cause symptoms of simple bronchitis, but magnified
the effects of smoking.

Wiles and Faure (1977) also studied white South African gold
miners and found that they had an increased prevalence of
bronchitic symptoms in the absence of cigarette smoking and that
there was an additive effect among the workers who did smoke
cigarettes. Among the nonsmokers with the lowest dust exposure, no
workers had chronic cough with phlegm, but 15 to 20 percent of
workers with the highest dust exposures had these symptoms.
Twenty-five percent of smokers in the low dust category reported
bronchitic symptoms. Among the miners who smoked, 50.5 percent
suffered from chronic cough and phlegm production, demonstrating
a simple additive effect.

A cross-sectional study of 931 Swedish long-term foundry workers
with varying exposures to silica was published in 1976 (Karava et al.
1976). Less than 4 percent of the study population had evidence of
silicosis on chest x ray. Two percent of the nonsmokers exposed to
lesser amounts of dust reported simple chronic bronchitis compared
with 9 percent of the nonsmokers with high dust exposure, but the
difference was not significant (p>O.lO). However, 16 percent of the
smokers exposed to slight or moderate levels of dust had chronic
cough and phlegm production, significantly less than the 30 percent
of smokers with high dust exposure (p<O.Ol). Foundry dust may
have potentiated the effect of cigarette smoking.

In summary, silica exposure appears to interact with cigarette
smoking to increase the prevalence of chronic bronchitis, at least in
white South African gold miners.

186


Cement

A cross-sectional survey of 847 cement workers and 460 controls
not exposed to occupational hazards found that 19.0 percent of the
cement workers had chronic simple bronchitis, compared with 9.62
percent of the control group, using the Medical Research Council
(MRC) (British Medical Journal 1966) criteria for bronchitis (Kalacic
1973a, b, 1974). However, the study group had more current smokers
and was somewhat older than the control group (Kalacic 1973a). The
nonsmoking cement workers had significantly more chronic simple
bronchitis than the nonsmoking control subjects: 11.7 and 2.2
percent, respectively (p< .OOl). The cement workers who smoked
cigarettes reported a 21.2 percent rate of chronic simple bronchitis,
twice the rate of the nonsmoking cement workers.

An investigation of the relationship between chronic bronchitis
and occupation among 14,154 persons in numerous occupations,
including 344 cement workers (Deutsche Forschungsgemeinschaft
1978), revealed a positive association between the symptoms of
chronic bronchitis and exposure to cement dust only in heavy
smokers and younger nonsmokers.

In summary, cement dust exposure may cause chronic simple
bronchitis independent of cigarette smoking. The interaction be-
tween the two exposures is likely to be additive.

Grain

Although for several decades cereal grain dust has been known to
affect human lungs (Williams et al. 1964; Kleinfeld et al. 1968), the
nature of grain-related chronic lung disease and its relationship to
cigarette smoking has been elucidated only in recent years. Compli-
cating factors have included the variety and overlap of the lung
diseases associated with grain dust (asthma, allergic alveolitis, grain
fever, and chronic obstructive lung disease) and the multitude of
potentially toxic materials found in grain dust (various cereal grains,
fungi, mites, insects, and pesticides) (Dosman et al. 1979).

Dosman and colleagues (1980) compared 90 lifetime nonsmoking
grain workers with 90 lifetime nonsmoking control subjects selected
randomly from a hospital service plan in the same Canadian
Province. Study subjects and controls were individually matched for
age, resulting in a mean age of 30.8 years for both groups. Using
modified MRC criteria for the diagnosis of chronic bronchitis, the
investigators found that 23.1 percent of the grain workers had cough
and phlegm production compared with 3.1 percent of the control
subjects, an eightfold difference. Among the grain workers, the rate
of chronic bronchitis rose with duration of employment from 14.3
percent of the workers with less than 5 years of employment to 35.7


percent of the workers with over 20 years' tenure, an increment not
seen with increasing age among the control workers.

Other studies of smaller groups of nonsmoking grain handlers
have been less impressive. Broder and colleagues (1979) compared
two groups of Canadian grain workers (26 and 39 workers, respec-
tively) with 40 civic workers: all three groups had never smoked.
Mean duration of employment was at least 9 years. Symptoms of
chronic simple bronchitis occurred in 12 and 8 percent of the grain
handlers, respectively, and in 3 percent in the control workers. Do
Pica and colleagues (1977) reported that 30 percent of 57 grain
workers who did not smoke met the MRC criteria for chronic
bronchitis. No control group was studied.
Comparison of 610 grain elevator workers in British Columbia

with 136 civic workers and 187 noncedar sawmill workers (Chan-
Yeung et al. 1980) showed no significant differences in prevalence of
cough or phlegm production among the nonsmokers. However, the
two control groups had higher rates of symptoms than the control
groups from other studies.

Dosman, Cotton, and their colleagues (Cotton et al. 1983; Dosman
et al. 1984) updated their 1980 study with reports of larger cross-
sectional studies in 1983 and 1984. Rates of chronic bronchitis in 195
lifetime nonsmoking grain workers (approximately 15 percent)
versus 195 age-matched lifetime nonsmoking control workers (about
3 percent) were similar to those found in the previous study (Dosman
et al. 1980).

The interaction between smoking and grain dust exposure has
received some attention. Dosman and others presented data relevant
to chronic simple bronchitis in an editorial (Dosman et al. 1979).
Rates of chronic cough with phlegm production in the four exposure
groups are shown in Table 1. Smoking had a somewhat greater effect
than grain dust on the prevalence of symptoms of chronic bronchitis.
The combination of exposures reflected an additive effect of the
individual exposures. A later study by Dosman's group (Cotton et al.
1983) yielded very similar results, with an additive interaction
between smoking and grain exposure, albeit each group experienced
lower rates of chronic bronchitis than in the 1979 study.

Other studies are less definitive about the nature of the interac-
tion between cigarette smoking and grain exposure on the preva-
lence of chronic simple bronchitis, either because they lacked a
nonexposed control group (Do Pica et al. 1977) or because smoking or
grain exposure did not show significant independent effects on rates
of chronic bronchitis (Chan-Yeung et al. 1980; Broder et al. 1979).
The results of these studies suggest at most an additive effect
between smoking and grain exposure.

188


TABLE l.-Prevalence of chronic bronchitis in grain-
      exposed workers and controls

Exposure group                 Percent wth chronic bronchitis

Morbidity ratio

Sonsmokmg controls                      3.5                 1

Zonsmokmg grainexposed workers              16.5                 4:

Smok7g controls                        25.0                 71

5 ooking graineqosed workers                36.5                 10.4

Polyvinyl Chloride and Vinyl Chloride

Polyvinyl chloride (PVC) and related compounds, including vinyl
chloride monomer and products of decomposition, have been impli-
cated in asthma (Bardana et al. 19801, lung cancer (Wagoner 19831,
and pulmonary fibrosis (Mastrangelo et al. 1979; Cordasco et al.
1980; Lilis 1980).

In a series of studies in the mid-1970s, Miller and Lilis and
colleagues (Miller et al. 1975; Lilis et al. 1976; Miller 1975, 1980)
evaluated approximately 900 active or retired polyvinyl chloride
production workers exposed to a variety of levels of PVC dust and
vinyl chloride gas in three separate facilities. Rates of chronic cough
and phlegm production were 20.4 and 16.0 percent, respectively,
among the workers in two of the plants, most of whom were smokers.
Nonsmokers were not analyzed separately for symptoms, and no
control group was studied. The authors (Miller et al. 1975) stated
that the prevalence of chronic simple bronchitis in PVC production
workers was similar to that found in studies of industrial and
nonindustrial populations.

Gamble and colleagues (1976) studied 327 either active or retired
PVC and vinyl chloride workers at one plant and found a smoking-
adjusted prevalence of chronic simple bronchitis of 2.5 percent.
Soutar and colleagues (1980) performed a cross-sectional study of
818 Scottish PVC manufacturing workers, most of whom were
actively working. Airborne dust levels were used to calculate a dust
index. The authors found no relation between dust exposure index
and prevalence of chronic cough and phlegm production.
In conclusion, the studies of the effects of PVC dust and vinyl
chloride gas have not shown an association with symptoms of chronic
simple bronchitis.

Welding

Welding entails a variety of methods, materials, and potentially
hazardous exposures (Challen 1974; Parkes 1982). Welders may be

189


exposed to irritants such as nitrogen dioxide, ozone, and phosgene, to
metal fumes such as cadmium, zinc, and iron, and to dusts including
free silica and asbestos (Parkes 1982). Hence, the task of elucidating
welders' respiratory disorders independent of cigarette smoking, if
any, and tying these disorders to specific exposures has been difficult
(Parkes 1982; Morgan and Seaton 1984).

In an early study, Hunnicutt and colleagues (1964) compared 100
electric arc welders with over 10 years of welding experience in a
shipbuilding plant with 100 other workers in the same plant.
Smoking and welding had equivalent effects on rates of cough and
phlegm production and the effects were additive.

Fogh and colleagues (1969) examined 156 welders, mostly electric
arc welders, and 152 control workers from shipyards and engine- and
tank-producing facilities. The groups had similar smoking habits and
similar rates of chronic simple bronchitis.

Peters and colleagues (1973) compared the pulmonary status of 61
welders, 63 pipefitters, and 61 pipecoverers from the same shipyard.
Age (mean, 50 years) and smoking habits of the three groups were
similar. No welders had radiographic evidence of siderosis. No
differences between groups in rates of chronic cough were observed.

In a Roumanian study (Barhad et al. 1975), 173 shipyard welders
were compared with 100 shipyard workers of other trades, but with
similar age and smoking habits, and no significant difference in
rates of chronic simple bronchitis were observed.

Antti-Poika and colleagues (1977) investigated symptoms in 157
electric arc welders without siderosis on chest x ray and 108 control
workers from engineering shops, matched for age, smoking, and
social class. The study workers and the control workers were
relatively young, with mean ages of 36.1 and 36.8 years, respectively.
Under the modified MRC criteria, chronic simple bronchitis was
reported in 24 percent of the welders versus 14 percent of the
controls (p< .Ol). Nonsmokers and smokers were not analyzed
separately.

Oxhoj and colleagues (1979) studied 119 electric arc welders and 90
clerks from a shipyard. The nonsmoking welders and the ex-smoking
welders had higher rates of chronic cough and expectoration than
the comparable controls (31 and 11 percent, respectively). The
welders who smoked experienced the highest rates of symptoms (77
percent) compared with the controls who smoked (43 percent).
Hence, smoking and welding had an approximately equivalent
ability to produce chronic simple bronchitis and the effects were
additive.

In conclusion, chronic simple bronchitis has been related to
welding apart from smoking habits in some of the studies reviewed.
Smoking and welding have produced additive rates of respiratory
symptoms in those studies that have shown an effect.

190


Sulfur Dioxide

Archer and Gillam (1978) compared 953 copper smelter workers
and 252 control workers drawn from a nearby copper mine mainte-
nance shop. With the smokers and nonsmokers combined, symptoms
of chronic simple bronchitis were noted in 15.8 percent of the smelter
workers compared with 9.5 percent of the control workers (p< .05);
the smelter workers smoked slightly more than the control workers.
Smoking was more important than the sulfur dioxide exposure in
causing symptoms of cough and phlegm production, and the effects
of the two factors appeared to be additive.

Other Exposures

Rubber curing workers had a 25.8 percent rate of chronic cough
and phlegm production versus 14.3 percent for the controls (p< .Ol)
(Fine and Peters 1976). The difference between nonsmokers was not
significant (5.9 and 12.0 percent in controls and workers, respective-
ly). However, the difference between smokers was significant (17.4
and 29.2 percent in controls and curing workers, respectively;
p= .03).

In a comparison of 312 coke ovensmen with 464 other coke
workers of similar ages (Walker et al. 19711, chronic simple
bronchitis was reported in 32 percent of the smoking ovensmen
versus 23 percent of the other coke workers who smoked (p < .02).
Among the nonsmokers, 9 percent of the ovensmen noted these
symptoms compared with 6 percent of the other coke workers, an
insignificant difference. Hence, coke oven exposure potentiated the
bronchitic effect of smoking.

Summary and Conclusions

1. Chronic simple bronchitis has been associated with occupation-
al exposures in both nonsmoking exposed workers and popula-
tions of exposed smokers in excess of rates predicted from the
smoking habit alone. Among these exposures are coal, grain,
silica, the welding environment, and to a lesser extent, sulfur
dioxide and cement.

2. The evidence indicates that the effects of smoking and those
occupational agents that cause bronchitis are frequently addi-
tive in producing symptoms of chronic cough and expectora-
tion. Smoking has commonly been demonstrated to be the more
important factor in producing these symptoms.

191


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194


CHAPTER 6

ASBESTOS-EXPOSED WORKERS


CONTENTS

Introduction

Asbestos-Exposed Populations

Lung Cancer

Lung Cancer in Nonsmoking Asbestos Workers
Lung Cancer in Cigarette-Smoking Asbestos Workers
Threshold

Cessation of Exposure
Mechanisms of Carcinogenesis in Cigarette-Smoking
Asbestos Workers

Animal Studies of the Carcinogenic Interactions Be-
tween Cigarette Smoke and Asbestos
Concepts of Carcinogenesis
Conclusions

Chronic Lung Disease
  Chronic Lung Disease Death Rates
  Pulmonary Function Testing
  Small Airways Function
  Chest Roentgenographic Changes
  Roentgenographic Changes in Non-Asbestos-Exposed
   Populations

Roentgenographic Changes in Asbestos-Exposed Popu-
lations

Interstitial Fibrosis in Asbestos-Exposed Populations
  Immunologic Response to Cigarette Smoke and Asbes-
   tos Dust

Humoral Immunity
Cellular Immunity
Sister Chromatid Exchange Frequency

Public Health Implications

Summary and Conclusions


References

197


introduction

Cigarette smoke and asbestos are agents with welldocumented
risks associated with exposure. Large numbers of individuals have
had exposure to either or both of these agents sufficient to generate
significant excess death and disability. The focus of this review is the'
effects of combined exposure to asbestos and cigarette smoke. The
literature that establishes the causal nature of the risks associated
with each of these exposures and the nature and extent of the
disease that can occur is extensive, and has been reviewed in detail
elsewhere (US PHS 1964; US DHEW 1979; US DHHS 1980, 1981,
1982, 1983, 1984; Selikoff and Lee 1978; Ontario, Royal Commission
1984; NRC 1984). However, populations with asbestos exposure
commonly have coincident cigarette smoke exposure, and the
magnitude of the risk of lung cancer and chronic lung injury
produced by smoking necessitates a careful examination of the
smoking habits of asbestos-exposed workers in order to define the
risks of isolated and combined exposures.

A number of conditions or diseases known to be associated with
smoking, asbestos, or both, including mesothelioma, heart disease,
pleural plaques, adverse reproductive outcomes, and cancers other
than lung, are not discussed here; the focus of this chapter is lung
cancer and chronic lung disease, the disease processes for which the
largest amount of data on the effects of combined exposure is
available.

Asbestos-Exposed Populations

Some exposure to both cigarette smoke and asbestos appears to be
an inescapable consequence of living in the urban U.S. environment.
The relatively omnipresent nature of cigarette smoking as a social
phenomenon makes at least incidental exposure to cigarette smoke a
universal experience, and the digestion of lung tissue from individu-
als with no known asbestos exposure commonly reveals low concen-
trations of asbestos bodies and asbestos fibers (Churg and Warnock
1977, 1980). It is technically extremely difficult to establish the
presence or absence of an effect in populations who have had no
exposure to asbestos other than the levels in ambient air or who
have not had repetitive exposure to smoke through active or
involuntary smoking. However, it is generally accepted that these
extremely low dose exposures do not substantially alter the occur-
rence of lung cancer or chronic lung disease in the general
population (Ontario, Royal Commission 1984).

The same statement cannot be made for individuals with repeti-
tive low dose or indirect exposures to either of these agents, however.
Evidence continues to accumulate that shows that nonsmoker
exposure to environmental tobacco smoke may carry with it an

199


   I
    Tremdlte
Cab% (%022) (OHh

    I
     Crocidolite
    Blue asbestos
Na2Fell,Fell12 (Si.O& (OH)Z

   Actu&e
Ca, (Mg. Fe). (Si.O& (0%

FIGURE l.-Principal varieties of asbestos
SOURCE Chatfield (1981 t

increased risk of lung cancer (IARC, in press). The exposure of the
wives and children of asbestos workers to asbestos on work clothing
and in the home environment is thought to be associated with an
increased risk for mesothelioma and possibly other diseases (Selikoff
and Lee 1978). The risk from these low dose exposures is smaller
than the risk for individuals directly exposed to these agents (active
cigarette smokers and workers occupationally exposed to asbestos
dust).

"Asbestos" refers to a specific group of fibrous silicates, the
principle varieties of which are listed in Figure 1. Commercial use of
asbestos stems from its qualities of resistance to heat and acid and its
ability to be woven into fabric (Zoltai and Wylie 1979). Commercial
products known as asbestos differ in the configurations and dimen-
sions of their fibers as well as in their chemical makeup and
crystalline structure. These properties determine, in part, the
deposition patterns of fibers in the respiratory tract and the
mechanisms whereby the fibers interact with the cells of the lung.

200


The asbestos minerals are classified according to structural
features into two groups, serpentine and amphibole. Chrysotile, a
serpentine (white asbestos), comprises pliable, curl:,, fibers that are
formed individually from fibrillar subunits. Layers of linked silica
tetrahedra alternate with layers of magnesium hydroxide octahedra
to form long, hollow, scroll-like structures. Chrysotile accounts for
approximately 95 percent of the world usage of asbestos today. The
major producers are the Soviet Union and Canada.

The amphibole types of asbestos (crocidolite. amosite, tremolite,
actinolite, and anthophyllite) are generally made up of straight,
needle-like fibers consisting of strips of silica tetrahedra linked by
one or more cations (calcium, sodium, magnesium, and iron). The
mineral names are often distinguished by adding the modifier
asbestos after the name for those minerals that may occur both as a
fiber and not as a fiber. In this text, crocidolite refers to asbestiform
richterite and amosite refers to asbestiform grunerite. In the United
States, amosite and, to a lesser extent, crocidol;te were widely used
in the past, but their commercial importance has aecreased dramati-
cally in the last two decades (Craighead and Mossman 19821. The
amphiboles tremolite, actinolite, and anthophy'lite are minor con-
taminants of some chrysotile and industrial talc products. are
present in both asbestiform and nonabestiform types, and are not
produced for commercial use.

The occupations and industries in which the major mortality
studies of asbestos-exposed workers have been conducted are pre-
sented in Table 1. Groups not described in this table, but for whom
there is considerable concern about substantial asbestos exi; xxc,
include workers in the building and demolition trades and mainte-
nance workers.

The number of workers exposed to asbestos in the United States
has been variously calculated, but a detailed review by Nicholson
and colleagues (1982) estimated that 18.8 million workers have had
more than 2 months of exposure in occupations where significant
asbestos exposure may have occurred.

An earlier chapter of this Report documents that a:rf and
occupation are associated with substantial differences in s   Ing
behavior. These differences would be expected to substantial ' ;. ter
lung cancer and chronic lung disease mortality; therefore, a careful
examination of the smoking habits of asbestos-exposed popula..  ,is is
needed in order to interpret the data on mortality and dzw:.:`..
incidence and prevalence reported in the literature. Table 2 m-r ~2:
the smoking habits of asbestos workers from a number of L' .:  es of
asbestos-exposed populations. In most of the studies cii ash&o<-
exposed populations, approximately ; r1 to 80 percent of male asbest.cs
workers smoked. In some subsets of workers, well over 9C percent of
the individuals were current smokers or had smoked in the past. Li

201

157-964 0 - 8b - 8


TABLE l.-Mortality from asbestos-related diseases in various cohort studies
             --                                                          `bbeat0ai.e    Lung cancer
w of                                     Percent   Number in    TOtal    MC%O-   (pneum*
activity        Study         P1tX-e     Fiber type   smoking    cohort     deaths   thelioma   coniceia)   oteervd Expected   SMR


Mining      McDonald et al.   Quebec      chrysotile              10,939    3,291 10        42      230      164 125
          (1980)
         Nicholson et al.   Quebec      Chrywtile                 544      118     1        26       28      11.1 252
         (1979)
         Rubino et al.     IdY       Chrysotile                 952      332     0         9       11'      10.4 106
         (1979)
         Hobbs et al.      WeStem      Crocidolite              6,200     526 17'        14       60      36.2   157
          w8o)          Australia
         Mew-man et al.    Finland     Anthophyllite   66.7        1,092      248     0        13       21      12.6   167
         (1974)

Friction     Berry and      England     Chryeotile            M 9.113    1.640     8        NS      1435     139.5   103
materials      Newhow                Crocidolite '           w 4,347      346     2       NS       6'      11.3 53
         w63)
         McDonald et al.    Connecticut   Chryeotile              3,641    1,267     0        12'      13      49.1   146.7
         mw                   Crocidolite'
                         Anthophyllite'

Geneml      Henderson and    United Statea   Cbryaotile     81         1,075      781     6        31       63'     23.3   270.4
manufacturing   EIlt.ZliiP                 Crwidolite
          (1979)                   Ammite
         Newhowe and    England     Chryeotile            M 2.887      545 46       NS      103'     43.2 238
        Berry (1979)              Crocidolite             W   693      200 21       NS       27=      3.2 844
                                Amosite


TABLE l.-Continued

Type of
activity

Study         Place

Fiber type

                             Aabeatosie    Lung cancer
Percent   Number in    Total     MHdO-   (pneumo-
smoking    cohort     deaths   thelioma   conic&)   Observed Expected   SMR

Textiles

Pet0 et al.
(1977)
Pet0 (1980)


Dement et al.
(1982)
McDonald et al.
(1983a)
McDonald et al.
(1983b3


Robin et al.
(1979)

England

England

South
Carolina
South
Carolina
Pennsylvania



Pennsylvania

Chrysotile
Crocidolite (?)
Cbrysotile
CmcidoIite (?)
Chryeotile
Crocidolite '
Chrywtile
Cncidolite *
Chryeotile
Amoeite
CrocidoMe '
Cbryeotile
Amoaite
CrocidoMe '

         1,106      317    10       NS       511     23.8   214


           679      239     7        10       40      23.3   172


62.4          768      191     1        15       26       7.5   348


89"        2,543      857     1        21       59      29.6   199.5


75*        4,137     1,392    14        74       53      50.5   105



        M  2,722      912    13        NS       49      36.1   136
        w   554      128     4        NS       14       1.7   824

Cement
products

Weill et al.
(1979)


Finkelstein
(1963)
Thomas et al.
(1982)

New Orleans



Scarborough


CanJilT

Chryaotile
Crwidolite
Ammite'
Chrymtiie
Cmcidolite
Chryaotile
Cnxidolite'

5,645      601     0'       NS       51      49.2   104



535      138    19        NS       26       5.4   480


1,592      351     2        NS       28      33.0    85

Gas mask     Jones et al.     England      Crocidolite                 578      166    17        NS       12       6.3   190
manufacturing   (1960)

Insulation
producta

Seidman et al.     New Jersey    Ammite                  820      528    14        30       93      22.8   408
(1979)


l-3
2   TABLE l.-Continued

- --

5pe of
activity

Study

Place

Fiber type

                             Aabeetaeie     Lung cancer
Percent   Number in Total    Me%%-   (pneumw
smoking    cohort     deaths   thelioma   conimie)   OkrVed  Expected   SMR

Insulators

Newhouse and
Berry (1979)
Selikoff et al.
(1979)
Selikoff,
Seidman et al.
(1980)

Shipyard     Rmaiter and
workers       GoleE (1980)

England

Chrysotile

I.368      83 10        NS       215      5.6   375

          Ammite
United States   Chrysotile     82.3       17,800    2,271    175       168      486      105.6   480
and Canada   Amcaite
New York and  Chryeotile                 632      478    38        41       93      13.3   699
New Jersey   Amcsite

Eneland

Chrvsotile     66.8        6,076    1,043 31         9       84      119.7 70

Ckidolite
Amcsite

NOTE: NS, not stated; M, men; W, women

' Includes one suspected cade of mesothelioma.
z According to the mortality study, which WBB restricted to deaths before January 1.1978. The text of this study also noted 26 caeea of meaothelioma diagnosed to January 1.1979
' Pleural mesotheliomas included in lung cancer total given by the authors but taken out of the lung cancer total for the purpoee of this Table
`Minimal usage.
n Authors stat.4 that none of the casea were clearly attributable to asbestos exposure.
`Male eversmokers. 1910-1919 birth cohort.
`Two c-sea did not meet witaria for entry into the cohort.
`Includes mewtheliomaa


and colleagues (1983) showed lower rates of smoking among shipyard
workers in South Carolina. Only 42.9 percent reported that they
were current smokers, and 24.8 percent had ceased smoking. This
decline in smoking found in the United States is not evident in
studies of asbestos workers in Great Britain.

Lung Cancer

Cigarette smoking is the major cause of lung cancer in the U.S.
population considered as a whole (US DHHS 1982). Among U.S. men
aged 50 to 70 (the group most commonly examined in occupational
mortality studies), over 10 percent of the deaths were due to lung
cancer in 1977 (McKay et al. 1982). The prevalence of smoking and
the percentage of deaths due to lung cancer vary substantially in the
studies of asbestos-exposed populations reported in the literature,
but in the largest study (Hammond et al. 19791 of heavily exposed
workers with a high smoking prevalence (82.3 percent), 21.4 percent
of the deaths were due to lung cancer.

The high incidence of lung cancer in both asbestos-exposed
workers and the U.S. population, together with the potency of
cigarette smoking in determining lung cancer risk, makes the
determination of the smoking habits of asbestos-exposed populations
essential to any evaluation of lung cancer. The prevalence of
smoking varies markedly among men born in different years of this
century, between blue-collar and white-collar workers (see the
chapter on smoking patterns), and among the populations of asbestos
workers studied in the literature. In particular, men born between
1910 and 1930 have a higher prevalence of smoking than men born
earlier; men born after 1930 have had lower prevalences of smoking
at any given age than the men born between 1910 and 1930. Levels
of asbestos exposure have also not been constant with time. Since the
recognition of the hazards of asbestos exposure, improved control of
asbestos dust has reduce the levels of asbestos in mines and
manufacturing plants and. more recently, in other areas where
asbestos exposure may also occur. These temporal trends of smoking
prevalence and asbestos dust levels result in complex relationships
between cumulative asbestos dust exposure and cumulative smoking
exposure. The oldest workers (those born before 1910) may have
higher cumulative asbestos dust exposure at any given age than
younger workers, but will have a lower smoking prevalence.
Workers born between 1910 and 1930 are likely to have both a
higher smoking prevalence and a higher cumulative asbestos
exposure at any given age than workers born after 1930. Therefore,
in many studies of currently employed asbestos workers, cumulative
asbestos exposure will be somewhat correlated with smoking preva-
lence, and biased estimates of dose-response relationships with

205


!z  TABLE 2.-Smoking characteristics of asbestosexposed workers


                  Number and type
   Study             of population                  Smoking characteristics (percent)                     Comments

Selikoff et al.
(1968)

370 union laal members,
aged 674, New Jersey

Hammond et al.     17,800 union local
(1979)        members, New Jersey

Langlands et al
(1971)

252 insulation workers,
Belfast

Ferris et al.
(1971)

183 shipyard workers

Murphy et al.
(1971)

101 shipyard pipecoverers.
New England

Harries et al.
(1972)

2,443 male dockyard
workers, Great Britain

Harries and Lumley
(1977)

McMillan et al.
(1979)

945 royal naval dockyard
workers, Great Britain

719 royal naval shipyard
workers, Great Britain

SMfEX
76.5

SM'
54.2

Age <4Oyears 69'
  >40 years 74

SM
54.6

SM
66.4

64.7

67.2

46.7

NW
13


Ex
22.2

NS1F.X
45.4

EX
26.8

2.2

16.2

28.7

Pipe/cigar
10.5


  NS
10.8

pipe/cigar
  5.9

' Never smoked
regul=ly


o 82.9% smoked
>20 cigdday

' 19% smoked
>25 cigdday

NS
6.9

33.1

16.6

22.7


TABLE 2.-Continued

Study


Kolonel et al.
(1980)



Pearle
(1982)

  Number and type
   of population


Male shipyard workers,
Hawaii


131 male shipyard workers

           Smoking characteristics (percent)                      Comments


Asbestosexposed workers    63.8
Nonexpzesd workers       62.5
General population       58.8

                 75.6

Li et al.         3,991 shipyard workers,
(1983)           South Carolina

SM       EX       NS
42.9       24.8       32.3

Be&lake et al.
(1972)

Asheetcm workers, Canada

SM'       NS
85.3       14.7

Meurman et al.
(1973. 1974)

Liddell et al.
w32)

Berry et al.
(1972)

Meurman et al.
(1979)

Anthophyllite mine workers,
1936-1967

SM'
66.7

615 asbestos workers,
Bueb=

1,203 male asbestos
workers

Asbestos workers, Finland

        NS
        33.8


SM       Ex       NS
74.5       19.5        6

Cohort survivors    66.7
Dsceasd workers   79.8

o Smokera=ever
smoked 1 cig/day
for 2 1 yr.;
includes pipe
and cigar

o 26.1% smoked
>15 cigslday


TABLE 2.-Continued

Study

Number and type
of population

Smoking characteristics (percent)

Commmts

Weill et al.
(1975)
  and
Selikoff et al.
(1979)

859 aebest~~~ cement mfg.                        SM       EX        NS
workers, New Orleans                           51        26        23

Greenberg et al.
(1976)

890 ssheat-os workers,
Texas

84

Weiss and Theodos
(1978)

40 ashestce workers

55.7'      22.7       21.6

' 22.7% smoked
>1 pack/day

Berry et al.
(1979)

Asbestos textile factory
workers, Great Britain

SM       EX        NS
69.2       13.8        17

Selikoff, Seidman,
et al. (1980)

933 am&e asbestoe
workers, examined 20 yra.
from employment start date

SM
61.7

EY
12.1

NS
13.4

Ottlet
12.6

Skerfving et al.     241 a&e&m workers,                          64.3
ww          Sweden


Weiss et al.       45 asheatce workers, aged                         SM       EX        NS
(1981)        240, reexamined                             42.2       31.1       26.7               ~-__-


TABLE 2.4ntinued

Study


McDermott et al.
(1982)

  Number and type
   of population


Two groups of a&?st.cm
workers, Swaziland

         .-


   Smoking chsrxtetitica (percent)                      bmments



       SM       EX        NS
Group     38        10

Group     3.4        4

Acheeon et al.      Amosite asbestos workers.
(1964)          Great Britain

Berry et al.       1,253 male and 423 female
(1965)         asbestos factory workers

NOTE: SM = Smoker; EX = Exsmoker; NS = Nonsmoker.

       77        5        19




Men      74.5       19.6        5.9
Women    49.4       22.7       27.9


asbestos may result. These associations between asbestos exposure
and smoking must be considered when examining the literature and
are particularly important when drawing conclusions from studies
that either do not control for smoking or control for smoking
inadequately. For these reasons, this discussion is limited largely to
those studies that have provided data on the smoking habits of their
populations.

Examination of the relationships among smoking, asbestos expo-
sure, and lung cancer includes consideration of a series of separate
questions. Does asbestos exposure exert an effect in the absence of
active smoking exposure? What are the effects of combined expo-
sure? Is there a threshold of exposure below which no effect occurs?
What happens to the risk following smoking cessation and after
cessation of new asbestos exposure?

Lung Cancer in Nonsmoking Asbestos Workers

The most direct way to demonstrate that asbestos exposure results
in an increased lung cancer risk independent of cigarette smoking is
to monitor disease occurrence in asbestos-exposed individuals who
have never smoked cigarettes regularly. However, because lung
cancer is a relatively rare phenomenon in people who have never
smoked cigarettes, even among asbestos-exposed populations, a large
population of nonsmokers is required before a statistically signifr-
cant number of cases would be expected. The relatively high
prevalence of smoking in asbestos-exposed populations decreases
even further the number of nonsmoking asbestos-exposed workers
available for study, making the evaluation of risks for the nonsmok-
ers difficult. For example, no lung cancer deaths were identified
among the nonsmokers in the original cohort of asbestos insulation
workers reported by Selikoff and colleagues (1968).

Some authors have attempted to increase subject numbers in the
nonsmoker category by combining ex-smokers or light smokers with
never smokers (Blot et al. 1980). However, the risk of developing lung
cancer remains elevated in ex-smokers compared with nonsmokers
for at least 10 to 15 years after cessation, and the excess risk is
proportionate to the amount smoked (US DHHS 1982). Smokers of
less than 10 cigarettes per day have less risk than heavy smokers,
but the relative risk for lung cancer in these light smokers compared
with individuals who have never smoked regularly still varied from
2.3 to 9.5 in the major prospective studies on smoking mortality (US
DHHS 1982). Thus, combining people who have never smoked with
ex-smokers and light smokers is inappropriate and may introduce
bias when the effects of asbestos exposure alone are being assessed.

Several studies have examined populations large enough to
address the question of the risk of asbestos exposure in individuals
who have never smoked regularly. Hammond and colleagues (1979)

210


examined the mortality experience of the 17,800 members of the
International Association of Heat and Frost Insulators and Asbestos
Workers who were alive on January 1,1967. This group was followed
to December 1976, and the mortality of the 12,051 workers more
than 20 years after onset of exposure was analyzed. Of this group,
smoking histories were available for 8,220, of whom 6,841 (83.2
percent) had been regular smokers at some point and 891 (10.8
percent) had never smoked regularly. Of the 891 workers who had
never smoked regularly, death certificates indicated that 4 died of
lung cancer. The expected number of deaths was calculated from the
mortality experience of a population of blue-collar workers who had
never smoked regularly, drawn from the American Cancer Society
(ACS) prospective mortality study of 1 million men and women. The
resulting expected number of lung cancer deaths of 0.7 and the
observed number of 4 yielded a relative risk for asbestos exposure of
5.33. When the deaths were classified according to the best estimate
of the cause of death from all available data, rather than from the
death certificate alone, one additional case of lung cancer was
identified in a worker who had never smoked regularly.

Selikoff, Seidman, and Hammond (1980) reported the mortality of
933 men who began working in an amosite asbestos factory between
June 1941 and December 1945. Of these men, 78 (8.4 percent) were
known to have never smoked regularly; the death certificates of 5 of
this group listed lung cancer as the cause of death. When the best
estimate of cause of death was used, only three men were believed to
have died of lung cancer. The expected number of deaths was 0.2,
based on the ACS mortality study. This led to a relative risk of 25
(5/0.2) for workers who had never smoked regularly.

McDonald and colleagues (1980) examined the mortality experi-
ence of Quebec asbestos miners and millers and reported a dose-
response relationship between cumulative asbestos exposure and
lung cancer in nonsmokers. They compared the standardized mortal-
ity ratio (SMR) for lung cancer in miners who had never smoked,
using the mortality rates for the Province of Quebec, which are based
on both smokers and nonsmokers. The SMR increased from 0.18
among nonsmoking miners with less than 30 million particles per
cubic foot times years (mppcfoy) of exposure to 0.36 in miners with 30
to 299 mppcfey of exposure and 1.24 in nonsmoking miners with
more than 300 mppcfoy of exposure. There were 19 lung cancer
deaths among nonsmoking asbestos miners. These authors (McDon-
ald et al. 1980) also performed a cas+control study of the 245 miners
who had died of lung cancer. The distribution of cumulative asbestos
exposure among the 20 nonsmoking miners with lung cancer and 20
nonsmoking control miners matched for year of birth and smoking
status was examined, and the relative risk for lung cancer was found

211


to have increased from 1 in nonsmoking miners with less than 30
mppcfoy to 10 in nonsmoking miners with more than 1,000 mppcfey.

Liddell and colleagues (1984) reexamined the same po~,rlation of
Quebec asbestos miners after recording their smoking &tory by
pack-years of exposure. They identified 223 cases of lung cancer in
men who worked in the asbestos mines and mills of Quebec for a
month or more before January 1967 ind who were followed to the
end of 1975. The controls were selected from men in the same cohort,
born in the same years as the lung cancer cases, but still living.
Never smokers represented 23 of the 223 lung cancer cases and 201
of the 715 controls. The relative risks (RR) were calculated on the
basis of the mortality experience of the entire asbestos-exposed
population (whole population RR, l.O), and the risk in even the most
heavily exposed nonsmokers was still lower than the risk in the
entire population, which included both smokers and nonsmokers.
The RR for lung cancer increased from 0.19 in the nonsmoking
miners who had experienced a cumulative exposure of less than 100
fibers per milliliter times years ((f/mL)y) to 0.37 for those with 101 to
1,000 (f/mL)y and 0.87 for those nonsmoking miners with over 1,000
(f/mL)y, thus demonstrating a dose-response relationship with
cumulative asbestos exposure for lung cancer in the workers who
had never smoked regularly.

Berry and colleagues (1972) conducted a retrospective study of the
lung cancer mortality in more than 1,300 male and 480 female
asbestos factory workers over a lo-year period and compared their
mortality with the national lung cancer rates (Table 3). The national
lung cancer rates were converted to smoking-specific rates by
multiplying them by factors from the study of mortality of British
physicians by smoking status (Doll and Hill 1964) in order to develop
smoking-specific expected numbers of deaths. No lung cancer deaths
were recorded among the men who had never smoked, and only one
lung cancer death was recorded among the women who had never
smoked. The expected number of deaths was also very low, and so
even a single death was greater than expected, and it occurred in the
group of women with heavy asbestos exposure. The women in the
highest asbestos exposure category who had never smoked had 3.5
times the number of subject years at risk when compared with men
in the same exposure category (1,404 to 399) owing to the higher
prevalence of never-smoker status among women in the study. This
difference in number of individuals at risk may have contributed to
the demonstration of a lung cancer death among nonsmoking women
but not among men. Subsequently, Berry and colleagues (1985)
followed prospectively 1,253 male and 423 female asbestos factory
workers from the same plants. Smoking habits were determined in
1971 at the start of the study, and the population was followed
through 1980. The expected number of lung cancer deaths was

212


calculated from the death rates for England and Wales multiplied by
the lung cancer SMR for greater London, and an adjustment for
smoking status was made using the data from the mortality study of
British physicians. Observed and expected numbers of lung cancer
deaths by smoking status and level of asbestos exposure are
presented in Table 4. One lung cancer death occurred among the
men who had never smoked (0.1 expected) and three lung cancer
deaths occurred among the nonsmoking women (0.2 expected).

Meurman and colleagues (1979) reported 1 lung cancer death (of 23
total lung cancer deaths), a nonsmoking male anthophyllite miner.
Acheson and colleagues (19841 also reported 1 death from lung
cancer among the nonsmokers employed in an amosite manufactur-
ing factory, with an expected number of 1.1. However, the expected
number was calculated from age-specific population rates that
included both smokers and nonsmokers rather than from the rates
for a population of nonsmokers. Each of these studies supports an
increased risk for lung cancer in nonsmoking asbestos workers, but
the conclusions are based on a single death in a population.

In summary, the evidence that asbestos exposure results in an
increased lung cancer risk in the absence of cigarette smoking is
based on a small number of cases, but has been confirmed in several
different populations of asbestos workers. The high smoking preva-
lence in asbestos workers introduces the possibility that environmen-
tal tobacco smoke may increase the risk of lung cancer among the
nonsmokers, particularly if the synergism demonstrated between
active smoking and asbestos exposure pertains to environmental
tobacco smoke as well. In spite of these concerns, the available
evidence supports the conclusion that nonsmokers with substantial
occupational asbestos exposure are at increased risk of developing
lung cancer and that the risk increases with increasing cumulative
asbestos exposure.

Lung Cancer in Cigarette-Smoking Asbestos Workers

The risk of lung cancer in cigarette smokers has been examined in
a number of asbestos-exposed populations, and the increased risk of
lung cancer in smokers, coupled with the high prevalence of smoking
in many of these populations, has generated substantial numbers of
lung cancer deaths for analysis. These populations differ in smoking
habits, type of asbestos and duration and intensity of exposure, type
of activity that resulted in exposure, and duration of the followup of
the population.

A number of authors have compared the lung cancer rates in
asbestos-exposed populations with the rates in control populations
(Table 1). This approach can establish an excess mortality in a
population, but may not identify the causes of that excess. To
establish a causal link between an exposure and lung cancer, specific

213


E  TABLE 3.-Comparison of number of observed and expected deaths from cancers of the lung


                       NUDlber      Subjecbyeam                    observed lung      Adjusted observed
   Smoking habits on           of          at risk         Obeerved deaths         cancer deaths        lung cancer     Expected lung
   January 1,lW         Bubjecta       (adjusted)         (all cauees)         WD 162, 163)           deaths        cancer deaths

Men

Low/moderate aebeatas expure
Never smoked
Exsmokers
Smokers
Not known

Severe asbestos exposure
Never smoked
Exsmokers
Smokers
Not known

Women

Low/moderate asbestos exposure
Never smoked
Smokera
Not known

Severe a5beatoe exposure
Never smoked
Smokers
Not known

4-i            376              2
38            335              1
509         4,423             32
219           2.122             20

41            399             11              0                 0             0.0
39            415              3              2                1.6             0.2
663          6,920             82             3%5)              25.5             9.9
281          2,722             29              4                10.9             2.4

25            271              8              0                 0             0.0
45            577              6              1                 1             0.3
19            195              0              0                 0             0.1

120

1,404             23             2w               1.7             0.2
3,474             52              19(4)              15.5             1.4
1,547              9              0                2.6             0.4

0
:2,1
0

0             0.0
0             0.1
4.6             6.2
3.4             2.0

' Fires in parentheses indicate number of pleuralmesotheliomas.
SOURCE. Berry et al (1972).


TABLE I.-Observed and expected deaths from cancer of the lung during 1971-1980

Smoking habits in 1971        Number of subjects      Subject-years at risk        Total deaths

Lung cancer deaths

ObkWWd    Expected'

Low/moderate asbestos exposure

Never smoked
Exsmokem
Smokenr

45                 396               6              1         0.10
123              1.092               18              3         1.07
441                3.557               84             17        11.29

Severe anbestce exposure

Never smoked                  29                 273               2              0         0.06
&smokers                    123              1,003               343              8         1.25
Smokers                     522               4,394              1%             35        14.63

Low/moderate asbestos exposure

Never smoked
Exsmokers
Smokers

17                 128               5              0         0.04
12                  93               3              0         0.09
27                 220               4              0         0.32

   Severe ah&on exposure

     Never smoked                  101
     Exsmokera                    84
    Smokers                     162


' Calculated af?.er allowing for the effect of smoking, =x. sge, period, and region.
soIJlK!E: Belly et al. (1985).

799               26              3         0.20
659               24              2         0.50
1,413               52             10         2.02


criteria must be applied to the entire body of information available
on the exposure. This approach has been carefully and comprehen-
sively followed for both cigarette smoking (US DHHS 1982) and
asbestos exposure (Selikoff and Lee 1978), and the evidence is
sufficient to establish a causal role for both of these agents in
producing lung cancer. This section confines itself to an examination
of their interaction.
Selikoff and colleagues (1968) were the first to demonstrate
increased lung cancer risk among asbestos workers in an investiga-
tion that assessed smoking habits. In a group of 370 asbestos;
insulation workers, none of the 48 workers who had never s: 1~ 1-9~
regularly or of the 39 workers who smoked only pipes or cigt :s
developed lung cancer. Of the 283 cigarette-smoking workers, 24 died
of lung cancer during the 4 years and 4 months of the followup
period, although only 2.98 lung cancer deaths were expected on the
basis of smoking-specific death rates.
A more extensive evaluation of the risk of cigarette smor;ing for
asbestos insulation workers was provided (Hammond et al. 1979) by a
prospective evaluaLic,n of the 17,800 members of the International
Association of Heat and Frost Insulators and Asbestos Workers
discussed earlier. Of this population, 8,220 workers were more than
20 years beyond their onset of asbestos exposure and had a known
smoking status. Fifty-four percent of this group were cigarette
smokers at the start of the study. The comparison group was drawn
from the ACS study of 1 million men and women, and consisted of
73,763 white men with no more than a high school education and not
employed as farmers, but with a history of occupational exposure to
dust, fumes, vapors, gases, chemicals, or radiation, who were living
on January 1, 1967, and were traced thereafter. The control group
was followed only until September 30, 1972, and the asbestos
workers were followed through 1976; therefore, the lung cancer
death rates in the control group were adjusted upward to reflect
changes in the U.S. national mortality experience for lung cancer
during the time period of differential fol!owup.
There were 1,332 deaths among wcrkers more ihan 20 years after
onset of exposure whose smoking habits were known; 314 (23.6
percent) deaths were due to lung cancer, using the best estimate of
cause of death. Death certificar,e data indicated 272 lung cancer
?eai :A>, Figure 2 portt.:ya the il ,ztality ratios for smokers and
:)i,nsmokerx in the col>Lrol and t.iC asbestos-exposed populations,
with tne mortality raGo of nonsmokers in the control group set at 1.
The lung cancer death rates increased from 11.3 per 100,000 among
nonsmokers in the control group to Z3.4 in the nonsmoking asbestos
workers, 122.6 for smokers in the contrG1 group, and 601.6 for
smoking asbestos workers. The lung cancer relative risk with
combined exposure (53.24) is far larger than the sum of the


individual risks for cigarette smoking and asbestos exposure sepa-
rately, and is quite close to the product of the separate mortality
ratios (5.17 and 10.85) together.

.\,curate data on the intensity of asbestos exposure for individual
workers (dose) were not available for this group of insulation
workers,  .ld so an asbestos dose-response relationship was not
examinea. Dosage data were available for cigarette smokers in this
population, however, and the ratio of observed to expected lung
cancer deaths (with the expected deaths calculated from the rates in
nonsmoking non-asbestos-exposed controls) increased from 5.33 in
asbestos workers who never smoked regularly to 7.02 in pipe and
cigar smokers, 36.56 in ex-smokers, 50.82 in smokers of fewer than
20 cigarettes per day, and 87.36 in asbestos workers who smoked one
pack or more per day.

Interaction between smoking and asbestos exposure in the devel-
opment of lung cancer has also been explored in other populations.
In sonle studies the numbers have been too small to clearly
differentiate between an additive and a multiplicative effect with
combined exposure; however, the data have been consistent with an
effect that is at least more than additive. This interaction of
cigarette smoking and asbestos exposure has been demonstrated in
asbestos factory workers (Berry et al. 1972, 19851, Quebec miners and
millers (McDonald et al. 1980; Liddell et al. 19841, amosite asbestos
factory workers (SeXoff, Seidman, and Hammond 1980) and Finn-
ish anthophyllite miners and millers (Meurman et al. 1979).

A dose-response relationship between cigarette smoking and lung
cancer in the general population has been readily demonstrated in a
number of prospective mortality studies (US DHHS 1982); however,
dose-response relationships for asbestos exposure and lung cancer
have been more difficult to establish. The carcinogenicity of asbestos
may vary with the type of asbestos, and possibly with the length or
diameter of the fiber. There are also potential differences in the
carcinogenic risk associated with the different stages and processes
of converting asbestos from the raw mineral in the mine into a
finished manufactured product. As a result, it is difficult to classify
the asbestos exposure of different study populations with a single
measurement that quantifies the carcinogenic dose. Even if such a
scale were agreed upon, actual measurements of asbestos dust levels
in the work environment are often not available. Measures of dust
exposures for individual workers are even less frequently available.
The quantification of asbestos dust exposure has frequently used
estimates of likely exposures based on work conditions and job
classification, rather than actual measurements of asbestos dust in
the air, because of the absence of these measurements for most
workers. This lack of information has been particularly problematic
for workers employed more than 20 years ago, a group now at high

217


67.36

53.24

Nonsmokers Nonsmokmg   Smokers   Smokrq    Smoking
not exposed   asbestos   not exposed   asbestos  ( > 1 pack/day)
to asbestos   workers   to asbestos   workers    asbestos
                                workers

FIGURE 2.-Relative risk of dying of lung cancer for
      smoking and ntilsmoking asbestos workers
      and smoking and nonsmoking control group
        members
SOURCE Hammond et al (19791.

risk of developing lung cancer. Finally, cumulative asbestos expo-
sure, age, and cumulative cigarette smoking exposure are generally

218


correlated. Older employees worked under conditions of much higher
asbestos exposure than their younger counterparts, and these same
older cohorts probably also had higher prevalences of cigarette
smoking, as described in the chapter on smoking patterns by
occupation. Confounding between cumulative asbestos exposure and
cumulative cigarette smoke exposure may result when dose-re-
sponse relationships between cumulative asbestos exposure and lung
cancer are examined without a control for differences in smoking
habits among the different asbestos exposure groups.

Berry and colleagues (1972) examined dose-response relationships
in a population of 1,300 male and 480 female asbestos factory
workers in Great Britain. Workers were categorized as having low to
moderate asbestos exposure or severe asbestos exposure, and the
expected number of lung cancer deaths was calculated from stand-
ardized mortality rates for lung cancer for the greater London area.
An adjustment for cigarette smoking status, derived from the
mortality study of British physicians by Doll and Hill (19641, was
used to estimate rates for smokers and nonsmokers. The results are
presented in Table 3. The small number of lung cancer deaths makes
interpretation somewhat difficult, but it appears that the increased
lung cancer death rate is limited to smokers with severe asbestos
exposure.

McDonald and colleagues (1980) examined Quebec miners and
presented evidence for a dose-response relationship between cumu-
lative asbestos exposure and lung cancer risk in the smoking miners.
They compared the lung cancer mortality rates in the Quebec miners
with the mortality rates for the Province of Quebec. Table 5 shows
the SMRs for lung cancer in miners by level of cumulative asbestos
exposure and smoking habits. Heavy smokers consistently had
higher SMRs than moderate smokers at the same level of cumulative
asbestos exposure, and the SMRs increased with increasing cumula-
tive exposure to asbestos in each of the smoking categories. Using
the same population of miners, these authors conducted a case-
control study of 245 lung cancer victims and a similar number of
control miners matched for smoking habits and year of birth. The
distribution of cumulative asbestos dust exposure was examined, and
the results in cigarette smoking miners showed an increase in
relative risk with increasing cumulative exposure. The relative risk
of cigarette smokers in the lowest exposure category (< 30 mppcfay)
was set at 1.0, and the relative risk increased to 1.12 at 30 to 300
mppcfoy of exposure, 1.58 at 300 to 1,000 mppcfoy, and 1.99 at
2 1,000 mppcfoy of exposure.
A more quantitative description of the smoking habits of the same
Quebec miners was provided by Liddell and colleagues (1984). Their
data are presented in Table 6. The dust exposure measurements
were made as particles per cubic foot with midget impingers, and

219


TABLE 5.-Deaths from lung cancer in relation to dust
      exposure and smoking habit

                 Dust exposure umppcf.yl accumulated to age 45

                c 30          3s-299         2300          All

Smoking habit      0    SMR      0    SMR      0    SMR      0    SMR

Nonsmokers        5    0.18      6    0.36      a    1.24      19   0.38


Mxkratc smokers    73    1.14     64    1.35     52    2.31     189    1.41

Heavy smokers      13    2.12      11    2.39      10    4.50      34    2.63

All smoking habits   91    0.93     81    1.18     70    2.25     242    1.23

SOURCE. LIddell et al 119841

individual exposures were calculated on the basis of the work
histories and the measurements of impinger dust counts in the work
environment between 1949 and 1966. These counts were then
converted to fibers per mL. Two hundred and twenty-three cases of
lung cancer were identified and matched to 715 controls born in the
same year, and a case-control analysis was conducted. As is shown in
Table 6, the relative risk of developing lung cancer increases with
increasing asbestos exposure category for each of the cumulative
pack-year categories. The analysis also suggests that the interaction
between cigarette smoking and asbestos exposure is greater than
additive.

Thus the studies that have examined the question of a dose-
response relationship for asbestos exposure and lung cancer in the
face of an adequate control for cigarette smoking have shown an
increasing risk of lung cancer as asbestos exposure increases. This
suggests that a dose-response relationship for asbestos exposure and
lung cancer does exist, and that it is not explained by differences in
smoking habits.

Threshold

The question whether a level of asbestos exposure exists below
which an exposure does not result in an increased risk of lung cancer
is one that is both technically extremely difficult to answer and
extremely important to those required to make policy with regard to
asbestos exposure. Current understanding of carcinogenesis and host
defenses against cancer are not advanced sufficiently to allow either
the acceptance or the rejection of a threshold. It is common practice
to assume a linear relationship between the dose of a carcinogen and
the development of carcinoma, and to assume that the dose-response
relationship does not have a threshold. The linear nonthreshold
model allows the extrapolation of data obtained for higher exposures

220


TABLE 6.-Risks of lung cancer, by cigarette smoking and
      asbestos exposure, relative to all 223 cases and
      715 referents for whom smoking histories were
      reliable; unmatched analysis

Expsure accumulated up to 9 years before death of cake
              mf mL'\

                                      High and
                         Low       !&dlUrn     very high
Pack-years '                   " 1001      ,I l.ooo1      / 2 l.ooo'       All

0       Nu;nher of cases            6          7          10        23
      Number of referentI         103         61          3i        201
      Relative risk             0 19        0 3;         n ei       0.37

1. ~ 40   Number of case5            29         2;          34        90
      Number of referents         123         93          63        279
      Relative risk             0.76        0 93         173       1.03

240     Number of cases            40         35          35        110
      ?;umber of referents         117         79          33        235
      Relative risk             1.10        1.42         2.88       1.50


All      Number of cases            75         69          73       223
      Xumber of referents         343         233         139        715
      Relative risk             0.70        0 35         1.82       1.00

' Number of cigarettes a day 20 x duration m pan
SOURCE: Liddell et al. 119841

to the very low exposures. This extrapolation is substituted for the
examination of the very large populations that would have to be
examined in order to demonstrate the small expected excess risk
with low dose exposure. Such models are particularly attractive for
exposures for which human epidemiologic data are limited or absent.
As discussed earlier, however, minimal exposure to cigarette smoke
and asbestos is probably a nearly universal experience in urbanized
society. Because of the large population exposed, more careful
examination of the available evidence on the risks of these exposures
is necessary.

The number of cigarettes smoked per day by an individual is a
readily available measure of the dose of smoke exposure in the active
cigarette smoker; therefore, it has been possible to examine relative-
ly completely the dose-response relationship for cigarette smoking
and lung cancer. There is a consistent increased risk for lung cancer
among smokers in the lowest category of number of cigarettes
smoked per day in the major prospective mortality studies on
smoking (US DHHS 1982). In the study of U.S. veterans (Kahn 19661,
a relative risk for lung cancer of 3.77 was demonstrated in those who
smoked only occasionally compared with those who had never
smoked regularly (the relative risk for those who smoked 1 to 9
cigarettes per day was 4.07 compared with those who never smoked

221


regularly). It seems clear that for the active cigarette smoker there is
no safe cigarette and no safe level of cigarette smoking (US DHHS
1982). Furthermore, recent data (IARC, in press) suggest that
repetitive exposure to environmental tobacco smoke may be accom-
panied by an increased risk of lung cancer, thereby suggesting that
the dose-response relationship may extend even to those individuals
who do not actively smoke cigarettes.

The quantification of asbestos exposure is far more difficult. One
method is to quantitatively estimate the number of asbestos fibers in
digested lung tissue. Asbestos fibers are demonstrable in the lungs of
the majority of urban dwellers (Churg and Warnock 1977); however,
the number of fibers per gram of lung tissue in urban dwellers
without known asbestos exposure is usually several orders of
magnitude below that found in occupationally exposed workers, and
the type of asbestos varies as well. Churg and Warnock (1979)
assessed this urban asbestos exposure as a risk factor for lung cancer
by comparing the number of asbestos bodies in 103 patients with
lung cancer compared with the number in control patients matched
for age, sex, smoking habits, and in some cases, occupation. No
differences in the number of asbestos bodies per gram of lung tissue
were found between the lung cancer patients and the control
population, suggesting that, at this level of exposure, asbestos did not
increase the risk of lung cancer in these patients. However, the small
number of patients in this study limits the power of the study to find
a small effect of asbestos lung burden on lung cancer risk.

Confounding by cigarette smoking is another potential source of
bias in evaluating the effects of low levels of asbestos exposure.
Several of the studies presented in Table 1 do not show excess lung
cancer risks at low levels of asbestos exposure, a pattern consistent
with the existence of a threshold. However, lung cancer rates in the
general population are determined largely by smoking habits, and if
the asbestos-exposed populations have even modestly lower lifetime
smoking rates, the effect of asbestos exposure may be masked. This
bias is of particular importance at the relatively low levels of
asbestos exposure at which the effect of cigarette smoking would be
expected to predominate. Thus, in interpreting standardized mortali-
ty ratios at or below 1, careful consideration must be given to
confounding by the smoking habits of the workforce before conclud-
ing that the levels of asbestos exposure experienced by these
populations do not result in an increased lung cancer risk. In
addition, modest differences in the number of cigarettes smoked per
day or the age of initiation of regular smoking between the exposed
population and the population from which the SMR is derived could
counterbalance a modest risk due to asbestos exposure even in
populations with similar smoking prevalences.

222


For lung cancer, the measurement of a threshold in epidemiologic
studies is further constrained by the certainty with which the
absence of an effect can be established. The precision and the
accuracy of an estimation of the expected number of deaths in a
workforce is heavily influenced by the detail with which the smoking
behaviors are determined and the accuracy with which the lung
cancer risk of a given smoking history can be estimated.

In the U.S. population during 1977,lO percent of the men who died
between the ages of 50 and 70 died of lung cancer (McKay et al.
1982). Therefore, a workforce with smoking patterns similar to the
U.S. population would be expected to have a similar mortality
experience, in the absence of any asbestos exposure. A 10 percent
increase in the risk of lung cancer in a workforce (SMR 110, RR 1.1)
due to asbestos exposure would mean that 1 percent of the deaths
among workers aged 50 to 70 would be excess lung cancers due to
asbestos, a level of risk unacceptable as the basis for an industrial
hygiene standard. However, even with carefully determined smoking
histories for a worksite, no data are currently available that would
allow the calculation of expected death rates in smokers and
nonsmokers with precision sufficient to establish that an increase of
10 percent was not simply an error in the estimates. In addition,
estimates of the smoking habits of the U.S. population are not known
with enough precision to adjust national or regional death rates for
the smoking patterns of a given workforce so that a 10 percent
difference could be considered significant. The result is a dilemma
for those who would try to measure a threshold level, or an
"acceptable" exposure level, for occupational exposure to asbestos:
an effect too small to measure in statistical terms is still too large to
be acceptable in human terms.

A final caution in the determination of a threshold for lung cancer
risk secondary to asbestos exposure, and in the use of such a
threshold to establish environmental dust standards, is the potential
differences between a threshold for lung cancer and one for
mesothelioma or other asbestos-related disease. Mesothelioma,
which is not associated with cigarette smoking, may occur following
exposure to low levels of asbestos, and a level of dust exposure
defined as a "safe" level for lung cancer risk may possibly continue
to produce an increased risk of mesothelioma.

A pragmatic approach to the problems of defining a threshold or
establishing safe levels has been to define asbestos exposure stan-
dards on the basis of the lowest level of asbestos dust exposure that
can be produced with existing technology. This approach reduces the
risk, but does not answer the question whether the exposure of a
worker is "safe."

An alternate approach has been to use the existing exposure-
response data. In the face of uncertainty about the shape of the

223


exposure-response curve for asbestos exposure and lung cancer and
whether a threshold exists, an assumption that asbestos has a linear
exposure-response relationship with lung cancer and no threshold
for effect has been suggested as both reasonable and a way to set
standards (Pete 1979; NRC 1984). By definition, in this approach
there can be no "safe" level of exposure (i.e., no threshold), only an
"acceptable" degree of risk. However, using this method, once an
"acceptable" level of lung cancer in a working population has been
defined, the level of asbestos exposure that would result in that level
of risk can be estimated. A corollary of this approach is that asbestos
is assumed to contribute to the lung cancer that develops in
populations of workers who have been exposed to asbestos regardless
of their level of exposure; by extension, the asbestos found in the
lungs of urban dwellers with no known occupational asbestos
exposure is assumed to make a small (but finite and definable)
contribution to all lung cancers. The evidence that does exist (Churg
and Warnock 1977) suggests that asbestos exposure makes no
"measurable" contribution to lung cancer in individuals without a
definable exposure, but it is impossible to establish the absence of
"any" effect.

If the issues of liability can be separated from the issue of
threshold, then the problem of reducing and eliminating asbestos-
related disease and disability could be approached with a broader
focus. The focus could be expanded beyond improving technology for
reducing exposure to asbestos to include other methods of reducing
the cancer risk associated with asbestos exposure. If the goal is to
reduce the lung cancer deaths associated with asbestos rather than
simply reducing the levels of asbestos dust in the worksite, then the
deaths due to the interaction between smoking and asbestos must be
dealt with, and the elimination of smoking will be a potent adjunct to
environmental asbestos dust control in this task, particularly for
those workers who have already received substantial asbestos
exposure. A public health "feasibility" threshold could then be
defined, not in terms of what dust levels were achievable, but rather
in terms of what lung cancer death rates were achievable. This
threshold would be the lowest cancer risk achievable, given our
current technology, and would include minimizing asbestos expo-
sure, maximizing smoking cessation, and applying techniques for
early diagnosis and treatment.

In summary, although the level of asbestos exposure that occurs in
the general population does not appear to be accompanied by an
increased risk of lung cancer, the demonstration of a clear threshold
below which there is no effect in occupationally exposed populations
is not possible.

224


TABLE `I.-Lung cancer mortality ratios with cessation of
      cigarette smoking in male smokers who smoked
      more than 20 cigarettes per day compared with
      those who never smoked regularly

Asbestos lnsularlon
  workers2



    10 4





    115


    42


    34

Never smoked
regularly

1                 I

`Data from Hammond 197!?
' Data from Hammond 19791

Cessation of Exposure

A decline in the relative risk of developing lung cancer following
cessation of cigarette smoking was demonstrated in cigarette-smok-
ing asbestos workers by Hammond and colleagues (1979). Table 7
shows the lung cancer mortality ratios in asbestos workers who are
current smokers and who have quit for varying periods of time,
compared with those workers who have never smoked regularly. A
companion set of numbers is provided of the relative risks for lung
cancer in men not exposed to asbestos, but who are current smokers
or have quit for varying periods of time, derived from the American
Cancer Society study of 1 million men and women (Hammond 1972).

Several authors have attempted to approach the question of the
risk of lung cancer following cessation of asbestos exposure by
examining the relative risks of asbestos exposure in workers
following retirement (Walker 1984; Selikoff, Hammond et al. 1980).
The data in Figure 3 and Table 8 reveal that the relative risk for
lung cancer in asbestos workers increases and then declines with the
increasing number of years from initial exposure. The workers with
the longest interval from onset of exposure are also of the greatest
age within the populations examined. Because of this link with age,
the interpretation of this decline in relative risk as indicating that
cessation of asbestos exposure results in a decline in lung cancer risk
must be made with great caution. Examination of national age-
specific mortality rates for lung cancer (Figure 4) also shows a
decline in male lung cancer death rates with increasing age. This
decline with age is an artifact of the cross-sectional nature of data

225


presented in Figure 4. When cancer death rates are examined by
birth cohort (Figure 51, no decline with age can be demonstrated. The
explanation for this seeming discordance in the data is the differ-
ences in pattern of cigarette smoking in different birth cohorts in the
U.S. population (Figure 6) (US DHHS 1982). Those birth cohorts that
currently represent the oldest age groups have lower smoking
prevalences than the birth cohorts in the younger ages (those born
between 1910 and 19301, and this decreased smoking prevalence
resulted in a decreased lung cancer mortality. The risk ratios
presented in Figure 3 are comparisons with the risk in the general
population, and therefore represent the combined effect of the
increased smoking prevalence among asbestos workers and the
increased risk due to the asbestos exposure. To the extent that the
age-related changes in smoking prevalence among older asbestos
workers presented in Table 9 represent a return toward or below the
smoking prevalence in the general population, a decline in the risk
ratio among older asbestos workers would be expected. Regardless of
the reason for the change in risk ratio among older workers (i.e.,
either differences in smoking behavior or decline in risk following
cessation of asbestos exposure), the magnitude of the decline is
modest, particularly when the rapidly increasing baseline risk of
lung cancer in the general population with increasing age used to
calculate these risk ratios is considered.

A somewhat different approach to this question was taken by
Seidman and colleagues (19791, who examined the mortality experi-
ence of a group of workers exposed to asbestos over a very limited
period of time during World War II and followed them for 35 years
after the onset of this exposure. These workers had an extremely
intense exposure to asbestos, but only very brief exposures with no
subsequent asbestos work-exposure history. If the risk of lung cancer
declines significantly following the cessation of exposure to asbestos,
then these workers would be expected to have a declining risk of
developing lung cancer with increasing duration from the onset of
asbestos exposure. Figure 7 shows the ratio of observed to expected
lung cancer deaths for the lo-year periods beginning 5, 15, and 25
years after the onset of exposure in workers who had worked less
than 9 months and those who had worked more than 9 months in
this plant. In both cases the risk is greater in workers for the lo-year
period beginning 25 years after onset of exposure than for the period
beginning 15 years after exposure. The small number of deaths
recorded in the study limits its interpretation; however, the data are
consistent with the conclusion that cessation of asbestos exposure
may not be associated with a decline in the relative risk of
developing lung cancer with increasing duration of time since last
exposure.

226


6.1

m
f 6
h
B 5
P
0 4

l-l   5.7
  I

5.0
r-l /I

I r

4.9
1

                                             3.9
i              3.4 3.5                     -
5
%   3-    - 2.6
;   2-
a"

l-I-r---.-.-II-.--..-      .1,-
    . . .
n

   "
        <to   lo-14 15-19 2&24 25-29 30-34 35-39 40-44 245

            Numbecofyearssubsequenttoonsetofe~wre

observed 0    7 29 59 105 112 65 40 69
-0.7
Expead     ----~--- 2.7 6.5 17.0 21.0 16.4 11.5 6.1 17.0

FIGURE 3.-Ratios of observed to expected deaths from
      lung cancer among 17,806 asbestos insulation
      workers observed prospectively, 1967 and 1976,
      in byear periods subsequent to beginning

employment in this trade

NOTE: The decline in ratios after the 30. to Syear period may be the result of B "survivor effect." because
deaths associated with cigarette smokmg 1e.g. myocardial infarction. lung cancer) tend to selectively change the
composition of the surviwng cohort in relatmn to smoking status wth time.
SOURCE: Selikoff. Hammond et al. (1980).

A similar result was reported by Blot and colleagues (1980) in a
case-control study of male lung cancer patients. They found a small
excess risk of developing lung cancer in workers who had been
employed in shipyards for only a few years during World War II, and
the relative risk in these workers was similar to that for workers
who had worked regularly in the shipyards.

In summary, the data suggest that elimination of further asbestos
exposure may prevent the further increase in relative risk that
would accompany an increase in cumulative exposure. However, the
relative risk of developing lung cancer persists even after prolonged
avoidance of additional asbestos exposure. In contrast, the cessation
of cigarette smoking appears to reduce the risk of developing lung
cancer in asbestos insulation workers compared with those workers
who continue to smoke, and the time course of this reduction in risk

227


TABLE 8.-Changes in the ratio of observed to expected
      deaths with time since first employment, four
       cohort studies

Years since             Quebec               New York-     Asbestos
initial      North Amerum   miners and    Factory    New Jersey     cement
exposure      insulators      millers 2      workers3     insulators '     workers '

< 10

! 1-15

16-20

21-25

26-30

31-35

36-40

4145

46250

Total number
of deaths

2.55    171

3.40   1291

3.48   159)

5.00  (1051

6.08  (1121

5.68   (65)

4.93   (40)

3.89   (691

(466,

                   0.00   (0)     0.77   (1)

                             1.25   (31

000   CO!     2.38   141     8.67  (26)     1.54   (6)

                             2.33   (71

1.94   (71     3.73  cx3)               3.33   (5)

                   6.63  (67)     3.08   (4)

4.19  (16~     1.37  6)

1.6i   151

128J        (33)        (93)        (26)

I Data from Sehkoff, Hammond et al. (19801.
`Data from Nicholson et al. (1979).
3 Data from Nicholson et al. 119791.
' Data from Selikoff et al (19791
a Data from Weill et al. 119791
NOTE Number of deaths gven III parentheses
SOURCE Walker c 19841

is similar to that found among smokers in the general population
who stop smoking.

Mechanisms of Carcinogenesis in Cigarette-Smoking
Asbestos Workers

An increased risk of developing lung cancer has been observed
with all commercially used types of asbestos. Most studies indicate
that crocidolite exposure may produce a higher human lung cancer
risk than chrysotile (Weill et al. 1979; Enterline and Henderson
19731, but some studies have shown the opposite (McDonald et al.
1983a, b; Dement et al. 1982). All of the four major histologic types of
bronchogenic carcinoma develop in asbestos workers who smoke
(Churg 1985; Auerbach et al. 1984; Whitwell et al. 1974). Although
an increased risk of lung cancer with exposure to asbestos in
nonsmokers has been demonstrated in a number of epidemiologic
studies (Hammond et al. 1979; McDonald et al. 19801, it remains
unclear whether the asbestos fiber by itself acts as a complete
carcinogen for lung cancer in the respiratory tract of man. This is in
contrast to the role of asbestos as a carcinogen in mesothelioma,

228


FIGURE 4.-Age-specific mortality rates for cancer of the
      bronchus, trachea, and lung, white men and
       women, United States
SOURCE. McKa> of al / 19821

229


, ~~

30-

I
4&

1         1         1        1
5s       60-       70-       eo-

   Age

1885


1990


1875

FIGURE L-Age-specific mortality rates for cancer of the
      bronchus and lung, by birth cohort and age at
       death, men, United States, 1950-1975
SOURCE Data derived from McKay et al. 11982).

230


  70 -







  60----







  50 -







  40 -

E
0
a"


  30 -







  20 -







  10







   o-

l-1950

-1960

1900   1910   1920    1930   1940    1950 1960    1970   1980


                     Year

FIGURE 6.-Changes in the prevalence of cigarette
      smoking among successive birth cohorts of
       men, 1900-1978

SOTE Calculated from the resulLs of more than 13.ooO lnterwews conduct& dunng the last two quarters of
1978, prowded by the Natmnal Center for Health Statlstlcs. D~vwon of Health Interview Statlstia.
SOURCE US DHHS r19821.

where asbestos exposure alone is clearly able to produce the tumor
and where cigarette smoking does not alter the mesothelioma risk.
Laboratory investigations have been undertaken to evaluate the
mechanisms through which asbestos interacts with the combustion
products of cigarettes to induce neoplasms. In this regard, the
carcinogenic properties of polycyclic aromatic hydrocarbons (PAH),
documented chemical carcinogens in cigarette smoke, have been

231


TABLE 9.-Prevalence of smoking among asbestos
      insulation workers whose smoking history was
       known

Age

Current          Former
smokers          smokers

NWW
smoked
regularly

PW
and
tiger

25-29             64.8            19.3            13.0          2.5

30-34             61.0            19.3            13.5          6

35-39             60.9            22.2            11.6          4.9

40-44             61.3            25.0             9.2          45

4S-u             55.8            26.8             9.8          56

5M4             53.7            32.2             9.1          5.0

55-59             50.1            34.1             9.8          6.0

6&64             45.4            35.1            10.4          91

65-69             42.3            33.7            12.4         li.6

7&74             30.7            34 3            17.5          17 5

X-79             51.5            34.3             7.1          71

B&84             37.1            33 3            11.1          18.5

2%              30.0            35.0            25          10.0

Source Hammond et al t 19791

evaluated in combination with asbestos both in tissue cultures and in
grafts of respiratory tract epithelium (reviewed in Craighead and
Mossman 1982; Mossman, Light et al. 1983). This section summarizes
the results of these experimental studies.

Animal Studies of the Carcinogenic Interactions Between
Cigarette Smoke and Asbestos

When animals are administered asbestos in inhalation chambers
or by intratracheal instillation, differences among species and
strains appear to influence the occurrence of lesions. For example,
only benign lesions (papillomas and adenomas) are found in ham-
sters, guinea pigs, and rabbits after prolonged inhalation of asbestos
(Botham and Holt 1972a, b; Gardner 1942; Reeves et al. 19741,
whereas cats (Vorwald et al. 1951) and nonhuman primates (Wagner
1963; Webster 1970) develop fibrosis of the lung but not tumors.
Small numbers of neoplasms (squamous cell carcinoma., adenocarci-
noma, small and large cell carcinoma) have been reported in rats
(Davis et al. 1978; Reeves 1976; Reeves et al. 1974; Wagner et al.
1974), but benign neoplasms and fibrosarcomas (tumors rare in the
human lung) predominate. Mice also appear to develop both benign
and malignant tumors after inhalation of asbestos (Bozelka et al.
1983; Gardner 1942). Bozelka and colleagues (1983) found a large

232


Starting
p01llt
(Years)



    5


   15


   25









    5


   15


   25

Lung cancer

Worked c 9 months

Worked > 9 months

0    1    2    3    4    5    6    7    6    9   10   11   12

               Rabo of observed lo expected

FIGURE 7.-Observed compared with expected weighted
      average probabilities of lung cancer death in
      lo-year periods, starting at 5-, 15-, and 25-year
      points after beginning of work in an amosite
      asbestos factory, 1941-1945, for men who
        worked less than or more than 9 months
NOTE: Computed by assigmng wwghts of 55 and 45 percent to the prababllitles given in Sadman and colleagues
t19791 for men aged 40 to 49 and 60 to 59, respecuvely. at the start of the 1Gyear pen&
SOURCE- Sadman et al !19791.

number of lesions of questionable malignancy in the lungs of Balb/c
mice 12 to 18 months after a 75day exposure to chrysotile asbestos.

Unfortunately, it is difficult to evaluate many of these animal
studies critically because satisfactory controls were not employed
and data on exposure regimens and concentrations of asbestos are
often not available. In addition, adequate pathologic documentation
of the lesions is often lacking. Benign adenomas could occur
spontaneously in many lesser species (Mitruka et al. 19761, and
luxuriant squamous metaplasia and bronchiolization of the respira-
tory mucosa may be misinterpreted as malignant lesions. These last
epithelial changes may occur as a response to injury induced by
asbestos (Davis et al. 1978; Mossman et al. 1980; Reeves et al. 1974;
Wagner 1963; Woodworth et al. 1983a, b).

233

157-964 0 - 86 - 9


Several investigators have administered chrysotile to rats and
hamsters in combination with either cigarette smoke or ben-
zo[a]pyrene (BaP), a major polycyclic aromatic hydrocarbon (PAH) in
cigarette smoke (Table 101 (Miller et al. 1965; Pylev and Shabad
1973; Shabad et al. 1974; Smith et al. 1968; Wehner et al. 1975). A
striking increase in neoplasms (both benign and malignant) of the
respiratory tract was observed. In contrast, a synergistic effect on
tumor development was not apparent in rats exposed to asbestos and
cigarette smoke by inhalation (Shabad et al. 1974; Wehner et al.
1975); however, the majority of the animals in these studies died
prematurely of pulmonary fibrosis.

The effects of asbestos on the carcinogenicity of PAH in the
respiratory tract have been evaluated using grafts of tracheal tissue
implanted into syngeneic animals. Two model systems have been
developed. In the first, the tracheas of rats are excised and formed
into tubular sacs by ligatures at the ends and then transplanted
subcutaneously (Topping and Nettesheim 1980; Topping et al. 1980).
When relatively large amounts of chrysotile are introduced into the
lumina of these grafts, inflammatory changes appear and fibrosarco-
mas develop in a substantial proportion of animals (Topping et al.
1980). On the other hand, epithelial tumors (carcinomas) appear
when low concentrations of the PAH dimethylbenz[a]anthracene are
introduced into the tracheal grafts before chrysotile (Topping and
Nettesheim 1980). The amounts of PAH used in these experiments
were insufficient to cause tumors; therefore, the asbestos acted as a
promoting agent.

In the second model system, organ cultures of hamster trachea are
exposed to crocidolite asbestos and implanted into syngeneic recipi-
ents after various periods of incubation in vitro (Craighead and
Mossman 1979; Mossman and Craighead 1979, 1981, 1982). Neo-
plasms failed to develop in these experiments. However, tumors, the
majority of which were carcinomas, were found when the PAH 3-
methylcholanthrene (3MC) was coated on the surface of the crocido-
lite fibers and precipitated onto the epithelial surfaces of the
tracheal organ cultures prior to transplantation. This tissue served
as the nidus for the development of squamous cell carcinomas in the
hamsters implanted with the cultures. In these experiments, asbes-
tos appeared to be a carrier of PAH, because 3MC also produced
tumors when absorbed to nonfibrous particulates such as kaolin,
hematite, and carbon (Mossman and Craighead 1979,1982).

Concepts of Carcinogenesis

The concepts of initiation and promotion were developed to
explain the complex, multistep process of chemical carcinogenesis.
"Initiation" is defined as the irreversible DNA damage of a cell
induced by a carcinogenic agent. In contrast, tumor "promotion" is a

234


TABLE lO.-Tumors occurring in rodents after exposure to asbestos in combination with components
      of cigarette smoke

Number of tumors/Number of animals

Chrysotile

Agent alone

Combination

Tumor types

Animal

Reference

Inhalation

5151

12151 (smoke)

9/51 (+smoke)

Adenoma, papilloma. carcinoma

Rat

Wehner et al.
  (1975)

O/46            ND'

O/16 (+smoke)
O/21 (+BaPY

ND

Rat

Shabad et al.
  (1974)

Intratracheal instillation

    ND

13137 (BaP)

18135 ( + BaP)

Adenoma, papilloma, carcinoma

Hamster

Smith et al
(1966)

o/17

lo/34 (BaP)

24/31 (+BaP)

Adenoma. papilloma. carcinoma

Hamster

Smith et al
(1966)

o/49




0110

O/19 (BaP)



4110 (BaP)

6111 (+Bap mixed)
6/21 (+BaP adsorbed)


  15/10" c+BaPj

  Adenoma, carcinoma,
reticulosarcoma, mesothelioma

  Papilloma, carcinoma

Bat




Hamster

Pylev and Shabad
   (19731


Miller et al.
   (1965)

' ND = no details provided
z BaP = benzcjalpyrene.
' Anunals developed multiple tumors.


sequential process whereby a second, but unrelated, generally
noncarcinogenic substance acts to enhance the effect of an initiator.
Initiated cells undergo proliferative changes and differentiation that
ultimately result in transformation to a malignant lesion. Much of
the information that has accumulated on classical tumor promoters
and their mechanisms of action was derived from studies with mice
in which the animal's skin was painted with PAH, followed by
repeated applications of phorbol esters (or related compounds)
(reviewed in Slaga et al. 1982). Nonetheless, the concepts of initiation
and promotion appear broadly relevant to carcinogenesis in the
mammary gland, liver, colon, urinary bladder, brain, and lung (Marx
1978). In this regard, a wide variety of chemical, physical, and
infectious agents interact with tissues to induce a constellation of
inflammatory and proliferative changes ultimately resulting in
malignancy.

It is doubtful that the action of asbestos in increasing lung cancer
risk is as a tumor initiator (reviewed in Craighead and Mossman
1982; Mossman and Craighead 1981). Few epithelial tumors develop
in experimental animals when PAH are not used in conjunction with
asbestos. Moreover, chrysotile and crocidolite do not seem to damage
the DNA of hamster or human tracheobronchial epithelial cells
(Fornace 1982; Mossman, Eastman et al. 1983). In most (but not all)
studies using cell culture systems, asbestos is neither mutagenic nor
carcinogenic (Chamberlain and Tarmy 1977; Daniel 1983; Kaplan et
al. 1980; Reiss et al. 19821, but the malignant transformation of
hamster embryo fibroblastic cells by asbestos, glass fibers, and silica
particles has been reported recently (Hesterberg and Barrett 1984;
Oshimura et al. 19841. Under these circumstances, asbestos may not
act like a classical mutagen, but appears to cause alterations in
chromosomal structure (Barrett et al. 19831, perhaps consequent to
its cytotoxic effects.

In contrast, asbestos exhibits many of the properties of classical
tumor promoters when introduced into grafts of tracheal tissue
(Topping and Nettesheim 1980) and monolayer cultures of hamster
and human tracheobronchial tissues (reviewed in Craighead and
Mossman 1982; Mossman and Craighead 1981; Mossman, Light et al.
1983). Like the phorbol esters, asbestos appears to induce perturba-
tions of the plasma membranes of cells, such as the stimulation of
membrane-associated enzymes (Mossman et al. 1979) and the
generation of oxygen free radicals (Mossman and Landesman 1983).
In addition, both asbestos and fibrous glass induce the biosynthesis of
polyamines, important biochemical markers of cell division and
proliferative changes in the tracheobronchial mucociliary epitheli-
urn (Landesman and Mossman 1982; Marsh and Mossman 1984).
This is accompanied by the development of squamous metaplasia, a
putative premalignant change. These alterations in cell function and

236


structure are not observed in tissues exposed to nonfibrous mineral
analogs of asbestos and glass, an observation indicating that the
fibrous geometry of the material is important (Woodworth et al.
1983b).

Cigarette smoke contains ciliostatic and toxic chemicals that
impair mucociliary transport and the function of phagocytic cells
(Warr and Martin 1978). Thus, intrapulmonary deposit,ion and
clearance of asbestos might be affected, resulting in increased
retention of asbestos in the lungs. In addition, the development of
squamous metaplasia consequent to exposure to both PAH and
asbestos (Mossman et al. 1984) might contribute to the retention in
the respiratory tract of asbestos and the constituents of cigarette
smoke.

Studies using artificial membranes and cells in culture suggest
other possible mechanisms of synergism between PAH and asbestos.
PAH are not carcinogenic in their natural state and must be
metabolized by a mixed-function, microsomal enzyme system (aryl
hydrocarbon hydroxylase, AHH) to degradative products and electro-
philic forms interacting with DNA (Freudenthal and Jones 1976). In
this regard, the association (adduct formation) of modified metabo-
lites of PAH with the DNA of "target" cells is thought to be a critical
event in initiation of those cells. A number of studies suggest that
the addition of asbestos and PAH to tracheobronchial epithelial cells
(Mossman and Craighead 1982), microsomal preparations from lungs
(Kandaswami and O'Brien 1981), and phagocytes (McLemore et al.
1979) affects the normal metabolism of PAH as measured by an
increase (or decrease) in activity of AHH enzymes. Unfortunately,
these results are inconsistent, possibly a reflection of the different
experimental systems evaluated. Accordingly, this important area of
carcinogenesis needs further exploration.

PAH are ubiquitous in the environment and are associated with
airborne particulates (Natusch et al. 1974). Thus, the ability of
asbestos and other particles to act as "condensation nuclei" for
chemical carcinogens has been explored using tracheobronchial
epithelial cells (Mossman, Eastman et al. 1983: Eastman et al. 1983)
and artificial or isolated cell membranes (Lakowicz and Bevan 1979;
Lakowicz et al. 1978). Transfer of PAH to cell membranes by
asbestos appears to occur more rapidly than with use of nonfibrous
particulates (Lakowicz and Bevan 1979; Lakowicz et al. 1978).
Moreover, the normal uptake of BaP and the formation of BaP-DNA
adducts by tracheal epithelial cells are increased when BaP is
adsorbed to chrysotile and crocidolite asbestos (Mossman, Eastman
et al. 1983; Eastman et al. 1983).

The pulmonary alveolar macrophage (PAM) is a key cell in the
response of the host to asbestos. PAMs accumulate at sites of
deposition of asbestos in the tracheobronchial tree (Brody et al.

237


19811, a process associated with activation and release of lysosomal
enzymes (Davies et al. 1974) and the generation of oxygen free
radicals (McCord and Wong 1979). In addition, these cells possess the
enzymatic capability to convert PAH to active metabolites (Autrup
et al. 1978) and may facilitate the transfer of hydrocarbons to
tracheobronchial epithelial cells and other cell types (Shatos and
Mossman 1983). Thus, either damage to or activation of macrophages
by asbestos and the components of cigarette smoke could influence
the process of carcinogenesis.

Conclusions

Several mechanisms by which cigarette smoke and asbestos may
interact to increase carcinogenic risk are possible, but they remain
unproved in man. First, asbestos fibers could serve as carriers of the
carcinogens of cigarette smoke into the cell. Physical transport of
this type has been demonstrated experimentally, and there is
evidence to suggest that asbestos transfers PAH to cell membranes
with unusual efficiency in comparison with other particulates. While
this mechanism is an intriguing possibility, it presupposes the
interaction of smoke constituents with aerosols of asbestos fibers in
the atmosphere. Events of this nature remain hypothetical and
unproved. A second mechanism is based on experimental evidence
accumulated in both animals and cell culture systems. In this
schema, asbestos serves as a promoter in the respiratory epithelium
to alter the properties of the epithelial cells and to enhance
neoplastic transformation in cells initiated by the combustion
products of cigarettes. Biological evidence supporting this mecha-
nism of carcinogenesis is compelling in experimental models of
carcinogenesis, but not easily tested in man.

The possible role of macrophages in the metabolism of PAH
adsorbed to asbestos is an intriguing consideration. These cells are
biologically activated in the smoker and in the lungs of those exposed
to asbestos. They frequently accumulate in large numbers in the
airspaces of individuals exposed to these and other pollutants. One
can only speculate on whether or not the alveolar macrophage
contributes to the metabolism of chemical carcinogens under these
circumstances.

Although obvious information gaps exist, consideration of the
experimental results described here and the contemporary concepts
of neoplastic transformation suggest several mechanisms of interac-
tion between components of cigarette smoke and asbestos. On the
one hand, asbestos appears to resemble a classical tumor promoter
after initiation of tracheobronchial epithelial cells by the carcinogen-
ic chemicals found in cigarette smoke. Alternatively, asbestos
appears to act as a vehicle for the transfer of PAH across cell
membranes and affects the metabolism of these carcinogens, factors

238


favoring the process of initiation. Finally, asbestos and the toxic
constituents of cigarette smoke injure cells, a situation potentially
encouraging the retention of these inhalants in the respiratory tract.

Chronic Lung Disease

Cigarette smoke (US DHHS 1984) and asbestos exposure (Selikoff
and Lee 1978) are well-established causes of chronic lung injury. As
in the preceding discussion of lung cancer, the enormous body of
literature that established the pathogenicity of each of these agents
is not presented; rather, this section focuses on the effects of
combined exposure. In contrast to their effect on the risk of
developing lung cancer, asbestos and cigarette smoke produce
different patterns of injury in the lung. The pattern of lung injury
associated with cigarette smoking is characterized by inflammation,
excess mucus production, narrowing of the airway lumen, and
emphysema (US DHHS 1984). The result is a reduction in maximal
expiratory flow rates and increased static lung volumes. The pattern
of lung injury associated with asbestos is fibrosis of the small
airways extending into the alveolar structures with obliteration of
alveoli, leading to a reticular nodular pattern of interstitial fibrosis
on chest roentgenogram and decreased lung volumes, with relative
preservation of the forced expiratory volume in 1 second (FEV,) as a
percent of the forced vital capacity (FVC) (Selikoff and Lee 1978).

In spite of these relatively distinct patterns of lung injury,
interpretation of the pattern of injury in combined exposure is
difficult. Both agents may act separately, but simultaneously, to
injure the lung. The injury in an individual worker is the combina-
tion of the injuries due to cigarette smoke, asbestos and other
environmental agents, and all other injurious processes that have
occurred during that individual's lifetime. The presence of a lung
injury secondary to one agent or process does not prevent the lung
from being injured by a second agent. In evaluating impairment in
an asbestos-exposed smoker, it may be difficult to apportion the
impairment between the two agents because both cigarette smoking
and asbestos exposure may alter a given lung function test in the
same direction (e.g., both of them reduce the diffusing capacity
(DLCO)), or they may change a test in opposite directions (e.g., an
increase in total lung capacity (TLC) due to smoking may mask a
decline in TLC due to asbestos). When a given physiologic test is
influenced in opposite directions by cigarette smoking and asbestos,
the degree of injury to the lung may be underestimated by the
change in that test. For example, the relative preservation of TLC in
cigarette-smoking asbestos workers does not represent a relative
protection of the lung in combined exposure, but rather reflects the
emphysematous destruction of alveolar walls secondary to cigarette

239


smoking (.which increases TLC) being combined with the asbestos-
related fibrosis and obliteration of other alveolar units (which
reduces TLC).

Interstitial fibrosis of the lung is a well-described and well-
established sequel of heavy asbestos exposure. In an individual, the
fibrosis is attributed to asbestos when a pattern of lung injury on
chest roentgenograph or lung biopsy consistent with that found in
asbestos-exposed populations is found in conjunction with a history
of significant asbestos exposure or with levels of asbestos in lung
tissue consistent with significant asbestos exposure. Fibrosis due to
other causes such as exposure to coal dust, silica, or infection needs
to be considered in evaluating individual patients, and both diagno-
sis and attribution to a specific etiologic agent may be difficult in the
very early stages of the fibrotic process. However, by the time the
process has progressed to the degree that it causes significant
disability or death, the diagnosis is usually readily evident and the
substantial asbestos exposure generally necessary to cause this
degree of fibrosis is also easily identifiable.

Chronic Lung Disease Death Rates

Cigarette-induced chronic lung injury does not produce the
extensive fibrosis commonly found in individuals dying of asbestos-
induced interstitial fibrosis, and therefore does not interfere in the
diagnosis, or attribution to asbestos, of the severe fibrotic lung
disease in these individuals. However, cigarette smoking can cause
significant lung destruction and disability, and therefore it may
contribute to the mortality and degree of disability in individuals
with asbestos-induced interstitial fibrosis, independent of any effect
of cigarette smoking on the degree or extent of fibrosis. In addition,
because death and disability occur only after extensive lung injury,
the independent (i.e., additive) lung injuries due to smoking and
asbestos might sum to produce a level of disability that could exert a
synergistic effect on death rates.

Frank (1979) presented data on the death rates in smoking and
nonsmoking asbestos insulation workers (Table 11). The population
was drawn from the 17,800 asbestos insulation workers studied by
Hammond and colleagues (1979) and included those workers with
more than 20 years of exposure whose smoking habits were known.
The age-standardized death rates from chronic lung disease (includ-
ing asbestosis) were increased by either cigarette smoking or
asbestos exposure, and the rate in cigarette-smoking asbestos
workers was well above the sum of the rates for non-asbestos-exposed-
smokers and nonsmoking asbestos workers, This "synergism" was-
also present when only asbestosis deaths were considered, with them
death rate almost three times higher in cigarette-smoking asbestos
workers than in nonsmoking asbestos workers. This study revealed a


greater than additive effect for cigarette smoking and asbestos
exposure on death rates from chronic lung disease and asbestosis.
This may reflect a "synergistic" effect on death rates of the
"addition" of the two separate injuries, rather than an effect of
cigarette smoking on the degree of fibrosis produced by a given dose
of asbestos. In addition, these data reflect the fact that a death
certification of asbestosis does not rule out the possibility of a second
disease process existing in the lungs of that individual.

Pulmonary Function Testing

The most frequently used measures of lung function are lung
volumes and measures of maximal expiratory airflow, either as the
volume expired during a given time (e.g., forced expiratory volume in
1 second, FEV,) or as the rate of expiratory airflow at a given lung
volume or between two lung volumes (e.g., forced expiratory flow
from 25 to 75 percent of the forced vital capacity, FEFzMw).
Classically, diseases are divided by their pattern of abnormality on
lung function testing into obstructive (processes that predominately
limit expiratory airflow) and restrictive (processes that predominate-
ly decrease lung volumes and specifically decrease the total lung
capacity). Both of these processes may occur in a single individual,
resulting in a mixed pattern (both reduced lung volumes and
reduction in volume-adjusted expiratory flow rates).

Obstructive lung disease is marked by reductions in the rate of
expiratory airflow; normal or, more typically, increased TLC; and
substantial increases in residual volume (RV) and functional residu-
al capacity (FRC) (Figure 8). Restrictive diseases are marked by a
reduction in TLC. The flow rates in restrictive disease are usually
normal or even increased once an adjustment for the decreased lung
volume has been made. FEV, is obviously limited by the total
volume that can be expired, as well as by the amount of obstruction
to expiratory airflow. For this reason, FEV, is commonly divided by
the forced vital capacity (FVC), and expressed as the percentage of
the FVC that can be expired in 1 second (FEV,/FVC%). This
adjustment of FEV, for reductions in FVC aids in separating the
decline in FEV, that is due to a restrictive process (i.e., reduced TLC)
from that which represents increased resistance to, and decreased
driving pressure for, expiratory airflow.
The pattern of lung function change in cigarette smokers has been

well described (US DHHS 1984), and consists of a reduced FEV, and
FEV,/FVC%, an increased RV and FRC, and an increased TLC
(particularly in those individuals with emphysema). In addition,
FEFwwG, DLCO, and flows at specific lung volumes are also usually
reduced.

The pattern of change with the development of interstitial fibrosis
due to asbestos is also clear. Figure 9 shows the changes in lung

241


TABLE Il.-Age-standardized death rates for combinations of cigarette smoking, no smoking, asbestos
     exposure, and no asbestos exposure; selected causes of death

Gl-CUp

All
CfdB?S

All
cancer

Noninfectious
pulmonary diseases
(total includes
  aS!J.?ShiS)

Asbestosis

All
other
causes

Death rates per lOO,C%U man-years
I. No adeatos work and no smoking                980.9           208.2              28.6               -'           743.9
II. No asbestos work, but smoking                 1580.7           353.1             103.8               -1          1123.8
III. Asbestos work and no smoking                 1430.9           563.9              77.1               77.1           789.9
IV. Asbestas work and smoking                  2659.0           1317.0             286.5              225.5          1005.5

Mortality ratice
No asbestos work and no smoking (I + I)              1.00            1.00             1.00                            1.00
No asbestos work, but smoking (II + I)               1.61            1.70              3.60                            1.51
Asbestca work and no smoking (III + I)               1.46            2.71              2.68                            1.06
Asbestos work and smoking (IV i I)                 2.71            6.33              9.95                            1.42

Excess in death rates
V. Smoking only (II-I)                        599.8           144.9              75.0               -1           379.9
VI. Asbestos work only (111-I)                    450.0           355.7              48.3               77.1            46.0
VII. Synergism (IV-I-V-W                     626.3           608.2             i34.4              148.4          -114.3

Percent excess in death rates
Smoking only (1cOV i I)                       61             70              260                             51
Asbestos work only (lOWI i I)                   46            171              -68                              6
Synergism WIOVII i I)                        64            292              467                            -15

NOTFK Rate per 100,ooO man-years standardized for age on the distribution of the man-yearn of all the asbestos msulation workers 2 20 years after onset of asbestos work. Rates for the asbestos
work-expoeure groups are based on cause of death coded according to the best available evidence.
' Death rates not available for the no asbestos work-exposure group.
SOURCE: Frank (1979).


Total lung

FlJ~tlO~al

esldual capacity

volume

COLD

Total lung

capacity

Functional

rasldual capackty

Resrdual

volume

I
   Normal

Total lung

Aestncttve
lung dfsease

FIGURE &-Lung volumes in normal individuals and in
     patients with chronic obstructive lung disease
      and restrictive lung disease

volumes and Figure 10 shows the changes in the forced expiratory
flow rates for the Quebec asbestos workers at several levels of
increasing cumulative exposure to asbestos dust (Becklake et al.
1972). The lung function tests were performed on 1,027 men aged 21
to 65 who represented an age-stratified random sample of the 6,180
men employed in the Quebec asbestos mines and mills on October 31,
1966. An additional 184 men between the ages of 61 and 65 were also
studied to increase the number of workers in the highest exposure
categories. The data in the figures represent the averages of the test
values for smokers and nonsmokers after they had been standard-
ized for age, height, and weight. Smokers were defined as those who
had ever smoked at least one cigarette per day for 1 year; therefore,
this category includes former smokers.

The pattern in nonsmoking asbestos workers is that of restriction;
there is a steadily declining TLC with increasing dust exposure.

243


t&l:                             *
                           
2 R       1            d
     -            : ,.,:,, :. .::: No
"6  ::     1               :.:.:
     -                      ..:.:.:.:,:.:
  ,-             -6
                              :.,. 1.
                  c
6  2    1               : :.:.: :. :j,..: 1. ..:
               -+

  0
  -  z    I               ,. ,. 0
  "                                          "

FIGURE 9.-Standardized mean values for subdivisions of
      lung volume (TLC[SS], IC, FRC, and RV) in
       nonsmokers and smokers, divided by dust
        index

FEV, also declines with increasing exposure, but this decline can be
accounted for by the decline in FVC, as FEV,/FVC% does not
decline with increasing exposure in nonsmokers and is above 80
percent in all but the lowest exposure category. FEFzs-75% is also
preserved in all but the two highest exposure categories. The FEFs

244


FIGURE lO.-Standardized mean values for flow rates
       (MMF, FEVTA, FEV,, and FVC) in
       nonsmokers and smokers, divided by dust
         index

NOTE in,= number of mdividuals m each subgroup
SOURCE Becklake et al 11972~

w measurement would also be expected to decline with a fall in
FVC, independent of any change in the degree of obstruction to
airflow. Thus, in this group of nonsmoking asbestos workers, the
pattern of asbestos-induced lung disease is a reduction in lung
volumes with preservation of FEV,/FVC%.


The changes in lung function in the smoking asbestos workers in
this study can be contrasted with those of nonsmoking asbestos
workers with comparable cumulative exposure histories (Figures 9
and 10). The static lung volumes (Figure 9) are larger for smokers
than nonsmokers at each level of cumulative asbestos exposure.
FEFz+x~, and FEV, are lower, as is FEV,/FEV%. There is a
progressive decline in FEV,/FVC% with increasing cumulative
asbestos exposure in the smokers but not in the nonsmokers. This
decline is probably attributable to the increase in cumulative
cigarette smoking exposure (and related injury) that occurs with
increasing cumulative asbestos exposure (Rossiter and Weill 19741,
because of the correlation between these cumulative measures. The
picture that evolves from this study of the effect of combined
cigarette smoke and asbestos exposure is one of an obstructive
process superimposed upon a restrictive process, In addition, in the
population of workers with relatively heavy asbestos exposure, TLC
is reduced in both smokers and nonsmokers, suggesting that the
restrictive pulmonary process exerts a greater effect than those
changes that tend to increase TLC (e.g., emphysema). The relative
preservation of TLC that occurs in cigarette-smoking asbestos
workers in comparison with nonsmoking workers should not be
interpreted as a protective effect of smoking, because it almost
certainly represents more extensive lung damage (i.e., the combina-
tion of emphysematous and fibrotic processes) in the lungs of the
cigarette smokers. It is also important to note that the data from this
study show a relatively clear dose-response relationship between
cumulative asbestos exposure and degree of restrictive impairment.

The pattern of lung function response in smoking and nonsmoking
workers found in this study is consistent with the premise that
asbestos exposure causes a relatively pure restrictive lung disease
and cigarette smoking causes a relatively pure obstructive process.
In combined exposure, the lung functional changes represent the
combination of the effects of these two independent processes. A
number of other studies have examined the lung function in smoking
and nonsmoking asbestos workers, and the data from these studies
can be used to explore this relationship further.

A general morbidity study was conducted of civilian naval
dockyard workers in Great Britain, and lung function tests were
performed on 612 male registered asbestos workers (Harries and
Lumley 1977). The measurements were standardized to a height of
1.7 meters and to a constant age within each of five age ranges.
Smoking habits were classified as smoker, nonsmoker, or ex-smoker.
TLC showed no relationship to age, smoking status, or duration of
asbestos exposure. There was a tendency for smokers to have a lower
FEV, than nonsmokers, and the difference increased with age. FEV,
and duration of asbestos exposure were related only for those aged

246


50 to 59. The differences in FVC between smokers and nonsmokers
were less than the differences in FEV1, demonstrating a relative
preservation of FEV,/FVC in nonsmokers, and a relationship
between duration of exposure and FVC was again present only in the
50- to 59-year-old age group. The absence of a relationship between
TLC and duration of exposure may be due to the somewhat lower
intensity of asbestos exposure in this population in comparison with
the Quebec miners.

In a companion study of the same naval dockyards, Rossiter and
Harries (1979) examined the lung function in 1,200 men aged 50 to
59. The sample included all men in the register of asbestos workers,
1 in 3 of those currently in occupations where intermittent exposure
to asbestos might occur, and 1 in 30 of the remainder. Lung function
measurements were standardized to age 55 and a height of 1.7
meters. Smoking was characterized as nonsmoker, ex-smoker, or
current smoker, and lung function was analyzed by duration of
exposure to asbestos. FEV, was lower in the smokers than in the
nonsmokers, and the workers in the registered asbestos-exposure
group had lower values than workers in other occupational groups.
This was particularly true of the group of asbestos laggers who had
been employed prior to 1957. The differences in FVC among the
different smoking habits were less than the differences for FEV,.
The FEV,/FVC ratio was markedly influenced by smoking. Even
among those workers employed before 1957, the FEV,/FVC ratio
was preserved in nonsmokers but declined among cigarette smokers.

Weill and colleagues (1975) adopted a somewhat different ap-
proach by developing predictive equations specific for the smoking
status of the worker, as well as age and height, for the individual
function tests. FEF2675~ was lower and declined more rapidly in
smokers than in nonsmokers (Figure 11) in the population used to
develop the predictive equations. The researchers applied these
smoking-specific regression equations to 859 workers who were
employed in two asbestos manufacturing plants in New Orleans on
November 3, 1969. Dust exposure measurements were derived from
midget impinger samples taken between 1952 and 1969 and from
estimates of exposures derived from interviews with employees who
had worked prior to this time period. Figures 12 and 13 reveal a
decline in TLC with increasing cumulative asbestos exposure; as
would be expected, this decline is accompanied by declines in the
vital capacity, FEVI, and FEFzx,~. However, there is no decline in
FEV,/FVC with increasing duration of exposure. The decline in TLC
and vital capacity at the lower exposure levels occurred entirely in
the group with x-ray changes, but for the two highest exposure
categories, the decline in TLC and vital capacity occurred even in the
group with no roentgenographic changes. Again, this study suggests
that the effect of asbestos dust exposure in a manufacturing plant is

247


Nonsmokers
(n=57)

35                45                55

Age, years

FIGURE Il.-Relationship between FEVB-75% and age for
      the smokers, ex-smokers, and nonsmokers in
      the standard group (height taken as 175 cm
       [5 feet 9 inches])
SOURCE Weill et al G 19751

largely that of a restrictive process producing a decline in TLC, with
the decline in FEV, and maximal midexpiratory flow between 25
and 75 percent of FVC (MMF 25-75~) being a reflection of the decline in
lung volumes rather than an indication of the presence of airflow
obstruction.

Several analyses have focused on the pattern of pulmonary
function response rather than on isolated test values (Fornier-
Massey and Becklake 1975, Becklake et al. 1976; Muldoon and
Turner-Warwick 1972; Murphy et al. 1972, 1978). These authors
were attempting to determine whether asbestos exposure results in
chronic obstructive lung disease, either in the absence of cigarette
smoking or in excess of the level to be expected solely from smoking.
The stratified sample of 1,027 Quebec asbestos miners and millers
described earlier in this section was also analyzed by the pattern of
pulmonary function response (Fornier-Massey and Becklake 1975;

248


Total lung capaccty

Percent standardlzed

All sublects

No x-ray

Any x-ray
change

V~tal capacity                                   .     .   . . .

                100

Percent standardmd

All subjects

No x-ray        Any x-ray
change        change

Functmal residual CapaCitY

                100

Percent standardnzed

All subjects

No x-ray
change

Any x-ray
change

FIGURE 12.-Relationship between lung volumes and dust
         exposure
SOURCE We111 et al t 19751

Becklake et al. 1976). These workers were categorized as having a
normal, undifferentiated, obstructive, or restrictive pulmonary func-
tion picture on the basis of a combined score of the percentage
deviations from the predicted value of five pulmonary function tests


FEV,

Percent standardzed

All subjects

No x-ray        Any x-ray
change         change

FEV,lVC             105

Percent standardzed

change

Any x-ray
change

Percent standardmed

All sublects

No x-ray
change

Any x-ray
change

FIGURE 13.-Relationship between expiratory flow and
       dust exposure
SOURCE We,ll et a, 119751.

(Table 12). The deviation of the percentage predicted value was
scored from 7 through 13 for each value, with lower numbers
representing those measurements indicative of restrictive disease

250


and higher codes representing those values indicative of obstructive
disease. Scores of 45 to 55 were considered consistent with a normal
profile when all five coded values were between 9 and 11, and
consistent with an undifferentiated profile when a mathematical
balance of codes under, equal to, and over 10 resulted in a score of 45
to 55. Scores under 45 were assumed to represent restrictive profiles
and scores over 55 to represent obstructive profiles. Forty-three
percent of the population had normal lung function profiles, and 26.5
percent had undifferentiated lung profiles. The remainder was
divided relatively evenly between the restrictive and obstructive
lung profiles, with 14.9 percent having a restrictive defect and 14.3
percent having an obstructive picture. In Table 13 are revealed the
results in smokers and nonsmokers, stratified by increasing asbestos
exposure category. The data seem to suggest that neither obstructive
nor restrictive lung disease occurs in nonsmoking asbestos workers
and that restrictive and obstructive lung disease occur with equal
frequency in asbestos miners who smoke. In addition, it appears that
there is, if anything, a negative dose-response relationship between
restrictive lung disease and increasing cumulative asbestos expo-
sure. These results are particularly remarkable in the face of data
from the same group of workers presented earlier in this section,
which show a relatively clear dose-response relationship between
cumulative asbestos exposure and decline in TLC and FEV, in both
smokers and nonsmokers. The authors have interpreted this data to
suggest that an association between smoking habit and the develop-
ment of asbestos-related fibrosis may exist and that asbestos workers
who smoke may develop either obstructive or restrictive lung
disease. The inconsistencies between the data on pattern pulmonary
function tests and the measures of individual test responses de-
scribed earlier may be explained by the effects of changes in lung
volumes on some of the measurements used to code the lung function
profile. FEVY,Q and MMEFzw~~~ are measurements that, when
reduced, are used in this coding scheme to define an individual as
being obstructed. Both of these are measurements of airflow
obstruction in the presence of normal lung volumes, but may also be
reduced in the presence of diminished lung volumes secondary to
restrictive lung disease. Indeed, examination of the pattern of
pulmonary function response in nonsmoking asbestos miners (Figure
10) reveals that with increasing cumulative asbestos exposure, the
decline in TLC in these workers was accompanied by a decline in
FEVW and MMEFz~-w+. This pattern, consistent with progressive
restrictive lung disease, would define the worker by the coding
scheme as having obstruction, or would counterbalance those scores
for a restrictive category, thereby placing the worker in the
undifferentiated category. A similar effect would occur in asbestos
miners who smoke. As can be seen in Figure 10, the decline in FEV,,

251


TABLE 12.-Coding of lung function profile

code

Volumes          Flow rates
(RI'. TLC)       (FEVw MMF)

(FEV, PVC)%
percent predicted

7          <70            > 130           >116

8          70-79           121-130          111-115

9          80-89           111-120          llo-106

10          90-110           90-110           95105

11          111-120           80439           90-94

12          121-130           7iL79           ass9

13          > 130            <70           <84

SOURCE Fornw-kiasey and Becklake (19751

FEVX~, and MMEFzs-75o is greater in smoking asbestos miners than
in nonsmoking miners. This pattern, which is consistent with a
combination of restriction and obstruction in these workers, would
result in a progressive increase in the coding scheme obstructive
score, and therefore may account for the absence of a dose-response
relationship between asbestos exposure and restrictive lung disease
in the asbestos workers who smoke. With increasing severity of
restrictive lung disease, more and more workers would be catego-
rized as having an obstructive or undifferentiated pattern and thus
would drop out of the restrictive category.

A similar approach was taken by Muldoon and Turner-Warwick
(1972), who categorized the lung function results in a consecutive
series of 75 subjects with a history of exposure to asbestos who were
referred to the Pneumoconiosis Medical Panel of London. The
researchers categorized workers as having obstructive, restrictive,
mixed, or normal lung function. They reported that the workers with
obstruction did not have heavier smoking histories than the subjects
with restrictive or normal lung function. However, examination of
the data presented in their report reveals that, although the
percentage of current smokers in the obstructive and restrictive
groups was somewhat similar, there were marked differences in the
frequency of former smokers. Indeed, all of the workers who had
obstructive disease had a history of cigarette smoking. There were 13
workers in the group; 8 were current cigarette smokers and 5 were
former cigarette smokers, of whom 3 had stopped smoking less than
1 year prior to the study. Of the entire group examined, there were
only four workers who had never smoked cigarettes, and all of these
workers fell into the restrictive category.

Murphy and colleagues (1972, 1978) also attempted to answer the
question whether an increased prevalence of obstructive lung disease
occurs in asbestos workers. They examined a group of 101 shipyard

252


TABLE 13.-Effects of chrysotile exposure on the health of
      1,015 current Quebec asbestos workers

Dust index 1            c 10    lo-99   10x199    2cc-399    4c&799    >a00

Prevalence percent2
Chronic bronchitis
Dyspnea
Function profile3
  prevalence percent
Restrictive
Obstructive
Percentage fall in function'
vc
FEV,
DLCO,, rest
DLCO,, exercise

Prevalence percent'
Chronic bronchitis
l&pIlea
Fun&on profile-3
  prevalence percent
Restrictive
Obstructive
Percentage fall In function'
vc
FEV,
DUO,, rest
DLCO,, exercise

10
0



3
0


0
0
0
0






23
4



8
12


0
0
0
0

Konsmokers

19       19       46       21       49
19       24       31       13       44

3       3
1       0

-10      -16
-9       -9
-11      -15
-8       -9


Smokers

22      30      29       46      45
15       18       21       30      32

14       16       10        4       13
12       13       12       23       12

-3       -7
-3       -8
-4      13
0       -2

1

-18      -19      -23
-13      -15      -22
-18      -12      -15
-18      -18      -20

-10
-10
1-5
0

-13
-15
-3
-5

1

-14
-15
0
-7

SOTE For all measurements. prevalence percent has been age-standardized to the total working population BS
of October 31. 1966 This was to allow for the smaller of number of men for whom function profiles were analyzed
' Expressed in mllhon particles per cubic foot years '
1 Based on a total sample of 1.015 men I
"Basedon995men 2
SOURCE Becklake et al 119761

pipe coverers and compared them with 95 control subjects. The
prevalence of smoking in these two populations was approximately
the same. There were significant differences between the asbestos-
exposed workers and the control population in vital capacity and
FEV, in measurements taken both in 1966 and in 1972. However,
there was no difference between the two groups in FEV, as a percent
of FVC at either time point. In 1972, there was a significant
difference between the two groups in the reported symptom of
wheezing apart from colds. When this symptom was combined with
the prevalence of an abnormal FEV,/FVC%, using the criteria of
Ferris and Anderson (1962) for obstructive lung disease, the asbestos
workers had a significant higher prevalence of obstructive lung
disease in comparison with the control population. However, this

253


increased prevalence resulted from their reported symptoms and not
from differences in measured pulmonary function.

In summary, lung function has been examined in several popula-
tions of smoking and nonsmoking asbestos workers. In populations of
nonsmoking asbestos workers, a dose-related decline in TLC and a
decline in FEV, and in FEFZMSS consistent with the decline in TLC
can be identified, a pattern consistent with a primarily restrictive
lung function profile. In populations of cigarette-smoking asbestos
workers, the decline in TLC is somewhat less than in nonsmoking
asbestos workers and the decline in FEV, and FEFXJSS is somewhat
more. The percentage decline in FEV, compared with the percentage
decline in FVC is greater in smoking asbestos workers, but not in
nonsmoking asbestos workers. When smoking asbestos workers are
compared with control populations with similar smoking habits,
there is a significantly greater decline in FVC and TLC, but the ratio
of FEV, to FVC is similar in the asbestos-exposed and the non-
asbestos-exposed populations. The data are therefore consistent with
independent effects of asbestos and cigarette smoking on lung
function. This issue has been examined statistically by Samet and
colleagues (1979) and by Rossiter and Weill (1974); an additive effect
of smoking and asbestos exposure on the FVC was present, but there
was no statistically demonstrable synergism.

Regan and colleagues (1971) evaluated the relative power of 16
clinical-radiological-pulmonary function variables in evaluating as-
bestosis and chronic airway disease. A decreased diffusing capacity
for carbon monoxide (DLCO) and a decrease in the vital capacity had
the greatest power to measure the severity of either obstructive or
restrictive lung disease in workers with both smoking and asbestos
exposure, but had little ability to distinguish between the two
processes. The best indicator for distinguishing between restrictive
lung disease and obstructive airway disease was FEV, as a percent-
age of the vital capacity. This variable had a better ability to
distinguish between obstructive and restrictive disease than either
the clinical or the chest roentgenogram findings or other tests of
pulmonary function.

The absence of an effect of asbestos exposure on FEV,/FVC%
must be interpreted with caution. Although this test is the best
measure of the presence of airflow obstruction in the presence of
restrictive lung disease, it is not sensitive to changes in the small
airways. Because both cigarette smoking and asbestos exposure have
been shown to result in changes in the small airways of the lung, it is
important to examine the effects of these two exposures on tests of
small airway function.

254


Small Airways Function
Airways in the lung with diameters of 2 mm or less are considered
small airways and consist of bronchioles and respiratory bronchioles
(airways with both nonrespiratory epithelium and alveoli in their
walls). Considerable obstruction can be present in these airways
without significantly altering the airway resistance or lung mechan-
ics. In addition, abnormalities in the small airways are a prominent
part of the abnormality present in chronic obstructive lung disease
(COLD). The relationship of cigarette smoking to abnormalities in
tests of small airways function, and of pathologic abnormalities of
the small airways to functional changes, was reviewed in a previous
Report of the Surgeon General (US DHHS 1984). Changes in the
small airways of cigarette smokers may occur within the first few
years of smoking, are more prevalent in heavy smokers, and increase
in frequency with increasing duration of the smoking habit. Because
the small airways are also involved in people who develop cigarette-
induced COLD, tests of small airways function are usually abnormal
in people with chronic airflow obstruction on conventional spirome-
try; however, it is not yet clear whether the early and reversible
inflammatory changes in the small airways of smokers are the first
stage in the pathophysiologic process of developing COLD or are
merely a nonspecific irritant response to smoke that does not
predispose to the development of COLD.
The response of the lung to asbestos also involves the small
airways, and there has been considerable interest in functional
changes of the small airways of asbestos workers. Relevant questions
are these: Does asbestos cause changes in the small airways
independent of smoking? Do the morphologic changes in the small
airways caused by smoking differ from those caused by asbestos? Do
the changes in the small airways of asbestos workers progress to
airflow obstruction, as measured by standard spirometry, indepen-
dent of cigarette smoking?
Woolcock and colleagues (1969) demonstrated that a group of
bronchitic subjects with normal lung volumes and flow rates had
abnormal tests of small airways function. Cosio and colleagues (1978)
and Berend and colleagues (1979) were able to correlate abnormali-
ties of tests of small airways function with morphologic changes in
the small airways. The morphologic changes consisted of a respira-
tory bronchiolitis with goblet cell metaplasia, inflammation of the
bronchiolar wall, smooth muscle hypertrophy, peribronchiolar fibro-
sis, and pigmentation of the bronchiole. Tests of small airways
function (closing capacity and slope of the single breath nitrogen
washout) were abnormal, with lower degrees of pathologic change;
however, abnormalities on spirometric testing (FEV,/FVC and
FEF25-754r) were also correlated with more severe morphologic
changes in the small airways.


The changes in the small airways of asbestos workers have been
examined (Wright and Churg 1984; Churg and Wright 1984), and
differences in the pattern of injury from that produced by cigarette
smoking alone were identified. The researchers examined lung
sections from 15 patients who had been exposed to asbestos and had
abnormalities of the respiratory bronchioles, and compared these
individuals with 15 control subjects matched for age, sex, and
smoking status. Almost all of the subjects smoked (13 of 151, so it was
not possible to examine the differences between smoking and
nonsmoking asbestos workers or to rule out an interaction between
smoking and asbestos. However, two distinct patterns seem to
emerge. Churg and Wright found changes in the membranous
bronchioles of the cigarette-smoking controls similar to those found
by others (Casio et al. 1978; Berend et al. 1979), including inflamma-
tion, pigmentation, and periobronchiolar fibrosis. The changes in the
membranous bronchioles of the asbestos workers (almost all of whom
were smokers) were qualitatively identical to those in the non-
asbestos-exposed smokers; but quantitatively, the degree of fibrosis,
the amount of pigmentation, and the percentage of membranous
bronchioles involved was greater in the asbestos-exposed individuals.
In the asbestos-exposed group, 67 percent of the membranous
bronchioles showed marked fibrosis in comparison with 19 percent in
the control population of smokers. The clearest distinction and the
most diagnostically useful lesions occurred in the respiratory
bronchioles and alveolar ducts. Forty-eight percent of the respiratory
bronchioles and 35 percent of the alveolar ducts showed marked
fibrosis in the asbestos-exposed group in contrast to 4 percent of the
respiratory bronchioles and 0 percent of the alveolar ducts in the
control population. These data suggest that cigarette smoking
produces an inflammatory response with only modest amounts of
fibrosis in the membranous bronchioles, and that the addition of
asbestos exposure results in a marked increase in the fibrosis around
the membranous bronchioles and an extension of this fibrosis to the
respiratory bronchioles and alveolar ducts. Because there were so
few nonsmokers examined in this study, the questions whether
asbestos exposure alone causes an inflammatory response and
whether the fibrotic lesions characteristic of asbestos exposure are
influenced by smoking could not be addressed.

Given this description of the pathologic response of the small
airways to cigarette smoke and asbestos dust, examination of the
physiologic testing of the small airways in asbestos workers should
focus on several questions: Does asbestos exposure alter the function
of the small airways in people who have never smoked? Does this
alteration in small airways function result in reductions in the rate
of expiratory airflow (as occurs in cigarette smokers) independent of
the reductions in lung volume that occur secondary to asbestos

256


exposure? (The increased resistance in the small airways may be
compensated for by an increased elastic recoil of the lung available
to drive expiratory airflow.) Does asbestos exposure increase the
prevalence of abnormalities on tests of small airways function above
that expected from smoking alone?
A number of researchers have examined small airways function in
asbestos workers. Jodoin and colleagues (1971) examined 24 workers
with normal chest roentgenograms whose asbestos exposure ranged
from 6 months to 24 years. Two groups with comparable age and
smoking prevalence, but with differing exposure to asbestos dust,
were defined among those 24 workers. The more heavily exposed
group had a 30 percent increase in lung static recoil pressure and
had reduced rates of expiratory airflow for any given transpulmo-
nary pressure, suggesting increased resistance in the small airways.
This increased resistance did not result in obstruction on spirometric
testing, as both FEV,/FVC% and FEFz+xc~ actually increased in the
workers with heavier asbestos exposure. In five of the subjects with
heavier exposure, but with a normal FEV, and FEV,/FVC%, the
maximal expiratory flow was reduced throughout the entire range of
lung volume despite an increased driving pressure, suggesting that
the degree of small airway obstruction was greater than the degree
of increase in driving pressure. However, all five of the subjects were
cigarette smokers; therefore, the reduced airflow could not be
identified as due to the asbestos. The authors provided no separate
analysis of the data for the nonsmokers in the study.
Several other authors (Harless et al. 1978; Cohen et al. 1984;
Rodriguez-Roisin et al. 1980; Siracusa et al. 1983) have also
presented evidence suggesting that asbestos exposure results in
small airway dysfunction; however, the data on nonsmokers were
not presented in a manner to allow evaluation as a separate group,
or included ex-smokers with never smokers, making interpretation
difficult.
Begin and colleagues (1983) examined airways function in 17
lifetime nonsmoking asbestos workers with an average of 28 years of
exposure in the asbestos mines and mills of Quebec. Seven workers
met the diagnostic criteria for asbestosis and 10 did not; none of the
workers met the diagnostic criteria for chronic bronchitis, emphyse-
ma, or asthma. The lifetime nonsmokers without asbestosis had
relatively normal lung function, but there was a slightly lower
maximal expiratory flow at 25 percent of the vital capacity and a
significantly elevated isoflow volume, suggesting dysfunction in the
small airways. The seven workers with asbestosis had clear evidence
of smali airway obstruction with a threefold or fourfold increase in
upstream resistance at low lung volumes. These data were supported
by histologic evidence of peripheral airway obstruction and narrow-
ing on lung biopsies in three of these men. However, this obstruction


in the small airways was not severe enough to significantly reduce
the usual spirometric parameters of airflow obstruction, and none of
these men had a significant reduction in FEV,/FVC%. The authors
attributed this phenomenon to the higher pressures available to
drive airflow in these workers with restrictive lung disease.
Cohen and colleagues (1984) attempted to examine the relation-
ship of smoking and asbestos exposure in a cross-sectional study of a
group of asbestos litigants. Unfortunately, ex-smokers were included
with the group of nonsmokers. This results in an increasing
prevalence of ex-smokers with increasing age, and ex-smokers have
reduced lung function (US DHHS 1984); correspondingly, with
increasing duration of asbestos exposure, there would also be an
increasing prevalence of ex-smokers. This confounding of their
exposure data makes meaningful interpretation impossible.
In summary, the evidence suggests that asbestos exposure can
result in small airways dysfunction in nonsmoking workers, but this
small airways dysfunction does not result in obstruction on standard
spirometric testing. FEV,/FVC% remains normal in these non-
smoking asbestos workers even in the presence of substantial
increases in the airway resistance at low lung volumes and decreases
in TLC. This picture differs from that in small airway dysfunction in
cigarette smokers, where there is a decline in the FEV,/FVC%. This
difference may be accounted for by the differences in elastic recoil
pressure of the lung produced by these two injuries. Asbestos
exposure results in increased elastic recoil of the lung, which
provides an increased driving pressure that compensates for the
increased resistance in the small airways. Thus, the rate of expirato-
ry airflow is preserved. In contrast, the elastic recoil either remains
normal or frequently decreases (in emphysema) with cigarette-
induced lung injury, and therefore there is no compensatory increase
in driving pressure to maintain the rate of expiratory airflow in the
presence of an increased resistance in the small airways. In
combined exposure to cigarette smoke and asbestos, the largely
inflammatory response in the small airways due to smoking may
occur conjointly with the largely fibrotic response in the same
airways due to asbestos, and the resultant increase in the resistance
in the small airways may be large enough to reduce expiratory
airflow even in the presence of an increased elastic recoil.
In conclusion, asbestos exposure can result in reduced lung
volumes in both smoking and nonsmoking workers, and may result
in small airway dysfunction. However, the evidence does not suggest
that airflow obstruction, as measured by a reduced FEV,/FVC, is a
result of asbestos exposure in nonsmoking asbestos workers or that it
is worse than would be expected from the smoking habits of asbestos
workers who smoke.


Chest Roentgenographic Changes

One of the hallmarks of interstitial fibrosis due to asbestos is an
abnormal chest roentgenogram, and despite the fact that biopsy-
proven disease may be present with a normal roentgenogram (Epler
et al. 1978), the x ray commonly reflects both the presence and the
extent of fibrosis. Occasionally, particularly in early asbestos-in-
duced lung disease, the chest roentgenogram may not be abnormal
and the only abnormalities may be a reduced diffusing capacity or
decreased lung volumes. The chest roentgenogram is less frequently
abnormal in cigarette-induced chronic obstructive lung disease, but
roentgenographic abnormalities can occur, particularly in advanced
disease or when extensive emphysema is present. The abnormalities
produced by these two processes are usually quite different on chest
roentgenogram once the disease process is sufficiently advanced, and
confusion about the roentgenographic diagnosis in severe disease is
unusual.

The radiographic changes associated with asbestos include small
irregular opacities, which commonly begin as a reticular pattern in
the lower lung fields and may progress to diffuse interstitial
densities throughout the entire lung with reduced lung volumes
(Selikoff and Lee 1978; Fraser and Pare 1979). The abnormalities
that have been reported with COLD include overinflation, promi-
nence of lung markings ("dirty lungs"), tubular shadows, and in the
presence of significant emphysema, oligemia, and bullae (Fraser and
Pare 19791.

Roentgenographic Changes in Non-Asbestos-Exposed
Populations

The literature establishing asbestos as a cause of interstitial
fibrosis is extensive, and no significant scientific debate remains over
the potential for occupational asbestos exposure to result in intersti-
tial fibrosis; substantial numbers of asbestos workers have developed
interstitial fibrosis as a direct consequence of their inhalation of
asbestos dust. A review of this evidence is beyond the scope of this
chapter and can be found elsewhere (Selikoff and Lee 1978). The
questions raised by the combination of cigarette smoking and
asbestos exposure do not include whether cigarette smoking is an
independent competing cause of the extensive fibrotic process found
in many workers following prolonged heavy exposure to asbestos.
Cigarette smoking has not been shown to independently cause this
kind of reaction in the lung. Therefore, this section focuses on three
questions concerning the relationship of cigarette smoking to the
roentgenographic changes caused by asbestos. In the absence of
asbestos exposure, are the chest roentgenograms of cigarette smok-
ers more likely to be interpreted as positive for interstitial fibrosis
than those of nonsmokers? Do cigarette-smoking asbestos workers

259


have a higher prevalence of chest roentgenograms interpreted as
positive for interstitial fibrosis than nonsmoking asbestos workers?
Do cigarette-smoking asbestos workers have more severe interstitial
fibrosis on chest roentgenograms than nonsmoking asbestos workers
for comparable asbestos exposures?

The determination of whether radiologic findings consistent with
interstitial fibrosis are present is part of the standard clinical
interpretation of the chest roentgenogram. However, the Interna-
tional Labour Office (ILO) (1980) developed a classification by which
the roentogenographic changes of pneumonconiosis can be measured
and reported in a standardized way. Small opacities are character-
ized as rounded or irregular, and the profusion of the opacities is also
described and quantitated on a numerical scale (from O/O to 3/4).
This classification was designed as a descriptive rather than a
clinical tool; as such, it is structured to be sensitive to the earliest
roentgenographic changes. This sensitivity allows the investigation
of early or mild disease, but also may reduce specificity. Using this
classification, other mild, but not pneumoconiotic, disease in the
general population may be interpreted as positive. Indeed, given the
variety of causes of interstitial fibrosis other than inhalation of
inorganic dust, the absence of any false positives by this classifica-
tion would be surprising, and therefore the questions are the
magnitude of this false positive rate and whether cigarette smoking
influences that rate.

The semiquantitative IL0 classification system can have substan-
tial variability of interpretation, particularly at the lower levels of
abnormality (Werner 1980). Table 14 shows the differences between
the highest and lowest categorizations of 32,695 chest roentgeno-
grams interpreted according to the IL0 classification by three
different readers as part of a study of asbestos-related disease. In
general, there was good agreement, but in a number of cases marked
differences of interpretations occurred, including the same radio-
graphs being interpreted by different readers as negative (O/O) and
as substantially positive (2/2). Werner discussed some of the
problems generated by these differences in interpretation and
offered some potential remedies, but the data pointed out that a
system designed to be sensitive to low levels of abnormality may be
expected to have a some variability of classification, particularly
around the threshold of abnormality.

Weiss (1967, 1969) published a pair of studies evaluating the
prevalence of a roentgenographic interpretation of interstitial
fibrosis in smokers and nonsmokers drawn from the general
population. The first study involved the examination of 70 mm chest
photofluorograms of 999 men and women who came consecutively to
the central survey unit of the Philadelphia Tuberculosis and Health
Association. The films were evaluated for increased bronchovascular

260


TABLE 14.-Analysis of x rays of asbestos workers, lowest readings by highest readings (IL0 U/C
       scale)

L0wee.t
reading


01.

o/o

O/l

l/O

l/l

l/2

211

212

213

312

313

314

01.



2

o/o



857

20449

O/l



94

3406

46

l/O



47

2162

149

29

l/l



56

2699

385

189

53

Highest reading


   l/2      2/l      212      213     312     313     3f4     TOtal



    15       2       6      2             2            1063

   693      153      283      47             18            29910

   152      39      85      12       1       2             871

   100      43      69      10       1       2             443

    55      39      101      32       6       7      1       294

    1       3      25      10             6      1       46

                  8       5             3              16

                  3       9       3       6      2       23

                         2             6              8

                                                    0

                                      1              1

                                                    0

TOtd      2      21306      3546      2387      3382      1016      219      580     129      11      53      4     32695

SOURCE: Werner (1980)


markings or diffuse pulmonary fibrosis; 3.1 percent of the subjects
had abnormal films, with a prevalence of 1.5 percent in nonsmokers
and 4.4 percent in cigarette smokers. Dose-response relationships
were present for the number of cigarettes smoked per day and for
the duration of smoking. A second study evaluated 2,825 adults,
again using 70 mm photofluorograms; this time interpretation was
by readers other than the author, and the purpose of the evaluation
was to examine the population for COLD rather than for interstitial
fibrosis. The prevalence of diffuse interstitial fibrosis was 0.6 percent
in nonsmokers and 2.1 percent in smokers.

Kilburn (1981) criticized these studies on the basis of their use of
`70 mm films and the failure to use the IL0 criteria for grading the
roentgenographs. Epstein and colleagues (1984) applied the IL0
criteria to 200 admission chest roentgenograms at an urban universi-
ty medical center. Small opacities with profusions of l/O or greater
were found in 22 (11 percent) of the subjects, none of whom had a
documentable dust exposure or any known medical disease that
caused interstitial lung disease. Of the 22, 12 (55 percent) were
current or former cigarette smokers. Murphy and colleagues (1978)
also used the IL0 criteria in examining 68 shipfitters and pipefitters
without known exposure to asbestos who were selected to serve as a
control group for a study of similar workers with known exposure to
asbestos. Of the control workers, 60 had chest roentgenograms
classified as O/l or less, 6 (8.8 percent) had readings of l/O to l/2, and
1 had a reading higher than l/2. A previous study of the same group
of workers (Murphy et al. 1972) had classified 14 percent of the
controls as having slight abnormalities (l/O to l/2) and 2 percent as
has having moderately advanced abnormalities (2/l to 213). None of
the control group were classified has having more advanced disease,
and the results were not presented by smoking status.

In summary, the data suggest that a small percentage of chest
roentgenograms of the general population may have changes that
can be interpreted as interstitial fibrosis, and that slightly larger
percentages of hospitalized patients and shipyard workers with no
known asbestos exposure may have chest roentgenograms read as
positive for interstitial fibrosis by the IL0 criteria. Both the
prevalence in these populations and the severity of the changes are
far lower than those found in populations with significant asbestos
exposures (Murphy et al. 19781, and they may reflect the sensitivity
of the chest roentgenogram and the IL0 classification to other causes
of lung injury. The "dirty lung" described in smokers (Fraser and
Pare 1979) may contribute to the smoking-related prevalence of
"diffuse interstitial fibrosis" described by Weiss (1969) in the general
population, but it is unlikely to be confused with the more advanced
forms of fibrosis found in severe asbestos-related lung injury.
However, the prevalence of changes in the general population,

262


particularly in the population of shipyard workers with no known
asbestos exposure, suggests that classifying a mildly positive chest
roentgenogram as asbestosis in the absence of a clear exposure
history should require other confirming evidence of asbestos-induced
lung injury. This caution may be particularly true for cigarette
smokers.

Interstitial Fibrosis in Asbestos-Exposed Populations

As was mentioned earlier, cigarette smoking is not a competing
cause of the diffuse severe interstitial fibrosis that occurs in some
workers secondary to their inhalation of asbestos dust. However,
modest peribronchiolar fibrosis (Cosio et al. 1978; Berend et al. 1979)
and occasional fibrosis of respiratory bronchioles (Wright and Churg
1984) do occur as a response of the small airways to cigarette
smoking, in addition to the periobronchiolar inflammation that is
the predominant early response to cigarette smoking. These bron-
chioles are also the site of the early response to asbestos dust
(Craighead et al. 1982J and therefore the threshold for radiologic
perception of an abnormality may be crossed more frequently, or
earlier, or at a lower dose of asbestos exposure in cigarette-smoking
asbestos workers than in nonsmoking workers. In addition, the
inflammatory response to cigarette smoke may enable or facilitate
the fibrotic response to asbestos dust. Therefore, the question of a
different exposure-response relationship between asbestos exposure
and roentgenographic changes for smoking and nonsmoking asbestos
workers should be considered.

Weiss (1984) recently reviewed the evidence relating cigarette
smoking and roentgenographic fibrosis in asbestos-exposed popula-
tions. In Table 15, drawn from this review, is shown the prevalence
of radiologic "asbestosis" in studies of asbestos-exposed populations.
In general, the prevalence was higher in smokers than in nonsmok-
ers; in several studies the difference was statistically significant. The
highest prevalence ratios for smokers compared with nonsmokers
are recorded in the populations with the lowest overall prevalence of
roentgenographic fibrosis, and it is the studies where a high
prevalence of disease is present that show similar rates of roentgeno-
graphic fibrosis among smokers and nonsmokers (if studies of
populations of less than 100 are ignored). This observation is in part
an obligatory result of the mathematics involved (a given difference
in prevalence between smokers and nonsmokers produces a smaller
prevalence ratio when there is a high prevalence than when there is
a low prevalence), but it is also the effect that would be expected if
the effect of smoking were a small independent risk of radiologic
fibrosis or if the effect was to increase the frequency with which

263


smoking asbestos workers cross the threshold for perception of
roentgenologic abnormality.

The demonstration of an increased prevalence of roentgenographic
changes interpreted as fibrosis in cigarette smokers does not
establish that the changes are produced by smoking. As has been
discussed earlier, cigarette smokers may have had a different
cumulative asbestos exposure than nonsmokers in some of the
populations studied. Liddell and colleagues (1982) examined the
prevalence of roentgenographic fibrosis in a group of 515 asbestos
miners born between 1891 and 1920 and found an increased
prevalence of roentgenographic fibrosis with increasing age and
cumulative asbestos exposure. Smokers and nonsmokers had similar
prevalences of changes, but the smokers had marginally lower
cumulative asbestos exposure. Harries and colleagues (1976) exam-
ined a younger population of shipyard workers with a lower
prevalence of roentgenographic fibrosis (Table 16). The prevalence of
changes was slightly higher in smokers than in nonsmokers, and
seemed to increase in smokers after 10 to 14 years of asbestos
exposure in comparison with after 20 to 24 years of asbestos
exposure for nonsmokers. Dosage measures were not available for
this study. Samet and colleagues (1979) examined a population of 383
asbestos workers with a prevalence of roentgenographic fibrosis (l/O
or greater) of 33.7 percent. They tested for interaction between
smoking and asbestos exposure and found a small additive effect for
roentgenographic changes, but no synergism between cigarette
smoking and asbestos exposure. Rossiter and Berry (1978) examined
the interaction of smoking and duration of asbestos exposure in a
population with a lower prevalence of roentgenographic fibrosis and
found a duration-response relationship for asbestos exposure only
among cigarette smokers. The number of workers at risk in the
nonsmoking category was small, however, making it difficult to
determine whether the absence of a dose-response relationship in
nonsmokers resulted from differences between smokers and non-
smokers or was simply a reflection of the low rate of disease in the
population.

In summary, cigarette smokers appear to have a higher prevalence
of radiologic abnormality compatible with interstitial fibrosis than
nonsmokers among populations of asbestos-exposed individuals with
low prevalence of roentgenographic fibrosis (and presumably low
levels of asbestos exposure). This difference is not apparent in
populations with higher prevalences of roentgenographic fibrosis
(and presumably higher asbestos exposures). One study (Harries et
al. 1976) suggested that cigarette smokers develop an abnormal chest
roentgenogram after a shorter duration of asbestos exposure than
nonsmokers. There is little evidence to suggest that smokers develop
more severe fibrosis (in contrast with a higher prevalence of fibrosis)

264


=;   TABLE 15.-Results of prevalence studies of the cigarette factor in asbestosis

I
:                                     Smokers                     Nonsmokers

0                                          Asbestosis                     Asbestosis                 95% confidence limits
I                                                                           PFf&llC~
EE    Study                      Number     Number     Percent     Number     Number     Percent      ratio '      Lower    UPF

I
z     Weiss (1971)

Langlands et al. (1971)

Harries et al. (1972)

Harries et al. (1976)

Weiss and The&s (197RI
Chrysotile
Chrysotile + amosite

Hedenberg et al. 11978)

Rossiter and Harnes (1979)

McMillan et al. (1960)

Selikoff et al. (19Ro)

Pea& (1982)

Liddell (1982)

  73        29

  91        35

1,635       49

17.788       181

39.73

38.46

3.00

1.02

25        6       24.00       1.66       0.81       3.76

33        9       27.27       1.41       0.56       2.53

em        20        2.48       1.21       0.72       2.03

5.552        11        0.20       5.10       2.9R       8.65

31        8       25.81         9        2       22.22
33        26       42.11        10        0        0.00

103        7        6.80        94        1        1.06

944        39        4.13        142        3        2.11

1,346        18        1.34       3n5        0        0.00

228       180       78.95        56        44       78.57

99        9        9.09        32        1        3 13

341        89       26.10       174        46       26.44

1.16
m

6.42

1.96

m

100

2.90

099

0.29       4.57
1.26'      56.31 z

1.07      38.34

O.fTl       6.30

1.092     102.232

0.43      2006

0.61       1.59

1 Smokers to nonsmokers

`Calculated by substitutmg 0 5 for 0 casea of pulmonary fibrow in the nonsmoker group
SOURCE Weiss (1984)


TABLE 16.-Prevalence (percentage) of suspected or
      definite pulmonary fibrosis among 23,340 male
      in-yard British dockyard workers during 1972
       and 1973, by smoking habit and duration of
       asbestos exposure

  Nonsmokers

         With
        fibrosis
Yumber    rpercent I

Smoking hablt

   Ex-smokers

         With
        fibrosis
NLldEr    lpercenti

   Smokers

        With
        fibrosle
Number   ipercelr

j' 5           3,516       0.1      2,746       04      7,300      06

5-9             784       02        581       03       1.666      0.5

lo-14            392       00       442       11        979      1.5

15-19           293       03        320       1.6        869      2.5

20-24            20R       10       330       1.7        66:      31

2w29            140       1.1        214       2.6        486      2.8

230            219       0.9        357       2.2        811      3.1


Total          5.552       02      4,990       0.8      12,798      1.1

than nonsmokers. These data are consistent either with a small
independent risk of interstitial fibrosis on chest roentgenogram
produced by smoking (as suggested by the studies in non-asbestos-
exposed populations) being added to the risk of fibrosis due to
asbestos exposure or with the combination of asbestos-induced and
smoking-induced changes in the small airways resulting in asbestos
workers who smoke crossing the threshold for perceptible abnormali-
ty earlier than nonsmokers. However, it is clear that if cigarette
smoking contributes to the development of interstitial fibrosis in
asbestos-exposed workers, the contribution is a minor one in
comparison with the effect of asbestos dust exposure.

Immunologic Response to Cigarette Smoke and Asbestos
Dust

There is an extensive literature on both animal models and
humans regarding alterations in the immune system following
exposure to either asbestos or cigarette smoke; however, clinical and
laboratory studies of combined exposure to asbestos and cigarette
smoke are more limited.

266


Humoral Immunity

Two independent studies (Kagan et al. 1977; Huuskonen et al.
1978) reported elevated polyclonal immunoglobulin (Ig) levels in
populations of workers with asbestosis. Lange (1980) also correlated
serum Ig levels with asbestosis. This study differentiated groups by
sex and age, characteristics that can also affect the immune system.
Cigarette smoking did not significantly correlate with serum Ig
levels, whereas individuals with roentgenographically demonstrated
asbestosis had increased levels of IgA and IgG. Asbestos workers,
including those with interstitial fibrosis, were also evaluated for
symptoms of chronic bronchitis. Male workers exhibiting symptoms
for longer than 5 years had lower IgG and IgA values than asbestos
workers without chronic bronchitis or with symptoms of bronchitis
present for less than 5 years. Elevated IgA or IgM levels were found
in a subgroup of male asbestos workers who were heavy smokers, as
assessed by the duration of smoking multiplied by the average
number of cigarettes smoked per day. The authors concluded that
the asbestotic process and not the presence of chronic bronchitis was
responsible for the high serum IgA and IgG levels (variable results
have been reported regarding the level of serum IgA with chronic
bronchitis) (Falk et al. 1970; Medici and Buergi 1971; Varpela et al.
1977). The immunoglobulin level alterations were found in workers
with demonstrable lung disease. Therefore, it is unclear whether this
alteration is involved in the pathogenesis of the disease or is an
epiphenomenon, because the measurements were made when dis-
ease was already present.

Cellular Immunity

Wagner and colleagues (1979) evaluated factors affecting the
peripheral blood leukocytes and T lymphocytes in 138 asbestos-
exposed men. T lymphocyte subsets were identified by the ability of
lymphocytes to rosette with erythrocytes, after incubation either for
1 l/2 hours (T helper cells) or overnight (T suppressor cells). Age,
length of asbestos exposure, smoking history, evidence of roentgeno-
graphic fibrosis or pleural changes, and spirometric abnormalities
were assessed. The smoking history in these asbestos-exposed
workers was the factor that correlated best with lymphocyte
changes. The group with roentgenographic changes of asbestosis and
a history of smoking had an increased percentage in E-rosettes after
1 l/2 hours. This suggests an increase in the number of the T helper
cells. Among workers with parenchymal chest roentgenographic
changes, those who smoked had an increased number of the T helper
cells compared with those who did not smoke. The number of T
suppressor cells was not affected by the smoking history or by
roentgenographic change.

267


Age and smoking as individual factors affecting lymphocyte
percentage or number have also been assessed. There is some
controversy about the effects on T lymphocytes. Silverman and
colleagues (1975) showed no correlation between percentage of T
lymphocytes and smoking or aging. Friedman and colleagues (1973)
and Alexopoulos and Babitis (1976) did not demonstrate the effect of
age on the percentage of T lymphocytes, but the absolute number of
lymphocytes declined with age. Teasdale and colleagues (1976) and
Smith and colleagues (1974) demonstrated a decline in the percent-
age and total number of T lymphocytes with age. Friedman and
colleagues (1973) showed that the total number of leukocytes,
including lymphocytes, increased in smokers until age 50, and then
declined.
The effect of asbestos exposure on lymphocytes was studied by
Kang and colleagues (1974) and by Kagan and colleagues (1977). The
findings of both groups of investigators were similar. Kang and
colleagues reported decreased erythrocyte-binding lymphocytes. Ka-
gan and colleagues showed a decrease in percentage and in absolute
number of T lymphocytes in a group of workers with asbestos
exposure. Smoking as a contributing factor was not reported in these
two studies.
More recently, these findings were substantiated by Miller and
colleagues (1983) with the use of monoclonal antibody markers to
differentiate T lymphocyte subsets. Smoking, length of asbestos
exposure, and chest x-ray findings were evaluated. A decrease in
percentage of T lymphocytes (OKRsub3)+) and in the suppressor subset
of T lymphocytes (OKmb a~+), with an increase in the ratio of helper
T Cells to suppressor cells (OKmub 4i-/OKTcSub a~+), was found in the
group of 40 asbestos-exposed individuals compared with nonexposed
inGviduals. Those with short asbestos exposure (less than 5 years)
u~re similar to controls, and those with more than 5 years of
exposure had the abnormalities. When assessing radiographic
changes, those without chest roentgenographic changes had lympho-
cyte parameters similar to nonexposed individuals, those with
pleural plaques had increased circulating helper cells (OKTcsub 41+),
and those with interstitial changes had decreased percentages of T
lymphocytes (OKnsub 31-j and suppressor cells (OKn,,,b s)+) and an
increased ratio of helper to suppressor cells (OKmb 4)+/0Kkb a,+).
Smoking habit did not influence these results. Miller and colleagues
(1983) theorized several possibilities to explain the findings. The
asbestos exposure may initially stimulate the immune system,
accounting for the increase in the helper cells in subjects with
pleural plaques. There may be an isolated toxic effect to suppressor
cells affecting the percentage of this subset, and thus the total
percentage of T lymphocytes. Lymphocytes may be distributed in
organs (i.e., the lung) once fibers are inhaled, and thus the peripheral


blood lymphocyte parameters are altered. Although the differences
are most striking in subjects with roentgenographic changes, the
lymphocyte alterations may not be related to the pathogenesis of
these changes, but may be a secondary change due to chronic disease.

In other studies (Ginns et al. 1982; Miller et al. 1982), smoking was
also found to cause T lymphocyte subset changes. These changes
were found in heavy smokers (50 to 120 pack-years) and not in light
to moderate smokers (10 to 49 pack-years). Heavy smokers had
increased total T lymphocytes (GR.riiub 3'- ), a decreased percentage of
T helper cells (GKTtSUb 4)+), an increased total number of T suppressor
cells tORnsUb st-), and a decreased ratio of helper to suppressor cells.

De Shazo and colleagues (1983) also examined lymphocyte subsets
in 31 current and former asbestos-cement workers compared with 52
healthy controls after adjustments had been made for possible
confounding effects of age, race, and smoking. The asbestos workers
had significantly decreased percentages and numbers of B and T
lymphocytes in the peripheral blood. Analysis of T lymphocyte
subpopulations revealed that total T cell numbers (OKn,,t, 31-j and
helper-inducer T cell numbers (OKTtsub aI* ) were decreased by similar
proportions. These decreases were negatively correlated with time
since the end of exposure to asbestos. In both workers and controls,
lymphocyte proliferative response to phytohemagglutinin was corre-
lated positively with the number of (OKnBUb 4,-j cells and negatively
with age. No relationship was detected between any of the immuno-
logic aberrations noted in the workers and the radiographic category
of pneumoconiosis, estimates of cumulative asbestos exposure, or
abnormalities of pulmonary function.

Lymphocyte function was assessed by Campbell and colleagues
(1980) by the mitogen lymphocyte transformation response of
peripheral blood lymphocytes. Allowing for the decline in response
seen with increasing age, there was an increase in response to
phytohemagglutinin (PHA) and pokeweed mitogen (PWM) in asbes-
tos workers who smoked compared with ex-smokers and nonsmok-
ers These findings were in agreement with those reported by
Haslam and colleagues (1978).

Sister Chromatid Exchange Frequency

An in vitro cytogenetic assay, sister chromatid exchange (SCE)
frequency, has been utilized to demonstrate chromosomal breakage
in different mammalian cell lines following exposure to asbestos. In
a study reported by Rom and colleagues (1983), 25 asbestos insulators
had a small increase in frequency of SCE in peripheral blood
lymphocytes compared with controls. The SCE rate increased
slightly with increasing years of exposure to asbestos, when age and
smoking were controlled. Smokers had similar rates of occurrence of
SCE among both controls and asbestos workers. In nonsmokers,

269


those with asbestos exposure had a significantly increased SCE rate
compared with controls. Butler (1980) and Crossen and Morgan
(1980) did not detect a difference in SCE frequency.

Public Health Implications

The data are unequivocal that cige.rette smoking and asbestos
exposure have produced substantial death and disability. The
residual public health questions generated by these data focus on
how to reduce the future risk of illness and death. As asbestos
exposures are reduced, clinically disabling interstitial fibrosis should
become a rare phenomenon in workers currently beginning their
work careers. As asbestos exposures are reduced, it will become
increasingly difficult to identify an increase in lung cancer death
rates among asbestos workers that is greater than those of the
general population. While the risk of developing mesothelioma is not
associated with smoking, the risk of developing mesothelioma should
be reduced by the lower exposure levels that currently exist, but
persists even at very low levels of exposure. A reduction in the
current U.S. standard (2f/cc) is being considered; once adequate
asbestos dust controls are applied and enforced, future gains in
reducing asbestos exposure are likely to come from reducing the
exposure of workers employed in jobs other than asbestos mining
and manufacturing. These jobs include construction workers who
may be exposed during the demolition or remodeling of existing
structures constructed with asbestos materials, and maintenance
workers who may be similarly exposed to existing asbestos-contain-
ing materials. Current concerns are the risk involved in removing
asbestos from existing buildings in order to reduce environmental
contamination and the need to educate the workers involved in these
tasks to prevent their exposure as they remove these materials.

Unfortunately, little can be done to reduce the current asbestos
burden in workers exposed prior to the introduction of environmen-
tal controls. For these workers, it is clear that the single most
important intervention that would alter their future disease risk is
the cessation of cigarette smoking. The elimination of cigarette
smoking in this population would not only substantially reduce the
number of future lung cancer deaths but also moderate the
contribution of cigarette-induced COLD to the restrictive ventilatory
limitation that may develop in these workers. The issues of liability
and responsibility for the disease that is occurring in these workers
will continue to be argued for an extended period of time, but these
arguments should not confuse or impede the efforts to alter the
future disease risk in these workers. The goal is not, and should not
be, to eliminate only that disease burden attributable to future
asbestos exposure, but rather to reduce as much as possible, by any

270


means possible, the enormous risk of death and disability that
currently exists for these workers. Smoking cessation is therefore an
intrinsic and essential part of any effort to reduce asbestos-related
disease and disability.

Summary and Conclusions

1. Asbestos exposure can increase the risk of developing lung
cancer in both cigarette smokers and nonsmokers. The risk in
cigarette-smoking asbestos workers is greater than the sum of
the risks of the independent exposures, and is approximated by
multiplying the risks of the separate exposures.

2. The risk of developing lung cancer in asbestos workers
increases with increasing number of cigarettes smoked per day
and increasing cumulative asbestos exposure.

3. The risk of developing lung cancer declines in asbestos workers
who stop smoking when compared with asbestos workers who
continue to smoke. Cessation of asbestos exposure may result
in a lower risk of developing lung cancer than continued
exposure, but the risk of developing !ung cancer appears to
remain significantly elevated even 25 years after cessation of
exposure.

4. Cigarette smoking and asbestos exposure appear to have an
independent and additive effect on lung function decline.
Nonsmoking asbestos workers have decreased total lung capac-
ities (restrictive disease). Cigarette-smoking asbestos workers
develop both restrictive lung disease and chronic obstructive
lung disease (as defined by an abnormal FEV,/FVC), but the
evidence does not suggest that cigarette-smoking asbestos
workers have a lower FEV,/FVC than would be expected from
their smoking habits alone.

5. Both cigarette smoking and asbestos exposure result in an
increased resistance to airflow in the small airways. In the
absence of cigarette smoking, this increased resistance in the
small airways does not appear to result in obstruction on
standard spirometry as measured by FEV,/FVC.

6. Asbestos exposure is the predominant cause of interstitial
fibrosis in populations with substantial asbestos exposure.
Cigarette smokers do have a slightly higher prevalence of chest
radiographs interpreted as interstitial fibrosis than nonsmok-
ers, but neither the frequency of these changes nor the severity
of the changes approach levels found in populations with
substantial asbestos exposure.

7. The promotion of smoking cessation should be an intrinsic part
of efforts to control asbestos-related death and disability.

271


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J.C. red.). Biological Effects of Mineral Fibres. Vol. 2. IARC Scientific Pub. No. 30.
Lyon, International Agency for Research on Cancer, 1980, pp. 571-577.
WHITWELL, F., NEWHOUSE, M.L., BENNETT, D.R. A study of the histological cell
types of lung cancer in workers suffering from asbestosis in the United Kingdom.
British Journal of Industrial Medicrne 31(4):298-303, October 1974.
WOODWORTH, C.D., MOSSMAN, B.T., CRAIGHEAD, J.E. Squamous metaplasia of
the respiratory tract: Possible pathogenic role in asbestos-associated bronchogenic
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compliance as a test for obstruction in the small airways. Journal of Clinical
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WRIGHT, J.L., CHURG, A. Morphology of small-airway lesions in patients with
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Annals of the New York Academy of Sciences 330:701-709, December 14, 1979.

`283


CHAPTER 7

RESPIRATORY DISEASE
  IN COAL MINERS


CONTENTS

Introduction

Prevalence of Smoking in Coal Miners

Coal Workers' Pneumoconiosis
  Prevalence of Coal Workers' Pneumoconiosis
  Pulmonary Function Abnormalities in Simple and
   Complicated Coal Workers' Pneumoconiosis
Relationship of Small Opacities to Emphysema and
   Airways Obstruction

Lung Function in Subjects With Rounded or
Regular Opacities
Lung Function in Subjects With Irregular Opaci-
ties

Respiratory Symptoms and Exposure to Coal Dust
  Bronchitis and Dust Exposure

Respiratory Mortality in Coal Miners

Lung Function in Coal Miners
Emphysema, Exposure to Coal Dust, and Cigarette
   Smoking

Dust Exposure, Cigarette Smoking, and Ventilatory
Function

Summary and Conclusions

References

287


Introduction

An association between respiratory disease and coal mining has
been recognized since the 16th century, when Agricola and Paracel-
sus wrote of the diseases of miners (Hunter 1978). The first
description of coal workers' pneumoconiosis (CWP! was given in the
early 1800s by Laennec (Meiklejohn 1951) when he described cystic
and noncystic melanotic masses in the lung, and in addition,
melanotic parenchymal infiltrates in the lung. The melanotic masses
were almost certainly progressive massive fibrosis (PMF) and the
black infiltrates, simple CWP. It is clear from Laennec's description
that he recognized an association between coal mining and the
deposition of "la matiere noire pulmonaire." An excellent history of
coal miners' lung disease in Great Britain can be found in a series of
articles by Meiklejohn (1951, 1952a, 195213).

Over the years, a large number of names have been attached to the
conditions that affect the lungs of coal miners. Many early physi-
cians assumed that there was a single respiratory condition arising
from coal dust exposure, which was variously referred to as spurious
melanosis, miners' asthma, anthracosis, miners' phthisis, and silico-
sis. With the passage of time, it became evident that, aside from the
lung diseases that commonly affect the general population, coal
miners are prone to develop occupationally related lung diseases,
namely coal workers' pneumoconiosis, silicosis, and chronic bronchi-
tis (Morgan and Lapp 1976). Silicosis is covered elsewhere in this
Report; therefore this chapter discusses coal workers' pneumoco-
niosis and chronic bronchitis.

The paramount importance of exposure to coal dust in the
development of CWP is generally accepted, and complicated CWP is
clearly associated with significant and often disabling chronic
airflow limitation as well as with other respiratory impairments
(Morgan and Seaton 1984; Morgan and Lapp 1976). Less certain is
the magnitude of the role of coal mine dust as a cause or
contributory factor in the development of bronchitis and emphyse-
ma. The effects of long-continued inhalation of coal and other dusts
are currently of major interest to epidemiologists and to those
practicing occupational medicine. Clearly the results of the studies
designed to characterize the effects of coal dust on lung function are
of vital importance to officials concerned with compensation for
occupationally related pulmonary disability. In these studies it is
important to evaluate as potentially independent effects the role of
coal dust in producing radiologic CWP and the role of coal dust in
producing physiologic airflow obstruction (Weeks and Wagner 1986).
This separation of the radiologic and physiologic responses to coal
dust is even more critical when considering the effects of combined
exposure to coal dust and cigarette smoke.

289


The respective contributions of cigarette smoking, dust exposure,
and other environmental and occupational factors in the develop-
ment of respiratory impairment in coal miners are examined in this
chapter by reviewing the evidence currently available from mortali-
ty and morbidity studies of coal miners compared with appropriate
reference populations and the evidence on the frequency and extent
of pulmonary impairment in coal miners. The roles of dust, cigarette
smoking, and various confounding factors are taken into account and
apportioned where possible.

At the present time, there are approximately 150,000 underground
coal miners in the United States. Ten years ago, the figure was about
170,000, but the closure of a number of mines in Appalachia has
reduced the number of employed underground miners, In addition,
60,000 to 70,000 workers are employed in open cast or surface mines,
but this number is constantly changing. Exposure to coal mine dust
is greater in those employed underground; miners working at the
face or in transportation are the most heavily exposed. Miners
employed underground on maintenance and other activities are less
exposed, and surface miners are the least exposed (Doyle 19701.

Prevalence of Smoking in Coal Miners

The prevalence of smoking for various populations of miners in
different countries and during different time periods is presented in
Table 1. In general, the prevalence of smoking among U.S. coal
miners is currently similar to, or slightly higher than, the rates in
the overall U.S. male population. However, coal mining as an
occupation introduces a distortion in the pattern of smoking because
of the prohibition against smoking while in the mine. As a result, the
entire consumption of cigarettes by miners is limited to those periods
when they are not underground; for a given number of cigarettes
smoked per day, the pattern among miners would consist of periods
of more intense smoking interspersed with long periods of not
smoking (i.e., during working hours), in contrast to the more even
consumption of cigarettes throughout the day that characterizes
most cigarette smokers.

Coal Workers' Pneumoconiosis

Coal workers' pneumoconiosis (CWP) is defined as the deposition of
coal mine dust in the lungs and the reaction of tissue to its presence
(Morgan and Seaton 1984). However, the term is commonly applied
only to the chest roentgenographic changes produced by coal dust,
and the other tissue responses to coal dust are classified by their
symptomatic, physiologic, or pathologic manifestations (e.g., chronic
bronchitis, airflow obstruction, or emphysema). The radiologic

290


TABLE l.-Smoking characteristics of coal workers

Study


Higgins et al.
(1968)

  Number and type
   of population


755 mining town residents.
Great Britain

Smoking characteristics (percent)


    SM          NSIEX
    15           25

Cammenta

Tokuhata et al.
(1970)

801 anthracite coal miners,
Pennsylvania

Ashford et al.
( 1970)

30.@30 underground and
surface workers. Great
Britain

SM           NS           EX
78.7          15.3            6

Rae et al.        3,379 workers, 20                                SM           NS
(1971)         colleries. Great Britain                            19.2          208

Large colleries
Age 140
  40-49
  250
Independent
Age <40
  40-49
  250

64.1           15.9
74.0          26.0
71.6          28.4


76.4          23.6
60.5          19.5
71.3          22.7

Ex-smokers not
differentiated from
smokers

SWIG and Pelaic
119711

Lignite and brown coal
miners, Yugoslavia

SM           NS           EX
64.7          23.6           11.7

M


TABLE k-Continued

Study

Number and type
of population

Smoking characteristics (percent1                      Comments

Mlnette
(1972)

204 cd miners, Belgium

SM
70.6

NS'
29.4

o Nonsmokers
include smoken
who did not
inhale

Phelpe
(1972)

256 miners, U.S. Rocky
Mountain region

SM
65.6

Skrabski-Kopp
et al. (1972)

1,066 coal miners,
Hungary

SM
75.6

Lowe and Khosla
(1972)

3.012 excoal miners,
9,361 controls, Great
Britain

Ex-miners      86.6
Controls       80.7

NS
34.3

NSIEX
24.4

KibdstiE et al.
(1973)

Bituminous coal
miners. United States

SM           NS
50.8          25.4

Ortmeyer et al.     Coal miners and ex-miners,             Coal miners,    60.9          19.7
(1974)        Appalachia                       Ex-miners      47.1          52.3

EX
23.8

19.4

2039year-old
miners smoked at
a rate above 65%

Fairman et al.
(1977)

987 surface coal miners,
six U.S. states

70.7          29.3


TABLE l.-Continued

Study

Number and type
of population

Smoking characteristica (percent)                      Comments

Armstrong et al.     Cod and gold miners,
(1979)           Australia

Szymaykiewia
(1979)

Miners, Poland

Potkonjak        970 cd nunera, 536
(1979)         controls with no dust exposure


Cochrane and Moore   Coal miners, Great Britain
(1960)

Ram et al.         242 active and retired
(1981)         miners, Utah

Love and Miller     1,677 colliery workers,
(1982)           Great Britain

Cod miners
Gold miners

Miners
Controls

Age 2x34
SM/cigs
1-14
b 14
Age 55-64
SM/cigs
1-14
  `-a 14

54
52.1


NSIEX
24.3

Pipe only
3.6





16

SM          NWEX
56.7          41.3
66.3          33.7


13.7

46
47.9


SM
71.3


32
39.3
60


32
2a

SM           NS           EX
38           23.6           36.4

SM           NS           EX
66.1           12.8           4.5

16.5% were
intermittent
smokers

NCYIIC SM=Smoker; EX=Exsmoker: NS=Nonsmoker.




manifestations of CWP are classified into two forms: simple, and
complicated (often known as progressive massive fibrosis, PMF).
Simple CWP is a reaction solely to the inhalation of coal dust.
Although the efficiency and integrity of the lung defenses are
important factors in the development of disease, cumulative dust
exposure is of paramount importance. Characteristically, after a
period of exposure, i.e., 10 to 15 years, small rounded opacities begin
to appear in the upper lung fields of some miners. With continued
exposure, they gradually spread to the middle and lower zones, and
the increasing profusion of these opacities is used to categorize
simple CWP on a 0 to 3 scale. The opacities are indistinguishable
from those seen in silicosis. Simple CWP does not progress in the
absence of further exposure. Moreover, increasing category of simple
CWP is not associated with a decrement in ventilatory capacity
(Cochrane et al. 1961; Gilson and Hugh-Jones 1955; Morgan et al.
1974).

Complicated CWP is defined as the presence of an opacity greater
than 1 cm in diameter on the chest radiograph of a subject who
already has simple CWP (IL0 19801, and the volume of lung occupied
by the large opacities on the radiograph is used to categorize
complicated CWP into category A, B, or C. For the most part,
complicated CWP develops on a background of category 2 or category
3 simple CWP. Necessary for its development is the presence of a
fairly high dust burden in the lungs, plus some other factor or factors
as yet not fully recognized or understood.

Prevalence of Coal Workers' Pneumoconiosis

In 1969 the National Coal Study was commenced by the National
Institute for Occupational Safety and Health (NIOSH) (Morgan et al.
1972). Selected for study were workers at 31 coal mines, of which 2
were anthracite and 29 were bituminous. In the initial survey, an
overall CWP prevalence of nearly 30 percent was found; 2.5 percent
had PMF. A decreasing prevalence was noted from east to west, and
there was a clear-cut relationship between the years spent under-
ground and radiographic category. The disease was much more
common in workers at the face than in surface workers. The
prevalence of CWP in this study was undoubtedly overestimated,
however. Part of the reason was that the early films were interpre-
ted according to the 1958 International Labour Office (ILO) classifi-
cation. In addition, some of the readers were inexperienced and
tended to overread. The second round of the National Coal Study
revealed a prevalence of 8 percent; the findings at the third round
were just under 5 percent, with 3.85 percent having category 1; 0.48
percent, category 2; 0.04 percent, category 3; and 0.17 percent, PMF.

The decline in the prevalence of pneumoconiosis noted between
the first and third rounds of the National Coal Study is partly

294


accounted for by the use of different readers, partly by more
stringent reading criteria, partly from the use of the IL0 standard
films as yardsticks, and partly from improved coal dust control. An
exodus of workers with higher categories of disease between the first
and subsequent accumulations of subjects with radiographic evi-
dence of pneumoconiosis also played a role, since those with CWP
qualified for compensation.

Both simple CWP and PMF are related to cumulative lifetime
exposure to coal dust. The reduction or elimination of category 2 and
category 3 simple CWP through effective dust control not only is
possible but is rapidly being achieved in the United States and Great
Britain (Jacobsen 1980). Since complicated pneumoconiosis develops
almost entirely in subjects who have the higher categories of simple
CWP (i.e., those with a high dust burden), the effective prevention of
category 2 and category 3 simple CWP should almost completely
eliminate PMF as well. The removal from further coal dust exposure
of miners with early categories of simple CWP should also aid in
reducing the incidence of PMF.

Pulmonary Function Abnormalities in Simple and
Complicated Coal Workers' Pneumoconiosis

The radiologic changes of simple CWP are associated with the
development of certain relatively minor pulmonary impairments.
These include an increased alveolar-arterial gradient for oxygen,
abnormalities of the distribution of inspired gas, and a modest
increase in lung volumes (Morgan and Lapp 1976). The increase in
lung volumes is a consequence of the focal emphysema that is an
integral part of the pathology found with simple CWP (Morgan and
Seaton 19841.

Complicated pneumoconiosis is associated with a reduction in lung
volume and diffusing capacity, ventilation perfusion mismatching,
an obliteration and destruction of the pulmonary vascular bed that
leads to nonhypoxic pulmonary hypertension and car pulmonale,
and with the presence of generalized airways obstruction (Gilson and
Hugh-Jones and Seaton 1955; Lyons et al. and Seaton 1981; Morgan
and Seaton 19841.

Relationship of Small Opacities to Emphysema and
Airways Obstruction

The small opacities present in the lung in the various pneumocon-
ioses can be classified as either rounded (regular) or irregular.
Small rounded opacities have a fairly rounded and regular margin.
They are classified according to their size into p, q, and r types: p is
up to 1.5 mm in diameter, q is between 1.5 and 3 mm, and r is
between 3 and 10 mm. Usually only one type of opacity is present,

295


but mixtures are occasionally found in the same lung. The reading of
the film should be based on the predominant opacity noted.

Irregular opacities are also classified according to size: s opacities
are up to 1.5 mm in width, t opacities are between 1.5 and 3 mm
wide, and u opacities are between 3 and 10 mm. Irregular opaciti,s
are characteristically seen in asbestosis. In some smokers scanty
irregular opacities may be observed.

Rounded and irregular opacities occasionally occur together,
usually in a person who has experienced various exposures or in a
person with either silicosis or coal workers' pneumoconiosis who also
is a heavy smoker.

Lung Function in Subjects With Rounded or Regular Opacities

A number of investigations have shown that the p, or punctate,
type of opacity seen in simple CWP is associated with a reduced
diffusing capacity (Sartorelli et al. 1963; Lyons et al. 1967; Seaton et
al. 1972; Musk et al. 1981). In addition, an increased parenchymal air
space size has also been observed in subjects with a p type of opacity
(Hankinson et al. 1979). No detectable difference in lung function
between subjects with the p, q, or r type of opacity was observed in
this study.

These physiological changes have also been demonstrated in
nonsmoking miners with simple CWP (Hankinson et al. 1979; Seaton
et al. 1972). The indices of lung function that were tested in the
miners with the p and q opacities were similar (Hankinson et al.
1979) except for the diffusing capacity, which was significantly lower
in those with the p type of lesion (Seaton et al. 1972). Static
compliance was reduced marginally, but not significantly, with the q
type of opacity. The type of opacity was not significantly related to
differences in dynamic compliance at increased rates of breathing
(Seaton et al. 19721.

Musk and colleagues (1981) examined the lung function in 125 coal
miners identified in 1968 as having the simple pneumoconiosis of
coal workers and reexamined 9 years later. Pulmonary function was
related to both smoking history and coal dust exposure. Miners who
smoked in 1978 had lower forced expiratory volume in 1 second
(FEVJ, forced vital capacity (FVC), and FEV,/FVC ratio and a
higher ratio of residual volume to total lung capacity (RV/TLC)
compared with nonsmokers. Ex-smokers had a lower carbon monox-
ide diffusing capacity (DLCO) than nonsmokers. Total dust exposure
was inversely related to FVC and lung elastic recoil at TLC. After
correcting for the effects of age, height, and smoking category,
miners whose radiographs showed predominantly p and r types of
opacities had a reduced DLCO when compared with miners with the
q type of opacity. In the researchers' experience, irregular opacities
were also associated with a reduced DLCO, and were thought to

296


reflect the presence of both emphysema and diffuse fibrosis. In
addition, the r type of opacity, but not the p type, was associated with
reduced maximal recoil at TLC, and reduced recoil at 50 percent of
TLC and at 1 L below TLC, and with an increased RV and RV/TLC
percent compared with miners with the q type of opacity. The
decreased compliance in subjects with the r type of opacities noted by
Musk and colleagues (1981) may be a consequence of the exposure of
some of these subjects to silica. Irregular opacities were not
associated with increased obstruction or with smoking; here the
results of Musk and colleagues differ from almost all other studies.

Lung Function in Subjects With Irregular Opacities

The significance of irregular opacities in the lungs of coal miners
has been the subject of a number of investigations. Lyons and
colleagues (1974) pointed out that there was a positive association
between the presence of irregular opacities and emphysema and
impairment of FEV,. Unfortunately, this was a post-mortem study
in which no smoking histories were available. Subsequently, Aman-
dus and colleagues (1976) investigated the significance of irregular
opacities in the lungs of 6,166 working U.S. coal miners for whom
complete smoking histories were available. Irregular opacities on the
chest radiographs were shown to be associated with smoking,
bronchitis, age, and years worked underground. Smoking was not
associated with the presence of regular opacities. Although irregular
opacities were observed in nonsmokers, they were 2.5 times more
common in those who smoked. Among nonsmoking miners, there
were no significant differences in the lung volumes or flow rates of
the men with normal chest x rays, irregular opacities, rounded
opacities, or mixed opacities. Smokers had similar FVCs in each of
the radiologic categories when compared with nonsmokers, but FEV,
and FEV,/FVC were lower and RV and TLC were higher. In
addition, smokers with irregular opacities had a lower FEV, and a
higher RV and TLC than smokers with normal chest x rays or
rounded opacities. A study by Cockroft, Berry, and colleagues (1982)
of coal workers and ex-workers showed that irregular opacities were
related to age, smoking, and underground exposure in those receiv-
ing disability benefits.

Cockcroft, Seal, and colleagues (1982) examined the relationships
among lung function tests, irregular opacities on chest radiograph,
and the pathologic changes of emphysema in 46 men who had been
referred for lung function tests during life and who had died between
1970 and 1979. Irregular opacities on radiograph were associated
with a reduced DLCO and reduced TLC, an increased pathologic
score for emphysema, and to a lesser extent, an increased pathologic
score for fibrosis. Smoking histories were obtained in all but five of
these workers, and there was no association of smoking with any

297

157-964 0 - 86 - 11


particular lung function or pathologic finding. However, almost all
of the subjects in the study were current smokers (two were
nonsmokers and two were former smokers), which limited the ability
of the study to examine the effects of smoking.

The majority of the evidence indicates that simple CWP is
associated with mild overdistension or hyperinflation of the lungs.
There is some evidence, especially in miners with the p type of
opacity. that there is also a reduction in DLCO. The decreased DLCO
does not appear to be associated with increasing airways obstruction,
but with focal dust emphysema. The available data indicate that
cigarette smoking plays a much greater role in reducing DLCO than
does the presence of simple CWP (Frans et al. 1975).

Irregular opacities occur occasionally in the lungs of coal miners
and former miners. For the most part, they are associated with
smoking, age, bronchitis, and years spent underground. Bronchitis
may be the common denominator in the production of irregular
opacities, and the increased prevalence of bronchitis in smoking coal
miners may be the reason for the increased prevalence of irregular
opacities found among smokers in some studies. Irregular opacities
are seen in nonoccupationally exposed groups (Carilli et al. 1973), in
subjects exposed to silica, in asbestos miners and millers (Morgan
1978), in workers who manufacture manmade fibers (Weill et al.
1983), and in workers with other conditions, suggesting that irregu-
lar opacities may be a nonspecific response associated with the
presence of bronchitis, regardless of its etiology.

Respiratory Symptoms and Exposure to Coal Dust

The relationship between dust exposure and bronchitis was noted
by Thackrah (1832) and Greenhow (1860) in the 19th century.
Although these pioneer workers noted a higher prevalence of
bronchitis and other respiratory ailments in the dusty trades as a
whole, they particularly emphasized the importance of textile dust
as a cause of bronchitis.

Until recently the use of the terms "chronic bronchitis" and
"emphysema" implied that these two conditions were invariably
associated and that both, for the most part, were related to cigarette
smoking. In this context, "bronchitis" implied a condition character-
ized by cough and sputum, usually associated with a reduction in
ventilatory capacity or frequently leading to one (Fletcher et al.
1959). Subjects with these symptoms who also had concomitant
chronic airflow obstruction were usually diagnosed as having
chronic bronchitis and emphysema, assuming from the association of
the two diseases that they were part of the same process. At the time
the committee appointed by the Medical Research Council (MRC) of
Great Britain published its statement (British Medical Journal

298


1966), it was known that not all subjects with chronic bronchitis
showed an associated reduction of FEV1, but the committee did not
elaborate fully on the implications of the term "bronchitis." It was
assumed, moreover, that there was a relationship between the
symptoms of cough and sputum and a decreased ventilatory capaci-
ty, and that sooner or later most or all subjects with chronic
bronchitis would develop some degree of irreversible airways ob-
struction. The MRC's (1965) division of bronchitis into obstructive
bronchitis and simple bronchitis, a condition characterized by the
presence of cough and sputum in the absence of airways obstruction,
was the first step taken toward a better understanding of the
implications of a diagnosis of bronchitis. Subsequently, the general
use of the MRC questionnaire on chronic bronchitis for symptoms
without reference to lung function led to an appreciation of the
pathophysiology of this condition (MRC 1965), and the pathological
features of bronchitis as described by Reid (1960) in her studies
provided a means of quantitating the severity of the condition.

Bronchitis and Dust Exposure

Many of the studies showing an association between dust exposure
and an increased prevalence of chronic bronchitis have been carried
out with coal miners. Coal miners represent a clearly defined and
relatively large group of subjects who seldom change their occupa-
tion, and thus present an ideal study population. Ashford and
colleagues (1970) showed that the prevalence of cough and sputum
increased with age and, it may be inferred, with cumulative dust
exposure. Shortly thereafter, Rae and colleagues (1971) demon-
strated a relationship to dust exposure. Kibelstis and colleagues
(1973) showed, in a U.S. population of more than 9,000 working coal
miners, that cough and sputum were related to dust exposure and
also to cigarette smoking. When only nonsmokers were considered,
there was a gradient in the prevalence of bronchitis from the least to
the most dusty jobs. This occurred independent of age. In smokers,
the effect of cigarette smoking almost completely overwhelmed the
effects of dust and age, at least as far as symptoms were concerned.
Similar findings have been reported in Belgian coal miners (Minette
1976; Vuylsteek and Depoorter 1978).
The effect of dust and cigarette smoke on bronchial gland
dimensions in coal miners has recently been investigated (Douglas et
al. 1982). These investigators demonstrated that both dust and
cigarette smoking had an effect on the Reid index and that they led
to mucous gland hypertrophy. There is thus a fairly widespread
acceptance that the long-continued inhalation of coal dust and other
dusts may lead to an increased prevalence of cough and sputum in
the absence of cigarette smoking. Moreover, it has been demon-
strated that the prevalence of dust-induced bronchitis is related to


cumulative dust exposure (Rogan et al. 1973; Kibelstis et al. 1973).
The topic of industrial bronchitis is more fully discussed in another
chapter of this Report, but the data suggest that there is an
independent and additive effect of coal dust exposure and cigarette
smoking on the prevalence of chronic bronchitis.

Respiratory Mortality in Coal Miners

Early mortality data of coal miners showed a high death rate from
respiratory disease. This was true for both Great Britain (Registrar
General 1958) and the United States (Enterline 1964; Guralnick
1963). Although there may be some doubt as to the precise accuracy
of such data, it is probably true that there was an increased
standardized mortality ratio (SMR) for respiratory disease among
coal miners. There was, however, little convincing evidence to
establish that coal dust was a major causative factor in this increase.
Tuberculosis, emphysema, and bronchiectasis were more common in
coal miners, and most of the increased mortality could be explained
by an increased prevalence of these diseases. In addition, Enterline
(1964, 1972) had shown in a series of retrospective analyses that the
SMR for coal miners as a group was elevated, but a substantial
portion of the excess was a consequence of trauma and accidents.
When deaths due to these excesses were excluded, excess mortality
still persisted. Much of the excess was due to respiratory disease, and
although the death rate for chronic bronchitis and emphysema was
reported to be increased, so also were the death rates for tuberculosis
and lung cancer. While it is easy to postulate a relationship between
occupation and bronchitis, it is also clear that bronchitis and lung
cancer have a common causative agent, namely cigarette smoke. In
addition, coal miners, particularly in the United States, constituted a
distinctly underprivileged group during the early part of this
century, and as such suffered from overcrowding and poor medical
care, both of which contributed significantly to a higher death rate
from bronchiectasis and tuberculosis and other infectious diseases.

Over the past two decades, a number of well-controlled epidemio-
logical studies of morbidity and mortality of coal miners have been
carried out in both Great Britain and the United States. Liddell
(1973a) looked at the frequency of time off from work because of
illness in a cohort of 29,084 men. He showed that miners spent more
time off work than nonminers. The highest rate of incapacity was
present in the lowest paid workers; this applied as much to coal face
miners as to surface workers. Pneumoconiosis was associated with
greater time off work. An additional investigation of the mortality of
5,362 British miners who died in 1961 showed that they had higher
death rates for accidents and pneumoconiosis than the general
population, but lower death rates for cancer in general and for lung

300


cancer in particular (Liddell 1973b). There was a wide disparity
between the SMR of miners employed at the face (49) and the SMR of
those working on the surface (82). This disparity can be explained in
that surface miners may smoke while at work, but underground
miners cannot, and that the less healthy miners tend to move away
from coal face work and to be employed in easier jobs on the surface.

Ortmeyer and colleagues (1973; Lainhart et al. 1969) studied the
death rate of Pennsylvania coal miners who had been awarded
compensation for occupationally related respiratory disability. The
overall SMR was the same as that of white men in Pennsylvania.
Excess death rates were found in subjects with a reduced ventilatory
capacity, in particular when the FEV,/FVC was below 50 percent,
and in ex-miners with stage B and C complicated CWP. "Disabled"
miners with simple CWP had a normal SMR. Later, Ortmeyer and
colleagues (1974) studied a group of randomly selected Appalachian
miners and ex-miners. They showed that the overall life expectancy
for miners and ex-miners combined was the same as that for the
general U.S. population and for the States from which the cohort
originated. The effects on mortality of the years worked under-
ground, cigarette smoking, and airways obstruction were investi-
gated. Ex-miners had a slightly but significantly increased death
rate. Simple CWP had no effect on life expectancy; however,
complicated CWP was associated with decreased longevity. Although
both cigarette smoking and airways obstruction were associated with
an increased SMR, the number of years of work underground had no
discernible effect.

About the same time these reports were published, Cochrane
(1973) described his findings from a 20-year followup of the male
population of the Rhondda Fach in Wales. Survival rates for miners
and ex-miners were independent of the radiographic presence of
simple CWP or category A complicated pneumoconiosis. Further
studies of the same cohort from the Rhondda Fach showed a normal
life expectancy in those with simple CWP and category A complicat-
ed CWP (Cochrane et al. 1979). The death rate for bronchitis and
other respiratory diseases was elevated. The smoking habits of this
population were not examined.

A 20-year followup of a population sample from Derbyshire
(Cochrane and Moore 19801, aged 25 to 34, included four groups of
workers whose work was categorized as nondusty, pure coal mining,
pure foundry, or other and mixed. There were no significant
differences in the SMRs of the dust-exposed group of miners,
compared with the non-dust-exposed group of miners; however, only
20 deaths were recorded in the study.

Rockette (19771, in a NIOSH-supported study, investigated the
mortality rates among coal miners covered by the United Mine
Workers of America (UMW) Health and Retirement Fund. Unfortu-

301


nately, unlike the studies of Ortmeyer and colleagues (1973,1974), in
this investigation the population was not randomly chosen and
smoking histories were not available. A 10 percent sample of miners
eligible for benefits in January 1959 was randomly selected from the
original 550,000. Doubt exists whether miners covered by the UMW
Health and Retirement Fund are necessarily representative of U.S.
coal miners as a whole. The SMR for all causes was 101.6 and for all
cancer, 97.7. The SMRs for asthma, emphysema, and tuberculosis
were significantly elevated at 174, 144, and 145, respectively. The
SMR for lung cancer was minimally but significantly elevated at
112; however, a disproportionate number of miners from southwest-
ern West Virginia were subsequently shown to have been included in
the cohort. The death rate for lung cancer in this part of the United
States is significantly higher than the rate for the United States as a
whole and for other parts of West Virginia. In the absence of
smoking histories, little can be made of such a small increment in
mortality. Deaths due to accidents were high (SMR 144). The SMR
for bronchitis was 89.7, but, as previously mentioned, the SMR for
emphysema was elevated. There was a significantly increased death
rate for stomach cancer, but the SMR for pneumoconiosis could not
be determined because of difficulties with death certification and
classification.

A lengthy report of coal miners' morbidity in relation to x-ray
category, lung function, and exposure to airborne dust (Miller et al.
1981) described the findings for 31,611 British miners who were
surveyed at 24 pits from 1953 to 1958. Again, the coal miners had a
lower mortality than British men in general. Although this was
attributed to the healthy worker effect, no supporting evidence for
this conclusion was given. Miners with PMF had an increased death
rate. Mortality from bronchitis was associated with increased dust
exposure, but it is apparent that with increased dust exposure, there
would also be an increased cumulative exposure to cigarette smoke.
Appropriate data whereby the two effects could be separated were
not available, since cumulative cigarette smoking history or, indeed,
a smoking history of any kind was not available. Deaths from lung
cancer were not increased.

Higgins and colleagues (19811, in a followup study of a group of
miners from Richwood and Mullens, West Virginia, were unable to
show any significant difference in the mortality of miners and ex-
miners as compared with nonminers. The death rates from respira-
tory diseases were appreciably higher in coal miners; however, there
are doubts as to the accuracy of the cause of death on the death
certificates because compensation was often awarded to ex-miners'
families solely on the basis of a death certificate that mentioned
respiratory disease (Comptroller General 1980, 1982). Another
problem encountered was that some miners had moved away from

302


the district and could not be traced. In many instances, their status
proved impossible to determine. A clear-cut effect of smoking on
mortality was evident in nonminers, but was less evident in miners
and ex-miners. Here again the advent of black lung compensation
may have been an incentive for disability applicants to underesti-
mate their smoking habits.

The publication of the Registrar General's Decennial Supplement
(1970-1972) on occupational mortality (1978) indicated that mortali-
ty rates for coal miners were somewhat increased for both under-
ground and surface workers. The SMR for most respiratory diseases
other than lung cancer showed a mild to moderate increase.

Jacobsen (1976,1977) concluded that coal miners as a group have a
normal SMR. He also indicated that there was no excess death rate
from bronchitis and emphysema among coal miners, nor was there
an increase in mortality from these conditions with increasing time
worked in dusty occupations. Among men with no pneumoconiosis,
there was a clear and significant mortality gradient with increases
in estimates of cumulative exposures to airborne dust. However, the
decision to study the SMR of selected subgroups of miners whose
cigarette smoking habits were unknown, and in whom other possible
confounding factors may have been present, detracts from his
conclusions. The demonstration that the presence of bronchitis in
coal miners is associated with increased mortality and morbidity is
of little special significance for coal miners because the same
situation applies to the general population. The increased mortality
and morbidity are for the most part attributable to cigarette
smoking in the general population, and only if it were possible to
show an increased death rate in nonsmoking bronchitic coal miners
would this observation be convincing evidence that the presence of
bronchitis of itself portends premature disability and death.

In conclusion, the majority of recent mortality studies have shown
that coal miners have a normal life expectancy. Although there is an
increased SMR in miners with PMF, the overall prevalence of PMF
in working miners is so low that any effect it has on the SMR is more
than counterbalanced by decreased death rates from lung cancer and
heart disease. Although in certain studies, death rates from bronchi-
tis and emphysema have been found to be elevated, this has not been
a consistent finding; in other studies, especially those in which it has
been possible to quantitate the effects of cigarette smoking, no
increased death rates have been demonstrable. There is little or no
evidence that the inhalation of coal mine dust contributes to excess
morbidity or mortality in regard to lung conditions other than PMF,
such as emphysema, asthma, tuberculosis, or pneumonia. By way of
contrast, cigarette smoking has repeatedly been shown to have a
clear and easily demonstrable effect on the death rate of both miners
and nonminers. There is some recent suggestion that cigarette

303


smoking prevalence increased in British coal miners between 1965
and 1975, possibly related to their increased standard of living, but it
is too early for any discernible changes in cigarette consumption to
be reflected in mortality and morbidity statistics.

Lung Function in Coal Miners

Although there is no substantial clinical effect of an increasing
category of simple CWP on the ventilatory capacity of coal miners,
most studies in which coal miners have been compared with a
suitable reference population of nonminers have demonstrated a
significant decrement in the ventilatory capacity of the miners
(Higgins 1972). Regardless of radiographic evidence of simple CWP,
FEV, of coal miners--or any other suitable index of ventilator-y
capacity-is generally reduced in comparison with FEV, of nonmin-
ers. This suggests that decrements in FEV, and simple CWP are both
related to dust exposure, but the two measures represent separate
biologic responses in the lung to the inhalation of coal dust.

Higgins studied three populations in the United Kingdom, all of
which contained a significant proportion of miners and ex-miners,
along with a comparable reference population. The areas chosen
were Leigh, the Rhondda Fach, and Stavely (Higgins 1960; Cochrane
et al. 1961). The reduction in the ventilatory capacity of miners that
was observed could not be explained on the basis of cigarette
smoking; indeed, coal miners at that time generally smoked less
than nonminers. Since then, several other studies have found similar
results and the data have been reviewed by Higgins (1972). Possible
explanations for the observation that coal miners have a lower
ventilatory capacity and that this finding is unrelated to radiograph-
ic findings are. that (1) coal dust can produce or exacerbate
emphysema or airway narrowing and that these changes occur
independent of the changes that result in an abnormal radiograph,
or (2) the lower ventilatory capacity in miners results from either
industrial selection or differential migration. Thus, were the more
healthy miners to leave their employment and move to other parts of
the country to seek new jobs, those who remain would be less healthy
and almost certainly have lower lung function. Although the second
hypothesis is a consideration, especially during hard times when
unemployment in the coal mines is high, recent studies have shown
that it is the weaker and the less muscular man who is more likely to
leave the coal mine within the first few months of his employment
(McLintock 1971). Thus, the first hypothesis seems much more
probable and requires further consideration.

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Emphysema, Exposure to Coal Dust, and Cigarette Smoking
The pathology associated with CWP, both simple and complicated,
has been well described, and it is generally accepted that simple
CWP has a relatively specific set of histological findings (College of
American Pathologists 1979). Initially, dust starts to accumulate
around the second division of respiratory bronchioles. As this occurs,
there may be a little reticulin or, exceptionally, some collagenous
fibrosis. Subsequently, the respiratory bronchiole dilates to form a
condition known as focal emphysema. Gough (1947) and Heppleston
(1947, 1954) suggested that this condition develops as a result of
weakening and atrophy of the smooth muscle in the bronchiolar
wall. The site at which focal emphysema develops is identical to that
of the centrilobular emphysema found in cigarette smokers. Some
researchers, however, believe that the focal emphysema of coal
workers seldom extends to involve the gas-exchanging regions of the
lung, namely, the respiratory bronchioles and alveoli (Heppleston
1972). Heppleston (1972) and Gough (1968), moreover, claimed to be
able to distinguish focal emphysema from centrilobular emphysema,
and suggested that the former is characterized by an absence of
bronchiolitis in the smaller airways. Not all researchers accept these
opinions (Cockcroft, Seal et al. 1982).
Dust exposure has long been associated with increasing severity of
focal emphysema. Gough (1968) wrote that in a young coal miner
with short exposure to dust, dying of accident or of nonpulmonary
disease, there is an accumulation of coal dust specifically related to
the terminal and respiratory bronchioles. The lungs can evidently
withstand this deposition without harm for some years. Emphysema
then develops, and in miners who have been exposed for 20 years,
some degree of dilatation of the proximal order of the respiratory
bronchiole is usual and may be marked. After 40 years of dust
exposure, the majority of miners will show focal dust emphysema
(FDE), although there is a surprising range in the quantity of dust
deposited, and in the degree of emphysema, in miners working under
similar conditions. FDE refers to dilatation of the respiratory
bronchioles and there can be no doubt, because of the time sequence,
that the dust deposition precedes the emphysema. Although Gough's
remarks imply that there is a direct relationship between dust
exposure and the development of focal emphysema, until recently
his views were not entirely accepted. In a similar context, there is a
clear-cut relationship between coal dust exposure and the develop-
ment and progression of simple CWP (Jacobsen 1980).
Ryder and colleagues (1970) reported the results of a survey in
which they correlated pathological, physiological, and radiological
findings from the lungs of 247 deceased South Wales miners and ex-
miners, most of whom had been diagnosed as suffering from coal
workers' pneumoconiosis during life. The researchers were particu-


iarly ;,oncerned with the relationship of emphysema to dust exposure
and TO the radiological findings present antemortem in these
subjects. A control series of autopsies was drawn from nonmining
nlen autopsied at the same hospital and matched for age `by decade.
Whole lung sections were made and emphysema was quantified with
standard techniques. Virtually all of the mining population had been
examined by the Pneumoconiosis Panel during life, and most were
receiving benefits. Post-mortem findings of emphysema were then
related to clinical findings, ventilatory capacity measurements, and
radiological findings. Emphysema was much more common among
the disabled coal miners than among the control population of
nonminers, but it is difficult to interpret this observation, as the
miners were largely selected from among those who had respiratory
disability and the control population was not selected in anv similar
way. They also found that miners with the punctate type of opacity
were more likely to have emphysema than those with nodular or
micronodular lesions. Lung function showed no correlation to
progressive x-ray changes for simple pneumoconiosis, but declined
with increasing severity of progressive massive fibrosis. The mean
emphysema score increased with increasing age in the control
population, but not in the miners. The absence of a relationship
between emphysema score and age in the miners may be secondary
to their having been selected (even at the younger ages) because they
presented with respiratory disability. The mean emphysema score
correlated well with antemortem measurements of FEV1, but was
not greater in those miners with categories B and C of progressive
massive fibrosis than in miners with lesser degrees of radiologic
change. The absence of smoking data in this population of disabled
miners and the poor correlation of emphysema score with radiologic
change makes it difficult to ascertain the relative contributions that
cigarette smoking and coal dust exposure may have made to the
emphysema found in this population.

A later publication on the same population of disabled miners
(Lyons et al. 1972) included some smoking data. Lung function
declined with increasing severity of radiologic progressive massive
fibrosis, but actually improved with increasing severity of radiologic
simple pneumoconiosis. This dichotomy of lung function and radio-
graph may be due to the selection of the autopsy population largely
from those who had been disabled from pneumoconiosis in life, as the
certification of disability may require more severe functional abnor-
malities in the absence of radiographic abnormalities than it would
in the presence of advanced simple pneumoconiosis on the radio-
graph. They again showed a correlation of lower FEV, with
increasing emphysema score, but not with the Reid index of
bronchitis. Smokers had lower mean FEV, values than nonsmokers
and ex-smokers among miners with simple pneumoconiosis and

306


grade A PMF, but there was no difference in mean FEV, for smokers
and nonsmokers among workers with more advanced PMF. The
authors suggested that the emphysema is a more important determi-
nant of ventilatory impairment than the radiograph and that the
emphysema is due to coal dust in both simple pneumoconiosis and
progressive massive fibrosis. However, they presented no data to
evaluate the possibility that emphysematous change due to cigarette
smoking may have been responsible for the link between emphyse-
ma score and lung function and for the absence of a correlation with
the radiologic changes of pneumoconiosis.

Leigh and colleagues (1983) described the results of 886 post-
mortem examinations of Australian miners, relating years spent
underground at the coal face to bronchial gland wall ratio, the
presence and extent of emphysema in the lungs, radiographic
findings, and cigarette smoking history. Emphysema was related to
years spent underground at the coal face and to radiological evidence
of CWP. Radiological evidence of pneumoconiosis was negatively
associated with smoking. Even more surprisingly, smoking was not
correlated with gland wall ratio or emphysema. This absence of any
relationship between cigarette smoking and emphysema is unique in
the published literature and suggests a bias in the selection of
subjects who underwent post-mortem examination or in the manner
in which smoking habits were analyzed.

A relatively recent post-mortem study of coal miners and nonmin-
ers from South Wales compared the prevalence and extent of
emphysema in subjects who had died of ischemic heart disease
(Cockcroft, Berry et al. 1982). A greater percentage of smokers and
ex-smokers had emphysema (17/34) than never smokers (l/5) among
the coal miners, but there were too few cases of emphysema among
the nonminers to compare smokers and nonsmokers. Coal miners
were noted to have more emphysema than nonminers, but the
frequency of emphysema in the control population was very low.
While the degree of emphysema in these subjects was quantitated in
the absence of knowledge of the deceased subject's occupation, the
characteristic features of coal miners' lungs (i.e., the formation of
macules and the presence of pigment and the accompanying focal
emphysema) would invariably indicate the deceased subject's occupa-
tion during life. There was a legal requirement for a post-mortem
examination for coal miners. Whether the pigment present also
highlighted and accentuated the emphysema is unknown.

Ruckley and colleagues (1984) examined the lungs of 460 British
coal miners at post-mortem examination for signs of dust-related
fibrosis and emphysema. Smoking habits had been determined
previously by questionnaire. The prevalence of emphysema was 9
percent in the nonsmoking miners whose lungs showed only
circumscribed dust accumulations of which any solid center was less

307


than 1 mm in size, 33 percent in nonsmoking miners with lungs
showing one or more palpable lesions between 1 and 10 mm in size,
and 75 percent in nonsmokers with PMF. The corresponding
prevalences of emphysema among smokers with similar pathologic
findings were 52.7 percent, 70.3 percent, and 85.3 percent, respec-
tively. Ex-smokers generally had intermediate percentages. The
percentage of the population with any emphysema increased with
the increasing content of dust in the lung, but the percentage of the
population with more than one-third of the lung affected showed no
increase with increasing concentration of dust in the lung. These
data suggest that both smoking and coal dust contribute to emphyse-
ma, but that extensive emphysematous change is more closely
related to extent of cigarette smoking.

Morgan and colleagues (1971) examined lung volumes in coal
miners and showed that both cigarette smoking and increasing
simple CWP grade increased the TLC and RV, and the effects
appeared to be additive. This suggests that simple coal workers'
pneumoconiosis is associated with a slight loss of the elastic recoil.
Such an observation is best explained by the presence of so-called
focal dust emphysema (FDE).

In summary, there is little doubt that simple CWP and dust
exposure may lead to the development of focal dust emphysema. The
type of emphysema seen in coal miners is probably still best referred
to as focal dust emphysema, since there is some evidence that it does
not progress to severe centrilobular emphysema (Ruckley et al. 1984)
in the absence of cigarette smoking. Whether a morbid anatomical
distinction between the two conditions is possible is not certain.

Studies of right ventricular function in coal miners and ex-miners
both during life and at post-mortem examination (Morgan and
Seaton 1984) have shown that car pulmonale or right ventricular
hypertrophy do not occur except in cigarette smokers or in miners
who have PMF (Fernie et al. 1983).

Dust Exposure, Cigarette Smoking, and Ventilatory
Function

In a long-term prospective study of 3,581 miners who worked at
the coal face, Rogan and colleagues (1973) showed that dust exposure
was inversely related to ventilatory capacity. Lifetime cumulative
exposures to coal dust were available. The researchers were able to
demonstrate a progressive reduction in ventilatory capacity with
increasing exposure to dust. The presence of pneumoconiosis was not
associated with an additional decrement of ventilatory capacity
beyond that due to cumulative dust exposure, smoking habits, and
stature. Smokers showed a more rapid decline in FEV, than
nonsmokers, but an effect of cumulative dust exposure was apparent
in both smoking and nonsmoking miners. Among the nonsmokers,

308


FEV, was generally lower in the most dust-exposed group than in
the low exposure group, but the rate of decline per year remained
the same from age 30 to age 60 in both exposure groups. The age-
related regression coefficients were the same in the heavily and
lightly dust-exposed nonsmokers. Subjects with PMF were excluded
from the analysis. Among smokers, the rate of decline in FEV, with
age was greater than for the nonsmokers in each exposure category,
but the absolute FEV, in smokers at a given age was uniformly
lower for the group with high dust exposure than the group with low
dust exposure.

Kibelstis and colleagues (1973) were also able to demonstrate a
slight effect of dust exposure on the ventilatory capacity of their
nonsmoking miners. These investigators divided their population
according to whether the men had worked at the face, in transporta-
tion, in miscellaneous other jobs, or on the surface. Dust measure-
ments performed for these various jobs and work places had shown a
gradient, with the greatest exposure at the coal face and least on the
surface (Doyle 1970). Nevertheless, individual cumulative dust
exposure measurements were not available for the subjects. When
the nonsmoking coal face workers were compared with the non-
smoking surface workers, there was a slight but significant differ-
ence in FEV,. Thus, the coal face workers had an FEV, of 98 percent
of the predicted value; that of the surface workers was 102.4 percent.
The difference in FEV, for the smoking and the nonsmoking coal
face workers was 6 percent; the difference between the smoking
surface workers and the nonsmoking surface workers was 10.5
percent. The effects of cigarette smoking were therefore substantial-
ly larger than those of dust exposure. Among the ex-smokers and
nonsmokers, there was a significant difference in function between
coal face workers and transportation workers and their counterparts
who worked on the surface. Among the smokers, no such difference
was present, with smoking apparently overwhelming the effects of
dust. Airways obstruction was three times more common in the
smokers than in the nonsmokers.

An extensive West German study of 6,700 workers employed in
coal mines, steel works, cement works, asbestos factories, and other
heavy industry related dust exposure to smoking habits and other
factors (Deutsche Forschungsgemeinschaft 1978). Each subject un-
derwent a clinical examination, chest radiograph, and spirometry
along with measurements of airways resistance and arterial blood
gas analyses. The study showed that the most important factors
related to the prevalence of bronchitis and airways obstruction were
age and smoking habits. Among younger workers, there seemed to be
an additive effect of smoking, age, and dust, with the combined effect
of all three equaling the sum of their separate effects. Among older

309


workers, smoking appeared to play a relatively greater role in the
production of airways obstruction.

Hankinson and colleagues (1977) characterized the physiological
impairments that are associated with the inhalation of coal dust and
cigarette smoke. This study relied on flow volume curves as a method
of assessing ventilatory capacity, but in addition to the standard
spirometric measurements, lung volumes were calculated by a
radiological method using posteroanterior and lateral chest films.
Since TLC could be calculated, it was possible to express the flow
rates, not only as a percentage of vital capacity (VC) but also at
absolute lung volumes. Four age- and height-matched groups were
selected on the basis of their smoking history and on the presence of
bronchitis, that is, cough and sputum. Thus the four groups consisted
of smokers with bronchitis, smokers without bronchitis, nonsmokers
with bronchitis, and nonsmokers without bronchitis. Flow-volume
curves of the four groups are shown in Figures 1 and 2. The
differences between the four groups reveal that cigarette smoking
effects the flows at all lung volumes. In contrast, nonsmoking
bronchitics for the most part showed decreased flows at high lung
volumes, although there was some mean reduction in flows at lower
lung volumes, indicating that the small airways were not entirely
spared. When the flows were expressed at absolute lung volumes, it
became evident that smokers had an increased RV and an increased
TLC. In contrast, the nonsmoking subjects with and without
bronchitis had a normal TLC and RV. The increased TLC suggests a
loss of retractive forces in the lung and the presence of subclinical
emphysema. Bronchitis in nonsmoking subjects was not associated
with an increase in TLC.

A number of longitudinal studies have been carried out with
groups of coal miners. Love and Miller (1982) followed 1,677 men
from five British collieries for 11 years. Loss of FEV, was found to
increase with cumulative dust exposure, after allowing for age,
smoking, and colliery effect. The investigators classified smoking
according to the smoking status that was recorded in all three
surveys, that is, as nonsmokers, ex-smokers, or current smokers.
Miners who were recorded as smokers at the first survey and as ex-
smokers at the second and third surveys were designated as
intermittent smokers. According to Love and Miller (1982), the
average decrement in FEV, from the effects of dust was about one-
third of that due to smoking. They further stated that if men left the
industry because of ill health and respiratory impairment, the
average loss of FEV, would have been underestimated. This could
apply to men who retired from the workforce because of the effects of
dust, cigarette smoking, or both in combination.

There are several problems with this study. First, only 1,677
subjects were studied, 29 percent of the population of 6,191 in the

310


(n)= 428

d
G

30    40    50    60    70

Volume, percent forced wtal capacity

FIGURE l.-Mean flow volume curves expressed as
       percentage of forced vital capacity
SOYRCE Hankmson et al lYT:i

first survey. No data were provided to establish that the 1,677
survivors had similar characteristics to the original 6,191 subjects. It
is essential to know that the ventilatory capacities, age, height, and
smoking habits of the survivors did not differ from those of the
original cohort. Second, no quantification of smoking was available.
FEV, was regressed against age, regular smoking habit, and dust.
Unfortunately, smoking was treated as an unchanging variable such
as height, although Fletcher and colleagues (1976) had shown that
the effects of cigarette smoking increase with pack-years. Similarly,
Kibelstis and colleagues (1973) showed that while cough and sputum
relate well to current smoking habits, pack-years are a better
predictor of the prevalence of airways obstruction.

Attfield (1985) examined changes in ventilatory function among
smoking and nonsmoking miners in the United States. They
recorded the decline in FEV, over an ll-year period in a group of
1,072 U.S. miners. Over that time the loss in FEV, was 0.1 L more in

311


(n)=426

7 -

6t

P
8   5-
P
2
1
=   4
4
Il.

  3
2 ;
1 i

  " I

/
6       7       6       5       4       3       2       1

                 Absolute lung volume. lhS

FIGURE 2.-Mean flow volume curves expressed as
       absolute lung volumes
SOCRCE Hankrnson et al 119771.

the smoking miners than in the nonsmoking miners, in a multiple
regression model. The effect of coal dust exposure over the 11-year
period ranged from 0.036 to 0.084 L, depending on the regression
model used for the coal dust exposure.

The relative importance of cigarette smoking versus dust and
other factors in occupational lung disease has been reviewed by
Elmes (1981). He concluded that while control of occupational
exposure to coal dust remains critical, substantial future improve-
ment in respiratory health can be achieved by reducing the
prevalence of smoking among miners.

Summary and Conclusions

1. Coal dust exposure is clearly the major etiologic factor in the
production of the radiologic changes of coal workers' pneumo-
coniosis (CWP). Cigarette smoking probably increases the
prevalence of irregular opacities on the chest roentgenograms

312


of smoking coal miners, but appears to have little effect on the
prevalence of small rounded opacities or complicated CWP.
2. Increasing category of simple radiologic CWP is not associated
with increasing airflow obstruction, but increasing coal dust
exposure is associated with increasing airflow obstruction in
both smokers and nonsmokers.

3. Since the introduction of more effective controls to reduce the
levels of coal dust exposure at the worksite, cigarette smoking
has become the more significant contributor to reported cases
of disabling airflow obstruction among coal miners.
4. Cigarette smoking and coal dust exposure appear to have an
independent and additive effect on the prevalence of chronic
cough and phlegm.

5. Increasing coal dust exposure is associated with a form of
emphysema known as focal dust emphysema, but there is no
definite evidence that extensive centrilobular emphysema
occurs in the absence of cigarette smoking.

6. The majority of studies have shown that coal dust exposure is
not associated with an increased risk for lung cancer.

7. Reduction in the levels of coal dust exposure is the only method
available to reduce the prevalence of simple or complicated
CWP. However, the prevalence of ventilatory disabilities in
coal miners could be substantially reduced by reducing the
prevalence of cigarette smoking, and efforts aimed at reducing
ventilatory disability should include efforts to enhance success-
ful smoking cessation.

313


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ASHFORD, J.R., MORGAN, D.C., RAE, S., SOWDEN, R.R. Respiratory symptoms in
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318


CHAPTER 8

SILICA-EXPOSED WORKERS


CONTENTS

Silica Exposure

Population at Risk

Smoking Behavior of Silica-Exposed Workers

Definitions of Health Effects

Epidemiological Findings

Pathogenesis of Silica-Related Health Effects

Silica Exposure and Cancer
Epidemiologic Studies of Smoking, Silica Exposure,
   Silicosis, and Cancer
    Silica-Exposed Cohort Studies
     Metal Ore Mining
      Steel Industry
     Workplaces With Exposure to Silica Only
    Followup of Silicotics

Research Recommendations

Summary and Conclusions


References

321


Silica Exposure

The oxides of silicon (SiO,) are found in a number of polymorphic
structures consisting of three-dimensional networks of silica tetrahe-
dra (Zoltai and Stout 1984). When SiO, is bound with cations, it is
considered to be "combined" silica. When not combined, it exists in
its "free" forms-polymorphic crystalline, cryptocrystalline (minute
crystals), and amorphous (noncrystalline) (Parkes 1982). Whether
SiO, is in a free form is important from the standpoint of
occupational toxicity. The crystalline phases of SiOz, including
quartz, tridymite, and cristobalite, are recognized as causative
agents in silicosis. Diatomite tends to form amorphous silica, and
crystalline lenses are found in diatomaceous earth deposits. Diatom-
ite is converted to the biologically active cristobalite with calcining
at temperatures from 1000" C to 1723" C (Parkes 1982).

Occupational exposures to free silica are diverse. Major industries
with recognized significant silica exposures include metal mining,
coal mining, and nonmetallic mineral extraction, stone, clay, and
glass processing, iron and steel foundries, and nonferrous foundries.
A more complete listing of occupations with potential exposure to
silica is found in Table 1. Some of these exposures, including silica
flour production and use, sandblasting and certain mining, quarry-
ing and tunneling operations, result in exposure predominantly to
silica. However, many silica exposures, including most mining
operations and foundry exposures, are mixed-dust exposures, which
has implications for the type and extent of biological response seen
among exposed workers.

A general pattern of noncompliance with the current permissible
exposure limit (PEL) for free silica has been documented in recent
papers appearing in the American medical literature. These reports
have included the Occupational Safety and Health Administration
(OSHA) compliance data for 205 foundries in which 40.6 percent of
samples exceeded the PEL (Oudiz et al. 1983); OSHA data showing a
53 percent rate of noncompliance with the silica PEL in 27 silica
flour mills (Banks, Morring, Boehlecke 1981; Banks, Morring,
Boehlecke et al. 1981); and gross excesses (greater than hundredfold)
of the silica standard in sandblasting operations, which remain a
poorly regulated industrial process in the United States but are
banned in several other developed countries (Samimi et al. 1974).

Population at Risk

Estimates of the population at risk for potential silica exposure are
available from the National Institute for Occupational Safety and
Health (NIOSH) National Occupational Hazard Survey, which was
based on a probability sample of 5,000 industries between 1972 and
1974 (NIOSH 1978). From these survey results, NIOSH estimated


TABLE l.-Occupations with potential exposure to silica

Abrasive blasters
Abrasive makers
Auu, garage workers
Bisque-kiln workers
Brick layers
Buffers
Burhstone workers
Carborundum makers
Casting cleaners (foundry)
Cement makers
Cement mixers
Ceramic workers
Chemical glass makers
Chippers
Coal miners
Construct workers
Cosmetic makers
Cutlery makers
Diatomaceous earth calciners
Electronic equipment makers
Enamellers
Fertilizer makers
Flint workers
Foundry workers
Furnace liners
Fused quartz workers
class makers
Glaze mixers (pottery)
Granite cutters
Granite workers
Grinding wheel makers
Grindstone workers
Hard rock miners
Insecticide makers
Insulators
Jewelers
Jute workers
Kiln liners
Masons
Metal buffers
Metal burnishers
Metal polishers
Miners
Mortar mixers
Mortarmen

Oil purifiers
Oilstone workers
Optical equipment makers
Paint mixers
Polishing soap makers
Porcelain workers
Pottery workers
Pouncers (felt hat)
Pulpstone workers
Quarry workers
Quartz workers
Refractory makers
Road constructors
Rock crushers
Rock cutters
Rock drillers
Rock grinders
Rock screeners
Rubber compound mixers
Sand cutters
Sand pulverizers
Sand blasters
Sandpaper makers
Sandstone grinders
Sawyers
Scouring soap workers
Silica brick workers
Silicon alloy makers
Silver polishers
Slate workers
Smelters
Sodium silicate makers
Spacecraft workers
Stone bedrubbers
Stone cutters
Stone planners
Street sweepers
Subway construction workers
Tile makers
Toothpaste makers
Tube mill liners
Tumbline barrel workers
Tunnel construction workers
Whetstone workers
Wood tiller workers

SOCRCE Aspen Systems 119781

that 3,200,OOO active workers in 238,000 plants were potentially
exposed to silica; however, this estimate was based on workers in an
area where free silica is used, and the number of workers with
clinically significant exposures would be appreciably lower. This
estimate excluded former workers who were retired, working
elsewhere, or disabled and the large industrial sector of agriculture
where some silica dust exposure occurs (Popendorf et al. 1982).

324


Significant physical factors for occupational respiratory disease
risk include the percentage of free silica, the respirable fraction of
the mineral dust (which may have a higher silica content (Ayer et al.
197311, and the concentration of dust (total and respirable) in the
worker's breathing zone. In addition, other workplace contaminants
may combine with silica particles to alter the toxicity of the given
mineral dust exposure. Individual factors such as pulmonary deposi-
tion and clearance, atopic status, genetic constitution, and immune
response may also be important risk factors in silica-related disease;
however, they are sometimes difficult to measure and have been less
well studied. Hence, studies of workers exposed to silica must
provide clear documentation of the exposures in the workplace as
well as documentation of other personal and environmental factors
that may influence biological response.

Smoking Behavior of Silica-Exposed Workers

The smoking behavior of workers in a variety of settings where
silica exposure can occur is detailed in Table 2. These studies in the
United States and abroad indicate that a very large proportion of
people who are exposed to silica are also smokers.

Definitions of Health Effects

Several health effects are associated with occupational exposure to
silica dust. The causal role silica plays in some disease responses,
namely silicosis and silica-induced alveolar lipoproteinosis ("acute
silicosis"), is quite clear and widely accepted. Silica is recognized as
playing an important causal contributing role in a second group of
pulmonary responses-silicotuberculosis, mixed-dust fibrosis (usual-
ly mixed with iron oxides), and the fibrosing alveolitis arising from
exposure to calcined diatomaceous earth (diatomite pneumoconiosis)
(Parkes 1982). Smoking appears to play no significant causal role in
the etiology of the first two categories of silica-induced diseases. In a
third group of health effects, silica dust appears to be a risk factor in
simple chronic bronchitis as characterized by mucus hypersecretion
and in chronic airways obstruction, which is often associated with a
progressive decline in expiratory flow rates and is largely irrevers-
ible. This last group of pulmonary responses is nonspecific, recog-
nized to be multifactorial and causally linked to cigarette smoking. A
causal relationship between silica dust and chronic bronchitis or
chronic airways obstruction is less clear. This issue is of considerable
importance because of the prevalence of chronic bronchitis and
chronic airways obstruction in modern society and the large size of
the population at potential risk of silica exposure.


E  TABLE 2.-Smoking characteristics of silicaexposed workers


                 Number and type
   Study              of population                   Smoking characteristics (percent)                      Comments

Prow          240 gold miners.
(1970)           South Africa


Brinkman et al.     301 automotive industry
(1972)         workers. aged 40-65

SluisCremer       Men expmed to dust,
(1972)          Carletonville. South Africa

Theriault et al.
(3 papers)
(1974)

792 granite workers. Vermont

  Armstrong et al.     Coal and gold miners,
   (1979)           Australia
.

Born et al.
(1963)

Trona miners. Wyoming

Light (I-200)'
Moderate (2Olm)
Heavy (>6CO)

Exposed workers
Nonexpcmed workers

SM
65.8
11
22.3
32.5


70
60.7


SM
60.4

SM           EX'           NS        `Not smoked in
57           30            12         last 6 months

Gold miners

SM
66.3


42.6

NS/EX
34.2

' Numerical rating
of cigs/day x years
smoked

30
39.3

EX           NS
25.6           13.9

NSIEX
33.7

33.6           23.6

NOTJZ.: S.M=Smoker; EX=Ehsmoker; NS=Nonsmoker.


Epidemiological Findings

Early observers of occupational diseases, including Ramazzini in
1713 (1964), wrote about the respiratory problems of miners and
stone cutters, and recognized silicosis among miners, stone cutters or
hewers, and potters. Silicosis, and its previously described associated
health effects, have been given a variety of names that reflect the
several faces of silica exposur&ust consumption, ganister disease,
grinders' asthma, grinders' consumption, grinders' rot, grit consump-
tion, masons' disease, miners' asthma, miners' phthisis, potters' rot,
rock tuberculosis, stonehewers' phthisis, and stonemasons' disease
(Hunter 1955). Greenhow (18781, in his treatise on bronchitis,
recognized that "irritants which act immediately upon the bronchial
membrane may produce inflammation by means of either mechani-
cal or chemical irritation. Fine coal and metal dust, stone and
porcelain grit, and even the flue of cotton wool . inhaled into the
lungs during various industrial processes are all of them mechanical
irritants which become fruitful causes of bronchitis in certain classes
of operatives" (p. 30).

Mortality studies of silica-exposed cohorts have consistently shown
increased mortality rates for tuberculosis and nonmalignant respira-
tory disease, largely accounted for by silicosis (Guralnick 1962;
Registrar General 1958, 1978; Davis et al. 1983; Armstrong et al.
1979; McDonald et al. 1978; Fox et al. 1981). Although none of these
studies accounted for the effects of smoking, the consistency and
magnitude of the increased rates suggest a causal relationship
between silica exposure and these cause-specific mortality rates.
Davis and colleagues (1983) demonstrated dose-response relation-
ships between exposure category, tuberculosis, and silicosis, but
found no excess mortality from bronchitis and pneumonia. Finkel-
stein and colleagues (1982) investigated mortality among 1,190
Ontario miners receiving compensation awards for silicosis and
found nonmalignant respiratory disease (excluding tuberculosis) to
be the most frequent cause of death (standard mortality rate, 765).

NIOSH recently assessed causes of disability among employees of
the mining industry, based on the Social Security Disability Benefit
Awards and Allowances to Workers for 1969-1973 and 1975-1976
(Osborne and Fischbach 1985). The observed proportional morbidity
rate (PMR) for pneumoconiosis from silica and silicates (they were
not distinguished) was found to be somewhat higher (4,894) than for
other mining occupations. Workers employed in boring, drilling, and
cutting jobs appeared to experience increased disability from respira-
tory diseases, specifically pneumoconiosis including silicosis. These
findings, based on somewhat more recent exposures than the
previously cited mortality studies, confirm the major mortality
findings, but suffer from the same methodological problems. Again,
smoking data were not available or analyzed, and it is recognized

327


that those disabled in the mid-1970s very likely were exposed to
silica three or four decades previously; therefore, their disabilities
reflected previous dust exposures.

Early morbidity studies of workers exposed to silica dust focused
on rates of sickness, respiratory symptoms, and physical findings,
supplemented in the 1920s with chest radiography. The U.S. Public
Health Service (US PHS) conducted the first major U.S. silicosis
study of the hard-rock mining industry in 1913-1915 (Higgins et al.
1917; Lanza and Higgins 1915). Their studies reported that 60.4
percent of the 720 miners examined suffered from pulmonary
diseases attributable to mine rock-dust exposure. Dust samples
collected with a Draeger liter bag-granulated sugar filter apparatus
were reported to average from 30 to 50 mg/m3 (Higgins et al. 1917).
Although these concentrations would appear to be quite high, they
are difficult to interpret according to modern-day respirable dust
sampling and analysis (x-ray diffraction for free silica content).

Subsequent US PHS silica studies included Harrington and
Lanza's (1921) 1916-1919 study of copper miners in Butte, Montana,
in which 42.4 percent were judged to have some dust-induced lung
injury and 25.5 percent to have advanced disease. Dreessen and
colleagues (1942) studied 727 metal miners in 1939, and Flinn and
colleagues (1963) studied 67 underground mines employing 20,500
miners from 1958 to 1961, but found varying silicosis prevalence
from mine to mine and widely divergent exposures to free silica. The
silicosis prevalences of 9.1 percent and 3.4 percent, respectively,
were found to be associated with longer duration of exposure and
especially with face work exposures (Dreessen et al. 1942; Flinn et al.
1963). Earlier, Flinn and colleagues (1939) had reported an impor-
tant study (19361937) of West Virginia potteries that included 2,516
workers with an overall silicosis prevalence of 7.8 percent. Free silica
content ranged from 1 to 39 percent, dust concentrations varied from
3 to 440 million particles per cubic foot (mppcfl, and mean particle
diameters were judged to be 1.2 pm (but without data on the
concentration of respirable dust). A strong dose-response relation-
ship between dust concentration, duration of pottery exposure, and
silicosis prevalence was documented. It was suggested that no new
cases of silicosis would occur if dust concentrations in this industry
were brought below 4 mppcf. Renes and colleagues (1950) studied 18
ferrous foundries in 1948-1949, and found 9.2 percent of 1,937
foundrymen to have pulmonary fibrosis. Free silica content averaged
30 percent, with a mean particle size of 3 pm, and 82 percent of the
samples had levels below 6.9 mppcf. Mechanical shakeout operations
were found to have the highest dust concentrations (10 to 75 mppcfl,
and silicosis was noted to be more prevalent among foundrymen with
20 or more years of exposure. It was suggested that conditions had
improved in foundries and that most of the pulmonary fibrosis was

328


due to previous exposures. Early studies of the refractory (silica)
brick industry documented high percentages of free silica, often in
the form of cristobalite and tridymite from burned bricks. Keatinge
and Potter (1949) and Fulton and colleagues (1941) studied 1,035
exposed workers in this industry, finding 52 percent to have some
stage of silicosis. A relationship with dust concentration and
duration of exposure was again documented, as was an apparent
increased risk among men exposed to burned brick dust (Keatinge
and Potter 1949; Fulton et al. 1941).

Epidemiological studies of workers in the Vermont granite indus-
try have provided an important and interesting chronology of data
on the natural history of silica-associated respiratory diseases. Early
US PHS studies of this industry (Russell et al. 1929) documented
high dust concentrations (37 to 59 mppcf) and a very high prevalence
of silicosis. On the basis of dust with a free silica content of 35
percent, a presumptive "safe limit" of dustiness was suggested to lie
between 9 and 20 mppcf. A subsequent US PHS study (Russell 1941)
essentially confirmed the findings of the original study, noted an
increased progression of silicosis among the highly exposed cutters,
and concluded that a limit below 10 mppcf for this industry would be
desirable. Subsequent followup studies in 1955 by the US PHS and
the Vermont State Board of Health (Hosey et al. 1957) found that the
prevalence of silicosis had decreased from 45 percent in 1937-1938 to
15 percent in 1956, that the silica content of the dust averaged a
somewhat lower 22 to 25 percent free silica, and that nearly all
workers with silicosis had been exposed prior to implementation of
dust controls in 1937. This report was consistent with an earlier
report by Ashe (19551, and was subsequently supported by a further
followup study by Ashe and Bergstrom (19651, which reported no
cases of silicosis among 1,478 granite workers employed after 1937,
and a study by Davis and colleagues (1983) that reported only one
case in the same population.

All of these early studies of silica exposure concentrated on
radiographic evidence of silicosis and tuberculosis and the associa-
tion with silica content and concentration. These studies formed the
basis for environmental control of silica exposures, demonstrated the
effectiveness of dust control, and provided a widely held impression
that silica exposures, and hence disease arising from silica expo-
sures, were well controlled.

Beginning in the 195Os, British epidemiologists introduced stand-
ardized respiratory questionnaires, field spirometry, and sound
epidemiological methodology to the study of bronchitis and chronic
obstructive lung disease, and were the first to use these methods to
assess respiratory effects among industrial workers. This allowed
assessment of other risk factors, including cigarette smokmg, and
quantitation of major risk factors compared with appropriate

                                             329
157-5L.4 3 - 66 - 1,'


reference populations. At the same time, on the basis of clinical case
series, it was becoming clear that bronchitis and nonspecific airways
obstruction were more common than pneumoconiosis among work-
ers exposed to coal mine dust and silica dust. The significance of
these health effects was not clear. Modern epidemiological studies
began with the Higgins and colleagues (1959) investigation of
Stavely, an English industrial town of 18,000 and home to a
significant number of coal miners and foundry workers. This study
and other cross-sectional studies of silica exposure that have assessed
standardized respiratory symptoms, lung function, smoking, and
occupation (only those with non-coal-mining silica exposures) are
summarized in Table 3.

Review of these studies has found them to be heterogeneous in
regard to workforce composition, free silica content and dust
concentration (if reported), and other associated occupational expo-
sures that may contribute to respiratory symptoms and declines in
lung function. In some instances associated occupational exposures
other than silica dust appear to be as important or more important
than silica dust (Higgins et al. 1959; Gamble et al. 1979; Manfreda et
al. 1982; Graham et al. 1984). Two of these studies found lung
function to be somewhat better among exposed workers than among
reference subjects (Clark et al. 1980; Graham et al. 1984). However,
in both of these studies, one of potash miners and one of taconite
miners, it is very likely that the free silica exposure, although not
documented, was low. One study of fluorspar miners (Parsons et al.
1964) and one of copper miners (Federspiel et al. 1980) suggest a
significant dust effect on bronchitis prevalence and a somewhat
lower lung function among exposed miners. Specific environmental
data on free silica content or dust concentration were not provided in
either study, although most likely some of the dust exposure in these
mines was silica.

Four of the studies reviewed in Table 3 have documented
significant exposures to free silica with the relative absence of other
exposures: the Welsh slate workers study (Glover et al. 19801, the
Vermont granite workers study (Theriault, Burgess et al. 1974;
Theriault, Peters, Fine 1974; Theriault, Peters, Johnson 1974) and
two studies of South African gold miners (Sluis-Cremer et al. 1967;
Wiles and Faure 1977). Silicosis was reported in all four study
populations, ranging from 5 to 33 percent. Sluis-Cremer and
colleagues (1967) surveyed the prevalence of chronic bronchitis in a
mixed mining and nonmining population in Carletonville on the
Witwatersrand, South Africa. Chronic bronchitis was more common
among miners who smoked than among nonminers who smoked, but
there were no significant differences in prevalence of bronchitis
between miners and nonminers who did not smoke. The prevalence
of bronchitis was substantially higher among smokers than among

330


Study,
country

Number and     Age
type of     (mean or
population     range)

Bronchitis (ratio)


S/NS   Exp/Not

       Lung function              P"eum*
                               conic&
S    NS     A     EXP    Not A    (percent)         Comment

Higgine et
al. (1959),
United
Kingdom

Current and ex-   55 to
foundry workera; 64
105 exposed, 81
nondusty
occupations

Not
available
for
foundry
workera
alone

1.2

Not available for foundry   82.1 90    -7.9      14.0   Foundry workera both "pure"
workers alone                          with free silica exposure and
               (Indirect MBC based on          "mixed" with chemical fumes
               FEVd                (HCI. H,SQ, caustic soda,
                                 and benzol) and other dusts;
                               increased respiratory
                               symptoms and decreased lung
                                function mainly in "mixed"
                               foundry workers suggests
                                other dusts and fumes likely
                                more important than "pure"
                                foundry work

Parsons et
al. (1964),
Canada

Fluorspar
mining; 301
ev-4 5%
co"trola

,383
(20 to
70)

Not
available

5.5

Generally higher for nonminers; decreased lung
function in chronic bronchitic me" appeara more
important than dust eategory @a.& on indlrect
MBC, MMF, PFR)

1.93

No specific SiO, expasurea or
dust measurements available;
exposure determined from job
category and tenure

    Sluis     Cold mining;     35 and     1.8      1.22                 Not studied                 5    Free silica content range 5&
    Cremer et   582 expceed, 285   older                                               70%, but generally low dust
   al. (19871,   community                                                       levels; smoking somewhat
    South      controls                                                           more common among miners;
    Africa                                                                 significant increase in chronic
                                                                      bronchitis prevalence among
                                                                      smoking and ex-smoking but
                                                                      not nonsmoking miners
                                                                      suggests possible interaction
                                                                      between smoking and
E                                                                   "underground aerial
w                                                                           pollution"


TABLE 3.-Continued


          Number and    Age     Bronchiti 3 (ratio)              Lung function              Pneume
Study,       type or     (mean or ---                                            coniosie
country      population     range)    SINS   l&p/Not     S    NS     h     EXP    Not h    (percent)         Comment


Higgins et   60 foundry      25 to    Not      Not     Not reported separately     3.49    3.55   -.c6     23.1    No environmental
al. w66),   workers, 100     34     reported   reported   for foundrymen                         measurements, but typical
United     "nondusty"                                                       SiO, foundry exposures; 9-
Kingdom    workers                                                       year followup mortality
                                                                higher among foundry
       43 foundry      55 to                                     2.27    2.36   -39          workers than others,
       workers, 52      64'                                              appreciably higher among
      "nondusty"                                         (FEV7S%)             foundry workers with silicwis
        workers

Theriault   792 granite        44    Not      Not        4.2    4.1    + IO     4.2    4.1   +.10     31    Single "A" radiograph reader;
L al. (3     workers           =pod   repoti                                   dow+response relationship
PapeM                                  (FVC)                             between FVC and granite
(1974).      189 marble        41                                             duet and quartz dust; 2 mL
United     workers                                                       FVClduetyear decline, 9 mL
States                                                              F'VC/smoking-year decline

Wilea and   2,209 gold       4.5ta      2.3      5.3      2.53    3.77    -1.24    3.60    3.64   -.24     6.7    7@-250 particles/cm' dust
Fare      miners with      54
(1977).                                                              counts; 75% free BO,;
       2 10 years'                  (low duet       (MMEF)            flow duet           significant dust
South      service                                                      YS.             exposure/chronic bronchitis
Africa             highYsbust                    high dust           doee-reeponee relationship in
                            C&gOries)                    C&gOrieS)           all smoking categories; much
                                                                stronger smoking effect on
                                                                lung function, but no dase-
                                                       response &lationehip


TABLE 3.-Continued


         Number and     Age     Bronchitis (ratio)             Lung function              Pneume
Study,       type of     (mean or                                               -   conk&
country      population     range)     SINS   Exp/Not     S     NS    A     EXP    Not A    (percent)         Comment



Gamble et    121 talc miners     39.7      3.5      1.2      3.74    4.13    -.39     3.66    3.64   -.14     2.2    2040 w/m' free silica; 0.2%
al. (1979),                                                             talc,   2.96 mg/m' respirable dust;
United     1,077 potash       39.2                     (FEV,)                          .I07   anthophyllite, tremolite, and
States      miners                                                    potash   crysotile asbestos fibers found;
       (reference group)                                                 17/24 jobs ;,2f/cc; decrea..
                                                                lung function and pleural
                                                                thickening significantly
                                                                           aesaciated

Clark et     240 iron ore       49.3    None       1.0     c478.5    61.4    -2.9    861.4   80.0   t1.4     c2    Taconite has iron. quartz.
al. (198X,   miners. 220            among                                            and numerous silicates, esp.
United     yE2X-S              nonsmoking           mv,/Fvc)                        grunerite-cummingtonite; 25-
States     underground            miner8                                          40% total dust quartz;
                      repxted                                       significant smoking effect, no
       86 not exposed     50.1                                                dust effect on lung function
-
Federspiel    133 surface      Not       98.4   None       GM.5 92.5    -7.0    492.5   98.0   -5.5    Not     No dust level or SiO,% data;
et al.      workers       given           among                               reported   no SO, miner exposure. little
(196OJ                          nonsmoking    FEV,)                            or no surface worker SO,
United     112 copper                    nonminers                                  exposure; mining and
States      miners                                                       smoking additive effect on
                                                                bronchitis; signiticantly
                                                                   reduced nonsmoking miner
                                                                   FEV, and FVC and smoking
                                                                           miner FVC


i%   TABLE 3.-Continued

6

             Number and    Age     Bronchitis (ratio)             Lung function              Pneumw
   Study,       type of     (mean or                                                conioaia
    country      population    range)     SINS   Exp/Not     S    NS A     Exp Not A   (percent)         Comment

Glover et
al. (19801,
United
Kingdom

725 slate
workers

530 nonexposed

1.8      4.4

3.06 3.23


mv,1

-.17

3.23

3.53

-30

33

13-325 reepirable quartz in
reapirable dust; no smoking
category/radiographic opacity
association; no dust
concentrations available, but
thought "high"; respiratory
symptoms dependent on
pneumonconiceie category per
multiple regression, except
nonsmokers with previous TB
(in 4&50% of slate workew
age >w

Manfreda
et al.
(1982).
Canada

241 hardrock     25to      9.0      9.5      23     7    +16    0     7     -7      <l   Zinc, copper, nickel mining
miners         54                                             study; 69% silica in dust,
                       (Prevalence of FEY, abnormalities baaed on 95th          20-25% >TLV; some
382 nonexposed                 percentile of nonsmoking general population)           underground worker (95) NO,
men (community                                              exposure, some smelter
sample)                                                     worker (107) SO, exposure
                                                         (10% >TLV); low sulfm?
                                                           worker (39) duet exposure;
                                                    nonsmoking miner bronchitis
                                                    significantly increased;
                                                    significantly reduced lung
                                                           function in smelter workers,
                                                      not miners; probable selection
                                                        processes noted

NOTE: Bronchitin rat& and lung function comparisons are of nonexpwed smokers 6) and nonsmokers (NS) to 888e88 smoking effect and of nonamokiing exposed workers (Exp) and nonexpoeed
worken, (Not) to BBBBBB exposure effezt. Combined smoking and exposure et&& are not shown, but are add- under omxnent.


nonsmokers in both the dust-exposed and the nonexposed popula-
tions. Evaluation of Vermont granite shed workers (Theriault,
Burgess et al. 1974; Theriault, Peters, Fine 1974; Theriault, Peters,
Johnson 1974) revealed that both smoking and cumulative dust
exposure contributed to the differences in FVC and FEV, among
these workers, but the effect of smoking was larger than the effect of
dust exposure, using a multiple regression technique. A dose-re-
sponse relationship between silica dust exposure and decreased lung
function was demonstrated in both the Vermont granite shed
workers and the South African gold miners (Wiles and Faure 1977).
Glover and colleagues (1980) examined 725 workers and former
workers from the slate mines and quarries of North Wales and 530
men from the same area who had never been exposed. The
prevalence of chronic cough ranged from 5.2 percent in the nonsmok-
ers not exposed to dust to 19.4 percent in the nonsmokers with dust
exposure. Smokers with no exposure to dust had a prevalence of
cough of 27.5 percent; the prevalence was 38.9 percent among the
smokers with dust exposure. FEV, (standardized to a fixed height)
was lower in the smokers than in the nonsmokers. The dust-exposed
nonsmoking workers had a lower mean FEV,, but the values for the
dust-exposed and the nonexposed smokers were similar. The regres-
sion coefficients for FEV, with age were 20 mL per year in the
nonexposed nonsmokers and 38 mL per year in the dust-exposed
nonsmokers, but the coefficients for smokers were similar between
the dust-exposed (40 ml/year) and nonexposed (46 ml/year) men.
The absence of an effect of dust exposure among the smokers in some
of these studies may be the result of the cessation of smoking by
those workers with declining lung function, as suggested by the
observation that the mean FEV, and regression coefficient for
decline in FEV, with age among slate workers was worse in ex-
smokers than in either current smokers or nonsmokers. In contrast,
the values for ex-smokers in the general population were between
those for smokers and those for nonsmokers.

Only a few prospective studies of silica-exposed workers have been
reported in the literature. Four of these studies are summarized in
Table 4 (Higgins et al. 1968; Pham et al. 1979; Kauffmann et al. 1982;
Manfreda et al. 1984). Two other prospective studies of silicaexposed
workers are not included in this table because of methodological
questions. Brinkman and colleagues (1972) followed a group of
foundry workers with silica exposure and with silicosis over an ll-
year period. Only a third of the men known not to have died in that
interval were restudied, however, raising questions about the
validity of the finding of no apparent difference between the silica-
exposed workers and the unexposed workers in decline in lung
function over time. The original cross-sectional study found poorer
lung function among silica-exposed workers and silicotics. Musk and

335


colleagues (1977) conducted a 4-year followup study of Vermont
granite workers and reported a substantially higher annual loss in
lung function than predicted from previous cross-sectional studies of
this population. However, reassessment of some of these data has
raised questions about the adequacy of the pulmonary function
testing (Graham et al. 1981). Reana!ysis of the population revealed
that Vermont granite workers had an annual decline in FEV, of 44
mL per year and those who had left the industry had a decline of 72
mL per year (Eisen et al. 1983). The smoking habits of those who
continued working (20 pack-years) and those who had left the
industry (27 pack-years) were similar. There was no statistically
significant relationship between lifetime dust exposure and decline
in FEV, for either the workers who were still working or those who
had left the industry.

One of the four studies reviewed in Table 4 found no increased
decline in lung function over time among silica-exposed workers
(Higgins et al. 1968). On followup, however, the mortality rate
among the foundrymen in the original study (Table 3) was appreci-
ably higher, particularly among those with silicosis and among older
workers. Smoking habits were recorded in this study, and the
foundry workers who smoked had lower mean FEV, values than the
nonsmoking foundry workers in both the 25 to 34 and the 55 to 64
age groups. Pham and colleagues (1979) found consistently increased
declines with age in all measures of lung function studied (FEV,,
FVC/FEV,, RV/TLC, and fractional uptake of CO) among silica-
exposed steel workers compared with unexposed workers. Results for
smoking and nonsmoking workers were not reported separately.
Lung function of the exposed men in the original survey was
somewhat higher than in the unexposed workers (although they had
much more bronchitis), suggesting that selection processes (healthy
worker effect) occurred in this study. Kauffmann and colleagues
(1979, 1982) also found increased declines in smoking-adjusted lung
function over time among workers exposed to mineral dust (especial-
ly silica), and argued that the mineral dust and silica exposures were
most likely to be causal. Their findings are consistent with this
conclusion, but exposures were assessed by type of job, and informa-
tion on silica dose or interval progression over the 12 years of study
is lacking. Manfreda and colleagues (1984), in a 5-year followup
study of hard-rock miners and smelter workers, reported significant
declines in FEV,/FVC for both smoking and mining industry
exposure. These effects were quantitatively similar, but may reflect
more of a smelter effect than a mining (silica dust) effect, as that was
the finding on their original cross-sectional study. The prospective
study abstract does not address this question.

336


TABLE 4.-Prospective studies of workers occupationally exposed to silica

Study,
country

Number and       Age
type of        (mean or
population        range)

    Annual decline in lung function


s    NS     A     EXP   Not     A                  Comments

Higgins et
al. (19661.
United
Kingdom

60 foundry workers,
100 "nondusty"
workers

43 foundry workers,
100 "nondusty"
workers

25-34





5574

(Ages in
1957)

36' 21    -17       29   30 -1      Somewhat higher increased annual lung function
                          decline in older men, not strongly associated with
                          occupation, but strongly influenced by smoking


32' 54    -22      37 34 +3      ' Heavy smokers only

   (FEV 76)

Pham et
al. 119791,
France

196 steel (foundry
and roll sheet)
workers


166 unexposed
workers

49.5





49.6

(Ages at
first
exam)

7.4% 0.6%   -6.6%    At baseline, bronchitis prevalence significantly
               higher in steel vs. unexposed workers (37.8 vs.
               17.51, lung function somewhat higher in steel
              workers; over Byear followup. somewhat more
  (%FEV          increased steel worker bronchitis prevalence
predicted)         (45.3121.9); more steelworker than unexposed
               worker all-parameter lung function consistent
Matched for age,         decline; no silica content or dust concentration
height, smoking          environmental data
   status


TABLE 4.-Continued



            Number and       Age          Annual decline in lung function
Study,         type of        (mean or
country        population       range)       S    NS     A     Exp   Not     A                  Comments



Kauffmann     178 mineral dust         41      No smokingspecific lung      52 42    -10     la-year followup study of 11 factories, including
et al.       expmd workers (55            function decline given                  several mineral dust exposures, of which only
ww,      expoeed to silica)       (41) o                       (57)   (42)   C-15)    silica is separable; no silica monitoring data;
France                                                 significant FEV, annual adjusted declines in
        177 unexpceed          41                       CFEV,)         mineral dust exposed workers (esp. silica exposed)
          workers                                           interpreted a~ work related and consistent with
                                                   Annual declines       silicaexposed worker original crw-aectional
                                          adjusted for         decreased lung function assessment
                                          smoking statue
                                                    and amount        `Numbers in parentheses, of 55 silica-expceed
                                                       workers only

Manfreda      179 hard rock         2544       3.4% 2.0%  -1.4%     3.1%    1.6%   -1.5%    (See Table 2 for crowsectional results)
et al.       miners, 254                                         Cough and phlegm prevalence greater among
(19&o.      unexpcwd                 (Percentage decrease in   (Percentage decrease in    miners at baseline, no change over time; adjusted
Canada      (community sample)           FJW,/FVC, over 5 years,   FEV,/FVC, over 5 years,   FEV, and FJW,/FVC declines significant for
                           adjusted for age and    adjusted for age, height,    smoking and FEV,/FVC decline significant for
                                  height)          and smoking)      mining expoeure; data suggest FEV,/FVC more
                                                       sensitive indicator; data con.&.ent with mining
                                                     and smelter exposure and smoking additive effect

NCFlW S=Smoker; NS=Nonemoker; Exp=Expaeed; Not=Not exposed.


Pathogenesis of Silica-Related Health Effects

The characteristic pathology of the various forms of silicosis are
well described in recent texts dealing with occupational respiratory
diseases (Parkes 1982; Kleinerman and Merchant 1983). The mature
lesion of silicosis is the hyalinized nodule that is spherical and
typically varies in size from 3 to 12 mm. The nodules are more
commonly found in upper lobes, but are found throughout the lung
and are frequently subpleural. Microscopically, the nodules have a
whorled appearance composed of lamina of acellular hyalin. The
borders of the lesions are typically serpiginous and are composed of
pigment (especially if associated with a coal exposure), chronic
inflammatory cells (mainly lymphocytes and plasmacytes), and
connective tissue extending into the surrounding lung parenchyma.
With phase microscopy, doubly refractile silica particles 1 to 5 urn in
size may be observed within the lesions and within macrophages in
the surrounding infiltrate.

Acute silicosis, or acute silicoproteinosis, differs from classical
nodular silicosis in that the principal finding is alveolar proteinosis
associated with a diffuse interstitial reaction. Scanning electron
microscopy and x-ray microanalysis have demonstrated small bire-
fringent silica and silicate particles (less than 1 urn in diameter) in
these processes (Abraham 1978,1984).

Progressive massive fibrosis may develop on a background of
silicosis through the enlargement and sometimes the coalescence of
the nodular lesions of silicosis into conglomerate silicosis. These
lesions form most commonly in the apical or middle portion of the
upper lobes and are frequently complicated by tuberculosis. Cavita-
tion of these lesions may occur with or without tuberculous infection
(Kleinerman and Merchant 1983).

The mechanisms that produce silicosis, and particularly conglom-
erate silicosis, are still not fully understood. The cellular events
leading to lung injury appear to arise from the cytotoxicity of the
respirable silica particle for a principal lung defender, the alveolar
macrophage. Upon phagocytosis of the silica particle, cell death is
caused by the release of proteolytic and hydrolytic enzymes into
macrophage cytoplasm. The release of these cytoplasmic constitu-
ents, including the still biologically active silica particle and
fibroblast stimulating factor, may then lead to fibrosis (Allison et al.
1966,1977).
As has been noted with other types of pneumoconiosis, silicosis
(and particularly conglomerate silicosis) is associated with a high
prevalence of circulating autoantibodies (ANA and RF) (Jones et al.
1976; Turner-Warwick et al. 1977). Although silica exposure and
particularly silicosis may be associated with rheumatoid arthritis
and several other collagen-vascular diseases, the role of these
antibodies in the etiology, onset, and progression of silicosis is not

339


clear (Parkes 1982). Angiotensin,-converting enzyme (ACE) elevation
has also been reported among silicotics (Gronhagen-Riska 1979;
Nordman et al. 1984). Nordman and colleagues (1984), in a case-
reference study of the Finnish Occupational Diseases Register from
1965 to 1977, reported an association between ACE activity and
progression of silicosis. Smoking, age, and bronchitis .were not
related to ACE activity, which was thought to reflect accumulation
and increased degradation of macrophages. Histocompatibility anti-
gens (HLA) have also been studied as possible genetic risk factors for
silicosis, but with variable results. Koskinen and colleagues (1983)
found that the prevalence of HLA-Awl9 was higher in their Finnish
silicosis patients than in the silica-exposed referent population and
that the highest risk of developing advanced silicosis was associated
with the phenotypic combination Awl9 and B18. However, Sluis-
Cremer and Maier (1984) reported only a decrease in HLA-B40
among 45 South African gold miners. These variable associations are
statistically weak and may be related to the number of statistical
tests performed on the multiple HLA antigens.

The pathogenesis of airways obstruction in silica-exposed workers
is less well understood. Although increased rates of bronchitis and
decreased lung function have been observed in epidemiological
studies comparing silica-exposed and unexposed workers, it appears
that these findings are largely separate from the clinical and
epidemiological picture of silicosis. In the largest and best controlled
study of a reasonably pure silica-exposed sample of 1,973 white gold
miners (Irwig and Rocks 1978), chronic bronchitis was found to be
equally common among those with radiographic evidence of silicosis
and those without. The smoking habits of miners with radiographic
silicosis and of those without silicosis were not significantly different
statistically. Silicotics reported only more days away from work, a
finding the authors suggested may have been as related to their
compensation status as to their disease. Comparison of lung function
between silicotics and their silica-exposed referants revealed equiva-
lent FVC, FEV,, and FEFz~:~~ among silicotics.

Recent pathological evidence of a nonfibrous mineral dust small
airway lesion has been provided by Churg and Wright (1983). This
pathological process, which they labeled mineral dust airways
disease (MDAD), is similar to that produced by tobacco smoke. This
pathological process involves primarily respiratory bronchioles, with
a lesser extension into alveolar ducts. This lesion generally involves
more pigmentation and more thickening of the bronchiole walls than
is typically found in cigarette smokers. In a recent study by Churg
and colleagues (1985) of 13 cases of patients with MDAD, 7 had
occupational histories consistent with a primary silica exposure.
Only 1 of 121 cases without a clear history of dust exposure was
found to have MDAD. Those. with MDAD, matched for age and

340


smoking habit with 13 cases without MDAD, were found to have
significantly poorer lung function, including clinically relevant
lower mean levels of FEVI, FEF25-75~1, and FVC and increased
RV/TLC and AN, per liter as percentages of that predicted. It was
also noted that significantly more membranous and respiratory
bronchiole fibrosis occurred among subjects with MDAD. The
similarity in location, morphology, and physiological impairment
between the pathology induced by mineral dust and that observed
with cigarette smoking suggests that the cellular events giving rise
to them may be similar. Although a good deal is known about the
pathogenesis of the process arising from cigarette smoke (US DHHS
1984), systematic experimental studies of mineral dust airways
disease have not been reported.

Silica Exposure and Cancer

Initial concerns about the association between silica exposure and
cancer arose during the 1930s among investigators in England,
Canada, and South Africa. In the early research on this topic, the
focus was on the proportion of lung cancers arising among autopsied
cases of silicosis compared with that among nonsilicotics or members
of the general public. All of the early research (Dible 1934: Anderson
and Dible 1938; Kennaway and Kennaway 1947; Klotz 1939; Irvine
1939) was characterized by the lack of any data on smoking.

Early assessments of the association between silicosis and lung
cancer were summarized by Hueper (1966). More recently, Hepple-
ston (1985) summarized the autopsy findings from South Africa
(Becker and Chatgidakis 1960; Chatgidakis 19631, from Switzerland
(Ruttner and Heer 19691, and from Germany (Otto and Hinuber
19721, but again no smoking data were presented. The reports from
South Africa and Switzerland showed no differences in the ratio of
lung cancers between silicotics and controls. However, Otto and
Hinuber (1972) showed that porcelain workers with silicosis had
more than twice the proportion of lung cancers as the noncases.
Early studies suggested that silicotics have an increased lung cancer
risk (Dible 1934; Klotz 1939; Mittmann 1959) or that silicotics with
respiratory cancer have greater concentrations of silica in lung
tissue (Anderson and Dible 1938). However, data from Bridge (19381,
Heppleston (19851, Hueper (1966), and Irvine (1939) suggested that
lung cancer risk among silicotics is less than or equal to that of men
without silicosis, regardless of their occupation. In reviewing the
evidence, Hueper (1966) observed that the data support the idea that
lung cancer is a coincidental finding among silicotics and that there
is no etiological relationship.

None of these studies addressed the smoking status of the subjects,
a crucial omission in any study of lung cancer. Furthermore, age was

341


not adjusted, nor were there any quantitative estimates of the silica
exposure or assessments of the severity of the silicotic lesions.

Epidemiologic Studies of Smoking, Silica Exposure,
Silicosis, and Cancer
Silica-Exposed Cohort Studies

Occupational silica dust exposure is common in many industries;
therefore this section is organized so that exposure studies in work
settings that are similar can be examined together, i.e., metal ore
mining, the steel industry, and workplaces where exposures are to
silica only.

Metal Ore Mining

McDonald and colleagues (1978) conducted an enlarged followup
study from 1937 to 1973 of the Homestake Veterans Association
cohort that included 1,321 men with at least 21 years of employment
at the mine. Standardized mortality ratios (SMRs) were calculated
using South Dakota mortality rates as opposed to U.S. rates. The
South Dakota lung cancer rates were lower than those for the United
States as a whole. Using dust exposure data from company midget
impinger samples, the authors examined the pneumoconiosis (mostly
silicosis) and cancer risks in five categories of dustiness, collapsing
them when indicated owing to small numbers. The data showed
striking trends for pneumoconiosis and tuberculosis, but no gradi-
ents emerged for respiratory cancer.

Brown and colleagues (1985) also conducted an assessment of the
Homestake gold miners. The cohort included 3,328 white male
miners employed at least 1 year between 1940 and 1965 and followed
until June 1, 1977. The authors calculated SMRs using person-years
and contrasted mine mortality rates with rates for U.S. white men.
An index of dust exposure by job location was assembled for the
purpose of assessing dose-response gradients. The SMR for malig-
nant neoplasms of the trachea, bronchus, and lung was 100, with no
trends in latency or dust exposure by length of employment.

Katsnelson and Mokronosova (1979) examined the mortality at a
U.S.S.R. gold mine and at several brick plants from 1948 to 1974.
Dust concentrations were not specifically stated for workers in the
gold mine, and an approximation of the SMR (which the authors
termed "relative risk") was calculated to compare the cancer risk
among gold miners with the cancer risk of residents of a nearby town
(excluding those who worked with chromate dusts and adding to the
comparison group those who worked less than 3 years in the plants
under study). The authors reported a relative risk (RR) of 7.9
(p < 0.001) for lung cancer among the male underground gold miners;
without the silicotics, the RR was 3.1 (~~0.02). Surface workers had

342


a nonsignificant RR of 1.6. No lung cancer deaths occurred among
women during these years. No smoking data were presented for gold
mine workers, although data presented for workers at a silica
firebrick plant and an aluminosilicate brick plant indicated that two-
thirds to three-fourths of the men smoked, whereas only 0 to 15
percent of the women did. There appeared to be an inverse gradient
of the proportion of lung cancers by stage of silicosis or silicotubercu-
losis (although no standard classification such as that of Internation-
al Labour Office (1980) is given).

Armstrong and colleagues (1979) followed 1,974 Kalgoorlie gold
miners from Western Australia (whose smoking habits were mea-
sured between 1960 and 1962) for silicosis incidence and mortality
through 1975. Expected death rates were obtained from the age-
specific death rates of Western Australia during 1963-1967, 1968-
1972, and 1972-1976. There were significant (p<O.Ol) mortality
excesses for respiratory cancer (SMR 140) and for pneumoconoisis
and silicosis (SMR 640). The authors compared the cancer risk of the
underground miners and the surface miners and also the association
between silicosis, smoking, and lung cancer. They observed a 40
percent excess of lung cancer among underground workers and a 13
percent excess risk of pulmonary cancer among silicotics (both
nonsignificant). In 1961-1962, the Kalgoorlie miners had a greater
prevalence of smoking (66.3 percent) than either the coal miners
(58.7 percent) or the male residents of Busselton, Australia, in 1966
(53.2 percent) and tended to smoke more cigarettes per day. The
authors stated that the lung cancer risk was probably a function of
the heavier cigarette smoking habits of the miners and that there
was little evidence to link experience underground (and thus
exposure to silica) to lung cancer risk.

Costello (1982) conducted a followup study of 12,258 white "metal
ore" miners who were part of a 1958-1961 U.S. Public Health
Service (US PHS) survey of silicosis and the metal mining industry.
SMRs were calculated using as expected values the 1968 through
1970 white male mortality rates in the 16 States where the mines
were located. The results showed that the cohort as a whole had an
all-causes SMR of 105.9 (p < 0.01); the SMR for cancer of the trachea,
bronchus, and lung was 126.6 (p < O.OOl), and the SMR for pneumoco-
niosis (mostly silicosis) was 343.6 (p<O.OOl). Both digestive tract
cancers and hypertensive heart disease were significantly reduced.
Costello presented several cause-specific and ore-specific SMRs that
were all significant at ~~0.05. Respiratory cancer SMRs were 130.0
among lead zinc miners, 354.6 for mercury miners, and 346.5 for
chromium miners. Highly statistically significant SMRs for pneumo-
coniosis were obtained among copper, lead zinc, molybdenum, and
gold or silver ore miners. In the US PHS 195%1961 survey, 14.5
percent of the metal miners were nonsmokers, 10.9 percent were ex-

343


smokers, 70.5 percent were current smokers, and 37 percent were
pipe and cigar smokers. The smoking status of 0.4 percent was
unknown. Costello argued that on the basis of a relationship between
lung function tests and lung cancer, cigarette smoking was the major
predictor of excess lung cancer in these metal ore miners.

Steel Industry

Gibson and colleagues (1977) conducted a retrospective cohort
study of the Dofasco steel mill workers in Hamilton, Ontario,
Canada, from 1967 to 1976. The authors compared foundry workers
with nonfoundry workers and reported a lung cancer SMR of 250
(p < 0.0005). They used metropolitan Toronto male mortality rates to
calculate expected values. The authors noted that the finishing area
had the highest mean level of total suspended particulates (much of
it silica), respirable particulates, and benzene-soluble fraction of
total suspended particulates. The molding and furnace work areas
had similar industrial hygiene characteristics. No smoking histories
were available for the cohort as a whole. However, 22 of the 24 men
with lung cancers were cigarette smokers. The authors proposed that
smoking and particulate exposure (containing adsorbed organic
material) might be an explanation for the excess lung cancers.

Blot and colleagues (1983) conducted a case-control study of lung
cancer among white men in eastern Pennsylvania to assess the
association with employment in the steel industry. Interviews with
next of kin provided information about residential, occupational, and
smoking histories. The authors demonstrated a smoking-adjusted
odds ratio of 2.2 for usual employment in the steel industry (95
percent confidence interval, 1.5 to 3.3). The odds ratio for lung cancer
was also calculated by smoking category and was significantly
elevated for light smokers and heavy smokers but not for nonsmok-
ers or for moderate smokers.

Workplaces With Exposure to Silica Only

In contrast with workers in the foundry and mining industries,
where silica exposure is most likely to be "contaminated" by
combination with organic foundry fumes or asbestiform materials, or
radon in the case of mining, some workers are exposed to "pure"
silica. These workers are found in several industries, including
ceramics or firebrick manufacture, granite quarrying, or tunnel
digging.

Katsnelson and Mokronosova (1979) examined lung cancer at two
aluminosilicate fireclay plants and at a silica firebrick plant.
Although the firebricks and the fireclay dusts contain high levels of
quartz, no dust samples were collected in the plants. The relative
risk (RR) for lung cancer for the male workers was 4.0 (p < 0.01) and

344


4.5, respectively, at the fireclay plants, and a nonsignificant SMR of
5.1 was reported for the female workers at the first plant. At the
firebrick plants the RR was 2.0 (p < 0.05) for male workers and 0.8 for
the female workers.

Vermont granite workers are exposed to quartz dust with a
concentration of approximately 30 percent free silica. Davis and
colleagues (1983) conducted a proportional morbidity rate (PMR)
study of 969 deceased white granite workers whose x rays were on
file at the Vermont Division of Industrial Hygiene and who had died
between 1952 and 1978. The authors developed a dust exposure
index for the purpose of assessing exposure profiles for their study
subjects. They analyzed the data, excluding tuberculosis and silicosis
after both of these causes of death showed powerful excess disease
risks. Slight excesses for digestive tract, lung, larynx, and prostate
cancers were reported, including a PMR of 1.3 for general respira-
tory cancer (95 percent confidence intervals, 1.0 to 1.6). No apparent
trends emerged relating dust exposure categories with either diges-
tive cancer, respiratory diseases, or lung cancer. Smoking data were
not available for the subjects.

Costello and Graham (19851 conducted a cohort study of 5,414
Vermont granite workers from 1950 to 1982. The authors used the
personnel information on tile in the Occupational Hygiene Division
of the Vermont State Health Department to ascertain date of hire
and date of death. Significant overall excess mortality was observed
for silicosis (SMR 586.6) and tuberculosis (SMR 473.81, but the
excesses were confined to workers hired before 1940. However, no
increased risks were observed for either respiratory system cancer or
lung cancer. The latency time may have been too short to determine
the lung cancer risk among granite workers hired after 1940.
Information was lacking on smoking and dust exposure, and the
Vermont records regarding employees at risk were incomplete.

Selikoff (1978) examined a 932-man cohort of unionized New York
City tunnel workers from 1955 to 1972. These men were exposed to
silicious dusts containing sizable amounts of quartz, schists, and
gneises, but there was little likelihood of exposure to asbestos. There
was an SMR of 495 for pulmonary tuberculosis, an SMR of 160 for
lung cancer, and a gradient in the risk of respiratory cancer
according to the number of years worked. No smoking data were
available, and it is possible that this elevated risk may be a reflection
only of long-term smoking habits and not of silica exposure.

Followup of Silicotics

Westerholm (1980) conducted a followup study from 1931 to 1969
of silicotics from the Swedish Pneumoconiosis Register. For those
whose silicosis arose from employment in mining, quarrying, or
tunneling (MQT) and whose silicosis was diagnosed between 1931

345


and 1948, the lung cancer PMR was 590 (p<O.Ol); for MQT workers
whose silicosis was diagnosed between 1949 and 1969, the PMR was
380 (p<O.Ol). The other significant finding was among workers in
the steel and iron industry (SII) whose silicosis occurred between
1949 and 1969; their PMR was 220 (p <0.05). Westerholm and
colleagues (1985) extended the study from 1961 to 1980 to follow up
712 silicosis cases and 810 noncases from the Swedish silica exposure
registry, matched for age, industry, and occupation. For MQT
workers, the SMR was 538 (p< 0.05) and for SII workers, 385
(p< 0.05). Smoking was not adjusted in the first study, and in the
second, it was indirectly accounted for by the selection of controls
from the same cohort as the silicosis cases.

Finkelstein and colleagues (1982) studied 1,190 Ontario, Canada,
silicotic miners diagnosed between 1940 and 1975. The authors
reported an overall SMR of 198 (p < 0.011, with SMRs of 303 (p < 0.011
and 195 (p < 0.05) for silicotics diagnosed between 1940 and 1949 and
between 1950 and 1959, respectively. No smoking data were collect-
ed.

Schuller and Ruttner (1985) examined the mortality from 1960 to
1978 of 2,399 cases of silicosis in Switzerland. To account for the
sequelae of silicosis isuch as tuberculosis and car pulmonale), the
authors calculated age- and period-specific mortality odds ratios
(MOR). The lung cancer MORs by industry were as follows: miners
229 (p < 0.01); stone workers 118 (p < 0.61; foundrymen 327 (p< 0.001);
others plus ceramic workers 237 (p < 0.05); and ceramic workers 205
(p=O.25). The overall MOR for all Swiss silicotics was 223 (p< 0.05).
The authors noted that smoking is a major cofactor because smokers
have more chest symptoms, thus making silicosis more easily
detected, and because a high proportion of workers in silica-exposed
jobs are smokers, ranging from 60 percent to 85 percent. Because of
the lack of significant lung cancer risk among stone workers with
silicosis (having less confounding exposure to polycyclic aromatic
hydrocarbons than workers in foundries), the authors argued against
silica being a carcinogen, but postulated an interaction of occupation
and smoking. The authors cited the need for cohort studies of
workers in these industries with silica exposure, including detailed
smoking information. An additional question is the relation of lung
cancer risk by degree of silicosis.

Neuberger and colleagues (1985) examined the relative risk for
lung cancer among Austrian silicotics from 1955 to 1979. The overall
risk adjusted for age and sex was 1.4 (p< 0.05). The lung cancer
relative risk increased from 1.31 in the 1955 to 1959 period to 1.42 in
the 1975 to 1979 period. No information was provided on smoking, on
industry-specific risks, or on possible silica exposure levels.
Kurppa and colleagues (1985) examined the subsequent mortality
of 961 cases of silicosis diagnosed in Finland between 1935 and 1977.

346


Using the Finnish male population as a comparison group, they
observed 80 lung cancer deaths instead of the age-adjusted expected
number of 25.6, a SMR of 312 (99 percent confidence interval, 230 to
414). The authors also found SMRs of over 700 for pulmonary disease
and tuberculosis. When the lung cancer risk was examined by
industry, the SMR results were as follows: mining 436 (p<O.Ol);
stone industry 271 (p<O.Ol); steel casting 184; iron foundries 225;
and other industries 343 (p<O.Ol). The authors demonstrated that
the SMRs for each industry showed a 40 percent or more risk
increase (despite small numbers) regardless of whether the silicosis
was diagnosed between 1935 and 1959 or between 1960 and 1977.
The authors did not have smoking data.

Zambon and colleagues (1985) examined a cohort of 1,234 silicotics
from the Veneto region of Italy who were diagnosed from 1959 to
1963, and followed them through 1980. Complete occupational and
smoking histories were available. Overall, the cohort had striking
excesses of infectious disease (tuberculosis) and respiratory disease
(silicosis) mortality, with SMRs of 1,960 and 741, respectively. There
was a significant (p<O.O5) lung cancer SMR of 228 and a nonsignifi-
cant SMR of 206 for cancer of the larynx (based on only seven cases).
There was a gradient of lung cancer risk using years since first silica
exposure as a surrogate for dose (risk did not begin to rise until 20
years after the first exposure). The gradient was maintained across
mining and tunneling industries; tunneling and quarrying industries
had significant overall SMRs of 239 and 569, respectively. The
authors reported that only 13.2 percent of the cohort were nonsmok-
ers and only 3 of 49 deaths occurred in this group; thus, they believed
that the excess mortality was very likely due to smoking.

Research Recommendations

1. Further prospective dose-response studies on chronic bronchi-
tis and airways obstruction assessing silica concentration,
smoking, and airway reactivity should be undertaken.
2. Systematic, well-controlled studies of lung tissue from silica-
exposed workers to assess the pathology and associated impair-
ment of small airways disease should be undertaken.
3. Experimental studies of the interaction of cigarette smoke and
silica dust on the pathogenesis of small airways disease should
be undertaken.

4. The potential for silica to act as a carcinogen alone or in
combination with other exposures should be investigated in
carefully controlled studies that include a detailed examina-
tion of the smoking habits of the participants.
5. Priority should be given to compliance with the current silica
permissible exposure limit.

347


6. Systematic surveillance of silica-exposed populations to docu-
ment silica dose and silica-associated health effects should be
extended by government agencies, unions, and industry.

Summary and Conclusions

1. Silicosis, acute silicosis, mixed-dust silicosis, silicotuberculosis,
and diatomaceous earth pneumoconiosis are causally related to
silica exposure as a sole or principal etiological agent.

2. Epidemiological evidence, based on both cross-sectional and
prospective studies, demonstrates that silica dust is associated
with chronic bronchitis and chronic airways obstruction. Silica
dust and smoking are major risk factors and appear to be
additive in producing chronic bronchitis and chronic airways
obstruction. Most studies indicate that the smoking effect is
stronger than the silica dust effect.

3. Pathological studies describe mineral dust airways disease,
which is morphologically similar to the small airways lesions
caused by cigarette smoking.

4. A number of studies have demonstrated an increased risk of
lung cancer in workers exposed to silica, but few of these
studies have adequately controlled for smoking. Therefore,
while the increased standardized mortality ratios for lung
cancer in these populations suggest the need for further
investigation of a potential carcinogenic effect of silica expo-
sure (particularly in a combined exposure with other possible
carcinogens), the evidence does not currently establish whether
silica exposure increases the risk of developing lung cancer in
man.

5. Smoking control efforts should be an important concomitant of
efforts to reduce the burden of silica-related illness in working
populations.

348


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354


CHAPTER 9

OCCUPATIONAL EXPOSURES
TO PETROCHEMICALS,
  AROMATIC AMINES,
    AND PESTICIDES


CONTENTS

Introduction

Petrochemical, Aromatic Amine, and Pesticide Work-
place Exposures

Prevalence of Smoking in the Petrochemical, Aromat-
ic Amine, and Pesticide Industries
Interactions of Workplace Exposure and Cigarette
Smoking

Studies of Workers Exposed to Petrochemicals
Refinery, Coke Oven, and Gas Workers
  Rubber Workers

Studies of Workers Exposed to Aromatic Amines

Studies of Workers Exposed to Pesticides

Occupational Exposures and Smoking as Causal Factors
in Specific Diseases
  All Cancers
  Lung Cancer
  Bladder Cancer
  Other Specific Cancer Sites
  Chronic Lung Disease

Research Recommendations

Summary and Conclusions

References

357


Introduction

Workers employed in industries that produce or use petrochemi-
cals, aromatic amines, and pesticides can be exposed to chemicals
that threaten their health. Substantial proportions of these workers
smoke tobacco. It is possible that the hazards of smoking and
occupation have independent damaging effects on health, but it is
also possible that the two exposures act synergistically. It is the
purpose of this chapter to review the available evidence bearing on
the hazards of working in industries where petrochemicals, aromatic
amines, and pesticides are produced or utilized, and to explore the
likelihood that smoking and chemical exposures interact to enhance
the risk of various cancers and chronic obstructive lung disease.
Unfortunately, there are very limited data on such potential
interactions.

Petrochemical, Aromatic Amine, and Pesticide Workplace
Exposures

The word "petrochemical" means any substance derived from
petroleum or natural gas. By this definition, petrochemicals are
pervasive in modern industry and agriculture, and worker exposure
might logically include almost the entire workforce. Historically,
however, concern about adverse effects on human health has focused
mainly on industries where petroleum is separated into its many
valuable components (refineries) or where the various products of
that separation are used in such a way that workers are substantial-
ly exposed (manufacture of rubber and processing of leather, for
example). Workers exposed to the products of inefficient hydrocar-
bon combustion (vehicle exhaust, coke production) are also objects of
concern because they inhale unburned hydrocarbons and also the
many reactive substances generated by pyrolysis.

A number of aromatic amines, such as betanaphthylamine and
benzidine, are used in the manufacture of dyes for the textile and
garment industries. Industrial exposure to some of these chemicals
has been reduced because of the known carcinogenicity of betana-
phthylamine and similar compounds. However, naphthylamines are
sometimes used as antioxidants in the manufacture of rubber
products, and significant numbers of workers are still exposed to
benzidine, 4-aminobiphenyl, and other hazardous aromatic amine
products. The groups of interest with regard to exposure are,
therefore, rubber workers and people employed in the manufacture
of aromatic amine dyes.

Workers exposed to pesticides include manufacturers, formulators,
custom applicators, and end-users, principally farmers. Farming, as
an occupational category, has been included in some epidemiologic
studies. Degrees of pesticide exposure on the part of farmers vary
enormously both qualitatively and quantitatively; therefore, the

359


assumption that the health status of farmers is a reflection of
pesticide toxicity is, at best, dubious. This chapter focuses on the few
studies of the health status of workers engaged in pesticide manufac-
ture, formulation, or application.

Prevalence of Smoking in the Petrochemical, Aromatic
Amine, and Pesticide Industries

Information on smoking habits has been very limited in occupa-
tional epidemiologic studies; there are no published reports that
specifically describe the smoking habits of workers in the petrochem-
ical, aromatic amine, and pesticide industries. A number of surveys
have demonstrated the tremendous variability in smoking preva-
lence between occupational groups. The variation in smoking
prevalence between occupational groups, discussed in chapter 2 in
this Report, indicates that operatives and laborers have a higher
prevalence of smoking and earlier ages of initiation.

Because levels of exposure to hazardous and potentially hazardous
substances in the workplace are also greater in operatives and
laborers, smoking can potentially confound attempts to relate
workplace exposures to the development of certain diseases known to
be related to cigarette smoking, such as lung and bladder cancer and
chronic obstructive lung disease. The independent contributions of
occupation and smoking to disease risk cannot be determined, nor
can interactions be evaluated, without adequate measures of both
exposures. Assumptions of equal smoking exposure within and
between occupational cohorts are often tenuous. Few of the studies
reviewed in this chapter measured occupational or tobacco exposure
adequately.

Interactions of Workplace Exposure and Cigarette Smoking

A synergistic effect of two factors is one that exceeds the expected
effects of the two factors acting additively. Reif (1984) has defined
synergy quantitatively and unambiguously. Essentially, if the risk
ratio for workers in a given occupational setting significantly
exceeds the expected additive effects of two exposures acting
separately, potentiation, or synergy, of the two factors is inferred.
When the combined action equals the sum of the effects of the two
agents working independently, the factors are additive. Similarly, if
two factors work independently, but their dual effect is less than the
sum of their independent effects, antagonism exists. Weiss (1980)
reported that the risk of developing lung cancer after exposure to
chloromethyl ethers (CME) was greater in nonsmokers and ex-
smokers than in current smokers. This example of possible antago-
nism leads to speculation that the excess mucus that blankets the
airways of smokers might diminish the carcinogenic effect of CME.

360


This may result because chloromethyl ethers are direct-acting
carcinogens that hydrolyze in water.
To the extent possible, interactions between workplace exposure
and cigarette smoking are discussed in terms of Reifs definitions.

Studtes of Workers Exposed to Petrochemicals
Refinery, Coke Oven, and Gas Workers

The Bureau of Labor Statistics (US DOL 1984) reported that
83,200 workers were employed in petroleum refining in September
1984. These workers are exposed in varying degrees to crude
petroleum and to various fractions produced in the refining process,
including polycyclic aromatic hydrocarbons (PAH). Many of these
substances have been shown to produce lung and kidney cancer in
animals (IARC 1972).

Because of exposure to known carcinogens, a number of cohorts of
refinery workers have been investigated. The results of these cohort
mortality studies, summarized in Table 1, were not consistent
regarding cancer risk, but were consistent in their lack of well-
defined chemical exposures and the absence of information on
smoking habits of individuals within the cohort. Some of these
investigations suggested an increased risk of death for specific
cancer types; others suggested a decreased risk.

Hanis and colleagues (1979) showed statistically significant in-
creases in risk of death due to esophageal and stomach cancer
combined and due to lung cancer. Combined mortality due to bladder
and kidney cancer was also slightly greater than expected. Smoking
could not be ruled out as a contributor to the increased risk in this
group of refinery workers.

Thomas and colleagues (1982) observed increased proportionate
mortality ratios for stomach and pancreatic cancer in their study of
2,500 refinery workers. Risks of death due to leukemia, prostatic
cancer, brain neoplasia, and skin cancer also appeared to be
elevated. The role that smoking might play in relation to the
findings for stomach and pancreatic cancer was not discussed.

Hanis and colleagues (1982) demonstrated elevated risks of death
due to pancreatic and kidney cancer in a cohort of refinery and
chemical workers. Pancreatic and kidney cancer mortality was
greater than expected by approximately 50 percent, but these
elevations in observed deaths were not statistically significant.
Although smoking information was not available for the entire
cohort, 17 of the 24 pancreatic cancer deaths occurred in men who
smoked (15 smoked cigarettes, 2 smoked cigars). Wen and colleagues
(1983) also showed a slight, but nonsignificant, increase in pancreatic
cancer in a cohort of refinery workers.

157-964 0 - 86 - 13                             361


E%
E3  TABLE l.-Epidemiologic studies of mortality among petrochemical industry workers and workers in
          related industries

Study            Type of population

Study design

Major findings

Hank+ et al
(1979)

Tberiault and
Goulet
(1979)

Rushton and
Aldemon
(1981)

Thomas et al
(1982)

Hanis et al.
(1982)

Waxweiler et al.
(198.3)

15,032 male petrochemical
workers

1,205 male refinery
workers

34,708 male petrochemical
workers

2,509 oil refinery workers

8,666 refinery and
chemical plant workers

7,595 petrochemical plant
men

Historical prmpective
mortality

Historical prospective
mortality

Historical prospective
mortality

Proportionate
mortality

Historical prospective
mortality

Historical proepective
mortality

Compared with nonexposed workers, men working in refineries had a relative risk of
3.25', 1.89', and 1.08 for dying of esophagus/stomach, lung, and bladder/kidney cancer,
respectively '

Three primary brain cancer deaths in tbii small cohort, less than one expected; fewer
than expected lung cancer and respiratory disease deaths'

Fewer than expected deaths due to lung cancer (SMR 0.78'), bladder cancer (SMR
0.77). and bronchitis (SMR 0.64')'

Proportionate mortality ratios (PM%) 1.42' for pancreatic cancer, 1.14 for lung cancer,
and 0.57 for respiratory disease, compared with U.S. men; PMRs elevated for stomach
(1.52), prostate (1.38). skin (1.81), and lymphatic cancers (1.61) and leukemia (1.83)'

SMRa 0.92, 0.99, 1.53, 1.55 for death due to lung, pancreatic, bladder, and kidney
cancer, respectively; medical records inadequate to control for smoking; of deaths due
to pancreatic cancer, 71 percent (17124) were in men with a history of tobacco
SUlOki@

SMR 1.98 for mortality due to "total brain tumors"; SMR 0.78 for lung cancer and
0.64 for bladder cancer in hourly petrochemical workers; SMR 0.57' for nonmalignant
respiratory disease de&he in white hourly workers'


TABLE l.-Continued

Study

Type of population

Study design

Major Rndinga

Austin and
Schnatter
(1983)

Well et al.
(1983)

McGraw et al.
(1985)

Hanis et al
(1985a. b)

Redmond et al.
(1972)

Doll et al
(1972)

6,588 white male
petrochemical workers

16,888 refinery workers

3,976 refinery workers

21,698 petrochemical
workers

3,530 coke oven workers,
subgroup of 59,000
steelworkers

3,028 gas workers

Historical prospective
mortality

Historical prospective
mcrtality

Historical prospective   Fewer than expected deaths due to all cancers (SMR 0.91) and all respiratory tract
mortality         diseases (SMR 0.44'); SMR 2.13' for leukemia'

Historical prospective
mortality

Small but significant increaeee in all cause and circulatory disease mortality in workers
expoeed to petrochemicals. differences not explained by smoking; small, statistically
insignificant increaeea in all malignancy deaths and prostate and lung cancer deaths,
compared with U.S. mortality rates. no significant increase in mortality for any cause
in this cohort'

Historical prospective
mortality

Historical prospective
mortality

Essentially same cohort aa Waxweiler et al. (1983); similar results'

Fewer than expected deaths due to lung cancer (SMR 0.99), bladder cancer (SMR
0.46'). and nonmalignant respiratory diseases (SMR 0.68'); SMR 1.09 for cancer of
pancreas; SMR 2.28' for bone cancer'

Male coke oven workers had relative risks of 2.85' and 2.05' for dying of lung cancer
and bladder cancer, respectively; relative risk 1.11 for other respiratory diseaw'

Compared with unexpowd workers. coal carbonization process workem had a relative
risk of 2.40', 2.35*, and 1.83' for dying of lung cancer, bladder cancer, and bronchitis,
respectively '

`SCM significantly different from l.M) at p< .06.
' Smoking hi&x-y not considered.
' Smoking history considered.


Hanis and colleagues (1985a) expanded their previous work to
include current employees and retirees of two additional U.S.
refineries and chemical plants. They analyzed 3,198 deaths from
1970 through 1977 in an exposed population of 21,698 workers;
standardized mortality ratios (SMRs) were calculated, using for
comparison U.S. population mortality rates specific to age, sex, race,
calendar year, and cause. Ninety-one percent of deaths in the
refinery and chemical workers occurred among retirees. Although
this study identified some causes of death that appeared to be either
unusually frequent or infrequent in one or another of the three
chemical plants studied, no statistically significant excesses or
deficits of cause-specific mortalities were found for the cohort as a
whole, relative to the general U.S. population. Specifically, neither
brain tumors nor gastrointestinal cancers nor lymphopoietic malig-
nancies were found to be unusually common in the full worker
cohort, as previous studies of chemical plant workers had suggested.
At one of the three plants, deaths caused by malignant neoplasms in
general and by digestive organ cancers in particular were signifi-
cantly in excess, but this result was counterbalanced by the
unusually low mortality experience from these causes at the other
two plants. The authors were impressed that certain subgroups of
digestive and urinary organ cancers were increased. They speculate
that smoking could have played a significant role in these findings.

In a second report on the same cohort, Hanis and colleagues
(1985b) used direct standardization of mortality rates. This report
categorized workers into nine occupational groups, of which five had
"potential exposure" to petrochemicals in their work (process
operators, mechanical workers, laborers, service workers, and labo-
ratory technicians and field workers), and four had "no exposure"
(officials and managers, professionals, technicians, and office and
clerical workers), and compared mortality experience between these
groupings. Comparisons used age, sex, race, and calendar-year
adjusted rates. In the aggregate, all-cause mortality was higher for
the potentially exposed workers (236.1 deaths/lO,OOO/year) than for
the nonexposed workers (189.1 deaths/lO,OOO/yearX This increase
resulted   from    more  circulatory  system  deaths (145.6
deaths/lO,OOO/year versus 106.6 deaths/lO,OOO/year) and malignant
neoplasms (49.8 deaths/lO,OOO/year versus 41.0 deaths/lO,OOO/year)
among the potentially exposed workers. The mortality rate for
respiratory system diseases excluding lung cancer was lower for the
potentially exposed workers (10.8 deaths/lO,OOO/year versus 14.7
deaths/lO,OOO/year). Smoking histories (ever smoked or never
smoked) were available for 70 percent of the cohort. As a group,
workers who had ever smoked had significantly elevated mortality
rate ratios (relative risks) for all causes (1.91, all malignant neo-

364


plasms (2.3), circulatory diseases (1.7), respiratory diseases (3.5), and
diseases of the digestive system (2.2).
Among workers who had ever smoked, all-cause mortality and
diseases of the circulatory system were increased in the subgroup of
potentially exposed workers compared with the nonexposed workers
(risk ratios 1.2 and 1.4, respectively). Rates for the potentially
exposed groups who had never smoked were not elevated compared
with the rates for the nonexposed who had never smoked. The
number of deaths in these groups was small, so power for these
comparisons is low. The analysis did not specifically test for an
interaction between smoking and petrochemical exposure. Addition-
al followup of this particular cohort may permit a more powerful
analysis, including examination of the interaction of smoking and
petrochemical exposure for specific cancer sites.
Certain epidemiologic studies have been directed at the hazards of
specific tasks performed in the course of petroleum refining. The
refining of lubrication oils involves exposure to unique solvents
(benzene, hexane, methylethylketone, xylene, and toluene) and to
the oils themselves, which have some carcinogenic potential. A
recent study (Wen et al. 1985) focused on mortality among 1,008.
male refinery workers engaged in the lubricatingdewaxing process
at any time between 1935 and 1978; 210 observed deaths were
analyzed by cause. Standardized mortality ratios were calculated,
using for comparison rates specific for age, sex, race, and cause,
based on the U.S. population at 5-year intervals from 1935 to 1975.
Recently measured air concentrations of solvents were far below
regulatory workplace standards. The standardized mortality ratio
for all causes was 0.70 (significantly less than 1.0, p=O.Ol) and for
malignant disease, 0.86 (not significantly different from 1.0). Of the
site-specific cancer mortality ratios, only that for bone cancer was
significantly elevated (SMR 10.3), but the elevation was based on
only three cases, and subsequent investigation showed that only one
of these was truly a mesenchymal tumor of bone origin. The other
two represented metastatic cancers, one from a lung tumor and the
other from a glial (brain) malignancy. Eight prostate cancer deaths
were identified; the corresponding SMR of 1.82 was not significant.
No deaths from cancer of the mouth or pharynx were observed, thus
failing to confirm a previously reported association of these cancers
with lubricating oil refining. No significant excess of leukemia
deaths was found (SMR 1.67). No data on smoking habits were
collected.
The other studies of refinery workers summarized in Table 1
showed an average or a decreased risk for lung and bladder cancer.
Most showed a decreased risk for nonmalignant respiratory disease
deaths, leading one group of researchers (Waxweiler et al. 1983) to
speculate that strict enforcement of antismoking policies might be


responsible for the reduced risk of smoking-related diseases in
refinery workers.

Cohort mortality studies in industries with similar environmental
exposures are also described in Table 1. Redmond and colleagues
(1972) described the increased risk of lung cancer and bladder cancer
mortality in coke oven workers. The risk appears to result from
exposure to PAH emitted in the exhaust created during the coking
process. Unfortunately, smoking information was not collected in
this classic study.

Doll and colleagues (1972) showed comparable results in their
cohort study of gas workers. Coal carbonization workers who are
exposed to PAH emitted by retort ovens had significant increases in
mortality resulting from lung cancer, bladder cancer, and bronchitis.
Smoking histories on a 10 percent random sample in this cohort
showed that the smoking habits of gas workers in the retort houses
did not differ from the habits of other gas workers. The authors
concluded, therefore, that differences in smoking prevalence did not
explain the mortality excess experienced by gas workers in retort
houses. They commented that the sample size was too small to tell
whether there was any interaction between smoking habits and the
occupational hazard.

Rubber Workers

Workers engaged in the manufacture of rubber products have long
been of concern to occupational health professionals because their
work environments are commonly contaminated with dusts and the
fumes of hundreds of industrial chemicals, including hydrocarbon
solvents. The carcinogenic potential of a number of materials used in
rubber manufacture-benzene, betanaphthylamine, and other
amine and nitroso derivatives of hydrocarbons-is well documented
in man, laboratory animals, or both. Worker exposure to some of the
most likely carcinogens has been described (Mancuso and Brennan
1970; Monson and Fine 1978). In addition, exposure to talc, carbon
black, and the dust from the milling and grinding processes
represents a continuing hazard to the respiratory tract.

The feedstocks and solvents used in this industry are chemically
diverse, and the mix of chemical exposures changes from one year to
the next. Worker exposures are so different from one plant to
another and from one time to another that it is questionable whether
rubber manufacturing should be considered an "industry." Diver-
gent findings from the many studies since Case and colleagues (1954)
first attributed an excess of bladder cancer in rubber workers to
their occupational exposure may well result from the diversity and
evolution of pollutants in this unique work environment.

Production workers employed. in manufacture, fabrication, and
reclamation of rubber in September 1984 totaled 188,000 (US DOL


19841. There are no current estimates of the frequency or intensity of
smoking in this specific segment of the workforce. Because of
smoking restrictions at some worksites where explosion hazards
exist, smoking may not be quite as pervasive among rubber workers
as it is in other blue-collar populations who work where similar
restrictions are not in effect.

Epidemiologic studies aimed at determining the risk of cancer
attributable to employment in the rubber industry are summarized
in Table 2. All of these studies are surveys of mortality experience
over the last several decades. All but two were of the historical
prospective design. In none was smoking taken into consideration as
a factor contributing to cancer mortality. Direct information regard-
ing the smoking habits of decedents was probably difficult, or
impossible, to obtain. Also, with the exception of bladder cancer, the
forms of malignancy most often identified as possibly excessive
(brain, hematopoietic, lymphatic) are not commonly regarded as
smoking-related cancers.

An early analysis of proportionate mortality in Akron, Ohio,
rubber workers suggested excess rates of cancer affecting the
respiratory, genitourinary, and central nervous systems (Mancuso et
al. 1968). A subsequent historical prospective study (McMichael et al.
1974) analyzed 1,783 deaths by cause in a cohort of 6,678 male
workers employed from January 1964 and compared cause-specific
SMRs with rates based on the U.S. male population and on
previously published rates for steelworkers. Elevated ratios suggest-
ed excess risks of malignant disease of the stomach, prostate, and
lymphatic and hematopoietic systems. There was no indication of
excess risk of cancer of the lung or bladder at one Akron plant, and
only slight risk elevations at five other plants. No attempt was made
to assess the impact of smoking. A followup study (McMichael et al.
19751 tended to associate leukemia deaths with job assignments
involving solvent exposure.

In a prospective mortality study of rubber workers, Fox and
colleagues (1974) demonstrated an increased risk of mortality due to
all cancers combined and to bladder cancer specifically. In subsam-
ples of this cohort, specifically workers in the tire sector and the hose
rubber sector, significant increases in lung cancer mortality were
observed. These sectors of the workforce had known exposures to
asbestos. Smoking histories were not available in this study,
although deaths due to bronchitis and emphysema were fewer than
expected in tire workers.

A study of mortality and morbidity among Akron rubber workers
included a cohort of 13,570 workers (Monson and Nakano 1976;
Monson and Fine 1978). Information was assembled from death
certificates, and incidence data were also collected from local
hospital tumor registries. Comparisons were made between the

367


E  TABLE Z.-Epidemiologic studies of mortality among rubber workers

Study

Type of population

Study design

Controls

Disease status studied

Major findings

hlancuao et al
(1968)

1,877 rubber workers;
463 deaths

Histalical
pnspective

Office workers in
rubber industry

Mancuao and
BIWluaIl
(1970)

Fox et al.
(1974)

McMichael
et al.
(1974)

McMichael
et al.
(1975)

1,877 rubber worken,

40.867 cablemakers

6,678 male rubber
workers

6,678 male rubber
workers; 8 leukemia
deaths

Historical
prospective
mortality

HistOI-iUll
proepective
mortality

Hieblical
pmspective
mortality

Case-control

Office workers in   Cancer of gallbladder,
rubber industry    ducts, salivary glands

U.K. male
population

U.S. male
population

Other deceased
rubber workers
(matched)

All cauaea

Apparent exceaa mortalities from various
malignancies among "nonoffice" workers, including
cancers of the gastrointestinal tract, lung, and
hematopoietic t&sues; mortality from nonmalignant
diseases of the circulatory and respiratory systems
also apparently elevated, not tested statistically

Apparent excess mortalities in particular plants
and jobs from cancer of the gallbladder. bile ducts,
and salivary glands, not tested statistically

All die&Wee

Elevated SMR for all neoplasme and bladder
cancer mortality; greater than expected lung
cancer mortality in tire makers and hoserubber
sector; fewer than expected deaths from bronchitis

All diaeaW

Elevated SMRa for neoplaems of gastrointestinal
tract and lymphatic and hematopoietic systems; no
exce88 of lung or bladder cancer or chronic
pulmonary disease

Leukemia

Significant excees of mortality from lymphatic
leukemia associated with past exposure to solvents


TABLE 2.4ntinued

Study        Type of population

Study design

cantmle

Diaeaae statue Etudied

Major findings

Mormon and
Nakano
(1976)

13.571 white male
rubber workera

Hietmical
proepective
mortality

White U.S. men

All caueea

Excess deaths fmm specific cancera at specific
work sites: gaatrointeatinal/pr-ing, lung/tire
curing, bladder/all workers, brain and
lymphatic/tire building, leukemia/all workem

Moneon and
Fine
(1978)

13,750 rubber
workers; 1,359 deaths

Historical
pmapective
mortality,
morbidity

US. men, and
within-plant
mmpriafm

Cancer

Excess rates of cancer of gastrointestinal tract,
lung. bladder, skin. brain, and hematopoietic
tissuea in specific jobs

Arp et al.
(1983)

15 caaen of lymphatic
leukemia

Caae-contml

Other deceaned
employees,
matched

Lymphcqtic leukemia

Caaea more likely than controls to have had
exposure to benzene and other coal-tar-baaed
solvents

NOTE: Smoking history WUB(I not mneidered in any of thme studies.


cohort and the general male U.S. population, and also between
cancer incidence in specific departments and incidence in all other
departments combined. There appeared to be increased risks of
various malignancies associated with certain work areas, notably
cancers of the gastrointestinal tract, lung, bladder, skin, and brain,
as well as lymphomas and leukemia. Interestingly, bladder cancer
was not found to be in excess among workers presumably exposed to
betanaphthylamine, and lung cancer did not occur with unusual
frequency in work areas where operators had previously been found
to exhibit respiratory morbidity. Lung cancer was found in excess
among workers engaged in tire curing and molding and in deicing
and fuel cell operations. No effort was made to take into account the
role of smoking as a factor causing cancer in this worker cohort.

Studies of Workers Exposed to Aromatic Amines

Since the work of Rehn (18951, there has been increasing evidence
that exposure to aromatic amines used in the dye-making industry is
an important cause of bladder cancer. Case series reported in the
United States (Evans 1937) and in the United Kingdom (Case et al.
1954) added evidence that naphthylamines and benzidine were the
likely carcinogens accounting for the high incidence of bladder
cancer in exposed chemical workers. Other studies of bladder cancer
risk and exposure to aromatic amines have been reviewed recently
(Clayson 1981; Johnson 1983). In addition, Melick and colleagues
(1971) demonstrated that 4-aminobiphenyl is a bladder carcinogen,
and there is concern that benzidinederived dyes may also be
carcinogenic (Johnson 1983).

Approximately 83,700 workers were employed in the manufacture
of industrial organic chemicals in September 1984 (US DOL 1984).
Some unknown fraction of these workers is exposed to aromatic
amines. The National Institute for Occupational Safety and Health
(NIOSH) (1979) estimated that 79,000 workers in various categories
are exposed to benzidine and related chemicals. Since many of the
aromatic amines are regulated as carcinogens and because new
methods are available for synthesis of dyestuffs, exposure to
aromatic amines has decreased (Johnson 1983). However, benzidine
derivatives are still commonly used and have not been studied as
extensively as other aromatic amines. Benzidine derivatives are
known to be excreted as free benzidine in the urine of rhesus
monkeys (Rinde and Troll 1975).

Mancuso and El-Attar (19671 conducted a retrospective cohort
mortality study of 639 men who manufactured betanaphthylamine
and benzidine. Fourteen deaths due to bladder cancer and one due to
kidney cancer were observed, although less than one case was
expected on the basis of the rates for Ohio residents. Six deaths due

370


to pancreatic cancer were also observed. Smoking histories were not
obtained.

Zavon and colleagues (1973) identified a small cohort of workers
involved in the manufacture of benzidine. These workers averaged
13 years of exposure to benzidine. Of the 25 workers, 13 developed
bladder tumors and 4 developed kidney tumors. Smoking histories
were not reported, so the possibility of interaction cannot be
addressed.

A risk assessment of a cohort exposed to aromatic amines has
recently been reported (Schulte et al. 1985). Thirteen confirmed
cases of bladder cancer occurred in a cohort of 1,385 workers in a
plant where betanaphthylamine and benzidine were manufactured
and used intermittently from 1940 to 1972. Cases were identified
from an ongoing mortality survey, from a bladder cancer screening
clinic, and from a survey of local urologists. Incidence rates were
calculated on the basis of person-years of exposure, and were
compared with the Surveillance, Epidemiology, and End Results
(SEER) program's incidence rates for the entire United States.
Overall, bladder cancer incidence in the cohort was 3.9 times the
incidence in the U.S. general population. The incidence rate in-
creased dramatically with duration of employment; this increase was
independent of age. Peak incidence occurred with people younger
than most bladder cancer victims in the general population. Smok-
ing histories were evaluated; no significant differences in smoking
patterns were found between cases and controls.

The relationship between exposure to aromatic amines and
bladder cancer has also been explored in case-control studies. These
studies are reviewed later in this chapter.

Investigation of the carcinogenicity of betanaphthylamine and
other aromatic amines has provided important insights into the
nature of chemical carcinogenesis in general. Decades ago, it was
realized that bladder carcinogenesis was a species-specific phenome-
non: betanaphthylamine induced bladder tumors in dogs but not in
rats or mice (Scott 1962). Carcinogenic potential apparently depends
on the pathway of biotransformation of the amine compound and the
efficiency of urinary excretion. This differs markedly in various
species. Because the oxidation products formed are dependent on
activities of various oxidizing enzymes (mainly hepatic), substances
capable of modifying these enzyme activities (induction or inhibition)
could influence the carcinogenicity of the aromatic amines. There is,
therefore, a rational biochemical basis for xenobiotic interactions. It
is now known that aromatic amines are capable of causing tumors in
many organs and tissues of laboratory animals in addition to the
urinary bladder. The distribution of cancers induced is again
remarkably different among species (Clayson 1981). Finally, it is
noteworthy that tobacco smoke contains measurable amounts of

371


carcinogenic aromatic amines (Wynder and Stellman 1981), and that
betanaphthylamine and an oxidation product thereof have been
identified in the urine of a cigarette smoker (Connor et al. 1983).

Studies of Workers Exposed to Pesticides

The Bureau of Labor Statistics (US DOL 1984) estimated that
36,700 workers were involved in the manufacture of agricultural
chemicals in September 1984. This estimate does not, of course,
include the much larger number of people exposed while usirg these
chemicals, such as farmers and gardeners. These end-users exposed
to pesticides could easily number over 1 million individuals.

A mortality survey of workers in pesticide application analyzed
311 deaths (Wang and MacMahon 1979a), comparing mortality rates
for various causes with rates characteristic of the general U.S.
population. Elevated SMRs were found for cancer of the lung, skin,
and bladder, but only the elevated ratio for bladder (R 277) was
statistically significant. The ratio did not correspond to the intensity
of exposure, being much higher in those applications with minimal
exposure. No attempt was made to assess the role of smoking as a
factor accounting for the excess cancer mortalities. In a similar
companion analysis of 113 deaths among workers engaged in the
manufacture of chlordane and heptachlor (Wang and MacMahon
1979b), the investigators found a different pattern of mortality: there
was no indication of excess cancer mortality at any study site.
Smoking effects could not be taken into account. As is usual in
occupational mortality surveys, overall mortality was substantially
lower among the employed than in the general U.S. population
(McMichael 1976).

Barthel (1981) surveyed 1,658 German male pesticide applicators
in a retrospective cohort study, of whom 169 developed malignant
tumors that resulted in death. These workers had applied a variety
of fungicides, insecticides, and herbicides, usually in dust form. This
report tabulated the specific pesticides that were used and included
the period of time the cohort was likely to have been exposed to each
specific pesticide. Compared with the male population of East
Germany, this cohort had a l.&fold greater than expected mortality
from bronchogenic carcinoma. Those individuals with the longest
exposure to pesticide had the greatest risk of lung cancer mortality,
e.g., a threefold increase in men exposed to pesticides for more than
19 years. Smoking was measured in a subsample of exposed workers
and compared with age- and sex-matched controls selected at
random from people receiving a chest x ray at a clinic for the general
public. This source of controls can be criticized as being biased for
people with chest disease and, therefore, smoking prevalence.
Nonetheless, the pesticide-exposed workers and the controls had

372


similar smoking habits: 49.7 percent of the pesticide applicators were
smokers versus 49.1 percent of the controls from the screening clinic.
Lifetime tobacco exposures were also similar for the two groups.

Barthel speculated that the increased risk of lung cancer death
could be partly attributed to arsenicals used prior to 1955 and
possibly to asbestos present in the carrier substances (talcum, kaolin,
and bentonite) used in pesticide dust formulations.

Mortality surveys were conducted (Ott et al. 1974) to detect excess
cause-specific death rates among workers engaged in the manufac-
ture of arsenical pesticides. Proportionate mortality ratios were
calculated for the arsenic-exposed workers (173 decedents) and were
compared with ratios derived from the mortality experience among
approximately 1,800 nonexposed workers at the same company.
Arsenic exposure was found to pose an average 3.5-fold increased
risk of lung cancer, the magnitude depending on the estimated
intensity (airborne arsenic concentrations) and duration of arsenic
exposure. An elevated risk ratio was also found for lymphatic and
hematopoietic malignancies (3.9), but this was based on just five
cases (1.3 expected). There was no evident increase in risk for any
other malignant disease. A cross-sectional review of smoking histo-
ries of the arsenic-exposed workers showed no differences from the
employee population in general, and no relationship to arsenic
dosage estimates.

A subsequent study examined causes of death among 1,393 persons
(male and female) over several decades at a pesticide manufacturing
plant in Baltimore, Maryland, where several hundred workers had
been exposed to airborne arsenical compounds, mainly in the 1940s
and 1950s (Mabuchi et al. 1979). Additional workers had been
exposed to various other pesticides, including organochlorines and
carbamates. Those who had left employment were traced. The
mortality experience of the white population of the city of Baltimore
was used for comparison, allowing the calculation of SMRs for the
target population. As in the study by Ott and colleagues (1980),
significantly and substantially elevated ratios were found for lung
cancer among male workers exposed to arsenicals specifically. The
ratios increased with the duration of employment in arsenical
manufacture, suggesting a dose-response relationship. Two cases of
anemia were identified, one pernicious and the other aplastic. No
excess of lymphatic cancer was identified. Among workers involved
in the manufacture of nonarsenical pesticides, the mortality pattern
was essentially the same as that of the Baltimore city white
population. Although the smoking habits of decedents were not
determined, the authors offered cogent arguments in support of an
occupational rather than a smoking causality: (1) SMRs for smoking-
related causes of death other than lung cancer were not elevated in
the arsenic-exposed group, and (2) the strong dose-response relation-

373


ship between arsenic exposure and lung cancer would not be
expected to be paralleled by a concomitant increase in smoking risk,
when no such relationship was found among workers engaged in the
manufacture of nonarsenical pesticides.

Mortality among workers engaged in the manufacture of 2,4,5-T
has been examined (Ott et al. 1980). These workers were presumably
exposed to chlorodioxins. Mortality occurring among 204 workers
from 1950 to 1971 was compared with that recently tabulated for all
U.S. men. Of 11 deaths, only 1 was due to cancer; this was a
respiratory tract malignancy in a 68year-old retiree who had been
exposed to the 2,4,5-T manufacturing process for 8 years and who
smoked up to two packs of cigarettes daily.

As with the petrochemical worker mortality studies, the few
studies of workers exposed to pesticides lack specific information
from which to measure the contribution of smoking to the increased
risk of cancer. Because cohorts of workers manufacturing pesticides
are not large, it is unlikely that epidemiologic studies will be done to
address specific questions regarding smoking and pesticide interac-
tions.

Occupational Exposures and Smoking as Causal Factors in
Specific Diseases

Several investigations have examined the role of occupational
exposures as risk factors in the development of specific diseases. The
case-control design has the disadvantage of being nonspecific and
sometimes unreliable in identifying exposure that occurred in the
workplace. The main advantage of this approach is the opportunity
to collect information on other risk factors, specifically smoking,
together with the greater statistical power that results from
studying a larger number of cases than might occur in a specific
industrial cohort. In this section, epidemiologic studies of various
cancer types and chronic lung disease are reviewed.

All Cancers

Dubrow and Wegman (1984) examined the occupational character-
istics of 16,629 cancer victims who died in Massachusetts between
1971 and 1973. They calculated the age-standardized mortality odds
ratios for various types of cancer within 321 occupational categories,
relying on death certificate indication of the "usual occupation" of
the decedent, and attempted to adjust for social class. To limit the
confounding effect of smoking on cancer incidence, they used
adjustment factors based on published estimates of smoking frequen-
cy in major occupational groupings, together with lung cancer risk
ratios for smokers and ex-smokers. The estimates of smoking
frequency within occupational groups were based on a 1970 National

374


Health Interview Survey of 75,827 American men and women
reported by Sterling and Weinkam (1976). The authors not only
reported their own findings, but also compared their results with
those from 11 other large-scale mortality surveys.

In this study a large number of occupations wherein death caused
by particular forms of cancer appeared to be excessive was identified.
Certain associations, such as lung cancer in shipyard workers, have
been confirmed by other studies; the associations are plausible in
terms of well-known exposures, especially exposure to asbestos.
Significant excesses of bladder cancer were found among chemical
workers and engineers, cosmetologists, leather workers, and garage
mechanics, again generally in accord with the view that particular
occupational exposures pose carcinogenic risks. High rates of certain
cancers in schoolteachers, clergymen, administrators, judges, and
lawyers are much more difficult to understand in environmental
terms.

To the extent that the adjustment for smoking effects used in this
analysis can be relied upon, the study would appear to show that
certain occupations are, in fact, associated with excess risk of cancer,
quite apart from the risk of smoking. It is not possible to estimate the
relative magnitudes of the two risk factors, or the existence of
interaction between them.

Data from the Third National Cancer Survey (TNCS) Interview
Study of 7,518 incident cases were used to seek associations between
various occupations and types of cancer (Williams et al. 1977). Data
assembled on each case included a synopsis of lifetime employment,
education, residential location, and use of tobacco and alcohol, as
well as age, sex, race, and socioeconomic status. The large number of
cases and the detailed information available made possible a number
of adjustments and comparisons not possible in other studies. The
main analytical strategy was to compare, serially, the proportions of
specific main lifetime industries and occupations among patients
with cancer at one site with proportions of patients having cancers at
other sites combined as a control group (intercancer comparisons).
The advantages and limitations of this approach were discussed by
the authors. Even when smoking was controlled for statistically,
people engaged in trucking were found to be at excess risk of lung
cancer, a finding supported by the Massachusetts cancer mortality
survey (Dubrow and Wegman 1984). Other transport, service,
manufacturing, and construction workers were also at excess risk of
lung cancer. As often happens, some associations were discovered
that are difficult to understand mechanistically: excess leukemia
and multiple myeloma in salespeople and malignant melanoma in
schoolteachers, for example. The study does not present relative risk
ratios for smoking within occupational categories from which the
relative importance of the two factors might be assessed. As in the

375


Massachusetts mortality survey (Dubrow and Wegman 19841, it must
be concluded that to the extent smoking effects were adequately
controlled by statistical design, certain occupations appear to be
associated with significant risks of cancer, independent of the role of
smoking. Unavoidably, the occupational classes used for this kind of
study are broad: the actual exposure circumstances within these
classes that might be conducive to cancer can only be speculated.

Viadana and colleagues (19761 studied 11,591 white male cancer
patients and controls who were hospitalized at Roswell Park
Memorial Institute between 1956 and 1965. They used occupational
histories to classify cases and controls as being exposed to "chemi-
cals" and "combustion products," and into specific groups within
these broad classifications, e.g., operatives in the chemical industry
or bus, cab, or taxi drivers. Operatives in the chemical industry had
an increased relative risk of having cancer of the stomach (RR 4.25,
p<O.O5). The relative risks for lung and laryngeal cancer were
slightly, but not significantly, increased.

Relative risks for larynx (RR 3.63, p<O.O5), pharynx (RR 3.38,
p< 0.051, and bladder (RR 6.77, p<O.O5) cancers were significantly
elevated for operatives in the leather industry. Relative risks were
altered after controlling for smoking, but the risks associated with
occupation appeared to be independent of smoking. The influence of
smoking on the risks associated with occupation were difficult to
assess, because the relative risks adjusted for age and smoking were
not tabulated. Instead, these results were discussed selectively.
Although the information needed to investigate the interaction
between smoking and occupation was available, this report did not
discuss this issue.

Lung Cancer

Stayner and Wegman (1983) used a case-control design to study
the relationship between smoking, lung cancer, and occupation,
based on a portion of the data from the Third National Cancer
Survey. The analysis was limited to men aged 30 to 84 when
diagnosed as having lung cancer who had responded to an int.erview
that included occupational and smoking histories. Occupation was
coded in broad categories defined for the 1970 census. Cases and
controls were grouped as "ever" or "never" users of tobacco to
control for smoking exposure. Controls were selected from survey
participants with other types of cancer, excluding those individuals
with the types of cancer that have been associated with occupation
or smoking (e.g., lip, mouth, pharynx, larynx, esophagus, pancreas,
bladder, liver, skin, brain, and blood and bone marrow). These
exclusions left 900 controls to be compared with 420 cases. Blue-
collar workers had an odds ratio (OR) of 1.24 (p < 0.05) for developing
lung cancer after adjustment for smoking status and age. This

376


difference was due in part to the increased odds for developing
squamous cell carcinoma (OR 2.11, p<O.O5) compared with average
odds for developing adenocarcinoma (OR 0.97) and small cell
carcinoma (OR 1.22). When the data were analyzed using more
narrowly defined occupational groups, no statistically significant
associations were found. However, when histologic types were
considered separately, laborers had higher odds ratios for small-cell
carcinoma (OR 2.47, p< 0.05) and squamous cell carcinoma (OR 1.97,
p < 0.05) after adjustment for smoking.
Stayner and Wegman reported positive associations between
smoking and all three histologic types of lung cancer. They did not
consider the potential interactions between smoking and occupation
in discussing their data. Their report did illustrate the importance of
considering histologic type when conducting etiologic studies of lung
cancer.
Few studies of occupational risk focus on women. Leung (1977)
reported an association between cooking with a kerosene stove and
lung cancer in Chinese women living in Hong Kong. This case-
control study was conducted to identify factors that might account
for the relatively high mortality rates for lung cancer experienced by
women in Hong Kong. In 260 consecutive cases of histologically
proven lung cancer, 92 percent (166/180) of the men and 56 percent
!45/80) of the women smoked cigarettes compared with 59 percent of
the male smokers and 11 percent of the female smokers in a
"nonrandom" popu!ation sample. In a second series of 44 lung cancer
cases in women. 91 percent i40/44) used a kerosene stove daily for
over 2 years compared with 36 percent of the families sampled in
seven areas of Hong Kong.
The sampling schemes used in this study could easily produce
biased results. Smoking prevalence in the community was based on a
convenience sample and might have underestimated the prevalence
of smoking by women. Kerosene stove usage could be associated with
many other environmental e::?3sures that might be related to lung
cancer. Nevertheless, strong ilssociations between smoking and
kerosene stove use and lung cancer were found among women. The
author concluded that the question of synergy between stove usage
and smoking requires further study.
In a case-control study of lung cancer, Pastorino and colleagues
(1984) estimated the proportions of lung cancer attribut.able to
smoking and occupational exposure to known or suspected carcino-
gens. Lung cancer cases were drawn from a well-defined geographic
area in northern Italy where a large proportion (74 percent) of
employed men work in industry. In this area, 240 incident cases of
lung cancer in men occurred between 1976 and 1979. Twenty-nine
cases were excluded because diagnostic criteria were not met and 7
cases could not be reached for interview, leaving 204 cases (85


percent of total) for analysis. Controls were selected at random from
the electoral rolls of men living in the same region and matched with
cases for age within 2 years. Of the 366 controls enrolled, 15 could
not be reached for interview. Interviews were conducted by two
occupational physicians and two public health nurses. Occupational
histories focused on specific exposure to asbestos, tars and mineral
oil, chromium, nickel, arsenic, bis-chloromethyl ether, chloromethyl
methyl ether, vinyl chloride, and polycyclic aromatic hydrocarbons
as contained in soot. "No exposure" was defined strictly as a work
situation where the subject could not have been exposed to these
materials. "Possible" and "probable" exposures were defined on the
basis of descriptions of specific job tasks. Ten percent of the control
interviews and 50 percent of the case interviews were with next of
kin.

The relative risk for lung cancer was strongly related to cigarette
smoking in a dose-related way. Relative risk ranged from 2.3 for
smokers of 1 to 9 cigarettes per day to 9.0 for smokers of 30 or more
cigarettes per day. Occupational exposures were also positively
associated with lung cancer. The relative risk for possible exposure
was 1.6, and for probable exposure, 2.7. The authors estimated that
81 percent of lung cancers could be attributed to smoking (95 percent
confidence interval, 69 to 93) and that 33 percent could be attributed
to occupational exposure to known carcinogens (95 percent conti-
dence interval, 19 to 47).

Pastorino and colleagues (1984) illustrated how relative risk varies
positively with occupational exposure and cigarette smoking. The
relative risk increased in men without occupational exposure from
1.0 in nonsmokers to 2.7,6.2, 9, and 11 in men who smoked 1 to 9, 10
to 19, 20 to 29, and 30 or more cigarettes per day, respectively. In
men with possible and probable occupational exposure, the relative
risk increased from 2.5 in nonsmokers to 3.8, 14, 19, and 20 in men
who smoked 1 to 9, 10 to 19,20 to 29, and 30 or more cigarettes a day,
respectively. Occupational exposure was subcategorized by exposure
to asbestos and PAH, the most common occupational exposures in
this study. Both were independently associated with lung cancer
risk. The relative risks associated with asbestos and PAH exposures
in combination with smoking were more consistent with additive
effects, but a specific analysis of the possible interactions was not
discussed.

Bladder Cancer

In the last 15 years, many case-control studies and analyses of
mortality statistics have been used to examine relationships between
occupation and bladder cancer. In only a few has enough historical
information been aggregated in detail sufficient to permit explora-
tion of interactive effects between occupation and smoking.


A case-control study of bladder cancer patients in the hospitals of
Leeds, England, failed to show that smoking was a risk factor for
bladder cancer, but did indicate that the prognosis was worse in
patients who continued to smoke (Anthony and Thomas 197OaJ
Controls for this study were lung cancer patients and surgical cases
interviewed 5 years previously at the same hospital. They were not
matched to cases by age. In an expansion of this study, Anthony and
Thomas (197Ob) matched cases to controls (again using previously
interviewed patients) with respect to age, sex, residence, and
smoking habit (never smoked, greatest amount ever smoked, cessa-
tion of smoking). They then calculated risk ratios for aggregates of
cases according to their "predominant occupations" and "employ-
ment in suspect environments." They identified significantly elevat-
ed risks of bladder cancer among workers in the chemical dye
industry, textile workers, tailors, engineering workers, and hairdres-
sers. Because cases and controls were matched for smoking habit,
risks were presumably attributable only to occupation.

In an extensive case-control study of bladder cancer in the
Boston-Brockton, Massachusetts, area in 1967-1968, Cole and col-
leagues (1971, 1972) examined occupation and smoking information
obtained by interviewing 470 incident cases and 500 age- and sex-
matched controls. Controls were selected at random from published
"resident lists." Smoking was taken into account with respect to
intensity (cigarettes per day) and also estimated total dose (pack-
years). Thirteen occupational exposure categories were used in
classifying patients and controls: dyestuffs, rubber, leather, printing,
paint, petroleum, other organic chemicals, other chemicals, fumes
and dust, manufacturing (not elsewhere classified), farming, service,
and office. From this study the authors calculated mean relative risk
ratios of 1.89 and 2.00 for bladder cancer in male and female
smokers, respectively, and demonstrated gradients of risk in both
sexes, based on numbers of cigarettes smoked per day. The maxi-
mum mean relative risk ratio (3.8) was for women who smoked more
than one and one-half packs per day. Standardization by occupation-
al categories did not alter the relative risk estimates for smoking.

When risks were analyzed by occupational categories (ever em-
ployed), significantly elevated ratios were found in only two catego-
ries: those working with rubber and rubber products (1.57) and those
working with leather and leather products (2.00). People exposed to
dyestuffs, paint, and other organic chemicals exhibited apparent
elevations of risk, but the number of cases available for study was too
small to yield statistically significant increases. Relative risks were
very similar whether or not controlled for smoking. Examined in
terms of "usual occupation" instead of "ever employed," risk
associations with occupation tended to be weaker, but rubber and
leather industries were again identified as those most likely to

379


involve an occupational hazard of bladder cancer, even when
controlled for smoking. Risk attributable to hazardous occupation
(work in industries involving exposure to chemicals) was estimated
to be 7 to 18 percent of the total bladder cancer risk, depending on
the basis used for specifying occupation. Relative risk ratios ranged
from 1.21 to 1.75.

The epidemiology of bladder cancer with respect to beverage
habits as well as smoking and occupation was addressed in three
Canadian studies. Miller (1977) conducted a case-control study of 349
bladder cancer cases from British Columbia, Nova Scotia, and
Newfoundland, matching each case to controls by age, sex, and
residence (but not by smoking). Control subjects were recruited from
the residential neighborhoods of the subjects. Questionnaires admin-
istered in the homes inquired into the occupations of the respon-
dents, as well as their smoking and coffee-consuming habits.
Significant relative risk ratios (2.0 to 10.5) were found for cigarette
smoking, and showed a substantial dependence on estimated lifetime
consumption of cigarettes. Occupational risks were evaluated only
with respect to seven categories: chemical, rubber, photography,
spray painting, petroleum, medicine, and "other." Risk ratios were
2.0 or more in all categories, and were statistically significant in two:
"chemical" (12.0) and `<other" (2.1). No details of the nature of
chemical exposures were offered, and no analysis of smoking habit
within occupational categories was presented. The number of case
control pairs within the six specific categories was small (total 78),
and no occupation-based risk ratios for nonsmokers were stated
explicitly. Population-attributable risk percentages calculated by the
authors for men were occupation (known and suspect), 35 percent;
cigarette smoking, 56 percent; coffee drinking, 27 percent; and total,
118 percent. For women the percentages were 1,29, and 13 percent,
respectively; the total was 43 percent.

An extension of this study on bladder cancer published in 1980
(Howe et al. 1980) included 632 case-control pairs from the same
Canadian provinces. Strong relative risks for smoking were con-
firmed in men and women, the magnitudes depending on daily
usage, duration, and estimated lifetime consumption. Associated
with significantly elevated bladder cancer risk in men were workers
in the chemical, rubber, petroleum, welding, and railroad industries,
guards and watchmen, nurserymen, metal machinists, material
recorders, and military personnel. Risk ratios for military personnel
and clerical workers declined when smoking was controlled for;
other risk ratios reportedly did not. This analysis was based on
responses to a query as to whether subjects had ever worked in the
specified jobs, not on usual occupation. Despite the size of the study,
the number of discordant matched pairs was relatively small: fewer
than 50 in all occupational categories except agriculture, military,

380


and mechanics. No excess risk was indicated for people engaged in
the dyeing of cloth or tanning, but the number of pairs available for
analysis was not sufficient to provide reliable estimates. Discordant
pair ratios of 4/3 and 5/l were recorded for past contacts with
benzidine and bis-chloromethyl ether, respectively, on the part of
male respondents. The numbers were too small to permit an
examination for the confounding effects of smoking. Very few
women were employed in the suspect industries, and no significant
risk elevations associated with occupation were identified among
women.

Miller and colleagues (1978) matched each of 265 incident bladder
tumor patients diagnosed at the Ottawa Civic Hospital Urology
Clinic to two control patients treated at the clinic who did not have
bladder tumors. Administered questionnaires inquired into previous
disease in self and family, occupational exposures, use of coffee,
tobacco, and sweeteners, exposure to radiation, and prior treatment
with antituberculosis drugs. Relative risk calculations and discrimi-
nant analysis identified the following significant risks, in apparent
order of importance: in men, a family history of allergy (1.8),
occupational exposure to radiation (1.6), occupational exposure to
chemicals (1.5), cigarette smoking (1.6), and a history of gout (1.7). In
women, coffee drinking (1.6) and a history of tuberculosis (2.0) were
identified as risks; a history of allergy in the patient appeared to be
protective (0.3). Chemical exposures were identified tentatively as
paints, varnishes, lacquers, gum and wood chemicals, and industrial
chemicals. Risk ratios derived from this study are uniformly low, and
those for factors traditionally regarded as important for bladder
cancer (smoking and occupation) are lower than a risk ratio having
no previously recognized association with the disease (family history
of allergy, in men only). This aspect of the findings casts a degree of
doubt on the soundness of the study design, particularly the use of
patients with urologic disease other than bladder cancer as controls.
Discriminant function analysis presumably identified both smoking
and occupational exposure to chemicals and radiation as indepen-
dent risk factors for bladder cancer. No data were offered from which
to determine whether these risks are additive or synergistic.

Calculating proportionate incidence ratios for bladder cancer
within broad occupational categories used by the Los Angeles
County/University of Southern California Cancer Surveillance Pro-
gram, Weinberg and colleagues (1983) examined incidence data for
Los Angeles County over the period 1972-1976. They found higher
relative risks of bladder cancer among managers and salesmen (high
on the socioeconomic scale) than among service workers, laborers,
and transportation workers (low on the socioeconomic scale). The
latter group have been reported to be the heavier smokers (CDC
1976; Bonham and Leaverton 1976). The authors argued that, at

381


least in the Los Angeles area, the occurrence of bladder cancer in
relation to social class corresponds more closely with coffee-drinking
habits (greater in the upper classes) than with smoking or occupa-
tion. The social class distribution of bladder cancer incidence in Los
Angeles contrasts sharply with the report of Adelstein (1980) in
England, who found from analysis of death certificate and census
data for 1970-1972 that cancer in general and bladder cancer in
particular were afflictions primarily of the lower socioeconomic
classes. The discrepant relationships to social class categories may be
attributable to the different parameters used in the two studies
(incidence versus mortality), to the disparate cultural and economic
circumstances of the populations examined, or specifically, to
different spectra of environmental carcinogens in the two regions.
Interestingly, the two studies are in essential agreement with
respect to lung cancer but not bladder cancer.

Glashan and Cartwright (1981) and colleagues (Cartwright et al.
19811, in a case-control study, matched 991 incident cases of bladder
cancer treated at three West Yorkshire clinics over 3 years to age-
and sex-matched controls "without malignant disease." The source
of the controls was not mentioned, but presumably they were clinic
patients. Elevated relative risk ratios for smoking (not quantitatively
defined) were found in men 0.8) and women (1.6). Significantly
elevated relative risks were found for chemical industry workers and
printers, but not for leather workers, hairdressers, or dye users.
Nonsmoking dye manufacture process workers experienced an
apparent increase in risk of bladder cancer (RR 1.9, not statistically
significant), but dye process workers who smoked were at highly
significant risk (RR 4.6). A similar relationship was found among
printers. The risk ratios for nonsmokers were admittedly based on
few subjects. Risk ratios for dye process workers increased strikingly
with duration of employment (>29 years, RR 10.5). The chemical
nature of the dyes to which workers were actually exposed was not
discussed.

A case+control study of 212 cases of bladder cancer in rural
Denmark drew upon general population controls matched to cases by
sex, age, and region of residence (Mommsen et al. 1982, 1983).
Multivariate logistic regression was used to identify factors (evalu-
ated by questionnaire) associated statistically with the malignancy.
Significant relative risk ratios were found for tobacco use (l&2.1),
work with petroleum, asphalt, oil, or gasoline (2.9-3.8), industrial
work (2.21, work with chemical materials (2.0), alcohol use (2.3), and
previous venereal disease (2.9). Farmers, who were presumably
exposed to pesticides, were at less than average risk of developing
bladder cancer. The report did not explore the interactive effects of
occupation and tobacco use.

392


A case-control study in the greater New Orleans area, wherein 82
patients with bladder cancer and 169 matched general population
controls were interviewed by telephone, was used to identify
smoking of filter cigarettes (but not of unfiltered cigarettes or other
tobacco products) as a risk factor for bladder cancer (Sullivan 1982).
Matching criteria were not specified. A large number of employment
categories and chemical exposures appeared to involve risks, most
prominently mechanical engineers and people exposed to paint
thinners, coal, petroleum, metals, welding materials, office supplies,
and industrial equipment.

In a study in northern New Jersey (Najem et al. 1982), 75 cases
were compared with 150 patient controls, matched by age, sex, race,
place of birth (in New Jersey or elsewhere), current residence, and
the clinic providing care. Occupations were recorded only when job
tenure was more than 1 year. Smoking habits were characterized as
never smoked, former smoker, or current smoker. Several criteria
were used to test the significance of associations, and significant
risks were analyzed to test for the confounding effects of smoking.
Significant risk ratios were identified for cigarette smoking (2.0) and
work in dye (3.1), petroleum (2.5), and plastics (3.4) industries, but
not for employment in rubber, textile, printing, rodenticide, or cable
industries, although some ratios did exceed 1. When the significant
occupational risk ratios were analyzed within the three strata of
smoking status, ratios for current smokers were essentially the same
as those calculated without controlling for smoking. Curiously, the
occupational risk ratios for nonsmokers in the dye, plastics, and
petroleum industries consistently exceeded the ratios for current
smokers, but the ratios for ex-smokers were consistently lower (1.3 to
1.5). Some ratios were based on only a single case in a smoking-
occupation cell.

In a recently reported case-control study at Turin, Italy, 512 male
bladder cancer patients diagnosed from 1978 to 1983 were compared
with 596 patient controls (225 urologic, 371 surgical) (Vineis et al.
1984). Smoking and occupational information was assembled by
interview. Highly significant relative risk ratios were found for
cigarette smoking, the magnitude depending on smoking intensity,
on age when smoking started, and possibly on brand of cigarettes
smoked. Occupational risk analysis was based on 64 patients
classified as "exposed": 14 cases and 2 controls employed more than
6 months in dye production (said to include exposure to benzidine
and betanaphthylamine), plus 28 cases and 20 controls employed in
the rubber industry. From this, the authors calculated risk ratios
strongly suggesting interactive effects of occupational exposure and
smoking, most striking in workers less than 50 years of age, and
dependent on smoking intensity (relative risk was 144.0 for hazar-
dously employed workers who smoked). The relative risk for

383


hazardous occupation among nonsmokers of all ages (there were only
five chemically exposed: two cases, three controls) was 3.7. The
relative risk for smoking among the nonexposed of all ages was 5.2.
The risk for the occupationally exposed who smoked was 11.6
relative to nonexposed nonsmokers. The risk ratio relationships
based on all age groups are more suggestive of an additive overall
effect than of synergy. The small number of occupat,ionally exposed
nonsmokers in the study limits the confidence that can be placed in
the analysis.

Smith and colleagues (1985) recently examined relationships of
occupational solvent exposure and smoking to incident cases of
bladder cancer in regions of the United States served by the National
Cancer Institute's Surveillance, Epidemiology, and End Results
(SEER) program and included in the National Bladder Cancer Study
(NBCS) of 1978. Controls selected from the NBCS study were
frequency-matched to the cases by age and sex. Among nonsmokers
reporting at least 6 month's exposure to chlorinated and simple
hydrocarbon solvents used in dry cleaning and in other industries,
the relative risk of bladder cancer was significantly elevated only in
women (RR 1.38), and this was not significantly related to duration
of exposure. In both men and women chemically exposed, however,
the risk of bladder cancer increased progressively and significantly
from nonsmokers to former smokers to current smokers. There was
no evidence of interaction between the effects of occupation and
smoking. The evidence of a smoking effect was consistent and
substantial in this study (highest RR 4.681, but indications of a
solvent exposure effect were weak and of borderline statistical
significance.

Inhalation of combustion effluents is thought to pose a risk of
cancer at various sites, including the bladder. For a case-control
study of 81 male bladder cancer patients in Quebec (1970-19751, age-
and sex-matched individuals living in the patients' neighborhoods
were recruited to serve as controls (Theriault et al. 1981). Detailed
histories were taken covering lifetime employment and residence,
medications, personal habits, and water supply. Smoking habit was
characterized qualitatively and quantitatively. Information on de-
ceased cases was received from next of kin. These authors calculated
a mean relative risk of bladder cancer of 5.70 among currently
smoking workers in the electrolysis department of an aluminum
reduction plant. Relative risk for smoking among other workers was
1.82, and risk associated with electrolysis department employment
alone was 1.90. (It was necessary to base the latter estimate on ex-
smokers because there were no nonsmokers so employed.) The
independent risk ratios are not statistically significant, but the
range of values for electrolysis workers who smoked extended from
2.0 to 12.30. To the extent that the ratio estimates can be relied

384


upon, they suggest a strong interaction between smoking and
occupational exposure.

Silverman and colleagues (19831, in a population-based case-
control study of 303 white male bladder cancer cases in Detroit
(1977-19781, explored occupational, dietary, and personal habit
associations. Controls under 65 years of age were chosen from the
Detroit population by random digit dialing, operating with a pool of
2,110 households. Controls of retirement age were selected at
random from Health Care Financing Administration lists. A total of
296 controls were recruited for home interviews. Analysis of
occupational associations relied on an "ever employed" query, and
responses were classified according to the industry identified and by
occupation. An apparent strong interaction involved truck driving as
an occupation and cigarette smoking. Among people who had never
been truck drivers, smoking one or two packs of cigarettes per day
increased the risk of bladder cancer by a factor of 1.6; smoking more
than two packs increased the risk ratio to 2.1. The ratio for truck
drivers smoking less than one pack per day was 1.3; for smokers of
one or two packs per day, the ratio was 6.8. The risk ratio for heavy
smokers could not be calculated because none of the controls
reported smoking more than two packs per day. A relationship with
the inhalation of diesel exhaust was suspected, but could not be
confirmed from the data.

Not unexpectedly, the case-control studies used to test a relation-
ship of pesticide exposure to urinary tract cancer are inconclusive.
Pesticides are chemically and toxicologically diverse; worker expo
sures to them are equally varied. It is unlikely that in epidemiologic
studies based on broad occupational categories carcinogenic risk
would be detected, if indeed it exists. Several case-control studies of
bladder cancer have indicated that as an occupational group, people
"working in agriculture" are at no more than average risk of urinary
tract cancer, or are actually at less than average risk (Anthony and
Thomas 1970b; Cole et al. 1972; Howe et al. 1980). In some studies of
exposures to pesticides, specifically, nonsignificantly elevated risk
ratios have been shown (Najem et al. 1982; McLaughlin et al. 1983).
In Canada, bladder cancer was found to be significantly associated
with crop spraying and nursery work as occupations (Howe et al.
1980). These associations were said to be unaffected by controlling
for smoking.

Other Specific Cancer Sites

Cancer of the kidney and upper urinary tract has received less
attention than bladder cancer. In a nationwide case-control study of
202 patients with renal adenocarcinoma (Wynder et al. 19741, the
past personal and occupational histories of the patients were
examined in relation to histories from other hospitalized patients.

385


Relative risk among heavy smokers (more than one pack per day)
under 50 years of age was 8.0, but only 2.1 in patients over age 50.
Moderate smokers (up to one pack per day) were at intermediate
risk. Except for a tentative identification of employment in textiles
as a risk factor, no associations with occupational exposures to
metals, dyes, or other organic chemicals were found.
In the Boston area, 43 cases of cancer of the renal pelvis and ureter
were studied in relation to bladder cancer cases and randomly
chosen general population controls (Schmauz and Cole 1974). Only
among smokers of more than two and one-half packs of cigarettes per
day did a significant risk appear (RR 10.0). Of the occupational
categories identified, only leather working exhibited a suspect
relationship to cancer at these sites.
Occurrences of renal cell carcinoma (495) and cancer of the renal
pelvis (74) in the Minneapolis-St. Paul area from 1974 to 1979 were
studied for heritable and environmental risk factors (McLaughlin et
al. 1983, 1984). Controls were chosen randomly from the metropoli-
tan area population. Because half of the cases were already deceased,
background data had to be obtained through next-of-kin interviews.
With respect to cancer of the renal pelvis, the risk of disease
increased steadily in both men and women in relation to smoking
intensity (maximum RR 10.7 in men, 11.1 in women). The only links
to occupation appeared in relation to exposures to hydrocarbons:
coal, natural gas, and mineral and cutting oils. There were not
enough cases to permit analyses for smoking risk within occupations.
Renal cell carcinoma also appeared to be related to cigarette
smoking, but relative risk ratios were much lower (2.3 in male, 2.1 in
female heavy smokers), and the dose-response relationship was not
as consistent as in the case of renal pelvis or bladder cancer.
Analysis for "usual industry of employment" failed to identify any
significant occupational associations.
Musicco and colleagues (1982), in a case-control study of brain
neoplasms in Italy, sought to associate the occurrence of gliomas
(various types and grades) with occupations of victims prior to
diagnosis during 1979 and 1980. Forty-two cases were matched with
nonglioma patients at the Neurological Institute C. Besta of Milan.
The controls were matched by age, sex, and area of residence. They
suffered from a variety of chronic diseases, some probably character-
ized by physical and or mental disability from a relatively early age.
Smoking was defined as a minimum l-year usage, and total lifetime
usage was estimated. More than 20 pack-years was considered heavy
smoking. The authors found a significantly elevated risk ratio (5.0)
for "agricultural work after 1960" when the data were analyzed
without stratification. When stratified by sex, age, and residence, the
ratio was 1.9 (not significant). The relative risk was 1.3 for smoking
and 1.6 for heavy smoking, neither statistically significant. No


occupational risk ratios for nonsmokers were calculated. Particular-
ly with respect to occupational risk calculations, the appropriateness
of neurologically afflicted patients as controls must be questioned.
Nonetheless, the authors were inclined to indict modern pesticides
and fertilizers as causal factors for gliomas.

Austin and Schnatter (19831, in a followup case-control study of 21
patients dying from a brain tumor in a Texas petrochemical worker
cohort, indicated that the tumors were of several different types.
Efforts to identify unique past chemical exposures of brain tumor
victims were not successful.

Using case-control methodology in reviewing 142 cases of pancre-
atic adenocarcinoma in several large U.S. clinical centers, Wynder
and colleagues (1973) demonstrated that cigarette smokers were at
increased risk of developing this disease. Risk ratios increased
progressively with the number of cigarettes smoked per day.
Controls for this study were patients in the same hospitals who had
been interviewed for other epidemiologic studies. Controls did not
include patients suffering from tobacco-related cancers (mouth,
larynx, lung, esophagus, bladder, kidney) or other tobacco-related
diseases (bronchitis, emphysema, coronary heart disease). Fifteen
male cancer patients reported having been occupationally exposed to
"dyes, chemicals, metal dust, saw dust, grease, oil, or gas fumes," but
there was no difference between cases and controls with respect to
the frequency with which this exposure was reported.

A case-control study in New Jersey (Stemhagen et al. 1983) of 265
victims of primary liver cancer occurring from 1975 to 1980 was
conducted by interview of family members. Controls were selected
from hospital records and death certificates, and were matched by
age, sex, race, and county of residence. No evidence was adduced to
indict smoking as a factor in causing this disease. Significantly
elevated risk ratios were derived for farm laborers but not for farm
owners or farm managers or for people engaged in manufacturing
pesticides. Other people apparently at risk were gasoline service
station employees, those employed at eating and drinking establish-
ments, and those providing laundry and dry cleaning services. It was
not possible to identify specific past chemical exposures that might
have contributed to the risk.

A recent study of 102 cases of primary liver cancer in Sweden
utilized controls matched by age, sex, race, year of death, and
municipality where the decedent had lived (Hardell et al. 1984). No
association with smoking history was found. Occupational exposure
to solvents appeared to double the risk of liver cancer. No other
occupations or chemical exposures were identified as risk factors,
although a strong association with alcoholism was indicated.

Investigation of 207 cases of large bowel cancer in a Quebec
community explored several risk factors in cases and controls, the

387


latter selected from the communities where the cases resided, and
matched by age and sex (Vobecky et al. 1983). Smoking was not
identified as a significant risk factor, although a slightly elevated
risk ratio (1.2) for smoking (alone) was calculated. Industrial
exposure at a local synthetic fiber factory did appear to be a
significant association (RR 2.2). When the risk of industrial exposure
and smoking were considered in combination, a higher risk was
evident (2.81, at a stronger level of significance. A moderate degree of
smoking+ccupation interaction is suggested.

Chronic Lung Disease

The likelihood that exposure to dusts and fumes in rubber product
manufacture plays a causative role in the chronic obstructive lung
disease encountered in this industry was examined in two studies.
Fine and Peters (1976) assessed symptomatology and pulmonary
function in 65 white male workers engaged an average of 7 years in
rubber processing at three Akron tire plants. Air sampling showed 1
to 3 mg/m3 of respirable dust in the work environments. Smoking
habits were classified as never smoker, former smoker, current
cigarette smoker, and current and former pipe and cigar smoker.
Controls (189) were chosen from plant workers not exposed to
polluted air. Processing workers reported a much higher prevalence
of cough and phlegm than controls; this was true among nonsmokers
as well as smokers in the various categories. Smoking nearly doubled
the frequency of this symptom complex in the processing workers.
However, dyspnea and wheeze, generally considered indicative of
chronic obstructive lung disease, were no more prevalent among
processing workers than among controls. Reported frequencies of
bronchitis, pneumonia, asthma, and winter colds were not signifi-
cantly greater among these workers than among controls. Pulmo-
nary function testing yielded important findings. In comparing all
workers with all controls, only the ratio of forced expiratory volume
in 1 second to forced vital capacity (FEV,/FVC) was significantly
lower in the particulate-exposed workers. However, the exposed
group and the control group were subdivided according to whether
they had been employed in their respective jobs for more or less than
10 years. Although the long-term processing workers were older and
had smoked longer than the controls, decrements in flow rates and
FEV, /FVC were not significantly correlated with years of cigarette
smoking. Using appropriate adjustments for age, the long-term-
exposed  employees  exhibited significant deficits in FEVI,
FEV,/FVC, and flow rates at 50 and 25 percent of FVC. Multiple
regression analysis confirmed that duration of employment in
rubber processing was a significant predictor of reduced FEV, and
FVC. Employment for more than 10 years appeared to cause a
significant decline in FEV,/FVC and the FVC-standardized flow rate


at 50 percent FVC. These results were independent of smoking
variables, ethnicity, socioeconomic status, and age. The absence of a
correlation between decrement in lung function and cigarette
smoking and the small number of workers in this study raise
questions about the generalizability of the data in this study.

Lednar and colleagues (1977) examined the work history and
smoking habit backgrounds of 73 former rubber workers who were
retired prematurely between 1964 and 1973 with medically docu-
mented, disabling pulmonary disease. They were members of a
cohort of 4,302 workers employed in 1964 at an Akron plant. Thirty-
nine were retired with emphysema, 10 with lung cancer, 8 with
asthma, and 16 with other pulmonary conditions. Work background
and likely exposure to dusts and fumes were determined from
company records; smoking histories were obtained from question-
naires mailed to retirees or relatives. The investigators utilized two
control groups, the first consisting of disabled employees retired
because of diseases other than pulmonary (disabled controls) and the
second of currently employed workers and early retirees free of
acknowledged pulmonary disease (nondisabled controls). Relative
risk ratios were calculated for smoking and for occupational
exposures to dusts and fumes. Relative risks for pulmonary disability
retirement in relation to smoking and various occupational titles
were also calculated. Risk ratios for smoking alone (based on
smokers and nonsmokers at worksites not otherwise contaminated)
were consistently greater than 1.0, but they were significant only in
the case of maintenance workers. For all workers combined, the
smoking risk ratio was 2.95 (p<O.O5). Ratios for occupational
exposure alone were remarkably elevated in some job classifications,
but none were significant. When the combination of smoking and
occupational exposure was considered, however, substantially and
significantly elevated risk ratios were found for workers engaged in
extrusion (15.81, finishing and inspection (7.81, curing (6.71, and other
tasks. Furthermore, combined exposure to dust and cigarette smoke
appeared to increase by tenfold to twelvefold the risk of pulmonary
disability. The data suggested interactive effects between smoking
and occupational pollutants, more in the range of potentiation than
simple addition.

Another suggestion of enhanced adverse effects from cigarette
smoke and irritating air pollutants has come from examination of
workers exposed to airborne contaminants from the milling of
rubber (Sparks et al. 1982). For the factory worker population as a
whole, productive cough was definitely more common among current
smokers than among nonsmokers: 35.5 percent of the smokers versus
6.5 percent of the nonsmokers in parts of the plant where dust
concentrations were minimal. Among workers exposed to irritating
dust, 8 percent of the nonsmokers experienced a productive cough

389


and 42.5 percent of the smokers were so affected. In a work area
where dust concentrations were highest, but did not generate
complaints of upper respiratory tract irritation, 3.3 of the nonsmok-
ers and 29.3 of the smokers reported productive cough. The
combination of irritating fumes or particles with cigarette smoke
may stimulate bronchial mucus secretion more than either factor
acting alone.

In a recent longitudinal study of 3,799 male coke oven workers,
Madison and colleagues (1984) examined relationships between a
series of risk variables (age, current smoking status, job location) and
indices of pulmonary function (FEV1, FVC, and detailed exfoliative
cytology of sputum). Covariance and multiple logistic regression
analyses were done to identify the principal factors predicting FEV,
and FEV,/FVC. Measurements were done in 1978 and in 1982.
Appropriate adjustments were made for height, weight, and years at
the coke oven. Data from Caucasians and blacks were analyzed
separately. Both smoking and job location (six categories) had
significant detrimental effects on FEV, and FEV,/FVC in Caucasian
workers. In blacks, smoking adversely affected FEV, and FEV,/FVC
but job location did not.

Sputum cytology included examination for various cells (reactive
bronchial epithelial cells, metaplastic epithelium, histiocytes, poly-
morphonuclear leukocytes); prominence in each specimen was
graded on a scale of 0 to 4, and atypical metaplasia was rated as
mild, moderate, or severe. The investigators found excessive promi-
nence of certain exfoliated cells well correlated with reduced FEV,
and FEV,/FVC, a result apparently not caused by smoking, because
the percentage of workers showing cells was equivalent in both
smoking categories. Multiple logistic regression was done to identify
factors principally responsible for metaplasia in Caucasians: age and
smoking were the strongest predictors, but job location was also a
significant factor. Among blacks, only smoking and age were
significantly predictive.

Madison and colleagues (1984) believe that their use of data from
two examinations, plus sputum cytology, identified work-related
pulmonary injury not demonstrated in earlier cross-sectional studies
and that the findings may portend pulmonary disability in some
workers. The interval between examinations was not considered long
enough to permit time trend analysis. These authors reported no
measurement of airborne particulate or fumes at the six job
locations.

Research Recommendations

1. Efforts to minimize workplace exposure to known and suspect-
ed carcinogens should continue and not be delayed in anticipa-

390


tion of definitive evidence of hazard from occupational or
environmental studies in humans.

2. Efforts to assist smokers in their efforts to quit smoking must
continue in all sectors of the population. Blue-collar workers
have a higher prevalence of smoking and a higher exposure to
materials that might interact with cigarette smoke to increase
disease risk. Because of these dual exposures, an intensive
effort should be made to reduce the smoking rates of these
workers.

3. Epidemiologic studies to assess the health impacts of smoking
or work exposures to noxious substances should take both
factors into account as potentially causative. Additionally, the
possibility of interaction should be kept in mind, and whenever
possible, tested for.

4. Laboratory animal studies designed to explore the health-
damaging effects of tobacco smoke should include experiments
capable of identifying interactions with major industrial pollu-
tants.

5. There should be continuing research aimed at identifying the
principal constituents of common industrial pollutants that act
as cancer initiators and promoters. There should also be
continuing efforts to demonstrate the mechanism of tissue
damage caused by cigarette smoke and various industrial
pollutants, alone and in combination.

6. Modern tissue culture techniques employed to identify carcino-
gens should be exploited as test systems for interactive effects
between tobacco smoke constituents and industrial pollutants.

Summary and Conclusions

1. The biotransformation of industrial toxicants can be modified
at least to some extent by the constituents of tobacco smoke
through enzyme induction or possibly inhibition. Both tobacco
smoke and some industrial pollutants contain substances
capable of initiating and promoting cancer and damaging the
airways and lung parenchyma. There is, therefore, an ample
biologic basis for suspecting that important interactive effects
between some workplace pollutants and tobacco smoke exist.
2. In mortality studies of coke oven workers and gas workers,
convincing evidence has indicated that work exposures to oven
effluents are causing an excess risk of lung cancer in spite of
the lack of adequate information on smoking. Other mortality
studies that suggest small increases in smoking-related dis-
eases, such as pancreatic cancer in refinery workers, cannot be
interpreted without more information on smoking.

391


3. For bladder cancer, the interactions between smoking and
occupational exposure are unclear, with both additive and
antagonistic interactions having been demonstrated.
4. The risk of pulmonary disability in rubber workers was
increased when smoking and occupational exposure to particu-
lates were combined. There are few empirical animal experi-
ments that demonstrate interactive effects between cigarette
smoking and various industrial chemicals for lung disease.

392


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noma of the kidney. Journal of the Nutional Cancer Institute 53(6):1619-1634,
December 1974.

WYNDER, E.L., STELLMAN, SD. Environmental factors in the causation of bladder
cancer. In: Connolly, J.G. ted.). Carcinoma of the Bladder. Progress in Cancer
Research and Therapy, Vol. 18. New York, Raven Press, 1981, pp. 25-36.
ZAVON, M.R., HOEGG, U., BINGHAM, E. Benzidine exposure as a cause of bladder
tumors. Archives OfEnvironmental Health 2711-7, July-December 1973.

397


CHAPTER 10

COTTON DUST EXPOSURE
AND CIGARETTE SMOKING


CONTENTS

Introduction

Influence of Cigarette Smoking on the Natural History of
Byssinosis

Cigarette Smoking Patterns Among Workers Exposed
to Cotton Dust

Acute Effects of Smoking and Cotton Dust Exposure
on Respiratory Symptoms
Effects of Smoking and Cotton Dust Exposure on
Pulmonary Function Tests
Chronic Clinical Effects of Cotton Dust Exposure

Mechanisms of Cotton Dust Lung Injury
  Inflammation (Bronchitis)
  Airways Constriction

Chronic Inflammatory Lung Destruction

Cotton Dust Exposure and Mortality From Respiratory

Disease and Lung Cancer

Control of Cotton Dust Exposure

Summary and Conclusions


References

401


Introduction
Exposures to cotton, hemp, and flax dust have been associated
with two acute pulmonary responses: irritant (industrial) bronchitis
and chest tightness (byssinosis). These symptoms, often accompanied
by reduction in lung function, have occurred in 2 to 30 percent of
cotton textile workers within hours of resuming exposure following a
weekend or holiday @chilling 1956; Morgan et al. 1982). These
elements of the acute cotton dust pulmonary response may not occur
together, and may represent responses of distinct pulmonary mecha-
nisms. The exposure variables or host characteristics that lead to
cough rather than to bronchoconstriction are currently under
careful study (Hogg and Eggleston 19841. The effects of cigarette
smoking upon these different responses is also incompletely under-
stood.
In the manufacture of cotton textiles, cotton dust exposure occurs
most intensely when the tightly packed bale is opened and when
abrasive crushing and carding remove the "trash" (plant bracts and
other parts, dirt, bacteria, and fungi) and align the fibers for
spinning (Gideon and Johnson 1978). Normally, as the cotton fibers
are spun, twisted, and woven into cloth, progressively less dust is
generated. By the time cotton cloth is processed, the procedure is
practically free of cotton dust (Kilburn 1983).
Cross-sectional studies have shown that byssinosis prevalence is
greatest among cotton textile workers in the dusty preparation jobs
(e.g., carder, stripper, or grinder) (Figure 1). Byssinosis prevalence
has been related to the duration of cotton dust exposure, to the
quality of the raw cotton, and to the levels of lint-free cotton dust
(Molyneux and Tombleson 1970; Merchant, Lumsden, Kilburn,
O'Fallon et al. 1973b; Kamat et al. 1981). At a cotton dust level of 0.2
mg/m3 (lint-free dust of approximately 15 urn or less), approximately
15 percent of the cotton textile workers have some grade of
byssinosis (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b).
While a small sex-specific effect (male disadvantage) has been noted
(Berry et al. 19741, no age effect has been shown after adjustment for
exposure (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b; Berry
et al. 1974). Cigarette smoke interacts with cotton dust exposure in
cotton textile workers and has been associated with increased
byssinosis prevalence and severity (Berry et al. 1974). The frequency
of byssinosis has been closely correlated with the presence of chronic
bronchitis, and both symptoms have been associated with ventilatory
impairment (Imbus and Suh 1973). Cross-sectional studies have
correlated cotton dust exposure with two components of ventilatory
impairment: reduction in the baseline level of forced expiration and
reversible loss of function across a work shift. The relationship of
byssinosis and bronchitis with ventilatory impairment and its


   Z!






   2(

P
1
s   1t
6
1
3
h

   1C






    5






   c

26.2

I cotlon
[7 Cotton/Synthetic

16.2

Preparation

Yarn production    Slashing/Weaving

Miscellanecus

FIGURE l.-Byssinosis prevalence by work area and raw
        material use

NOTE- Average prevalence- cotton. 5.7. percent. cotton/synrhetlc, 4 4 percent.
SOURCE Imbus and Suh (19731.

relationship to cigarette smoking is discussed in greater detail later
in this chapter.

Influence of Cigarette Smoking on the Natural History of
Byssinosis
Cigarette Smoking Patterns Among Workers Exposed to
Cotton Dust

The smoking patterns of cotton dust exposed workers have been
reported by a number of authors and are presented in Table 1.
In summary, current studies show that male cotton workers tend
to smoke to a greater degree than do female cotton workers. Male
textile workers in Western Europe and in Canada smoke with

404


TABLE l.-Prevalence of smoking in studies of cotton workers

Study

Number and type
of population

Smoking characteristica (percent)                     Comments

Schrag and Gullett
(1970)

Kari-Koskinen and    967 female cotton workers,
Hirvonen (1970)     Finland

Merchant, Kilbum.   435 cottonsynthetic blend
et al. (1972)      workers, North Carolina

Kilburn, Kilburn     1,046 female textile
et al. (1973)      workers, North Camliia

Szymczykiewin et
al. (1970)

For et al.
(1973)

509 cotton textile workera

637 men, 2,530 women

Cotton workers, 35 mills,
Great Britain

Age
17-29
30-39
4049
iw-60

CigslbY
l-14
15-24
>24

2.6

SM           EX           NS
54.7           12.0          33.3


SM
45.2
35.6

Syn. wool workers
Cottonmill workers

Men
Women

60.5
6.9

SM           NS           EX
62           31.6           6.3


36.2
21

SM
36

EX/NS

Percent smoking
~1 pack/day not
available

16.9


39.8
14.1
9.0
5.0

63.1

>53% began
smoking at 15-19
years of age


E  TABLE L-Continued


                 Number and type
   Study             of population                 Smoking characteristics (percent)                     Cmnmenta

Imbus and Suh     10,133 cotton workers.
11973)         North Carolina

Men       78
Women      43

Smokers include
ever smoked
1 cig/day for 1
Y-r

Berry et al.
(1974)

14 cotton and 2 manmade
fiber milla. Great Britain

Men       75.6
Women      56.5

Former smokers
not reported

Zwkin et al.
(1976)

Wool workers and controls

Workers   Men        47
      Women       0
Controls   Men        55
      Women       0

Khogali
(1976)

271 ginnery workers, Sudan

SM
36.5

Jones et al.
(1977)

153 cottonmill workers,
southeast United States

SMIEX
70

Almost l/2
smoken said
smoked <5
cigs/day

Bouhuys et al.
(1977)

Card and weave room
workers, South Carolina

         SM
Men      X-41
Women     15-25


TABLE l.-Continued

Study

Number and type
of population

Smoking characteristics (percent)                     Comments

Palmer et al.
(1978)

Bouhuys et al.
(1979)

203 gin workers

Textile workers, aged 245,
South Carolina

Ginnera


Pressmen


Others


Controls

Women
Carding

SM           EX
51.1          25.5
(16.0)'         (9.6)
57.1           19.1
(7.3)         (4.1)
45.5          15.1
(15.3)         (8.0)
52.3          19.2
(11.4)          (9.1)

SM           EX           NS
18           14            68
20           10            70
17           14            69
20           10            69
15           11            74

Jones et al.       Cotton and wool/synthetic
(1979)          mill workers

&,rii,g
Weaving
Others'
Men
Carding

. -
Preparing
Weaving
Others'

Mill 1
Mill 2
Mill 3
Mill 4       38.0          62.0

SM'           NS
52.6          47.2
66.9          33.1
64.8          35.2

26           44            26
37           4.5            16
50           42            8
38           37            16
20           3.5            30

NS
23.4


23.8


39.4


28.5

`( )=mean
pack-years
(1 pk/day/year)

* Includes cloth
room workers and
miscellaneous job
CAgOrieS

' Smokers include
ex-smokera


TABLE k-Continued

Study

Number and type
of population

Smoking characteristics (percent)                      Comments

Barman
(1979)

-

70 cottonmill workers

MUI
Women

Sparks and Peters
(1960)

Grimard and Adams
(1981)

Becketal
(19821

Cotton duetexposed workers

Men
Women

Textile workers, Canada

Men
Women

118 male and 162 female
cottm textile workers

Men
Workers
Controls
Women
Workers
Controls

SM           EX
44           28
58

44           28
55           -


76.6
60.4

27
16

31
43

NOTE SW Smoker; EX Exnmoker. NS. Nonrmoker


greater frequency than do American workers, with many studies
showing the proportion of smokers to be well over 70 percent.

Acute Effects of Smoking and Cotton Dust Exposure on
Respiratory Symptoms

The symptoms 01 ?ilonddy ches t t;,htness begin gradually, S or 4
hours after the cotton texrile worker returns to work. A dry cough
and shortness of breath on exertion frequently accompany the
sensation of chest tightness. However. the physiologic reaction
associated with Monday chest tightness is not confine2 to the chest.
X low grade temperature. a 20 to 3n percen: increase in the
peripheral white blood cell I polymorphonuclear ieukocyte 1 count,
and a general malaise have been frequently reported These systemic
symptoms suggest the presence of a host in!lammarory response;
however, the relationship between these systemic symptoms and the
symptom of che?t tightness is not well defined.

By 1936, an association had heen recognized between Monday
chest tightness and detectable loss of ventilatory capacity and
increased breathlessness iPrausnltz 19361. Recognition that in sus-
ceptible cotton mill workers. Monday chest tightness may be
followed by permanent respiratory disabi!ity led to the evolution of a
standard byssinosis case definition. Schilling and colleagues (19551
developed specific questions concerning Monday chest tightness for
the British Medical Research Council's respiratory symptom survey
questionnaire (British Medical Journal 1960). A positive response to
the standardized questions regarding Monday chest tightness de-
fined the presence of byssinosis.

Molyneux and Tombleson (19701 conducted one of the first
prospective studies of byssinosis. 4t the initial examination, these
investigators interviewed 1.359 workers from 14 cotton spinning
miZc and 227 -xorkers from 2 manmade fiber spinning mills in
Lancashire. United Kingdom. Followup examinations were conduct-
ed at 6-month intervals over 3 J.ears, from 1963 to 1966. Byssinosis
and bronchitis prel-alence were :Ieterl..A
                  ~;ned by the use of the Jledical
Research Council's questionnaire on respiratory sy!:iptoms [British
.Medicai .Journal 196Oi, to which :t.e Roach and Schilling t1960)
questions on chest tightness wert- added. Bjs;inosis bvas graded as
follows (Molyneux and Tombleson 197Oj.'

Grade 0: No evidence of chest tightness or breathing diffi-
    culty on the first day of the workweek
Grade 1 `2: Occasional chest tightness on !`rlondays


Grade 1: Chest tightness or difficulty in breathing on
    Mondays only
Grade 2: Chest tightness or difficulty in breathing on
    Monday and other days

Age, length of exposure to cotton dust, and smoking habit were
determined by questionnaire. Individuals were considered smokers if
they regularly smoked one or more cigarettes per day. Hexlet and
total dust air samplers were used to measure the mass concentration
of the respirable, medium, and fly components of the total airborne
dust.

Byssinosis prevalence (adjusted for age, sex, and mill type) showed
a progressive increase with increasing duration of cotton dust
exposure (Table 2) (Molyneux and Tombleson 1970). A rearrange-
ment of the data from this Lancashire mill workers study and
calculation of the Mantel-Haenszel (weighted) odds ratios (Mantel
1963) shows an interesting relationship between smoking, byssinosis,
bronchitis, and sex. A similar relationship is demonstrated by data
from studies of American cotton mill workers (Merchant et al. 1972;
Imbus and Suh 1973). Cigarette smoking was associated with an
overall 2.21-fold excess risk of bronchitis in the Lancashire cotton
mill workers (Table 3). Cotton mill workers of both sexes who smoked
had a consistently greater prevalence of bronchitis than did non-
smokers. The magnitude of the smoking effect was similar for men
12.2%fold) and women (2.16-fold). The presence of bronchitis con-
ferred an approximately twofold excess risk of developing byssinosis
(Table 4). This risk was significant for men and for women, for
smokers as well as for nonsmokers. Once the presence of bronchitis
had been controlled for, however (Table 51, cigarette smoking did not
add significant additional risk for developing byssinosis.

One may interpret these observations to show that among cotton
mill workers both cotton dust exposure and cigarette smoking
produced the symptoms of bronchitis. Bronchitis, in turn, seemed to
confer additional risk for the development of acute chest tightness
(byssinosis). Cigarette smoking, therefore, seems to facilitate the
development of byssinosis in smokers exposed to cotton dust, perhaps
by the prior induction of bronchitis. Applying an additive logit model
(6 dust levels x 3 lengths of exposure x 4 combinations of sex and
smoking habit) to these data, Berry and colleagues (1974) found that
cigarette smokers had a modest (1.4-fold) increase in the adjusted
prevalence of byssinosis when compared with nonsmokers and ex-
smokers. Two years after the initial questionnaire survey, these
investigators were able to reinterview about half of the original
population (669 cotton workers and 127 manmade fiber workers).
Incidence and remission rates were tabulated for byssinosis and
bronchitis by length of exposure, sex, and smoking status. The
incidence of both bronchitis and byssinosis was greater among

410


TABLE 2.-Prevalence (percent) of byssinosis in nine
        exposure groups

Number
in group

Prevalence
adjusted for
age. mill type.
and sex

CL4        305            52             8.8            8.0
%9        155           23 3            20.5           19.2
l&14        168           28 0            22 3           21.0
15-19        187           35.8            29 5           27.5
20-24        117           36.8            30 9           31.1
2529        115           43.5            40 2           42 4
30-34        94           30.9            302           35 1
3639        99           35 4            36.5           414
140        119           33 6            37.7           418

SOURCE Malyneux and Tombleson (19701

TABLE 3.-Age-adjusted association of bronchitis and
      smoking, by byssinosis status and sex

Smoker

   Bronchitis             Bronchitis         Chi square and
  with byssinosis        without byssinosis        odds ratio for
                                    the association of
N   Present   Absent     N   Present   Absent    smoking/bronchitis'

Yes     127
No     33

557c
554

45%
45%

Men

301   46%     54%        X*=15.20
105   21%     79%         OR = 2.28
                 cp<o.ooo1i

Women

Yes
NO

125   48%
78   33%

52%
67%

322   31%     69%        x*=21.10
268   16%     84%         OR=2.16
                 ip<0cw11

Chi Square?
Odds Ratio'.



Chi !F+quare?
Odds Ratlo3:

X2=2.83
OR=1.49
(p=O.cE!

X2=36.8
OR~2.63
,pc O.ocGlI

X*=36.3
OR~2.21
`p' O.Klol,

' Weighted by Mantel-Haenszel technique for byssmosls frequency
`Weighted by Mantel-Haenszel technique for sex dlstributlon
`Weighted by Mantel.Haenszel technique for frequency of both byssmosls and sex
SOURCE: Molyneux and Tomhleson 119701

smokers than among nonsmokers or ex-smokers of both sexes;
however, these differences were not statistically significant (Berry et
al. 1974).

411


TABLE 4.-Age-adjusted association of bronchitis and
     byssinosis by smoking status and sex

Association of byssmosls and bronchicls

Odds ratio

p-Value

Men and women combined

Cigarette smoker

Sonsmoker

1.73         00002

3.13       <O.cxMl

Combmed smoking status

Men

Women

1.80         0.001

2.25        <O.oool

Combined overall                    2.02       < O.oool

SOURCE. Data from Molyneux and Tombieson (1970)

TABLE 5.-Age-adjusted association of byssinosis and
      smoking by bronchitis status and sex

   Association of byssmosis and smoking


   Men and women combined

    Bronchitis present

     Bronchitis absent


   Combined bronchitis status

     .Men

     Women


   Combined overall


SOURCE Data from Molyneux and Tombleson 11970).

Odds ratio     pValue





0.82         0.39

1.44         0.03




1.19         0.45

1.17         0.36


1.18         0.23

More than 10,000 Burlington Industries textile employees (95
percent of the workforce) from 19 plants participated in a 1970
survey conducted by Duke University with the cooperation of
Burlington Industries and the North Carolina State Board of Health
(Imbus and Suh 1973). Each participant received the modified
British Medical Research Council Respiratory Questionnaire for
determining the prevalence of byssinosis and bronchitis. Byssinosis
was graded according to the classification of Roach and Schilling
(1960). Chronic bronchitis was defined as grade 0, no evidence of
sputum production; grade 1, simple chronic bronchitis; and grade 2,
chronic bronchitis with an exacerbation (Imbus and Suh 1973).
Smokers were defined as those regularly smoking one or more
cigarettes per day (Molyneux and Tombleson 19701. Forced expira-
tion was measured in all participants before the beginning of the
work shift on the first day of the workweek. Approximately 80

412


FIGURE 2.-Byssinosis prevalence by grade, smoking
       status, and dust level among men working in
      synthetic/wool mills and cotton/blend mills,
       North Carolina, 1970-1971
SOURCE: Merchant. Lumsden. Kilburn. O'Fallon et al. (1973ai

percent underwent spirometry again 6 hours into the work shift
(Imbus and Suh 1973).

Like Molyneux and Tombleson (1970) in their study of the
Lancashire mill workers, the North Carolina investigators found
that smoking was responsible for a doubling of the bronchitis risk
and that the presence of bronchitis was strongly associated with
byssinosis. After controlling for the effect of bronchitis, there was no
additional significant smoking effect on the risk of chest tightness at
the observed dust levels. Cigarette smoking seemed to play a greater
role in byssinosis prevalence as cotton dust levels rose (smoking-
cotton dust interaction). Figure 2 shows no cigarette smoking effect
on byssinosis prevalence at low dust levels. However, at the highest
dust levels, cigarette smoking was found to interact with cotton dust
exposure to substantially increase the acute symptom prevalence
(Merchant et al. 1972; Merchant, Lumsden, Kilburn, O'Fallon et al.
1973a).

No "safe" level of cotton dust exposure has been identified for
cigarette smokers (Merchant, Lumsden, Kilburn, O'Fallon et al.
1973b). However, among nonsmokers, these investigators found no
case of byssinosis below a cotton dust level of 0.2 mg/m3. An

413


.l  2  3  4  .5           1            15           2

               Median dust level (mg/mJ)

FIGURE 3.-Byssinosis prevalence by median dust level
      among current smokers and those who never
      smoked, preparation and yarn area workers,
      linear regressions and fitted profit dose-
        response curves

NOTE. Group 1 ION. smokers. group 2 IM. nonsmokers
SOURCE Merchanr. Lumsden. Kllburn. O'Fallon et al t1973bl

examination of a large population found one case in a nonsmoker
below this level (Figure 3). Workers with byssinosis who stopped
smoking but did not change their work area lost their byssinosis
symptoms (Merchant et al. 1972). These observations suggest that
there may be a "safe" level of cotton dust in the absence of other
inhaled irritants. Cigarette smoking seems to lower this threshold of
susceptibility to chest tightness below the present limits of cotton
dust detection. At least in some individuals, this threshold may be
restored by smoking cessation.

The repeated demonstration of a linear dose-response relationship
of symptoms with cotton dust levels led to the development of cotton
dust exposure standards to protect the majority of the workforce
(Roach and &hilling 1960; McKerrow et al. 1962; Merchant et al.
1972; Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b). The

414


American Congress of Government Industrial Hygienists' I ACGIH)
early cotton dust standard was based upon the work of Roach and
Schilling (19601, which concluded that 1 mg/m" gross (total) dust was
a safe level for occupational exposure. Further study, however, found
that the biologic activity of cotton dust resided primarily in the
respirable dust fraction McKerrow et al. 1962). The use of total dust
as the only measure of exposure has sometimes resulted in a
misleading lack of association between cotton dust level and
byssinosis symptoms (McKerrow et al. 1962; Molyneux and Tomble-
son 1970; Merchant et al. 1972).

High correlations between byssinosis symptoms and respirable
dust levels were observed, using the vertical elutriator to sample
dust of an aerodynamic diameter of 15 pm and less (Merchant,
Lumsden, Kilburn, O'Fallon et al. 1973131. In Figure 3, cigarette
smokers are shown to have a slightly higher prevalence of byssinosis
symptoms than nonsmokers at each measured dust level. A linear
dose-response model fits the data at low dust levels. At respirable
dust levels from 0.1 to 0.75 mg/m3, the byssinosis prevalence in
nonsmokers rose from 5 to 24 percent, and in smokers, from 8 to 53
percent. The tapering of the dose-response curve at higher dust
levels has been attributed to self-selection by less susceptible cotton
workers (Kilburn 1983).

To minimize the acute symptoms and to inhibit possible chronic
consequences, the Occupational Safety and Health Administration
(OSHA) (US DOL 1981) has modified the permissible exposure limits
to acknowledge the importance of the respirable fraction of cotton
dust (approximately 15 pm or less aerodynamic equivalent diame-
ter). The OSHA standard specifies that employees engaged in yarn
manufacturing may not be exposed to respirable cotton dust levels
greater than 0.200 mg/m3 over an g-hour average, and employees
assigned to the slashing/weaving processes can be exposed to no
more than an 8-hour average of 0.750 mg/m3 of cotton dust (US DOL
1981). No specific accommodation has been made to recognize the
increased byssinosis susceptibility of cigarette smokers.

Effects of Smoking and Cotton Dust Exposure on
Pulmonary Function Tests

In a cross-sectional study of 61 textile workers on carding
machines, Zuskin and colleagues (1975) found a rough correlation
between the grade of byssinosis and the l-second forced expiratory
volume (FEV,) before dust exposure. These observations confirm
those of Merchant, Halprin and colleagues (1974) (Figure 41. It is
suggested that those with byssinosis symptoms start the workweek
with a lower FEV, than those without symptoms (age, height, sex,
race unaccounted for), and at least for the individuals with byssinosis
grade l/2, that overnight exposure cessation is insufficient for

415


Uondav

Tuesday

Vvedwsday

\

    230 730     2.30
Thursday      Friday

Tme (davs)

FIGURE 4.-FEV, during &day exposure of 25 carders
SOI'RCE \lerchant Ha!pnn ct ~1 !`I:;

complete respiratory recovery and that a longer abstinence period (a
weekend. for example) is necessary to restore preexposure levels of
ventilatory function (Merchant, Halprin et al. 19741.

The baseline (initial) ventilatory function, measured as percent of
predicted FEV, and forced vital capacity (FVC), showed that among
nonsmokers (Table 61, a mild decrease was noted in those with
bronchitis alone (without byssinosisl and a more marked decrease
was observed in those with byssinosis alone (without bronchitis). In
men. the lowest value tr'as observed among bronchitics with byssino-
sis. Smoking further reduced the baseline ventilatory function in
every category (except nonbroncbitic, byssinotic women). (The au-
thors pointed out that the small sample size may have made the
slightly higher ventilatory function value among this group of
women somewhat uncertain.) There was also an interaction of the
effects of cigarette smoking with cotton dust exposure upon baseline
forced expiration, similar to that found for symptoms of chest
tightness (Merchant, Lumsden, Kilburn, O'Falion et al. 197313).

Studies of pulmonary function among 61 textile workers showed
that cotton dust exerts its acute effect primarily upon the conducting
airways rather than upon the gas-exchanging parenchyma (Zuskin
et al. 1975). Zuskin and colleagues observed a significant reduction


TABLE 6.-Average percentage of predicted FEV, in
       smokers and nonsmokers with and without
      byssinosis and bronchitis

Average percent of predicted FEV,
     (sample size!

Subjects


Male nonsmokers

Nonbyssinotic       Byssinotic

Nonbronchitlc
Bronchitic


Male smokers

89.4 (9931           84.5 1281
88.2 (591            80.1 (161

Nonbronchitic
Bronchitic


Female nonsmokers

85.9 13.1721          81.5 (1571
61.2 14341           73.7 11091

Nonbronchitic
Bronchitic


Female smokers

857 (1.7291          76.6 (471
82.9 (681            78.4 (11)

Nonbronchitic
Bronchitic

82.6 (1,213)          77.0 WI,
81.3 (93)            73.5 (151

SOURCE: lmbus and Suh (19731

across a workshift in FEV, and midexpiratory flow at 50 percent
(MEFsoQ) and a statistically significant increase in residual volume.
In contrast, plethysmographically determined total lung capacity (a
measure of alveolar volume) and the single-breath diffusing capacity
(a measure of gas diffusion) were unchanged.

In Figures 5 and 6 are shown the effects of byssinosis, bronchitis,
and smoking on FEV, measured before and after 6 hours' work,
adjusted to a base age of 40 years. People with bronchitis alone
(without byssinosis) and people with byssinosis alone (without
bronchitis) experience a decline in FEV, during the workday. People
with a combination of both conditions, however, show the greatest
decrement. Although forced expiration change across a work shift
also shows a strong association with dust levels (Merchant, Lumsden,
Kilburn, O'Fallon et al. 1973131, the relationship of cigarette smoking
to the cross-shift decline in function is less clear. Merchant,
Lumsden, Kilburn, O'Fallon, and colleagues (1973a) found no
smoking effect on acute ventilatory function change within any dust
level, over all dust levels, or as part of a dust times smoking
interaction (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a).
Zuskin and colleagues (1969) and Jones and colleagues (1979)
reported similar observations. However, Haglind and Rylander

417


Men

NEY. NBR         NBY, BR        BY. NBA          BY, BR
            B

3.400

2.700

m Nonsmokers        wm~mma Smokers

FIGURE 5.-Byssinosis, bronchitis, and smoking effects on
      FEV, in men before and after 6 hours' work,
      adjusted to base age 40 years
NOTE B. before work. A. after 6 hours' work.
SOURCE. Imbus and Suh cl9731

(1984) found that cigarette smokers seemed to have a lower effect
threshold. Among cigarette smokers, the threshold for a 5 percent
decrease in FEV, was 0.58 mg dust/m3, compared with a threshold
in nonsmokers nearly threefold greater (1.63 mg/m3). These results
confirmed the findings of Merchant and colleagues (1975) among a
group of 12 cotton workers in an exposure chamber. In addition to
the lower threshold, Haglind and Rylander (1984) reported a larger
FEV, decrease among smokers than among nonsmokers at the same
exposure levels. These findings and the others previously mentioned
suggest that cigarette smoke may enhance the airways reaction to
cotton dust.

Cross-shift change in ventilatory function has been shown to
depend upon the type of cotton dust as well as the level (Table 7)

418


     Women
2.500 _

       NBY. NBR       NBY. BR         BY, NBR         BY. BR

      B
2.400 '

                   B

- Nonsmokers

FIGURE 6.-Byssinosis, bronchitis, and smoking effects on
       FEV, in women before and after 6 hours'
      work, adjusted to base age 40 years
NOTE. B. before work: A. after 6 hours' work
SOURCE. lmbus and Suh Cl9731

@chilling 1956; Roach and Schilling 1960; Merchant, Lumsden,
Kilburn, O'Fallon et al. 1973b; Merchant et al. 1975; Castellan et al.
1984). Under the conditions of an experimental card room (using
carding machines under typical commercial production conditions),
concentrations of gravimetric elutriated cotton dust and the corre-
sponding acute FEV, change were measured (Table 7). In Figure 7 is
shown the significant association of dust concentration and ventila-
tory response found by Castellan and colleagues (1984). Bacterial
endotoxin, a contaminate of cotton dust, was found in this study to
correlate even more closely with a decline in ventilatory function,
but Diem and colleagues (1984) found that the across-shift decline
was more closely correlated with the log dust level than with the
number of gram negative rods or log endotoxin level.

419


TABLE 7.-Slopes of dose-response regressions for
      individual cottons, using vertically elutriated
      gravimetric dust as an exposure index

Change Ipercentage per mg/m3 of dust!

Cotton type                         FVC        FE\`,       FEF-us

Cahfornia jtnct middling                 4.9 '         -0.4 i        14.0'
California strict low middling               -2.3 =         -3.4 3       -l&O3
Califorma strwt low middling spotted          -273         -3.1 3       -13.2*
Texas stnct low middling                 -2.33         -2.9 3       -18.45
Texas strict low middling spotted             -3.6 3         x2=       -27.33
Mississippi strict low middlmg              -3.1 3         -3.53       -20.1 3
Mkssippi strict low middling spotted         -15.93        -24.4 a       43.6 3

SOTE Regrewons based on spirom?tnc responses of 54 persons FVC=forced vital capacity, FEV, =forced
expnatory volume m 1 second; FEF-~7 = maximal flow at 75 percent of expired vital capaelty.
1 p=not s1gmflcant
*p'ooI
`p/OooOl.

SOURCE Ca~tellan et al. r19841

Chronic Clinical Effects of Cotton Dust Exposure

Nonreversible reduction in forced expiration is usually caused by
an increase in airways resistance (particularly in the small airways),
a reduction in elastic recoil (emphysema), or both (Bates et al. 1971).
Chronic cough and sputum production may be a nonspecific irritant
reaction to particle deposition in the conducting airways. Similar
reactions have been seen in cigarette smokers and workers exposed
in dusty trades including mining (coal and metal), manufacturing
(cement and plastics), and foundry work (Morgan and Seaton 1975;
Hank&on et al. 1977; Morgan 1978; Kilburn 1983).

Chronic airflow obstruction is associated with increased age-ad-
justed total mortality and respiratory disease mortality. However,
once adjustment has been made for airflow obstruction, cough and
chronic mucus hypersecretion (the symptoms of chronic bronchitis)
have little additional predictive value for chronic obstructive lung
disease (COLD) mortality (Peto et al. 1983). Since there are both
significant morbidity and mortality consequences associated with
the development of chronic obstruction but not with simple bronchi-
tis, it is important to determine whether the acute symptoms of
bronchitis and chest tightness associated with cotton dust exposure
are associated with chronic airflow obstruction to a greater extent
than could be explained by cigarette smoking alone.

The contribution of the acute byssinotic symptoms (grades l/2 and
1) to the subsequent development of airflow obstruction and the
chronic forms (grades 2 and 3) of byssinosis is not well documented
(Douglas et al. 1984). The term "byssinosis" is often applied to the
acute response to inhalation of cotton dust as well as to the

420


-12oL  1   '   -   .   .   1   .   ,   .   .   .
   0.00    0 10    0 20    0 30    0 40    0 50    060

A               Elutnatec oust bng/m')

00

-10 0

-12.0
    0    100   200   300    400    500   600    700

B              Elutnated endotox~n (ng/m3)

FIGURE `I.-Percentage of change in forced expiratory
       volume in 1 second (FEV,) (mean*SE) for
      each subgroup of people exposed for 6 hours
       to a clean room and to dust from various
      cottons (54 persons in two equal-sized
      subgroups; seven different cottons)
NOTE 4 Plot of change ,n FE\`, `percen?~ versus vertically elutnated al&me- grawnetr~ dust concentratmn
Imgtm3~. B Plot of change I" FE\`, qx?rcentl versus rertirall~ elurnated anborne endotoxln conwntratmn Ing m3r
SOCRCE Casrellan Ed al ~19R.t

421


permanent dyspnea with impaired function. Although a link of
pathogenesis between the two has been assumed, and is supported by
finding impairment in textile workers without other exposures, no
longitudinal study has been done that documents this transition
(Kilburn 1983).

Nevertheless, chronic airflow obstruction has been found more
frequently in cotton textile workers than in control populations
(Bouhuys et al. 1977; Wegman et al. 1983). Obstruction has been
found particularly among the older, cigarette-smoking cotton textile
workers (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a; Beck,
Maunder, and Schachter 1984). Whether cotton textile workers are
compared with a control population of synthetic fiber and wool
workers (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a), with
farmers and workers from other industries (Bouhuys et al. 19691, or
with the population of a rural town (Beck, Schachter, and Maunder
1984), there is a cross-sectional correlation between occupational
exposure to cotton dust and impaired ventilatory function.

Followup studies that document a greater fall in ventilatory
function among those with byssinosis help to establish the transition
between acute and chronic effect (Bouhuys and Zuskin 1976). Beck,
Schachter, and Maunder (1984) have compared the frequency of
pulmonary function abnormality among South Carolina cotton
textile workers with the pulmonary function survey results among
residents of a Connecticut community. These researchers report that
both byssinosis and smoking were associated with subsequent
impairment of age- and height-adjusted respiratory function. They
found that even asymptomatic cotton textile workers had significant
lung function impairment compared with controls. In general, cotton
textile workers had lower lung function among smokers and
nonsmokers, for both men and women and among those with and
without symptoms, but these differences were only statistically
significant for the nonsmoking asymptomatic female subgroup (the
subgroup with the largest number of individuals). Smokers also had
lower FEV, than nonsmokers in each of the subgroups. However, in
the absence of cotton dust measurements, nonoccupational factors
related to control selection may be postulated to have contributed to
these findings (Tockman and Baser 1984).

Other followup studies of cotton textile workers provide inconsis-
tent support for the importance of byssinosis to subsequent ventilato-
ry impairment. Zuskin and Valic (1975) reported on a lo-year
followup of selected members of a worker cohort exposed to coarse
cotton dust. These investigators found both an increased prevalence
of byssinosis on followup examination and approximately twice the
rate of mean annual decline in FEV, among men who had byssinosis
initially, compared with those who later developed it or to those who
did not report this symptom. Smoking was not found to contribute

422


significantly to the development of byssinosis. Contrasting results
were reported by Berry and colleagues (19731, who examined cotton
textile workers at several plants and found that the cotton textile
workers had a 54 mL per year decline in FEV, compared with 32 mL
per year in workers in the synthetic textile mill; however, most of
this excess decline could be attributed to workers in only one mill.
FEV, declined 19 mL per year faster in smokers than in nonsmokers.
However, despite these differences between the cotton workers and
the control group, no difference in annual FEV, decline was found
between the subjects with and without byssinosis symptoms. Cotton
textile workers with acute (grades 0 or 11 byssinosis symptoms and
those with bronchitis following cotton dust exposure may be a subset
of the population at risk of further ventilatory deterioration. The
sensitivity and specificity of these symptoms for subsequent lung
injury is yet to be established by cohort studies.

Followup studies of cotton textile workers have been weakened by
several sources of bias. Self-selection of workers for continued
employment in dusty environments introduces bias into studies that
examine only the currently available workforce, who may be
healthier than workers who have left the industry. Berry and
colleagues (1973) reported that less than half of the subjects were
available sufficiently often to calculate an annual FEV decline.
Merchant, Lumsden, Kilburn, O'Fallon, and colleagues (197313)
reported substantial evidence of selection away from dust exposure
in the cotton textile industry, which results in the presence of
relatively resistant workers in dustier areas at the time of cross-
sectional surveys. As Beck, Schachter, and Maunder (1984) have
shown, it is feasible to survey the retired workforce in addition to
those currently active in order to account for workers who retire
prematurely because of poor respiratory health. To finally determine
the magnitude of the cotton dust effect on chronic lung function of
cotton textile workers, studies must carefully distinguish the sepa-
rate indices of cotton dust lung injury, and impairment rates must be
tabulated over the entire population at risk. However, documenta-
tion of the association between exposure and lung injury will become
increasingly difficult as industrial hygiene control reduces the levels
of occupational cotton dust exposure.

Mechanisms of Cotton Dust Lung Injury

Epidemiologic observations have suggested that cigarette smoking
and cotton dust have complementary effects on the airways. A
discussion of the mechanisms of cotton dust lung injury may
facilitate an understanding of this interaction.

42.1


Inflammation (Bronchitis)

Considerable effort has been devoted to the search for specific
agents responsible for the symptoms and changes in lung function
associated with cotton dust exposure. These investigations have
focused upon water-soluble extracts found in the cotton bract. An
animal model has been developed that partly reflects the sequence of
clinical findings seen in cotton textile workers. Hamster inhalation
of condensed vegetable tannins from card room floor sweepings
stimulated the recruitment of leukocytes to the trachea, bronchi,
and small bronchioles, with a time course similar to that of
byssinosis symptoms in humans (Kilburn, Lynn et al. 1973). Tannins
isolated from cotton bract have been shown to cause pneumocyte
lysis (Ayars et al. 1984). Other agents in cotton dust have also been
found to have pharmacologic activity (Hitchcock 1974; Ainsworth et
al. 1979). Compounds that have been identified in cotton bract
extract in significant concentrations include tannin, 5-hydroxytryp-
tamine, endotoxin, and histamine (Rylander 1981; Bouhuys and
Lindell 1961; Rohrbach et al. 1984; Russell et al. 1982).

Pharmacologic activity has also been isolated from the compo-
nents of bacteria and fungi found in cotton bract. Studies by Cinkotai
and colleagues (1977) have demonstrated a close relationship be-
tween the prevalence of byssinotic symptoms and the airborne
concentration of gram-negative (endoagar) bacteria. In Figure 8 are
shown a close correlation between byssinotic symptoms and levels of
gram-negative bacteria, a more variable relationship with gram-
positive (nutrient agar) bacteria, and no relationship with fungi or
with airborne dust. Human exposure to airborne gram-negative
bacteria may result in symptoms related to the presence of endotox-
in lipopolysaccharide within the bacterial cell walls (Rylander 1982).
This material could activate complement (Wilson et al. 1980) with
subsequent generation of anaphylatoxins, release of histamine and
leukotactic substances, and induction of an inflammatory response.

Cotton bales from different geographic areas may be contaminated
with different levels of gram-negative bacteria. Cottons grown in dry
areas with irrigation were found to have smaller amounts of gram-
negative bacteria (Rylander et al. 1985). The culturing of viable
organisms was found to be a misleading index of byssinosis potency,
however, because endotoxin activity persists after bacterial death
(Rylander et al. 1985). Airborne endotoxin levels correlated with
byssinosis symptoms, blood neutrophil levels, and airways response
(Rylander et al. 1985). Castellan and colleagues (1984) have reported
a high correlation between endotoxin exposure and ventilatory fall
in experimental exposures (part B of Figure 7). Their data show no
evidence for an endotoxin exposure t,hreshold, but this conclusion
depends on the validity of the four outlying observations presented
in the figure. In an experimental card room, Haglind and Rylander

424


B
tt
h 40
F
a,
a

  30




  20




  IO

10    2.0    30 40   150
Awborne dust less "fly" (mglm~)

1oKl 2ooo   3coo   4cm

     Endoagar bacterra (n/ma)
c cotton malls       * Wwlm~ll
C cotton waste mills    A Tea packtng plant
o Willowing mill      A Pipe tobacco factory

        0
C
     0
0

        0
         0
I+
  Q 0
  @

loo00     2oooo     75mo
Numenl agar bacrerla (n/m')

O D

    0
0

0
     0
QO
       0        o
?
                      25ocm

          Fungi (n/ml)

FIGURE &-Concentration of endotoxins in airborne dust
      correlated with the prevalence of byssinotic
       symptoms
SOURCE Clnkotai et al f19771

(1984) found a dose-response relationship between the average FEV,
decrement across a work shift and the amount of airborne dust or
endotoxin. These data have been used to suggest that endotoxin
contamination of cotton, rather than the plant dust itself, is
responsible for the byssinosis syndrome. However, Buck and col-
leagues (1984) have reported that cotton bract extract contains a
bronchoconstricting agent or agents distinct from endotoxin and
have suggested that an interaction may exist between the effects of
endotoxin and these other agenb; Diem and colleagues (1984) have

157-964 0 - 86 - 15                               425


shown a closer correlation in across-shift decline in lung function
with log cotton dust levels than with log endotoxin levels or the
number of gram negative bacteria.

Cloutier and colleagues (1984) noted that many of the hypothesized
mechanisms of byssinosis, including bacterial endotoxin effects
(Rylander et al. 1979, 1985; Rylander 1981, 1982), nonallergic
histamine release (Bouhuys and Lindell 1961; Ainsworth et al. 1979;
Noweir et al. 19841, and airways smooth muscle contraction by a 5-
hydroxytryptamine (SHT), receptor agonist (Russell et al. 19821,
require that the byssinotic agent cross the airway epithelium.
Normally the respiratory epithelium bars inhaled substances from
access to the interstitium, to airway smooth muscle, or to the
bloodstream (Cloutier et al. 1984). The application of aqueous cotton
bract extract to canine trachea has been found to disrupt this barrier
by inhibition of transepithelial ion flux (Cloutier et al. 1984).
Alteration in the active ion transport may result in an altered
osmotic balance in the airway. Although the components of cotton
bract extract responsible for the altered ion flux are unknown,
Cloutier and colleagues (1984) consider tannin and 5-HT to be likely
causes, endotoxin to be a possible cause, and histamine to be an
unlikely cause. Other components of the cotton bract, including
lacinilene C-7 methyl ether, have also been mentioned as possible
etiologic agents (Kilburn 1980).

Inhalation of cigarette smoke can also induce alteration of active
ion transport by the airway epithelium (Welsh and Karp 1983).
Inhalation of the smoke from one cigarette decreased the electrical
potential difference across the tracheal epithelium owing to an
inhibition of the rate of chloride ion secretion. Active ion transport
by the airway epithelium plays an important role in the regulation
of the volume and composition of the respiratory tract fluid.
Inhibition of transepithelial ion flux by cotton dust (Cloutier et al.
1984) and by cigarette smoke (Welsh and Karp 1983; Kennedy et al.
1984) may produce the symptoms of acute bronchitis, and each could
conceivably have an additive effect upon the other.

Alteration of the osmolarity and the ion concentration of inhaled
aerosols can produce both cough and bronchoconstriction (Eschen-
bather et al. 1984). These investigators found that in asthmatics, the
stimuli for cough could be distinguished from those for bronchocon-
striction. They suggest that afferent airway nerve depolarization
may occur as a result of anion flux imbalance (outward anionic flux
cannot be balanced owing to the inhibition of inward anion
movement) and that cough is the reflex response (Eschenbacher et
al. 1984). Alternatively, Hogg and Eggleston (19841, noting that
disruption of epithelial tight junctions has resulted from transtra-
cheal osmotic gradients, propose a mechanism whereby the vagal
irritant reflex receptors located close to the tight junction might be

426


deformed by this osmotic disruption. In addition, epithelial injury
and sensory receptor sensitization account for increased susceptibili-
ty to cough following airways irritation in asthmatic subjects (Empey
et al. 1976). It is possible that acute bronchitis in cotton workers may
be caused, in part, by similar mechanisms.

Airways Constriction

Cotton dust exposure may induce airways narrowing in atopic
individuals (Jones et al. 1980; Parkes 1982). Skin Lest atopy identifies
those at risk of acute bronchoconstriction (cross-shift FEV, change)
following exposure to high concentrations of cotton dust (elevated
levels of both total and respirable dust) (Jones et al. 1980). These
results do not necessarily imply that a specific immunoglobulin E
(IgE) response is triggered or that elevated levels of IgE (beyond
those found in atopic individuals) must be detected in serum (Pepys
et al. 1973). The cotton dust bronchoconstrictor response seen in
atopics may be nonspecific. Agents extracted from cotton dust have
been documented to produce lung injury and physiologic response in
previously unexposed volunteers. The presence of an airways
response in individuals not previously exposed suggests a pharmaco-
logic or irritant mechanism rather than an idiosyncratic (allergic)
one (Buck and Bouhuys 1981; Wegman et al. 1983; Douglas et al.
1984; Haglind and Rylander 1984; Schachter et al. 1985). The
nonimmunologic character of the cotton dust lung response is
supported by the failure to find precipitating antibodies in the sera
of cotton textile workers to extracts of cotton bract, carpels, stems,
leaves, cotton lint, or card room cotton dust (Kutz et al. 1981).

Release of bronchoconstricting mediators from the mast cells
beneath the bronchial epithelium does not require development of
immune hypersensitivity (Dosman et al. 1981; Findlay et al. 19811.
The nonspecific reaction induced by cotton dust contrasts with the
specific hypersensitivity reactions due to inhaled organic dusts such
as complete allergens, e.g., grain dust (Dosman 1977); incomplete
haptens, e.g., penicillin (Davies et al. 1974); simple but very reactive
copolymerizing compounds, e.g., isocyanate (Butcher et al. 1977); or
wood dusts (Chan-Yeung et al. 1973). These specific hypersensitivity
reactions are found in relatively few of the exposed individuals, even
after a suitable period of exposure (Dosman et al. 19811, and atopy is
not required for mediator release (Lam et al. 1979; Bryant and Burns
1976; Boushey et al. 1980).

Nonspecific hyperreactivity may be acquired as a result of chronic
exposure to inhaled occupational irritants (Lam et al. 1979). One
mechanism for triggering mast cell degranulation and subsequent
smooth muscle contraction may result from PGF release from
macrophages activated by cotton dust. An aqueous extract of cotton
plant "trash" has caused in vitro elaboration of prostaglandins (PGF,


PGE, and PGA) from rabbit alveolar macrophages (Fowler et al.
1981). Bronchoconstriction also may result from changes in airway
osmolarity through stimulation of airway mast cells (Findlay et al.
1981) or vagal afferents (Empey et al. 1976; Orehek et al. 1976;
Golden et al. 1978; Boushey 1982).

Epithelial injury similar to that observed following a viral upper
respiratory infection might expose and stimulate the rapidly adapt-
ing sensory receptors of the airway and result in reflex (vagal)
bronchoconstriction (Empey et al. 1976). The rapidly adapting
sensory receptors extending between the airway epithelial mucosal
cells are believed to be involved in ozone-induced hyperreactivity
(Golden et al. 1978). Controlled exposures to other agents such as
nitrogen dioxide (Orehek et al. 1976) and sulfur dioxide (Boushey
1982) have also resulted in hyperreactivity, possibly owing to vagal
sensory fiber stimulation. In addition, byssinosis-like symptoms of
cough, chest tightness, substernal soreness, and shortness of breath
have been reported by healthy subjects after a controlled 2-hour
exposure to ozone at 0.5 to 0.6 ppm (ambient air-pollution concentra-
tions) (Golden et al. 1978). Epithelial injury and sensory receptor
sensitization may contribute, therefore, to both cough (bronchitis)
and airways constriction (byssinosis).

Barter and Campbell (1976) showed that the rate of deterioration
in FEV, correlated with methacholine reactivity, independent of the
effect of cigarette smoking. Hyperreactivity may therefore indicate
the individuals at risk of subsequent loss of function. Although
atopic individuals may have an increased susceptibility to broncho-
constriction, at present there is no evidence that atopics are at
greater risk of lung disease associated with cotton dust exposure.
Perhaps the recent development of an assay for the pharmacologic
activity of cotton dust (Douglas et al. 1984) will provide a sufficiently
sensitive measure of cotton dust exposure to determine the role of
the cholinergic bronchial response in textile workers.

It is possible that the hyperreactivity model for chronic obstructive
lung disease may help explain a greater risk of accelerated ventilato-
ry deterioration in cotton textile workers. Van der Lende and
colleagues (1970) suggested that airways hyperreactivity might be an
underlying factor that led to irreversible obstruction among those
exposed to airways irritants. Barter and Campbell (1976) demon-
strated an accelerated rate of longitudinal ventilatory function
decline in those with hyperreactivity.

Chronic inflammatory Lung Destruction
Emphysema has been demonstrated post mortem in the lungs of
cotton workers (Edwards et al. 1975; Pratt et al. 1980). A significant
degree of emphysema, as measured by a reduction of lung elastic

428


recoil pressure at total lung capacity, was found only in older (aged
56 to 69) hemp workers (smoking status unspecified) by Guyatt and
colleagues (1973). These workers had at least 20 to 30 years of cotton
dust exposure. The younger population (aged 31 to 51), studied with a
variety of pulmonary function measurements by Zuskin and col-
leagues (1975), showed no emphysema as documented by normal
values of the single breath carbon monoxide diffusing capacity. This
finding of emphysematous changes only among older workers is
consistent with the data for smokers in the general population, and
therefore does not demonstrate a specific effect of cotton dust
exposure. Kilburn (1981) reported the prevalence of radiographic
changes consistent with emphysema (flattening of the diaphragms
and radiolucent or avascular zones of lung) in 233 male cotton textile
workers and found that these radiographic changes were present
only in the smokers and former smokers in the population.

The data in Tables 8 and 9 are from the study of Pratt and
colleagues (1980), who examined fixed, inflated lung specimens from
unselected autopsies performed at the Durham (North Carolina)
Veterans Administration Medical Center. The findings from the 565
cases with known smoking histories are presented. The mean
percentages of centrilobular emphysema (CLE), mucous gland vol-
ume, goblet cell metaplasia, and pigmentation grouped by employ-
ment or nonemployment as a cotton worker and by smoking status
are shown in Table 8. There were 44 cotton workers, 8 of whom were
nonsmokers. The statistical results of covariance analyses performed
on these data are shown in Table 9. Cotton dust exposure is
significantly associated with mucous gland volume and peripheral
goblet cell metaplasia in nonsmokers. Cigarette smoking and pipe
smoking showed associations with centrilobular emphysema, but no
association of emphysema was found with cotton dust exposure.
Examination of the main lobar and segmental bronchi showed no
morphologic differences between smokers and nonsmokers (Edwards
et al. 1984). These data may be interpreted to show that airways
inflammation (bronchitis) rather than parenchymal destruction
(centrilobular emphysema) follows chronic cotton dust exposure.

Cotton Dust Exposure and Mortality From Respiratory Disease
and Lung Cancer

Owing partly to the difficulty in following cohorts of cotton textile
workers and partly to the lack of a smoking history among the
recorded deaths, there have been few studies of mortality related to
cotton dust exposure. In a mortality study of two cohorts of cotton
textile workers, Henderson and Enterline (1973) found lower mortal-
ity rates overall (SMR 71.7 to 89.6), lower respiratory disease
mortality (SMR 36.4 to 76.1) and lower lung cancer mortality (SMR

429


E  TABLE &-Mean percentages of centrilobular emphysema, mucus glands, goblet cell metaplasia, and
         pigmentation

Group

N

Mean percent     Mean percent
  CLE '         CLE &ases
(all cases)        with CLE)

Gland volume
(percent)

Goblet cells
(percent.l

Pigment&on
(percentJ

All
Noncotton
Cotton


All smokers
Smokers
  (noncotton)
Smokers (cotton)

565        56.2          9.3           24.9            12.1             17.1           53
521        56.4           9.2           24.7            12.0            16.7           5.4
44        57.6          10.4           26.9            13.0            21.6           45


460        56.3          11.1            26.4            12.6            lA.3           6.3


424        56.1          11.0           26.2            12.6            18.0           6.8
36        57.9          12.6           28.4            12.0            20.4           4.7

Nonsmokers              105        57.3           1.0            6.7             9.8            12.0           2.6
Noncotton               97        57.4           1.1            6.9             9.3            10.7           2.5
cotton                 8        56.5          0.4            3.0            16.3            28.0           3.8

Cigarettes               427        55.6          11.6           26.6            12.6            18.6           6.7

Pipe/cigar                33        65.1           5.6           23.0            12.8            12.2           3.3


`CLE =centnlobular emphysema.
SOURCE: Pratt et al (1980).


TABLE 9.-Covariance model results (F-test probabilities)

Cigarette smoker   Pipe smoker   Textile exposure   cigarette textlIe

Pipe smokers excluded

CLE '
Pigment
!vlucus
Goblet

.cm
NS
SS
.02

oool                     3SZ           SS
CiXIl                     SS           SS
SS                      ss           9s
ss                      ss           43


    Cigarette smokers excluded

CLE
Pigment
MUCUS
Goblet

20.5 to 65.3) than expected from the mortality rates of Georgia white
men. In a more recent study, Merchant and Ortmeyer (1981) found a
doubling of respiratory disease mortality (SMR increased from 61 to
126) with increasing duration of cotton dust exposure from less than
20 to more than 30 years, although no overall mortality excess was
observed. Berry and Molyneux (1981) also found no excess mortality
associated with cotton dust exposure. Although consistent with
previous studies, this last observation must be considered prelimi-
nary because less than 10 percent of the Lancashire cotton mill
workers under study have died.

Two studies of cancer rates among North Carolina cotton textile
employees showed no excess of lung cancer mortality (Heyden and
Pratt 1980). Data from the Third National Cancer Survey contain a
representative sample of incident cancer cases occurring over 3 years
in a population of 21 million men and women who were interviewed
to determine their occupation, socioeconomic status, and tobacco and
alcohol consumption (Williams et al. 1977). These data indicated a
slight (2.06), nonsignificant odds ratio excess risk for lung cancer
among male cotton textile workers. While this observation is of
interest because the odds ratio was adjusted for smoking, it depended
upon only three cases of lung cancer. At this time, therefore, there is
no evidence to suggest a lung cancer excess among cotton textile
workers.

Control of Cotton Dust Exposure

The feasibility of controlling cotton dust exposure by preprocess-
ing the cotton (heating, washing, or steaming) has been studied by
Merchant, Lumsden, Kilburn, Germino, and colleagues (1973).

431


Although washing the cotton removed detectable biologic effects, the
cotton became difficult to spin. Steaming the cotton, while practical
for the manufacturer, resulted in an unexpected consequence
(Merchant, Lumsden et al. 1974); while it initially removed some of
the cotton dust, the steaming process also bound dust to the cotton
fiber. Although cotton steaming led to a lower dust level and a
smaller fall in cross-shift ventilatory function in the preparation
area, subsequent release of the bound dust during spinning resulted
in increased dust levels and symptoms of byssinosis and bronchitis in
the areas when these processes were performed (Merchant, Lumsden
et al. 1974).

The inability to control cotton dust levels by treating the cotton
has led to the imposition of Occupational Safety and Health
Standards for containment of dust (US DOL 19811. Although these
standards have resulted in substantial cost to the cotton textile
industry, progress in reducing byssinosis has been made by the
implementation of competent air hygiene practices (Kilburn 1983;
Gideon and Johnson 1978) using commercially available lint and
dust control systems (Barr et al. 19741.

Summary and Conclusions

1. Byssinosis prevalence and severity is increased in cotton textile
workers who smoke in comparison with workers who do not
smoke.

2. Cigarette smoking seems to facilitate the development of
byssinosis in smokers exposed to cotton dust, perhaps by the
prior induction of bronchitis. Cotton mill workers of both sexes
who smoke have a consistently greater prevalence of bronchitis
than nonsmokers.

3. The importance of cigarette smoking to byssinosis prevalence
seems to grow with rising dust levels (a smoking?cotton dust
interaction). At the highest dust levels, cigarette smoke was
found to interact with cotton dust exposure to substantially
increase the acute symptom prevalence.

4. Nonsmokers with byssinosis have lower preshift lung function
and a greater cross-shift decline in lung function than asymp-
tomatic workers, and those workers with bronchitis generally
have lower preshift lung function than those without bronchi-
tis. In general, smokers have lower lung function than non-
smokers among cotton workers, both in those with bronchitis
and in those with byssinosis.

5. Although the average forced expiration values measured at the
start of a shift are reduced among smokers, the cross-shift
decline in function does not seem to be affected by smoking
status.

432


6. The contribution of the acute byssinotic symptoms (grades l/2
and 1) to the subsequent development of what have been
termed the chronic forms (grade 3) of byssinosis (which include
airways obstruction) is not well documented; however, chronic
airflow obstruction has been found more frequently in cotton
textile workers than in control populations, and this lung
function loss appears to be additive to that caused by cigarette
smoking.

7. Cotton dust exposure is significantly associated with mucous
gland volume and peripheral goblet cell metaplasia in non-
smokers, a pathology consistent with bronchitis. Among ciga-
rette smokers, the interaction of cotton textile exposure and
smoking is demonstrable for goblet cell hyperplasia. Centrilo-
bular emphysema is found only in association with cigarette
smoking and pipe smoking. There is no emphysema association
found with cotton dust exposure.

8. The evidence does not currently suggest an excess risk of lung
cancer among cotton textile workers.

433


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industry. ArchiL,es ofEnL?ronnwntal Health 19151:666673. November 1969.

439


CHAPTER 11

IONIZING RADIATION
AND LUNG CANCER


CONTENTS

Introduction

Human Exposure to Radiation From Radon Daughters

Smoking Habits of Exposed Miners

Risks of Lung Cancer Among Smoking and Nonsmoking
Miners

U.S. Uranium Miners
Swedish Miners
Canadian Miners

Other Epidemiological Studies Relating Radiation and
Cancer

Comment on Epidemiological Studies

Interaction of Radiation and Cigarette Smoke (or Its Con-
stituents) in the Generation of Animal Tumors

Interactions of Radiation and Chemical Carcinogens

Comment on Animal Studies

Polonium 210 in Cigarette Smoke

Hypothesis That Reconciles Discrepancies in Epidemiolog-
ical Data

Interaction of Radiation and Cigarette Smoke on Other
Aspects of the Respiratory Tract
  Larynx and Nasal Sinuses
  Pulmonary Function and Fibrosis

Research Recommendations

Summary and Conclusions

References

443


Introduction

The major focus of this chapter is the interaction of cigarette
smoking with radiation exposure; epidemiologic and experimental
studies are reviewed. Radon is a noble gas that is created as a
consequence of the radioactive decay of radium 226. Its half life is 3.8
days. Radon is of much less health concern than are its immediate
decay products (PO-218, Pb-214, Bi-214, and PO-214), which have a
collective half-life of approximately 30 minutes. Known collectively
as radon daughters, they decay to lead 210, which has a half life of 22
years. Because there are small amounts of radium in all rocks and
soils and in most building materials, radon is ubiquitous and is
constantly being emanated from ground surfaces; when it diffuses
into the atmosphere, it is rapidly diluted. Radon levels are enhanced
whenever radon is emanated into an enclosed space rather than into
the open air; therefore, radon levels in most underground mines are
higher than in open air. There are elevated levels of radium in
uranium and phosphate ores, so there are naturally enhanced levels
of radon and its daughters in such underground mines (NCRP
1984a).

Human Exposure to Radiation From Radon Daughters

When radon in air decays, its daughters, being ionized metal
atoms, tend to become attached to the nearest solid object, usually a
dust particle. These dust particles and attached ions are inhaled by
people breathing the air, and a fraction is deposited within the lungs.
From the standpoint of radiation dose to the critical cells, the
amount deposited on the tracheobronchial epithelium is important.
Because radon daughters decay rapidly, they deliver their radiation
before they can be removed by normal lung clearance mechanisms.
Particles deposited by inertial forces (impaction) would also be
present preferentially at bifurcations. Although alpha, beta, and
gamma radiations are emitted by radon daughters, the alpha
radiation delivers over 95 percent of the radiation dose to the
epithelium. The beta and gamma contribution to dose is therefore
generally disregarded (NCRP 1984b).

Exposures to radon daughters are generally measured in working
levels (WL) or working level months (WLM). One WL is defined as a
concentration of any combination of short-lived radon daughters in
air that produces, from complete decay, 1.3 times lo5 MeV (million
electron volts) of alpha energy per liter. A person exposed while
working for 1 working month (170 hours) in such an atmosphere
would receive an exposure of 1 WLM. The maximum permissible
exposure for underground miners is 4 WLM per year, which is
approximately equivalent to an average monthly exposure of 0.3 WL
for 12 working months per year. In the past, many miners in both

445


uranium and nonuranium mines received cumulative exposures of
between 10 and 10,000 WLM. It is primarily from the study of these
groups that our information on the health hazards of radon
daughters has come. Although inadequately studied, average levels
of radon daughters in homes appear to be close to 0.004 WL in the
United States (NCRP 1984a).

Use of the awkward WL is justified on the grounds that exposure
to the alpha radiation from radon daughters cannot be readily
converted to more universal measures of radiation such as "rad" or
"rem." Many attempts to do so have been made, yielding values
ranging from 0.1 to 10 rad per WLM. A further problem involves
estimating the Quality Factor for the alpha radiation involved.
Although use of 20 for this factor is recommended (ICRP 1981), the
epidemiologic data indicate that from 10 to 15 may be appropriate
(Radford 1984).

Smoking Habits of Exposed Miners

Although information on cigarette usage has not been obtained on
all mining groups that have been studied for lung cancer, it has been
obtained in many of them (Table 1). Cigarette smoking histories of
U.S. uranium miners were obtained between 1950 and 1960, when
they were admitted to a prospective study group (Lundin et al. 1971).
It was found that white uranium miners in the United States
smoked a little more heavily than comparable men in the U.S.
population and that Navajo miners were extremely light smokers
(Tables 2 and 3) (Archer et. al. 1976). Swedish miners have a much
lower smoking prevalence than U.S. miners (Cederlof et al. 1975;
Radford and Renard 1984).

Risks of Lung Cancer Among Smoking and Nonsmoking
Miners

Although the cancerous nature of the fatal lung disease of miners
in the Joachimsthal and Schneeberg mining areas of central Europe
was not noted until 1879 (Harting and Hesse 1879), the disease had
been known for three centuries (Pirchan and Sikl1932). Lung cancer
may have resulted in the death of 40 percent or more of the miners
(Arnstein 1913). It is now generally agreed that most of these lung
cancer deaths may be attributed to radon daughters-and they were
occurring at a high frequency prior to the introduction of cigarettes
to Europe.

U.S. Uranium Miners

When the first lung cancer among nonsmoking underground U.S.
uranium miners was observed in 1965, there had already been

446


TABLE l.-Epidemiological reports on interaction of
      smoking and cancer

Study

Group studied

Saccomanno et al.   U.S. uranium

miners

Lundin et al
0969)

Lundin et al
(19711

U.S. uranium
miners

Archer et al.      U.S. uranium
(1973)           miners

Axeleon and
Sundell 0978)

Archer et al.
0976)

Dahlgmn 0979)

Homung and
SamuelE 0981)

Gottlieb and
Hueen (l982,

Damber and
Larason 0982)

Eklling 0982);
Edling and Axelson
(1983)

Whittemore and
McMiIIan 0983)

Radford and
Renard (1984)

U.S. uranium
miners

Swedish lead-
zinc miners

U.S. uranium
miners

Swedish lead-
amenic-sulfide
miners

U.S. uranium
miners

U.S. Navajo
uranium
miners

Swedieh
miners

Swedish iron
miners

US. uranium
miners

Swedish iron
miners

CaSe
collection

Cohort

Cohort

Case-control

~ntrol

Cohort

Case-control

Cohort, Cox
regreaeion


case
collection

Case-control

CaEe-contml

Nested c88e-
control

Cohort

Lung




Lung




Lung



Lung





Lung



Lung



Lung




Lung



Lung




Lung



Lung




Lung



Lung

One cancer among
nonsmokers ~6. >tX among
smokers

Ten times more lung cancer
in smokers then
nonsmokers

Smoker I-L period shorter;
histologic type distribution
came in smokers and
nonamokere

Smoker I-L period much
shorter

Smoking not large factor in
exceea lung cancera

Smoking little role in
Navajo lung cancers

Smoker I-L period shorter

Smoker I-L period shorter

Smoker I-L periods slightly
shorter

447


TABLE l.-Continued

Study


Archer 09851



Samet, Kuh%t
et al. 0984)

Group studied


U.S. uranium
miners

U.S. Navajo
uranium
miners

Type of
analysis


cllsecontro1



Case-control

cancer
site


Lung



Lung

     ResUlts


Smoker I-L period
significantly shorter

Smoking little role in
Navajo lung cancers

Hinds et al.      Hospital
(1979)         patients

cLk?e-mntr01 Larynx   Prior dental x rays

Prentice et al.
ww

A-bomb
survivors

Cohort

Esophagus
and lung

TABLE 2.-Cigarette smoking habits of white U.S. uranium
     miners at study entry and of U.S. nonminer
           men

Smoking status

Uranium miners
  (percent)

Nonminers
(percent)

Nonsmokers '                  28.8              45.4

11 pack/day                  54.2             39.8

> 1 pack:day                  16.9             14.8

Includes smokers of pipes or qars only and ex-smokers
SOURCE Adapted from Lundm et al 119711

TABLE 3.-Cigarette smoking habits of Navajos in U.S.
     uranium miner study group, at entry

Packs'day

Percentage
smoking at entry

Percentage
former smokers

Percentage
never smoked

       000           -

      001419         15.1

      0 24.59          14.6

      0 6499          07

      210           2.7

SOURCE Adapted from Archer et al 11976~

-          62.8

2.3           -

17           -

0.000          -

0001          -

nearly 80 lung cancer deaths among cigarette-smoking U.S. uranium
miners (Archer 1985). Because approximately one-third of the
miners did not smoke cigarettes, the discrepancy was so striking that

448


it led some observers to blame cigarette smoking for the entire
problem and to conclude that if uranium miners did not smoke, they
would rarely develop lung cancer.

A second lung cancer among nonsmoking uranium miners was
observed in a mortality analysis of the U.S. uranium miner cohort
published in 1969 (Lundin et al. 1969). These two cases represented a
fourfold excess of lung cancers (only 0.5 case was expect.ed among
nonsmokers&the same relative risk noted for cigarette smokers (15
expected versus 60 observed). Since the U.S uranium miners were
known to smoke at a somewhat higher rate than other U.S. men
(Table 2), in an analysis of how much extra cancer could be due to
this extra smoking, Lundin and colleagues (1971) concluded that this
extra smoking could account for no more than a 50 percent increase;
a fivefold to tenfold increase had been observed. The discrepancy
between smoker and nonsmoker lung cancer rates suggested an
interaction between the two agents.

A later study of white U.S. uranium miners reported that the
incidence of lung cancer varied both by cumulative amount of
radiation exposure and by the intensity of cigarette smoking (Figure
1) (Archer et al. 1978). The mean exposure of these miners was about
870 WLM. Approximately 780 of the uranium miners in the U.S.
study group were Navajo Indians. They had a much lower smoking
prevalence than white miners (Table 31, but nevertheless had
elevated lung cancer rates (Archer et al. 1976; Gottlieb and Husen
1982; Samet, Kutvirt et al. 1984). Many of those who developed lung
cancer had smoked little or not at all (Table 4). Most of the lung
cancers were therefore attributed to mining exposure (Samet,
Kutvirt et al. 1984).

The role of other factors in the lung cancers of U.S. uranium
miners was also studied. The induction-latent (I-L) period (time from
start of mining to diagnosis of cancer) was shortened by increased
age at the start of mining, by cigarette smoking, and by high
exposure rates (Archer 1981). The attributable lung cancer risk
tended to decline among miners who had reached the age of 65 and
had 25 or more years of latency (Roscoe et al. 1983). An updated
analysis of these data, using deaths occurring through 1982 and an
adjustment of expected numbers of deaths for smoking habits,
indicated that the drop in attributable risk appeared to occur mainly
among the smokers, not the nonsmokers (Figure 2) (Roscoe et al., in
press).

Because the I-L period is dependent on factors other than cigarette
smoking (Archer 1981) and the smoking-related shortening of the I-L
period was minimal in miners exposed to low radiation dose rates
(Radford 19841, a more detailed case-control study was done of U.S.
uranium miners (Archer 1985). There were 35 lung cancer cases
among nonsmoking underground uranium miners (defined as smok-

443


0

180

600        1080       1600

Cumulabve exposure (working level months)

2400

FIGURE l.-Influence of cigarette smoking and radiation
      exposure on bronchogenic cancer incidence
      among U.S. uranium miners
SOCRCE Adapted lrom Archer et al 119%

ing a total of less than four pack-years of cigarettes and not smoking
within 10 years of cancer diagnosis) whose lung cancer was diag-
nosed between January 1964 and January 1984. A few of them had
smoked a pipe or cigars occasionally, but not regularly. Because not
all of the lung cancer cases were members of the study group,
supplemental smoking information was obtained from hospital
records and relatives. Two controls were chosen for each case from
among 334 smoking U.S. uranium miners. Controls were matched on

450


TABLE 4.-Smoking habits of 21 Navajo uranium miners
      with lung cancer

             Cv+wettes:day     Number of men



                    00            8

                    1            2

                    1-3            6

                    4-8            5

SOURCE Adapted from Samet. Kutwrt er al 11984i

`\ \ \ \


i

k                          1
  i
i                   I                          1
)                   I       ra-                        l-
c5   5-99   IO-149    15-24.9     >25<5  599  lc-14 9     15-249     225
              interval bn years after start 01 mmg

T

FIGURE 2.-Influence of age at observation and induction-
      latent period on attributable lung cancer
      deaths among U.S. uranium miners
NOTE Error bars are 90 percent confidence intervals
SOURCE Adaw+d from Roxoe et al `III press)

birthdate, on year when their mining started, and on the magnitude
and rate of exposure to radon daughters. The mean I-L period was
23.f' and 18.5 years for nonsmokers and smokers, respectively


(p<O.OOl). The mean age at death was 54.7 and 50.2 years,
respectively (p < O.OOi).

Two sophisticated analyses using Cox regression methods were
done of the U.S. uranium miner cohort in an attempt to determine
the relative contribution of various factors to the miners', lung
cancers. One of the analyses used a cohort approach (Hornung and
Samuels 1981); the other used a nested case-control approach
(Whittemore and McMillan 1983). Both concluded that the interac-
tion between smoking and radiation effects was multiplicative.

Swedish Miners

Axelson and Sundell (1978) conducted a case-control study of lung
cancer patients in the area around two adjacent lead-zinc mines that
had begun operating prior to 1920. Twenty-nine lung cancer cases
were identified from parish death register data; the controls were
the three individuals entered in the register just before and just after
each lung cancer case, but who had not died of lung cancer. Of the 29
cases, 21 had underground mining exposure in comparison with only
19 of the 174 controls. The mean radon daughter exposure of the
lung cancer cases was approximately 300 WLM. Smoking informa-
tion was obtained for both groups (some from relatives). Data on the
21 lung cancer deaths of miners were collected over a 20-year period
(19561976). The mean age at death was 70 and 59 years, respective-
ly, for nonsmokers and smokers with lung cancer. The mean I-L
period was 43 and 34 years, respectively, for nonsmokers and
smokers with lung cancer. The nonsmokers contributed 47 percent of
the lung cancers, whereas only 19 percent of the controls were
nonsmokers.

Damber and Larsson (1982; Larsson and Damber 1982) performed
a case-control study of 604 male lung cancer deaths in the three
northernmost counties of Sweden. Two control groups were selected
from among deceased and living populations. Decedent controls were
drawn from the national registry for causes of death and matched for
sex, year of death, and municipality to the lung cancer cases. Living
controls were selected only for those lung cancer cases under the age
of 80 (467 cases) and were drawn from the national population
registry and matched for age, sex, and year of birth. Twenty-five of
the cases and only 10 of the controls had underground mining
exposure. The relative risks for smoking and underground mining
exposure were these: nonsmoking individuals with no underground
mining exposure, 1; nonsmokers with underground mining exposure
(2.4 decedent controls, 7.0 living controls); smokers with no under-
ground mining exposure (6.8 decedent, 7.4 living); and smoking
miners (18.2 decedent and 16.1 living). The mean age at death was 69
and 63 years, respectively, for nonsmokers and smokers among the
miners with lung cancer. The mean I-L period was 43 and 35 years,

452


respectively, for nonsmokers and smokers among the miners with
lung cancer. The mean exposure was not given, but was probably
about 100 WLM, as many of the subjects were the individuals studied
by Radford and Renard (1984). This difference was considered to
represent a multiplicative effect of cigarettes and radon daughters,
but it was not possible to rule out an additive effect.

Case-control studies were done with a different group of Swedish
iron miners (Edling 1982; Edling and Axelson 1983). Cases were
deaths from lung cancer, and controls were miners who died from
nonmalignant causes, matched for birthdate, sex, and year of death.
Mean exposures were about 100 WLM. There were 44 cases among
miners, and a standardized mortality ratio (SMR) of 11.5 to 16.2 was
calculated for lung cancer. Of these 44 cases, 38 were smokers and 6
were nonsmokers. The risk ratio was 1.5 to 2 times greater among
smokers than among nonsmokers. The mean age at death was 67 and
61 for nonsmokers and heavy smokers, respectively. The mean I-L
period was 40 and 37 for nonsmokers and heavy smokers, respective-
ly. The authors concluded that the interaction was probably additive.

A retrospective cohort study was done of another group of workers
from two iron mines, one worked since 1890, the other since 1920
(Radford and Renard 1984). Death data were collected for a 26-year
period (1951-1976). There were 50 lung cancer deaths that occurred
10 or more years after start of mining. The mean exposure was about
94 WLM (84 WLM corrected for exposure immediately prior to
death). Smoking information was obtained from relatives for all lung
cancer deaths and by questionnaire from approximately half of those
study members alive in 1973. Using general population data on
smoking and mortality, a dose-response relationship for radon
daughter exposure was demonstrated. There were 18 lung cancer
deaths among nonsmokers versus 32 among smokers. The relative
risk due to radon daughter exposure was 10 for nonsmokers and 2.9
for smokers (p<O.OOl), and the radiation exposures were approxi-
mately equal for both groups. The absolute excess lung cancer risk
attributable to radon daughter exposures was slightly higher for
smokers than for nonsmokers. The mean I-L periods were 41.3 for
nonsmokers and 38.8 years for smokers. The mean age at death from
lung cancer was approximately 65 years, but was not calculated by
smoking status. The authors concluded that the interaction was
slightly more than additive.

Canadian Miners

In studies of a group of Canadian fluorspar miners there were only
2 lung cancer deaths among nonsmokers versus 76 among smokers
(Wright and Couves 1977; Morrison et al. 1981). Smoking data were
incomplete, but it was estimated that only 5 percent of the miners
were nonsmokers. The mean exposure was approximately 600 WLM.

453


The followup period was from 1933 to 1977, an interval of 44 years.
The mean I-L period was 25 years and declined with increasing age
at start of mining. The mean age at death was 52 years.

An analysis of sputum cytology results from 249 active Canadian
uranium miners found that the frequency of atypical cells in sputum
was related to both cigarette smoking and radiation exposure. Few
atypias were seen among nonsmokers, and this was interpreted as a
potentiation of the radiation effect by smoking (Band et al. 1980).

Other Epidemiological Studies Relating Radiation and Cancer

Because of the high cost of imported fuel, the Swedes were among
the first to emphasize the closing of cracks and adding insulation to
dwellings in order to conserve heating fuel. Sealing the indoor
environment also resulted in an elevation in the radon levels in the
indoor environment. These radon exposures have resulted in a
substantial interest in Sweden in the role of radon as well as in the
role of cigarette smoking on their lung cancer death rates.

A case-control study was conducted in rural areas of Sweden,
limited to people who had lived at the same address for 30 years
before death (Axelson 1983). Measurements of radon in different
types of houses led the researchers to classify wooden houses without
basements as low radon, and brick or concrete houses with base-
ments (especially those built on alum shale or granite deposits) as
high radon. Smoking histories were obtained on half of the cases
from questionnaires completed by relatives. In the high exposure
housing, smokers had a lung cancer crude risk ratio of 8.3; in the low
exposure houses the ratio was only 2.0. There was no difference in
smoking habits between inhabitants of the two types of houses. The
researchers felt that this indicated a multiplicative or synergistic
interaction. A second study of Swedish residents did not alter that
conclusion (Axelson 1983; Edling et al. 1984).

In a case-control autopsy study of 204 Japanese A-bomb survivors
with lung cancer who subsequently died, the relationship of smoking
to radiation exposure was examined (Ishimaru et al. 1975). An
increase in lung cancer risk was seen with increasing radiation
exposure and increasing amount smoked, but no interaction could be
discerned.

A cohort study of 40,000 A-bomb survivors studied the relationship
of cigarette smoking and radiation exposure to cancer mortality
(Prentice et al. 1983). Subjects were stratified by smoking and
radiation categories, and multiplicative and additive models were
examined. There were 281 lung cancers. The lung cancer risk rose
with both increasing radiation and increasing smoking. Cancer of
some sites showed an absence of or a negative correlation, but both
esophageal and lung cancer risk rose with both increasing radiation

454


TABLE 5.4nteraction of radiation and cigarette smoking
      among Japanese A-bomb survivors

Relative nsk estimates

        Number         Nonsmokers                  Smokers
          of
Cancer site   cancers    10 rad   l&99 rad   ., IOC rad      10 rad   IO-99 rad   < 100 rad

Stomach     658      1       1.2

Esophagus     58      1       32


Lung       281      1       1.1


SOCRCE Adapted from Prennce FL al 19831

14        13      10       13


65        56      6.6       78


2 3        24      24       36

and increasing smoking (Table 5). The use of Cox regression analysis
did not distinguish between an additive or a multiplicative interac-
tion.

Preliminary findings from a case-control study among A-bomb
survivors suggest that gamma radiation and cigarette smoking
combine in an additive fashion to increase lung cancer risk (Blot et
al. 19841.

Comment on Epidemiological Studies

With the exception of some of the U.S. studies with over 300 lung
cancer cases, most of the human studies were of relatively small
populations, with small numbers of lung cancers. Although confi-
dence in the risk estimates and the mean I-L periods derived is
decreased, there is no reason to suspect that the small population
sizes provided any qualitative distortion of the smoking-radiation
interaction. The studies varied in the quality of their radiation dose
estimates and of their smoking information. Some of the smoking
data was obtained by interview, some retrospectively from relatives,
and some at entry into the study with no consideration given to
subsequent changes in smoking habits. Because of the small num-
bers, pipe and cigar smokers and ex-smokers were sometimes
combined with other groups or light smokers and heavy smokers
were often combined. Some had smoking information on little more
than half of the population. The observations of protective, additive,
or multiplicative effects cannot be easily dismissed. These observed
differences could all be correct for specific groups at specific times
without violating any biological principles.

The mean I-L periods in the various studies differ considerably, as
do the relationships between nonsmoker and smoker I-L periods. It
should be noted that in all of the studies the I-L period was shorter
among smokers than among nonsmokers, although in some studies

455


the difference was small. In studies of radiation and cancer, it ,has
frequently been noted that the observed latent period is strongly
dependent on age at exposure and on the length of the followup
period. That is, subjects who are young at first exposure and who are
followed for most of their lives will exhibit a much longer mean
latent period than will a group first exposed during middle age and
followed for only 25 years. The intensity and magnitude of exposure
may also have an influence on the I-L period (Archer et al. 1979).
Longer I-L periods were noted among Europeans than among U.S.
miners. Longer followup periods and higher radiation dose rates and
doses are probably responsible for this difference.

Cigarette smoking habits may also influence the measured I-L
period for developing lung cancer following onset of radon daughter
exposure independent of any biologic interaction. Even without
significant radon daughter exposure, a number of smoking miners
would have developed lung cancer, and some may have done so prior
to the latent period required for radiation-induced cancers. This
phenomenon would be particularly important in those individuals
whose radiation exposure (but not their smoking exposure) began
late in life. The effect of this independent development of lung
cancer due to cigarette smoking would be to shorten the I-L time
calculated for radon daughter exposure in smokers compared with
nonsmokers, and for workers who joined the workforce later in life
compared with those whose exposure began at a younger age.

Differences in age at start of mining and years of followup between
the nonsmokers and smokers within a cohort might well influence
the relative risks calculated for the two subgroups within any study.
However, even if age at start, years of followup, and percentage
ultimately developing lung cancer are the same for nonsmoking and
smoking subgroups, their relative frequency of induced lung cancer
might vary considerably with time, as indicated in Figures 2 and 3.

Interaction of Radiation and Cigarette Smoke (or Its
Constituents) in the Generation of Animal Tumors

A number of animal experiments have explored the possible
interactions between cigarette smoke or cigarette smoke condensate
(CSC) and ionizing radiation. These experiments have used x-ray or
alpha or beta radiation. Some have used rat or mouse skin as the test
object; others have used the lungs of living animals.
Bock and Moore (1959) found that intense x-ray exposure of a
small portion of the mouse body increased the sensitivity of distant
areas of the skin to cancer induction by painting with CSC.
An experiment using CSC and beta radiation from `%r on mouse
skin (400 mice) was reported at two separate time points (Suntzeff et
al. 1959; Cowdry et al. 1961). In this experiment both the beta

456


-- Smokmg "ramurn mtners

50          60
Age at observatm (years)

FIGURE 3.-Hypothetical lung cancer distribution among
      smoking and nonsmoking uranium miners
      with uniform radon daughter exposure and
      among U.S. white men

radiation and CSC were applied periodically (both separately and
together! so that large total doses of both were used. The first report
gave results at 18 months and considered the interaction to be
synergistic. Fifty-four percent of the mice with combined agents had
skin cancer versus 37 and 5 percent, respectively, when the agents
were used singly. However, when the study was completed by
following the mice until they died naturally, the sum of the skin
cancers among the groups treated with single agents was nearly as
large as the number found among the mice treated with both agents.
Cancers appeared 6 to 7 months earlier in mice treated with both
agents.

A preliminary experiment using CSC and beta particles on rat
skin (McGregor 1976) found a threefold increase in skin tumors over
that, induced by beta radiation alone. The effect was attributed to
tumor promotion activity because the CSC applications were started
2 months after beta exposure and because the amount of CSC used
did not produce any tumors when used alone. This was followed by
further experiments (McGregor and Meyers 1982), using 916 rats.
CSC was applied immediately after exposure to 1,600 rad of beta


particles in one group and 2 months after in another group. When
applied immediately, severe ulceration resulted, making-tumor yield
difficult to interpret. When applied 2 months after radiation,
malignant and nonmalignant yields were increased (p < 0.01). Again,
the levels of CSC used produced no significant increase in cancers by
themselves. The experiments were terminated at 14 and 18 months.
so the ultimate cancer yields were not determined, but at the end of
the experiment there were 2.5 times as many cancers in the beta-
plus-CSC group as in the beta-alone group. At 50 weeks, however, the
ratio was higher (3.41, indicating that tumors appeared earlier in the
group treated with both agents.

Nenot (1977) studied rats that inhaled cigarette smoke plus
americium 241, which delivered alpha radiation to the lungs. The
smoke increased the yield of lung cancers and made them appear
earlier. It was interpreted as a cancer-promoting effect by cigarette
smoke, because the smoke alone did not produce cancer at the doses
used.

The carcinogenic effects of radon daughters, uranium ore dust,
and cigarette smoke in dogs have been reported (Cross et al. 1978,
1982; NCRP 1984b3. Dogs were exposed to radon daughters plus
uranium ore dust, to radon daughters plus ore dust plus cigarette
smoke, to cigarette smoke alone, or to sham cigarettes with room air.
Daily cigarette smoking periods both preceded and followed the dust
plus radon daughter exposures. There were seven lung cancers
among the 20 nonsmoking dogs and none among the controls or the
dogs exposed to smoke alone. Although no dogs were exposed to dust
alone, other experiments suggest that they would not have developed
lung cancer. Exposure to 20 cigarettes per day resulted in pulmonary
emphysema and fibrosis. These two conditions, however, were much
more severe in the dogs exposed to mixtures that included radon
daughters and uranium ore dust. Two nasal carcinomas were found
in the dogs exposed to ore dust and radon daughters, and one in the
group exposed to these two agents plus smoke. There were none in
the other two groups. In these studies, cigarette smoke appeared to
be protective.

In an extensive series of experiments in France, cigarette smoke
was inhaled by rats, either before or after a series of radon daughter
inhalations (Chameaud et al. 1980, 1981, 1982). The cigarette smoke
alone did not produce lung cancers at the levels used. When the
smoke was given in the weeks preceding radon daughter inhalation
it had no effect; when the exposure to smoke was delayed until after
radon daughter exposure was completed, or given during radon
daughter exposure, significantly higher numbers of lung cancers-
were observed. These features were considered to be characteristic of
cancer promotion by cigarette smoke, although the terms "cocarcino-
genesis" and "synergism" were at times applied by the researchers.

458


Interactions of Radiation and Chemical Carcinogens

A number of experiments tested the interaction of radiation and
chemical carcinogens. Some of these chemicals are constituents of
cigarette smoke or are chemically related to such constituents.
Although most carcinogens can also act as cancer-promoting agents,
in these experiments the additional tumor promoters in cigarette
smoke were absent, making them less pertinent to the topic of
radiation and cigarette smoke interaction than the experiments
reviewed in the preceding section. With this in mind, they are
summarized below. Benzo[a]pyrene (BaP) and polonium 210 (PO-210)
were injected intratracheally in hamsters (McGandy et al. 1974;
Little and O'Toole 1974; Little et al. 1978). When given simulta-
neously, tumors appeared earlier, but the effects were additive.
When BaP was given 4 to 5 months after radiation, the effects
appeared to be synergistic, but because effects were small when BaP
was given first and saline injections had nearly the same effect, the
BaP action was considered to be mostly tumor promotion. A similar
study with intratracheal instillations of BaP and plutonium oxide
(PuO,) was done in rats (Metivier et al. 1984) and was considered to
show synergism. Both PuO, and PO-210 emit alpha particles.

BaP used with 150 roentgens of whole body x ray on mouse fetuses
resulted in more tumors (of all types) than was obtained with x ray
alone, but fewer than was obtained with the BaP alone (Urso and
Gengozian 1982).

Dimethylbenz[a]anthracene (DMBA) and 0.8 MeV electrons were
administrated to rat skin at 28 days of age (Burns and Albert 1984).
Multistage analysis of the interaction suggests the existence of two
dose-dependent stages for single doses of radiation and multiple
doses of DMBA, and also that prolongation of the radiation dose
either adds four presumably non-dose-dependent stages or stimulates
clonal growth of an early stage cell.

Rats .were given 600 WLM, then treated with 5-6 benzoflavone,
methylcholanthrene (MCA), or phenobarbital (Queval et al. 1979).
MCA is a carcinogen, the other two are not. Phenobarbital had no
effect. With both benzoflavone and MCA the number of tumors was
doubled. The latent period was greatly shortened with benzoflavone,
but only slightly with MCA. Benzoflavone suppresses tumor develop-
ment when used with BaP.

When rat fetuses were exposed to x ray and the mothers were
injected with ethylnitrosourea (ENU) 4 days later, as adults the rats
developed fewer neurogenic tumors than with ENU alone. This
reduction in tumors was not due to an increased mortality rate of the
f&ally exposed animals (Kalter et al. 1980).
The administration of 1.25 gray (Gy, whole body x ray followed by
injection of ENU was used to induce nervous system tumors
(Knowles 1982). The incidence of these tumors was consistently and

459


significantly higher in the group given ENU alone than in any of the
irradiated groups. The histology of tumors in all groups resembled
those induced by ENU.

When mice were irradiated in utero (36 rad x ray) and then given
urethane at 21 days of age, the yield of lung tumors was enhanced
over urethane alone (Nomura 1984). X ray alone yielded no tumors.
The x-ray effect was seen during the first 14 days of gestation, but
not during the later fetal or neonatal stages.

Intraperitoneal application of tetradecanoylphorbol acetate (TPA)
(a strong tumor-promoting agent) had no influence on the incidence
of malignant lymphomas following four doses of 1.7 Gy of x ray
(Brandner et al. 1984).

When beta particles from phosphorus 32 were used with TPA and
high fat, high protein diets as potential tumor-promoting agents, no
evidence of tumor promotion was found on liver cell transformation
(Berry et al. 1984).

Comment on Animal Studies

Although the results of the animal studies indicate that the
interaction between radiation and cigarette smoke, or its compo-
nents, ranges from no interaction to protection, promotion, and
synergism, there are several features common to many of the
experiments. When cigarette smoke or BaP is administered before
the radiation, there is little or no interaction with respect to tumors.
When administered several months after the radiation, the interac-
tion is greater. In addition, as a general rule, tumors appear earlier
in animals when cigarette smoke is used. In some of the experiments,
the early appearance of cancers caused investigators to apply the
word "synergism" to the interaction, but further followup plus the
production of few or no cancers by the smoke or CSC alone, usually
led tht in qestigators to conclude that the interaction was mainly one
of cancer promotion (Chameaud et al. 1981; McGregor and Meyers
1982). Some of the experiments with cigarette smoke components led
to the same conclusion (Little et al. 1978). This conclusion is
buttressed by the observation that the cancer-promoting activity of
cigarette smoke is greater than its initiating activity (Bock 1968,
1972; Van Duuren et al. 1971; Wynder 1983). Cancer promoters
sometimes increase the yield of cancers in animal experiments by
simply speeding up the appearance of the tumors. Nonspecific injury
sometimes promotes radiation-induced tumors.

Polonium 210 in Cigarette Smoke
Lead 210, which has a 22 year half life, is widely deposited on plant
foliage as a result of radon and radon daughter decay in the
atmosphere. It decays slowly to PO-210, which emits alpha particles

460


that are more dangerous than the beta particles emitted by lead 210.
Appreciable amounts of these two radioisotopes are found in tobacco
and in tobacco smoke, and may contribute to the cancer potential of
cigarette smoke (Radford and Hunt 1964; Kolb et al. 1966; Stahlho-
fen 1968; Black and Bretthauer 1968). A major fraction of the
inhaled PO-210 was shown to be absorbed from the lung directly into
the bloodstream (Little and McGandy 1968). Intratracheal instilla-
tion of PO-210 into the lungs of hamsters resulted in cancer at levels
as low as 15 rad (Little et al. 1978). Calculations of the radiation dose
from the PO-210 in cigarettes have been made repeatedly. Doses to
small portions of the bronchial epithelium were found in man to be
about 1 rad per year (Cohen et al. 19801, 8 rem per year (Steinfeld
1980), and 80 to 100 rad per lifetime (Martell 1983). Average
exposures to the bronchial epithelium, however, are much less than
these calculated doses, which are administered to very small selected
spots. There has been considerable debate as to how much the
radiation from PO-210 contributes to the lung cancer that results
from smoking, ranging from no effect (Hickey and Clelland 1982) to
most of the cancers (Wagner 1982; Ravenholt 1982; Martell 1983;
Winters and Di Frenza 1983). The consensus appears to reflect a
middle ground-that the radiation in cigarette smoke contributes to
its carcinogenicity, but that the chemical agents in smoke also
contribute (Radford 1982; Cross 1984).

To the extent that PO-210 in cigarette smoke induces lung cancer,
its effect would be expected to be directly additive to the effect of the
short half-life radon daughters. To the extent that chemical agents
are involved (either as cancer initiators or as promoters), an
interaction might be expected to occur. Both the animal data and the
human data reviewed indicate at least some interaction, which
therefore reflects action by the chemical constituents of cigarette
smoke, particularly as promoters.

Hypothesis That Reconciles Discrepancies in Epidemiological
Data

A hypothesis that could reconcile the discrepancies in the epidemi-
ologic data has been presented (Archer 1985). Alpha radiation dose
from radon daughters may induce a finite number of lung cancers in
an irradiated group, with most of these cancers being expressed. In
the absence of cigarette smoking, these cancers could have a longer
latent period and may or may not be fully expressed among the
population, depending on the force of competing causes of death
among the older members of the population and the presence or
absence of promoting agents. In the presence of continuing exposure
to cigarette smoke, these radiation-induced cancers could appear at


an earlier date following exposure (and at younger ages) than among
groups not exposed to cigarette smoke.

The lung cancers that would normally be induced by cigarette
smoke would still be present, and added to those induced by
radiation in a mining population. Thus, on a lifetime basis, there
would appear to be an additive effect (radiation plus smoking), plus
perhaps a few extra cancers that would not have been expressed if
the latent period had not been shortened by smoking. The earlier
appearance of cancers among smokers would give an appearance of
synergism in studies conducted within 20 or 30 years after the start
of exposure.

This hypothesis is best understood by examining Figure 3. In this
hypothetical graph it is assumed that an equal number of smoking
and nonsmoking miners of the same age are exposed at age 30 to the
same amount of radon daughters. The resultant curves of lung
cancer incidence reflect the distribution in time of the appearance of
the induced cancers. The shape of the curves might vary somewhat
from the curves for people who are first exposed at older ages. It is
evident from these curves that investigators who examine lung
cancer mortality data at different points in time after the subjects
had begun mining could obtain data indicating synergism (at 40 to 60
years of age), or additivity (at 60 to 70 years of age), or protectiveness
(at 70 or more years of age). The "synergism" noted in the U.S.
uranium miner studies (mean age at death was 55 years for
nonsmokers) would thus be explained (Saccomanno et al. 1967), as
would the "protection" found in one of the Swedish studies (mean
age at death was 70 years for nonsmokers) (Axelson and Sundell
1978). The "additive" effect noted by another Swedish study (mean
age at death was 65 years) with deaths collected over a 26-year
period (Radford and Renard 1984) would also be explained. The long
data-gathering period resulted in a collection of deaths from young
as well as aged miners. The short collection period used in another
Swedish study (Damber and Larsson 1982) (mean age at death was 69
years), interpreted as "synergism," may have resulted from a biased
sampling of deaths because they were from a 5-year period only, or
were from the entry into mining at different times or ages by
smokers and nonsmokers.

A mortality analysis of radon daughter-exposed miners within 25
years after they started mining would, according to the hypothesis,
give an early impression of synergism, just as early observations in
two of the animal studies did (Suntzeff et al. 1959; McGandy et al.
19741, even though lifetime studies would indicate otherwise.
According to some experts, even if the final incidence of lung
cancer in smoking and nonsmoking irradiated individuals were the
same, the net effect could be regarded as synergistic; this is because

462


smoking shortens the tumor-free life of those who develop cancer
iUI1'Sci. Comm. 1982).

Interaction of Radiation and Cigarette Smoke on Other
Aspects of the Respiratory Tract
Larynx and Nasal Sinuses

The attachment of radon daughters to dust particles that are
deposited in the airways (along with unattached ions) of animals and
man means that the upper respiratory tract and bronchi receive
higher total doses of radiation than any other part of the body.
Excess cancers of the larynx have been reported in uranium miners
(Tichy and Janisch 19731. Although this cancer site has been
associated with cigarette smoking, the possible interaction of the two
agents on the larynx has not been evaluated. Cancer of the sinuses
has been attributed to the radon and radon daughters that collect in
the paranasal sinuses of people with elevated radium body burdens
(Rowland et al. 1978; Schlenker and Harris 1979). Cancer of these
sinuses has not been attributed to cigarette smoke in U.S. popula-
tions. The nasal and pharyngeal and tracheal epithelium in man
may be sufficiently thick and covered by enough protective mucus so
that the alpha particles from radon daughters rarely penetrate to
those cells where permanent injury can result (presumably the basal
germinal layer). The thin epithelium of the bronchial subdivisions
apparently may not provide similar protection.

Pulmonary Function and Fibrosis

Epidemiologic studies have demonstrated that the pulmonary
function of uranium miners is compromised (Archer, Carroll et al.
1964; Archer, Brinton et al. 1964; Trapp et al. 1970; Samet, Young et
al. 1984). The loss in pulmonary function is followed in time by
greatly elevated mortality rates from or with nonmalignant pulmo-
nary disease (Archer et al. 1976; Archer 1980; Waxweiler et al. 1981).
In these analyses several diseases were grouped together-or
pulmonale, silicosis, pulmonary fibrosis, chronic obstructive lung
disease, emphysema, and related diagnoses-because diagnostic
criteria for them are known to vary greatly between physicians.
They usually reflect injury by inhaled toxic agents. Uranium miners
were also exposed to a third toxic agent, silica ialpha quartz), in ore
dust as well as to radon daughters and cigarette smoke.

Uranium ore dust and tobacco smoke, as well as radiation,
undoubtedly contribute to the nonmalignant pulmonary problems of
uranium miners. Both human studies and animal studies have
indicated that radiation contributes to the lung pathology and
functional loss (Archer, Brinton et al. 1964; Cross et al. 1978; Cross,
Filipy et al. 1981; Cross. Palmer et al. 1981). Very few of the uranium

463


miners disabled by shortness of breath had typical silicotic nodules
on x ray and were therefore unable to obtain workmen's compensa-
tion for silicosis. Neither the relative roles nor the interactions of
these three agents (radon daughters, cigarette smoke, silica) in these
conditions is well characterized.

The pathology of radiation pneumonitis after larger acute radia-
tion doses is well known (Gross 1981). Following irradiation at high
doses, there is death of some of the epithelial and endothelial cells
within 3 to 6 months, resulting in increased capillary permeability
and leakage of plasma proteins into the alveolar surface. Within 1 to
3 years, the pneumonitis is followed by a fibrotic reaction, which
may represent a healing of the radiation pneumonitis, but has the
effect of reducing the functional capacity and compliance of the lung.

After relatively low chronic doses of alpha radiation, as occurs in
uranium miners, such changes have not been reported, but some
fibrotic change is implied by the aforementioned epidemiologic
studies. The high linear energy transfer of alpha radiation leads to
the belief that cellular injury and repair after chronic low doses of
alpha radiation could slowly lead to fibrotic changes. The injury
would be so diffuse, however, that fibrosis would be detectible only
after many years. Loss of pulmonary function, fibrosis, and other
changes have been observed in the lungs of rats, hamsters, and dogs
chronically exposed to radon daughters, cigarette smoke or diesel
exhaust, and uranium ore dust (Gaven et al. 1977; Stuart et al. 1977,
1978; Wehner et al. 1979; Cross, Palmer et al. 1981; Cross, Filipy et
al. 1981; Cross et al. 1982; NCRP 1984b). Although these experiments
were not designed to evaluate the degree of interaction of the
different agents, it was clear that the fibrotic and other pathologic
changes were much more severe when the animals were exposed to
two or three of the agents together than when exposed to a single
agent.

The relatively low radon daughter exposures at which pulmonary
function effects (possibly due to radiation) have been found in
uranium miners (Samet, Young et al. 1984) suggest that there may
be no threshold for such effects.

Research Recommendations

1. The possibility that alpha radiation from background radon
daughters in homes may contribute to lung cancer in human
populations (Axelson 1983; NCRP 1984a, b; Harley 1984;
Radford and Renard 1984) and the interaction of both active
and involuntary tobacco smoking on this possible effect of
radon daughters need further investigation. They may have
important implications for the ventilation of homes and for the
effects of involuntary smoking.

464


2. The influence of tumor-promoting agents on radiation-induced
cancers has not been adequately. explored. Further animal
studies of this interaction are indicated.

Summary and Conclusions

1. There is an interaction between radon daughters and cigarette
smoke exposures in the production of lung cancer in both man
and animals. The nature of this interaction is not entirely clear
because of the conflicting results in both epidemiological and
animal studies.

2. The interaction between radon daughters and cigarette smoke
exposures may consist of two parts. The first is an additive
effect on the number of cancers induced by the two agents. The
second is the hastening effect of the tumor promoters in
cigarette smoke on the appearance of cancers induced by
radiation, so that the induction-latent period is shorter among
smokers than nonsmokers and the resultant cancers are
distributed in time differently between smokers and nonsmok-
ers, appearing earlier in smokers.

465


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471


CHAPTER 12

SMOKING INTERVENTION
     PROGRAMS
IN THE WORKPLACE


CONTENTS

Introduction

Criteria for Evaluating Worksite Programs
Changes in Participants' Smoking Behavior
  Worksitewide Program Effects
  General Effects

General Review of Worksite Programs
  Uncontrolled Studies
  Controlled Studies
  Remaining Issues

Special Issues Relevant to Worksite Programs
  Social Support

Physician Advice
Incentives

High Risk Populations
Multiple Risk Factor Reduction Programs
Organizational Characteristics and Other Factors

Implementation of Worksite Smoking Programs
  Promotion and Recruitment
Program Characteristics

Recommendations for Future Research
  Methodological Issues
  Substantive Areas

Summary and Conclusions

References

475


Introduction

Cigarette smoking by employees results in increased expenses for
employers. Smokers use the health care system up to 50 percent
more than nonsmokers (Fielding 1984); this means higher health
insurance costs for companies. Studies have reported higher rates of
work-related accidents, disability reimbursement payments, and
absenteeism among employees who smoke than among those who do
not (Terry 1971). Although it is difficult to assess exact dollar
amounts because of the variety of circumstances and assumptions
involved (Warner 1983), estimates of excess annual costs to employ-
ers per smoking employee generally run from $200 to $500 (Lute and
Schweitzer 1978; Kristein 1982). Costs attributable to smoking
among employees in the high risk occupations discussed in this
Report are likely to be considerably higher than these overall
estimates.

These data, as well as consideration for the welfare of their
employees, have led a number of businesses to establish workplace
antismoking programs. Because of the magnitude of the health
effects of smoking and the benefits of cessation, smoking cessation
programs are likely to yield a higher return on investment than
worksite health promotion programs targeting other risk factors
such as obesity and lack of exercise (Fielding 1984). Surveys reveal
that 11 to 15 percent of American businesses provide smoking
reduction programs and many more are considering such programs
(Dartnell Inst. 1977; NICSH 1980). In response to the recommenda-
tions of a panel of experts concerning priorities for health promotion
activities, the Health Insurance Association of America has estab-
lished a smoking reduction program that is available to its members
(Fielding 1984). From one-third to one-half of the large organizations
have designated no-smoking areas (Dartnell Inst. 1977; NICSH 1980).

A great variety of worksite smoking-modification approaches have
been devised, including monetary incentives and contests for not
smoking, distribution of self-help materials, physician messages and
health education lectures on the adverse effects of smoking, and
stop-smoking clinics (Chesney and Feuerstein 1979; Danaher 1980;
Klesges and Glasgow 1985; Orleans and Shipley 1982). Stop-smoking
sessions have been led by coworkers, volunteers from health
organizations, commercial cessation consultants, and health profes-
sionals. Ongoing multiple risk factor intervention programs, either
for the entire workforce or for individuals at especially high risk of
developing cardiovascular disease, have been offered. The purpose of
this chapter is to critically review the literature on such programs.
First, however, it is helpful to consider both the potential advantages
and the possible disadvantages of worksite smoking modification
programs versus the more traditional, clinic-based programs.

477


The potential advantages of worksite-based smoking modification
programs can be considered from the perspective of employees,
employers, and public health researchers. For employees, the
primary potential advantages appear to be increased convenience
(particularly if the program is held during work hours), reduced
expenditure if the company pays all or part of the program fee, and
the opportunity to participate with friends and coworkers rather
than a group of strangers. For the employer, potential benefits
include increased worker productivity, better employee morale, and
better employee and public relations from health promotion efforts.
The potential monetary savings from reduced absenteeism and
medical costs are also appealing.

For public health researchers, worksite programs offer the advan-
tages of a much larger number (and possibly different types) of
smokers involved in efforts to quit than would otherwise be the case,
greater ease in obtaining long-term followup data, and the opportu-
nity to provide sustained or ongoing programs rather than one-time
offerings. In worksite programs, treatment is conducted in the
environment in which participants spend a large portion of their
day, which should facilitate generalization of treatment effects and
potentially lead to the establishment of nonsmoking norms. Possibly
the greatest potential resource available in worksite programs from
all three perspectives is the additional incentive and motivational
components that can be brought to bear through both monetary and
social support manipulations.

It is important to realize, however, that these potential benefits do
not occur automatically (Klesges and Glasgow 1985), and that they
may be offset by possible disadvantages of worksite smoking
modification programs. From an employee perspective, participation
may interfere with work activities or be outwardly condoned, but not
supported, by a supervisor. Meetings may be held at inconvenient
times or in inconvenient locations. If promotional activities are not
handled appropriately, workers may feel coerced to participate.
From an employer's perspective, there are the direct costs of the
program, such as advertising, counselor time, and materials, as well
as indirect costs, such as time off work for employees to participate.
Sponsoring an antismoking program can also create employee
relations problems. Nonsmoking employees may resent the time off
work available to smokers and may demand that their own
participation in health promotion programs be subsidized. The
critical issue here may be company norms, whether time off is
consistent with previous company practice regarding other programs
for employee benefit. In organizations in which workers are exposed
to hazardous substances such as asbestos, unions may view smoking
cessation programs as attempts by management to absolve them-

478


selves of responsibility for occupationally related disabilities (Ellis
1980).
There are also problems from the perspective of public health
researchers in conducting programs in the workplace. Most of these
potential disadvantages result from a reduced degree of control over
variables that can influence outcome. For example, company pro-
gram planners (organizational steering committee) might decide to
conduct additional stop-smoking activities (e.g., changes in company
smoking policies, added incentives for not smoking, participation in
other health promotion activities, a contest with a rival business)
that are not part of the study design. Finally, some participants may
take part solely as a way of getting out of work rather than from a
desire to change their smoking behavior.

Criteria for Evaluating Worksite Programs

The criteria for evaluating program effects are considered under
three general headings: changes in participants' smoking behavior,
effects on smoking and health-related variables for all employees in
t.he organization, and "secondary" effects of a program on nonhealth
variables of concern to employers. Most reports on worksite-based
programs assess only one or two of these areas.

Changes in Participants' Smoking Behavior

The same considerations that apply to the measurement of adult
smoking behavior in clinic settings apply also to worksite smoking
modification programs. Specification of reported smoking data is
particularly important. Following a program, there is often a
bimodal distribution of smoking rate, with a number of individuals
successfully quitting and many nonquitters smoking at close to their
baseline rate. Presentation of reductions in the "average" number of
cigarettes smoked can therefore be misleading. It is important to
separate data about subjects who are abstinent from data about
those who are still smoking, albeit at a reduced rate, when reporting
either reductions in smoking behavior or biochemical indices of
smoking exposure.

It is critical, of course, to have information about the long-term (6
to 12 months minimum) effects of smoking modification programs
(Lichtenstein and Brown 1982; McFall 1978). Interest in research in
the "dynamics of cessation and relapse" is much more recent (US
DHHS 1983, p. 246; Ockene et al. 1982). It is helpful to know, for
example, whether a 30 percent long-term abstinence rate resulted
from the same 30 percent of participants remaining abstinent
throughout the followup period or from IO percent new quitters, IO
percent previous relapsers, and.10 percent who remained abstinent
throughout the assessment periods.

479


Objective verification of changes in smoking behavior has become
the standard for defining smoking behavior. Recent reviews have
been conducted of several biochemical measures of smoking status,
including carbon monoxide, saliva thiocyanate, and cotinine (Freder-
iksen and Martin 1979; Leupker et al. 1981; Benowitz 1983; Bliss and
O'Connell 1984). Simply having an informant, usually a spouse or
coworker, "confirm" a participant's smoking status may not be
sufficient corroboration. Such people are not in a position to
continuously observe a participant's smoking behavior throughout
the day and may be persuaded to falsify their report on the
participant's smoking behavior.

Worksitewide Program Effects

The impact of a worksite program may include effects on workers
other than those enrolled in the program and effects other than
smoking cessation. The localized nature of a worksite program and
the repetitive interactions of workers in the program with those who
did not participate may produce changes in the attitudes and
behaviors of the active workforce that promote smoking cessation
and improve employee morale and productivity. For these reasons,
one criterion for evaluating worksite programs should be the
fraction of the workforce whose smoking behavior is altered in
addition to the fraction of the participants who quit. All of these
effects are important in evaluating the reported success rate of a
program because a very high cessation rate for a program may have
little overall impact if only small numbers of employees are willing
to participate (Kanzler et al. 1976). Whenever possible, program
costs should be reported in addition to data on the effects on smoking
patterns of nonparticipating smokers. In the same vein, ongoing
worksite programs conducted over a number of years should attempt
to document the effects of a smoking modification program on
variables such as absenteeism, medical care expenses, and health
services utilization.

General Effects

Variables such as employee morale and productivity, commitment
to the organization, turnover, and employee-employer relations are
important potential secondary effects of a worksite program. Be-
cause these issues do not directly concern the topic of smoking and
health and have been infrequently assessed, they are not considered
in this review. It should be noted, however, that Brownell (1985)
makes a convincing case that if the field of worksite health
promotion is to prosper, concerted attention needs to be directed
toward demonstrating the effects of worksite programs on these
organization management issues. He argues that managers may be
more interested in such results than in changes in health status.

480


General Review of Worksite Programs

A large number of worksite smoking control programs have been
conducted. Unfortunately, only a small percentage of these programs
have been evaluated. The characteristics and results of experimental
investigations of occupational smoking control programs that have
presented more than anecdotal data are outlined in Tables 1 through
3. Many of these studies have consisted of pretest-posttest or post-
test-only evaluations without control conditions and have not
reported objective measures to validate self-reports of smoking
status. The sample size, type of worksite setting, and reported results
of such uncontrolled studies are listed in Table 1. Because of the
absence of comparison conditions, the lack of verification of smoking
status, and the general sparsity of information about program
procedures and treatment effectiveness in these reports, there are a
host of alternative explanations of their results. Therefore, they are
only briefly summarized.

Uncontrolled Studies

Although programs have been conducted in a variety of worksite
settings (Table l), the majority have been either conducted in
companies of small to moderate size with white-collar employees or
offered only to supervisory personnel. The number of participants is
generally small. Self-reported abstinence rates for these uncon-
trolled studies ranged from 25 to 90 percent (median, 60 percent) at
posttreatment and from 6.5 to 91 percent (median, 33 percent) at 6-
month or l-year followup. These figures, while encouraging, must be
interpreted with caution because it is often unclear whether the
reported rates have excluded subjects who dropped out of treatment
or followup, and because, in several studies, subjects received sizable
monetary rewards based upon reports of abstinence that were not
corroborated by objective measures of smoking.

Not known is the impact of the programs listed in Table 1 on
overall rates of smoking in the worksites in which they were
conducted (see Bishop and Fisher 1984). The majority of investiga-
tions do not report rates of participation in their programs, but the
studies that have reported (other than in very small companies as
noted below) have been discouraging. For example, Kanzler and
colleagues (1976) found that despite an intensive promotional
campaign, only 4 percent of smokers in their workplace began the
cessation program. Grove and colleagues (1979) found that of 409
smokers in their worksite, only 101 attended the first meeting, and
only 33 (8 percent of the smokers in the workforce) completed
treatment. Of these 33 subjects, only 9 were abstinent at 6-month
followup. Stachnik and Stoffelmayr (1981), noting these generally
low participation rates, stated: "The question of how one can


TABLE I.--Uncontrolled studies without objective measures
      of smoking status

Stud>

Number of WbJ`Xk
type of worksite

Cessatmn rate cpercent I

          Followup
Posttreatment    INO. months)

Andrew (19831        965 hospital employees

Bauer 119781

81 Bell Laboratorm
employees

Not reported


   90

26 (201

30 161

Bishop and Fisher
119841

lW6 employees in
each of six companies

254x

6X33
1121

Dawley et al 119841

15 VA hospztal
employees and 2 patlents

88

50 16,

Elhs (19WI

Asbestos company
employees

Not reported      30 (48)

Grove et al 119i91      33 Blue Cross employees          33         27 161

Heckler 119801

16 Thomas Llpton, Inc.
employees

Not reported

50 (1)

Kanzler et al (19761

9 psychiatric institute
employees and 21
commumty members

67

40 1121

33 engine manufacturing
company employees

Not repmtea

55 1121

Rosen and
Lichtenstein ,197:)

12 ambulance company
employees

58

33 112,
lat worki

Shepard 119801

26 electromcs mfg.
company employees

Not reported

35 148)
fat work1

Sorman i19791

Not reported

31 112,

Stachmk and
Stoffelmayr ,19831

Employees in three
compames bank,
manufacturer, and
health services

Nat reported

a&91
(61

increase participation in smoking cessation programs should receive
the same attention that the more standard question of which
cessation technique is most effective has received in the past" (p. 49).
The exceptions to these low participation rates are seen in studies in
the companies with fewer than 100 employees that have employed
incentive procedures (e.g., Rosen and Lichtenstein 1977; Sorman
1979; Shepard 1980; Stachnik and Stoffelmayr 1983).

482


Controlled Studies

Studies that have included control or comparison conditions are
presented in Tables 2 and 3'.  To emphasize the importance of
worksite and participant characteristics, these characteristics as
well as data on the public health issues of recruitment strategies
employed and on the participation and attrition rates experienced
are listed in Table 2. The type of intervention and experimental
design employed, short- and long-term cessation rates, and type of
biochemical validation of smoking status obtained, if any, are
described in Table 3. In this section, a general discussion of the
status of the worksite smoking modification literature with emphasis
on the characteristics of the most successful programs is followed by
a more detailed review and discussion of several important subtopics
within the occupational smoking modification field-the role of
social support, physician assistance, incentive approaches, employ-
ees at particularly high risk for the development of cardiovascular or
respiratory disease, multiple risk factor reduction programs, and
organizational characteristics that affect program success.

The varied programs conducted have ranged in intensity from a
brief physician message (e.g., Li et al. 1984) to ongoing programs
involving multiple components over a 4- to 5year period (e.g., Rose et
al. 1980). Recent programs have offered participants a variety of
behavior change options. In particular, 7 of the 14 studies outlined in
Tables 2 and 3 allowed subjects to select as goals either smoking
reduction or abstinence.

The most encouraging finding is that the long-term success rates of
the programs reviewed are relatively high. Although initial cessa-
tion rates do not appear to differ from those typically produced by
community-based smoking clinics, the longer term followup data are
more positive if viewed as a percentage of posttreatment cessation
outcome. Abstinence rates at 6 to 24 months after a program are
approximately 60 to 65 percent of those observed at posttest, in
contrast to the 20 to 30 percent figures classically cited for clinic
programs (Hunt and Bespalec 1974; McFall 1978). In fact, the lowest
maintenance rate in the studies summarized in Tables 1 and 3 was
26 percent of the posttest rate, and some studies report followup
results equal to or better than posttest (e.g., Malott et al. 1984; Meyer
and Henderson 1974; Schlegel et al. 1983). On the other hand, much
higher long-term abstinence rates, 50 percent or better of all
subjects, have recently been reported from a number of treatment
programs (US DHHS 19821, and results from the 22-center Multiple

483


lb
$  TABLE 2.-Worksite, subject, and procedural characteristics of controlled outcome studies


                              Participation rate        Characteristics of      Attrition rate
   Study         Size and type of worksite        (percent)           participants        @aTent)       Recruitment slrategies

Abrams et al.
(1985)

WO-employee medical
manufacturing company and
1.6Wemployee insurance
carrier

Gleegow et al.    6OGemployee telephone
we4         company

Glasgow et al. (in  VA hospital. health care
Pm)        services company, and
          savings and loan

Klesgee et al.
w35)

Four banks and one savings
and loan, 11%180 workers
each

Kornitzer.
oramaix et al.
U980)

30 Belgian factories

Li et al.
(1984)

Naval shipyard

Not reported
(estimated 6)

Not reported     25 female, 11 male
(estimated i8)     employees

Not reported

20 female, 9 male employees

88 with competition;
  53 without
  CP <ox4

84 agreed to screening

87

54 clerical end bluecollar
employees

82 female, 25 male
employeee

19,390 male employees, aged
do-59 years; high risk: upper
20 percent of risk
distribution

871 male shipyard workers

42

Not
repted


  7

9

Not
reported

17

Paycheck stuffers, p&ers. newsletter
articles

Employee organization sponsorship,
newsletter notice8, posters

Brochures, posters, newsletter notws
memoe

Brochures. announcements by bank
presidents, time off work for
participation; prize to bank with higheet
participation

Not reported

Participation asked at required screening


TABLE 2.-Continued

Study

Size and type of worksite

Participation rate
  (percent)

Characteristics of
participants

Attrition rate
(percent)       Recruitment strategies

Malott et al.
(198-u

Meyer and
Henderson
11974)

Neppa (1984)

Rand et al.
Il984I

Fhe et al.
11980)

Schlegel et al
1198.7)

Scott et *I.
(19831

Medical clinic and telephone      Not reported
company                  (estimated 7)

Varian Corporation; 240
employees, volunteers for
risk factor screening (13
percent of workforce)


Johnson & Johneon
Corporation

Large city hospital

Not reported

Not reported

Not applicable

24 large British industrial
fWW+

86 agreed to screening

28 Canadian military bases

Not reported

Large VA hospital

100

20 female, 4 male
employees, primarily clerical
and numee

36 employees identified at
screening aa high risk for
cardiovascular disease

36 white-collar employees: 20
women. 16 men

18 female employees

18,210 male employees. 40-
59 years old; high risk:
upper 12-15 percent of
distribution

243 armed forces perwnnel
65 percent male1

26 numm (22 women. 4
men)

0

0

67

Not
reported

612

Not
reported

0 of those
continued
at VA

Newsletter notices, brochures distributed
by supervisors, recruitment in
lunchrooms

Invitation to health screening

Posters, desk drops, company newsletter

Advertisements. word of mouth

Invitation to health screening exam

Posters. new8 releases

Individually approached


E  TABLE 3.-Design and outcome of controlled worksite smoking modification studies

Cessation rate (percent)

Study

Program intensity              Experimental
and componenta                 design

PC&
treatment

Followup
(No. months)

B&hem&
veriticatlon

Abram8 et al.
(1985)

Basic foursession nicotinefading
cewation program; four+eseion
mttintenance treatment

Basic program plus
health education (n= 181;
stress management (n = 18);
or social support (n = 18)

38'           331 (3)            co
33'            27'
6'             6*

Glasgow et al
(1984)

Seven weekly small group meetings
on brand changing and number
reduction; goal choices, abstinence or
controlled smoking

Gradual reduction (n = 12);
abrupt reduction (n= 13);
gradual plus feedback (n=ll)

Not
reported

33' (6)            a.3
0'
01

Glasgow et al.
(in pree.3)

(See Glasgow et al. 1984) Social
support with two meetings.
inatallmenta of manual, and phone
Cdls

Basic treatment progrsm (n=13)
vs. basic treatment plus
significant other social support
(n = 16)

54           25 (6)            co
36             23            SCN

Kleegea et al.
(1985)

(See Glasgow et. al. 1984)
Competition, with monetary prizes,
weekly feedback charta

Quasi-experimental;
basic treatment (n=16) vs.
basic treatment plus
competition (n=91)

31           14 (6)            co
22             18             SCN


TABLE 3.-Continued

Study

Program intensity               Experimental
and components                 design

   Ceesation rate (percent)

post-        Followup
treatment       (No. months)

Biochemical
verification

Kornitzer.
Dram& et al
( 1980)

Multiple risk factor program, written
advice and antismoking posters; high
risk subjects, semiannual physician
counseling and stop-smoking booklet

Treatment (n=7,398) vs.
screening only (n=8,824)

Not
reported

High risk
  19' (241
   12'
Random sample
   12.5
   12.6

No

Li et al.
.(1984)



Malott et al
(1984)

Oneeeeaion physician advice and
stopsmoking pamphlet



(See Glasgow et al. 1984) Coworker
support: partner support manual,
buddy system, individualized support
behaviors

5 to &minute behavioral
counseling (n =215) vs.
warning to quit (n=361)

Basic treatment program (n=12)
vs. basic treatment plus coworker
social support (n=12)

Not
reported



17
17

8.4' (3, 11)


  3.6 1


27 (6)
  17

Meyer and
Henderson
( 1974)

Multiple risk factor program, 9 to 12
meetings; 2- to 3.5hour behavior
modification group meetings with
*po=+=

Behavior modification (n=12) vs.
individual counseling (n-10) vs.
physician advice alone (n = 14)

40           20 (3)
25             25
0             33

co





co

No

Nepp (1984)

Nine written self-help modules;
minimal therapti contact

Quasiexperimental: minimal
contact (n-36) compared with
earlier group cessation program

22           14 (6)            co


TABLE 3.-Continued

Study


Rand et al.
(1984)

    Program intensity              Experimental
     and components                 design


Monetary incentives for low daily Co     Withinilubjecta design (n= 18):
levels, 1 week of reducing Co levels       baaeline-cutdown-abstinence
and 2 weeks of abstinence           l3ds

  Cessation rate (percent)

post-        Followup
treatment       (No. months)



  61         28 (3 wks)

Biochemical
verification



  co

Rose et al
(1980)

Schlegel et al.
(1983)

Multiple risk factor program: poeters
and stopemoking booklets; high risk
subjects, four company physician
consultations

Gmonth program; 16&page workbook;
abstinence or reduced smoking goal
choirs.?; base personnel were
therapists

Treatment (n=9,734) "8.
screening only (n=8,476)

Full treatment (17 sessions)
vs. minimal contact (4
-ions) ~8. self-help; crowed
with nicotine gum/no nicotine
gum

High risk
12' (5 yrs)
  0'
Others
  7'
  0'

45-68'        25-382 (12)
28-315          17-295
Cl4 3           7-10 8

No

No

Scott et al.
(1983)

Brief daily sessions with brand
fading, treatment manual, and Co
feedback, 3 months; abstinence or
reduced smoking goal choice

Treatment (n=16) vs.
no treatment (n=lO)

56'          25 (9)            co
0'             0

NOTE: The aample sizes reflect the number of subjects receiving each treatment condition. which in cane titancen differs fmm the total number of subjecta initiated into the study (see Table 2).
Except for the Kleegen and colleagues (1986) and the Li and c&zaguea Wf34) studies, in experiments using between-eubjecta designa there was random assignment to treatment conditions.
NOTE: CO=carhon monoxide; SCN=saliva tbiocyanate.
1.2 At each assessment point, conditiona that were aigniticantly different (p < 0.05) are identi&d hy different superscripts.
`Results of this factorial study are complex and diflicult to summarize with a notation system; see text for clarification (numbers for treatment conditions not reported).


Risk Factor Intervention Trial (MRFIT) study showed that long-term
abstinence rates actually rose from l-year to 6-year followup under
both intervention and control conditions (US DHHS 1983). These
results again indicate the need to separate point prevalence of
nonsmoking rates from continuous abstinence rates. Unfortunately,
data are seldom presented in terms of survival curves (e.g., Curry et
al., in press) or in a manner that permits assessment of the
consistency in smoking status over time.

These high followup rates suggest that the worksite may offer
more than a convenient location for cessation interventions, and
that interactions or changes in attitudes or behaviors in the worksite
may be important determinants of the successful maintenance of
abstinence. Although there are several potential explanations for
these relatively good maintenance data, the most obvious is the
ongoing contact that coworkers have with each other during the
followup period. Consistent with this hypothesis, the clinic-based
smoking cessation program in the MRFIT study, which produced one
of the most impressive maintenance rates of any study (Hughes et al.
1981; Ockene et al. 19821, involved ongoing contact over several
years. Even if coworkers are not highly supportive of each other,
they may come to provide no-smoking cues for other participants.

It is important to note that people involved in many of the
worksite studies described here are both self-selected and self-
motivated, as there are few usual care or no-treatment conditions.
Some of the high maintenance rates may be reflective of new
quitters who would stop in any program, or even without one.

This comparison of clinic-based programs and worksite programs
assumes that participants in each setting are similar. Although the
demographic and smoking history characteristics of subjects in these
reports do not appear to differ systematically from other studies in
the cessation literature, there may still be marked differences
between the groups. For example, since worksite programs generally
attract a higher percentage of smokers than do community-based
clinics, some of these subjects may be more recalcitrant smokers
(Bishop and Fisher 1984). The convenience of the worksite setting
may also attract more smokers. On the other hand, it may be that
only individuals who have repeatedly failed to quit on their own will
expend the time, effort, and money often involved in participating in
community clinics (Schachter 1982). To date, the primary determi-
nant of participant characteristics in the controlled outcome studies
(Table 2) seems to be the type of worksite in which a program is
conducted. Research is needed on the hypotheses concerning possible
differences between participants in worksite programs and smokers
attending community clinics.

Several differences between studies reporting high success rates
and those with less favorable results are clear. One of the more

157-964 C - 81 - 17                               489


striking differences to emerge is that the results of the better
controlled studies summarized in Table 3 (median posttest cessation
rate, 28 to 31 percent) are generally lower than those of the
uncontrolled studies outlined in Table 1 (median posttest cessation
rate, 60 percent). The most obvious explanation for this finding is
that most of the controlled studies included objective biochemical
indices of treatment outcome and subjects in these studies may have
more accurately reported their smoking status.

The intensity of smoking modification programming also appears
to be related to treatment outcome. Programs involving only a brief
session or two or relying primarily on self-help materials generally
produced the lowest cessation rates-from 4 to 14 percent long-term
abstinence (e.g., Li et al. 1984; Nepps 1984). In contrast, the best
cessation rate reported came from an intensive multicomponent
program involving 20 group meetings over a 7-month period
(Stachnik and Stoffelmayr 1983). The only worksite study to directly
compare different levels of program intensity found that a greater
number of sessions was associated with higher cessation rates
(Schlegel et al. 1983).

Another fairly consistent finding is that programs conducted in
larger worksites generally seem to produce poorer outcomes. Of the
abstinence-based programs, studies taking place in worksites with
100 or fewer employees (e.g., Miller 1981; Shepard 1980; Stachnik
and Stoffelmayr 1983) seem to attain the highest abstinence rates,
and the larger scale controlled trials (e.g., Kornitzer, Dramaix et al.
1980; Li et al. 1984; Rose et al. 1980) to result in much lower
abstinence rates. Bishop and Fisher (1984), who have conducted
programs in a variety of different sized worksites, concluded that
larger worksites also typically produce lower participation rates
than do smaller companies. However, a greater number of employees
may still be served.

Programs addressing multiple risk factors (e.g., Rose et al. 1980) in
worksite settings generally yielded poorer cessation rates (and
tended to be conducted in larger worksites) than did smoking-
modification-only programs. Multiple risk factor programs may
achieve greater overall reductions in morbidity and mortality
because of their effects on other risk factors, however. Finally,
programs providing incentives for smoking abstinence (e.g., Shepard
1980; Stachnik and Stoffelmayr 1983) were among those with the
more impressive outcomes, although not objectively verified. These
findings are discussed in more detail in the section on incentives.

Remaining Issues

Few worksite studies have investigated participant characteristics
associated with treatment outcome. The most consistent finding to
emerge is that smokers of lower numbers of cigarettes have greater

490


success at quitting than do heavier smokers (e.g., Kornitzer, Dramaix
et al. 1980; Li et al. 1984; Rand et al. 1984). This finding is consistent
with results of clinic-based programs (e.g., Ockene et al. 1982) and
suggests that special attention needs to be devoted to ways to
successfully treat heavy smokers.

Relatively little is known about the long-term effects of the non-
abstinence-based smoking reduction programs under review (Tables
2 and 3). Allowing subjects to choose the treatment goal of
abstinence or of reduced smoking may attract more participants,
provide initial success experiences that can be built upon in later
cessation efforts, and benefit those subjects not able to achieve or
maintain abstinence. On the other hand, such programs may
dissuade subjects from pursuing a goal of complete cessation and
allow participants to rationalize that smoking is not hurting them
because they have made changes in smoking rate, topography, or
cigarette brand. It is beyond the scope of this chapter to review the
complex literature on potential compensation effects resulting from
changes in smoking behavior (see McMorrow and Fox 1983; Moss
and Prue 1982). It should be noted, however, that subjects selecting
smoking reduction goals have generally shown reliable, although not
always large, reductions in carbon monoxide levels (e.g., Glasgow et
al. 1984).

There has been improvement in the research methodology em-
ployed in worksite smoking modification studies. The majority of
studies conducted in the recent past have included both comparison
conditions and biochemical measures of smoking exposure. There are
still, however, a number of methodological deficiencies in current
worksite studies. Comparison conditions do not usually include no-
intervention or usual care groups; differences among interventions
are most commonly studied, and randomization is not always used.
Little is known about participation rates (only one-third of the
studies listed in Table 2 provide information on the percentage of
smokers participating). Data are seldom presented on effects of a
program on all smokers in an organization, and no data have been
published on characteristics of employees who participate in work-
site programs versus those who do not. Finally, there are so few data
on the health benefits or cost effectiveness of specific programs that
this information was not included in Table 3. Only the large-scale
multiple risk factor reduction trials (Kornitzer, De Backer et al.
1980; Rose et al. 1980) have presented such data.

Special Issues Relevant to Worksite Programs
Social Support

One of the most frequently cited reasons for conducting smoking
modification programs in occupational settings is the potential for


invoking peer and environmental support for nonsmoking (Chesney
and Feuerstein 1979; Stachnik and Stoffelmayr 1981). It has been
argued that peer support has important, long-lasting effects on the
outcome of stop-smoking efforts (Janis 1983), and there have been
several calls for increased study of the role of social support in
smoking modification (Klesges and Glasgow 1985; Lichtenstein 1982;
Stachnik and Stoffelmayr 1981). There are also correlational find-
ings that suggest the importance of social support to successful
smoking cessation (e.g., Coppotelli and Orleans, in press; Mermel-
stein et al. 1983).

Given this background, it is surprising that a large-scale correla-
tional study of occupational settings by Caplan and colleagues (1975)
found that the degree of perceived support from coworkers was
inversely related to smoking status. Among workers with low levels
of job stress, ex-smokers reported lower levels of support than
current smokers. There was no relationship between social support
and smoking status for people with high levels of job stress.
However, Caplan and colleagues' measure of social support was not
specific to smoking cessation, and may have been more an index of
the employee's responsibility for supervising or otherwise interact-
ing with other worksite personnel. More recent studies by Malott
and colleagues (1984) and by Glasgow and colleagues (in press) have
found a complex relationship between social support and outcome of
worksite smoking modification programs. Using a measure that
produced a score for both supportive and nonsupportive (negative)
social interactions, these two studies found that the presence of
smoking-related negative social interactions was inversely related to
treatment success. The presence of positive social support, which is
more frequently the target of social support interventions, was not
related to outcome.

Social support procedures such as use of a buddy system and
inclusion of nonsmoking coworkers or family members in treatment
sessions have been part of a variety of worksite programs (e.g., Bauer
1978; Sorman 1979; Stachnik and Stoffelmayr 1983). Unfortunately,
it is impossible to evaluate the contribution of social support in these
studies because of the multitude of other intervention strategies also
employed. In a review of studies on the effects of worksite incentive
programs for smoking cessation, Shepard and Pearlman (in press)
concluded that incentive programs that included spouses produced
better outcomes than those that did not.

The few worksite smoking studies that have attempted to experi-
mentally manipulate the level of social support have produced
discouraging results. Abrams and colleagues (1985) compared a
social support/social skills training program including a buddy
system with health education and cognitive-behavioral stress man-
agement procedures as ways to improve the long-term effectiveness

492


of a nicotine-fading cessation program. By the end of the program,
subjects in the social support/skills condition had relapsed signifi-
cantly more than subjects in the other conditions, and these
differences persisted at followup. In addition, consumer satisfaction
ratings revealed that subjects liked the social support/skills program
less well than other options. Abrams and colleagues concluded on the
basis of these findings that factors such as social support, theoretical-
ly assumed to enhance treatment, may actually reduce the effective-
ness of a treatment program in some instances.

Malott and colleagues (1984) evaluated the effects of adding a
coworker support component to a multicomponent treatment pro-
gram offering subjects the options of abstinence or controlled
smoking. They found that the addition of coworker support did not
improve treatment outcome on any dependent variable and that
subjects found the condition with social support to be less credible
than the basic treatment program. A replication and extension of the
Malott group's (1984) study by Glasgow and colleagues (in press)
involved family or significant-other social support and included a
partner-support manual, two group meetings for supportive others,
individualization of support procedures, and semiweekly phone calls
to partners. The results of this study were consistent with those of
Malott and colleagues (1984): no incremental effects of the social
support program were obtained from any dependent variable.

Thus, in research conducted to date, the inclusion of existing social
support procedures has not been found to enhance outcome in
worksite smoking modification programs. This is not to say that
social support is not important to treatment success, but that the
issue is more complex than was initially believed. It may prove
difficult to alter existing levels of social support, and novel ways of
enhancing coworker and family support for smoking modification
need to be developed.

Physician Advice

Because as many as 70 percent of adults in our country visit their
physician at least once in a given year (US DHEW 1979), there has
been growing interest in finding ways in which physicians can
convince patients to give up smoking (Ewart et al. 1983; Russell et al.
1979).

Some of the best data come from recent European clinical trials
(Rose et al. 1980, 1982; Kornitzer, Dramaix et al. 1980). The Belgian
Heart Disease Prevention project (Kornitzer, Dramaix et al. 1980)
found that significantly more individuals at high risk for developing
heart disease stopped smoking in an intervention condition empha-
sizing semiannual physician messages than in a screening-only
control condition (see Table 3). When comparing a representative
sample of all intervention subjects (many of whom did not receive

493


the physician messages) with a similar sample of control subjects,
however, almost identical and fairly low cessation rates were
observed in both conditions.

The most intensive worksite physician-intervention program was
evaluated in a similar study conducted by Rose and colleagues (1980).
In this study, the 12 to 15 percent of subjects in the intervention
condition who were at greatest risk for cardiovascular disease were
provided four physician consultations, each approximately 15 min-
utes in length. Results were similar to the Belgian study in that a
greater percentage of the high risk subjects stopped smoking in the
intervention group than in the control condition (see Table 3). But
considering all participants (many of whom did not receive the
intensive physician messages), there were no significant differences
between conditions.

A series of four physician visits was also utilized in a carefully
controlled study by Rose and Hamilton (1978) of British civil
servants at high risk of cardiorespiratory disease. Although not
actually conducted in occupational settings (and therefore not
included in Tables 2 and 3), subjects for the study were recruited
through their worksite. This study produced the highest cessation
rates of any physician-advice study (self-reported abstinence rates of
51 and 36 percent at 1 and 3 years, respectively). Over a third of
these subjects were still smoking pipes and cigars, however, and a
relatively high percentage of "normal care" subjects also stopped
smoking (10 and 14 percent at 1 and 3 years, respectively). Although
there were differences in favor of the intervention condition in rate
of decline in airway obstruction and rates of phlegm production,
there were no differences between conditions in absenteeism over a
l-year period or in overall mortality over a 7- to lo-year period.
As these studies indicate, there are both advantages and disadvan-
tages in using physician stop-smoking messages in worksite settings.
One distinct advantage is that if stop-smoking advice is incorporated
into regularly scheduled physician visits, a relatively large number
of workers can be advised and treated quickly and cost effectively
(Lichtenstein and Danaher 1978). Another advantage of the physi-
cian model is that it is relatively unobtrusive in comparison with
management-sponsored programs (Danaher 1980). Physician advice
can also be used to augment other interventions rather than to
replace them, by assisting workers in deciding to seek help and by
promoting participation in intervention programs, therefore facili-
tating better use of these programs.

Although self-reported cessation rates resulting from physician
advice are low in an absolute sense, research is underway to attempt
to increase the impact of stop-smoking messages. Li and colleagues
(1984), in a study conducted in a navy shipyard clinic, found that
implementation of a 3- to Sminute session of behavioral counseling

494


by staff physicians significantly increased cessation rates over those
resulting from a simple warning to quit smoking (see Table 3). In
addition, the compliance of health care providers with treatment
protocols also affects outcome. For example, Li and colleagues (1984)
reported great difficulty in getting clinic physicians to consistently
deliver a brief 3- to 5minute message to patients, yet Ewart and
colleagues (1983) found that providing physicians with regular
performance feedback appears to improve the quality and quantity
of stop-smoking messages. Future research should identify proce-
dures to improve both the implementation and the out.come of
physician stop-smoking advice. Perhaps a stop-smoking message in
conjunction with other interventions may increase success rates.

Basic research on the effects of threatening communications such
as those describing health risks of smoking indicates that such
messages have their greatest impact if individuals know not only
what to do (e.g., stop smoking) but how to do it, and believe
themselves capable of acting (Leventhal 1970). The recent approval
of nicotine chewing gum by the U.S. Food and Drug Administration
and the availability of high quality self-help stop-smoking manuals
(e.g., Davis et al. 1984) now present an opportunity for physicians to
deliver a health warning accompanied by concrete recommendations
for what to do and how to do it. Recent data suggest that nicotine
chewing gum may assist heavier or more addicted smokers in
quitting (Fagerstrom 1978, 1984; Raw et al. 1980), and gum prescrip-
tions can be written at the same time that a stop-smoking message is
given. Only one study reviewed in this chapter has investigated the
use of nicotine gum (Schlegel et al. 1983). That study, which did not
involve physician advice, found that the gum enhanced treatment
outcome in self-help conditions, but in the context of an intensive 17-
session treatment program, subjects receiving the gum actually had
lower cessation rates than subjects not receiving gum. Particularly
in companies that employ their own medical staff or in which
employees are at risk because of occupational hazards, programs
combining physician stop-smoking advice with other intervention
options should be evaluated.

Incentives

Recently there has been increased interest in the motivational
factors associated with smoking behaviors (Shepard and Pearlman,
in press; Brownell 1985). This section focuses on two recent
approaches to increasing motivation: personal incentives and compe-
tition among participants.

Rosen and Lichtenstein 11977) published the first report on the
effects of an employee incentive program for stopping smoking. Of
the employees of a small ambulance company who smoked, 75
elected to participate in a program that involved a $5 per month

495


bonus for not smoking at work-for all employees regardless of their
initial smoking status. At the end of the year, the owner also
matched the total amount of bonuses received during the program.
No other intervention techniques were used, and no stop-smoking
meetings were held. This study underscores the potential power of
incentives to modify smoking behavior: at posttest, 58 percent of the
pretest smokers reported no longer smoking at work.

Sorman (1979) reported on a program that combined personal
incentives, a stop-smoking program, social support, low-calorie food
alternatives, and an exercise program. Of 202 employees, 55 enrolled
in the program in which each employee who quit smoking for 1 year
received a $200 reward. Thirty-one percent of the participants
reported having successfully stopped smoking for the entire year.
Shepard (1980) presented results from an ongoing incentive program
involving weekly $7 paycheck bonuses to employees not smoking at
work. After approximately 4 years, only 20 percent of the employees
reported smoking in the worksite compared with 67 percent at
pretest.

Stitzer and Bigelow (1982, 1983, in press) have conducted a variety
of studies that cogently demonstrate that contingent reinforcement
for reductions in carbon monoxide (CO) levels of expired breath
samples can produce reliable short-term reductions in CO levels in
hired cigarette smokers. A recent study (Rand et al. 1984) investi-
gated contingent reinforcement for smoking abstinence in 18 hospi-
tal employees. After 1 week of baseline smoking and a week-long
"cutdown test," subjects could earn $12 a day for 2 weeks if they
totally abstained from smoking and if their daily CO readings were
consistent with abstinence (< 11 ppm). Sixty-one percent of the
participants were abstinent throughout the 2-week contingency
period, and 28 percent remained abstinent throughout a 3-week
followup.

Finally, Stachnik and Stoffelmayr (1983) evaluated a comprehen-
sive 7-month-long worksite program involving sizable financial
incentives as well as health information, social support, and public
commitment to nonsmoking in the context of 20 gradually paced
group meetings. The program was conducted in three different
worksites, with from 47 to 70 percent of smokers enrolling in the
program and an astounding 80 to 91 percent of participants
reporting abstinence 6 months after participation in the program.
These results are obviously very impressive, but it is not possible to
evaluate the contribution of incentives versus the other procedures
employed.

Shepard and Pearlman (in press) recently reviewed 15 (mostly
unpublished) programs that used incentives to produce changes in
smoking behavior in the worksite. Some programs provide incentives
for not smoking at the worksite, and others have a goal of total

496


abstinence. Although incentive programs seem to be gaining in
popularity and self-reported cessation rates appear high, there are a
number of problems with evaluations of incentive-based smoking
programs. Most studies are uncontrolled, and with notable excep
tions (e.g., Rand et al. 19841, measures of smoking status during
nonwork hours and biochemical verification of smoking status are
lacking. Clearly, incentive programs deserve further investigation,
because they appear to be effective, relatively inexpensive, and easy
to implement in a variety of different settings.

Another approach to providing incentives for improvements in
health-related behaviors is to arrange competitions among different
worksites or teams within a given worksite. For example, Brownell
and colleagues (in press) report high participation rates, low attrition
rates, and impressive outcome data in a recent worksite obesity
competition. Given these promising results, Klesges and colleagues
(1985) conducted a worksite smoking competition among four banks.
Prizes to benefit both smokers and nonsmokers were awarded to the
bank with (1) the highest participation rate, (21 the largest reduc-
tions in carbon monoxide levels at posttest, and (3) the greatest
abstinence rate at the 6-month followup. All participants in this
study received a gradually paced smoking control program previous-
ly used in worksite settings (Glasgow et al. 1984). Finally, a
"Smoking Barometer" placed in the lobby or lounge of each worksite
provided employees with weekly feedback on how their bank was
doing compared with the other three.

Participation rates in the program were exceptionally high.
Overall, 88 percent of all bank employees who were smokers entered
the program, compared with a 53 percent participation rate at a
comparable savings and loan organization that received the identical
program without competition, a significant between-groups differ-
ence. There were, however, no differences between conditions in
cessation rates among participants in the program. This may have
been because subjects in the competition condition were more
nicotine dependent, as assessed by the Fagerstrom (19781 Tolerance
scale, than subjects in the noncompetition condition (p<O.O21.
Because of the higher participation rate, however, the competition
condition produced a higher long-term cessation rate (15 percent)
throughout the worksite than the comparison condition (7 percent).

One of the major advantages of incentive and competition pro-
grams is that they do not require large amounts of therapist or
participant time. If the success rates of the uncontrolled studies
(Table 1) can be replicated in controlled studies, incentive programs
may prove to be the most cost-effective approach to worksite
smoking modification. On the other hand, at least some people may
require additional guidance and support (Danaher 1980). One
convenient, low-cost method of providing skills training in the

497


context of incentive programs is through provision of self-help stop-
smoking materials (Glasgow and Rosen 1978; Windsor and Bartlett
1984). Although a number of worksite studies have employed written
self-help materials as part of multicomponent interventions (Li et al.
1984; Kornitzer, Dramaix et al. 1980; Nepps 1984; Rose et al. 1980),
self-help manuals have not been used in incentive programs for
smoking cessation and studies to investigate their unique contribu-
tion to treatment outcome have not been conducted.

Overall, the results of incentive- and competition-based programs
are very promising. However, almost all of these studies have been
conducted in small worksites, and systematic replications of these
findings in controlled investigations in larger companies are needed.
Future research should also investigate the types of personal
incentives (e.g., paycheck bonuses versus lotteries for quitters) and
competitions (e.g., within a worksite versus between worksites) that
work best in different organizations. Finally, nonsmokers should be
carefully considered in incentive programs-in their role as support-
ers of quitters and as nonsmokers, wit.h bonuses for all nonsmokers,
old and new-and worksite resources should be provided for all
employees.

High Risk Populations

With the exception of the few large-scale clinical trials listed in
Table 2 (e.g., Kornitzer, Dramaix et al. 1980, Li et al. 1984; Rose et al.
1980; Schlegel et al. 1983), the majority of participants in worksite
smoking programs have been young, from middle or upper socioeco-
nomic levels, and in occupations that do not place them at increased
health risk. Although smoking cessation efforts should continue with
such populations, an argument can be made for focusing efforts on
individuals at particularly high risk for cancer, cardiovascular
disease, or respiratory disease-the major causes of excess morbidity
and mortality due to cigarette smoking. Given limited resources, it
should be more cost effective to direct interventions primarily
toward those most likely to develop disease. Three overlapping
approaches have been used to reach the following types of high risk
smokers in the worksite: blue-collar male workers, workers at risk
because of occupational hazards, and individuals predisposed to
disease for reasons in addition to smoking (e.g., obesity, hyperten-
sion, abnormal lipid levels).

Few worksite programs have been offered by companies employing
primarily male blue-collar workers, even though such groups have
higher than average smoking rates. Although there is little or no
documentation of the reasons for this inconsistency, it may be due to
mistaken beliefs among health professionals that such individuals
would be less likely to participate in or follow through with a
smoking modification program. Ellis (1980) found that blue-collar

498


workers may be at least as interested in quitting as others in the
general population. Resistance on the part of some labor unions may
constitute another reason for fewer programs conducted in blue-
collar worksites.
Initial worksite smoking research with blue-collar workers has
been conducted both at military bases and in Veterans' Administra-
tion (VA) hospitals. Schlegel and colleagues (1983) offered programs
at 28 different military bases across Canada. Although their outcome
results were comparable with other studies, they did report relative-
ly low followthrough (compliance) rates with homework assign-
ments. Also, they must have failed to recruit a high percentage of
smokers, because an average of fewer than 10 smokers per base
participated. Perhaps a different intervention approach is needed for
blue-collar populations-one that does not require employees to
devote much time and effort, and one that tailors materials and
tasks to be appropriate socioculturally. Dawley and colleagues (1980,
1984) conducted research with employees and patients in VA
hospitals and have advocated increased smoking modification efforts
within the VA system. They point out that it is ironic that for many
years the Nation's largest health care provider sold cigarettes at
`cutrate prices, owing to tax-exempt status.
Little systematic research with smokers in jobs that place them at
risk because of occupational hazards has been reported. For example,
asbestos workers are at high risk for respiratory disease, and
asbestos workers who smoke increase their risk synergistically (US
PHS 1977; see the chapter on asbestos in this Report). Ellis (1980)
informally reported on the results of a program for former employ-
ees of an asbestos company that involved incorporating antismoking
advice into regularly scheduled appointments with company physi-
cians, pairing written self-help materials with feedback on physical
status, and offering individual smoking cessation counseling. Over a
4-year period, this relatively low cost intervention was associated
with a 30 percent reduction in the proportion of employees who
reported being smokers. A related publication by Ellis (1979)
provides suggestions for recruiting and treating asbestos workers.
The most extensive no-smoking program involving high risk
occupations has been been conducted by the Johns-Manville asbestos
company. In addition to a smoking ban throughout the worksite and
a company policy of no longer hiring new employees who smoke
(Cooper 1978), Johns-Manville launched an intensive antismoking
campaign at 14 company sites. This program involved an educational
campaign coordinated with SmokEnders cessation clinics and the
institution of the companywide smoking ban. Although systematic,
published reports of this program could not be located, Orleans and
Shipley (1982) reported participation rates of 15 to 20 percent in the
cessation clinics and an approximately 75 percent posttreatment


quit rate among participants (apparently without biochemical vali-
dation). In the only controlled study to date of worksite intervention
in high risk occupations, Li and colleagues (1984) recently studied
the effects of physician stop-smoking advice on asbestos-exposed
naval shipyard workers. They found, somewhat surprisingly, that
subjects who had abnormal pulmonary function tests did not have
higher cessation rates (4 percent prolonged abstinence) than workers
with normal pulmonary function tests (6 percent prolonged absti-
nence) who received the same intervention.

The third approach to reaching high risk participants has been to
conduct comprehensive health screenings to identify individuals at
risk for the development of chronic disease. Rose and colleagues
(1980) assigned people at high risk of developing heart disease who
worked in 24 large industrial companies to intervention or screen-
ing-only control conditions. High risk people in the intervention
condition were more successful at quitting smoking (12 percent
cessation at 5 years) than similar subjects in the control condition (0
percent cessation rate). Similar results were reported by Kornitzer
and Dramaix and colleagues (1980) in a parallel large-scale trial
conducted in Belgium (see Table 3).

In summary, some promising initial studies have been conducted
with high risk individuals. But such studies are few in number and
much more intensive study of ways to best reach high risk
individuals is needed.

Multiple Risk Factor Reduction Programs

A number of organizations have offered smoking cessation pro-
grams as part of employee wellness or lifestyle-modification pro-
grams. Such programs typically focus on achieving modifications in
several risk factors in addition to cigarette smoking, such as obesity,
elevated cholesterol levels, hypertension, and a sedentary lifestyle.
Some programs also include components on stress management and
modifying Type A behavior. Almost all programs include an initial
health screening to identify risk factors, but subsequently there is a
considerable divergence in approaches. Some programs focus solely
on high risk participants (e.g., Meyer and Henderson 1974; Ware and
Block 1982); others invite all employees to participate regardless of
risk status (e.g., Naditch 1984). There is also considerable variation
in how smoking programs are implemented, with some programs
holding separate meetings for smokers and others including informa-
tion on smoking modification as part of their general wellness
program.

The concept of providing smoking modification services as part of
a more general lifestyle program is appealing. Stopping smoking can
be seen as one aspect of adopting a more healthy lifestyle, and other
program components such as increased levels of exercise may

500


reinforce smoking abstinence (Morgan 1981). Many smokers, partic-
ularly women, are concerned about potential weight gain as a result
of smoking cessation, and such programs can address these concerns
(Ellis 1980).
  There are also potential disadvantages of multiple risk factor
reduction programs. They may be difficult to implement because
staff expertise is required in multiple areas and because some risk
factors, such as smoking, may not be relevant for all participants. In
addition, multiple risk factor reduction programs must present a
large amount of complex information, usually in a limited time, and
consequently the amount of attention devoted to a given risk factor
such as smoking must often be less than is the case in single
modality programs.
Two main types of multiple risk factor reduction programs have
involved smoking cessation. The first is large-scale clinical trials for
the prevention of coronary heart disease. The Belgian and British
WHO studies reported by Kornitzer and Dramaix and colleagues
, (1980) and by Rose and colleagues (1980) were conducted solely in
industrial settings and were discussed in detail in the 1983 Report of
the Surgeon General (US DHHS 1983). These studies are well
designed and have collected multiple dependent variables, including
indices of overall health risk or morbidity and mortality statistics.
  The other main type of multiple risk factor reduction program
that has been developed is worksite wellness programs conducted by
large companies for their employees. Examples include the STAY-
WELL program of the Control Data Corporation (Naditch 1984), the
Live for Life program of Johnson and Johnson (Nathan 1984), and
programs offered by IBM, the Campbell Soup Company, and the
Ford Motor Company (Parkinson et al. 1982; Ware and Block 1982).
Unfortunately, the outcomes of almost all industry-sponsored pro-
grams reported to date are difficult to interpret owing to varying
methods of reporting results, difficulties in following subjects, and
lack of objective measures of smoking status. Reports of company
wellness programs with more than anecdotal data on smoking
modification results (e.g., Grove et al. 1979; Sorman 1979) are
summarized in Table 1.
Cessation rates in multiple risk factor reduction programs in
worksites have ranged from 7 to 33 percent at followup. Many of
these rates are lower than those typically reported in other worksite
smoking studies and are not consistently better than comparison
conditions in controlled studies (Kornitzer, De Backer et al. 1980;
Meyer and Henderson 1974). Interpretation of these data is proble-
matic because of the lack of direct comparisons with smoking-
cessation-only interventions, because subjects with multiple risk
factors may be more recalcitrant than other subjects, and because


TABLE 4.-Organizational characteristics potentially
     affecting outcome of worksite smoking
       programs

Sue of works1te


Current worksite
smoking policies

Degree of management
support for program

History of health
promotion efforts
in the worksite

Sex ratio of employees

17)



(8)



(91





(10)

Union/management
relations


Percent of smokers
in the worksite

Growth oriented vs.
consolidating climate
of organization

Rank and sociometnc
standing of primary
contact person

t-5,   Job stability/turnover

(11)

Socioeconomic level
of employees

the risk factor reduction programs reported in this section tend to be
ongoing programs rather than one-shot smoking clinics.

Organizational Characteristics and Other Factors

Conducting outcome research in worksite settings involves a
number of unique factors that may mediate or interact with program
success. The organizational characteristics that may mediate pro-
gram success are outlined in Table 4. Although this list is certainly
not exhaustive, investigators should consider these factors when
conducting worksite smoking programs. An example of the potential
effects of organizational characteristics is the variability in outcome
reported by Glasgow and Klesges and their colleagues (Glasgow et al.
1984, in press; Klesges et al. 1985). The basic treatment programs
utilized in these studies were almost identical and were implemented
by many of the same therapists. Yet, the 6-month abstinence rates in *
the different organizations ranged from 14 to 33 percent.

Few of these variables have been addressed in worksite smoking
studies. Bishop and Fisher (1984) have conducted similar multilevel
smoking cessation programs in a number of different organizations,
ranging in size from 200 to 6,000 employees. They reported substan-
tially lower participation rates in large companies, a finding that is
consistent with results of studies of worksite weight loss programs
(Brownell et al., in press). Also, the studies outlined in Tables 1
through 3 suggest that the highest cessation rates are obtained in
smaller worksites. Taken together, these trends suggest that differ-
ent interventions and different ways to assure participation need to
be developed for large corporations. The problem may be one of


implementation, not design. Company policy regarding vesting
responsibility in division leadership may be a critical variable.
In terms of the second variable in Table 4, worksite smoking
policies, it is important to emphasize that smoking cessation groups
are but one way to influence rates of worksite cigarette smoking
(Bennett and Levy 1980). Although there have certainly been more
reports on cessation programs than on other approaches to occupa-
tional smoking control, evaluations of alternative procedures are
beginning to appear. In particular, Dawley and colleagues (Dawley
and Baldwin 1983; Dawley and Burton, in press; Dawley et al. 1980)
and Jason and colleagues (Jason and Liotta 1982; Jason and Clay
1978; Jason and Savio 1978) have studied the effects of no-smoking
signs and requests not to smoke. These studies indicate that the
posting of nonsmoking signs and the establishment of nonsmoking
areas temporarily reduce smoking rates, but that active enforcement
of such policies is necessary to produce substantial or lasting
decrements in smoking behavior (Dawley et al. 1980; Jason and
Liotta 1982; Jason and Savio 1978). One caveat to be kept in mind in
evaluating the effects of worksite smoking restrictions is that
workers may "compensate" by smoking more during breaks and
after work (Meade and Wald 1977). Evaluations of the effectiveness
of smoking restrictions should therefore assess smoking rates during
both work and nonwork hours and include objective measures of
smoking exposure.
Dawley and colleagues subdivided smoking modification efforts
into three categories: smoking control (limiting or restricting smok-
ing to designated areas); smoking discouragement (educational
efforts to encourage people to stop smoking); and smoking cessation
(more formal treatment programs). They also suggested that "work-
site smoking cessation programs operate most effectively when
offered in conjunction with worksite smoking control and discourage-
ment efforts" (Dawley et al. 1984, p. 3291, a highly testable
hypothesis that has yet to be experimentally investigated.
The potential to use modifications of the work environment to aid
in smoking cessation, including restricting smoking, removing
cigarette machines, and altering work rules or situations that
promote smoking, make the worksite more than simply a location for
cessation interventions. The elimination of environmental supports
for smoking, alteration of the smoker's self-image, changing the
perception of the smoker among peers, and revising the social norms
about smoking in the worksite may all provide a powerful motiva-
tion for the smoker to quit and support the successful maintenance
of cessation. These changes in the workplace environment and
attitudes may be more important than the components of the
behavioral intervention used to get workers to quit, and experimen-
tal verification of the impact of these changes would provide a useful


guide for the structuring of future comprehensive worksite interven-
tions. Because it would probably be unlikely that researchers would
gain access to experimental manipulation of some of the more
controversial aspects of guidelines (hiring policies and penalities for
smoking), opportunities that may arise to study such changes in
noncontrolled research would be worth pursuing.

Few data have been collected on the other variables listed in Table
4. Research on worksite smoking programs should at least provide
descriptive information to determine how these variables affect
program success. The fit between organizational and program
characteristics has been neglected in past occupational smoking
control research. It is hoped that future research will be able to
identify the types of programs that are most effective in each
different worksite setting.

Implementation of Worksite Smoking Programs
This section focuses on two major classes of implementation issues:
recruitment procedures and characteristics of intervention pro-
grams.

Promotion and Recruitment

The initial contact with a worksite can prove critical to the success
of a project. It is generally recommended that the initial meeting be
with the chief executive of the organization (Klesges and Glasgow
1985). Although this officer typically does not coordinate the
program, support from top-level management appears to be impor-
tant in program recruitment and implementation (Grove et al. 1979).
Another method of enhancing participation and organizational
involvement is the formation of a steering committee (Bishop and
Fisher 1984; Stachnik and Stoffelmayr 1981) composed of key
representatives from both labor and management. Employees should
perceive that the program is voluntary and that they have input into
its implementation. Steering committees of this kind may be
particularly important in large worksites with unionized employees.
Management support appears to be quite important to the success of
the committee (Bishop and Fisher 1984).

Upon securing permission to offer a program, it is helpful to
conduct a brief worksite needs assessment (e.g., Heckler 1980;
Kanzler et al. 1976; Klesges and Glasgow 1985). The survey can be
used to determine (1) the number and characteristics of smokers in
the worksite, (2) the number of smokers potentially interested in
participating, and (3) preferences concerning the types of programs
that might be offered (e.g., self-help versus group meetings; absti-
nence versus reduced smoking) and the most convenient times for
meetings to be scheduled.

504


During the recruitment phase, information about the program
should come from a variety of sources, such as posters, memos, and
brochures. Advertising experts recommend providing multiple expo-
sures to a "product" (in this case, a smoking program) to promote
attitude change and to convince participants to take action regard-
ing the product (Sawyer 1981). Promotional materials should include
information about the cost of a program, stress that participation is
voluntary and individual results are confidential, and counter
possible misconceptions (e.g., "I have to quit at the first session"; "1'11
lose my job if I don't participate"). It is helpful if at least one memo
or announcement comes from top management. At this stage,
human resources or personnel directors can be extremely useful in
suggesting the best ways to promote the program in their particular
setting. Involving the local media may also increase the credibility of
the program as well as provide no-cost advertising for both the
program and the worksite.

Prior to the actual implementation of a smoking program, some
programs prepare worksites for health-behavior change (Andrews
1983; Bennett and Levy 1980; Ellis 1979; Grove et al. 1979; Heckler
1980). These preparatory procedures have ranged from prescreening
health exams (Ellis 1979) to the initiation of smoking restrictions
(Andrews 1983; Bennett and Levy 1980). Warnings of the impending
restrictions with indications of the "target restriction date" allow
workers to prepare for changes, such as by joining available
programs. Although empirically untested, these recruitment proce-
dures may help to convince employees to join smoking programs.

Program Characteristics

The advantages of occupational smoking control programs dis-
cussed earlier do not automatically or necessarily occur. Programs
must be made convenient. Higher participation rates are usually
found in programs that offer time off work (e.g., Klesges et al. 1985;
Scott et al. 1983). Time off work for participation can be a double-
edged sword, however. It may increase the number of smokers who
participate primarily to be excused from their work stations, and it
may also create demands among nonsmoking employees for time off
work to attend other health-related classes. Generally, the benefits
of conducting programs during work hours outweigh the potential
costs, and if management is not willing to grant time off work, it may
at least be possible to negotiate time sharing between employee and
employer (e.g., l/2 hour of work time, l/2 hour during lunch hour or
after work). Investigators should also be aware of the difficulties
involved in scheduling group meetings in worksites where employees
work rotating shifts, such as hospitals.

In addition to being convenient, programs should be attractive to
participants. For example, allowing smokers to choose the type of


program (such as nicotine fading versus aversive smoking), the
modality of intervention (self-help manual versus group meetings),
the treatment goals (abstinence versus reduced smoking), and the
type of group leader (health professional versus peer facilitator) may
be helpful in attracting and retaining participants. Different compo-
nents of a comprehensive program, such as physician advice, no-
smoking policies, stop-smoking contests, or group meetings, may
mutually reinforce each other. While these suggestions await
empirical verification, providing smokers with a number of choices
should serve to increase participation rates.

Finally, feedback on progress may serve to increase the magnitude
of behavior change. For example, participants can be provided with
frequent feedback on carbon monoxide levels as they reduce their
smoking (e.g., Rand et al. 1984; Scott et al. 1983). Charts displaying
the weekly progress of different groups can be posted in employee
lunchrooms or lounges. Periodic progress reports to department
supervisors might also be helpful. To avoid stigmatizing particular
individuals, public feedback should be provided on progress by the
group rather than by individuals.

There are a number of problems in conducting worksite smoking
modification groups that should be avoided, or at least anticipated.
Group composition is one such sensitive issue. For example, mixing
high-ranking executives with production workers can almost elimi-
nate group discussion. However, this may depend on the company's
tradition of interaction among workers of different levels, on the
skills of the group leaders, and so on. Scheduling difficulties can
arise in settings were employees rotate shifts or travel frequently, or
where meeting rooms are scarce or distant from work stations. One
also needs to be sensitive to negativism or complaining, which can
become contagious; the group's focus must be kept positive. A
positive perspective is particularly important when conducting
competition or incentive interventions in which certain individuals
or groups must "lose." A more optimistic perspective that can be
used to encourage participants is that eveyone can win something by
changing their smoking, so there are no losers.

Finally, Marlatt and Gordon's (1985) concept of stopping smoking
as a `journey" can be quite helpful. On their journey, people may
experience temporary setbacks or detours (relapses), but this should
not prevent them from reaching their destination (abstinence). The
presence of an ongoing program that makes it easy to try different
options or to recycle a procedure can serve to reinforce this concept
and to improve long-term results.

506


Recommendations for Future Research

A number of suggestions for the implementation of worksite
smoking modification programs have been outlined. Given the
limited nature of the data available, few of these guidelines are
experimentally derived. Research is needed to empirically support or
refute these recommendations. This section discusses needs for
future research in the field of worksite smoking modification.
Recommendations are made on both research methodology and
substantive issues for further investigation.

Methodological Issues

Greater use should be made of creative experimental and quasi-
ex;erimental designs, as discussed by Cook and Campbell (1979). In
particular, it should be possible to sequentially introduce an
intervention or intervention components in different worksites using
time-series or multiple baseline designs or to investigate the
incremental effects of adding different strategies, such as physician
messages, incentives, and social support procedures, to a basic
treatment program.

Greater consistency across studies in the criteria used to define
smoking status would substantially aid in the interpretation of
results. Berglund and colleagues (1974) and Shipley and colleagues
(1982) have provided guidelines for reporting outcomes of smoking
cessation studies that should be more widely adopted. For calculat-
ing abstinence rates, a standard common denominator representing
the number of subjects entering a program should be used across all
points in time and any dropouts should be considered conservatively
as smokers. In studies in which it is deemed important to evaluate
reductions in smoking behavior (e.g., percent reduction in number of
cigarettes smoked or nicotine content) in addition to the proportion
of abstinent subjects, analyses should be conducted on nonabstinent
subjects only. This procedure avoids confounding the results due to
cessation with results due to changes in smoking rate or topography.
Worksite programs should report cessation success as the fraction of
the smokers in the workforce as well as the fraction who agreed to
participate in the program.

Objective verification of smoking status is particularly important
in programs involving financial incentives, competition between
rival organizations, social pressure and support to quit, or controlled
smoking instead of abstinence. Each of the biochemical measures of
smoking exposure has its own advantages and limitations (Benowitz
1983; Pechacek et al. 1984).

Another methodological problem faced by occupational smoking
modification programs concerns the consistency between units of
assignment and units of analysis (Biglan and Ary 1985). Typically,

507


whole companies are assigned to treatment or control conditions, but
results are analyzed using individual subjects as the unit. This
creates interpretive problems because of the potential dependency
among results of smokers within a given worksite (or treatment
group). Although there are no easy answers to this dilemma,
investigators should consider (1) conducting treatment in a suffi-
ciently large number of companies that the worksite can be used as
the unit of analysis; (2) utilizing hierarchical or nesting designs to
separate the effects of worksite from intervention condition (Myers
1972); or (3) when feasible, assigning individuals within worksites to
different treatment conditions.

Future research should pay greater attention to possible interac-
tions between worksite and treatment variables. For example,
interorganizational competition procedures may be highly effective
in worksites where employees feel highly committed to the company,
but ineffective in settings low in organizational commitment.
Organizational and social network factors may also interact with,
mediate, or enhance program impact.

More data also need to be collected on the "generalization" effects
of worksite smoking modification programs. Employers may be more
interested in program effects on employee morale, job satisfaction,
and absenteeism than on health outcomes such as smoking status.
Similarly, more information should be reported on the costs and
health benefits of occupational smoking reduction programs. Prog-
ress in this area would be facilitated by a systematic review of and
recommendation for procedures to be employed in determining the
cost effectiveness and cost benefit of worksite smoking programs.

Substantive Areas

Three primary objectives need to be achieved by future research in
worksite smoking modification. First, more research should be
conducted on ways to increase participation and followthrough rates
in worksite programs. For example, using various incentive proce-
dures (e.g., paycheck bonuses versus team competition versus
lotteries) might be expected to enhance participation. Further
investigations are needed on the impact on participation rates of
interventions such as quitting contests, self-help materials, *or
hotlines that do not require a large investment of time and effort by
participants. The majority of worksite smoking studies to date have
focused on group cessation programs, but surveys consistently
indicate that most smokers are not interested in participating in
such programs (US DHHS 1982; Schneider et al. 1984). For the
reasons discussed earlier, renewed emphasis on physician stop-
smoking messages is also indicated.

The second main content issue is how to enhance the outcome
rates of worksite smoking modification programs. One approach to

508


this problem is to evaluate the utility of comprehensive intervention
programs and environmental changes (no-smoking policies, cigarette
machine removal, prominent no-smoking posters) with cessation
groups. Other approaches are assessing the impact of multiple risk
factor programs versus single modality programs and of ongoing,
continuous intervention programs in place for a year or more versus
one-time-only program offerings.

The final category of recommendations for future research in-
volves investigating subject and therapist factors that affect treat-
ment outcome (Klesges and Glasgow 1985; Orleans and Shipley
1982). Additional study is needed of the enrollment patterns and
success rates of men versus women, white-collar workers versus blue-
collar workers, and heavy smokers versus light smokers. Also, little
is known about the characteristics of successful program leaders
(e.g., ex-smoker coworkers versus professional group leaders).

Summary and Conclusions

1. Smoking modification and maintenance of nonsmoking status
among initial quitters has the promise of being more successful
in worksite programs than in clinic-based programs. Higher
cessation rates in worksite programs are achieved with more
intensive programs.

2. Incentives for nonsmoking appear to be associated with higher
participation and better success rates. Further research is
needed to specify the optimal types of incentive procedures.
3. Success of a worksite smoking program depends upon three
primary factors: the characteristics of the intervention pro-
gram, the characteristics of the organization in which the
program is offered, and the interaction between these factors.
4. Research is needed on recruitment strategies and participation
rates in worksite smoking programs and on the impact of
interventions on the entire workforce of a company.
5. More investigations are needed on worksite characteristics
associated with the success of occupational programs and on
comprehensive programs including components such as quit-
smoking contests, no-smoking policies, physician messages, and
self-help materials in addition to smoking cessation clinics.
6. The implementation of broadly based health promotion efforts
in the workplace should be encouraged, with smoking interven-
tions representing a major component of the larger effort to
improve health through a worksite focus.

509


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515


INDEX

ABSTINENCE

worksite vs. clinic-based program
participants, factors, 483. 48%
490

AGE FACTORS
cancer mortality, age-specific rates
  for white men and women, 229
chronic bronchitis in coal workers,
  effect with dust exposure and
  smoking, 299-300
lung function in asbestos workers,
  smokers vs. nonsmokers, 246-247
lung function in occupationally ex-
  posed workers, effect with smok-
  ing, 166-167

T lymphocyte changes in asbestos
workers, with smoking, 267-269

AIRFLOW OBSTRUCTION
See also LUNG FUNCTION; RES-
  PIRATORY SYSTEM)
chronic effects of cotton dust expo
  sure, 420, 422-423
chronic obstructive bronchitis
  symptom, 183

coal and silica dust exposure as
risk factors, 330
coal miners, occupational relation-
ship, 289

coal miners, smoking as factor, 14
coal workers, dust exposure effect
in smokers vs. nonsmokers, 313
coal workers, small opacities in
pneumoconioses, relationship,
295-296

coal workers, smokers vs. non-
smokers, 309

cotton workers, smoking as additive
risk, 16

individual abnormalities, determina-
tion of occupational exposure vs.
smoking effects, 168
nonspecific hyperreactivity follow-
ing exposure to cotton dust, 427

AIRFLOW OBSTRUCTION-Contd
occupationally exposed workers,
  patterns of injury in large and
  small airways, 150-151
silica-exposed workers, pathogene-
  sis, 340

smokers, patterns of injury in
large and small airways, 148-
150

Amines See AROMATIC AMINES

ANIMAL STUDIES
(See also SMOKE INHALATION.
   ANIMAL)

carcinogenic effects of uranium ore
dust exposure in dogs, 458
carcinogenicity of chemicals in cig-
arette smoke, effect with radia-
tion, 459

carcinogenicity of cigarette smoke
and asbestos, 232-234
industrial pollutants, interactions
with tobacco smoke, recommend-
ed research, 391

lung function effects of radon
daughters, uranium ore dust,
cigarette smoke, 464
3-methylcholanthrene and crocido-
lite asbestos effects in hamster
trachea, 234

polycyclic aromatic hydrocarbons
and chrysotile asbestos effects in
trachea of rats, 234
radiation and cigarette smoke in
tumor formation, 456460

ANTISMOKING MATERIALS
components of controlled worksite
  smoking modification programs,
   486A88

517


INDEX

Antismoking campaigns See PRO-
GRAMS AND POLICIES;
SMOKING CONTROL PRO-
GRAMS; WORKPLACE INTER-
VENTION PROGRAMS

AROMATIC AMINES
(See also OCCUPATIONAL EXPO-
   SURES)

betanaphthylamine, carcinogenicity,
371-372

bladder cancer risk, interactive ef-
fects with smoking in exposed
workers, 383

chemical carcinogenesis as species-
specific phenomenon. 371
occupational exposure, disease
risks, 359-392

workplace exposures in cancer risk,
370

AROMATIC HYDROCARBONS
(See also BENZO[A]PYRENEl
asbestos exposure and smoking, in-
  teractive effects on metabolism,
   237-238

interactive effects with asbestos in
animals, 234

lung cancer in exposed workers, re-
lative risk, with smoking, 378

ASBESTOS

(See also OCCUPATIONAL EXPO-
SURES)

animal studies of carcinogenic in-
teractions with cigarette smoke,
232-234

carcinogenesis in exposed workers
who smoke, mechanisms, 228,
231

carcinogenesis role, tumor promoter
vs. initiator, 236237
carcinogenic risk, establishing dose
and exposure levels, 217-219
chest x rays of exposed workers,
lowest readings by highest read-
ings, 261

chronic lung disease risk, effect
with smoking, 239-266
commercial products, differences as
factors in respiratory tract fiber
disposition, 200-201
crackles and clubbing in exposed
workers, independent effects of
smoking, 156

ASBESTOS-Contd.
fibers as carriers of carcinogens in
  cigarette smoke, risk relation-
  ship, 238

health effects in chrysotile-exposed
smokers vs. nonsmokers, 253
industrial exposure standards and
environmental control, public
health implications, 270
interstitial fibrosis in exposed popu-
lations, smoking relationship,
263-264, 266

intrapulmonary deposition and
clearance, effect of chemicals in
cigarette smoke, 236237
low-dose environmental exposure as
disease risk factor, 199-200
lung cancer and chronic lung dis-
ease, combined risks of exposure
and smoking, 199
lung cancer in exposed workers,
risk with smoking, 13-14, 378
lung cancer in exposed workers,
sex ratio of observed vs. expect-
ed deaths, 214

lung cancer in exposed workers,
smoking status in risk determin-
ation, 205, 210, 213, 216-220
lung cancer in workers, interactive
effects of exposure level and
smoking category, 219-220
lung cancer risk in exposed smok-
ers vs. nonsmokers, summary
and conclusions, 271
lung disease and cigarette smoking
in exposed workers, 147
lung function changes in exposed
workers, smokers vs. non-
smokers, 241, 243-254
lung injury risk determination,
problems, 239-241
mortality, cohort study data by
type of exposure, 202-204
observed vs. expected mortality in
workers, 227-228
occupational exposure, public
health implications, 9-10
principal varieties and structural
features, 2W201
pulmonary fibrosis in dockyard
workers, by smoking habit and
exposure duration, 266

518


INDEX

ASBESTOS-Contd.
reduction/cessation of exposure and
  smoking, effect on lung cancer
  risk, 224-228

restrictive and obstructive lung in-
jury in exposed workers, 151
roentgenographic changes in ex-
posed vs. nonexposed workers,
smoking relationship, 259-260,
262

small airways injury in exposed
workers, smokers and non-
smokers, 256258
tumors in rodents following expo
sure, with/without cigarette
smoke components, 235

ASBESTOSIS

(See also OCCUPATIONAL DIS-
EASES)

prevalence in asbestos-exposed pop
ulations, smokers vs. non-
smokers, 263, 265

BACTERIA

endotoxins in cotton bract and bys-
sinosis symptoms in cotton work-
ers, relationship, 424-426

BENZO[A]PYRENE
(See also AROMATIC HYDROCAR-
   BONS)

carcinogenic interaction with chry-
sotile asbestos in rata and ham-
sters, 234

carcinogenicity in animals, interac-
tive effect with radiation, 459

BIRTH COHORTS
lung cancer mortality, occupation
  and smoking as factors, 102
race- and sex-related changes in
  smoking habits, 3%53

BLADDER CANCER
(See also CANCER; OCCUPATION-
  AL DISEASES)

betanaphthylamine and benzidine
manufacturing workers, exposure
duration as factor, 371
chemical workers, relative risk, 380
chemical workers, risk of naphthy-
lamines and benzidine exposure,
370

mortality in refinery and chemical
workers, study data, 362-363

BLADDER CANCER4ontd.
occupation and smoking, interactive
  effects, 37%385

occupational groups at risk, smok-
ing as factor, 383
radiation and chemical exposures
as risks, with smoking, 381
relative risk for cigarette smoking,
lifetime consumption as factor,
380

sex ratio of risk, by smoking habit
and occupation, 379-380
truck drivers, diesel exhaust inha-
lation and smoking in risk, 385

BRAIN CANCER
pesticideexposed workers, possible
  risk relationship. 386387

BRONCHI

(See also BRONCHIOLES; LUNGS)
radiation and cigarette smoke, in-
teractive effects, 463

BRONCHIAL CANCER
uranium miners, influence of radia-
  tion exposure and smoking, 450

BRONCHIAL DISEASES
simple and chronic bronchitis,
  symptoms, 299

BRONCHIOLES
(See also BRONCHI)
inflammatory response and fibrosis,
  effect of smoking vs. asbestos ex-
  posure, 255256
silica-induced injury, 340

BRONCHITIS

(See also BRONCHIAL DISEASES;
LUNG DISEASES; OCCUPA-
TIONAL DISEASES; RESPIRA-
TORY TRACT DISEASES)
age-adjusted association with byssi-
nosis, by smoking status and
sex, 412

age-adjusted association with smok-
ing, by byssinosis status and sex,
411

cement workers, dust exposure and
smoking as independent risk fac-
tors, 187

chronic simple and chronic obstruc-
tive bronchitis, symptoms, 183
coal and silica dust-exposed work-
ers. 330

519


INDEX

BRONCHITIS-Contd.
coal miners, dust exposure and
  smoking, risk determination,
   184-185

coke oven workers, exposure and
smoking as factors, 191
copper smelter workers, exposures
and smoking as risk factors, 191
cotton workers, agents responsible
for inflammatory response, 424
427

cotton workers, chronic exposure as
factor, 429

cotton workers, possible additive ef-
fect of dust exposure and smok-
ing, 426

cotton workers, smoking as factor,
410

grain workers, dust exposure and
smoking as risk factors, 187-189
occupational exposure, pattern of
development, 150
occupational exposures and smok-
ing risks, summary and conclu-
sions, 191

pattern of smoking-related develop
ment, 148

silicaexposed miners and other
workers, smokers vs. non-
smokers, 331334
simple and chronic bronchitis,
symptoms, 299
worksite chemicals or physical
agents as cause of occupational
bronchitis, 183

BYSSINOSIS

(See also DUST; OCCUPATIONAL
DISEASES; PNEUMOCONIOSIS
age-adjusted association with
bronchitis, by smoking status
and sex, 412

age-adjusted association with smok-
ing, by bronchitis status and
sex, 412

containment of cotton dust levels
as factor in reduced risk, 431-
432

cotton dust exposure duration as
factor, 410

cotton textile workers, job category
as factor in risk, 403

520

BYSSINOSIS-Contd.
cotton textile workers, smoking in-
  fluence on development, 16, 403-
   423

cotton workers, correlation wit,h en-
dotoxins in airborne dust, 425
cotton workers, definition of
grades, 409410
cotton workers, prevalence by me-
dian dust level, smokers vs. non-
smokers, 414

dust levels as factor in cotton
workers, 16

expiratory volume in cotton work-
ers with/without disease, smok-
ers vs. nonsmokers, 417
prevalence and severity in cotton
workers who smoke, dust exp+
sure level as factor, 432
prevalence data for nine exposure
groups, 411

textile mill workers, by grade,
smoking status, and dust level,
413

ventilatory deterioration risk in
cotton workers with acute symp
toms, 423

CANCER

(See also CARCINOGENESIS; OC-
CUPATIONAL DISEASES1
historical association with tobacco
use, 6

Japanese A-bomb survivors, relative
risk in smokers vs. nonsmokers,
455

leather industry workers, exposure
as risk independent of smoking,
376

mortality, age-specific rates for
white men and women, 229
mortality, age-standardized rates
with/without asbestos exposure
and smoking, 242
mortality, confounding of occupa-
tional exposure effects by smok-
ing, 114-122

mortality in rubber workers, study
data, 368-369

mortality ratios in metal ore min-
ers, smoking as factor, 343-344
occupational exposure relationship,
overview, 7


INDEX

CANCER--Contd.
occupational exposures and smok-
  ing as causal factors, 374388
radiation and cigarette smoke in-
  duction in animals, 456460
radiation and smoking in risk,
  summary and conclusions, 465
refinery and chemical workers,
  smoking and exposure as risk
  factors, 361, 364-366
workers exposed to "pure" silica,
  standard mortality ratios, 344-
   345

workplace and smoking, evaluation
of interactions, 12
workplace exposures and smoking
as risk factors, 101

CARCINOGENESIS
(See also CANCER)
animal studies of interactive effects
  of cigarette smoke and asbestos,
   232-234

animal studies of radiation and cig-
arette smoke effects, 456460
aromatic amines, pathway of bio-
transformation and urinary ex-
cretion efficiency, role, 371
concepts of initiation and promo-
tion, 234, 236239
enzymatic activity of pulmonary al-
veolar macrophages, role, 237-
238

hazardous occupational exposures
and smoking, possible synergism,
8

mechanisms in cigarette-smoking
asbestos workers, 228, 231
occupational exposures and smok-
ing as initiators and promoters,
107-108

CARCINOGENS
aromatic amines, regulation of
  workplace exposure, 370
asbestos, problems in establishing
  carcinogenic dose and exposure
  levels, 217-219

chemicals in cigarette smoke, inter-
active effects with radiation in
animals, 459-460
disposition and activation, effects of
occupational exposure and smok-
ing, 106-107

CARCINOGENS-Contd.
lung cancer risk of known or sus-
  pected occupational exposure,
  with smoking, 377-378
naphthylamines and benzidine,
  bladder cancer risk in exposed
  workers, 370

silica, research recommendations,
347

tobacco smcke at worksite, possible
occupational carcinogen in non-
smokers, 126

workplace exposures, recommenda-
tions for control, 390-391

CELLS

function and structure alterations
by asbestos fibers, role in carcin-
ogenesis, 236

CELLS, EPITHELIAL
asbestos as promoter of transforma-
  tion by carcinogens in cigarette
  smoke, 239

CESSATION OF SMOKING
(See also REDUCTION OF SMOK-
  ING; WORKPLACE INTERVEN-
  TION PROGRAMS)
asbestos workers, effect on lung
  cancer risk, 224-225, 227-228
asbestos workers, to alter future
  disease risk, 270-271
biochemical verification in control-
  led worksite modification studies,
   486-488

blue-collar vs. white-collar workers,
sex differences, 33
blue-collar workers, workplace envi-
ronment as factor, 10
coal miners to reduce respiratory
morbidity and mortality, 312-313
controlled studies, data by worksite
type, procedural characteristics,
484-485

controlled studies, design and out-
come data of smoking modifica-
tion programs, 486-488
cotton workers, effect on byssinosis
symptoms, 414

multiple risk factor intervention
programs, efficacy for worksites.
5m502
nicotine chewing gum as aid in
worksite programs, 495


INDEX

CESSATION OF SMOKING-Contd.
race, sex, and occupation as fac-
   tors, 53-55

uncontrolled studies, 481-482
workplace program effects, evalua-
tion criteria, 479-480
workplace program participants,
consumption level as factor in
success, 496-491
workplace program participants,
controlled studies, 483, 489-490
workplace program participants, ef-
ficacy of social support, physi-
cian's advice, 491-495
workplace programs, recommenda-
tions to reduce occupational
risks, 391

CESSATION OF SMOKING,
  METHODS

(See ak;o REDUCTION OF SMOK-
ING; SMOKING CONTROL
PROGRAMS; WORKPLACE IN-
TERVENTION PROGRAMS)
monetary incentives and competi-
tion in worksite programs, effica-
cy, 495-498

physician's advice in worksite pro-
grams, efficacy, 493-495
programs used in controlled work-
site smoking modification stud-
ies, outcome data, 486-488

CHEMICALS

(See also OCCUPATIONAL EXPO-
SURES)

bladder cancer in exposed workers,
risk factor with smoking, 384
occupational exposure, bladder can-
cer risk, with smoking, 381-382

CHEST X RAY
(See also HEALTH EXAMINA-
   TIONS,
abnormal in patients with asbestos-
   induced interstitial fibrosis, 259
abnormalities related to asbestos
  exposure vs. smoking, 259-260.
   262
asbestos workers, lowest readings
  by highest readings, IL0 U/C
  scale, 261
changes in non-asbestos-exposed
  workers, cigarette smoking rela-
  tionship, 259-260, 262

522

CHEST X RAY-Contd.
IL0 classification system, variabili-
  ty of interpretation, 260
lung injury from occupational expo-
  sures and smoking, efficacy for
  evaluation, 153-155
occupationally exposed workers, ef-
  fect of smoking, 154-155
pneumoconiosis defined as
  roentgenographic changes pro-
  duced by coal dust, 290

Chronic airflow obstruction See
AIRFLOW OBSTRUCTION;
RESPIRATORY SYSTEM

CHRONIC BRONCHITIS
(See also BRONCHIAL DISEASES;
  BRONCHITIS; LUNG DIS-
  EASES; OCCUPATIONAL DIS-
  EASES)
chrysotile asbestos workers, preva-
  lence in smokers vs. nonsmokers,
   253
coal miners, dust exposure and
  smoking as factors, with age,
   298-300
coal miners, occupational relation-
  ship, 289
occupational exposure and smoking,
  additive effect, 13, 15
silica-exposed workers, dust expo-
  sure and smoking as factors,
  330, 335
silicaexposed workers, research re-
  commendations, 347
surveys of prevalence, 145-146

CHRONIC LUNG DISEASE
(See also LUNG DISEASES; OCCU-
   PATIONAL DISEASES)
asbestos exposure and smoking, ef-
  fects of combined exposure, 239-
   266
etiology, occupational and lifestyle
  influences, 8
mortality in asbestos workers,
  smoking as factor, 240-241
occupational exposure relationship,
  overview, 7
occupationally exposed workers,
  risk evaluation techniques, 142
occupation-related and smoking-re-
  lated, relative frequencies, 145


INDEX

CHRONIC LUNG DISEASE-Contd.
pneumoconioses, bronchitis, and
  asthma, occupational exposure
  risk relationship, 141
workplace and smoking, evaluation
   of interactions, 12

CHRONIC OBSTRUCTIVE LUNG
DISEASE

(See also CHRONIC LUNG DIS
EASE; LUNG DISEASES; OC
CUPATIONAL DISEASES,
ICD addition 1967, effect on time
trends in respiratory disease
mortality, 143

mortality, occupation and smoking
as factors, 145

CIGARETTE SMOKE
(See also SMOKE INHALATION,
   ANIMAL)

animal studies of carcinogenic in-
teractions with asbestos, 232-234
asbestos fibers as carriers of car-
cinogens, interactive effect, 238
carcincgenic interactions with as
bestos, animal studies, 232-234
exposure measurement, importance
in workplace studies, 161
impairment of mucociliary trans-
port and function of phagocytic
cells, 236-237

large airways, small airways, and
parenchyma as sites of lung in-
jury, 14&151

tumor induction in animals. radia-
tion effect, 456-460
tumors in rodents following expo-
sure to asbestos and smoke com-
ponents, 235

COFFEE DRINKING
bladder cancer risk relationship,
  380, 382

COMPENSATION CLAIMS
apportioning impairment between
  occupational causes and cigarette
  smoking, 170
coal workers, establishing indepen-
  dent effects to determine disease
   causes, 289

COST BENEFITS ANALYSIS
(See also STATISTICAL ANALY-
   SIS)

COST BENEFITS ANALYSIS--Con&l.
worksite smoking interven-
  tion/control programs, 477

COUGH

(See also RESPIRATORY SYMP-
TOMS,

rubber workers, duration of em-
ployment as factor, with smok-
ing, 388-390

COUNSELING
physician's advice in smoking ces-
  sation programs, efficacy, 493
   495

Demographic factors See OCCUPA-
TIONAL GROUPS; OCCUPA-
TIONS

DUST

(See also OCCUPATIONAL EXPO-
SURES)

cement, independent risk factor for
bronchitis, with smoking, 187
coal dust exposure and bronchitis,
risk relationship, 184-185
coal dust exposure as emphysema
risk in miners, smoking role,
305-308

coal dust exposure, underground
vs. surface workers, 290
coal, exposure area and duration
as factors in pneumoconiosis,
294-295

cotton, bronchitis and byssinosis
risk in exposed workers, with
smoking, 16, 412-414
cotton, byssinosis in workers, by
median dust level, smokers vs.
nonsmokers, 414
cotton, chronic clinical effects of
exposure, 420. 422-423
cotton, endotoxins in airborne dust
in inflammatory lung injury,
424-426

cotton, hemp, and flax, industrial
bronchitis and byssinosis in
workers, 403

cotton, lung cancer and respiratory
disease mortality in exposed
workers, 429, 431
cotton, mechanisms of lung injury,
423-428

cotton, nonspecific hyperreactivity
to exposure. 427-428

523


INDEX

DUST-Contd.

cotton, standard maximum levels
for occupational exposure, 414-
415

grain, bronchitis risk factor in ex-
posed workers, with smoking,
187-188

lung diseases in exposed workers,
underreporting, 144
ventilatory function effects in coal
workers, with smoking, 308-312

EMPHYSEMA

(See also CHRONIC LUNG DIS-
EASE; OCCUPATIONAL DIS-
EASES)

coal workers, dust exposure and
smoking in risk, 14, 304, 313
cotton vs. noncotton workers, smok-
ers vs. nonsmokers, 430
cotton workers, smoking as causal
factor, 1617, 428-431, 433
parenchymal injury caused by
smoking, 149

radon daughters, uranium ore dust,
and cigarette smoke effects in
dogs, 458

surveys of prevalence, 145-146
time trends in mortality, effect of
changes in ICD categories. 143

ENZYME ACTIVITY
biotransformation of industrial toxi-
  cants by smoke constituents, 391
carcinogenesis, stimulation by as-
  bestos, 236237
carcinogenicity of aromatic amines,
   role, 371
silica-induced lung injury, relation-
  ship, 339-340

ENZYMES

angiotensinconverting enzyme, 340

EX-SMOKERS
(See also NONSMOKERS)
occupational differences, 11

GASTROINTESTINAL CANCER
synthetic fiber factory workers, in-
  teraction of exposure and smok-
  ing, 387-388

524

Health education See SMOKING
CONTROL PROGRAMS; WORK.
PLACE INTERVENTION PRO-
GRAMS

HEALTH EXAMINATIONS
chest x ray, efficacy for evaluating
  occupation and smoking risks,
   153-155
occupationally exposed workers,
  need for smoking information,
   131
physiological assessment, efficacy
  for evaluating occupation and
  smoking risks, 155157
respiratory symptoms history to
  evaluate occupation and smoking
  risks, 152-153

HEART DISEASES
etiology, occupational and lifestyle
  influences, 8

IMMUNE SYSTEM
alterations following combined ex-
  posure to cigarette smoke and
  asbestos, 266270

IMMUNITY

cellular, lymphocyte changes in as-
bestos workers, smoking habit
correlation, 267-270
humoral, immunoglobulins in as-
bestos-exposed workers vs. ciga-
rette smokers, 266-267

IMMUNOGLOBULINS
IgA and IgG levels in asbestos
  workers vs. cigarette smokers,
   266-267

INCENTIVES

monetary incentives and competi-
tion in smoking cessation, effica-
cy, 495-498

KIDNEY CANCER
mortality in refinery and chemical
  workers, study data, 362-363
occupations at possible risk, smok-
  ing as factor, 385-386

LARYNGEAL CANCER
uranium miners, possible interac-
  tion of radiation and smoking,
   463

LARYNX
(See abo RESPIRATORY SYSTEM)


INDEX

LARYNX-Contd.
radiation and cigarette smoke, in-
  teractive effects, 463

LIVER CANCER
occupational groups at risk, 387
solvent-exposed workers, risk rela-
  tionship, 387

LUNG CANCER
(See also BRONCHIAL NEO-
  PLASMS; OCCUPATIONAL DIS
   EASES
asbestos-exposed nonsmokers, risk
  determination, 210-213
asbestos-exposed smokers, risk de-
  termination, 213, 216220
asbestos-exposed workers, sex ratio
  of observed vs. expected deaths,
   214
asbestos-exposed workers, smoking
  status in risk determination,
  205, 210
asbestos exposure, multiplicative
  risk in smokers, 13
asbestos exposure risk in smokers
  vs. nonsmokers, summary and
  conclusions, 271
asbestos workers, expected vs. ob
served mortality, by smoking
  habit, 215
asbestos workers, interactive effects
of exposure level and smoking
  category, 219-220
blue-collar workers, odds ratio,
  37G377
Canadian fluorspar miners, risk
  with smoking, 453454
coal dust exposure and smoking in
  risk, 313
coke oven workers, occupational ex-
  posure as factor, 391
gold miners, risk in smokers vs.
  nonsmokers, 343
histological types, positive associa-
tion of smoking, 377
historical association with cigarette
smoking, 6
hypothesis to reconcile discrepan-
cies in epidemiological data,
  461463
hypothetical distribution in smok-
ing and nonsmoking uranium
miners, U.S. white men, 457

LUNG CANCER-Contd.
metal ore miners, smoking as risk
  factor, 34%344

miners, interaction of smoking and
cancer, study data, 447
mortality, causal relationship with
smoking, 101-104
mortality in coal workers vs. gen-
eral population, 301-304
mortality in male asbestos workers,
observed vs. expected weighted
average probabilities, 233
mortality in men, ratios by age,
smoking characteristics, 105
mortality in pesticide-exposed work-
ers. 372-374

mortality in refinery and chemical
workers, study data, 362-363
mortality in cotton workers, 429,
431

occupational exposure and smoking
risks, controlling for independent
effects and interactions, 124-125
occupational exposure relationship,
smoking status as source of con-
founding, 115122
occupational exposure to known or
suspected carcinogens, risk with
smoking, 377-378
occupational exposures and smok-
ing, causal relationship, 376378
polonium 210 in cigarette smoke in
carcinogenesis, with chemical
constituents, 461

race, sex, occupation, and birth co-
hort as factors, 39-40, 43
radiation and smoking in epide-
miology, studies on interactive
effects, 455-456

radiation-exposed miners, risk in
smokers vs. nonsmokers, 446
radon daughter exposure and
smoking as risk factors, I7
reduction/cessation of asbestos ex-
posure and smoking, effect on
risk, 224-228

residential exposure as risk factor,
research recommendations, 464
silica-exposed workers, 341-348
silicotics, proportional morbidity
rate during followup. 345-346
steel workers, risk ratios in smok-
ers vs. nonsmokers, 344

525


INDEX

LUNG CANCER-Contd.
Swedish miners, radiation and
  smoking in risk, 452-453
threshold of risk in asbestos work-
  ers, exposure level and smoking
  as factors, 220-224
uranium miners, induction-latent
  period in smokers vs. non-
  smokers, 451

uranium miners, risk in smokers
vs. nonsmokers, 449-452
women, risk factors, 377

LUNG DISEASES
(See also CHRONIC LUNG DIS-
  EASE; CHRONIC OBSTRUC-
  TIVE LUNG DISEASE; OCCU-
  PATIONAL DISEASES; PNEU-
  MOCONIOSIS; PULMONARY
  FIBROSIS; RESPIRATORY
   TRACT DISEASES)
hazardous occupational exposures
  and smoking, possible synergism,
   8-9
individual relative risk determina-
  tion, guidelines, 167-169
interstitial fibrosis in asbestos
  workers, 271
mortality, age-standardized rates
  with/without asbestos exposure
  and smoking, 242
mortality in asbestos-exposed work-
  ers, smoking status as factor,
   201
obstructive and restrictive, role of
  asbestos exposure and smoking,
   241, 243-254
occupational exposure and smoking
  effects, summary and conclu-
   sions, 169-170
occupational exposures and smok-
  ing, potential interactions, 159
pneumoconiosis, silicosis, chronic
  bronchitis in coal workers, 289
pneumonitis in uranium miners,
  radiation exposure as factor, 464
restriction and obstruction pro-
  cesses in occupationally exposed
   workers. 151
restrictive and obstructive in asbes-
  tos workers who smoke, 271
rubber workers, occupational expo-
  sures and smoking as factors,
   386390

526

LUNG DISEASES-Contd.
silica-exposed copper miners, early
  study of risk relationship, 328
statistical analysis of independent
  and interactive effects of smok-
  ing, 162-164

survey populations, prevalence of
cigarette smoking, 147

LUNG FUNCTION
(See also RESPIRATORY FUNC-
  TION TESTS)

asbestos exposure and smoking, ad-
ditive effects, 14, 271
asbestos exposure level as factor,
257

asbestos workers, forced expiratory
volume in smokers, ex-smokers,
nonsmokers, 248
asbestos workers, patterns of
change in smokers vs. non-
smokers, 241, 243-254
asbestos workers, predictive equa-
tion by smoking status, age,
height, 247

chrysotile asbestos workers, profile
of smokers vs. nonsmokers, 253
coal miners with irregular opaci-
ties, exposure, age, and smoking
as factors, 297-298
coal miners with rounded or regu-
lar opacities, 296
coal workers, 304
coal workers, dust exposure and
smoking effects, 296-297, 306
307

coal workers with pneumoconiosis,
abnormalities, 295

coding of lung function profile, 252
cotton textile workers, dust expo-
sure and smoking as factors, 16,
403, 415-419

cotton workers, hyperreactivity to
dust exposure as possible factor
in decline, 428

cotton workers, smoking as factor,
432

cotton workers, type of dust and
exposure level as factors, 419
cotton workers with byssinosis and
bronchitis, risk with smoking,
422-423


INDEX

LUNG FUNCTION-Contd.
cotton workers with/without
  bronchitis or byssinosis. smokers
  vs. nonsmokers, 417
expiratory flow and lung volume,
  asbestos dust exposure relation-
  ship, 249-250

foundry workers exposed to silica,
effects, 336

occupational exposure effects,
simultaneous contribution of ag-
ing and smoking, 166-167
physiological assessment in occupa-
tionally exposed workers, smok-
ing as factor, 157
prospective study data on silicaex-
posed workers, 337-338
restrictive vs. obstructive effect of
asbestos exposure, smoking as
factor, 248-252

rubber workers, duration of em-
ployment as factor, with smok-
ing, 388-389

silica-exposed miners and other
workers, smokers vs. non-
smokers, 331-334
silica exposure vs. smoking effects,
340-34 1

uranium miners, ore dust, radia-
tion, smoking effects, 463-464
ventilatory function decline in
smokers, 150

LUNG VOLUME
(See also RESPIRATORY FUNC-
  TION TESTS)

asbestos exposure effect in smokers
and nonsmokers, 258
asbestos workers, by dust index in
nonsmokers vs. smokers, 244
chronic obstructive vs. restrictive
lung disease patients vs. normal
individuals, 243

coal workers, additive effects of
dust exposure and smoking, 308
coal workers with pneumoconiosis,
295

coal workers with/without bronchi-
tis, smokers vs. nonsmokers,
31&312
dust exposure relationship, 249

LUNGS
(See also RESPIRATORY SYSTEM1

LUNGS-Contd.
asbestos deposition and clearance,
  effect of chemicals in cigarette
  smoke, 236-237
chronic inflammatory destruction
  in cotton workers, smoking fac-
  tor, 428431

coal workers, confounding of dust
exposure effects by smoking,
289-290

cotton workers, agents responsible
for inflammatory response, 424-
427

elastic recoil effects of asbestos ex-
posure and smoking, differences,
258

emphysema, mucus glands, goblet
cell metaplasia, pigmentation in
smokers vs. nonsmokers, 430
mechanisms of cotton dust-related
injury, 423-428

patterns of injury from asbestos ex-
posure and smoking, risk deter-
mination, 239

patterns of injury from occupation-
al exposures and smoking, 148-
151

silica-exposed workers, mechanisms
of injury, 339-341
small opacities in coal workers
with pneumoconiosis, smoking ef-
fect, 296

LYMPHOCYTES
age and smoking as correlates of
  changes in asbestos workers,
   267-269

Mathematical models See STATIS-
TICAL ANALYSIS

MESOTHELIOMA
wives and children of asbestos
  workers, risk, 200

MODELING TECHNIQUES
(See also STATISTICAL ANALY-
  SIS: WORKPLACE EXPOSURE
   STUDIES,
analyses to control potential con-
  founding of occupational expo
  sure by smoking, 129-130

MORBIDITY
(See also OCCUPATIONAL DIS-
  EASES; WORKPLACE EXPO-
   SURE STUDIES)


INDEX

MORBIDITY-Contd.
respiratory diseases, smoking as
  predominant cause, 142
silica exposure effects, early stud-
  ies, 328

MORTALITY

(See also OCCUPATIONAL DIS-
EASES; WORKPLACE EXPO-
SURE STUDIES)
asbestos-exposed persons, industrial
standards and smoking cessation
to reduce risk, 270
asbestos-related, data from cohort
studies, 202-204
asbestos workers, observed vs. ex-
pected, 227-228
asbestos workers, smoking as fac-
tor, 241

bladder cancer in chemical work-
ers, 370-371

bronchial and lung cancer in men,
by birth cohort and age at
death, 230

bronchial, tracheal, and lung can-
cer, age-specific rates, white men
and women, 229
cancer in rubber workers, 366-370
cancer risk in certain occupations,
375376

chronic respiratory diseases in
1960, 1970, 1980, by ICD catego
ry, 143

coal workers, cigarette smoking as
major factor, 303-304
lung cancer and chronic lung dis-
ease in asbestos workers, smok-
ing as factor, 201
lung cancer, causal relationship
with smoking, 101-104
lung cancer in asbestosexposed
workers, expected vs. observed,
by smoking habit, 215
lung cancer in asbestos-exposed
workers, sex ratio of observed
vs. expected, 214
lung cancer in male asbestos work-
ers, observed vs. expected
weighted average probabilities,
233

lung cancer in men, mortality ra-
tios by age, smoking characteris-
tics, 105

528

MORTALITY-Contd.
lung cancer in Swedish miners, ra-
  diation and smoking as factors,
   452453

lung cancer in U.S. uranium min-
ers, smoking as factor, 446, 44S-
452

metal ore miners, pneumonconiosis,
tuberculosis, cancer risks, 342
occupational exposure risk, smoking
prevalence and age distribution
as factors, 127-128
occupationally related, potential
confounding by smoking, 114-123
pesticide-exposed workers, 372-374
refinery and chemical workers,
smoking and exposure in risk,
361366

respiratory disease and lung cancer
in cotton workers, factors, 429,
431

respiratory diseases in coal work-
ers, 300-304

respiratory diseases, smoking as
predominant cause, 142
respiratory diseases, underestima-
tion with vital statistics, 144
selected causes, age-standardized
rates with/without asbestos expo-
sure and smoking, 242
time trends for respiratory dis-
eases, effect of changes in dis-
ease classifications, 143
tuberculosis and nonmalignant res-
piratory disease in silica-exposed
workers, 327

tuberculosis, silicosis and cancer in
silicotics, smoking factor, 347
workplace environment and ciga-
rette smoking as factors, 11

MORTALITY RATIOS
cancer and pneumoconiosis in met-
  al ore miners, smoking as factor,
   343-344

cancer, confounding of occupational
exposure effects by smoking,
114-118

lung cancer in asbestos-exposed vs.
control populations, smokers vs.
nonsmokers, 216, 218
. occupation and smoking effect, con-
trol of potential confounding,
  123


MORTALITY RATIOS-Contd.
silicotics, age at diagnosis and
  smoking as factors, 346-347

Motivation See INCENTIVES

NATIONAL HEALTH INTERVIEW
SURVEYS
(See also SMOKING SURVEYS)
current smokers, 1978-1980, by sex
  and occupation, 58-59
current smokers by sex and select-
  ed occupations, 61-63
net change in smoking prevalence
  by sex and occupation, 1970-
   1980, 64-65
occupations by category and code,
   57
percentage of population in select-
  ed occupations, 1978-1980, 66-67

OCCUPATIONAL DISEASES-Contd.
  CER; PNEUMOCONIOSIS; RES-
  PIRATORY TRACT DISEASES;
  SILICOSIS; TUBERCULOSIS)
acute and chronic respiratory ef-
  fects of exposure in cotton work-
  ers, 420, 422-423
airways inflammation and restric-
  tion in cotton workers, causes,
   424-428

asbestosis in exposed populations,
smokers vs. nonsmokers, 263-264
bladder cancer in chemical work-
ers, exposures and smoking as
factors, 378-384

bladder cancer in dye, petroleum,
and plastic industries, smoking
factor, 383

Neoplssms See CANCER

NONSMOKERS
(See also EX-SMOKERS)
asbestos workers, confirmation of
   status to establish disease risk,
   21G213
asbestos workers, exposure effects
  on small airways function, 257
asbestosis prevalence, 264
lung cancer in asbestos-exposed
  workers, risk determination,
   210-213
occupationally exposed, comparison
  group to control for potential
  confounding by smoking, 124-126

Obstructive airway diseases See
BRONCHIAL DISEASES; EM-
PHYSEMA; OCCUPATIONAL
DISEASES

INDEX

bladder cancer in truck drivers,
smoking factor, 385
bladder cancer in workers exposed
to benzidine and betanaphthyla-
mine, smoking factor, 383
bladder cancer in workers exposed
to radiation, 381
bronchitis in cement workers, dust
exposure and smoking as factors,
186

bronchitis in coal miners, dust and
smoking as factors, 185
bronchitis in copper smelter work-
ers, smoking as factor, 191
bronchitis in gold miners, silica ex-
posure and smoking as factors,
185-186

OCCUPATIONAL DISEASES
(See also AIRFLOW OBSTRUC-
  TION; ASBESTOSIS; BLADDER
  CANCER; BRAIN CANCER;
  BRONCHIAL CANCER;
  BRONCHITIS; BYSSINOSIS;
  CANCER; CHRONIC BRONCHI-
  TIS; CHRONIC LUNG DISEASE;
  CHRONIC OBSTRUCTIVE
  LUNG DISEASE; EMPHYSEMA;
  KIDNEY CANCER; LARYN-
   GEAL CANCER; LIVER CAN-
   CER: LUNG CANCER: LUNG
   DISEASES; PANCREATIC CAN-

bronchitis in grain workers, dust
and smoking as factors, 187-189
bronchitis in welders, additive ef-
fect of smoking, 190
byssinosis in cotton textile workers,
prevalence of smoking, 147
byssinosis in cotton textile workers,
smoking as factor, 16, 40-23
cancer, causal relationship of occu-
pational exposures and smoking,
374-388

cancer, evaluation of smoking and
workplace interactions, 12
cancer in pesticide-exposed workers,
smoking role, 372-374
chronic bronchitis and chronic air-
ways obstruction in silica-ex-
posed workers, smoking as fac-
tor, 15


INDEX

I.

OCCUPATIONAL DISEASES-Contd
chronic bronchitis in grain work-
  ers, prevalence of smoking, 147
chronic bronchitis, smoking and
  workplace interactions, 13
chronic lung disease, evaluation of
  smoking and workplace interac-
  tions, 12-13

OCCUPATIONAL DISEASES-Contd.
lung cancer in radiation-exposed
  miners, smokers vs. nonsmokers,
   446

lung cancer in Swedish miners, ra-
diation and smoking as risk fac-
tors, 452-453

lung cancer in uranium miners,
risk in smokers vs. nonsmokers,
449-452

development and organization of
1985 Report, 5

emphysema in coal workers, dust
exposure and smoking as factors,
305-308

historical perspective, 6
interstitial fibrosis in asbestos-ex-
posed populations, 263, 265-266
large bowel cancer in synthetic fi-
ber factory workers, smoking ef-
fect, 387-388

liver cancer in farm laborers, risk
relationship, 387
liver cancer in solvent-exposed
workers, 387

lung cancer and chronic lung dis-
ease in asbestos workers, smok-
ing factor, 201

lung cancer and respiratory disease
mortality in cotton workers, 429,
431

lung cancer in asbestos-exposed
nonsmokers, risk determination,
210-213

lung cancer in asbestos-exposed
smokers, risk determination, 213,
216220

lung cancer in asbestos workers,
interactive effects with smoking,
219-220

lung cancer in asbestos workers,
sex ratio of observed vs. expect-
ed deaths, 214

lung cancer in asbestos workers,
smoking status in risk determin-
ation, 205, 210
lung cancer in coke oven workers,
exposure risk, 391
lung cancer in miners, induction-
latent period in smokers vs. non-
smokers, 451

lung cancer in miners, interactive
effect of smoking, study data,
447448

530

lung cancer mortality ratios for as-
bestos workers, smokers vs. non-
smokers, 216, 218
lung disease in coal miners, preva-
lence of smoking, 147
lung disease mortality in asbestos
workers by exposure type, 202-
204

pneumoconiosis, silicosis, chronic
bronchitis in coal workers, 289
pulmonary fibrosis in dockyard
workers, by smoking habit and
asbestos exposure, 266
respiratory, mortality in coal work-
ers, 300-304

silica-induced, epidemiology, 327-
330, 335-336

simple and complicated pneumoco-
niosis in coal miners, radiologic
characteristics, 290, 294

OCCUPATIONAL EXPOSURE
STANDARDS

asbestos, for reduction of intersti-
tial fibrosis in workers, 270
coal dust, prevention/reduction of
pneumoconiosis, 295
cotton dust, development of maxi-
mum exposure levels, 414-415

OCCUPATIONAL EXPOSURES
(See also AROMATIC AMINES;
  AROMATIC HYDROCARBONS;
  ASBESTOS; CHEMICALS;
  DUST; PESTICIDES; PETRO-
  CHEMICALS; RADIATION; SILI-
   CA)

asbestos, chronic lung disease risk,
effect with smoking, 239-266
asbestos, disease risks in exposed
workers, smoking status as fac-
tor, 201, 205

asbestos, duration effect on fibrosis,
additive risk in smokers, 264,
266


INDEX

OCCUPATIONAL EXPOSURES-
Contd.

asbestos, establishing risk thres-
hold, smoking as factor, 223-224
asbestos, mechanisms of carcinogen-
esis in workers who smoke. 228.
231

asbestos, observed vs. expected
mortality by years since initial
exposure, 228

asbestos, public health implications. S
asbestos, reduction/cessation of ex-
posure and smoking, effects,
224-228

asbestos, relative risk of lung can-
cer, with smoking, 378
benzidine and betanaphthylamine,
bladder cancer risk, with smok-
ing, 383384

biological interactions with smok-
ing, 104, 106-109
cancer risk relationship, with
smoking, 101

carcinogens, recommendations for
control, 390-391

causal relationship with specific
diseases, with smoking, 374-390
cement dust and smoking, indepen-
dent risk factors for bronchitis,
187

chemicals, bladder cancer risk,
with smoking, 381-382
chronic disease epidemiology, factor
with smoking, 8

chronic lung disease risk relation-
ship, 141

coal dust, bronchitis risk factor
with smoking, 185
coal dust, control to reduce pneu-
moconiosis prevalence, 312-313
coal dust, disease risk, with smok-
ing, 298-299

coal .dust in miners, emphysema
risk, smoking role, 305308
combustion effluents, inhalation
and smoking as bladder cancer
risk factors, 384

control of smoking and exposure
levels to reduce disease risk. 11
cotton dust, acute effect on respira-
tory symptoms, with smoking,
409-410, 412-415

OCCUPATIONAL EXPOSURES-Contd.
cotton dust. byssinosis and bronchi-
  tis risk in workers who smoke,
   16

cotton dust, chronic clinical effects,
420, 422423

cotton dust, expiratory volume in
smokers vs. nonsmokers
with/without disease, 417
cotton dust, exposure level and
smoking in bronchitis and byssi-
nosis risk, 412-413
cotton dust, job category as factor
in byssinosis risk, 403
cotton dust, respiratory disease and
lung cancer mortality in exposed
workers, 429, 431
cotton dust, smoking influence on
byssinosis development, 403423
cotton dust, type and exposure lev-
el as factor in lung function ef-
fects, 419

lung disease relationship, evalua-
tion methods, 151-157
lung disease risk, with smoking,
summary and conclusions, 169-
170

lung function effects, simultaneous
contribution of aging and smok-
ing, 166167

lung injury patterns, comparison
with smoking-related injury,
348-151

pesticides, mortality in exposed
workers, 372-374
petrochemicals, aromatic amines.
pesticides, risks with smoking,
15. 359-392

petrochemicals, bladder cancer risk.
tobacco use as factor, 382
polycyclic aromatic hydrocarbons,
relative risk of lung cancer,
with smoking, 378
polyvinyl chloride and vinyl chlo
ride. bronchitis risk relationship,
189

"pure" silica, cancer risks, 344-345
radiation, bladder cancer risk, with
smoking, 381

radiation in miners, lung cancer
risk. 446

rubber processing, lung function ef-
fects. 388-390

531


INDEX

OCCUPATIONAL EXPOSURES-
Contd.

silica, chronic bronchitis symptoms
in exposed workers, smoking in-
teractions, 185186
silica, disease risk with smoking,
15, 323-348

silica exposure in uranium miners,
risks with smoking, 463-464
silica, importance of "free" vs.
"combined" forms in occupation-
al toxicity, 323

silica, lung cancer risk relationship,
341-348

silica, lung function and respirato-
ry diseases in smokers vs. non-
smokers, 330, 335
silica, noncompliance with permissi-
ble exposure limit, 323
silica, population at risk, NIOSH
survey, 323-324

silica, prospective study data on ex-
posed workers, 337-338
silica, research recommendations,
347-348

silica, respiratory disease risk, role
of smoking, 325

silica, smoking characteristics of
exposed workers, 326
silica, summary and conclusions
about disease risk, 348
solvents, risk of liver cancer in ex-
posed workers, 387
statistical interactions with smok-
ing effects, 104, 109-113
uranium ore dust, lung cancer risk
in miners, 446-452, 457

OCCUPATIONAL GROUPS
~See nlso OCCUPATIONS)
blue-collar workers, birth cohort,
  occupation, sex as factors in
  smoking, 3%55

blue-collar workers, efficacy of
smoking intervention programs,
499

blue-collar workers, smoking preva-
lence by age and sex, 23-26
blue-collar workers, workplace envi-
ronment as factor in smoking
behavior. 10

clerical and kindred occupations,
female smoking by birth cohort, 74

532

OCCUPATIONAL GROUPS-Contd.
clerical and kindred workers, cur-
  rent smoking by sex, 58-59, 61,
   64

cotton, hemp, and flax workers,
health effects of dust exposure,
403

craftsmen and kindred workers,
current smoking by sex, 58-59,
62, 64

craftsmen or kindred occupations,
male smoking by birth cohort,
71

farm workers, current smoking by
sex, 58-59, 62, 65
laborers, except farm, current
smoking by sex, 58-59, 62
managers and administrators, cur-
rent smoking by sex, 58-59, 61,
64

managers and administrators, male
smoking by birth cohort, 70
managers and salesmen, relative
risk of bladder cancer, 381
miners, disease risk of silica expo-
sure in smokers vs. nonsmokers,
331-334

operatives and kindred occupations,
male smoking by birth cohort,
72

operatives and kindred workers,
current smoking by sex, 58-59,
operatives, except transport, cur-
rent smoking by sex, 62, 64
professional, technical, and kindred
occupations, female smoking by
birth cohort, 73

professional, technical, and kindred
occupations, male smoking by
birth cohort, 69

professional, technical, and kindred
workers, current smoking by sex,
58-59, 61, 64

sales workers, current smoking by
sex, 58-59, 61, 64
service workers, current smoking
by sex, 58-59, 63, 65
transport operatives, current smok-
ing by sex, 62, 64
transport, service, manufacturing,
construction workers, lung can-
cer risk, 375


INDEX

OCCUPATIONAL GROUPS-Contd.
white-collar workers, birth cohort,
  occupation, sex as factors in
  smoking, 3&X
w bite-collar workers, smoking pre-
  valence by age and sex, 23-25
workers at high risk, three ap
  proaches for smoking interven-
  tion, 498-500

OCCUPATIONAL LUNG DIS-
EASES

(See also LUNG DISEASES; OCCU-
PATIONAL DISEASES)
occupational bronchitis, worksite
chemicals or physical agents in
risk, 183

prevalence not comprehensively do-
cumented, 146

underestimation of affected work-
ers, 144-146

OCCUPATIONS
(See also OCCUPATIONAL
  GROUPS)

aides, smoking habits by age, 83
archrtects, smoking habits by age,
83

asbestos workers, 9, 13-14, 219-220
asbestos workers, cancer mortality
risk, 375

asbestos workers, smoking interven-
tion program efficacy, 499-500
assemblers, smoking habits by age
and sex, 83

automotive workers, smoking habits
by age and sex, 84
banking, smoking habits by age
and sex, 84

barbers/beauticians, smoking habits
by age and sex, 84
bookkeepers, smoking habits by age
and sex, 84

Canadian fluorspar miners, lung
cancer risk, with smoking, 45%
454

cement workers, 187
chemical workers, cancer risk, 375
376

chemical workers, relative risk of
bladder cancer, 380
civil service workers, smoking hab-
its by age and sex, 85
clergy, smoking habits by age and
sex, 85

OCCUPATIONS--Contd.
coal workers, 14, 289
coal workers, smoking habits, 291
coke oven workers, 191
coke oven workers, lung cancer
  risk, 391

construction workers, smoking hab-
its by age, 85

copper miners, silica-induced lung
injuries. 328

copper smelter workers, 191
cotton textile mill workers, 147
cotton textile workers, smoking in-
fluence on byssinosis develop
ment, 403-423
cotton workers, byssinosis, bronchi-
tis, smoking effects on lung
function, 41S419
cotton workers, exposure effects on
lung function, with smoking,
415419

cotton workers, smoking habits,
404, 409

cotton workers, study data on
smoking prevalence, 405408
data entry operators, smoking hab
its by age, 85
dentists, smoking habits by age
and sex, 86

disabled, smoking habits by age
and sex, 86

dockyard workers, 266
doctors, smoking habits by age and
sex, 86

education, smoking habits by age
and sex, 86

electricians, smoking habits by age
and sex, 87

engineers, smoking habits by age
and sex, 87

executives, smoking habits by age
and sex, 87

factory workers, smoking habits by
age and sex, 87
farm laborers, liver cancer risk,
387

farm workers, 147
farmers, smoking habits by age
and sex, 88

firefighters, smoking habits by age,
88

food preparation workers, smoking
habits by age and sex, 88
foremen. smoking habits by age. 88

533


INDEX

OCCUPATIONS--Contd.
foundry workers exposed to silica,
  lung function effects, 335-336
gold miners, 186
gold miners, cancer risk, 342-343
grain workers, 147
granite shed workers, 147
granite workers exposed to silica,
  lung function effects, 336
heavy equipment operators, smok-
  ing habits by age, 89
hospital workers, smoking habits
  by age and sex, 89
housewives, smoking habits by age,
   89

law enforcement workers, smoking
habits by age, 89
lawyers, smoking habits by age
and sex, 90

leather industry workers, cancer
risk independent of smoking, 376
leather workers, bladder cancer
risk, 379-380

machine operators, smoking habits
by age and sex, 90
maids, smoking habits by age and
sex, 90

maintenance workers, smoking hab-
its by age and sex, 90
managers, smoking habits by age
and sex, 91

metal ore miners, respiratory can-
cer risk, 342

military personnel, smoking habits
by age, 91

miners, smoking habits by age, 91
nursing personnel, smoking habits
by age, 91

office workers. smoking habits by
age and sex. 92
painters, smoking habits by age, 92
pesticide-exposed workers, risks,
359-360, 372-374
pesticide workers, cancer risks,
372-374

petrochemical workers, bladder can-
cer risk, 382

pharmacists, smoking habits by age
and sex, 92

photo and printmg workers. smok-
ing habits by age, 92
plumbers, smoking habits by age,
93

534

OCCUPATIONS-Contd.
polyvinyl chloride and vinyl chlo-
  ride workers, 189
postal service workers, smoking
  habits by age and sex, 93
pottery workers, silicosis preva-
  lence, 328

printers, smoking habits by age
and sex, 93

railroad workers, smoking habits
by age, 93

real estate workers, smoking habits
by age and sex, 94
refinery and chemical workers ex-
posed to petrochemicals, risks,
359-392

refinery and chemical workers,
smoking and exposure in mortal-
ity risk, 361-366
rubber curing workers, 191
rubber workers, bladder cancer
risk, 379-380

rubber workers exposed to aromat-
ic amines, risks, 359, 366370
sales people, smoking habits by age
and sex, 94

shipyard workers, lung cancer risk,
375

silica-exposed workers, risks, 15,
323-347

social workers, smoking habits by
age and sex, 94
steel mill workers, smoking habits
by age, 94

steel workers, lung cancer risk, 344
Swedish miners, lung cancer risk
in smokers vs. nonsmokers, 452-
453

technicians, smoking habits by age
and sex, 95

telephone operators, smoking habits
by age, 95

textile and garment industry work-
ers exposed to aromatic amines,
risks, 359, 370-372
textile workers, smoking habits by
age and sex, 95

truck drivers, bladder cancer risk,
385

truck drivers, lung cancer risk, 375
truck drivers, smoking habits by
age and sex, 95

unemployed workers, smoking hab-
its by age and sex, 96


INDEX

OCCUPATIONS-Contd.
uranium miners, 147
uranium miners, pulmonary effects
  of exposure and smoking, 46%
   464

uranium miners, radiation and
smoking in lung cancer risk,
446452

uranium miners, smoking habits,
448
waiters/waitresses, smoking habits
by age. 96
welders, 189
welders, smoking habits by age, 96
woodworkers, smoking habits by
age, 96

PANCREATIC CANCER
daily cigarette consumption as fac-
  tor in risk, 387

PASSIVE SMOKING
lung cancer risk, with radon
  daughter exposure, research re-
  commendations, 464
occupational hazards, possible con-
  founding of risk in nonsmokers.
   126

PESTICIDES
(See also OCCUPATIONAL EXPO-
  SURES)
brain neoplasms in exposed work-
  ers, possible risk relationship,
   386-387
mortality in exposed workers, 372-
   374
occupational exposure, disease
  risks, 359-392

PETROCHEMICALS
(See also OCCUPATIONAL EXPO-
   SURES
mortality in exposed workers, 361-
   366
occupational exposure, disease
  risks, 359-392

PNEUMOCONIOSIS
(See also OCCUPATIONAL DIS-
   EASES,
coal workers, historical association.
   289
coal workers, pattern of develop-
   ment, 151

PNEUMOCONIOSIS-Contd.
coal workers pneumoconiosis and
  progressive massive fibrosis, pre-
   valence, 294295
coal workers, standard mortality
  ratios vs. general population,
   30@301
disability payments vs. estimated
  prevalence, 146
disease definition, 290
dust exposure as major etiologic
  factor in coal workers, 312-313
mortality ratios vs. cancer in metal
  ore miners, smoking as factor,
   343344
silica-exposed miners and other
   workers. 331-334

Prevention of smoking See PRO-
GRAMS AND POLICIES;
SMOKING CONTROL PRO-
GRAMS; WORKPLACE INTER-
VENTION PROGRAMS

PROGRAMS AND POLICIES
(See also SMOKING CONTROL
  PROGRAMS; WORKPLACE EX-
  POSURE STUDIES; WORK-
   PLACE INTERVENTION PRO-
   GRAMS)
economic advantages/disadvantages
  of worksite programs, 477-479
Johns Manville antismoking policy,
  cessation program, 499-500
worksite smoking control programs,
   477-510

PULMONARY FIBROSIS
(See also LUNG DISEASES; OCCU-
  PATIONAL DISEASES)
animals exposed to cigarette smoke
  and asbestos, 234
asbestos-exposed populations, smok-
  ing relationship. 263-264. 266
asbestos exposure as risk factor,
  14, 239-240

asbestos-induced, abnormal chest x
ray as indicator. 259
dockyard workers. by >mokmg hab-
it and asbestos ~X~OSUP. 866
fibrosing alveolitis in silica-exposed
xorkrrs. smoking role. 325
nonexposed vs. exposed asbestos
workers. smoking relationship,
259-260. 262


INDEX

PULMONARY FIBROSIS-Contd.
silica exposure as factor, enzyme
  activity in pathogenesis, 339
uranium miners, exposure effects,
  with smoking, 463464

Pulmonary function See LUNG
FUNCTION

PULMONARY MACROPHAGES
enzymatic activity, influence in
  carcinogenesis, 237-238
silica cytotoxicity in pathogenesis
  of fibrosis. 339

small airways of smokers, pattern
of lung injury, 148-149

RACE FACTORS
black blue-collar workers, smoking
   rates, 11

smoking prevalence, birth cohort,
sex, occupation as factors, 42-46,
48-55

RADIATION

(See also OCCUPATIONAL EXPO-
SURES,

bladder cancer risk, with smoking,
381

bronchial cancer risk in uranium
miners, with smoking, 450
cancer risk, with smoking, sum-
mary and conclusions, 465
human exposure levels from radon
daughters, 445-446
Japanese A-bomb survivors, cancer
risk in smokers vs. nonsmokers,
455

lung cancer epidemiology, studies
on interactive effects with smok-
ing, 455-456

lung cancer in Swedish miners,
risk factor with smoking, 452-
453

polonium 210 from tobacco smoke
as cancer risk, 46@461
pulmonary effects in uranium min-
ers, with smoking, 463464
radon daughters, interactive effects
with cigarette smoke exposure,
17

residential exposure, lung cancer
  risk with smoking, 454

REDUCTION OF SMOKING
t&e also CESSATION OF SMOK-
  ING; SMOKING CONTROL

536

REDUCTION OF SMOKING-Contd.
  PROGRAMS; WORKPLACE IN-
  TERVENTION PROGRAMS)
biochemical verification in control-
  led worksite modification studies,
   486-488
birth cohorts, by race, sex, and oc-
  cupation. 41-52
controlled studies, data by worksite
  type, procedural characteristics,
   484-485
controlled studies, design and out-
  come data of smoking modifica-
  tion programs, 486-488
worksite participants, controlled
  studies, 483, 489-490
worksite program effects, evalua-
  tion criteria, 479-480
worksite program participants,
  long-term effects, 491

RESEARCH RECOMMENDATIONS
(See also WORKPLACE EXPO-
   SURE STUDIES)
animal studies of health effects of
   tobacco smoke and industrial
  pollutants, 391
cancer risk with occupational expo-
  sure and smoking, 12
chronic lung disease risk with oc-
  cupational exposure and smok-
  ing, 12-13
health effects of occupational expo-
  sures and smoking, epidemiologic
  studies, 391
industrial pollutants, identifying
   constituents as cancer initia-
  tors/promoters, 391
lung cancer risk in occupationally
  exposed workers, 464
lung function effects in occupation-
  ally exposed smokers, 169
lung impairment, apportioning risk
  between occupational exposure
  and smoking, 170
methodology and evaluation issues
  in worksite smoking modifica-
  tion, 507-509
occupational exposure to specific
  agents, interactive effects with
  smoking, 169
-occupational exposures, 347-348
passive smoking risks, 464


INDEX

RESEARCH RECOMMENDATIONS
Contd.

statistical analysis of occupational
exposure and smoking interec-
tions, 169

workplace smoking intervention
programs, 17, 507-509

RESPIRATORY FUNCTION TESTS
LSee also LUNG FUNCTION)
asbestos workers and smokers, pat-
  terns of lung function changes.
   241. 243-254

chrysotile asbestos workers, percen-
tage decline in smokers vs. non-
smokers, 253

coal miners, 296297, 311-312
coal workers, dust exposure and
smoking effects, 308-312
coal workers, face workers vs. sur-
face workers, 309
cotton dust exposure and smoking,
effects, 415419

expiratory volume in cotton work-
ers, smokers vs. nonsmokers,
416-418

expiratory volume in men, byssino-
sis, bronchitis, and smoking ef-
fects, 418

expiratory volume in women, byssi-
nosis, bronchitis, and smoking
effects, 419

flow rates in asbestos workers, by
dust index in smokers vs. non-
smokers, 245

rubber workers, duration of em-
ployment as factor, 388
silica-exposed foundry workers, 336
ventilatory capacity in coal work-
ers, 304

RESPIRATORY SYMPTOMS
(See al.so COUGH1
chronic cough and phlegm in coal
  miners, smoking as factor, 14,
   313

coal dust exposure relationship,
298-300

cotton dust exposure and smoking,
acute effects, 409-410, 412-415
cough and phlegm in rubber curing
workers, smoking as factor. 191
rubber processing workers, duration
of employment as factor. 388
389

RESPIRATORY SYMPTOMSsontd.
silica-exposed workers, chronic
   bronchitis risk factor with smok-
  ing, 186

silica-exposed workers, dust expo-
sure and smoking as factors,
330, 335

standardized questionnaire to eval-
uate occupation and smoking ef-
fects, efficacy, 152-153
workplace exposures in non-
smokers, occupational bronchitis
criteria, 184

RESPIRATORY SYSTEM
(See also BRONCHI; BRONCHI-
  OLES; LARYNX; LUNGS)
airflow obstruction as symptom of
  chronic obstructive bronchitis,
   183

occupationally exposed workers,
patterns of injury, 151
pulmonary responses to silica expo-
sure, smoking as factor, 325
radiation and cigarette smoke, in-
teractive effects, 463464
smokers, patterns of injury in
large and small airways and
parenchyma, 148-151
ventilatory function in coal work-
ers, dust exposure and smoking
effects, 308-312

RESPIRATORY TRACT DISEASES
(See also BRONCHIAL DISEASES;
  EMPHYSEMA; LUNG DIS-
  EASES; OCCUPATIONAL DIS-
  EASES)
coal miners, dust exposure and
  smoking as factors, 14-15
historical association with coal
  mining, 289
morbidity and mortality, smoking
  as predominant cause, 142
mortality from nonmalignant dis-
  eases in silica-exposed workers,
   327
mortality in coal workers, 300-304
mortality in cotton workers, 429,
   431
mortality in refinery and chemical
  workers, study data, 362-363
mortality, underestimation with vi-
  tal statistics, 144

537


INDEX

RESPIRATORY TRACT DISEASES
Contd.
silica-induced, dust concentration
  and exposure duration in risk,
   328-329

silica-related, physical factors of OC-
cupational exposure. 325
ventilatory disability in coal work-
ers, cessation of smoking for re-
duction, 313

RISK THRESHOLD
asbestos exposure, confounding by
  cigarette smoking as source of
  bias. 222

lung cancer in asbestos workers,
smoking as source of bias, 222-
224

RISK REDUCTION
lung cancer, cessation of asbestos
  exposure effect, 225-228
respiratory disease in coal miners,
  dust control and smoking cessa-
  tion, 312-313
SEX RATIO

(See also OCCUPATIONAL
GROUPS: OCCUPATIONS;
SMOKING HABIT; WOMEN1
bladder cancer risk, by smoking
habit and occupation, 379-380
changes in smoking prevalence for
selected occupations, 64-65
cotton workers, smoking habits,
404

current smokers by sex, occupation,
amount smoked, 5863
daily cigarette consumption by age
and occupation, 27-31
employment patterns and smoking
prevalence, 23-26
General Electric Company employ-
ees, smoking status by occupa-
tional category and age. 78-81
lung cancer in asbestos-exposed
workers, observed vs. expected
deaths, 214

occupation and smoking behavior,
  current estimates and trends, 11
occupational categories, smoking
  habits by age, 83-96
selected occupations, 66-68

SILICA
(See also OCCUPATIONAL EXPO-
   SURES)

538

SILICA-Contd.
cancer risk in exposed workers,
   341-348

definitions of health effects, 325
disease risk in exposed smokers vs.
nonsmokers, 331-334
disease risk in exposed workers,
summary and conclusions, 348
epidemiological findings among ex-
posed workers, 327-330, 335-336
"free" vs. "combined" forms, impor-
tance to occupational toxicity,
323

industries with significant silica or
mixed dust exposures, 323
pathogenesis of related health ef-
fects, 339-341

population at risk for exposure,
NIOSH survev 323-324
prospective study' data on exposed
workers, 337-338
pulmonary effects in uranium min-
ers, with radiation and smoking,
463-464

research recommendations on
health effects, with other expo-
sures and smoking, 347-348

sILIcOsIs

(See also OCCUPATIONAL DIS-
EASES; PNEUMOCONIOSISl
coal miners, occupational relation-
ship, 289

dust concentration and exposure
duration, risk relationship, 329
dust exposure as risk factor, smok-
ing role, 325

lung cancer in patients, 341-342
lung cancer proportional morbidity
rate in followup of silicotics,
345-346

lung injury mechanisms in exposed
workers, 339-341
pottery workers, early studies of
risk relationship, 328
workers exposed to "pure" silica,
standard mortality ratios, 345

SKIN CANCER
radiation and cigarette smoke con-
  densate in induction in animals,
   456458

SMALL AIRWAYS
(See also RESPIRATORY SYSTEM1


INDEX

SMALL AIRWAYS-Contd.
abnormalities in chronic obstructive
  lung disease, 255
asbestos exposure and smoking, ef-
  fects, 271
changes in smokers, consumption
  and duration of habit as factors,
   255
dysfunction in asbestos workers,
  differences in exposure and
  smoking effects, 258
pattern of injury in asbestos-ex-
  posed workers, 256

SMALL AIRWAYS DISEASE
(See also OCCUPATIONAL DIS-
  EASES; RESPIRATORY TRACT
   DISEASES)
silica-exposed workers, research re-
   commendations, 347

SMOKE INHALATION, ANIMAL
emphysema induction in dogs, with
  radon daughters and uranium
   ore dust, 458
lung cancer induction in rats, with
  radon daughter exposure, 458

SMOKING
(See also WORKPLACE SMOKING]
statistical analysis of independent
   and interactive effects with occu-
  pational exposures, 162-164
synergistic vs. additive effect with
  occupational exposures, 360-361
workplace, environment as factor
  in initiation, 32

SMOKING CONTROL PROGRAMS
(See also WORKPLACE INTER-
   VENTION PROGRAMS1
clinic-based vs. worksite programs,
  validity of comparisons, 489
design and outcome of controlled
  worksite smoking modification
  studies, 486-488
organizational characteristics, other
  factors in program success, 502-
   504
primary objectives of worksite
  smoking modification programs,
   508-509
recruitment strategies of various
  worksite programs, participa-
  tion/attrition rates, 484-485

SMOKING CONTROL PROGRAMS-Contd
silica-exposed populations to reduce
   disease risk. 348
social support, physician's advice,
  nicotine gum, incentives, effica-
  cy, 491498

worksite. evaluation criteria, 479-
480

worksite. implementation. 504-506
worksite. overview of advantages
vs. disadvantages, 477-479
worksite programs to modify smok-
ing. three approaches, 503-504
worksite. review of uncontrolled vs.
controlled studies, 481483, 489-
490

SMOKING HABIT
(See also OCCUPATIONAL
  GROUPS; OCCUPATIONS;
  SMOKING PREVALENCE;
   WORKPLACE SMOKING1
asbestos-exposed workers, multipli-
  cative interactive effects, 9
asbestos workers, controlling for
  differences to reduce confound-
  ing. 219

asbestos workers, synergistic effect
on chronic lung disease mortali-
ty, 246-241

birth cohorts, race- and sex-related
changes in prevalence, 38-53
blue-collar vs. white-collar workers,
by sex and age, 23-26
blue-collar vs. white-collar workers,
initiation by age and sex, 29-32
coal miners. chronic simple bronch-
itis risk factor, with occupational
exposure. 185

coal miners, study data on smoking
characteristics, 291-293
cotton dust-exposed workers, 404,
409

cotton workers, disease risks. 1617
General Electric Company employ-
ees 1985. by occupational catego-
ry, age, sex. 7%81
gold miners, effect with silica expo-
sure on bronchitis symptoms,
186

male birth cohorts 1900-1978.
changes in prevalence. 231
Navajos in U.S. uranium miner
study group. 448. 451


INDEX

SMOKING HABIT-Contd.
pancreatic cancer patients, daily
  consumption as factor, 387
white U.S. uranium miners vs.
  nonminer men, 448

SMOKING PREVALENCE
(See also OCCUPATIONAL
  GROUPS; OCCUPATIONS;
  SMOKING HABIT; WORK-
   PLACE SMOKING)
asbestos-exposed workers, study
  data, 206-209

blue-collar vs. white-collar workers,
11

coal miners vs. US. male popu-
lation, 290

coal workers, 291
cotton workers, study data, 405-408
male birth cohorts 1900-1978, 230
radiation-exposed miners, 446
uranium miners, 448

SMOKING SURVEYS
American Cancer Society, by occu-
  pation, sex, age, 82-96
coal miners, prevalence data, 291-
   293

daily cigarette consumption by oc-
cupation for men and women,
27-31
General Electric Company employ
ees 1985, by sex, age, amount
smoked, 7%81
National Health Interview Surveys,
employment patterns and smok-
ing prevalence, 23-26
National Health Interview Surveys
for 197%1980, by sex and occu-
pation, 58
National Health Interview Surveys,
occupations by category and
code, 57
petrochemical, aromatic amine, and
pesticide industries, prevalence,
360
silica-exposed workers, study data,
325-326

SOCIOECONOMIC STATUS
bladder cancer risk relationship,
   381-382

540

STATISTICAL ANALYSIS
independent and interactive effects
  of smoking and occupational ex-
  posures, 162-164
interactions between occupational
  exposures and smoking, 104,
   109-113

occupational exposure effect on dis-
ease risk, confounding by smok-
ing, 114-123

occupational exposures and smok-
ing, quantifying interactive ef-
fects, 158
occupational exposures, confounding
of risk by smoking, use of com-
parison groups, 122-130
occupational risks, comparability of
internal and external control
groups, 166

THIOCYANATES
serum level measurement to docu-
  ment smoking status in work-
  place studies, 161

TOBACCO SMOKE
aromatic amines, possible role in
  carcinogenesis, 371-372
environmental levels as risk factor
  in nonsmokers, 199-200

TUBERCULOSIS
(See also OCCUPATIONAL DIS-
  EASES)
mortality in silica-exposed workers,
   327
silica-induced, smoking role, 325
workers exposed to "pure" silica,
  standard mortality ratios, 345

Tumorigenesis See CARCINOGENE
  SIS

Tumors See CANCER

URANIUM
(See also OCCUPATIONAL EXPO-
  SURES; RADIATION; SILICA)
dust, carcinogenic effects in dogs,
   458
lung cancer in miners, exposure
  and smoking risks, 446-452
miners, smoking habits, 448
pulmonary effects of exposures,
  with smoking, 463-464

WOMEN
lung cancer risks, 377


INDEX

Workplace See OCCUPATIONAL
GROUPS; OCCUPATIONS

WORKPLACE EXPOSURE STUD-
  IES

(See also RESEARCH RECOMMEN-
DATIONS)

asbestos, establishing risk thres-
hold, smoking as factor, 224-225
asbestos-related mortality, data by
type of exposure, 206-209
cancer mortality relationship,
smoking status as source of con-
founding, 114-122
case-control analyses to control
confounding by smoking, 129-130
chest x ray abnormalities in work-
ers, smoking effect, 154-155
chronic lung disease in occupation-
ally exposed workers, 142-148
confounding by smoking behavior,
sources and control, 114130
control of potential confounding by
smoking, use of comparison
groups, 123

cotton workers, respiratory system
effects, with smoking, 403431
duration and concentration of expo-
sure, determination methods, 162
external control populations, com-
parability with exposed group,
165

healthy worker effect in cross-sec-
tional design, smoking role, 164
healthy worker effect on mortality
risk evaluation, 128
high-risk populations, need for data
on smoking intervention efficacy,
498-500

internal controls, comparable smok-
ing status to control confound-
ing, 129

lung disease risk, with smoking,
summary and conclusions, 169-
170

mortality risk, adjustments when
smoking habits not known, 130-
131

occupation and smoking risks, use
of external vs. internal controls,
123-130

occupational lung disease and ciga-
rette smoking, prevalence in sur-
vey populations, 147

WORKPLACE EXPOSURE STUDIES-Contd
physiological assessment of work-
  ers, independent effects of smok-
  ing, 156

quantification of relative risk in in-
dividuals, 167

quantifying effects in populations,
concepts of smoking interactions,
15%160
quantifying occupational and smok-
ing risks, 160-168
questionnaire to establish smoking
status recommended, 161
relative risk of cancer, smoking
status as source of confounding,
115-122
silica, prospective study data on ex-
posed workers, 337-338
silica, research recommendations
on health effects, with other ex-
posures and smoking, 347-348
statistical analysis of independent
and interactive effects of smok-
ing, 162-164

WORKPLACE INTERVENTION
PROGRAMS
(See also RESEARCH RECOMMEN-
  DATIONS; SMOKING CON-
  TROL PROGRAMS)
asbestos workers, efficacy for smok-
  ing reduction/cessation, 499-500
controlled, characteristics, 483, 489-
   490
controlled studies, data by worksite
  type, procedural characteristics.
   484-485
design and outcome data from con-
  trolled smoking modification
   studies, 486488
evaluation criteria, 479480
general results and research needs,
   17-18
high-risk populations, large-scale
  studies needed, 49&500
implementation, 504-506
methodological deficiencies in com-
  parison conditions, participation
   rates, 491
methodological issues in program
  design, evaluation criteria, 507-
   508
monetary incentives and competi-
  tion, efficacy, 495498

541


WORKPLACE INTERVENTION
PROGRAMS-Contd.
multiple risk factor intervention
  programs, efficacy for smoking
   cessation, 490
organizational characteristics, other
  factors in program success, 502-
   504
overview of smoking control pro-
  grams, advantages vs. disadvan-
  tages, 477479
participant characteristics, program
  intensity, worksite size, outcome
  effects, 489490
physician's advice, efficacy, 493-495
program characteristics, advan-
  tages/disadvantages of various
  approaches, 505306
recommendations for future re-
  search, 507-509
research needed on variables that
  affect program success, 504
review, uncontrolled vs. controlled
  studies, 481483, 489490
social support for nonsmoking, rele-
  vancy in worksite programs,
   491493
summary and conclusions, 509
uncontrolled, without objective
  measures of smoking status, ces-

INDEX

WORKPLACE SMOKING
(See also SMOKING; SMOKING
  HABIT: SMOKING PREVA-
   LENCE)

asbestos workers, multiplicative in-
teractive effects, 9
biological, statistical, and public
health interactions with occupa-
tional exposures, 104-113
cotton workers, disease risks, l&17
lung disease risk, independent and
interactive effects with occupa-
tional exposures, 142
occupational categories, by age and
sex, 83-96

occupational environment as factor
in initiation, 32

occupational exposure studies, po-
tential for confounding, 114-130
occupationally exposed workers,
control groups to reduce poten-
tial confounding effect, 123
recent changes by occupation, age,
and sex, 33-38

workers exposed to respiratory haz-
ards, lung disease risk, 146150

WORKSITE See OCCUPATIONAL
GROUPS; OCCUPATIONS

sation rates. 482

542