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Air pollution and asthma: Effects of exposures to short-term sulfur dioxide peaks
ENVIRONMENTAL RESEARCH 40, 332-345 (1986)
Air Pollution and Asthma: Effects of Exposures to Short-Term Sulfur Dioxide Peaks 1 INGE F. GOLDSTEIN 2 AND A U R A L . WEINSTEIN
Division of Epidemiology, School of Public Health, Columbia University, 600 W. 168th Street, New York, New York 10032 Received November 30, 1984 Recent laboratory studies have shown exposures to SO2 at levels as low as 0.1 ppm and lasting as little as 10 min to lead to changes in respiratory functions as well as symptoms in asthmatic individuals exposed during exercise. The present study was conducted to determine whether similar responses to short-term SO2 peaks in the ambient air can be detected in a free-living population. Tests were made for an association between days with S Q peaks above various levels, as identified from hourly measurements obtained by the New York City Aerometric Network, and days with high numbers of emergency room visits for asthma at three inner-city municipal hospitals in New York City. No association was found. © 1986 AcademicPress, Inc.
INTRODUCTION The study of the health effects of air pollution remains an important one in light of the continuing controversy over air pollution standards. Recent laboratory studies (I-9) have shown exposures to SO2 lasting from 10 rain to 2 hr to cause functional changes as well as symptoms in certain individuals during exercise. In particular, the bronchoconstriction response was elicited in certain asthmatic subjects exposed to SO2 levels as low as 0.1 ppm for as little as 10 rain during exercise (2). In that study, responses were observed in all subjects with asthma while breathing concentrations of 0.5 ppm, a level which is substantially less than the OSHA occupational standard of 5 ppm as a time-weighted average over 8 hr (1). A federal hourly standard of 0.5 ppm SO 2 is currently under consideration in the light of these laboratory studies. Considerable literature has evolved linking ambient air poUution to adverse acute health effects in general, and to asthma in particular. In reports of two classic air pollution episodes (10, 11), greater frequencies and severities of symptoms were seen in asthmatic individuals than in the population as a whole; however, no specific pollutant could be implicated. Later studies of the relation of air pollution to asthma under less extreme pollution levels have been, as a whole, inconclusive, suffering from problems of potential confounding or unreliability in measurements (12-14). The relationships between temperature, hospital admissions for respiratory causes, and asthma on the one hand, and temperature and various pollutants on the other, could possibly have been responsible for I Supported by Grant R01-HL25793 from the National Heart, Lung and Blood Institute and Contract RP2265-01 from the Electric Power Research Institute. 2 To whom requests for reprints should be addressed. 332 0013-9351/86 $3.00 Copyright© 1986by AcademicPress, Inc. All rightsof reproductionin any formreserved.
AIR POLLUTION AND ASTHMA
333
most of the correlations between pollution and disease observed by Bates and Sizto (15), although the finding of a correlation of asthma admissions with ozone during two summer months, when asthma admissions were not significantly correlated with temperature, is suggestive. A study by Goldstein and Dulberg (16) found no relationship between emergency room visits for asthma and levels of SO2 and particulates (measured in units of coefficient of haze) in New York City. In all these epidemiologic studies, asthma attack rates were compared with pollution levels measured as averages over periods of a day or even longer, while the clinical studies have shown reactions to exposures lasting as little as 10 min. It is thus possible that the previous population-based studies were not capable of identifying the days when elevated pollutants could have caused increases in asthma attacks if what was effective in causing the attack was a short-term peak rather than a prolonged smaller elevation. Data on short-term fluctuations in pollution levels are not commonly available, and so in most cases there is little that can be done to study their effects. Data obtainable from the New York City Aerometric Network, however, represent a unique resource for studying in a freeliving population the effects of exposure situations demonstrated to produce adverse reactions under laboratory conditions, as hourly levels of SO2 and bihourly particulate levels are available starting in the late 1960s. We have therefore collected emergency room data from three large inner-city hospitals for the years 1969 to 1971, during which SO 2 levels declined to 20% of their original values following the implementation of the Clean Air Act of 1970. This decline was important for our study of the relationship between pollution and asthma, as will be seen. PLAN OF ANALYSIS
This paper reports the results of a study which examined the relationship between short-term S Q peaks (or elevated levels) and asthma attack incidence in two inner-city areas of New York City. The aerometric data were used to identify days in the period from January 1, 1969, through February 29, 1972, on which there were short-term peaks, which could then be compared with days of high numbers of emergency visits for asthma at municipal hospitals serving these communities. Asthma visits were examined both on the same days the SO2 peak readings occurred, and on the following days, to detect any delayed response. The neighborhoods selected for the analyses were those of Harlem in Manhattan, and the general area of Bedford-Stuyvesant in Brooklyn. The use of these neighborhoods affords several advantages in a study of air pollution and asthma. In the first place, the populations of these areas are predominantly lowincome nonwhites dependent almost entirely on the local municipal hospitals for medical care. Clinical impressions suggest asthma prevalence among low-income nonwhites to exceed by a factor of up to 3 - 4 the prevalence of asthma in the population as a whole. Household surveys of Puerto Ricans in Hartford, Connecticut (17), and of black adolescents and young adults in Harlem (18, 19) support these impressions, yielding prevalence figures of 9 to 11%. This high prevalence not only guarantees greater numbers for the analysis, but points to a serious
334
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public health problem that might be alleviated if contributing factors could be identified. Analyses were performed using 2 x 2 contingency tables. The statistical procedures used to test for an association between days of high SOz and days of high asthma were the two-sided X2 test with one degree of freedom, and, for tables with less than about 5 days expected in each cell, the two-sided Fischer-Irwin exact test (20). A two-sided test was used since an effect in either direction would have been of interest. The New York City Aerometric Network provided hourly determinations of SO2 levels at 40 stations spread out through the five boroughs of New York City (see Fig. 1). In order to ensure that pollution measures were representative of the exposures of the study population, data from Station 0, (the laboratory station) and Station 2 were averaged to represent exposures for Harlem, and data from Stations 18 and 19 were averaged to represent exposure for the general area of Bedford-Stuyvesant. In addition, data from Station 0 were compared with
AIR P O L L U T I O N A N D A S T H M A
335
Harlem Hospital emergency room data separately to take advantage of the greater reliability and availability of Station 0 data (there were few days on which data were missing). Days were classified as high days or not-high days on the basis of whether any hourly reading on that day was equal to or above a certain threshold value. In addition, the requirement that there be 18 hr or more of data or averages available was applied to the not-high days in order to reduce chances of a day being misclassified as not-high if an hourly peak had gone undetected due to missing data. 3 These considerations do not apply to high days, since if a high value was detected at a given hour, the day could not be classified as not-high no matter how many hourly readings were missing. Days with less than 18 hr of data available were, with the exception of weekend days, assumed to be randomly distributed, so that the use of unequal criteria for high days and control days should induce no systematic bias. At Stations 2, 18, and 19, at most only 12 hr of data were available every Saturday and Monday and no readings were available on Sundays due to the weekend shutdown of these stations. To control for this systematic difference, analyses for the averages of Stations 0 and 2, and Stations 18 and 19, were restricted to pollution measurements falling on days Tuesday through Friday. Three levels of SO2 concentration were chosen as thresholds for the classification of a day as high or not-high. The 0.5 ppm level corresponds to that recently proposed as the federal hourly standard and is a concentration at which most asthmatics responded while exercising strenuously under laboratory conditions. Aside from Station 0, which is situated in the area recording the highest level of air pollution in New York City, days when hourly levels exceeded 0.5 ppm were rare and thus there would be little statistical power to detect any but the strongest effects. The 0.1 ppm level corresponds to one of the lowest concentrations ever reported to elicit a bronchoconstriction response under laboratory conditions. Hourly levels over 0.1 ppm were encountered frequently at all stations in the aerometric network; indeed during the first study year there were few days, especially at Station 0, when levels did not exceed 0.1 ppm. This represents the lowest threshold that may reasonably be investigated. The 0.3 ppm level, midway between the other two levels, represents a compromise in terms of severity of expected response and data availability. All stations regularly experienced levels this high or higher, at least until 1971, yet these levels were not so common as to make control days scarce. Days with no hourly readings above 0.1 ppm (0.1 controls) represented the least polluted days and provided the most stringent controls. The 0.1 control days were compared with the days high by the 0.1 ppm criterion and also with days high by the 0.3 and 0.5 ppm criteria to provide the sharpest possible contrast in exposure levels. Similarly, 0.3 controls were compared with days high by both the 0.3 ppm and 0.5 ppm criteria (but not with days high by the 0. I ppm criterion). The 0.5 control days were only compared with days high by the 0.5 ppm criterion, since they included most of the days high by the 0.1 and 0.3 ppm criteria. Emergency room statistics at Harlem Hospital were examined to determine 3 Missing data were due to instrumentation malfunction.
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GOLDSTEIN AND WEINSTEIN
adult asthma attack incidence in Harlem, and statistics from Cumberland Hospital and Kings County Hospital were pooled to obtain rates for the general area of Bedford- Stuyvesant. " H i g h " numbers of emergency room visits were defined in two ways. "Adays," which were taken to represent asthma epidemic days, were defined as in (16) as being all days for which the probability of observing the actual number of visits was less than or equal to 0.05 assuming a nonhomogeneous Poisson distribution. As was done by Goldstein and Dulberg (16), the expected number of visits on a given day was taken as the 14-day moving average of asthma visits for the 7 days preceding and the 7 days following the day in question in order to control for seasonal effects and long-term trends in asthma attack incidence. In the second approach, high days were defined as days on which the observed number of visits was simply greater than or equal to the 14-day moving average centered around that day. Days already identified as A-days by the first approach were excluded to allow for a possible intrinsic difference between A-days, which were taken to represent asthma epidemic days, and nonepidemic days. The analysis of above-average days was only carried out for Harlem Hospital data compared with Station 0 measurements taken on the same day for the first year of data (1969). This is the most favorable subset of the data to be used for the analysis, since 1969 contained the greatest number of high-pollution days and the air pollution data from Station 0 in Harlem are the most complete. Since a greater number of A-days were observed in the autumn that in any other season, the use of a full year of data gives us more opportunity to detect factors related to increases in asthma visits that are less extreme than those represented by the A-days than does the use of fall seasons alone, as done by Goldstein and Dulberg (16). In any model assuming a causal relation of SO2 peaks to asthma attacks, the SO2 exposure must precede the asthma attack. Data available for the present analysis included the time of day of SO 2 measurements; however, the actual hour of the day for emergency room visits was not readily available for all of the hospitals. The analysis was therefore done at the level of days, neglecting the timing of the SO 2 peaks and asthma visits within the days. Without knowledge of times of visits, those visits that occurred before a pollution peak and so could not have been influenced by that peak would be included among all the visits examined for a relation to that peak, thus serving to attenuate any relation that may be present. The extent of this problem is minimized, however, by the observation that most of the pollution peaks occur early in the day, so that the majority of emergency room visits on a given day would have occurred after the times of highest SO 2 levels anyway. This problem is also avoided when asthma visits are examined for days following the day on which a high SO2 reading was observed, but in this case the time allowed between exposure and outcome might also allow for exposures to other etiologic agents which would introduce considerable scatter into the results.
Potential Difficulties Day-of-the-week effects. Previous studies of fall seasons in the same data set
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AIR POLLUTION AND ASTHMA
TABLE 1 PROPORTIONS OF DAYS a WITH AT LEAST ONE HOURLY VALUE ABOVE THREE THRESHOLDS BY DAY OF THE WEEK, STATION 0, DECEMBER 1968 THROUGH FEBRUARY 1972 Threshold 0.1 p p m 0.3 p p m 0.5 p p m Total days (N)
Sun
Mort
Tues
Wed
Thurs
Fri
Sat
Overall
0.635 0.060 0.018
0.745 0.133 0.024
0.769 0.112 0.030
0.749 0.108 0.012
0.763 0.095 0.018
0.775 0.148 0.012
0.685 0.095 0.000
0.732 0.107 0.016
167
165
169
167
169
169
168
1174
a With 18 or m o r e hr of data available.
(16) and studies of an expanded data set including 9 years of data from the three hospitals over all seasons (21) show a pronounced excess of asthma visits on Sundays and Mondays for adults in all seasons, with the excess greatest in the fall season. To account for effects of social factors, which might influence the utilization of medical care facilities independently of the incidence of disease, day-ofthe-week patterns were also examined for nonasthma respiratory disease, and for illness other than respiratory disease or trauma. An excess of emergency room visits for these causes was again found on Mondays, however, Sundays were found to have about the same or fewer average visits than other days of the week. The day-of-the-week effect for nonasthma visits may be attributed to such social factors as a reluctance to return to work or school after a weekend, or the availability of medical care, which might also account for the high frequency of asthma visits on Mondays. Unless there is something special about social responses to an asthma attack as opposed to other respiratory problems, the excess in asthma visits on Sundays may be taken as representing a true increase in incidence. A day-of-the-week effect can also be seen in the SO 2 data from Station 0, examined according to the proportions of the different days of the week with at least one hourly reading over a given threshold (see Table 1). Here it may be seen that, at least for the two lower levels, there were fewer SO 2 peaks on the weekends (Saturday and Sunday) than on weekdays (Monday through Friday). Comparison of the day-of-the-week patterns of asthma and of SO2 peaks reveals a potential problem for the analysis. If day of the week, acting through whatever mechanisms, can cause asthma to be high on Sundays and Mondays, and pollution to be low on Saturdays and Sundays, then a causal relation between pollution and asthma might be overwhelmed by the competing influences of factors dependent on the day of the week. (Such factors might include the social factors giving rise to Monday highs for emergency room visits, cyclic etiologic factors giving rise to Sunday highs for asthma, and weekly patterns of fuel combustion.) An alternative explanation for the contrasting day-of-the-week patterns of asthma and SO2 peaks is that low pollution levels give rise to increases in asthma, but such an explanation seems unlikely. Trends in asthma following reduction of air pollution in New York City. Contrasting secular trends in SO2 and asthma attack data also pose a potential difficulty. On the one hand, SO 2 levels and the frequencies of the variously defined SO 2 peaks declined steadily over the 3-year period of the study. On the other hand, the numbers of asthma visits in the three hospital emergency rooms re-
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GOLDSTEIN AND WEINSTEIN
mained relatively constant when changes in hospital utilization are accounted for, as may be seen in Table 2, where the percentage contribution of asthma and total respiratory visits to the total emergency room count are tabulated. Although absolute numbers of total emergency room visits increased in this interval, visits due to asthma and respiratory causes in general kept pace with the increase in utilization, so that the apparent asthma attack incidence did not decrease with the decrease in pollution levels. These two trends might be taken as evidence that sulfur dioxide levels, whether measured as hourly levels or long-term averages, cannot be factors contributing to rates of emergency room visits for asthma. Alternatively, it may be that exacerbations of air pollution trigger prematurely asthma attacks that had been developing over a period of time, thus affecting the distribution of attacks without affecting their number. For this reason, in an analysis over the entire period from 1969 to 1971, a relation between asthma and SO2 in the first year may be diluted in the second and third years, as instances where pollution is sufficient to cause significant elevations in asthma decline. Analyses were therefore performed separately for the first year of data and for the 3-year period as a whole. Days of high average S02 levels vs days with high hourly SO 2 levels. Previous studies of the relation of health indicators to pollution variables have been sensitive to charges that daily or longer-term average pollutant level may not reflect the occurrence of short-term peaks, which may have a greater significance for health. The availability of hourly data from the New York City Aerometric Network permits the evaluation of the relation of days with high average SO2 levels to days with high hourly SO 2 readings, which are taken to represent days with short-term peaks. We therefore compared the days identified as high in SO2 by Goldstein and Dulberg (16) according to the criterion of a daily average SO2 level corresponding to a probability of less than 0.10 on a normal distribution, with days identified as high based on the presence of an hourly value above 0.3 ppm. As can be seen from Table 3, for the period from the fall of 1969 through the
TABLE 2 PERCENTAGES OF TOTAL ADULT EMERGENCY ROOM VISITS REPRESENTED BY ASTHMA AND TOTAL RESPIRATORY DIAGNOSES IN THREE NEW YORK CITY HOSPITALS 1969-1971 Cumberland Hospital %
Na
1969 1970 1971
5.27 5.10 5.20
63,288 71,280 75,465
1969 1970 1971
16.27 15.56 16.53
63,288 71,280 75,465
Kings County Hospital %
Harlem Hospital
N
%
N
Asthma visits 3.33 3.21 3.05
151,545 163,716 172,439
b 3.99 3.06
104,189 103,263
Respiratory visits 13.92 14.93 15.26
151,545 163,716 172,439
b 13.30 12.57
104,189 103,263
a N is the total number of emergency room visits for all causes. b Data for Harlem Hospital, 1969, are incomplete.
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AIR P O L L U T I O N A N D A S T H M A
TABLE 3 OVERLAP OF DAYS OF HIGH SO 2 IDENTIFIED BY DAILY AVERAGE AND BY HOURLY READINGS,
AUTUMN1969 TO WINTER1970-1971 No. of days high according to Hourly criterion
Daily average criterion
Both criteria (overlap)
City-wide average compared with Station O, 2, 18, and 19 hourly data Autumn 1969 17 5 Winter 1969-1970 32 5 Spring 1970 9 6 Summer 1970 1 6 Autumn 1970 8 6 Winter 1970-1971 12 4 Total
79
32
Station 0 daily average compared with Station 0 hourly data Autumn 1969 16 5 Winter 1969-1970 25 7 Spring 1970 7 8 Summer 1970 0 10 Autumn 1970 7 9 Winter 1970-1971 10 10 Total
65
49
3 5 5 0 3 2 18 5 7 5 0 4 6 27
winter of 1970-1971 (for which the G o l d s t e i n - D u l b e r g analysis had been done) in no season did the days identified as high by the two criteria entirely overlap. Instead, for m o s t seasons there existed a substantial n u m b e r of days classified as high by one or the other criterion, but not both. These comparisons d e m o n s t r a t e that the previous analysis of the same data set, and p r e s u m a b l y other analyses based on daily averages, was not sufficient to investigate the hypothesis that a s t h m a is related to hourly peaks. The results of those studies thus do not apply to the present investigation.
RESULTS
A-Days The analysis involved a test for an association between A-days and days of high SO2, defined by various criteria, which were contrasted with days of not-high SO2. Proportions of high and control SO2 days that were also A-days were first c o m p a r e d for individual seasons within a year, and, when no clear difference a m o n g the seasons emerged, the seasons were combined into calendar years and within the 3-year period as a whole. Significance testing of the association between A-days and days of high SO 2 for the first year and overall (see Table 4) resulted in no P values less than 0.05. For the 1 out of 57 associations that app r o a c h e d a P v a l u e o f 0.05 ( H a r l e m H o s p i t a l c o m p a r e d w i t h S t a t i o n 0, 1969-1971, same day, 0.3 high, 0.3 control, P = 0.051), comparison of the same
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high days with more stringent controls (0.1 level--days with no reading above 0. l ppm) did not produce the stronger relationship that would be expected if A-days were truly related to pollution levels. We conclude that this almost-significant result arose due to chance. It is interesting to note that the second lowest P value (P = 0.075, Harlem Hospital compared with Station 0, 1969 visits on day following SO2 measurements) was obtained for a situation in which the rate of Adays was higher on days for which no hourly value exceeded 0.1 ppm than on days which had at least one hourly reading above 0.1 ppm. This result further supports the contention that differences are due to chance, since the direction of the difference is not consistent. If a one-sided test of significance had been used, the former result would be significant, but the interpretation that it is due to chance woud be unchanged, since it would not be coherent with other results.
Above-Average Asthma Days In order to detect any less extreme effect of SO2 peaks on emergency room statistics for asthma, analyses were also made of associations between days of above-average asthma visits, excluding A-days and days of high SO2, by various criteria, for a subset of the available data. No outstanding seasonal effects in the comparison other than what would be expected when small numbers are involved are evident. To avoid problems of zero cells and to reduce the likelihood of a significant result arising due to chance, formal statistical analysis was done only for the year 1969 as a whole (see Table 5). Again, no relation even comes close to significance, and no clear direction of association is seen.
DISCUSSION The present study was undertaken to examine the relationship between ambient SO2 peaks and asthma in two inner-city areas of New York City. Statistical tests were made for an association between days on which high hourly levels of SO 2 were recorded by stations of the New York City Aerometric Network, and days on which high numbers of asthma emergency room visits were seen at three inner-city municipal hospitals. The measurements were made at locations within TABLE 5 SIGNIFICANCE TESTING OF ASSOCIATION BETWEEN NON-A-DAYS WITH VISITS ABOVE A 14-DAY MOVING AVERAGE AND HIGH SO 2 MEASURED BY STATION 0, ON THE SAME DAY, 1969 a High SO 2 level (ppm)
Control SO 2 level (ppm)
AS
KS
AS
A--S
P value b
0.1 0.3 0.3 0.5 0.5 0.5
O. 1 O. 1 0.3 O. 1 0.3 0.5
104 22 22 6 6 6
157 36 36 8 8 8
15 15 97 15 97 115
34 34 155 34 155 181
0.291 0.571 0.946 0.609 0.970 0.986
a See note to Table 4. b All significance Testing done by
X2
test.
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the catchment areas of the hospital emergency rooms studied. Three different criteria for high SO2 were used, spanning a range from that definitively associated with asthma symptoms in the laboratory but rarely encountered in the environment, to that producing responses under certain conditions in the laboratory but so common in the environment as to make comparison days extremely rare. Comparisons were made between days on either side of a dividing line, and days representing opposite extremes in air pollution levels. Two separate types of outcome variable were examined: asthma epidemic days, defined as being days of asthma visits greater than the 0.05 level on the Poisson distribution [which occur more often than expected due to chance (16)], and days when asthma visits were above a 14-day moving average but which were not epidemic days. To allow for any time lag, asthma emergency room visits on days following high and not-high SO2 measurements were compared as well as asthma emergency visits on the days of high and not-high SO2. An attempt was made to look for gross seasonal effects, as well as to control for secular trends of decreasing pollution levels. Certain of the P values approached the customary cutoff value of 0.05, however, no more than would be expected due to chance given the large number of statistical tests performed. Considerations of plausibility support the conclusion that the marginally significant results obtained result from the play of chance, as these relations do not persist as the comparisons become more extreme, as would be expected of a true relationship. In addition, the direction of association is not consistent. Thus we can conclude that there is no significant association between days when high hourly levels of SO 2 were measured and days with high numbers of emergency room visits for asthma in New York City. A possible factor accounting for the finding of no statistical significance in any investigation is that of power. If the numbers of observations made were not sufficient to allow the probable detection of an association of a given magnitude if it existed, then failure to detect such an association cannot be attributed solely to the lack of association. To test for this possibility, calculations were performed for three test comparisons believed to be representative of those used in the analysis. The method used was that of Levin (22) with the number of strata equal to 1 and the odds ratio taken as the measure of excess risk. In this analysis, the odds ratio represents the ratio of the odds of a day being a day of high asthma if it is high in SO2, with the odds of its being a day of high asthma if it is not high in S Q ; it does not relate to odds for individuals. In order to translate this odds ratio into a meaningful figure in terms of emergency room utilization or population morbidity, calculations of the absolute and percentage increases in emergency room visits corresponding to each hypothetical value of the odds ratio for days were performed according to the method outlined in (16). As can be seen from Table 6 although power to detect an odds ratio of 2, corresponding to 7.8 and 5.4% increases in the numbers of visits, was poor, the analysis should have been able to detect a 20-25% increase in visits, at least for the comparisons using days high by the 0.3 ppm criterion. Power would be expected to be lower in comparisons of the averages of Station 0 and 2, and Station 18 and 19 data, due to the fewer observations available for these averages (due to missing data), but will be greater for analyses done over the entire study period. Power would also be greater for corn-
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TABLE 6 POWER CALCULATIONS FOR TEST OF ASSOCIATION BETWEEN DAYS OF HIGH SO 2 AND A-DAYS (ON THE SAME DAY) FOR SELECTED COMPARISONS OF STATION 0 DATA AND HARLEM HOSPITAL RECORDS FOR 1969
Odds ratio 2
3
4
5
6
1.15 7.8 12
2.01 13.7 25
2.68 18.2 38
3.21 21.8 48
3.65 24.8 56
1.15 7.8 30
2.01 13.7 55
2.68 18.2 78
3.21 21.8 88
3.65 24.8 94
0.76 5.4 34
1.41 10.0 74
1.95 13.9 92
2.41 17.3 98
2.83 20.1 99
0.1 high vs 0.1 control m(o)) a
% Increase b Power (%) 0.3 high vs 0.l control A(co) % Increase Power (%) 0.3 high vs 0.3 control A(co) % Increase Power (%)
A(co)is definedas the absolute increase in asthma visits as a functionof~o,the odds ratio for days. b % Increase is the correspondingpercentageincrease in visits.
parisons of rates of above-average emergency room visits on days of high and not-high SO2 since the distributions of visits between above- and below-average are more uniform. The results show that emergency room visits for asthma are not associated with high hourly measurements of SO2 at locations situated in areas served by the hospitals despite laboratory demonstrations that levels of SO2 similar to the ones encountered here induce airway responses and symptoms in exercising asthmatics. But the nature of the study must constrain the inferences that may be drawn from it. The present study was an ecological study, conducted at the levels of populations and of areas, so that all the uncertainties involved when associations are not examined in individuals apply. In the first place, exposures were measured at one or two locations (usually on the roofs of buildings) assumed to be representative of the population exposures. The demonstration (23, 24) of small-scale variations in pollution patterns with little spatial correlation, and the dependence of these variations on meteorological and other factors, however, make the representativeness of the measures uncertain. In the second place, even if the measurements were representative of what people breathed when they were outside, they most assuredly did not represent SO2 levels indoors, which are known to be substantially less than outdoor levels. Indoor exposures take on an even greater importance when it is realized that, on the average, our study population spends over 90% of its time indoors (25), and that a wide variety of agents known to trigger asthma attacks are found in the home. Other factors that may tend to obscure a true relationship between asthma and SO2 include the apparent requirement that at least fbr the 0.01 ppm SO2 levels susceptible subjects be breathing through their mouths when the peak pollution level is encountered, and
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GOLDSTEIN AND WEINSTEIN
that other etiologic agents and social factors may cause A-days when pollution is low.
The Role of Temperature A factor not included in the present analysis is ambient temperature. As temperature is associated both with levels of atmospheric SO 2 and with asthma, it may act as a confounder, giving rise to a spurious direct or inverse relationship between asthma and SO2 caused by the covariation of both outcome and exposure variables with temperature. It is therefore important to make sure that any result obtained in a study of asthma and air pollution reflect the true relationship between these factors and not the relation of these factors with a third factor (temperature). In the present case, examination of the probable directions of relationship of temperature with the two variables in question shows that temperature is not a plausible cause for the lack of a relationship. A drop in temperature is usually associated with an increase in pollution as more fuel is burned to provide heat and electricity. A drop in temperature is also most plausibly associated with an increase in asthma, due to the demonstrated sensitivity of some asthmatic individuals to cold air. The most plausible effect of temperature, if it did play a role as a confounder, would thus be to create a spurious direct relation between SO2 and asthma, and not to conceal one that truly existed. Since no relation between SO2 and asthma was found, it may be concluded that the role of temperature was insignificant in the present analysis. It must be emphasized that the present results do not rule out a relationship between asthma and ambient levels of SO2. Sulfur dioxide peaks may yet trigger asthma attacks in some asthmatics under natural conditions, but the ecological approach may be too crude to detect an effect. More useful studies to answer the questions posed by the laboratory research on SO2 and to account for the high prevalence of asthma in inner-city areas would have to be conducted on the individual level, where the actual exposures of an individual could be assessed and correlated with asthma attack incidence over time. Korn and Whittemore (26) have developed a statistical methodology for use in the analysis of individuallevel studies on acute health effects of air pollution, and we hope to use it in a study currently under way among inner-city residents with asthma. REFERENCES 1. Sheppard, D., Wong, W. S., Uehara, C. F., Nadel, J. A., and Bousbey, H. A. (1980). Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Amer. Rev. Respir. Dis. 122, 873. 2. Sheppard, D., Saisho, A., Nadel, J. A., and Boushey, H. A. (1981). Exercise increases sulfur dioxide-induced bronchoconstriction in asthmatic subjects. Amer. Rev. Respir. Dis. 123,486. 3. Linn, W. S., Bailey, R. M., Shamoo, D. A., Venet, T. G., Wightman, L. H., and Hackney, J. D. (1982). Respiratory responses of young adult asthmatics to sulfur dioxide exposure under simulated ambient conditions. Environ. Res. 29, 220. 4. Linn, W. S., Shamoo, D. A., Spier, C. E., Valencia, L. M., Anzar, U. T., Venet, T. G., and Hackney, J. D. (~993). Respiratory effects of 0.75 ppm sulfur dioxide in exercising asthmatics: Influence of upper respiratory defenses. Environ. Res. 30, 340. 5. Linn, W. S., Venet, T. G., Shamoo, D. A., Valencia, L. M., Anzar, U. T., Spier, C. E., and
AIR POLLUTION AND ASTHMA
6. 7.
8.
9.
10. 11.
12. 13. 14. 15. 16. 17.
18. 19. 20. 21. 22. 23. 24. 25.
26.
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Hackney, J. D. (1983). Respiratory effects of sulfur dioxide in heavily exercising asthmatics: A dose-response study. Amer. Rev. Respir. Dis. 127, 278. Koenig, J. Q., Pierson, W. E., and Frank, R. (1980). Acute effects of inhaled SO 2 plus NaC1 droplet aerosol on pulmonary function in asthmatic adolescents. Environ. Res. 22, 145. Koenig, J. Q., Pierson, W. E., Horike, M., and Frank, R. (1981). Effects of SO2 plus NaC1 aerosol combined with moderate exercise on pulmonary function in asthmatic adolescents. Environ. Res. 25, 340. Koenig, J. Q., Pierson, W. E., Horike, M., and Frank R. (1983). A comparison of the pulmonary effects of 0.5 ppm versus 1.0 ppm sulfur dioxide plus sodium chloride droplets in asthmatic adolescents. J. Toxicol. Environ. Health 11, 129. Kirkpatrick, M. B., Sheppard, D., Nadel, J. A., and Boushey, H. A. (1982). Effect of the oronasal breathing route on sulfur dioxide-induced bronchoconstriction in exercising asthmatic subjects. Amer. Rev. Respir. Dis. 125, 627. Firket, J. (1931). Sur les causes des accidents survenues dans la vall6 de la Meuse, lors des brouillards de d6cembre 1930. (1931). Bull. Acad. R. M~d. Belg. 11, 683. Shrenk, H. H., Heimann, H., Clayton, G. D., Gafafer, W. M., and Wexler, H. (1949). Air pollution in Donora, Pa.: Epidemiology of the unusual smog episode of October 1948--Preliminary report. Public Health Bulletin No. 306. Zeidberg, L. D., Prindle, R. A., and Landau, E. (1961). The Nashville air pollution study. I. Sulfur dioxide and bronchial asthma: A preliminary report. Amer. Rev. Respir. Dis. 84, 489. Chiaramonte, L. T., Bongiorno, J. R., Brown, R., and Laano, M. E. (1970). Air pollution and obstructive respiratory diseases in children. N.Y. State J. Med. 70, 394. Whittemore, A. S., and Korn, E. L. (1980). Asthma and air pollution in the Los Angeles area. Amer. J. Public Health 70, 687. Bates, D. V., and Sizto, R. (1983). Relationship between air pollutant levels and hospital admissions in southern Ontario. Canad. J. Public Health 74, 117. Goldstein, I. E, and Dulberg, E. (1981). Air pollution and asthma: Search for a relationship. J. Air Pollut. Control Assoc. 31, 370. Guarnaccia, E (1982). "Ethnicity and Illness. II. Childhood Asthma in a Low-Income Community in Hartford, Connecticut." Paper presented at the Annual Meetings of the American Anthropological Association, Washington, D.C., December 4. Brunswick, A. E, and Josephson, E. (1972). Adolescent health in Harlem. Amer. J. Public Health Suppl., Part 2, October. Brunswick, A. E (1980). Health stability and change: A study of urban black youth. Amer. J. Public Health 70, 504. Fleiss, J. L., (1981). "Statistical Methods for Rates and Proportions," 2nd ed., pp. 19-22,24-26. Wiley, New York. Goldstein, I. E, and Cuzick, J. (1983). Daily patterns of asthma in New York City and New Orleans: An epidemiologic investigation. Environ. Res. 30, 211-223. Levin, B. (1982). On the accuracy of a normal approximation to the power of the MantelHaenszel procedure. J. Stat. Comput. Simul. 14, 201. Goldstein, I. E, and Landovitz, L. (1977). Analysis of air pollution patterns in New York City. I. Can one aerometric station represent the large metropolitan area? Atmos. Environ. 11, 47. Goldstein, I. E, and Landovitz, L. (1977). Analysis of air pollution patterns in New York City. II. Can one aerometric station represent the area surrounding it? Atmos. Environ. 11, 53. Goldstein, I., Hal-tel, D., and Andrews, L. (1984). "Indoor Exposure of Asthmatics to Nitrogen Dioxide." Paper presented at Indoor Air 1984, Third International Conference on Indoor Air Quality and Climate, Stockholm, Sweden, August 20-24. Korn, E. L., and Whittemore, A. S. (1979). Methods for analyzing panel studies of acute health effects of air pollution. Biometrics 35,795.
Air Pollution and Asthma: Effects of Exposures to Short-Term Sulfur Dioxide Peaks 1 INGE F. GOLDSTEIN 2 AND A U R A L . WEINSTEIN
Division of Epidemiology, School of Public Health, Columbia University, 600 W. 168th Street, New York, New York 10032 Received November 30, 1984 Recent laboratory studies have shown exposures to SO2 at levels as low as 0.1 ppm and lasting as little as 10 min to lead to changes in respiratory functions as well as symptoms in asthmatic individuals exposed during exercise. The present study was conducted to determine whether similar responses to short-term SO2 peaks in the ambient air can be detected in a free-living population. Tests were made for an association between days with S Q peaks above various levels, as identified from hourly measurements obtained by the New York City Aerometric Network, and days with high numbers of emergency room visits for asthma at three inner-city municipal hospitals in New York City. No association was found. © 1986 AcademicPress, Inc.
INTRODUCTION The study of the health effects of air pollution remains an important one in light of the continuing controversy over air pollution standards. Recent laboratory studies (I-9) have shown exposures to SO2 lasting from 10 rain to 2 hr to cause functional changes as well as symptoms in certain individuals during exercise. In particular, the bronchoconstriction response was elicited in certain asthmatic subjects exposed to SO2 levels as low as 0.1 ppm for as little as 10 rain during exercise (2). In that study, responses were observed in all subjects with asthma while breathing concentrations of 0.5 ppm, a level which is substantially less than the OSHA occupational standard of 5 ppm as a time-weighted average over 8 hr (1). A federal hourly standard of 0.5 ppm SO 2 is currently under consideration in the light of these laboratory studies. Considerable literature has evolved linking ambient air poUution to adverse acute health effects in general, and to asthma in particular. In reports of two classic air pollution episodes (10, 11), greater frequencies and severities of symptoms were seen in asthmatic individuals than in the population as a whole; however, no specific pollutant could be implicated. Later studies of the relation of air pollution to asthma under less extreme pollution levels have been, as a whole, inconclusive, suffering from problems of potential confounding or unreliability in measurements (12-14). The relationships between temperature, hospital admissions for respiratory causes, and asthma on the one hand, and temperature and various pollutants on the other, could possibly have been responsible for I Supported by Grant R01-HL25793 from the National Heart, Lung and Blood Institute and Contract RP2265-01 from the Electric Power Research Institute. 2 To whom requests for reprints should be addressed. 332 0013-9351/86 $3.00 Copyright© 1986by AcademicPress, Inc. All rightsof reproductionin any formreserved.
AIR POLLUTION AND ASTHMA
333
most of the correlations between pollution and disease observed by Bates and Sizto (15), although the finding of a correlation of asthma admissions with ozone during two summer months, when asthma admissions were not significantly correlated with temperature, is suggestive. A study by Goldstein and Dulberg (16) found no relationship between emergency room visits for asthma and levels of SO2 and particulates (measured in units of coefficient of haze) in New York City. In all these epidemiologic studies, asthma attack rates were compared with pollution levels measured as averages over periods of a day or even longer, while the clinical studies have shown reactions to exposures lasting as little as 10 min. It is thus possible that the previous population-based studies were not capable of identifying the days when elevated pollutants could have caused increases in asthma attacks if what was effective in causing the attack was a short-term peak rather than a prolonged smaller elevation. Data on short-term fluctuations in pollution levels are not commonly available, and so in most cases there is little that can be done to study their effects. Data obtainable from the New York City Aerometric Network, however, represent a unique resource for studying in a freeliving population the effects of exposure situations demonstrated to produce adverse reactions under laboratory conditions, as hourly levels of SO2 and bihourly particulate levels are available starting in the late 1960s. We have therefore collected emergency room data from three large inner-city hospitals for the years 1969 to 1971, during which SO 2 levels declined to 20% of their original values following the implementation of the Clean Air Act of 1970. This decline was important for our study of the relationship between pollution and asthma, as will be seen. PLAN OF ANALYSIS
This paper reports the results of a study which examined the relationship between short-term S Q peaks (or elevated levels) and asthma attack incidence in two inner-city areas of New York City. The aerometric data were used to identify days in the period from January 1, 1969, through February 29, 1972, on which there were short-term peaks, which could then be compared with days of high numbers of emergency visits for asthma at municipal hospitals serving these communities. Asthma visits were examined both on the same days the SO2 peak readings occurred, and on the following days, to detect any delayed response. The neighborhoods selected for the analyses were those of Harlem in Manhattan, and the general area of Bedford-Stuyvesant in Brooklyn. The use of these neighborhoods affords several advantages in a study of air pollution and asthma. In the first place, the populations of these areas are predominantly lowincome nonwhites dependent almost entirely on the local municipal hospitals for medical care. Clinical impressions suggest asthma prevalence among low-income nonwhites to exceed by a factor of up to 3 - 4 the prevalence of asthma in the population as a whole. Household surveys of Puerto Ricans in Hartford, Connecticut (17), and of black adolescents and young adults in Harlem (18, 19) support these impressions, yielding prevalence figures of 9 to 11%. This high prevalence not only guarantees greater numbers for the analysis, but points to a serious
334
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public health problem that might be alleviated if contributing factors could be identified. Analyses were performed using 2 x 2 contingency tables. The statistical procedures used to test for an association between days of high SOz and days of high asthma were the two-sided X2 test with one degree of freedom, and, for tables with less than about 5 days expected in each cell, the two-sided Fischer-Irwin exact test (20). A two-sided test was used since an effect in either direction would have been of interest. The New York City Aerometric Network provided hourly determinations of SO2 levels at 40 stations spread out through the five boroughs of New York City (see Fig. 1). In order to ensure that pollution measures were representative of the exposures of the study population, data from Station 0, (the laboratory station) and Station 2 were averaged to represent exposures for Harlem, and data from Stations 18 and 19 were averaged to represent exposure for the general area of Bedford-Stuyvesant. In addition, data from Station 0 were compared with
AIR P O L L U T I O N A N D A S T H M A
335
Harlem Hospital emergency room data separately to take advantage of the greater reliability and availability of Station 0 data (there were few days on which data were missing). Days were classified as high days or not-high days on the basis of whether any hourly reading on that day was equal to or above a certain threshold value. In addition, the requirement that there be 18 hr or more of data or averages available was applied to the not-high days in order to reduce chances of a day being misclassified as not-high if an hourly peak had gone undetected due to missing data. 3 These considerations do not apply to high days, since if a high value was detected at a given hour, the day could not be classified as not-high no matter how many hourly readings were missing. Days with less than 18 hr of data available were, with the exception of weekend days, assumed to be randomly distributed, so that the use of unequal criteria for high days and control days should induce no systematic bias. At Stations 2, 18, and 19, at most only 12 hr of data were available every Saturday and Monday and no readings were available on Sundays due to the weekend shutdown of these stations. To control for this systematic difference, analyses for the averages of Stations 0 and 2, and Stations 18 and 19, were restricted to pollution measurements falling on days Tuesday through Friday. Three levels of SO2 concentration were chosen as thresholds for the classification of a day as high or not-high. The 0.5 ppm level corresponds to that recently proposed as the federal hourly standard and is a concentration at which most asthmatics responded while exercising strenuously under laboratory conditions. Aside from Station 0, which is situated in the area recording the highest level of air pollution in New York City, days when hourly levels exceeded 0.5 ppm were rare and thus there would be little statistical power to detect any but the strongest effects. The 0.1 ppm level corresponds to one of the lowest concentrations ever reported to elicit a bronchoconstriction response under laboratory conditions. Hourly levels over 0.1 ppm were encountered frequently at all stations in the aerometric network; indeed during the first study year there were few days, especially at Station 0, when levels did not exceed 0.1 ppm. This represents the lowest threshold that may reasonably be investigated. The 0.3 ppm level, midway between the other two levels, represents a compromise in terms of severity of expected response and data availability. All stations regularly experienced levels this high or higher, at least until 1971, yet these levels were not so common as to make control days scarce. Days with no hourly readings above 0.1 ppm (0.1 controls) represented the least polluted days and provided the most stringent controls. The 0.1 control days were compared with the days high by the 0.1 ppm criterion and also with days high by the 0.3 and 0.5 ppm criteria to provide the sharpest possible contrast in exposure levels. Similarly, 0.3 controls were compared with days high by both the 0.3 ppm and 0.5 ppm criteria (but not with days high by the 0. I ppm criterion). The 0.5 control days were only compared with days high by the 0.5 ppm criterion, since they included most of the days high by the 0.1 and 0.3 ppm criteria. Emergency room statistics at Harlem Hospital were examined to determine 3 Missing data were due to instrumentation malfunction.
336
GOLDSTEIN AND WEINSTEIN
adult asthma attack incidence in Harlem, and statistics from Cumberland Hospital and Kings County Hospital were pooled to obtain rates for the general area of Bedford- Stuyvesant. " H i g h " numbers of emergency room visits were defined in two ways. "Adays," which were taken to represent asthma epidemic days, were defined as in (16) as being all days for which the probability of observing the actual number of visits was less than or equal to 0.05 assuming a nonhomogeneous Poisson distribution. As was done by Goldstein and Dulberg (16), the expected number of visits on a given day was taken as the 14-day moving average of asthma visits for the 7 days preceding and the 7 days following the day in question in order to control for seasonal effects and long-term trends in asthma attack incidence. In the second approach, high days were defined as days on which the observed number of visits was simply greater than or equal to the 14-day moving average centered around that day. Days already identified as A-days by the first approach were excluded to allow for a possible intrinsic difference between A-days, which were taken to represent asthma epidemic days, and nonepidemic days. The analysis of above-average days was only carried out for Harlem Hospital data compared with Station 0 measurements taken on the same day for the first year of data (1969). This is the most favorable subset of the data to be used for the analysis, since 1969 contained the greatest number of high-pollution days and the air pollution data from Station 0 in Harlem are the most complete. Since a greater number of A-days were observed in the autumn that in any other season, the use of a full year of data gives us more opportunity to detect factors related to increases in asthma visits that are less extreme than those represented by the A-days than does the use of fall seasons alone, as done by Goldstein and Dulberg (16). In any model assuming a causal relation of SO2 peaks to asthma attacks, the SO2 exposure must precede the asthma attack. Data available for the present analysis included the time of day of SO 2 measurements; however, the actual hour of the day for emergency room visits was not readily available for all of the hospitals. The analysis was therefore done at the level of days, neglecting the timing of the SO 2 peaks and asthma visits within the days. Without knowledge of times of visits, those visits that occurred before a pollution peak and so could not have been influenced by that peak would be included among all the visits examined for a relation to that peak, thus serving to attenuate any relation that may be present. The extent of this problem is minimized, however, by the observation that most of the pollution peaks occur early in the day, so that the majority of emergency room visits on a given day would have occurred after the times of highest SO 2 levels anyway. This problem is also avoided when asthma visits are examined for days following the day on which a high SO2 reading was observed, but in this case the time allowed between exposure and outcome might also allow for exposures to other etiologic agents which would introduce considerable scatter into the results.
Potential Difficulties Day-of-the-week effects. Previous studies of fall seasons in the same data set
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AIR POLLUTION AND ASTHMA
TABLE 1 PROPORTIONS OF DAYS a WITH AT LEAST ONE HOURLY VALUE ABOVE THREE THRESHOLDS BY DAY OF THE WEEK, STATION 0, DECEMBER 1968 THROUGH FEBRUARY 1972 Threshold 0.1 p p m 0.3 p p m 0.5 p p m Total days (N)
Sun
Mort
Tues
Wed
Thurs
Fri
Sat
Overall
0.635 0.060 0.018
0.745 0.133 0.024
0.769 0.112 0.030
0.749 0.108 0.012
0.763 0.095 0.018
0.775 0.148 0.012
0.685 0.095 0.000
0.732 0.107 0.016
167
165
169
167
169
169
168
1174
a With 18 or m o r e hr of data available.
(16) and studies of an expanded data set including 9 years of data from the three hospitals over all seasons (21) show a pronounced excess of asthma visits on Sundays and Mondays for adults in all seasons, with the excess greatest in the fall season. To account for effects of social factors, which might influence the utilization of medical care facilities independently of the incidence of disease, day-ofthe-week patterns were also examined for nonasthma respiratory disease, and for illness other than respiratory disease or trauma. An excess of emergency room visits for these causes was again found on Mondays, however, Sundays were found to have about the same or fewer average visits than other days of the week. The day-of-the-week effect for nonasthma visits may be attributed to such social factors as a reluctance to return to work or school after a weekend, or the availability of medical care, which might also account for the high frequency of asthma visits on Mondays. Unless there is something special about social responses to an asthma attack as opposed to other respiratory problems, the excess in asthma visits on Sundays may be taken as representing a true increase in incidence. A day-of-the-week effect can also be seen in the SO 2 data from Station 0, examined according to the proportions of the different days of the week with at least one hourly reading over a given threshold (see Table 1). Here it may be seen that, at least for the two lower levels, there were fewer SO 2 peaks on the weekends (Saturday and Sunday) than on weekdays (Monday through Friday). Comparison of the day-of-the-week patterns of asthma and of SO2 peaks reveals a potential problem for the analysis. If day of the week, acting through whatever mechanisms, can cause asthma to be high on Sundays and Mondays, and pollution to be low on Saturdays and Sundays, then a causal relation between pollution and asthma might be overwhelmed by the competing influences of factors dependent on the day of the week. (Such factors might include the social factors giving rise to Monday highs for emergency room visits, cyclic etiologic factors giving rise to Sunday highs for asthma, and weekly patterns of fuel combustion.) An alternative explanation for the contrasting day-of-the-week patterns of asthma and SO2 peaks is that low pollution levels give rise to increases in asthma, but such an explanation seems unlikely. Trends in asthma following reduction of air pollution in New York City. Contrasting secular trends in SO2 and asthma attack data also pose a potential difficulty. On the one hand, SO 2 levels and the frequencies of the variously defined SO 2 peaks declined steadily over the 3-year period of the study. On the other hand, the numbers of asthma visits in the three hospital emergency rooms re-
338
GOLDSTEIN AND WEINSTEIN
mained relatively constant when changes in hospital utilization are accounted for, as may be seen in Table 2, where the percentage contribution of asthma and total respiratory visits to the total emergency room count are tabulated. Although absolute numbers of total emergency room visits increased in this interval, visits due to asthma and respiratory causes in general kept pace with the increase in utilization, so that the apparent asthma attack incidence did not decrease with the decrease in pollution levels. These two trends might be taken as evidence that sulfur dioxide levels, whether measured as hourly levels or long-term averages, cannot be factors contributing to rates of emergency room visits for asthma. Alternatively, it may be that exacerbations of air pollution trigger prematurely asthma attacks that had been developing over a period of time, thus affecting the distribution of attacks without affecting their number. For this reason, in an analysis over the entire period from 1969 to 1971, a relation between asthma and SO2 in the first year may be diluted in the second and third years, as instances where pollution is sufficient to cause significant elevations in asthma decline. Analyses were therefore performed separately for the first year of data and for the 3-year period as a whole. Days of high average S02 levels vs days with high hourly SO 2 levels. Previous studies of the relation of health indicators to pollution variables have been sensitive to charges that daily or longer-term average pollutant level may not reflect the occurrence of short-term peaks, which may have a greater significance for health. The availability of hourly data from the New York City Aerometric Network permits the evaluation of the relation of days with high average SO2 levels to days with high hourly SO 2 readings, which are taken to represent days with short-term peaks. We therefore compared the days identified as high in SO2 by Goldstein and Dulberg (16) according to the criterion of a daily average SO2 level corresponding to a probability of less than 0.10 on a normal distribution, with days identified as high based on the presence of an hourly value above 0.3 ppm. As can be seen from Table 3, for the period from the fall of 1969 through the
TABLE 2 PERCENTAGES OF TOTAL ADULT EMERGENCY ROOM VISITS REPRESENTED BY ASTHMA AND TOTAL RESPIRATORY DIAGNOSES IN THREE NEW YORK CITY HOSPITALS 1969-1971 Cumberland Hospital %
Na
1969 1970 1971
5.27 5.10 5.20
63,288 71,280 75,465
1969 1970 1971
16.27 15.56 16.53
63,288 71,280 75,465
Kings County Hospital %
Harlem Hospital
N
%
N
Asthma visits 3.33 3.21 3.05
151,545 163,716 172,439
b 3.99 3.06
104,189 103,263
Respiratory visits 13.92 14.93 15.26
151,545 163,716 172,439
b 13.30 12.57
104,189 103,263
a N is the total number of emergency room visits for all causes. b Data for Harlem Hospital, 1969, are incomplete.
339
AIR P O L L U T I O N A N D A S T H M A
TABLE 3 OVERLAP OF DAYS OF HIGH SO 2 IDENTIFIED BY DAILY AVERAGE AND BY HOURLY READINGS,
AUTUMN1969 TO WINTER1970-1971 No. of days high according to Hourly criterion
Daily average criterion
Both criteria (overlap)
City-wide average compared with Station O, 2, 18, and 19 hourly data Autumn 1969 17 5 Winter 1969-1970 32 5 Spring 1970 9 6 Summer 1970 1 6 Autumn 1970 8 6 Winter 1970-1971 12 4 Total
79
32
Station 0 daily average compared with Station 0 hourly data Autumn 1969 16 5 Winter 1969-1970 25 7 Spring 1970 7 8 Summer 1970 0 10 Autumn 1970 7 9 Winter 1970-1971 10 10 Total
65
49
3 5 5 0 3 2 18 5 7 5 0 4 6 27
winter of 1970-1971 (for which the G o l d s t e i n - D u l b e r g analysis had been done) in no season did the days identified as high by the two criteria entirely overlap. Instead, for m o s t seasons there existed a substantial n u m b e r of days classified as high by one or the other criterion, but not both. These comparisons d e m o n s t r a t e that the previous analysis of the same data set, and p r e s u m a b l y other analyses based on daily averages, was not sufficient to investigate the hypothesis that a s t h m a is related to hourly peaks. The results of those studies thus do not apply to the present investigation.
RESULTS
A-Days The analysis involved a test for an association between A-days and days of high SO2, defined by various criteria, which were contrasted with days of not-high SO2. Proportions of high and control SO2 days that were also A-days were first c o m p a r e d for individual seasons within a year, and, when no clear difference a m o n g the seasons emerged, the seasons were combined into calendar years and within the 3-year period as a whole. Significance testing of the association between A-days and days of high SO 2 for the first year and overall (see Table 4) resulted in no P values less than 0.05. For the 1 out of 57 associations that app r o a c h e d a P v a l u e o f 0.05 ( H a r l e m H o s p i t a l c o m p a r e d w i t h S t a t i o n 0, 1969-1971, same day, 0.3 high, 0.3 control, P = 0.051), comparison of the same
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high days with more stringent controls (0.1 level--days with no reading above 0. l ppm) did not produce the stronger relationship that would be expected if A-days were truly related to pollution levels. We conclude that this almost-significant result arose due to chance. It is interesting to note that the second lowest P value (P = 0.075, Harlem Hospital compared with Station 0, 1969 visits on day following SO2 measurements) was obtained for a situation in which the rate of Adays was higher on days for which no hourly value exceeded 0.1 ppm than on days which had at least one hourly reading above 0.1 ppm. This result further supports the contention that differences are due to chance, since the direction of the difference is not consistent. If a one-sided test of significance had been used, the former result would be significant, but the interpretation that it is due to chance woud be unchanged, since it would not be coherent with other results.
Above-Average Asthma Days In order to detect any less extreme effect of SO2 peaks on emergency room statistics for asthma, analyses were also made of associations between days of above-average asthma visits, excluding A-days and days of high SO2, by various criteria, for a subset of the available data. No outstanding seasonal effects in the comparison other than what would be expected when small numbers are involved are evident. To avoid problems of zero cells and to reduce the likelihood of a significant result arising due to chance, formal statistical analysis was done only for the year 1969 as a whole (see Table 5). Again, no relation even comes close to significance, and no clear direction of association is seen.
DISCUSSION The present study was undertaken to examine the relationship between ambient SO2 peaks and asthma in two inner-city areas of New York City. Statistical tests were made for an association between days on which high hourly levels of SO 2 were recorded by stations of the New York City Aerometric Network, and days on which high numbers of asthma emergency room visits were seen at three inner-city municipal hospitals. The measurements were made at locations within TABLE 5 SIGNIFICANCE TESTING OF ASSOCIATION BETWEEN NON-A-DAYS WITH VISITS ABOVE A 14-DAY MOVING AVERAGE AND HIGH SO 2 MEASURED BY STATION 0, ON THE SAME DAY, 1969 a High SO 2 level (ppm)
Control SO 2 level (ppm)
AS
KS
AS
A--S
P value b
0.1 0.3 0.3 0.5 0.5 0.5
O. 1 O. 1 0.3 O. 1 0.3 0.5
104 22 22 6 6 6
157 36 36 8 8 8
15 15 97 15 97 115
34 34 155 34 155 181
0.291 0.571 0.946 0.609 0.970 0.986
a See note to Table 4. b All significance Testing done by
X2
test.
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the catchment areas of the hospital emergency rooms studied. Three different criteria for high SO2 were used, spanning a range from that definitively associated with asthma symptoms in the laboratory but rarely encountered in the environment, to that producing responses under certain conditions in the laboratory but so common in the environment as to make comparison days extremely rare. Comparisons were made between days on either side of a dividing line, and days representing opposite extremes in air pollution levels. Two separate types of outcome variable were examined: asthma epidemic days, defined as being days of asthma visits greater than the 0.05 level on the Poisson distribution [which occur more often than expected due to chance (16)], and days when asthma visits were above a 14-day moving average but which were not epidemic days. To allow for any time lag, asthma emergency room visits on days following high and not-high SO2 measurements were compared as well as asthma emergency visits on the days of high and not-high SO2. An attempt was made to look for gross seasonal effects, as well as to control for secular trends of decreasing pollution levels. Certain of the P values approached the customary cutoff value of 0.05, however, no more than would be expected due to chance given the large number of statistical tests performed. Considerations of plausibility support the conclusion that the marginally significant results obtained result from the play of chance, as these relations do not persist as the comparisons become more extreme, as would be expected of a true relationship. In addition, the direction of association is not consistent. Thus we can conclude that there is no significant association between days when high hourly levels of SO 2 were measured and days with high numbers of emergency room visits for asthma in New York City. A possible factor accounting for the finding of no statistical significance in any investigation is that of power. If the numbers of observations made were not sufficient to allow the probable detection of an association of a given magnitude if it existed, then failure to detect such an association cannot be attributed solely to the lack of association. To test for this possibility, calculations were performed for three test comparisons believed to be representative of those used in the analysis. The method used was that of Levin (22) with the number of strata equal to 1 and the odds ratio taken as the measure of excess risk. In this analysis, the odds ratio represents the ratio of the odds of a day being a day of high asthma if it is high in SO2, with the odds of its being a day of high asthma if it is not high in S Q ; it does not relate to odds for individuals. In order to translate this odds ratio into a meaningful figure in terms of emergency room utilization or population morbidity, calculations of the absolute and percentage increases in emergency room visits corresponding to each hypothetical value of the odds ratio for days were performed according to the method outlined in (16). As can be seen from Table 6 although power to detect an odds ratio of 2, corresponding to 7.8 and 5.4% increases in the numbers of visits, was poor, the analysis should have been able to detect a 20-25% increase in visits, at least for the comparisons using days high by the 0.3 ppm criterion. Power would be expected to be lower in comparisons of the averages of Station 0 and 2, and Station 18 and 19 data, due to the fewer observations available for these averages (due to missing data), but will be greater for analyses done over the entire study period. Power would also be greater for corn-
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TABLE 6 POWER CALCULATIONS FOR TEST OF ASSOCIATION BETWEEN DAYS OF HIGH SO 2 AND A-DAYS (ON THE SAME DAY) FOR SELECTED COMPARISONS OF STATION 0 DATA AND HARLEM HOSPITAL RECORDS FOR 1969
Odds ratio 2
3
4
5
6
1.15 7.8 12
2.01 13.7 25
2.68 18.2 38
3.21 21.8 48
3.65 24.8 56
1.15 7.8 30
2.01 13.7 55
2.68 18.2 78
3.21 21.8 88
3.65 24.8 94
0.76 5.4 34
1.41 10.0 74
1.95 13.9 92
2.41 17.3 98
2.83 20.1 99
0.1 high vs 0.1 control m(o)) a
% Increase b Power (%) 0.3 high vs 0.l control A(co) % Increase Power (%) 0.3 high vs 0.3 control A(co) % Increase Power (%)
A(co)is definedas the absolute increase in asthma visits as a functionof~o,the odds ratio for days. b % Increase is the correspondingpercentageincrease in visits.
parisons of rates of above-average emergency room visits on days of high and not-high SO2 since the distributions of visits between above- and below-average are more uniform. The results show that emergency room visits for asthma are not associated with high hourly measurements of SO2 at locations situated in areas served by the hospitals despite laboratory demonstrations that levels of SO2 similar to the ones encountered here induce airway responses and symptoms in exercising asthmatics. But the nature of the study must constrain the inferences that may be drawn from it. The present study was an ecological study, conducted at the levels of populations and of areas, so that all the uncertainties involved when associations are not examined in individuals apply. In the first place, exposures were measured at one or two locations (usually on the roofs of buildings) assumed to be representative of the population exposures. The demonstration (23, 24) of small-scale variations in pollution patterns with little spatial correlation, and the dependence of these variations on meteorological and other factors, however, make the representativeness of the measures uncertain. In the second place, even if the measurements were representative of what people breathed when they were outside, they most assuredly did not represent SO2 levels indoors, which are known to be substantially less than outdoor levels. Indoor exposures take on an even greater importance when it is realized that, on the average, our study population spends over 90% of its time indoors (25), and that a wide variety of agents known to trigger asthma attacks are found in the home. Other factors that may tend to obscure a true relationship between asthma and SO2 include the apparent requirement that at least fbr the 0.01 ppm SO2 levels susceptible subjects be breathing through their mouths when the peak pollution level is encountered, and
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that other etiologic agents and social factors may cause A-days when pollution is low.
The Role of Temperature A factor not included in the present analysis is ambient temperature. As temperature is associated both with levels of atmospheric SO 2 and with asthma, it may act as a confounder, giving rise to a spurious direct or inverse relationship between asthma and SO2 caused by the covariation of both outcome and exposure variables with temperature. It is therefore important to make sure that any result obtained in a study of asthma and air pollution reflect the true relationship between these factors and not the relation of these factors with a third factor (temperature). In the present case, examination of the probable directions of relationship of temperature with the two variables in question shows that temperature is not a plausible cause for the lack of a relationship. A drop in temperature is usually associated with an increase in pollution as more fuel is burned to provide heat and electricity. A drop in temperature is also most plausibly associated with an increase in asthma, due to the demonstrated sensitivity of some asthmatic individuals to cold air. The most plausible effect of temperature, if it did play a role as a confounder, would thus be to create a spurious direct relation between SO2 and asthma, and not to conceal one that truly existed. Since no relation between SO2 and asthma was found, it may be concluded that the role of temperature was insignificant in the present analysis. It must be emphasized that the present results do not rule out a relationship between asthma and ambient levels of SO2. Sulfur dioxide peaks may yet trigger asthma attacks in some asthmatics under natural conditions, but the ecological approach may be too crude to detect an effect. More useful studies to answer the questions posed by the laboratory research on SO2 and to account for the high prevalence of asthma in inner-city areas would have to be conducted on the individual level, where the actual exposures of an individual could be assessed and correlated with asthma attack incidence over time. Korn and Whittemore (26) have developed a statistical methodology for use in the analysis of individuallevel studies on acute health effects of air pollution, and we hope to use it in a study currently under way among inner-city residents with asthma. REFERENCES 1. Sheppard, D., Wong, W. S., Uehara, C. F., Nadel, J. A., and Bousbey, H. A. (1980). Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Amer. Rev. Respir. Dis. 122, 873. 2. Sheppard, D., Saisho, A., Nadel, J. A., and Boushey, H. A. (1981). Exercise increases sulfur dioxide-induced bronchoconstriction in asthmatic subjects. Amer. Rev. Respir. Dis. 123,486. 3. Linn, W. S., Bailey, R. M., Shamoo, D. A., Venet, T. G., Wightman, L. H., and Hackney, J. D. (1982). Respiratory responses of young adult asthmatics to sulfur dioxide exposure under simulated ambient conditions. Environ. Res. 29, 220. 4. Linn, W. S., Shamoo, D. A., Spier, C. E., Valencia, L. M., Anzar, U. T., Venet, T. G., and Hackney, J. D. (~993). Respiratory effects of 0.75 ppm sulfur dioxide in exercising asthmatics: Influence of upper respiratory defenses. Environ. Res. 30, 340. 5. Linn, W. S., Venet, T. G., Shamoo, D. A., Valencia, L. M., Anzar, U. T., Spier, C. E., and
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