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Chapter 4 Concepts and Strategies in Planning Epidemiologic Studies on Air Pollution

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4 CONCEPTS AND STRATEGIES IN PLANNING EPIDEMIOLOGIC STUDIES ON AIR POLLUTION INTRODUCTION - This chapter addresses the principles that underlie the epidemiologic approach to air pollution research. Because ambient air pollution is generally less severe than in previous years, it is harder than it once was to detect most adverse health effects of pollution with a high degree of certainty. Research strategies that used to be demonstrably successful need further development and refinement if they are to be equally successful in solving the major research problems that remain. Initial success in protecting the public from the effects of air pollution has led to a situation in which the research questions must be more precise and the strategies chosen to address them more focused. The need for precision makes it necessary to seek out appropriately sensitive research tools and methods that will be capable of linking today's exposure with today's and tomorrow's health effects. This discussion of research strategies for the epidemi- ologic study of air pollution is guided by several prin- ciples. First, the development of research strategies and the specification of research questions must precede the creation of specific study protocols. Second, epidemiology should be part of a larger framework in which epidemiologic, toxicologic, and clinical studies inform, complement, and reinforce each other. Third, epidemiologic studies of air pollution should be highly sensitive to small risks of disease, because large numbers of people are exposed; to provide credible estimates of those risks, they will require careful attention to all potential sources of error at every 127

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phase of their design and conduct. Fourth, the multi- faceted nature of most air pollution problems requires that planning in epidemiology be interdisciplinary, involving collaboration between different scientific disciplines and between research sponsors and inves- tigators. Fifth, the link between epidemiology and regulation will be a two-way street, with research planning illuminated by a clear understanding of the practical issues and constraints involved in regulation, and the regulatory process influenced by the product and capabilities of research. COMMUNICATION OF EPID=IO=GY W ITH OTHER RESEARCH DISCIPLINES Optimal use of the epidemiologic approach requires that it communicate with the parallel disciplines of clinical research and animal toxicology. This is distinct from the development of multidisciplinary research teams. Communication between scientists in the separate disciplines is essential and should not be limited to scientists who are perceived to be working on the same research questions. This communication can always benefit from administrative sponsorship and encour- agement, including attention to such mundane matters as attendance at conferences, the locations of offices and laboratories, and participation in strategic planning of research and development of individual research projects . Interdisciplinary contact will improve any epidemi- ologic strategy in air pollution in at least three ways. First, results of experiments in the laboratory and clinic will generate useful hypotheses for epidemiologic studies. Examples are the observation of cellular, whole- animal, or human adaptational responses to irritants as a basis for studying the responses of various groups to short-term pollution episodes and the observation of a synergistic effect of two pollutants as a basis for selecting communities potentially at high risk. Second, clinical research and toxicology are needed to provide better epidemiologic research tools. The development and validation of short-term biologic markers that reflect long-term respiratory damage constitute a good example. Laboratory investigators concentrating on disease mech- anisms or therapy are often unaware of the potential applications of their work in population studies. For 128

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instance, a diagnostic test that is considered to be superfluous or too inaccurate for clinical work might be highly appropriate for testing large populations, because of its low cost and noninvasive nature. Research and development activity that leads to new research tools for epidemiology should be distinguished from empirical research on disease mechanisms and perhaps require separate administration and funding. Third, as discussed below, evidence from clinical research and toxicology is used by epidemiologists to strengthen the inference of causality in observed relationships between air pollution and health effects. Epidemiologic activity also contributes to clinical research and toxicology. It can be an excellent source of hypotheses for laboratory studies and, more important, provide an outlook on disease that is critical for setting priorities. Apart from its ability to produce data and answer specific research questions, epidemiology offers a perspective and a set of concepts that can be used to guide efforts in disease prevention and research design. CONSTRUCTING APPROPRIATE RESEARCH QUESTIONS ~ m e epidemiological method is the only way of asking some questions in medicine, one way of asking others, and no way at all to ask many. Research planners can reduce the chances of investing in inappropriate or inconclusive studies by clearly identifying research questions in advance. We refer here to a research question as a broad statement of a problem, rather than a specific epidemiologic hypothesis for an individual study. Major air pollution research questions seldom emerge ab-initio from the intellects of creative scientists. Most are public health questions that are developed through interplay of the interests and capabil- ities of the scientific community with extrascientific forces, such as the availability of research funds and the regulatory process. Once a question has been articu- lated and is determined to be important from the stand- point of public health, research planners have the goal and responsibility of finding the most productive inves- tigative strategy or determining that epidemiologic studies are not feasible. In practice, an iterative process is used both to develop and refine the formulation 129

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of research questions and to match each formulation with the optimal strategy. The cycle of marshaling facts to make a question explicit, devising a strategy, and then refining the question with new facts is parallel to the cycle of hypothesis-test-hypothesis that takes place at the level of individual studies. In this type of applied research, the development and refinement of the question and of the strategy are inseparable, and the investigator contributes equally to both. The importance of specifying research questions cannot be overemphasized. As in all scientific disciplines, epidemiologic research questions begin in a rather general form and are pruned to testable hypotheses that form the basis for design of individual studies. Every epidemio- logic study of the adverse health effects of air pollution has to be crafted around the pollutant in question and the adverse effect under consideration. The characteris- tics of the population at risk, the time between exposure and effect, and the amounts of exposure needed to produce an effect of a given magnitude are specified to some degree in the formulation of a study hypothesis. These elements of a hypothesis usually cannot be specified to the last detail; but, for a hypothesis to be useful, some specification of each element must at least be implied. Each study must conform to various investigative constraints. These constraints, which must be appreciated early in planning, are imposed by such factors as: . The frequency and natural history of the disease. The rate and the extent to which exposure to the pollutant in question changes over time. The availability of biologic markers of exposure or early effect. Other known or suspected causes of the health effects in question. The overall research strategy has to be chosen with the best possible understanding of these four separate dimensions, and the detailed research protocol has to be designed to take them fully into account. The more we recognize that exposures to pollutants change and that given diseases have various causes, the more challenging 130

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it becomes to design a penetrating and efficient epidemi- ologic research protocol. Protocols are most penetrating and rewarding when the detailed research plan focuses on a single answerable hypothesis. The few exceptions to this important general rule include broad epidemiologic surveys designed explicitly for surveillance and the development of new hypotheses. Epidemiology can be used to produce several different kinds of information about air pollution and health. The kind of information sought depends on the goals of the researcher. The remainder of this section discusses six types of broad research questions that can be addressed epidemiologiclly and briefly describes the capabilities of epidemiology to answer each type (for a more complete discussion of these issues, see, for example, Morris's Uses of Epidemiology 6 ) : 1. How does the state of health of a particular community with respect to disease Y compare with that of other communities? With itself over time? 2. What is the natural history of disease Y? clinical spectrum? How does it progress? 3. Is there any association between exposure X and disease Y? Is the association causal? 4. How much does the risk of disease increase as exposure increases (dose-response relation)? Is there a magnitude of exposure for which the disease risk is zero (a threshold)? 5. What are the risks of disease among various groups in the general population? 6. How much of disease Y is due to exposure X? How much will be prevented if exposure is reduced? Question 1, regarding the monitoring of the health of a population, can be addressed only with epidemiologic methods. The relation of this question to air pollution concerns is indirect, however, except for its role in identifying study populations on the basis of contrasting disease patterns. Question 2, about the pathogenesis and natural history of a disease, can be answered through clinical observation and through epidemiology; but this 131

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type of question is rarely at the center of interest in air pollution studies, because there appear to be no unique fair pollution diseases. n Moreover, although epidemiology can undoubtedly contribute to the under- standing of how an exposure results in disease, detailed information of this kind is normally best provided by intensive clinical and laboratory studies. Most applications of epidemiology in air pollution research have been to answer questions about correlations and causal relationships between air pollutants and various human health effects--Questions 3, 4, and 5. To address them, the epidemiologist normally uses the measure known as relative risk, the ratio of the incidence or prevalence of an adverse effect in one population to the incidence or prevalence in another population with a different degree of exposure. Epidemiology can be very effective in answering Question 3, about the existence of any association between air pollutants and disease, particularly if the relative risk involved is large (sometimes arbitrarily defined as 3.0 or greater).14 In such a situation, it is usually most sensible to compare populations at highest exposure with those whose exposures are low or nil. If the relative risk is extremely large and the disease is relatively rare in nonexposed persons, the association will often be noticed first by clinical observation, as in the case of the relationship between vinyl chloride and angiosarcoma of the liver or between asbestos and mesothelioma. It is reasonable to presume that, in most populations without extreme exposure, relative risks of overt clinical disease associated with air pollution are of low to moderate magnitude (approxi- mately 1.2-3.0). Detection and accurate quantification of effects of this magnitude present the greatest methodologic challenges to contemporary epidemiology. Nevertheless, because it is unethical to conduct studies involving deliberate long-term exposures or acute exposures that might produce irreversible effects, epidemiologic studies will remain the only way to detect pollution-related forms of common chronic or serious acute diseases in humans. Epidemiologic studies of air pollution have much greater limits in providing finely tuned information about dose-response relationships or about thresholds or 132

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"safe levels (Question 4), particularly when small relative risks of chronic diseases are produced by years of low-dosage exposure. In those situations, it is extremely difficult to discriminate, with the necessary degree of precision, among populations with relatively minor differences in exposure, for instance, long-term exposure to ozone at 0.08 ppm versus 0.12 ppm. In addition, if the amounts of individual pollutants are highly correlated and tend to rise and fall together from time to time and place to place, the role of each pol- lutant can be difficult to isolate. Larger exposures can be studied to construct models that simulate the behavior of pollutants at lower dosages, but the reliability of mathematical extrapolation is limited by its dependence on unavoidable and untestable assumptions about the dose-response relationships. Future studies will gradu- ally become better at providing quantitative information about the relationships between air pollutants and health, if the techniques for assessing exposure and effect mentioned in this report are developed and if research planning is appropriate. Epidemiology, the basic science of preventive medicine and public health, views disease at the population level, but it can be used to predict the risks of disease in individuals or groups with various characteristics of interest (Question 5). By virtue of the mandate of the Clean Air Act (if for no other reason), it is essential to understand the range of susceptibility to air- pollution-related disease in the general population. Except in a few instances of controlled-exposure studies of volunteers with defined characteristics, such as pre-existing illness, epidemiology is necessary to identify high-risk groups. But precise determination of dose-response relations for each sensitive group is generally not feasible today. The epidemiologic approach is uniquely suited to answer Question 6, although it seems to have been asked only rarely in relation to air pollution. This type of question, which deals with attributable risk rather than relative risk, asks how much of the overall burden of disease in a population is attributable to air pollution over the entire range of exposure. The answer has obvious and important public health implications, because it indicates the total amount of disease that is potentially preventable and the amount that would not 133

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occur if air pollution were reduced. Results of research to answer this kind of question are useful in making decisions about reducing exposures across the board, regardless of local or individual variations in suscep- tibility or risk and regardless of the relative impor- tance of direct effects and synergistic effects, which are more difficult to know ahead of time. Epidemiology offers a direct means for predicting and later assessing the public health impact of changes in the environment, whether positive or negative, deliberate or unintentional. In summary, Questions 1 and 2 are fundamentally epidemiologic, but are likely to be of limited interest in EPA's air pollution activities; epidemiology has made and can continue to make substantial contributions toward answering Questions 3 and 5 and, to a smaller extent, Question 4; and the epidemiologic approach has scarcely been applied to Question 6, although that application might be valuable. CONS IDERATIONS IN STUDY DES IGN, ANALYS IS, AND INTERPRETATION Epidemiologic projects concerning air pollution are among the most difficult to design. One reason is that ambient air pollution adds small increments to the respiratory morbidity risks of large masses of people, rather than large increments to the risks of a few. The dynamic and complex nature of air pollution makes it particularly difficult to measure, and its very nature surrounds it with confounding factors, such as temperature and humidity. Study design thus affords little margin-- yet frequent opportunities--for error. Furthermore, epidemiologic studies, unlike laboratory experiments, are not easily repeated, so elimination of potential errors during study design is of paramount importance. Evalua- tion of all potential errors (such as that caused by the combination of very low exposure and low risk of effect) might lead study planners to conclude that epidemiologic studies are not feasible for providing the particular information desired. The design of each study is a multistage process that begins with the extraction of a specific hypothesis from a general research question and ends with detailed budget estimates. In between, the designers must decide what 134

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exposure and what outcome are most pertinent and which measurements of each to use. They must then identify potential confounding variables, choose a study method and study populations that accommodate the hypothesis, and plan for the eventual analysis and interpretation of the data. This by no means involves a rigid sequence; the order of the steps varies, and often a decision about one step contains or implies decisions about others. Nonetheless, each step plays a distinct role in the study's integrity and the certainty that can be attached to its results. The overall goal is to design studies so as to increase their validity in detecting and estimating the magnitude of the relationships between air pollution and health. Validity has two components: sensitivity and specificity. Sensitive studies have a low probability of labeling a harmful situation as harmless, and specific studies have a low probability of labeling a harmless situation as harmful. Ideal studies are sensitive enough to detect small but widespread effects, yet specific enough to discriminate real from spurious effects. The complexity of the relationships among all the variables that could affect results of air pollution studies has two important implications: Study design and planning require expertise regarding the concepts of epidemiologic research design. The success or failure of future studies will depend increasingly on how well exposure, effect, and confounding variables have been characterized during study planning. Study designers must have as much prior information as possible concerning the distribution of the factors responsible for nonrandom errors and confounding in the various populations being considered for study. The information can be inferred from previous studies of similar populations or obtained directly from the study populations themselves either before or during the study in question. If the information is obtained during planning, it can be used to alter the design of the study, change sample sizes, or influence the selection of study populations. Random errors (and nonrandom errors that behave as random ones in populations) can be 135

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complete data on individual residential and occupational histories, exercise and other personal habits, and perhaps even preventive and curative medical expenditures. In an effort to uncover other data sets of potentially high value but relatively low cost, research planners should investigate the possibility of working with insur- ance companies, providers of prepaid health care, and agencies that collect DRG records on hospital admissions. In some cases, such groups might have mortality and morbidity data of high quality coupled with data on residential histories. These latter data are important if links between air pollution and chronic illness are to be investigated. By the same token, some international data bases might have great utility in epidemiologic analyses. Data from countries that have national health- insurance programs might permit not only cross-sectional analysis, but also time-series or longitudinal studies. These data, if available, will be most useful if they originate in countries where ambient air pollution data are of high quality. COST AND INFORMATION m e feasibility and limits of epidemiologic strategies are determined by their costs, as well as by their bene- fits. Estimating the productivity and cost-effectiveness of various ways to answer specific questions has become an integral part of epidemiologic research planning. For this purpose, benefits are usually conceived of as infor- mation value--the degree to which the study's results bridge the gap between the question and its definitive answer or provide spinoff knowledge for other studies. The benefits of a particular study are a function of its pertinence and of the quality and amount of information it delivers. Comparisons of the relative productivity of optional research strategies and studies might contribute more than any other planning effort to the establishment of research priorities and the ultimate refinement of question and design. Cost considerations can enter at two levels of planning. At the individual study level, the inves- tigator strives to reduce costs as much as possible without compromising the information value of the study. At the strategic level, the planner balances information 152

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needs versus costs and distributes many kinds of resources over a collection of studies. Planning at these two levels is interdependent, because the relative costs of possible studies are needed as input in the development of the research strategy, and the evolution of the strategy determines which study designs receive the most thorough cost estimation. Cost and productivity analysis must be viewed as an inherent part of the process of planning overall strategy, and not simply in terms of proposals for individual, isolated studies. The range of epidemiologic study costs is particularly wide, and the relationship between cost and information value is remarkably unpredictable. Some very inexpensive studies provide information of enormous value, and some large and expensive ones contribute little. The infer- ential value of a study often has more to do with its timing and context than with its cost. In most air pollution studies, it is easy to spend large amounts of money by directing resources at the wrong potential sources of error. For example, greater precision in exposure measurements might be unprofitable if sample sizes are inadequate or study populations are poorly characterized. A research program that aims to produce the best possible epidemiologic studies will have to include funding for complementary nonepidemiologic research, including methodologic and technical development and exposure characterization. Technologic research and development, designed to provide better tools for exposure and effect assessment, must be closely woven into epidemiologic research strategies. Some of the barriers to progress are technologic, just as others stem from ignorance of the biology of disease or the limita- tions of study method. From the viewpoint of the strategic research planner, investment in critical technology is cost-saving--when appropriate technology is lacking, it might be impossible to answer contemporary questions within reasonable costs. The removal of technologic constraints can often be hastened if scientists clearly specify their needs for research and development. An obvious example is the lack of a personal monitoring badge for nitrogen dioxide that can measure short-term exposures. The limits of epidemi- ologic research depend in part on the changing state of the art of measurement in several disciplines, so they 153

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differ from one problem to another and from one time to another. THE MILIEU OF EPID=IO~IC BESEECH The development of productive epidemiologic strategies in a difficult field like air pollution research will require time, organization, and patience. The creation of the necessary milieu for such research depends on several factors: Stable administrative and financial support. Adequate amounts of overall funding. An appropriate range of contact with sponsoring and regulatory agency personnel. Provisions for training and career development of new scientists. . Opportunities for assembling multidisciplinary research groups consisting of epidemiologists, atmospheric scientists, statisticians, and health effects scientists. . Opportunities for interaction among epidemiologists, clinicians, and toxicologists. Some potential adverse health effects of current air pollution can be detected only through serial observations over time. Such studies often entail followup of popula- tion groups for several years by well-organized research teams led with an exceptional degree of administrative skill. Successful examples of long-term studies include the 25-year British study of a cohort of children from birth to young adulthood and the Harvard Air Pollution Health Study of the growth and decay of lung function.5 2 6 The need for administrative and financial stability also applies to a sequence of closely linked studies. The Environmental Protection Agency's record of support for epidemiologic studies since 1970 is one of cataclysmic variation, from strong support to nearly complete with- drawal of funds, in spite of heavy reliance on epidemi- ologic research for risk assessment and standard-setting. A minimal long-term base budget for epidemiologic studies should be considered. With it, the research community 154

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could develop confidence in the stability of resources necessary for long-term studies of exposed populations. The conduct of long-term studies or of a sequence of studies in a research strategy relies on some degree of isolation from short-term changes in federal research managers and agency priorities. However, a portion of the epidemiologic research program should have the flexibility to respond quickly to short-lived oppor- tunities or demands and in so doing work closely with research sponsors and regulators. The expertise for designing and conducting epidemi- ologic studies of air pollution is a rare resource that, once established, needs to be cultivated and maintained. Mechanisms to encourage the training of qualified epidemic ologists and to assist in their career development are needed. Continued failure to provide the appropriate milieu for studies will have a downward-spiraling effect: many young and qualified investigators will avoid air pollution problems--a situation that will lead to a further decline in the performance of epidemiologic studies, which in turn impedes the recruitment of new trainees. . - the successful completion of epidemiologic studies on air pollution requires a continuing collaboration among members of various disciplines, including epidemiologists, atmospheric scientists, health effects scientists, and statisticians. It is essential that all members of a research team be active in the initial planning of a study to optimize the use of pertinent information and tools available from different fields. Monitoring specialists must be involved in population selection on the basis of characterization data and must help determine which types of exposure data need to be collected to evaluate the biologic model of concern. It is equally important for health effects scientists to be involved in planning, to ensure that the biologic markers or indexes of specified health effects are matched to the pollutants being monitored. The sensitivity and specificity of techniques, the appropriate time for sampling, and the doses of material received by target organs need to be considered. Statisticians are essential in planning, to help to ensure that data of the appropriate type and amount will be collected and that problems in data reduction, modeling, and analysis are anticipated. 155

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The difficulty and necessity of establishing multidisciplinary groups in the framework of existing academic and government research institutions must be recognized. And it is necessary for the epidemiology units to interact with clinicians and animal toxicologists in the same or other institutions. Five-year grants, specialized centers of research, and multiyear cooperative agreements are some of the mechanisms possible for creating stable and productive research groups. It is important to incorporate appropriate peer review of these centers and long-term projects into the funding process, to help to ensure quality. EPIDEMIOLOGIC DATA AND THE REGULATORY PROCESS At the heart of the regulatory process for ambient air pollutants in the United States is the determination of approximate "safe" exposures to specific pollutants. In some instances, for some aspects of the standards, epi- demiologic data can provide the direct basis for such determination. In other instances, epidemiologic studies cannot yet provide the type of quantitative answer required for control of a particular pollutant. Even in the latter case, the determination of a standard will hardly rely on a single definitive study, and standard- setting inevitably involves the careful weighing of many pieces of evidence of various kinds. It is often not recognized that it is the cumulative force of different studies (each of which could be faulted in one respect or other) that gives strength-to the data. Each piece of evidence can contribute to regulatory decisions; in the process of making regulatory decisions, the nature and extent of the uncertainty attached to each piece must be carefully evaluated. Although the proper domains of ~science" and "regula- tion,~ or risk assessment and risk management, are becoming well understood, problems of communication remain. Those charged with the responsibility of making decisions might find it difficult to understand why straightforward answers to simple questions are not forthcoming. Attempts (praiseworthy in themselves) to avoid overinterpretation of data can be interpreted as disbelief in the significance of any data; efforts to reduce what must remain subjective to a formal quasi- mathematical process, which the data base might be too 156

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fragile to support, might mislead those who are unfamiliar with the details of studies into believing that the data are stronger than they really are. Such difficulties cannot be resolved by refinement of data, although that is always desirable. What is needed is the opportunity for those who analyze the data in detail or participate in collecting them to exchange ideas with those who are involved with policy, until each side is sure that the other fully grasps the strengths and weaknesses of the data being relied on. One of the objectives of this chapter has been to describe how uncertainty in epidemiologic studies of air pollution might be characterized, so that it can be captured and conveyed properly to policy-makers. This uncertainty must be weighed against the uncertainty that has been built into the process for setting standards and margins of safety. Epidemiology has many uses in protecting the public from air pollution, beyond the setting of specific stan- dards. Epidemiologic studies can point out areas or major pollution sources that need regulation or some form of intervention and can monitor the health of communities, to assess the results of favorable or unfavorable changes in pollution. Research that is directly applicable to standard-setting should not always take priority over research that is needed for the understanding of broader health issues. Finally, evidence of safety is not the converse of evidence of risk; safety is often much harder to demon- strate. m at is the critical difference between the interpretation of studies that find an effect and studies that do not. There are several reasons for the differ- ence: statistical power of studies might be adequate to show large effects, if they are present, but not to exclude smaller effects that are of regulatory interest; nonrandom errors might be more easily dealt with in positive studies; clear demonstration of an effect in one population segment might create a presumption of effects elsewhere that is not balanced by similarly clear demon- stration of the lack of effects in other segments; and control measures might be required if a small part of the population is affected, but not rendered superfluous if a large part is shown to be unaffected. Thus, good large studies with negative results can often have less meaning 157

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than smaller poorer studies that are positive. Fairness is not the issue; negative studies, no matter how large and well conducted, can rarely be used to exclude important health effects in other populations and other circumstances. REFERENCES 1. Bennet, B.G., J.G. Kretzechmar, G.G. Akkland, and H.W. de Koning. Urban air pollution worldwide. Environ. Sci. Technol. 19:298-304, 1985. Berry, G. Longitudinal observations: Their usefulness and limitations with special reference to the forced expiratory volume. Bull. Physio-pathol. Respir. 10:643-655, 1974. 3. Cerkez, R., and A. Knezevic. Study of Pollution and Management of the Environment in the Urban Area of Sarajevo. Sarajevo, Yugoslavia: Institute of Hygiene and Environmental Protection and Radiological Protection, 1983. 60 pp. 4. Cohen, B.H., W.C. Ball, Jr., W.B. Bias, S. Brashears, G.A. Chase, E.L. Diamond, S.H. Hsu, P. Kreiss, D.A. Levy, H.A. Menkes, S. Permutt, and M.S. Tockman. A genetic-epidemiologic study of chronic obstructive pulmonary disease: 1. Study design and preliminary observations. Johns Hopkins Med. J. 137:95-104, 1975. 5. Colley, J.R.T., and D.D. Reid. Urban and social origins of childhood bronchitis in England and Wales. Br. Med. J. 2:213, 1970. 6. Ferris, B.G., Jr., F.E. Speizer, J. Worcester, and H.Y. Chen. Adult mortality in Berlin, N.H., from 1961 to 1967. Arch. Environ. Health 23:434-439, 1971. 7. Glindmeyer, H.W., J.E. Diem, R.~. Jones, and H. Weill. Non-comparability of longitudinally and cross-sectionally determined annual change in spirometry. Am. Rev. Respir. Dis. 125:544-548, 1982. 158

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8. Greaves, I., B.G. Ferris, Jr., W.A. Burgess, and D Essex. Respiratory effects of sulfur dioxide tSO2) among corn refinery workers. Am. Rev. Respir. Dis. 129:157, 1984. 9. Higgins, I.T.T. Trends in respiratory cancer mortality: In the United States and in England and Wales. Arch. Environ. Health 28:121-129, 1974. 10. Higgins, M.W., J.B. Keller, J.R. Landis, T.H. Beaty, B. Burrows, D. Demets, J.E. Diem, I.T. Higgins, E. Lakatos, M.D. Lebowitz, H. Menkes, F.E. Speizer, I.B. Tager, and H. Weill. Risk of chronic obstructive pulmonary disease: Collaborative assessment of the validity of the Tecumseh index of risk. Am. Rev. Respir. Dis. 130:380-385, 1984. 11. Kilburn, K.H., R. Warshaw, and J.C. Thornton. Pulmonary functional impairment and symptoms in women in the Los Angeles Harbor Area. Am. J. Med., 1985. (in press) Lebowitz, M.D., R.J. Knudson, and B. Burrows. Tucson epidemiologic study of obstructive lung diseases: I. Methodology and prevalence of disease. Am. J. Epidemiol. 102:137-152, 1975. 13. Mason, T.J., J.F. Fraumeni, Jr., R. Hoover, and W.J. Blot. An Atlas of Mortality from Selected Diseases. NIH Publication No. 81-2397. Bethesda, Md.: U.S. Department of Health and Human Services, National Cancer Institute, 1981. 309 pp. 14. Monson, R.R. Occupational Epidemiology. Boca Raton, Pla.: CRC Press, 1980. 219 pp. 15. Morgenstern, H. Uses of ecologic analysis in epidemiologic research. Am. J. Pub. Health 72:1336-1344, 1983. Morris, J. Uses of Epidemiology. New York: Churchill Livingstone, 1975. 262 pp. Pan American Health Organization. Red Panamericana de Muestro de la Contaminacion del Aire, Informe Final 1967-1980. (Pan American Network for the Sampling of Contaminated Air, Final Report 1967-1980). Serie Technica No. 23, 1982. 65 pp. 159

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18. Pengelly, L.D., A.T. Kerigan, C.H. Goldsmith, and E.M. Inman. The Hamilton study: Distribution of factors confounding the relationship between air quality and respiratory health. J. Air Pollut. Control Assoc. 34:1039-1043, 1984. 19. Piomel~i, S., L. Corash, M.B. Corash, C. Seaman, P. Mushak, B. Glover, and R. Padgett. Blood lead concentrations in a remote Himalayan population. Science 210:1135-1137, 1980. 20. Polissar, L. The effect of migration on comparison of disease rates in geographic studies in the United States. Am. J. Epidemiol. 111:175-182, 1980. 21. Portney, P.R., and J. Mullahy. and acute respiratory illness. press) Urban air quality J. Urban Econ. (in 22. Reid, D.D., J. Cornfield, R.E. Markush, S. Siegel, E. Pender son, and W. Heintzel. Studies of disease among migrants and native populations in Great Britain, Norway, and the United States: III. Prevalence of cardiorespiratory symptoms among migrants and native-born in the United States. Nat. Cancer Inst. Monogr. 19:321-346, 1966. 23. Rose, G. Sick individuals and sick populations. Int. J. Epidemiol. 14:32-38, 1985. 24. Tashkin, D.P., V.A. Clark, A.H. Coulson, M. Simmons, L.B. Bourque, C. Reems, R. Detels, J.W. Sayre, and S.N. Rokaw. The UCLA population studies of chronic obstructive respiratory disease: VIII. Effects of smoking cessation on lung function: A prospective study of a free-living population. Am. Rev. Respir. Dis. 130:707-715, 1984. Van der Lende, R., T. Kok, R. Peset, Ph.H. Quanjer, J.P. Schouten, and N.G.M. Orie. Longterm Exposure to air pollution and decline in VC and FEV1: Recent results from a longitudinal epidemiologic study in the Netherlands. Chest 80(Suppl.):23S-26S, 1981. 160

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26. Ware, J.H., Thibodeau, L.A., F.E. Speizer, S. Colome, and B.G. Ferris, Jr. Assessment of health effects of atmospheric sulfur oxides and particulate matter: Evidence from observational studies. Environ. Health Perspect. 41:255-276, 1981. 27. Willett, W.C., Bee. Polk, B.A. Underwood, and C.G. Hames. Hypertension detection and follow-up program study of serum retinal, retinol-binding protein, total carotenoids, and cancer risk: A summary. J. Nat. Cancer Inst. 73:1459-1462, 1984 161 .

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