Congressional Research Service
* The Library of Congress *
Washington, DC 20540-7000
March 23, 1994
FROM : Jane G. Gravelle
Senior Specialist in Economic Policy
Office of Senior Specialists
C. Stephen Redhead
Analyst of Biomedical Science
Science Policy Research Division
SUBJECT: Discussion of Source of Claims of 50,000 Deaths
from Passive Smoking
This memorandum is in response to your request for information
on the possible source of an estimated premature 50,000 deaths from
passive smoking effects.
This estimate is much larger than the (disputed) estimate of
3,000 premature deaths from lung cancer due to passive smoking
effects that was reported in a recent study by the Environmental
Protection Agency (hereafter EPA Report).  The 3,000 estimate is
the only one mentioned in a recent article on the cause of death in
the United States  and lung cancer is the only passive smoking
illness that is officially recognized by a government agency.
The approximately 50.000 number was mentioned in testimony by
the American Medical Association which states that passive
smoking may kill as many as 53,000 Americans annually. This
statement in turn appears to be ultimately traceable to an article
published in 1988 in Environmental International.  This article
used existing epidemiological studies (statistical studies of
incidence of disease among human populations) to estimate these
deaths which included, under one set of calculations, 37,000 lung
cancer deaths, 12,800 deaths from other cancers, and 37,400 deaths
from heart disease. (Wells actually reported estimate ranging from
38,000 to 53,000, with a preferred estimate of 46,000)
Each issue of Environment International contains an editorial;
the one in the issue containing the Wells article was directed at
that article. The editorial indicated that the study received mixed
reviews from reference (two recommended publication after revision
and the third recommended against publication on the grounds that
it was to speculative), but the editors chose to publish the paper
despite mixed reviews.
In the following three years there were a series of critiques
and rejoinders related to this paper.  The main criticisms
related to two points; that the evidence, particularly with respect
to heart disease, was at odds with information on physical levels
of exposure, and that there are of a variety of serious problems
with epidemiological studies. The original article and
correspondence are enclosed.  The following discussion elaborates
on those issues.
Generally, there are two ways that one might try to estimate
the number of premature deaths, if any, from passive smoking. One
could rely on estimates of physical absorption of the components of
smoke and then use those estimates to extrapolate based on studies
of the effects of active smoking. These are called dosimetric
approaches. Secondly, one might try to directly estimate the
effects of passive smoking by comparing disease rates of
individuals who are and are not exposed to passive smoke. These
studies are the epidemiological one.  Typically, they compare the
rates of disease in nonsmoking women married to husbands who smoke
and husbands who do not smoke. Obviously, one might be interested
in the extent to which the estimates derived from these two
approaches are similar, or are different.
Consider the lung cancer studies first. Even though these
premature deaths are only a small part of the total estimate in the
Wells article, discussing these estimates will clarify some of the
problems with the Wells estimate.
The recent EPA study estimated a risk for lung cancer of about
30 percent from passive smoking based on epidemiological studies.
This is, according to their analysis of the statistical studies,
nonsmoking wives of men who smoker have 30 percent more lung cancer
than nonsmoking wives of men who do not smoke. This risk is, in
turn, only a tiny fraction of the risk from active smoking
(probably around 3 percent), and the proportion of
passive-smoking premature deaths to active smoking premature deaths
estimated by the EPA is between two and three percent. 
A physical extrapolation approach would tend to yield smaller
effects. According to the EPA report, measures of cotinine in the
urine indicate that, overall, passive smokers have about 1/2 of one
percent of the level of active smokers.  Since the number of
current and former smokers are the same as the number of never-
smokers, the estimated premature deaths annually from passive
smoking for never smokers would be about 600 using a linear
extrapolation.  This number is considerably less than the EPA's
estimate of 2000 (the remaining 1000 estimate was for effects of
environmental tobacco smoke on former smokers who are about half
the number of never-smokers). There us also a section in the EPA
study that discusses extrapolations based on the physical exposure
to passive smoking; these estimates also tend to be smaller that
the epidemiological estimates and some are very low.
These are potential problems with both methods. The physical
extrapolation method used above assumes a linear relationship
between the incidence of a disease and exposure. Based on evidence
from the pattern for active smoking, however, a linear method may
not be correct. The evidence, however, tends to suggest that such
an adjustment would reduce the estimates based on physical
exposure. There is some evidence that disease rises with square of
the exposure or even with higher powers in the case of lung
cancer.  If the disease were to rise with the square of
exposure, then the estimate based on cotinine levels would be only
3 people rather than 600 people. Of course, it is possible that the
disease rises less than proportionally with exposure.  At the
same time, it is possible that there is a threshold which is so
small that individuals are not exposed to experience health damage.
It is also possible that continue is not the best measure of
exposure; some exposure measures show larger and some show smaller
Problems also occur with epidemiological studies. It is always
possible that relationships found with human population studies are
due to chance, even in a perfectly designed study, and while there
are statistical methods that assign probabilities of error, they
are still probabilities. In addition, the precision of the specific
estimates is always in question. 
There are also some specific problems that have been
identified with passive smoking studies. First, the measures of
exposure are based on interviews with subjects or their relatives
and are subject to considerable error. Secondly, the studies might
be picking up the effects of active smoking, through
misclassification of never-smokers as smokers. That is some
individuals who identify themselves as those who never smoked are
actually current smokers or former smokers and they may be more
likely to be married to smokers. Indeed, corrections were made for
this effect in the EPA report, but it is difficult to know whether
they are accurate. Finally, these studies do not or cannot fully
control for "confounders" -- other factors that might be
responsible for the effect that are simply unrelated with marriage
to a smoker. For example, smokers tend to be less concerned in
general about health risks and engage in other behaviors (e.g.
diet, lack of preventive health care) that might be shared with
their spouses and that may be the cause of the health effect.
The EPA chose the epidemiological studies as a basis of their
approach, but they nevertheless relied on the cotinine measures for
several aspects of their estimates (such as extrapolating from the
effects on spouses of smokers to the population in general.
While the estimates from at least some of the epidemiology
studies are significantly larger than the estimates of physical
exposure, these results are not magnitudes apart. The same cannot
be said, however, for the Wells estimates of deaths from heart
disease. Using the same type of linear physical extrapolation would
result in 700 deaths from coronary disease for never smokers, and
perhaps another 350 for former smoker, with a total of about a
1000. The portion of the Wells' 53,000 estimated from the
epidemiological studies, even for several years ago, is 37,000, a
number that is enormously larger.
This large estimate occurs because the epidemiological studies
show a very high risk estimate for passive smoking relative to
active smoking for heart disease and not for lung cancer. For
example, Wells indicates a 30 percent additional risk for heart
disease for males and a 20 percent rise for females, as compared to
a 70 percent risk for smokers. These relative risks are enormous
compared to both the dosimetric ratios and to the epidemiological
results for lung cancer. Note that although the risk ratios are not
that different from lung cancer, the absolute risk estimates are
much larger. The risk of lung cancer for nonsmokers is very low,
and any percentage of a small number is still a small number. The
risk for heart disease is much larger initially, and therefore any
significant percentage change in the risk is larger, Put another
way, even the epidemiological studies of lung cancer produced
passive-smoking related deaths of less than 3 percent of active
smoking related deaths, while the heart disease studies produced
estimates that were 26 percent of active smoking related deaths.
The biological plausibility of passive smoking effects on
cardiovascular disease has been the subject of some discussion.
Both Wells and Sleenland refer to a 1991 review article by Glantz
and Parmley that suggested that passive smoking may, in
experimental studies, promote the formation of plaques in blood
vessels, increase the tendency of blood platelet cells to aggregate
and form clots, and reduce the oxygen-carrying capacity of the
blood.  There are limited data to support or refute these
hypotheses. For example, while some studies of nonsmokers found
that passive smoking appears to promote platelet aggregation,
parallel studies of active smokers have not consistently shown any
effect on platelet function. 
Among the chemical components in passive smoke, carbon
monoxides and nicotine are the most likely to adversely effect
cardiovascular performance. Carbon monoxide binds tightly to
hemoglobin and diminishes oxygen transport in the blood stream.
Nicotine acts in the brain and throughout the body, promoting the
release of adrenalin and increasing heart rate and blood pressure.
Although these effects might impair performance, exposures from
passive smoke are generally thought to be at concentrations below
those at which physiological changes would occur in healthy
The most likely explanation of these large risks from passive
smoking epidemiological studies for heart disease is the absence of
control for other factors.  There are many important concerns
about health risks in general. In general, studies do not, and
perhaps cannot, control for many of those factors. If smokers;
wives share in these behaviors, the relationships found in the
epidemiological studies are spurious.
The Wells estimate of passive smoking deaths from cancers
other than lung cancer is even larger relative to active smoking
deaths than is the case of heart disease--about 50 percent. Again,
these cancers are influenced by many other factors and the same
general criticisms can be made about these epidemiological
estimates as in the case of heart disease.
In sum, this analysis suggests that the Wells estimates are so
high relative to measures of physical exposure that they seem
implausible. It also suggests that the absence of controls or the
inability to control for other factors may be a major problem in
relying on epidemiological estimates of the health effects of
 Environmental Protection Agency. Respiratory Health Effects
of Passive Smoking: Lung Cancer and Other Disorders. December
 J.Michael McGinnis and William F. Fooge. Actual Causes of
Death in the United States. Journal of the American Medical
Association. November 10, 1993, pp. 2207-2212.
 Statement of the American Medical Association, Health and
the Environmental Subcommittee, House Committee on Energy and
Commerce, Rn Adverse Health Effects of Exposure to Environmental
Tobacco Smoke, July 21, 1993.
 A. Judson Wells, An Estimate of Adult Mortality in the
United States from Passive Smoking. Environmental International.
Vol. 14, No.3 1988, 249-265.
 Letters from Alan W. Katzanstein, Peter M. Lee and Larry
Holcoim criticizing the Wells results; a clarifying letter from
Takoahi Hirayima, a rebuttal to Katzanstein and Lee from James L.
Repace and Alfred H. Lowrey, and a response from Wells were
published in 1990 (Vol. 16, No. 2, pp 175-190. In 1991, a letter
from Stanton A. Glantz criticizing Lee was published along with
Lee's reply (Vol. 17, no. 1, pp. 88-91). Later in 1991, a
response of Lee to the 1990 letters of Repace and Lowery, and
Wells, a letter from Muin J. Khoury clarifying a point raised in
Lee's letter, a joint letter from Glantz and Lee clarifying an
issue raised earlier in the year, and a response from Repace and
Lowrey, and Wells to Lee's letter were published (Vol. 17, no. 4,
370-387). In 1992 (Vol. 18, No. 3, pp. 315-317, 321-325) another
letter from Lee and response from Wells was published.
 A more recent paper of the same general type as the Wells
paper has been published on heart disease. See Kyle Sleenland,
Passive Smoking, and the Risk of Heart Disease, Journal of the
America Association, Vol. 267, No. 1, January 1, 1992.
 Of course, the original estimates of the effects of active
smoking on disease are based on epidemiological studies in large
part as well, but there are some problems that occur in passive
smoking epidemiological studies that are not as serious in active
 The risk of lung cancer in smokers and ex-smokers depends
on intensity, duration, and in the case of ex-smokers, time
elapsed since quitting. Passive smoking would involve three
percent of the risk of active smoking if there is a ten fold
active smoking risk (i.e. smokers have an additional estimated
risk of lung cancer that is ten times the disease rate of non-
smokers) which is typical of current estimates of the risk for
women as reported in the 1989 Surgeon General's Report (Reducing
the Health Consequences of Smoking. U.S. Department of Health
and Human Services, DDHS Publication No. (CDC) 89-8411). In
general the estimates of deaths from passive smoking, the EPA
actually used the additional risk (of wives married to smokers as
compared to wives married to non-smokers) in the U.S. passive
smoking studies, which was about 20 percent. If studies from all
countries are considered, the estimated risk from these studies
was 30 percent.
 The estimated attributable deaths from lung cancer due to
active smoking are 118,000. See C. Stephen Redhead, Mortality
and Economic Costs Attributable to Smoking and Alcohol Abuse,
Congressional Research Service Report 93-SPR, April 20, 1993.
 EPA Report, pp. 3-43.
 To extrapolate, multiply the percentage of cotinine by
the ratio of ever smokers to never smokers, and by the number of
deaths attributable to active smoking.
 Surgeon General's Report, p. 44.
 The argument has been made for a relationship in which
passive smoking can have large effects relative to active smoking
for some specific events in laboratory settings, which is largely
attributed to increased sensitivity of some nonsmokers. See
Stanton Glantz and William Parmley, 1991, pp. 1-12. Circulation
is a publication of the American Heart Association.
 For a discussion of the methods used by the EPA in
combining existing studies and the findings of studies published
later, see Appendix A in Cigarette Taxes to Fund Health Care
Reform, by Jane G. Gravelle and Dennis Zimmerman, Congressional
Research Service Report 94-214. March 8, 1994.
 Glantz and Parmley (1991).
 Samet, J.M., Environmental Tobacco Smoke, In
Environmental Toxicants, ed, M. Lippman, New York Van Rostrand
 U.S. Department of Health and Human Services, The Health
Consequences of Involuntary Smoking, 1986, Surgeon General's
Report, DHHS Publication Number (CDC) 87-8938.
 This position is taken by Gary L. Hubert, Robert E.
Brockie, and Vijay K. Mahajan in a paper written for the layman;
Passive Smoking and Your Heart, Consumers Research, vol. 75.,
April 1992, pp. 13-19, 32. These authors consider the results in
the Wells and Sleenland studies biologically implausible, and
also note that six of the nine epidemiological studies show
causes of heart disease (e.g. that, lack of exercise, lack of
preventive health cure) that may be engaged in by smokers. That
is, there is much evidence that smokers tend to be less
relative risks that are in excess of risks estimated for active
smokers and that most have very few controls for other factors
that might effect heart disease.