ENVIRONMENTAL RESEARCH 59, 336-349 (1992)

Health Indices of the Adverse Effects of Air Pollution: The Question of Coherence 1 DAVID V. BATES

Department of Health Care and Epidemiology, Mather Building, 5804 Fairview Crescent, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3 Received S e p t e m b e r 29, 1991

INTRODUCTION This communication has been prompted by the observation that authors of papers relating air pollution to adverse health effects very rarely discuss the interrelationships between health indices or examine their own finding in relation to other related indices. This comment applies to papers written by the present author as much as to the others. In the recent literature, there are at least 11 different indices of adverse health effects--as the Emperor said to Mozart, "there are too many notes." I have taken 44 papers on this topic published, with two exceptions, since 1980. These have been selected to describe the range of health outcomes studied. My intention is to examine the necessary, or possible, interrelationships between different indices. I do not intend to critique individual papers from the point of view of their internal strength, nor, initially, to try to distinguish between different combinations of pollutants; this question is discussed at the end. CLASSIFICATION OF HEALTH INDICES A basic differentiation is between those indices which deal with the effect of discrete episodes of air pollution and those that are concerned with long-term effects. It may be noted that the interrelationship between these two types of observation is often obscure and rarely discussed.

Episodic Data These include, during episodes of increased pollution: ---increased respiratory mortality ---increased hospital respiratory admissions --increased hospital respiratory emergency visits --increased physician visits or ambulance use --decreases in FEV 1 or PEFR - - s y m p t o m variation --changes in various indices of ill-health such as school or work absences or "reduced activity days." 1 B a s e d on an invited lecture delivered at the A W M A Meeting in V a n c o u v e r , BC, C a n a d a , 20 June 1991. 336 0013-9351/92 $5.00 Copyright © 1992by AcademicPress, Inc. All rights of reproduction in any form reserved.

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Long-Term Data In addition to the above observations, there is a series of nonepisodic or longterm data: --increased mortality from respiratory disease in regions of higher pollution --changing mortality from respiratory disease in same region as pollutant levels change --increased prevalence of symptoms or of respiratory disease indicators in regions of higher pollution --cross-sectional FEV~ differences between regions with different pollution. CLASSIFICATION OF INTERRELATIONSHIPS BETWEEN INDICES

"Coherence" is defined as follows in Webster's Third International Dictionary: "Systematic or methodologic connectedness or interrelatedness especially when governed by logical principles." Coherence theory is defined as "The theory that the ultimate criterion of truth is the coherence of all its separate parts with one another and with experience." In discussing the interrelationships between different indices, it is useful to categorize associated findings as contingent (meaning that if the principal finding is true, the contingent finding has to be present), probable, and possible. Such a classification is bound to be based on judgement. However, the absence of a contingent finding should throw doubt on the significance of the original observation; whereas the "probable" and "possible" categories might be considered "optional." RELATIONSHIPS BETWEEN INDICES

In Table 1, eight principal outcomes of the 44 studies are listed, together with suggested contingent, probable, and possible associated findings. The first of these is the finding of episodic increased respiratory or total mortality associated with increased pollution. Unless all those who died in excess of the expected number were already in hospital or died at home, one would necessarily expect that there would be increased hospital admissions in episodes of increased pollution. This, together with increased physician or hospital emergency visits, is therefore a contingent finding. A second common observation is that there is increased respiratory mortality on a long-term basis in regions with higher pollution. So many factors in addition to air pollution may influence this finding that differences attributable to air pollution may be hard to establish, but where such long-term differences exist, one would necessarily expect that there would be an increase in the prevalence of respiratory symptoms in more polluted regions and probably that the average FEV~ in random population samples would be lower in regions of higher pollution. Consequent on this, there might be an earlier age of death from respiratory disease. The third principal finding listed in Table 1 is that there is an association between hospital admissions for acute respiratory disease and pollutant levels. It is a contingent associated finding that there should be an increased hospital admission rate for respiratory disease in more polluted regions. A recent example of the

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fulfillment of this prediction is the documentation of an association between hospital admissions and pollutants in southern Ontario (Bates and Sizto, 1987) and the parallel observation of a significant "elasticity" between pollutants and respiratory admission rate in the same region, as reported by Plagionnakos and Parker (1988). For other principal findings, there do not appear to be any contingent associated findings, but there are various probable and possible associated findings. It might be noted that if there are cross-sectional FEV 1 differences with lower values in the more polluted region (PAARC, 1982, Holland and Reid, 1965), it might follow that there would be an earlier age of death from respiratory diseases; this has rarely been looked for (Catford and Ford, 1984). The relationship between hospital emergency visits and hospital admissions no doubt differs in different regions and in relation to age and diagnoses. The only carefully collected data of which I am aware indicated that, in the Sick Children's Hospital in Toronto, 25% of children brought to the Emergency Department with acute asthma are admitted (Canny et al., 1989). The same authors also noted that acute symptoms in such children generally began an average of 41 hr before arrival at the emergency department. This suggests that the 24 and 48 hr lag between pollutant level and outcome (whether admission or emergency room visit) which a number of analysts have used may be too restrictive. If so, then such calculations might miss part of the effect of an episode. COHERENCE AND DIFFERENT POLLUTANTS

The question may be asked as to how many of the contingent findings have been reported in association with specific pollutant patterns. It is often not possible to differentiate between the effects of SOz, sulfates, sulfuric acid aerosol, and particulates, but the pattern of pollution in which all rise together is well studied. For these pollutants, all six of the contingent findings (as indicated in column two of Table 1) are found. For the probable or possible associated findings, 14 of the 15 listed have been reported. It should not be overlooked that the original report on the London smog disaster of December 1952 (HMSO, 1954) documented not only the increased mortality during and after the episode, but also the fact that applications and admissions to hospitals of acute cases through the Emergency Bed Service approximately doubled during the days of the episode (see Table 12 in this report). In addition, attendance at a general practice in Beckenham in Kent for "lower respiratory disorders" rose from 5 to 7 a week in the 2 weeks preceding the episode to 20 to 25 in the 2 weeks of the episode. This report also contained the sentence, "It is probable, therefore, that sulphur trioxide dissolved as sulphuric acid in fog droplets appreciably reinforced the harmful effects of the sulphur dioxide." Two sites recorded peak SO2 levels above 1 part per million. Appendix A of this report recorded the deaths of livestock from pneumonia at the Smithfield Club's Show at Earl's Court in London held from 8 to 12 December 1952. All in all, one might conclude that there was strong evidence of coherence. The recent study by Wichmann and his colleagues (1989) of the pollution episode in Germany contained data on increased ambulance use, increased hospital admissions for respiratory and cardiovascular disease, and physician office visits (which interestingly did not seem to be a sensitive indicator in this instance).

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The recent analyses of the respiratory consequences of air pollution in Utah are unique. Air monitoring has shown that in this location, oscillations occur in PM10 levels without any significant SO2, NO2, or acid aerosol H2SO 4 accompaniments. About 40% of the particles originate from a single source. An initial report related hospital admissions for respiratory disease to the PM10 levels (Pope, 1989); this was confirmed in a later analysis (Pope, 1991). A third report indicated an excess of respiratory mortality in the impacted region (Archer, 1990), and a fourth (Pope, 1991) has shown that PM10 levels are associated with reductions in PEFR in normal children and increased symptoms and medication use in a panel of adult asthmatics in the area of concern. Thus in one location, without exposure to multiple pollutants, four different adverse health indices have been found to be associated with variations in the PM10 levels below the present U.S. standard: respiratory mortality, increased respiratory hospital admissions, reduced lung function, and increased symptoms and medication use. This is a unique example therefore of remarkable coherence and is particularly valuable as multiple pollutants were not present. The data taken together suggest strongly that the "reappraisal" of the U.S. particulate standard proposed by Holland and 11 distinguished collaborators (1979) is now itself in urgent need of reexamination. There are fewer studies of oxidant pollution, and so far only one of the contingent findings has been met. Of the probable or possible associated findings, 5 of 13 are met. These conclusions would be dependent on accepting evidence of higher respiratory mortality in regions of Los Angeles with higher air pollution, as reported in a preliminary paper in 1971 by Mahoney, and of the association of increased mortality in relation to ozone levels recently reported by Kinney and Ozkaynak (1991), and assuming that the variation in symptoms noted by Euler et al. (1988) is representative of the whole population. The difficulty with devising any index of internal coherence is that this inevitably requires a series of judgements of the reliability of individual findings and observations. DISCUSSION

Cardiovascular mortality is usually noted to increase in episodes in which respiratory mortality also increases. The relationship between heart disease and lung disease is extremely complex (Bates, 1989), but one can identify at least three different reasons why respiratory and cardiovascular mortality might be found to rise together in air pollution episodes: - - A c u t e bronchitis and bronchiolitis may be misdiagnosed as pulmonary edema. m A i r pollutants, such as acid aerosols or ozone, might increase lung permeability and precipitate pulmonary edema in people with myocardial damage and an increased left atrial pressure. m A c u t e bronchiolitis or pneumonia induced by air pollutants, in the presence of preexisting heart disease, might precipitate congestive heart failure. It is not known to what extent increased carbon monoxide in air pollution episodes might precipitate increased cardiovascular mortality (it was not being routinely measured during the London 1952 episode), but the possible relationship

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has been suggested by a number of authors. Associations between total mortality and general pollutant levels might be reflecting the effects of air pollutants through any of the mechanisms suggested. It is important therefore not to dismiss total mortality episodic data as not relevant to air pollutant effects. A more difficult question is whether these factors are sufficient to explain general associations between sulfates, for example, and total mortality (Chappie and Lave, 1982; Plagionnakos and Parker, 1988). It is unfortunate that the resources devoted to health research in association with air pollution have been generally too limited to permit detailed studies aimed at direct confirmation of the presence of coherent phenomena in the same region. Thus, although increased episodic mortality in relation to increased air pollution has been documented to occur in London and has been repeatedly studied, and although general indices of respiratory mortality in Britain are elevated compared to other countries (Catford and Ford, 1984), there does not appear to be any published evidence of increased episodic hospital admissions or emergency visits for respiratory or cardiovascular disease on a systematic basis (though apochryphal evidence indicates that these must have occurred). There is convincing data from 1965 of a lowered FEV 1 in the London population compared to populations outside London of equivalent socioeconomic status and smoking (Holland and Reid, 1965). But this cross-sectional study has not been repeated recently, so it is not known whether that phenomenon is still demonstrable. That it may be might be inferred from the PAARC study in France published in 1982 (PAARC, 1982). Furthermore, since a number of large-scale studies have indicated that a lowered FEVI is associated with reduced longevity (Bates, 1989), it might be concluded that a lowered FEV 1 demonstrated cross-sectionally indicates that respiratory morbidity has reduced survival. It should be noted that different indicators have very different significance-though the proportional seriousness of them is rarely discussed. For example, it might be argued that a 2% difference in FEV1 possibly attributable to living in a more polluted region can be ignored:(or has "no clinical significance"), although such a difference in a group mean might indicate a clinically significant drop in 5% of the population. But people do not go to hospital emergency departments complaining of a 2% loss of FEV1, still less do they get admitted for inpatient care on that account. The "strength" of different health indices (the pyramid or iceberg effect) from " w e a k " to "strong" is therefore important. A suggested listing is given in Table 2. It may be noted that each of these different indicators has it's own set of potential confounders. Population characteristics such as smoking habits or living conditions, as well as general climatic or housing conditions, are no doubt powerful confounders of differential rates of respiratory disease, but are irrelevant to time-series studies that show hospital admissions varying with poL lutants. These indicate an effect of the pollutant on the population as it exists in the region. In some writing on air pollution, it is assumed that all confounders are important in all types of study. In a perceptive review of air pollution and health indices in 1981, Whittemore (1981) noted the difficulty of deducing any strict dose-response conclusions from most health indices related to air pollution and the limitation of the interpretations

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TABLE 2 RELATIVE SIGNIFICANCEOF ADVERSE HEALTH INDICATORSOF EFFECTS OF AIR POLLUTION Least Changes in general indices of ill-health Small episodic FEV 1 declines Increased symptoms in populations in more polluted regions Cross-sectional FEV 1 differences Increased prevalence of respiratory diseases Increased hospital admission rate for respiratory disease in more polluted regions Cross-sectional respiratory mortality differences not related to episodes Increased hospital emergency visits in association with episodic increases in pollution Increased hospital admissions in episodes Increased respiratory or total mortality in episodes of increased pollution Most

that could be derived from them. We may have made some progress in this regard since then, but most studies (of particulate pollution, for instance) do not indicate that a convincing threshold value exists. Difficulties in environmental epidemiology have recently been discussed by many authors and in different conferences and symposia. Bailar (1989) recently listed general difficulties both in assessing exposure and in indices of outcome in such studies. Nevertheless, direct studies of the effects of environmental factors on populations cannot be avoided and are not replaced by other data. In assessing the "strength" of the total data in relation to a pattern of pollution (whether or not the differential responsibilities of different constituents can be determined), the question of coherence is central. Such coherence may exist at three different levels: within epidemiological data (as examined in this review); between epidemiological and animal data; and between epidemiological, controlled exposure human data and animal data. I have suggested that the coherence within epidemiological data for the pattern of pollution that follows SO2 emissions and particulate pollution is generally strong and therefore convincing. However, in the case of SO2, there is very little coherence between animal exposure data and the epidemiological data; hence, there is no basis of biological plausibility. This factor presumably underlies the serious underestimation of the current strength of the epidemiological data evident in such reports as that recently released by NAPAP (NAPAP 1990). The persistent association of particulate pollution with changes in mortality should serve as a challenge to us to explain the mechanism involved more precisely than is now possible. In the case of oxidant pollution, the coherence between animal data and controlled clinical data is generally strong, and the coherence between field and controlled exposure studies is satisfactory. However, the epidemiological component is weak; that is to say that the linkage between acute effects and long-term consequence has still to be elucidated. Coherence cannot be formally measured (as by some t test), which is why the tortuous process of standard-setting is so complex and interesting a task (Bates, 1988). And it is also why efforts to remove entirely the element of (nonstatistical) judgement from it are inevitably futile. When the problem is important what is

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required is more data, collected with all the precautions that we now realize are necessary if major confounders are to be avoided. Concordance between findings may occur fortuitously, as in the case of data from southern Ontario, or be planned, as in the recent studies from Utah. It is important to stress that in the future, coherence should be a subject for active search, once one health index has been shown to be associated with pollutants. In 1965, Hill (Hill, 1965) set out the aspects of an association that " w e especially consider before deciding that the most likely interpretation of it is causation." A recent volume (Rothman, 1988) contained useful discussion of these in the light of modern data. The criteria included biological plausibility, coherence, and consistency--that is, the replication of findings in different populations. Among these, we might now emphasize the feature of internal coherence within the epidemiological data which has been the subject of this enquiry. It is important to stress that epidemiological evidence stands on its own. As Rose recently remarked (Rose, 1989): If there has to be a choice between trusting observation or reason, it is surely safer to trust observation; for reason is so often based on incomplete information on transfer routes, doses and responses. The argument that what cannot be explained cannot occur is weak, for one can never exclude the explanation that has not been considered. In estimating risks, direct observations of evident health effects should take priority over theoretical explanations.

NOTES ON DISCUSSION OF AWMA PAPER Seven discussants received advance copies of the manuscript of this talk and were invited to add their own observations. They were introduced by Dr. David McKee (EPA). Dr. D. Dockery (Harvard University) Discussed the Harvard Six Cities Study in the context of coherence. Noting data on the rate of decline of FEV 1, he agreed that the age at which death occurred from respiratory disease was potentially an important indicator of long-term effects to which little attention has been directed. The longitudinal design of the Six Cities study, involving 14,000 children and 9000 adults reexamined at regular intervals, had indicated a possibly slower rate of decline in nonsmokers in the two cleanest cities compared to the others, but in general the lines of decline of FEV 1 were remarkably similar. Some preliminary survival data based on 12 years of follow-up indicated the possibility that in Steubenville and St. Louis this might be lower than in cleaner cities, but a longer period of surveillance was required. The cross-sectional aspects of the study had indicated more childhood bronchitis in the cities with higher levels of particulate pollution, with a difference of a factor of as much as 3 between the lowest and highest. In most of the data, interindividual differences were much greater than intercity differences. He stressed that the whole data set and the expanded design of this study enabled coherent observations to be collected. Dr. P. Lioy (EOHSI, NJ) raised the general question of coherence for exposure indices, which would provide a set of variables for use with coherent health indices. Any exposure indices must be examined for utility in episodic, periodic, and long-term situations. Such considerations raise questions as to what constitutes an exposure index for an individual versus the general population. Expo-

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sures to particulate pollution or ozone can be handled, in many circumstances, using less precise, "probable" indices, while the multiplicity of sources for volatile organics requires more exact indices. There is also a need to link available information on the biological effects (e.g., time and potency) with different types of exposure patterns encountered by a population, but these are different for such pollutants as carbon monoxide and ozone and are more difficult for acid aerosols, the latter being commonly associated, possibly synergistically, with a complex mixture, as in photochemical smog. He then discussed the possible future role of biological markers of exposure and emphasized the importance of having strong links for interdisciplinary discussion and research to establish interrelationships between exposure patterns and adverse effects. Dr. L. Folinsbee (EPA, Chapel Hill, NC) examined the coherence between short-term clinical study results and long-term health effect data. Controlled human exposure studies had demonstrated an array of results in different groups of subjects and in relation to different pollutants. One of the points that acute exposure studies had clarified was that ozone had nothing to do with eye irritation, though this had been shown in epidemiological studies to be highly correlated with oxidant levels. Controlled exposures to ozone had shown a strong relationship between ozone exposures and symptoms. They also showed that attenuation of ozone response occurred after repeated exposures to the same concentration, so that after 5 days of consecutive exposure no FEV1 drop occurred and there were no symptoms. Controlled exposure studies were also valuable in determining which symptoms were associated with which pollutants, whereas epidemiological studies could only indicate a general increase in symptoms in populations exposed to a complex mixture of pollutants. Further, controlled exposure to oxidants had shown that some individuals dropped out of the study before exposure was complete at some concentrations, and this had a corollary in epidemiological studies showing more work absences among citrus fruit workers in southern California on days of higher oxidant pollution. Dr. M. Lippman (NYU) discussed the question of coherence between animal data and between different kinds of human data. He began by commenting on the problem of defining "adverse effects"; in terms of FEV1 decline, a short-term change of 10% is often considered to constitute an adverse effect. The relationship between ozone controlled studies and the exposures that actually occur is important, and outdoor studies have indicated that larger effects are produced in normal subjects in the actual atmosphere than were found in chamber exposures to ozone. We need to remember that the easily measured functional responses are not the only things happening when actual exposures occur. Furthermore, different individuals have different responses, and although average responses may be consistent, some have more symptoms than others, a much larger FEV~ response, a greater influx of inflammatory cells, or greater changes in lung permeability after ozone exposure, and the timing of these responses may vary between individuals. The question of the time of a maximal response after exposure has been shown to be important in the case of NO 2 and has generally been insufficiently studied. Data from guinea pig exposures to sulfuric acid indicates differences between single exposures and exposures daily for several days in terms of the effect on

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particle clearance. Similar differences have been shown in rabbit exposures to sulfuric acid, in which particle clearance became considerably impaired after exposure ceased. Also, data from primate exposures to ozone indicate that exposures in alternate months may have greater effects than a continuous exposure. These results indicate how cautious we have to be in inferring the possibility of, or unlikelihood of, long-term effects in the human population. He ended by commenting on data from the UCLA study and from analyses of N H A N E S II data which suggest that ozone exposure may have led to long-term effects. Dr. Fred Lipfert (Consultant) discussed coherence between mortality and hospital morbidity data and noted some important differences in timing and relative • magnitudes. Based on a causative disease model, one would normally expect an acute episode to produce many more hospitalizations than deaths, as was the case during a recent subway fire in New York City. However, during the London episodes, for example, that of December 1957, the absolute magnitudes of the numbers of requests for emergency hospital beds and deaths were comparable. This leads to consideration of a model in which air pollution acts primarily to exacerbate existing disease; also the population of decedents may be fundamentally different from the underlying population of hospital users. He noted that coherence can be shown by fitting all of the London episodes onto the same dose-response function curve, plotted versus the average dose of smoke or SO2. However, the December 1952 episode is an outlier; it lasted longer and produced many more deaths even though average concentrations were about the same as during other episodes. Mortality in 1952 began to increase before the sharp rise in air pollution and stayed high long after the fog cleared; there may have been an underlying disease epidemic at the time. Also, the sharp rise in mortality preceded the onset of heavy fog. When nondimensional pollutionmortality regression coefficients (elasticities) are considered, these episodes are consistent with other time-series mortality studies in many locations, including a recent study in Santa Clara County, California; this is an indication of coherence over a wide range of air quality levels and populations. Reviewing Ontario hospital admissions data, he suggested that using the 24-hr average for each pollutant gives the best statistical results; when the various air pollutants are studied on such a comparable basis, it is frequently difficult to reliably distinguish among them. A further example of this phenomenon was shown from a recent cross-sectional study of all cause mortality in 900 U.S. cities, in which a long-range transport model was used to generate comparable dose estimates for SO2, SO4, and NOx; the effects of all three species were shown to be comparable, as well as those of several other measured air pollutants. The magnitudes of the mortality effects were similar to those of the time-series studies mentioned, which is a further indication of coherence and the applicability of the exacerbation model. Dr. Les Grant (EPA) reviewed the status of the NOx criteria document now being prepared by EPA. He noted that a preponderance of the studies of children living in homes with gas cooking, and hence with higher NOx exposures, find evidence of an increased prevalence of respiratory symptoms. The odds ratios are, with one exception, above 1.0, and these can be scaled to give an overall

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estimate of at least 1.2, or a 20% increase. This type of meta-analysis is very useful in determining risk, though exposure estimates in this instance are very approximate. The conclusion in the case of NOx is reinforced by the animal data, which provides a strong ground for biological plausibility. That kind of coherence between human and animal data is very important in the interpretation of studies of this kind. Dr. Mark Utell (University of Rochester) discussed the importance of different clinical criteria in relation to air pollution effects. He suggested that, instead of concentrating on indices of morbidity, perhaps we should concentrate on induced changes in physiological parameters. Noting the data presented by Dr. Dockery on "chronic bronchitis" in children, he suggested that we needed to give more attention to the refinement of questionnaires that might detect such phenomena. How do we get a handle on such effects when such affected individuals are unlikely to come to the emergency room? Another important area is the idea of coherence between different kinds of data. Controlled exposure data indicating endpoints like inflammatory responses and mediator release will give us a better idea of differences between responders and nonresponders. Using hospital data on the number of fiberoptic bronchoscopies performed in Rochester as an example, he warned us against using "numbers" without further examination as indicators of an event. Counting hospital events may also be misleading, and this may apply to asthma statistics. The panel discussion, chaired by Dr. Judy Graham, involved a lively exchange of questions and answers between members of the audience and the panel members. The topics included the interpretation of animal data, the distinction between episodic and long-term events, normal human and asthmatic responses to inhaled acidic aerosols, the definition of human morbidity, future combined studies of asthmatics visiting emergency departments and measurements of their sensitivity to pollutants, the effects of temperature and humidity on hospital admissions, the constancy of ozone and acidic aerosol levels over wide areas of country, factors influencing patient visits to doctors and hospitals, the Barcelona asthma study, the influence of epidemiological data on decisions made by regulating authorities, and the importance of coherence in assessing the "weight" of such data. REFERENCES Anderson, H. R. (1989). Increase in hospital admissions for childhood asthma: Trends in referral, severity, and readmissions from 1970 to 1985 in a health region of the United Kingdom. Thorax 44, 614-619. Archer, V. E. (1990). Air pollution and fatal lung disease in three Utah counties. Arch. Environ. Health 45, 325-334. Bailar, J. C. (1989). Inhalation Hazards: The interpretation of epidemiological evidence. In "Assessment of Inhalation Hazards: ILSI Monograph," (U. Mohr, Ed.), pp. 39-48. Springer-Verlag, Heidelberg. Bates, D. V. (1988). Standard-setting as an integrative exercise: Alchemy, juggling, or science? In "Inhalation Toxicology," (U. Mohr, Ed.), pp. 1-9. Springer-Verlag, New York/Heidelberg. Bates, D. V. (1989). "Respiratory Function in Disease," 3rd ed. Saunders, Philadelphia. Bates, D. V., Baker-Anderson, M., and Sizto, R. (1990). Asthma attack periodicity: A study of hospital emergency visits in Vancouver. Environ. Res. 51, 51-70.

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Bates, D. V., and Sizto, R. (1987). Hospital admissions and air pollutants in southern Ontario: The acid summer haze effect. Environ. Res. 43, 317-331. Brunekreef, B., Lumens, M., Hock, G., Hofschreuder, P., Fischer, P., and Biersteker, K. (1989). Pulmonary function changes associated with an air pollution episode in January 1987. J. Air Pollut. Control Assoc. 39, 1444-1447. Burney, P. G. J., Chinn, S., and Rona, R. J. (1990). Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-1986. Br. Med. J. 300, 1306-1310. Canny, G. J., Reisman, J., Healy, R., Schwartz, C., Petrou, C., Rebuck, A. S., and Levison, H. (1989). Acute asthma: Observations regarding the management of a pediatric emergency room. Pediatrics 83, 507-512. Catford, J. C., and Ford, S. (1984). On the state of public ill health: Premature mortality in the United Kingdom and Europe. Br. Med. J. 289, 1668-1670. Chappie, M., and Lave, L. (1982). The health effects of air pollution: A reanalysis. J. Urban Econ. 12, 346-376. Dales, R. E., Spitzer, W. O., Suissa, S., Schechter, M. T., Tousignant, P., and Steinmetz, N. (1989). Respiratory health of a population living downwind from natural gas refineries. Am. Rev. Respir. Dis. 139, 595-600. Derriennic, F., Richardson, S., Mollie, A., and Lellouch, J. (1989). Short-term effects of sulphur dioxide pollution on mortality in two French cities. Int. J. Epidemiol. 18, 186-197. Dockery, D. W., Speizer, F. E., Strum, D. O., Ware, J. H., Spengler, J. D., and Ferris, B. G., Jr. (1989). Effects of inhalable particles on respiratory health of children. Am. Rev. Respir. Dis. 139, 587-594. Dodge, R., Solomon, P., Moyers, J., and Hayes, C. (1985). A longitudinal study of children exposed to sulfur oxides. Am. J. Epidemiol. 121, 720-736. Euler, G. L., Abbey, D. E., Hodgkin, J. E., and Magie, A. R. (1988). Chronic obstructive pulmonary disease symptom effects of long-term cumulative exposure to ambient levels of total oxidants and nitrogen dioxide in California Seventh-Day Adventist residents. Arch. Environ. Health 43, 27% 285. Gold, D. R., Weiss, S. T., Tager, I. B., Segal, M. R., and Speizer, F. E. (1989). Comparison of questionnaire and diary methods in acute childhood respiratory illness surveillance. Am. Rev. Respir. Dis. 139, 847-849. Goren, A. I., and Hellman, S. (1988). Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel. Environ. Res. 45, 28-37. Groupe Cooperatif PAARC (1982). Air pollution and chronic or repeated respiratory diseases. II. Results and Discussion. Bull. Eur. Physiopathol. Respir. 18, 101-116. Hatzakis, A., Katsouyyanni, K., Kalandidi, A., Day, N., and Trichopoulos, D. (1986). Short-term effects of air pollution on mortality in Athens. Int. J. Epidemiol. 15, 73-81. Hertzman, C. (1990). Poland: Health and environment in the context of socioeconomic decline. Health policy Research Unit, University of British Columbia, Discussion Paper HPRU 90;:2D. Hill, A. B. (1965). The environment and disease: Association or causation? Proc. R. Soc. Med. 58, 295-300. Holland, W. W., et al. (1979). Health effects of particulate pollution: Reappraising the evidence. Am. J. Epidemiol. 110, 527-659. Holland, W. W., and Reid, D. D. (1965). The urban factor in chronic bronchitis. Lancet 1, 445-448. Imai, M., Yoshida, K., and Kitabatake, M. (1986). Mortality from asthma and chronic bronchitis associated with changes in sulfur oxides air pollution. Arch. Environ. Health 41, 29-35. Ito, K., and Thurston, G. D. (1989). Characterization and reconstruction of historical London, England, acidic aerosol concentrations. Environ. Health Perspect. 79, 35-42. Jaakkola, J. J. K., Vilkka, V., Haahtela, T., and Marttila, O. (1989). South-Karelia air pollution study: The effects of malodorous sulfur compounds on respiratory and other symptoms in adults. Am. Rev. Respir. Dis. 139, A29. Kinney, P. L., and Ozkaynak, H. (1991). Associations of daily mortality and air pollution in Los Angeles County. Environ. Res. 54, 9%120.

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