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Chapter 5
The Application of Epidemiology to
Selected Research Questions
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5
THE APPLICATION OF EPID=IO~Y
TO SELECTED RESEARCH QUESTIONS
INTRODUCTION
This chapter uses several case studies to illustrate
how epidemiologic strategies and study designs involving
both long-term planning and flexible short-term responses
can be applied to important current research questions.
We have stressed that the development of protocols for
epidemiologic research in air pollution requires substan-
tial amounts of focused interdisciplinary planning and
coordination. Therefore, the purpose of this chapter is
not to write protocols for specific studies. Instead,
for each selected problem dealt with here, we recommend
approaches or guides to particular components of strategy
and design development.
addressed:
.
considered.
The following components are
Selection of a study method.
Selection of study populations.
Selection of exposure variables.
· Selection of effect variables.
Selection of confounders to be considered.
Special opportunities for studies to be
· Limitations on the types of answers possible.
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ACUTE RESPIRATORY INFECTION
.
"Do any current patterns of exposure to air pollutants
lead to increased frequency or severity of acute respira-
tory infections? n
The study methods likely to be of use for this par-
ticular question are the prospective cohort method and
the case-control method. Ecologic studies are not fore-
seeable, because widely reported data on the incidence of
these conditions are lacking. The prospective cohort
method requires the study of a relatively common end
point, perhaps upper respiratory infections, as opposed
to more serious lower respiratory infections (such as
acute bronchitis and pneumonia). To achieve acceptable
statistical power with the cohort method in studying less
common events, large numbers of people must be followed
for long periods, and that creates problems related to
expense and the potential for loss of subjects to
followup.
However, small cohorts (panels) of children could
provide a sensitive basis for studies. The high
frequency of acute respiratory infection among preschool
children (four to eight episodes per year) makes it
possible to detect even small increases in the relative
risk among exposed populations. Thus, an increment of
25% typically could be detected readily in a population
of 200-300 children, whereas such small increments in
chronic disease prevalence would require several thousand
person-years of observation. Acute respiratory infection
in children is readily detected and reported by most
parents, but frequent contact with subjects or their
parents is necessary, because the events are short-lived
and easily forgotten. Methods to validate the presence
of an acute respiratory infection might present themselves
when our ability to measure immune responses in humans
has advanced.
Case-control methods might work nicely for the study
of serious but infrequent infections. Acute bronchiolitis
in infants, for example, can be caused by a number of
viruses and is a frequent reason for hospital admission
of children under the age of 2. Such infections have
been linked with a later risk of developing chronic
obstructive pulmonary disease (COPD) .2 ~ Cases of
bronchiolitis can readily be accumulated by active
pediatric hospital services, and the diagnoses can be
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accurately verified, with viral antibody titers or
cultures if necessary. Controls could be selected from
infants admitted with diagnoses not conceivably related
to air pollution. The youth of the subjects and the
acute nature of the illness make it fairly easy to deter-
mine lifetime exposures, both inside and outside the
home. Exposures are recent enough to permit monitoring
in homes for specific pollutants or for particular
emission sources, perhaps for a sample of the study group.
The specific pollutants of interest in studies of
respiratory infection might be nitrogen oxides, gas stove
emission, passively received cigarette smoke, woodsmoke,
acid aerosols, and recurrent summertime haze and ozone.
If a small-cohort frequent-event approach is taken, it
should be possible to use individual, rather than aggre-
gate, monitoring data on pollutant exposure. With a
large cohort, individual measurements could be made on a
sample to Anchor n or validate the aggregate data.
Cigarette smoking would be a serious confounding
variable in any studies in this field, and it is tempting
to restrict studies to children or nonsmokers. But the
exclusion of smokers from all studies would be a serious
mistake, because cigarette smoke and air pollution might
act synergistically to multiply the risk of developing a
respiratory infection. Smokers would therefore constitute
a useful hypersusceptible or sensitive population for
study. Furthermore, nonsmokers might be subjected to
some degree of risk through passive exposure. Besides
the usual confounders, studies of acute respiratory
infection will have to deal with unusual and difficult
codeterminants of risk, including epidemics in the
community, social class, season, number and age of
siblings, and frequency of contact with other people.
Some special opportunities for studies in this field
can be identified. The utility of national survey
samples--such as the National Health Information
Survey--will be increased by improvements in routinely
collected pollution surveillance data. Countries or
regions with centralized health services can provide
excellent opportunities for studies that require the
recording of discrete events, such as hospital admissions
due to respiratory infection.4 Finally, epidemiologic
surveillance systems that track the response of respira-
tory infection rates in communities to fluctuations in
. . . .
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pollution could prove useful as a preliminary form of
study.
The use of small cohorts with individual exposure
measurements could be a particularly sensitive means for
studying the impact of small excursions above existing
air quality standards. This is one of the circumstances
in which epidemiologic studies might be able to give
answers to threshold questions. The other study designs
mentioned above are better suited to "any-association" or
"dose-response" questions, depending largely on the extent
of detail in the exposure data. Obviously, studies based
on categorical data (e.g., frequency of use of gas stoves,
woodstoves, or kerosene heaters) will be less suitable
for the construction of dose-response curves than studies
based on continuous numerical data. Many studies of acute
respiratory infection will be able to determine which
among numerous pollution sources is responsible for an
effect. But few of them, even if conducted with indi-
vidual measures of several pollutants, will easily be
able to attribute an effect to a specific pollutant.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
"Do any current patterns of exposure to air pollutants
lead to an excess risk of developing chronic obstructive
pulmonary disease (COPD) or to exacerbation of existing
COED?
In many ways, this is the most difficult question for
epidemiologic studies and therefore the one that requires
the greatest care and ingenuity. The incidence of COPD
is relatively low, so prospective studies that use
clinical cases to determine the etiologic role of air
pollution are unfeasible, for reasons of cost and time.
That leaves two alternative strategies: studying the
onset of COPD retrospectively and studying the development
of early markers (physiologic or biochemical) that presage
the clinical disease.
All retrospective methods for studying this question
suffer from the lack of reliable, precise data on indi-
vidual lifetime exposure to ambient pollutants. A
case-control study of COPD would be attractive if this
difficulty could be overcome. Given lifetime residential
histories obtained through interview of the subjects,
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some index of cumulative exposure to pollutants could be
constructed. It would probably require expert subjective
assessment of pollution in various locales at various
past times, inasmuch as measurements would not likely be
available for the early years of the subjects' lives.
m is approach is not unlike the one common to retro-
spective studies of occupational cohorts, except that
fewer variables need to be considered in reconstructing
workplace exposures. The result would be a cumulative
pollution exposure index that would be relatively coarse
and insensitive to the role of individual pollutants.
A case-control study of nonsmokers with COPD is worth
considering because of the major etiologic role of smoking
in most cases. The incidence of COPD in nonsmokers,
however, is extremely low and would necessitate
collaboration of several medical institutions for
assembly of an adequate number of cases. (For example,
in the Tucson cohort, the prevalence of COPD in
nonsmoking adults was 2 per 1,000 persons." 3 ) If air
pollution causes COPD, it probably causes more cases
among smokers than among nonsmokers; therefore, studies
that yield information about the interaction of smoking
and air pollution in the etiology of COPD would be
extremely valuable.
That brings us back to the prospective cohort method.
It is the most effective means for addressing the question
of COPD etiology, if costs can be kept down and the
precision of exposure information and sample size can be
maintained. It should soon be possible to develop
predictive biochemical tests that capitalize on early
injury to connective tissue in COPD. So far, the studies
directed at detecting degradation products of elastin and
collagen appear promising. m e use of rapid decline of
FEV1 or of other measures of pulmonary function as
markers of COPD is desirable, in that rapid decline is
far more common than clinically apparent disease;
etiologic studies can therefore be shorter and cheaper
and have satisfactory statistical power.
Berry, Schlesselman, and others have shown that varying
the number of subjects followed, the frequency of lung
function measurement, and the length of follownp makes it
possible to maximize the chances of detecting an effect
of a given magnitude without wasting resources on excess
measurements. 6 2 2 Table 1 shows the numbers of
169
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subjects required for different followup periods. In
fact, only small panels of subjects (fewer than 100 in
the ~exposed" cohort) are required, if follownp extends
for 3 years and measurements are taken only once a year
Therefore, a large study can follow several cohorts
simultaneously, each with a different pattern of pollution
exposure. The inclusion of multiple cohorts mitigates
the Sample size of two" problem encountered in some
large cohort studies that use only two kinds of popula-
tions (see Appendix C). Perhaps more important, the use
of small cohorts makes it easy to incorporate precise
individual exposure measurements or to apply them to a
substantial fraction of each cohort.
.
Cross-sectional studies on the COPD question should
not be ignored. The first slice in time looked at in a
longitudinal study might be suitable for analysis as an
independent cross-sectional study. This requires
planning from the beginning, to ensure that estimators of
past exposure are available at baseline. Furthermore,
the last column in Table 1 shows that appreciable power
can be achieved in a cross-sectional study, if the
population consists solely of subjects who have had
several years of exposure before testing. For example,
in a two-population study (nexposed" and "nonexposed~),
only 174 persons exposed for a period of 5 years would
have to be studied to meet standard power requirements.
As previous discussions have pointed out, however, this
consideration accounts only for random errors; in the
case of cross-sectional studies of chronic respiratory
disease, the nonrandom error associated with retro-
spective exposure assessment would be a dominant concern
and would limit the types of answers that could be
expected.
A research strategy on the COPD question would be
enhanced by prior consideration of descriptive data on
COPD incidence or mortality. Such data (although not
perfectly reliable) could be used to locate "hot spots,.
where the occurrence of pollution-related cases might be
greatest. Figure 7 is a map of the United States showing
the distribution of mortality from chronic bronchitis
among white females between 1965 and 1971. 2 5 Mortality
among women during this period would presumably be less
influenced by smoking and occupational exposure than
mortality among men. One potentially interesting area
for the location of a study would be the Ohio Valley,
171
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where mortality rates were particularly high in a multi-
state area that included worrisome pollution sources.
Given the limitations of mortality data for respiratory
disease across geographic boundaries, a preliminary
ecologic study would not be advisable. However, pilot
studies in an area of high rates can explore the role of
local artifacts in diagnosis or reporting or the impact
of confounders, such as smoking. Case-control studies
should follow, and then perhaps cohort studies.
Special opportunities for studying the role of air
pollution in the etiology of COPD might be found. One
important opportunity could be provided by the antici-
pated decreases in the emission of acid-precipitation
precursors in some areas. The impact of sudden decreases
on the respiratory health of a surrounding population--
for instance, in a community near a midwestern power
generating plant--would be a potentially fruitful subject
for a cohort study. The growth of lung function in
children offers another opportunity. Rates of increase
in such indexes as FEV1 are sensitive indicators of
toxic lung injury, according to recent studies on the
effects of passive smoking and gas cooking. 2 7 Children
who fail to reach their highest potential plateau have
less reserve lung function and are presumed to be at
greater risk of dangerous decline in function. The
opportunity afforded by studies of heavily exposed
occupational groups or populations abroad should not be
overlooked.
Studies of the exacerbation of COPD call for a
-
strategy entirely different from the strategy for COPD
etiology, because exacerbation is considered acute,
rather than chronic. Small cohorts (panels) of carefully
screened subjects with chronic respiratory diseases can
be followed longitudinally. In an approach very similar
to that recommended for asthma or acute respiratory
infection, the goal is to ascertain the determinants of
the probability of exacerbation in a person over a given
period. Personal monitoring can be incorporated into the
design, to increase the precision of the study.
The kinds of answers that epidemiologic studies might
provide on the COPD question depend largely on the
accuracy of the exposure information used. Further
development of biologic markers that indicate the
breakdown of connective tissue in the lung will increase
173
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Descriptive studies that define the exposed populations
and clarify the nature of woodsmoke exposures under
various conditions should form an early part of the
research strategy on this question. Ecologic studies
comparing disease rates in communities with different
patterns of wood use as fuel can be performed quickly and
easily to form hypotheses and focus on populations at
risk. Case-control studies like the one described in
this chapter for acute bronchiolitis could easily
incorporate information on woodstove use. The major
thrust of the strategy, however, must be to establish
cohorts exposed to woodsmoke for prospective study.
Selecting the exposure variables to be measured
presents several choices. Categorical descriptors, such
as hours of woodstove use per day or concentration of
woodstoves in a neighborhood, must be developed. Indoor
and outdoor source contributions to individual woodsmoke
exposure must be distingusihed. Woodsmoke is a complex
mixture, so various surrogates or index of exposure must
be chosen. These could include benzo[a]pyrene, carbon
monoxide, nitrogen oxides, or respirable particles. Each
would have its own advantages, which would depend on the
end points under study. Modifying factors--such as
humidity, stove tightness, temperature fluctuations, and
house ventilation--might have to be considered. If car-
cinogenicity is of concern, biologic markers of exposure,
such as urine mutagenicity in the Salmonella/microsome
assay or detection of DNA-benzo[a]pyrene adducts in
nonsmokers, might prove useful. We should also note the
recent appearance of a small passive monitor for
polycyclic aromatic compounds. (Personal communication
from Tuan Vo Dinh, Oak Ridge National Laboratory)
The effect measurements in woodsmoke studies could
include symptom frequency, frequency of respiratory
infection or asthmatic attacks, transient or persistent
changes in lung function, changes in lung clearance, and
markers of genetic damage in somatic cells. Reporting of
acute respiratory symptoms in children might be par-
ticularly productive, as indicated by a recent study in
Michigan. The increase in the use of wood as a fuel
in the United states has been relatively recent (except
in some distinct populations, such as the Navajo Indians);
that makes it difficult to assemble groups that had
long-term exposure for studies of chronic effects, such
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as lung cancer. The greatest success could be achieved
with small-panel, time-series studies.
The existence of communities (e.g., in New England and
the Rocky Mountains) that have experienced rapid increases
in the amount of woodsmoke pollution suggests some pos-
sibilities for fruitful studies, particularly if local
ordinances lead to precipitous declines in exposure.
Many populations in developing countries that use wood or
other biomass as a primary fuel in village stoves have
lived under conditions involving extraordinary exposure.
A study of women cooks in central India measured total
daily exposures to benzo[a]pyrene equivalent to the
smoking of 20 packs of cigarettes a day. For several
years, epidemic cor pulmonale (terminal heart failure
usually due to lung damage) has been noted among young
women in Nepal who work at cookstoves.~8 t9 23
These situations are difficult to compare with the
U.S. experience, and the primary usefulness of studying
them would be in determining whether there could be any
possible associations between exposure and a given health
effect and in validating biologic markers. The introduc-
tion of relatively simple and acceptable devices to
reduce pollution from village cookstoves, such as
chimneys and vents, would provide an excellent basis for
health studies and at the same time take action on what
is already perceived as a serious and nearly worldwide
public health problem.8
The types of answers to be expected from foreseeable
epidemiologic studies on woodsmoke are limited. Such
studies are not likely to identify the specific com-
ponents of woodsmoke responsible for an effect. But
dose-response information for an index or surrogate of
woodsmoke could be obtained, particularly in relation to
acute health effects. Epidemiologic studies on this
question should make it possible to weigh the importance
of woodstove emission against that of other prevalent
sources of exposure.
EXPOSURE TO NITROGEN DIOXIDE
nDoes total exposure to nitrogen dioxide, from both
indoor and outdoor sources, lead to or exacerbate acute
or chronic respiratory diseases? n
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It now appears that, except perhaps in a few selected
areas, population exposures to nitrogen dioxide, NO2,
both average and peak, are determined primarily by
emissions from Invented indoor combustion sources.
Therefore, future studies must consider the joint impact
of indoor and outdoor sources of this pollutant. Char-
acterization studies will refine the understanding of the
categorical descriptors of NO2 exposure, but individual
exposure monitoring of relatively small cohorts will
still generally be necessary. Anchoring of aggregate
exposure estimates in a larger cohort through intensive
study of a selected sample is also possible. The
appropriate monitoring equipment is available and awaits
application in full-scale epidemiologic studies.
The frequency of respiratory infection is an important
end point in NO2 studies, to judge by the results of
laboratory animal work. The role of NO2 exposure in
serious respiratory infections among infants has already
been addressed in connection with the case-control study
discussed early in this chapter .2 7 Transient and
persistent changes in lung function and symptom frequency
are also of concern. In particular, new data on the
effect of specific NO2 sources on rates of lung growth
in children need confirmation and expansion. As mentioned
in Chapter 2, results of Japanese studies indicate that
urinary hydroxyproline excretion might provide a useful
early indicator of pulmonary connective-tissue degradation
due to NO2 exposures Further evaluation of the
hydroxyproline marker in population studies involving
high exposure is needed, to clarify the sources of
variability in these measurements.
The development of categorical descriptors for NO2
exposure (e.g., questions concerning kerosene-heater or
gas-stove use that delineate exposure magnitude) will
advance the testing of hypotheses regarding NO2 and
COPD in retrospective studies. The most precise data,
however, will be gained through longitudinal studies of
pulmonary function and measurement of individual
exposures. Once again, studies on acute health effects
should yield data that might eventually be used to
identify a threshold exposure.
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PERS ISTE:NT EXPOSURE TO OZONE AND ACID AEROSOLS
"Does persistent exposure to ozone or acid aerosols
(including sulfates) at high concentrations lead to an
increased risk of developing chronic obstructive
pulmonary disease?"
Average ozone concentrations remain high in some urban
areas of the country and are rising in others where the
density of automobile traffic has been increasing
dramatically. As mentioned in Chapter 3, persistently
high concentrations of acid aerosols (largely sulfur
species) are being reported in some areas. Populations
exposed to sulfates at annual average concentrations of
1 ~g/m3 to nearly 20 ug/m3 can be identified, and
they offer ample contrasts for study. There is a concern
over the potential influence of these patterns of
exposure on the risk of developing COPD. Results of
long-term animal exposure studies support this possibility
and a recent longitudinal study of an ozone-exposed
cohort in Los Angeles pointed to decrements in pulmonary
function among several age groups (unpublished manuscript,
R. Detels, University of California, Los Angeles). The
most important knowledge can now be gained by prospective
cohort studies, which alone will have the capacity to
describe exposure with the needed accuracy. That state-
ment presupposes that specially designed air monitoring
procedures will be relied on in lieu of routinely
collected data. Personal monitoring of a sample of the
cohort must also be used to determine the extent of
misclassification error involved in the use of central,
aggregate exposure data.
Cross-sectional studies, if large enough, will also be
useful and should be derived automatically from baseline
measures in longitudinal studies. Large cross-sectional
studies of pulmonary function in long-term residents of
polluted areas, compared with suitable controls, should
be particularly useful. The availability of standard
population values for pulmonary function that allow
adjustment for smoking is a recent development of note
(unpublished manuscript, A. Miller, Mt. Sinai School of
Medicine). Exposures can be measured accurately only at
or somewhat before the time of lung function measurement,
so the impact of past and current exposures must be
sorted out. Cohorts representing several different
average exposures to ozone should be followed, including
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some with widely contrasting exposures. Optimal sample
size, measurement precision, and control of nonrandom
error must all be considered, to ensure the feasibility
of such a study. Cohort size and followup time must be
kept to a minimum, so that loss to followup, a crucial
source of error in previous studies, can be restricted.
Frequent contact with cohort members is also essential
for this purpose.
EPISODIC EXPOSURE TO OZONE AND ACID AEROSOL HAZE
"Does episodic exposure to ozone or acid aerosols at
high concentrations lead to excess morbidity from acute
and chronic respiratory diseases?"
In addition to the problem of persistent exposure to
ozone and acid aerosols, there is an emerging regional
pattern of summertime "haze" episodes in the Northeast.
These episodes are characterized by high concentrations
of ozone and acid aerosol that are formed in the
atmosphere and transported over wide geographic areas.
Rural areas are affected by this phenomenon, and the
highest seasonal variations in these pollutants might be
found there. That suggests that a successful strategy
might involve study of acute responses to ozone and acid
aerosol during winter and summer in small cohorts of
rural subjects. The most sensitive population imaginabl
would be exercising asthmatics, but any group likely to
be outdoors and active during the haze episodes would be
a reasonable study group. In fact, Lippmann and
co-workers used such considerations in designing their
study of transient lung function changes in children at
rural summer camps in Pennsylvania and New Jersey.t 4
Exacerbation of COPD in rural persons with this disease
would also be an important topic for study, provided that
likely exposures of persons remaining mostly indoors
proved to be significant.
e
The regional episodic haze problem is also ideal for
the use of epidemiologic surveillance networks. Once in
place, these networks could detect increases in adverse
health effects on the basis of hospital admissions,
physician visits, or medication sales. During the summer
of 1984, one haze episode resulted in 7 consecutive days
of ozone above the national standard in the area from
Philadelphia to New York. Morbidity surveillance was
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nonexistent, and mortality surveillance nearly so. The
chief problem in such surveillance will be to separate
out the effects of high heat and humidity, which
invariably accompany these polluted air masses.
The potential chronic effects of episodic ozone and
acid aerosol will remain more difficult to study, in part
because of the relatively recent appearance of the pol-
lution pattern and because of the difficulty involved in
separating persistent from episodic exposures. Again,
rural areas that generally have low exposure to ozone and
primary acid aerosol, except during the summer, might be
preferable sites for studies. Persons without air con-
ditioning who spend much time outdoors would be receiving
the highest exposures. It might be feasible to couple
the-summertime acute studies on children with wintertime
followup of the same children over a period of 2-3
years. The expense of establishing a new cohort could
thus be reduced, exposures to the pollutants in the
summer verified, and the acute-study measurements used as
a baseline for observation of the rate of growth in
pulmonary function.
Given careful planning and adequate time and funding,
currently available epidemiologic techniques could
establish the acute impact of summertime excursions in
ozone and acid aerosol on sensitive populations.
EXPOSURE TO RADON
-
"Does exposure to radon and its progeny at current
indoor concentrations increase the risk of developing
lung cancers
A survey of radon concentrations in soil, water, and
indoor air in various parts of the United States would
assist the development of an epidemiologic strategy on
this question in several ways. First, although several
areas with relatively high radon concentrations in
buildings have already been identified, increasing the
list would expand the options for selecting study
populations and determine the potential size of the
population at risk. For example, a national survey in
Sweden has sampled radon concentrations in approximately
50,000 dwellings.2 4 Second, comparable data on radon
concentrations in numerous areas might be used in a
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preliminary ecologic analysis that combines radon exposure
data with local data on lung cancer mortality. Third, if
some descriptive studies were detailed enough, useful
information on factors influencing the entry, exit, and
transformation of radon in buildings could be generated.
This would sharpen the focus in assigning groups or
individuals to exposure levels and provide better cate-
gorical descriptors of exposure for questionnaires. For
example, it has recently been demonstrated that radon
progeny readily attach to particles found in cigarette
smoke, thereby increasing and prolonging the effective
dose experienced by both active and passive smokers.5
In addition to descriptive studies, case-control
studies of lung cancer in areas with wide contrasts in
radon exposure would be feasible. Relatively large
numbers of cases would be required for adequate statis-
tical power, because the risk is probably low, compared
with that associated with smoking. Natural experiments,
in which exposures within a community vary sharply
according to the specific location of a house or the use
of a different water supply or building materials, should
be actively sought. One such study, comparing residence
in wood versus stone houses, has already been conducted
in Sweden. 3 Aside from such geographically focused
studies, information on radon and lung cancer might be
derived from the large-scale case-control study or
prospective studies mentioned earlier in connection with
lung cancer. Such information will not be very sub-
stantial, because reliable means for evaluating exposure
of such large, heterogeneous populations are still
lacking.
Cohort studies of uranium miners and other types of
miners have successfully demonstrated that radon and its
progeny can cause lung cancer in humans. However, the
least-exposed miner group that showed a significant
excess of lung cancer still had cumulative lifetime
exposures at least several times higher than that likely
to be experienced by residentially exposed persons.~7
Cohort studies (either prospective or historical-
prospective) of residential exposure are therefore not
likely to be large enough to detect the potential excess
risk involved, unless short-term measures of risk that
occur more frequently (such as markers of genotoxicity)
are used. Sputum cytology analysis has been positive in
studies of uranium miners2 and could be clinically
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useful for screening these men, but morphologic abnor-
malities in exfoliated cells might occur so late as to
have almost the same frequency as lung cancer itself.
Chromosomal aberrations in peripheral blood lymphocytes,
however, have also been observed in radon-exposed miners
and in one study of home exposure and might prove to be a
useful end point for residential cohort studies. 7 2 0
Radon has decreased in mines in recent decades, and
many miners' long-term exposures are now comparable with
those of persons in some kinds of dwellings. Further-
more, some homes have been shown to exceed the permitted
occupational radon concentration. The current follownp
of miners, if done carefully and with large enough
cohorts, should be supported, to estimate risks in this
dose range. Recent work in dose modeling has clarified
some of the factors (including dust concentrations)
involved in extrapolating radon dosage from the mine
environment to the home.~°
The most useful direct approach to the radon-lung
cancer question is through the case-control method, so
exposure measures will most often be retrospective and
hence subject to considerable uncertainty. Nevertheless,
radon sources are relatively stable emitters, and,
assuming that changes over the years in exposure-modifying
factors (such as the sealing of buildings) can be
accounted for, retrospective estimates of exposure of
long-term residents to radon are likely to be more
accurate than those of exposure to most other air pol-
lutants. Estimation of rough dose-response relationships
should be possible, if a positive association can be
found. The accuracy of such estimates will depend
heavily on how well local exposure conditions have been
characterized. Questions of attributable risk and
interactive effects with smoking are important and should
be addressed in these studies.
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188
Representative terms from entire chapter:
respiratory infection
