HEALTH EFFECTS OF SULFUR OXIDES
A number of studies have focused on the effects of air pollutants in children. This is a useful group to study, in that their lesser mobility produces a more homogeneous pollution exposure and the effects of cigarette-smoking and occupational exposure are minimized. Furthermore, children appear to be at greater risk than healthy adults, owing presumably to their greater degree of mouth-breathing, relatively greater tidal volumes, and higher frequency of respiratory tract infections. The effects of air pollutants in children have been reviewed by a committee of the American Academy of Pediatrics (1970) and more recently by Wehrle and Hammer (1974).
An increase in the death rate of the very young has been noted in some, but not all, studies of air pollution episodes. Logan (1953) noted an increased neonatal and infant mortality in the December 1952 London fog episode, but Greenberg et al. (1967) did not observe any change in death rate in this age group during a less severe 2-week episode in New York in 1963. Lave and Seskin (1970), in their broad statistical analysis of the effects of air
pollution in the United States, have suggested an association with neonatal mortality.
A number of large-scale British studies have evaluated the effects of air pollution on the health of children. Colley and Reid (1970) surveyed respiratory disease prevalence in 1966 in over 10,000 children 6–10 years old in England and Wales with a questionnaire and measured peak expiratory flow rates. A social-class gradient was observed for chest disease, but a pronounced increase in prevalence was observed in each social class in association with greater pollution. This was particularly true in the children of unskilled and semiskilled workers. An unexplained excess in prevalence in Wales may represent an ethnic difference. Small differences in peak expiratory flow rate were found when the results were calculated independently for those with and without a history of respiratory disease or symptoms. The authors point out that differences may have been obscured by difficulties in standardizing the observers and the 70 peak flow meters used in the study.
Another British study of over 10,000 children was performed at about the same time by Holland et al. (1969) in different areas of Kent. They observed independent and additive effects of social class, family size, history of significant respiratory disease, and area of residence on pulmonary function, as measured by peak expiratory flow rate. Residential area appeared to have the greatest influence on pulmonary function; this suggested an effect of air pollution. However, the authors note that all four factors together accounted for only about 10–15 percent of the total variation; other determinants, possibly including host factors, are probably also important. Only minimal pollutant monitoring data are presented that describe the monthly average smoke concentrations in three of the four areas studied for November 1966 to March 1967. In the most polluted area, which had the lowest peak expiratory flow rates, the highest recorded monthly average smoke shade was 96 ug/m3.
A study by Douglas and Waller (1966) evaluated over 3,000 children 15 years old who
had been born in the first week of March 1946 and were followed regularly as part of a comprehensive health survey. Domestic coal consumption was used to divide areas into four pollution classes. The frequency and severity of lower respiratory tract infections were clearly related to air pollution. However, no consistent effect on upper respiratory infections, otitis, or tonsillitis was observed. The following factors demonstrated a gradient of air pollution effect, in that there was an increase at each succeeding stage of pollution severity: first lower respiratory tract infection before the age of 9 months and before age of 2 years; more than one attack in first 2 years for both boys and girls; hospital admission for bronchitis in first 5 years; pulmonary rales or rhonchi noted on two or more chest examinations or by the age of 15; excess episodes of school absences; and long periods of absence from primary school for bronchitis. Only small differences in social class among the air pollution categories were noted, and this factor was not evaluated further. Nor were other possible variables, such as crowding, assessed. Some data are given in the appendix concerning air pollution in 1962–1963. As indicated by the authors, this must be approached with caution, particularly as pollution was probably worse in earlier years. Taken as a whole, the data give an impression of linearity of response (lower respiratory infection) in children to air pollution beginning at somewhat higher than present U.S. standards for total suspended particles and sulfur dioxide.
This cohort of children born in 1946 was reevaluated at the age of 20 (Colley and Reid 1970). The most noticeable finding was the dominant effect of cigarette-smoking on the respiratory symptoms of these young adults. A history of chest disease before the age of 2 also had a significant, but smaller, effect. After adjustment for these two variables, air pollution had only a small and not statistically significant effect. The same was true for socioeconomic class. There was a tendency for the air pollution effect to be greatest in the lower socioeconomic classes; this suggests an
interaction between these two variables in the production of respiratory symptoms. As pointed out by the authors, the nonresponders to the follow-up questionnaire were overrepresented in the high-pollution category, which might tend to bias the results. However, the results are consistent with those of other studies and indicate that the effects of air pollution on young adults are minimal at most, particularly in relation to cigarette-smoking.
Lunn et al. (1970, 1967) evaluated children in Sheffield, England, in 1965 and were able to repeat the study on some members of the same group 4 years later, when air pollution had decreased. This type of study, in which a cohort is reevaluated after a change in the environment, has also been performed in Berlin, New Hampshire, and is of great value in ascertaining the effects of air pollution. At the time of the original study, there was a distinct gradient in air pollution in the four districts under evaluation. In 1964, the cleanest area had a mean daily sulfur dioxide concentration of 123 ug/m3 and mean daily smoke of 97 ug/m3. The mean daily sulfur dioxide and smoke values in the other areas were 183 and 230, 219 and 262, and 275 and 301 ug/m3. Questionnaires were sent to the parents of 5-year-olds living in the vicinity of the school. The children were then examined, and pulmonary function tests were performed. Socioeconomic class, number of children at home, and number of persons sharing the same bedroom all had some effect on the findings. However, when the data were evaluated within each social class, a distinct increase in respiratory morbidity for both upper and lower respiratory diseases was observed. For the lower socioeconomic classes, a history of persistent cough was obtained in 23.9 percent of the children in the cleanest area, and there were stepwise increments in from each area as the pollution increased—39.6 percent, 43.8 percent, and 60.9 percent. Lower-than-predicted forced expiratory volume (0.75 sec) and forced ventilatory capacity were observed only in the most polluted community. The 11-year-olds examined at the same time had similar, but less marked, differences between areas.
When the original 5-year-old group was reexamined 4 years later, in 1969, the differences between areas had narrowed and were not statistically significant. A major decrease in air pollution had occurred; in 1968, mean daily sulfur dioxide and smoke concentrations for the four areas were 94 and 48, 166 and 41, 186 and 118, and 253 and 169 ug/m3. There was also less respiratory disease in this 9-yearold group than in the 11-year-olds evaluated 4 years earlier. It should be emphasized that this lessening in a gradient of respiratory disease was associated with about a 45–80 percent decrease in particles, as measured by smoke, with only approximately a 10–25 percent decline in sulfur dioxide. Furthermore, during the latter part of the study, the smoke and sulfur dioxide concentrations were still appreciably above American air quality standards. Unfortunately, no data on ambient concentrations or gradients for sulfate are available.
Biersteker and van Leeuwen (1970) evaluated peak flow rates in about 1,000 schoolchildren in two districts of Rotterdam: a wealthy suburban area in which winter mean smoke concentration was about 50 ug/m3 and winter mean sulfur dioxide concentration was 200 ug/m3, and a poorer urban area with about 50 percent higher pollutant concentrations. Air pollution monitoring techniques are not described. Although the children in the cleaner area generally had higher peak flow rates, this could be accounted for by differences in height and weight. In fact, following multiple regression analysis, there was a slight but statistically significant increase in peak flow rates in the polluted area. The authors also observed a statistically significant increase in the prevalence of childhood chronic bronchitis in the more polluted area (5.5 percent), compared with the cleaner area (1.0 percent). A smaller, nonsignificant increase in asthma rate was also found (2.2 percent vs. 1.7 percent).
A number of Japanese investigators have also reported an association of sulfur dioxide and particles with prevalence of respiratory morbidity and a decrease in pulmonary function in children (Kagawa et al. 1974, Toyama 1964).
Responses appear to occur at relatively low pollutant concentrations. However, as discussed earlier, there is some question as to whether the results can be extrapolated to the U.S. population.
As part of the Nashville air pollution study, Sprague and Hagstrom (1969) observed that sulfation rates correlated with middle-class deaths in the age range of 1–11 months and that dustfall was associated with neonatal deaths. However, the authors found it difficult to remove socioeconomic factors, which varied with air pollution, as well as with neonatal and infant mortality. Furthermore, their assignment of arbitrary linear numbers to different socioeconomic classes is questionable.
Collins et al. (1971) studied environmental factors affecting child mortality in England and Wales during 1958–1964. Included in this analysis were indexes of domestic pollution, industrial pollution, proximity of a power station, social class, overcrowding, population density, and education. Each of these factors except power-station proximity was significantly correlated (p<0.001) with the mortality of infants less than a year old. Because all the social indexes were highly intercorrelated, it was difficult to disentangle their individual effects. However, partial correlation analysis showed that the bulk of the increased mortality could be attributed to domestic and industrial pollution. Unfortunately, the data are not presented in such a way as to permit assessment of a possible dose-response relationship.
As part of the Berlin, New Hampshire, study (described in more detail later), Ferris (1970) investigated the relation of air pollution to school absences and pulmonary function. First-and second-graders from seven schools were studied in 1966–1967. No consistent effect of air pollution on total school absence rates or school absences due to respiratory illnesses were observed. A relationship may have been obscured by the fact that not all children lived close to their schools. There were some statistically significant differences in pulmonary function, particularly peak expiratory flow rate, that suggested an effect of air
pollution. The worst school (school A) in terms of pulmonary function was subjected to much higher amounts of dustfall, but not of sulfur dioxide (as measured by lead peroxide candle), which suggests that the effect was due mainly to particles. However, school A’s pupils were of a lower socioeconomic class than those of most of the other schools. The only other school with pupils of a similarly low socioeconomic class (school J) was in an unpolluted area, and, although pupils in school A tended to have lower pulmonary function than those in school J, the difference was not reported to be statistically significant.
Anderson and Larsen (1966), in a similar study of first-graders in British Columbia, were also unable to show an effect of air pollution on school absences. However, there was a statistically significant decrease in peak expiratory flow rate in the two towns affected by a Kraft pulp mill, compared with that in the clean town. This may have been related to ethnic differences, which were not studied. Air monitoring data are not presented.
A recent study by Mostardi and Leonard (1974) reported a decrease in pulmonary function in high-school students in Barberton, Ohio, an industrialized area, compared with that in Revere, Ohio, a more rural community. These students had initially been evaluated in 1970 and were restudied in 1973. Socioeconomic factors were said to be similar. The Barberton students had a statistically significant and similar decrease in vital capacity in both periods: a decrease in 1-sec forced expiratory volume in 1970, but not 1973, and in maximal aerobic capacity on exercise (Vo2 max) when tested in 1973. No difference was observed in maximal midexpiratory flow rate, an index of small-airway disease. The finding of a difference in Vo2 max is of interest, in that this test is usually not performed in air pollution studies and has potential health significance. However, this result could conceivably be accounted for by a relative lack of routine exercise in the urban group, although participation in organized athletics was similar. The air monitoring data show that
Revere cannot be considered a low-pollution community, in that yearly mean concentration of total suspended particles, which decreased from 83 to 71 ug/m3 from 1969 to 1973, was generally greater than the U.S. air quality standard. Furthermore, the sulfur dioxide concentration (by lead peroxide candle, 0.96 mg of sulfur trioxide per 100 cm2 per day in 1971) was much higher than that recorded in Berlin, New Hampshire, although there is an unexplained decrease to 0.36 mg/100 cm2 per day in 1972. The air monitoring data for Barberton show a peak yearly mean 24-hr concentration of total suspended particles of 109 ug/m3 in 1969, which decreased to 77 ug/m3 in 1973, and peak yearly sulfur dioxide of 1.11 mg/100 cm2 per day. This study tends to support an association between a decrement in childhood pulmonary function with air pollution slightly above the current U.S. standards for total suspended particles and sulfur dioxide. The data, although suggestive, do not clearly indicate whether improvement in air quality had a positive effect. Potential criticism of the study includes the relatively small numbers of students tested and the lack of presented data on cigarette-smoking, although this question was apparently asked. In addition, a contemporary urban-rural difference in the use of nontobacco cigarettes is conceivable.
The Community Health and Environmental Surveillance System (CHESS) program has conducted a number of extensive studies of the health of children (EPA 1974). In the Salt Lake area, four communities were selected for a retrospective study of lower respiratory infection on the basis of an expected gradient for sulfur dioxide and suspended sulfates (Nelson et al. 1974). Pollutant concentrations for the period before 1970 were estimated from monitoring and emission data, as well as meteorologic factors. Information about lower respiratory infection in children 5–12 years old was obtained by questionnaires mailed to parents and distributed through the schools. Almost 9,000 nonasthmatic students were studied; the results indicated an increased incidence of total lower respiratory infection, croup, and
bronchitis, but not of pneumonia or hospitalization, in the most polluted community. This high-pollution community had an estimated mean sulfur dioxide concentration in 1967–1970 of 91 ug/m3, compated with 33 ug/m3 in the next highest area, and an estimated mean suspended sulfate concentration of 15 ug/m3, compared with 9 ug/m3. The concentration of total suspended particles in the high-pollution community in 1967–1970 was 63 ug/m3, which was lower than the concentrations in two of the other communities. The concentrations of suspended nitrates were similarly low in all the communities. Other factors evaluated—including the educational status of the father, mean family size, and parental smoking habits—did not appear to account for the increased incidences of croup and bronchitis in the high-pollution community. Investigation of physicians’ records tended to validate the questionnaire findings and did not reveal any difference in diagnostic patterns between communities. An analysis of the duration of residence in each area showed that the increased attack rates for croup and bronchitis in the high-pollution community were observed solely in children who had lived there for 3 years or longer. In this subgroup, the data on croup, which had the largest gradient, showed a 3-year attack rate in the high-pollution area of 26.4 percent, compared with 14.5–16.9 percent in the other communities. The 3-year attack rate for bronchitis was 23.6 percent, compared with 16.5–17.1 percent in the cleaner communities. These attack rates were adjusted for age, sex, and socioeconomic status.
It is noteworthy that people who had lived in the high pollution community for less than 3 years had much lower attack rates than short-term residents of the other communities. The explanations advanced for this finding are at best tentative. There were fewer short-term than long-term residents, so these anomalous findings decreased only slightly the overall gradient in lower respiratory infection attack rate for all residents. The questionnaire response rate was relatively low, 67 percent, and one-sixth of them had to be discarded because of inadequate information. Although a
small-scale study appeared to show no difference between respondents and non-respondents, this may have been insufficient to rule out bias. The authors also state that there was a difference in attack rate between the community with mean suspended sulfates of 9 ug/m3 and the two communities with lower suspended sulfates but higher sulfur dioxide concentrations. This statement, does not appear to be completely warranted by the data.
In general, the data do appear to substantiate an increase in lower respiratory disease in children exposed for a few years to sulfur dioxide at 90–100 ug/m3 and suspended sulfates at 15 ug/m3 in the presence of total suspended particles at concentrations below the air quality standard. No firm conclusions can be drawn, but the findings raise the suspicion of an effect of suspended sulfates.
A similar retrospective study was performed in almost 6,000 children living in five Rocky Mountain communities (Finklea et al. 1974). The gradient in sulfur dioxide and total suspended particles was much greater than in the Salt Lake Basin, and there was also a difference in suspended sulfates. Unfortunately, the analysis of the data was complicated by distinct differences in socioeconomic status and parental smoking, which varied with air pollution. After adjustment for age, sex, and socioeconomic status, an increase in the attack rate for lower respiratory infections in nonasthmatics was observed in pooled data from the two high-pollution communities. (In 1968–1970, those two communities had sulfur dioxide concentrations of 177 and 375 ug/m3, total suspended particle concentrations of 63 and 102 ug/m3, and suspended sulfate concentrations of 7.2 and 11.3 ug/m3; of the three low-pollution communities, two had relatively negligible concentrations of each pollutant, and the third, “low III” had a mean sulfur dioxide concentration of 67 ug/m3, a total suspended particle concentration of 115 ug/m3, and a suspended sulfate concentration of 7.3 ug/m3.) However, the results in nonasthmatics tended to be significant only when calculated for people who had two or more episodes and only in the subgroup that had lived
in the same community for 3 years or longer. As in the Salt Lake study, croup rates correlated better with pollution than did bronchitis. There was also a tendency toward an increase in pneumonia and hospitalization rates in the high-pollution communities, but this was not statistically significant. Again, the finding of less disease in newcomers to the high-pollution areas than in newcomers to the low-pollution areas was puzzling. A more clearcut increase in the attack rate for lower respiratory illness was observed in asthmatics, but this was a smaller group and the findings were not adjusted for socioeconomic status, etc. Accordingly, the asthma data are inadequate to support firmly the investigators’ contention of a pollutant effect in the “low III” community.
The findings are not as impressive as in the Salt Lake Basin, particularly in view of the larger gradient of sulfur dioxide and suspended particles (although not of suspended sulfates). Although comparison of these two similar studies is somewhat impeded by the larger difference in socioeconomic status between communities in the Rocky Mountain area, it should be noted that the relatively less polluted Salt Lake Basin area had higher adjusted attack rates—particularly multiple attack rates—of lower respiratory infection. Whether this represents physician diagnostic patterns, other local factors, or a difference in the administration of the two studies is unclear.
Somewhat different studies were performed in Chicago and New York in which the attack rate of acute respiratory disease in family members was obtained by telephone interview of mothers. In Chicago, data were obtained in 1969–1970 on over 2,500 families that had at least one child in nursery school (Finklea et al. 1974). No information about those who did not volunteer for the study is given. Families were assigned to pollutant categories by place of residence with reference to nearby monitoring stations. The three exposure categories were defined as Intermediate, High, and Highest, and the 1969–1970 monitoring data on sulfur dioxide and total suspended particles were 57 and 111 ug/m3 for the Intermediate category, 51 and 126 ug/m3 for
the High category, and 106 and 151 ug/m3 for the Highest category. Pollution concentrations had been much higher previously. Socioeconomic and other factors investigated were relatively similar in the three groups. Among families that had resided in the same area for 3 years or longer, there was a 48 percent increase in the risk of lower respiratory infection in the nursery-school children in the Highest category, compared with those in the Intermediate category. Older siblings had a 16 percent increase in the risk of lower respiratory infection, and younger siblings had a 9 percent increase. An increase in the risk of upper respiratory infection in children was observed only in the younger siblings. Increased illness rates in the highest-pollution community were also observed during an influenza epidemic. Relatively little information is presented for the High-pollution community.
A similar telephone survey was performed in New York in 1970–1971 (Love et al. 1974). Volunteers were obtained from two communities within New York City—Howard Beach in Queens and the Westchester area of the Bronx—that were categorized as having intermediate pollution and from Riverhead, Long Island, which was chosen as the low-pollution community. In the years preceding the study, both New York City communities had sulfur dioxide and total suspended particle concentrations well above air quality standards. However, at the time of the study, annual mean sulfur dioxide concentrations were 51–63 ug/m3, and the concentrations of total suspended particles were at or somewhat above the air quality standard of 75 ug/m3. In Riverhead, pollutant concentrations had generally been low; in 1971, the sulfur dioxide concentration was 23 ug/m3, and the total suspended particle concentration was 34 ug/m3. Suspended sulfate concentrations in 1971 were 13.2 and 14.3 ug/m3 in the two New York City communities and 10.2 ug/m3 in Riverhead. This less distinctive gradient presumably represents atmospheric oxidation of sulfur dioxide en route to Riverhead from the New York City area.
Only a slight increase in lower respiratory tract illness in New York City children, com-
pared with those in Riverhead, was observed. This was of borderline statistical significance (p=0.07). There was no difference in the attack rate for upper respiratory illness between the communities. Data are presented that suggest that respiratory illness was more severe in the intermediate-pollution communities. This was calculated by means of an arbitrary severity score whose assumed linearity is open to question. The problems with the New York City data include the proximity of the Howard Beach community to Kennedy Airport, possible differences in medical use patterns among the communities, and the lack of any trend in repeated lower respiratory tract infections in children, compared with those in other CHESS studies.
A conservative interpretation of the New York and Chicago CHESS family studies would be that they tend to add further weight to the reported association of childhood lower respiratory illness with concentrations of sulfur dioxide and total suspended particles above the current U.S. air quality standards. By themselves, however, they are not conclusive. Data on adults obtained in these studies are discussed below.
Hammer et al. (1974) have recently presented a paper on a further CHESS study in the New York area. Questionnaires concerning lower respiratory infection rates in children 1–12 years old were distributed to schoolchildren in the first through sixth grades to be filled out at home. The three New York communities previously studied and one additional area, Sheepshead Bay in Brooklyn, were evaluated. The past pollutant concentrations in Sheepshead Bay were estimated from the Howard Beach data, although the two communities are about 6 miles apart. Response rates for the questionnaire were about 80 percent. The 3-year lower respiratory infection attack rates were adjusted for the sex of the child and the educational status of the head of the household and are tabulated for the age groups 1–4 year, 5–8 years, and 9–12 years. White children in the Riverhead community tended to have lower rates for total lower respiratory illness, croup, and
(in children 5–12 years old) bronchitis, compared with the New York City communities. However, the largest gradients were observed for pneumonia and hospitalization rates in the group 1–4 years old; in these categories, Riverhead reported a much greater incidence than the New York City communities. Black children had an even greater increase than white children in lower respiratory infection, croup, and bronchitis associated with pollution. Again, there was a markedly reversed gradient for hospitalization: black children 1–8 years old in Riverhead were hospitalized with a frequency 6 times greater than that of black children in New York City. The statistical significance of these findings is difficult to determine from the unpublished manuscript.
The anomalous data on pneumonia are attributed to two physicians who were responsible for the care of a large part of the Riverhead community, although the extent to which this factor contributed to the findings is not indicated. Pneumonia rates were relatively low and therefore perhaps somewhat less reliable. It is also conceivable that hospitalization rates were affected by the availability of hospital beds. If the findings on pneumonia and hospitalization are ignored, the data show a slight but inconsistent effect of sulfur dioxide and total suspended sulfate concentrations higher than air quality standards (in conjunction with a gradient for suspended sulfates) on the lower respiratory infection rate in children. However, more information about this unpublished study would be useful.
Additional CHESS studies have evaluated pulmonary function in children. Forced expiratory volume (0.75 sec) was measured in over 2,000 schoolchildren 5–13 years old living in the three New York areas described above during the 1970–1971 school year (Shy et al. 1974). Boys 9–13 years old living in Riverhead had a slightly but significantly higher forced expiratory volume than those living in New York City. A similar nonsignificant trend for girls in this age group was also noted. In contrast, no differences in the pulmonary function of the group 5–8 years old were observed. The authors
suggest that the finding of an effect only in the older children is due to the recent improvement in New York City air quality, so that only those old enough to have been exposed to the much higher pollution of the past are affected.
In addition to some anomalous findings and possible unadjusted differences between the urban and suburban children (e.g., in cigarette-smoking), the major difficulty with this study appears to be the pulmonary function equipment, which has since been replaced because of instrument drift. This latter problem is perhaps overcome by the large numbers tested, but the findings require replication, particularly in view of the great importance of determining whether the costly control measures used in cities (such as New York) have led to a decrease in the adverse health effects of air pollution.
An earlier study in Cincinnati evaluated the forced expiratory volume of second-grade schoolchildren in six different schools paired for pollution (Shy et al. 1974), socioeconomic, and ethnic factors. Pulmonary function was measured four times a month in November 1967. February 1968, and May 1968 with the Stead-Wells spirometer, a standard but somewhat cumbersome instrument. Mean sulfur dioxide concentrations were 50 ug/m3 or less. The major pollution gradients were observed for total suspended particles, which averaged 96–114 ug/m3 in the high-pollution areas and 77–82 ug/m3 in the low-pollution areas; suspended sulfates, which averaged 8.9–9.5 ug/m3 in the high-pollution areas and 8.3–8.8 ug/m3 in the low-pollution areas; and suspended nitrates, which averaged 2.7–3.2 ug/m3 in the high-pollution areas and 2.4–2.6 ug/m3 in the low-pollution areas. Among white children, forced expiratory volume was lower in the more polluted areas, and this finding correlated best with suspended sulfates. Pulmonary function was not correlated with pollution in black children. Although the forced expiratory volume tended to be lowest in the winter months, when pollution was high, the results did not directly correlate with
pollutant measurements immediately preceding the pulmonary function measurement.
Both the New York and Cincinnari pulmonary function studies (Shy et al. 1973) have been criticized by Higgins and Ferris (1974), who, after pointing out inconsistencies in the data and the relatively small observed differences, assert that “random scatter seems to be a much more likely explanation than air pollution.”
Recently, Chapman et al. (1974) have presented a further CHESS study in which ventilatory function was evaluated in children living in Birmingham, Alabama, and Charlotte, North Carolina. These two cities are of interest, in that their sulfur dioxide concentrations are negligible and their particle concentrations tend to be high. In Charlotte, geometric mean total suspended particles had previously exceeded the air quality standard, but had declined; the concentration in 1972 was 70 ug/m3. Total suspended particle concentrations in Birmingham were appreciably higher; in 1972, the concentration was 127 ug/m3. A difference in suspended sulfates was also apparent; in 1972, Birmingham had a relatively high arithmetic mean concentration of 13.3 ug/m3, and Charlotte had a concentration of 9.7 ug/m3. Forced expiratory volume (0.75 sec) was measured in the fall, winter, and spring of the 1971–1972 school year in almost 8,000 children 5–13 years old in these two cities. In both black and white students and in both boys and girls, the forced expiratory volume was less in the more polluted city of Birmingham than in Charlotte.
As is true of other CHESS studies, the major positive finding is the consistency of an effect of air pollution, despite a number of experimental shortcomings. These include the necessity of changing the spirometer in the middle of the year because of equipment difficulties, the higher educational status of the Charlotte schoolchildren’s parents, the greater degree of school busing in Charlotte, and the use of different personnel to perform the testing in the two cities (it is hoped that this was overcome by supervisory personnel). Unexpected findings include an inverse relationship between pulmonary function and
socioeconomic class in Charlotte, a greater difference in females than in males (contrary to most other studies), and a decrease in the mean forced expiratory volume during the school year in Birmingham. It is not clear whether the anomalous data represent minor quirks of the population under study or indicate intercity variations in the performance of the pulmonary function tests. Continued study of these same children, thereby allowing each population to serve as its own control during changes in air pollution in the next few years, should provide important information.
Another recent study is that of Lebowitz et al. (1974), who noted a decrease in forced expiratory volume and maximal midexpiratory flow immediately after outdoor exercise in children living in a smelter community. This may have been related to pollution, but monitoring data are not given.
The studies described above support the contention that children are at risk when subjected to urban air pollution. This is particularly true for lower respiratory tract infections and for asthma, which is discussed in the next section. The findings further suggest that the current air quality standards for sulfur dioxide and suspended particles do not have appreciable safety factors in regard to this effect. Therefore, it should be assumed that concentrations of sulfur dioxide or total suspended particles above the present standards will result in an increase in childhood lower respiratory tract infection. There is a distinct possibility that suspended sulfates are directly related to this effect.
One crucial question concerning the benefits of further air pollution control cannot be definitely answered at present: whether repeated childhood respiratory infections result in an increase in respiratory morbidity in adulthood. Obviously, the association of air pollution with a transient minor childhood respiratory infection is of less potential public health and societal significance if such illnesses have no sequelae in adulthood. This is a controversial subject, with literature supporting both sides of the question (Colley and
Reid 1970, Holland et al. 1969, Reid 1969, Harnett and Mair 1963, Rosenbaum 1961). However, it must be emphasized that the advent of antibiotics may have greatly changed the impact of childhood bacterial respiratory illnesses while having little effect on viral illnesses. If it is accepted that the pulmonary consequences of bacterial infection may be more serious than those of the usual viral illness, then the fact that people born at the time that penicillin first became generally available are now only in their third decade makes it difficult to establish whether present recurrent childhood respiratory illnesses will lead to increased chronic respiratory disease in later adult life. Although, from the medical point of view, the available evidence indicates that it is prudent to assume that recurrent childhood respiratory infections do play a role in the eventual development of disabling chronic respiratory disease, there is at present no absolute scientific evidence to support this assumption.
Bronchial asthma is a disease characterized by attacks of marked hyperconstriction of the trachea and bronchi, leading to wheezing and gasping for breath. Treatment of an uncomplicated attack is generally aimed at bronchodilatation by pharmacologic means. As with the other respiratory disease states under discussion, it is difficult to provide a clearcut definition of this disorder without either being too restrictive or avoiding overlap with other pulmonary pathology.
In its most obvious form, bronchial asthma begins in childhood, and there is a seasonal incidence of attacks that appear to be related to an allergic precipitating factor. Between attacks, respiratory function is relatively normal, although an increased susceptibility to bronchoconstrictive agents has been noted. Bronchial asthma in adults may arise de novo or may represent childhood asthma that has failed to remit. Clinically, asthma has often been
divided into extrinsic and intrinsic types. In the former, exogenous allergens are known or suspected; the latter has no obvious cause or is associated with respiratory infections. Asthma in adults tends to be in the latter classification and, particularly when associated with respiratory infection, often has a peak incidence of attacks during the winter, rather than summer and fall, as observed with allergic individuals. It is particularly difficult in adults to formulate criteria that will distinguish true bronchial asthma from cases of bronchitis in which bronchoconstriction is more prominent than usual; such bronchitis is often characterized by the term “asthmatic bronchitis.”
The reported prevalence rates for asthma vary widely, with perhaps 3–5 percent being a reasonable estimate. The asthma mortality for all age groups in the United States in the last decade was around 2–3/100,000. This disease accounts for a reported 23 percent of all school-day absences due to chronic conditions (Gordis 1973).
Patients with allergic asthma are notably difficult to study, in view of their marked variability of response. One or more specific allergens are usually required to elicit an asthmatic attack, but many asthmatic people appear to undergo a marked hyperreactivity of the bronchial tract, so that a host of exogenous and endogenous factors, including psychologic stress, significantly interact in the genesis of an acute attack. Because asthmatics may represent an extreme on the scale of hypersusceptibility to bronchoconstriction, they appear to be ideal subjects for epidemiologic study of the acute response to air pollutants. However, the multiplicity of factors producing a response might also tend to obscure any specific reaction to pollutants. Furthermore, the seasonal nature of asthmatic attacks presumably reflects meteorologic factors, as well as variations in specific allergen sources. The extent to which factors that affect allergen concentrations are synchronous with factors that affect pollutant concentrations will have a great impact on any observed association between
asthma and air pollution. These considerations suggest that epidemiologic studies of the association between air pollution and asthmatic attacks should include relatively large numbers of asthmatics and pay careful attention to meteorologic conditions.
An association of asthma attacks with air pollution has been reported by a number of investigators and has been reviewed by Zweiman et al. (1972) and by Thomas and McGovern (1971). Retrospective questioning of residents of Donora after the 1948 air pollution disaster revealed that 87.6 percent of the asthmatics reported respiratory symptoms during this episode, compared with 77.2 percent of people with cardiac disease and 42.7 percent of the general population (Schrenk et al. 1949).
Zeidberg et al. (1961), as part of the Nashville air pollution study, evaluated 49 adults and 34 children with bronchial asthma over a 1-year period. Diaries obtained from each subject were used to calculate daily attack rates, which were then correlated with mean annual and daily sulfation rates according to place of residence. There was almost a doubling in daily asthma attack rates in areas with annual sulfation rates of 0.350 mg/100 cm2 per day or greater, compared with those in areas with sulfation rates of less than 0.150 mg/100 cm2 per day. This was due almost totally to more than a fivefold increase in adult male attack rates in the more polluted area. The 30 days with the highest sulfation rates had a 22 percent increase in asthma attacks, compared with the 46 days with the lowest pollution. When daily sulfation rates were analyzed according to asthma attack rates on the following day, the association was reported to be even more statistically significant, implying a delay in the manifestation of toxicity. The sulfation rates for the more polluted days are not specified, but other data make it probable that the high concentrations were near or below an equivalent 24-hr sulfur dioxide concentration of 0.14 ppm, which is the current standard. Linear correlation coefficients between monthly asthma attack rates and, various meteorologic conditions were calculated. These were
interpreted by the authors as not showing any consistent association of asthma attack rate with temperature. However, the tabulated data show that in four of 12 months there was a statistically significant inverse correlation of attack rate with temperature. Although not clearly stated, the lack of reported extensive analysis of the association of total suspended particles with asthma attack rates suggests that this was not believed to be a significant factor.
Panels of asthmatic subjects have also been evaluated as part of the ongoing CHESS studies in the New York City and Salt Lake City areas. The Salt Lake Basin was chosen, because a large part of its pollution is due to a single smelter source (Finklea et al. 1974). This results in appreciable concentrations of sulfur dioxide and suspended sulfates in association with relatively low concentrations of total suspended particles, nitrates, nitrogen dioxide, and other usual urban pollutants that might tend to obscure the effect of sulfur oxides. Four communities with different pollution concentrations were evaluated. In contrast with the other Salt Lake Basin CHESS studies, the data in the asthma study were related to daily air pollution within each community.
Approximately 50 panelists in each community, about half of whom were over 16 years old and who lived within 2 miles of the monitoring station, filled out a weekly diary from March to September 1971. The data evaluated were daily attack rates, 24-hr average pollution concentrations, and minimum temperatures. It should be noted that these communities were well within the annual average air quality standards for sulfur dioxide and total suspended particles during the time of the study. Only rarely were 24-hr standards exceeded. Between 16 and 33 percent of the original panel subjects withdrew from the study and were replaced at variable rates in the different communities.
The data were subjected to a complex series of statistical evaluations, and the final results were interpreted as demonstrating a definite association of relatively low concentrations of suspended sulfates with the asthma
attack rate when the minimal temperature was above 49 F. Simple correlation coefficients showed that the strongest association with asthma attack rates was the inverse of daily minimum temperature. In this analysis, a significant statistical association of suspended sulfates with asthma attacks was observed only in the high-pollution community; the low-pollution community had a negative association of asthma attack rates with suspended sulfates at all temperatures. Multiple regression analysis, which evaluated the effect of air pollutants after first considering that of minimum temperature, again showed a highly significant statistical association of sulfates with daily asthma attack rates in the high-pollution community. The data for all four communities were then combined to derive temperature-specific relative-risk models for the various concentration ranges of each pollutant. The base rate for the computation of excess risk was derived from the asthma attack rate on warm days on which there were low concentrations of the specific pollutant. Again, the most significant effect was noted for sulfates on days when the minimum temperature was greater than 49 F. In this temperature range, with the base asthma attack rate calculated for days in which 24-hr suspended sulfate concentrations were 6 ug/m3 or less, there was a 17 percent increase in risk associated with sulfate concentrations of 6.1–8.0 ug/m3, a 35 percent increase in risk associated with concentrations of 8.1–10.0 ug/m3, and a 50 percent increase in risk associated with concentrations greater than 10 ug/m3. Much smaller increases in risk were also reported in the same temperature range when the concentration of either total suspended particles or sulfur dioxide was above 60 ug/m3.
These data were also used to extrapolate expected risks for pollution concentrations at the 24-hr standard (not to be exceeded more than once a year). For sulfur dioxide, this was 254 percent, and for total suspended particles, 170 percent of the baseline on days when the minimum temperature was greater than 49 F.
Approximate “thresholds” for an effect on asthma attack rates were also calculated. As
stated in the summary of the 1970–1971 CHESS document (Finklea et al. 1974), these are worst-case estimates and are not to be taken as definitive findings. The estimated threshold for suspended sulfates is 1.4 ug/m3; for sulfur dioxide, 23 ug/m3; and for total suspended particles, 71 ug/m3. Those are all for days when the minimal temperature is greater than 49 F.
In the New York area, asthma panels were selected in three communities, two of which were designated as having intermediate pollution, and one, low pollution (Finklea et al. 1974). There were initially about 50 subjects in each panel who lived within 1/2 miles of a monitoring station, and the methods of data gathering and analysis were similar to those in the Salt Lake Basin study. All communities were consistently within the 24-hr standards for sulfur dioxide and total suspended particles at the time of the study. The study was performed from October 1970 to May 1971; that is a colder time of year than in the Salt Lake area and would miss part of the high-pollen season. The overall response rate was less than that for the Salt Lake Basin. Only 75 percent of the mailed diaries were usable in the analysis.
No consistent simple correlations were found between attack rates and individual pollutants or temperature. With multiple regression analysis after adjustment for temperature, some association of asthma attack rates with suspended sulfates was observed in two of the communities, and with sulfur dioxide and suspended nitrates in one community each. Temperature-specific relative-risk models were calculated for daily minimum temperatures of less than 30 F, 30–50 F, and greater than 50 F. Compared with those of the Salt Lake Basin studies, increases in relative risk were small. A 13 percent increase was noted for total suspended particles at 76–260 ug/m3 on days when the minimum temperature was 30–50 F. In the same temperature range for suspended sulfates, there was a 9 percent increase at 8.1–10.0 ug/m3 and an 8 percent increase when the 24-hr concentration was above 10 ug/m3. A 10 percent increase in asthma attack rate was also noted
when the minimum temperature was above 50 F and the suspended sulfate concentration was greater than 10 ug/m3. No consistent effect of sulfur dioxide on asthma attack rates was observed. Fitting of threshold functions resulted in an estimate for suspended sulfates of 12 ug/m3 when minimum daily temperature was 30–50 F and 7.3 ug/m3 for minimal temperature of less than 30 F. The threshold for total suspended particles was estimated at 56 ug/m3 when minimum daily temperature was 30–50 F; it was further calculated that, at 260 ug/m3, the 24-hr standard, there would be a 22 percent increase in asthma attack rate.
The 1970–1971 CHESS studies have received a good deal of criticism, although it must be noted that many of the potential problems are discussed in detail in the CHESS document (EPA 1974). Specific problems with the two asthma studies described above include the relatively poor response rate and high turnover, which may be inherent in diary studies of patients with this disorder; the presence of anomalous data, such as a decrease in the temperature-specific risk of asthma attacks associated with increasing sulfate concentrations on days when the minimum temperature was 30–50 F in the Salt Lake area; the failure to consider temperature change, rather than absolute temperatures; the lack of information on atmospheric allergens, which conceivably vary with pollution concentrations; and the tendency toward overanalysis and overinterpretation of the available data. Reasonable preliminary conclusions from these studies are that they do provide support for the association of air pollution with asthma attacks and that they further implicate suspended sulfates as an important deleterious component of polluted air. It does not appear to be necessary or reasonable at this time to draw firm conclusions concerning the 1970–1971 CHESS asthma studies, inasmuch as data have been collected and analyzed for later years and the reports will be forthcoming soon. If the more recent studies are able to replicate the 1970–1971 findings, this will provide much firmer support for the interpretations advanced by the CHESS investigators.
Other CHESS studies evaluating lower respiratory infection in children have also studied asthmatics. Increased attack rates of croup and bronchitis in this group were observed in both the Rocky Mountain and Salt Lake Basin study areas (Finklea et al. 1974, Nelson et al. 1974).
Investigators at the U.S. Environmental Protection Agency have also studied a panel of asthmatics in New Cumberland, West Virginia (Cohen et al. 1972). This small town was the location of a low-stack power plant that used high sulfur coal with no control measures. Of the 43 asthmatics identified in the community, the records of 20, mostly adults, were suitable for study. These people filled out weekly diaries for 7 months, which were used to calculate asthma attack rates in association with meteorologic factors and pollutant concentrations. Temperature was strongly and negatively associated with attack rates. After multivariate adjustment for the effect of temperature, all the pollutants measured—including total suspended particles, sulfur dioxide, suspended sulfates, and suspended nitrates—were also significantly correlated with asthma attack rate. However, after temperature and any single pollutant were taken into account, no significant relation with any of the other pollutants remained. Therefore, the data do not provide information on which, if any, single pollutant was responsible for the observed association. After adjustment for temperature, suspended sulfate was the pollutant most highly correlated with asthma attack rate; but, as pointed out by the authors, this may have been due to the exceptionally high correlation of suspended sulfates with temperature. Furthermore, the attack rate on days when the suspended sulfate concentration was higher than 20 ug/m3 was not significantly greater than that on days when it was lower than 20 ug/m3. In this high-low analysis, significant increases in attack rate were observed for daily total suspended particles and for daily sulfur dioxide when the points of demarcation were 150 ug/m3 and 0.07 ppm, respectively.
Other facets of this study include a commendable attempt to validate the diaries by physician visits and a relatively extensive monitoring system focused in a small area. In addition, it is one of the few point-source studies that have evaluated the effects of pollutants that originated in a power plant, rather than a smelter or pulp mill. Unfortunately, the results are handicapped by the very small number of asthmatics who were studied. In view of the great variability in the response of asthmatics, the justification for many of the highly sophisticated statistical techniques used in this study is perhaps open to question. Nevertheless, the general findings appear to support the contention that power-plant effluents are instrumental in potentiating asthma attacks.
Sultz et al. (1970) evaluated the incidence of hospitalization in Erie County, New York, for asthma, eczema (an allergic skin disorder), and diabetes mellitus in children under 15 years old, in comparison with total suspended particle concentrations and socioeconomic status. The study used the data of Winkelstein et al. (1967), who, on the basis of monitoring for 1961–1963, had previously divided Erie county into four areas of annual mean concentration of total suspended particles; less than 80, 80–100, 100–135, and more than 135 ug/m3. Four categories of social class were obtained by dividing the socioeconomic data for census tracts into quartiles. Asthma hospitalization data were obtained for 1956–1961, and eczema hospitalization data for 1951–1961. Standardized morbidity ratios were obtained by dividing the observed rates for given pollutant ranges or social classes by the total rates in the entire population. The morbidity ratios for asthma hospitalization rose steadily, from 86 percent for low pollution to 114 percent for high pollution. No consistent effect for social class was observed. There was an even steeper gradient for eczema, with morbidity ratios of 53 percent for low pollution and 130 percent for high pollution. However, there was also a wide difference for social class. The disparity between asthma and eczema hospitalization rates
in the high-pollution area, compared with the low-pollution area, was even greater when the analysis was restricted to males under the age of 5. Diabetes mellitus hospitalization rates did not appear to be associated with air pollution. No attempt was made to evaluate the effects of sulfur dioxide, nor were meteorologic conditions considered.
It is difficult to interpret the finding of an association of air pollution with an allergic skin condition. Although earlier authors had suggested that fossil-fuel combustion products, particularly sulfur dioxide, might be allergenic (Pirila et al. 1963, Pirila 1954), there is inadequate evidence to support this hypothesis. People with childhood eczema tend to develop allergic respiratory disease, but this would not account for their hospitalization with a skin condition. One possible conclusion is that this study illustrates a potential pitfall in epidemiologic studies of allergic asthma: that meteorologic conditions conducive to a distribution of pollutants in a given area may also predispose to a similar distribution of allergenic organic material.
Chiaramonte et al. (1970) studied emergency-room visits at a Brooklyn hospital during a 3-week period in November 1966 in which a sharp increase in sulfur dioxide concentrations occurred in the middle week. The highest 24-hr sulfur dioxide concentration was 0.8 ppm. A statistically significant increase in visits for all respiratory disease and for asthma was observed 3 days after the sulfur dioxide peak. This delay may have been complicated by the Thanksgiving holidays. No data on weather or on other pollutants are given.
A more recent study of the relation of asthma emergency-room visits to air pollution in New York City has been reported by I.Goldstein and Block (1974). They evaluated data from hospitals in Harlem and in Brooklyn near the Bedford-Stuyvesant area for the period of September–December 1970. Air monitoring information was obtained from nearby stations. With a linear multiple regression model, using asthma visits as the dependent variable and daily sulfur dioxide and average temperature as
the independent variables, they calculated multiple and partial correlation coefficients that demonstrated that, when temperature was held constant, there was a positive correlation between asthma visits and sulfur dioxide in Brooklyn, but not in Harlem. In both areas, the results were similar for younger and older groups and for different hospitals. Repeat analysis for the group under 13 years old in September–December 1971 at Kings County Hospital in Brooklyn replicated the 1970 findings. Negative correlations of asthma visits with temperature were observed, but these were not as strong as the positive correlations for sulfur dioxide. The tabulated data show a 50–90 percent increase in asthma emergency-room visits in the group under 13 years old on the 12 high-pollution days, when sulfur dioxide concentrations averaged 0.108 ppm. Mean daily sulfur dioxide in Harlem was similar to or slightly higher than that in Brooklyn.
Temporally, this study at least partially overlapped two other New York studies: the CHESS diary study, in which one of the panel areas was not too far from Brooklyn, and the study of Rao et al. (1973), which also used Kings County Hospital pediatric emergency-room asthma visits, including the period covered by I.Goldstein and Block (1974). As discussed below, the latter study, which used no temperature data and less sophisticated statistical techniques, did not find a correlation of asthma with sulfur dioxide concentration. The finding of strong correlations in Brooklyn but not in Harlem among similar ethnic and socioeconomic groups is unexplained. As suggested by the authors, this may indicate the presence of a causative agent that is distributed with sulfur dioxide in Brooklyn, but not in Harlem. In this respect, it should be noted that air pollution derived from the industrial areas of northern New Jersey has a tendency to pass over Manhattan before fumigating Brooklyn. Further analysis of these data for longer periods and with additional variables is underway.
Some studies have failed to show a positive correlation of air pollution with asthma
attacks. In an investigation of nighttime emergency visits to a hospital in Brisbane, Australia, Derrick (1970) reported that there was, if anything, a negative correlation between smoke shade concentration and asthma. In this area, the weather factors associated with an increase in asthma attacks were completely different from those resulting in high smoke shade concentrations.
Greenburg et al. (1964) noted a sharp increase in New York City hospital emergency-clinic visits in September that was related to the onset of cold weather, and not to air pollution. No statistically significant increase in symptoms in asthmatics in relation to air pollution was noted in a Chicago study by Carnow et al. (1969), although there was a slight tendency toward heightened morbidity on the day after increased sulfur dioxide concentrations. Meteorologic data are not presented.
Rao et al. (1973) also reported a negative correlation of smoke shade with pediatric emergency-room visits in Kings County Hospital in Brooklyn. No association with sulfur dioxide was observed. It is of interest that the period of this study, October 1970–March 1971, was also included in the CHESS investigation cited above. However, the report of Rao et al. has a number of serious deficiencies, including the lack of temperature data and the fact that the hospital district includes areas at an appreciable distance from the monitoring station. In addition, emergency-room visits may not constitute as sensitive an indicator as individual diaries. Glasser and Greenburg (1967), in a study of the November 1966 New York air pollution episode, noted an increase in emergency-clinic visits in only three of seven hospitals studied. This may, however, have been affected by the intervening Thanksgiving Day holiday.
Air pollution has also been postulated to be causally related to periodic outbreaks of asthma in New Orleans (Weill et al. 1964) and to the asthma observed in American servicemen stationed in the Yokohama (Phelps 1965) area after World War II. However, in neither case has a specific etiology been established, and the role of
products of stationary fossil-fuel combustion is in doubt.
Taken as a whole, the studies described here suggest that sulfur oxides and/or particles potentiate asthma attacks in susceptible people. Such effects might be reasonably expected to occur at pollutant concentrations somewhat above the present air quality standards in conjunction with specific meteorologic factors. The data also indicate a possible role of suspended sulfates. The degree of variability observed in these studies is probably due in part to inherent difficulties in the study of asthmatics. Whether these difficulties lead to a net underestimation of the relation of air pollution to asthma is not clear.
A puzzling facet of the association of asthma attacks with sulfur oxides is the apparent delay in the onset of the attack after peak exposures to sulfur dioxide reported in a number of studies. If particulate sulfates are the offending agents, it is possible that this lag reflects the time required for oxidation of sulfur dioxide. However, most asthma attacks occur late at night, when people tend to be indoors and at rest and when the air pollution burden is presumably at its lowest. Furthermore, the bronchoconstrictive effect of sulfur oxides observed in animals and man is usually relatively rapid. It is therefore difficult to envision the mechanisms for pollutant-induced asthma attacks on the basis of the available knowledge of sulfur oxide effects. Perhaps future studies should pay more attention to the exact time of attack and additional information should be obtained concerning the possibility that sulfur oxide exposure sensitizes the respiratory tract to the later action of other bronchoconstrictive agents.
CHRONIC BRONCHITIS AND EMPHYSEMA
Definition and Classification
Chronic lung disease may be divided into a number of classifications on the basis of such
characteristics as etiology, pathologic anatomy, and symptomatology. For some pulmonary disorders, there is generally good agreement as to the diagnostic criteria necessary to define the entity. However, most people with chronic respiratory disease have a disorder, or group of disorders, variously known as chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or chronic nonspecific respiratory disease. A major reason for the multiplicity of terms and the differing diagnostic criteria among physicians is that most patients have a combination of the pathophysiologic findings usually ascribed to different types. The following simplified discussion of chronic lung disease is presented mainly for the purpose of assisting laymen to understand the later discussion of the health effects of air pollution. (Asthma has already been discussed separately.)
Chronic bronchitis is best typified as a disorder characterized by the continuous hypersecretion of mucus into the airways, leading to problems associated with keeping the bronchial airways open. Any interference with mucociliary transport or any further stimulation of mucus production, both of which may be consequences of sulfur oxide inhalation, would have deleterious effects. Long-term exposure of animals to very high concentrations of sulfur dioxide has been found to produce an increased number of mucus-secreting cells and a pathologic picture resembling chronic bronchitis.
Emphysema, in its purest form, refers to destruction and dilation of alveoli, the air sacs where gas exchange occurs, and hyperinflation of the lung. In the United States, the term “chronic obstructive pulmonary disease” has often been used, and this can be divided into two types=Patients with type A, in which alveolar destruction predominates, tend to have severe shortness of breath, but little cough or sputum production. Patients with type B have mostly brochitic findings—they experience pronounced cough and sputum production with less shortness of breath. Although it is more common in type B disease, patients with both types often develop secondary heart disease (cor
pulmonale). These types appear to represent the extremes of a continuum, with most patients having a mixture of alveolar destruction and bronchial hypersecretion. In general, longstanding chronic bronchitis leads to emphysema, although emphysema is occasionally observed in the absence of bronchial hypersecretion. With respect to the effects of sulfur oxides, it is apparent that pollutants that tend to be absorbed in the upper airway, such as gaseous sulfur dioxide, are more likely to be associated with chronic bronchitis, whereas those which reach the alveoli, such as fine particles, might produce emphysema. Conversely, the presence of chronic respiratory disease could interfere with the clearance and disposal of inhaled pollutants, thereby potentiating their effects.
Obstruction to air flow during expiration is an important part of the clinical picture in patients with chronic bronchitis and emphysema. Acute bronchoconstriction, which is a feature of the response to inhaled irritants in laboratory animals and man, would be expected to worsen any preexisting obstructive component materially. Population studies of the effects of air pollutants have often used pulmonary function tests, such as peak expiratory flow rate and forced expiratory volumes, to assess airway obstruction. However, although these are excellent screening devices, more sophisticated measures of pulmonary function are required to assess accurately the pathologic processes and airway sites of respiratory obstruction. The term “chronic nonspecific respiratory disease” has been used by a number of epidemiologists in recent years and appears to be more appropriate for air pollution studies, in that the available information is usually obtained by questionnaires or simple pulmonary function testing and is therefore not sufficient to distinguish clearly between possible types of chronic respiratory disease.
There have been substantial international differences in the reported prevalence rates for chronic bronchitis (Reid 1962, Christensen and Wood 1958). This may be due in part to ethnic factors, extent of cigarette consumption, or
presence of air pollution, but to a large extent it represents differences in diagnostic criteria. Most of the studies about to be discussed are from the American or British literature, so it should be noted that the term “chronic bronchitis” is used far more often by the British. This does not negate the appropriateness of the British findings to chronic respiratory disease observed in the United States.
A discussion of the effects of air pollution in chronic respiratory disease would be incomplete without mention of two major determinants of lung function: cigarette-smoking and aging. Cigarette consumption has been clearly and consistently related to a loss of lung function and to a prevalence of chronic respiratory disease. Among those who smoke, it is a much larger determining factor in their disease than is exposure to usual concentrations of urban air pollutants. Of course, cigarette-smoking is voluntary, and breathing is not. A significant decrease in adult lung function occurs with age, so most indexes of pulmonary function are standardized for a given age range. Thus, a 30-year-old with pulmonary function in the normal range for a 70-year-old would be considered to have respiratory disease. The processes involved in “normal” aging are not understood, but, to the extent that they may represent an accumulation of minor pathologic insults, the inhalation of irritant air pollutants over many decades conceivably accelerates lung aging. This is, of course, speculative.
The classification and epidemiology of chronic respiratory disease in relation to air pollution have been reviewed by Ferris (1969, 1973) Higgins (1974), and Holland (1972).
There is an extensive literature dealing with the adverse health effects of industrial effluents. Epidemiologic studies relating respiratory morbidity and mortality to air pollution have been a fixture of the medical literature for quite some time. An early
example of the epidemiologic approach in which a geographic comparison of death rates is used to ascertain the effect of air pollution was reported by Ramazzini in 1713 (Wright tr. 1964):
“A few years ago a violent dispute arose between a citizen of Finale, a town in the dominion of Modena, and a certain business man, a Modenese, who owned a huge laboratory at Finale where he manufactured sublimate. The citizen of Finale brought a lawsuit against this manufacturer and demanded that he should move his workshop outside the town or to some other place, on the ground that he poisoned the whole neighborhood whenever his workmen roasted vitriol in the furnace to make sublimate. To prove the truth of his accusation he produced the sworn testimony of the doctor of Finale and also the parish register of deaths, from which it appeared that many more persons died annually in that quarter and in the immediate neighborhood of the laboratory than in other localities. Moreover, the doctor gave evidence that the residents of that neighborhood usually died of wasting disease and diseases of the chest; this he ascribed to the fumes given off by the vitriol, which so tainted the air near by that it was rendered unhealthy and dangerous for the lungs. Dr. Bernardino Corradi, the commissioner of ordnance in the Duchy of Este, defended the manufacturer, while Dr. Casina Stabe, then the town-physician, spoke for the plaintiff. Various cleverly worded documents were published by both sides, and this dispute which was literally ‘about the shadow of smoke’, as the saying is, was hotly argued. In the end the jury sustained the manufacturer, and vitriol was found not guilty. Whether in this case the legal expert gave a correct verdict, I leave to the decision of those who are experts in natural science.”
Studies of mortality depend heavily on the accurate filing of death certificates. Unfortunately, this is not a highly reliable source of data, particularly if it is used to sample the total amount and types of respiratory disease mortality in a given area. In patients with chronic pulmonary disease, the immediate
cause of death might be an otherwise minor respiratory infection or cardiac failure secondary to the pulmonary disease. Furthermore, the cause of death may not be directly related. The extent to which specific chronic respiratory diseases are listed as immediate causes of death or as underlying conditions depends on the familiarity of the certifying physicians with the individual cases, their diagnostic acumen, and local medical usage. In addition, death certificates are often filed according to place of death, which may not be where the person lived for most of his life.
Despite these possible complicating factors, the substantial rise in recent years of chronic respiratory disease mortality clearly indicates that this disorder is an increasingly important factor in the well-being of the general population (HEW 1974). Age-adjusted death rates for bronchitis, emphysema, and asthma combined in the United States in 1958 were 6.9/100,000 population (males, 11.4; females, 2.9) in 1958 and 12.1/100,000 (males, 21.4; females, 4.7) in 1967, on the basis of approximately the same classification of disease. A closer look at the data reveals that, despite this increase, there has been an absolute decline in reported asthma deaths, which formerly accounted for 60 percent of total chronic respiratory disease deaths and now account for less than 10 percent. This great increase in bronchitis and emphysema mortality is unlikely to be due simply to changes in diagnostic criteria. The increase in chronic respiratory disease death rate is more notable in white males than in nonwhite males; this is consistent with the apparent greater effect of pulmonary irritants on whites. During this period, death rates for influenza and pneumonia combined were relatively stable; they are currently about double the death rate for chronic respiratory disease.
The causal relation of severe air pollution episodes to increased mortality is firmly established (Glasser and Greenburg 1971, Greenburg et al. 1962, Logan 1953, Schrenk et al. 1949, Firket 1931). Older people with preexisting heart and lung disease are particularly at risk,
although increased mortality in all age groups was observed during the disastrous London fog of 1952. An important question concerning these severe episodes is whether the life span is shortened only for those who die immediately or for a larger portion—perhaps all—of the population. If these episodes only shorten slightly the life span of the severely ill, then one would expect to observe fewer than the usual number of deaths in the period after an episode. This has been observed on occasion, but never to the equivalent extent of the excess of deaths during an episode. However, the variable nature of mortality data does not permit the determination of whether life span is shortened only in relatively unhealthy people, who will then die in the days and weeks after exposure, or in a much larger segment of the population.
An extensive literature concerning the association of air pollution with respiratory disease mortality in Great Britain is available. In 1964, Martin reviewed a number of these studies, evaluating variations in mortality in relation to air pollution. For the London area, it appeared that there were critical concentrations of smoke (2,000 ug/m3) and sulfur dioxide (0.4 ppm) above which a marked immediate excess in mortality occurred during 1954–1957. Further study of the winters of 1958–1959 and 1959–1960 showed high correlations of death rates (computed as 15-day moving averages to remove seasonal trends) with both sulfur dioxide and smoke. The effect appeared to be a relatively immediate one, and it was difficult to determine a threshold from the plotted data. Pemberton and Goldberg (1954) evaluated the 1950–1952 mortality rates in county boroughs of England and Wales. A significant correlation with sulfur dioxide (sulfation rate) was observed for bronchitis mortality in males 45 years old and over. Much smaller associations of bronchitis death rates were observed with sulfation in females and with particles in either sex. Stocks (1959) noted an association of bronchitis mortality with air pollution for 1950–1953 in the county boroughs of England and Wales after adjustment for the effects of population density. Evaluation of a smaller
area in which more comprehensive air monitoring data were available showed a correlation of bronchitis mortality with dust deposit, but not with smoke shade, whereas the opposite was true for lung cancer.
Daly (1959) also reported a high correlation between fuel consumption and bronchitis mortality in middle-aged men residing in large towns in England and Wales for 1950–1952. After adjustment for social class, the correlation was somewhat smaller. Pneumonia mortality was only slightly related to fuel consumption.
During a similar period, 1950–1954, two studies were reported by Gorham (1959, 1958) that are of particular interest, in that he found that bronchitis mortality in England, Scotland, and Wales was strongly inversely correlated with the pH of winter precipitation. At a pH of 4 or lower in urban areas, the bronchitis mortality was 100/100,000; at a pH of 6 or higher, it was 60/100,000. He also noted that the rural bronchitis mortality was 46/100,000, which implies that rain acidity is not the only factor involved. A smaller, but still significant, correlation of bronchitis mortality with winter sulfation rate (a measure of sulfur dioxide) was also observed. A partial regression equation was calculated in which bronchitis mortality per 100,000 population is equal to 192 (0.838) a, where a is the pH of winter precipitation.
Gore and Shaddick (1958) evaluated standardized mortality ratios for deaths in a 2-year period (1954–1956) in different areas of London and compared them with pollution, social class, and percentage of people born in London. Smoke was directly related to bronchitis deaths, but sulfur dioxide was not. However, in association with length of residence, both these pollutants were significantly correlated with bronchitis mortality. Similarly, Hewitt (1956) observed a significant correlation of London bronchitis deaths, and deaths from all causes, with a composite index of sulfur dioxide and percentage born in London. These studies suggest that the duration of exposure to London pollution was important in eventual bronchitis deaths and indicate a long-term effect of pollution on
mortality. Similar studies have not been performed in the more peripatetic American population.
Burn and Pemberton (1963) divided the heavily polluted area of Salford, Great Britain, into five districts on the basis of smoke and sulfur dioxide concentrations. Deaths from all causes, bronchitis, and, to a lesser extent, lung cancer were related to air pollution in 1958–1959. Deaths from arteriosclerotic heart disease and strokes were not associated with pollution. The positive findings may be due in part to social-class differences, which could not be evaluated.
More pertinent to current considerations of air pollution control strategy is the question of whether daily variations in pollution concentrations at or somewhat above current U.S. air quality standards have any short-term effect on mortality. To evaluate this question, it is necessary to assess carefully the variations in daily mortality not due to air pollution. Of particular importance are factors that correlate with both air pollution and death rates, such as meteorologic conditions and influenza epidemics, the latter tending to occur during the winter heating season.
Among the studies of the effect of air pollution on short-term mortality in Great Britain is that of Boyd (1960), who related weekly temperature and pollution concentrations to mortality in the succeeding week. Both smoke and sulfur dioxide concentrations correlated with deaths due to respiratory disease, and the effects were most apparent at lower temperatures. One relatively unusual finding among British investigators was a better correlation with sulfur dioxide than with smoke. The sulfur dioxide data were tabulated as mean weekly sulfur dioxide concentrations of less than 0.1, 0.1–0.15, and more than 0.15 ppm. An increase in respiratory disease mortality was generally observed in each temperature range as sulfur dioxide concentration increased.
Numerous American studies have related mortality to air pollution. Those dealing with acute episodes have been cited elsewhere in this document. An interesting follow-up of the 1948
Donora disaster was performed by Ciocco and Thompson in 1957 (1961). People who reported illness during the acute episode later had an increased prevalence of illness and higher mortality rates than those who did not report being affected in 1948. This still held true, although to a lesser extent, when the analysis was restricted to those who had been in good health before the 1948 episode. The findings may be interpreted as indicating that air pollution shortens the life span of those who survive an acute episode or that those who respond to environmental stress are more susceptible to serious diseases. Most likely, the correct interpretation is a combination of the two.
Some relatively early U.S. Public Health Service studies were described by Rumford in 1961. Four pairs of Chicago health districts were selected for differences in industrial activity but similarity in socioeconomic status. Evaluation of white females showed an increased mortality from all heart and lung disease in the industrial areas. However, in Philadelphia, only deaths from chronic rheumatic heart disease could be related to dustfall. Even earlier studies by Mills (1952, 1948, 1943) had indicated a relation of sootfall to respiratory mortality in Chicago, Pittsburgh, Cincinnati, and Detroit.
An extensive series of studies, including mortality evaluations, were performed by the U.S. Public Health Service in Nashville, Tennessee, beginning in 1957 (Zeidberg et al. 1967). The area was divided into nine categories on the basis of socioeconomic class and pollution. The latter was determined by a very extensive monitoring system that obtained data on sulfation rate, soiling index, and dustfall. There was also direct monitoring of sulfur dioxide, which confirmed that Nashville had relatively low concentrations of this contaminant. The cutoff point for the high-pollution area, selected to be one standard deviation above the mean for the entire city, was based on a geometric mean sulfur dioxide concentration of 0.013 ppm and a sulfation rate of 0.4 mg/100 cm2 per day. The authors conclude
that the data indicated a direct relation between age-specific respiratory disease mortality and sulfation rate. However, there are a number of problems with their analysis. In an attempt to control for the large inverse effect of socioeconomic class on respiratory disease mortality, they studied the middle socioeconomic class. Although this group showed a direct relation of all respiratory disease mortality with both sulfation rate and soiling, no association with deaths due to bronchitis and emphysema was observed. Furthermore, the middle class was very broadly defined; this raises the possibility that the elimination of a socioeconomic effect was incomplete. Cardiovascular disease mortality was reported to have a small and inconsistent association with the soiling index, particularly in females (Zeidberg et al. 1967).
Wilkelstein and his colleagues (1968, 1967), performed a series of studies in Erie County (Buffalo), New York, in which monitoring data were used to divide the area into pollution categories. Mortality from all causes and mortality from chronic respiratory disease in white males 50–69 years old were found to be associated with concentrations of suspended particles. The standardized mortality ratios for chronic respiratory disease mortality in this group were 76 in air pollution category 1 (total mean suspended particles, less than 80 ug/m3), 98 in category 2 (80–100 ug/m3), 112 in category 3 (100–135 ug/m3), and 137 in the highest air pollution category (over 135 ug/m3). These data were apparently of great influence in the establishment of the U.S. air quality standard for total suspended particles, 75 ug/m3 (annual mean). However, socioeconomic class was inversely related to deaths from chronic respiratory disease, and the areas with greater pollution tended to be less affluent. The authors suggest that the air pollution effect is at least partially independent of the socioeconomic-class effect. This contention is supported by reasoning based on inspection of standardized data for various subgroups, rather than more detailed multiple regression analysis or assessment of statistical significance. In a
review of this work, Winkelstein (1970) in effect argues that these more sophisticated statistical tests are unwarranted, in view of the relative crudeness of the data obtained in epidemiologic air pollution studies. This is a crucial point, particularly because, without such further statistical analysis, it is difficult to obtain precise dose-response information or to assess minimal no-effect concentrations.
Evaluation of the Erie County mortality data in relation to sulfation rates did not reveal any association, nor was there any evidence of a synergistic effect with total suspended particles. However, the gradient for sulfation rate was not as pronounced as that for particles, and that may have affected the analysis.
It should be noted that both the Buffalo and Nashville mortality studies have been criticized on the basis of their lack of data on cigarette-smoking. Obviously, a difference in cigarette consumption in the local areas could account totally for the effect ascribed to air pollution. However, to the extent that lung cancer can be considered to be an excellent biologic indicator of cigarette-smoking, the failure to observe any difference in lung cancer rates related to air pollution in these two studies implies that the data are not confounded by a gradient in cigarette consumption.
New York City has been the site of a number of epidemiologic studies relating air pollution to mortality. Excess mortality during acute air pollution episodes was reported in a series of studies by Greenburg and his colleagues (Glasser et al. 1967, Greenburg et al. 1967, Greenburg et al. 1962). McCarroll and Bradley (1966) demonstrated that less severe air pollution episodes were also associated with increased mortality. However, of more pertinence to present questions concerning the required extent of air pollution control are studies that evaluated pollution concentrations and mortality on a daily basis over a long period.
Hodgson (1970) studied daily mortality in New York City from November 1962 to March 1965. Death rates were related to pollutant concentrations measured at one monitoring station in
Manhattan and to a measure of low temperature. Air pollution variables were highly related to mortality from respiratory and cardiac disease. Particle concentration was a better predictor of the effect than was sulfur dioxide concentration. Mortality from other causes was not associated with air pollution. Additional reported findings include the lack of an apparent threshold for an effect of pollutants on mortality and the fact that the environmental influence on respiratory and cardiac deaths is exerted only by pollution concentrations on the day of death and, to a lesser extent, on the preceding day. Excess mortality due to air pollution was calculated for average monthly increases in particles and sulfur dioxide, but the definition of the pollutant units is not clear. Possible criticisms might be related to inadequate adjustments of mortality data for meteorologic factors, influenza epidemics, and seasonal influences. In particular, a source of bias may have been introduced by the use of three winters and only two summers.
Glasser and Greenburg (1971) studied the effects of air pollution on mortality in New York City in 1960–1964 solely for the months October–March. Adjustments for remaining seasonal factors were made by use of a moving average, and deaths were recorded as deviations from the normal 5-year mean. These were related to smoke shade (COHS) and sulfur dioxide measurements from one New York City monitoring station. Temperature was recorded in terms of deviation from the expected daily normal. When deviations in daily deaths were compared with daily sulfur dioxide concentrations, a sharp increase in mortality was noted for the days when the sulfur dioxide concentrations were greater than 0.3 ppm. A slight gradual nonsignificant increase was also observed at lower concentrations of sulfur dioxide. The relation of smoke shade to deaths was more variable at lower concentrations, and a sharp increase in excess mortality was present only on the most polluted days. These findings were uncorrected for temperature. However, when regression analyses with meteorologic factors were performed, sulfur dioxide was still found to be
positively correlated with the deviation in daily mortality, and this association tended to be confirmed by a further analysis in which days with similar weather conditions were compared. The major increase in deaths was again associated with days when sulfur dioxide concentrations were above 0.3 ppm, although a gradual increase below this concentration was also observed. This study tends to support an association of deaths in New York City with daily sulfur dioxide concentrations higher than permitted (U.S. air quality standard, 0.14 ppm). However, it can be questioned whether the data have been sufficiently adjusted for more subtle meteorologic effects on the death rate, as well as for the effect of influenza epidemics.
Two more recent studies have used highly sophisticated statistical techniques to evaluate New York City mortality rates; although both have shown an association with air pollution, their results have been markedly different. Buechley et al. (1973) assessed daily variations in the death rate in the entire New York metropolitan area for 1962–1966 in relation to air monitoring data from one station in upper Manhattan. They also assessed a number of variables that were shown to affect the death rate, including temperature, day of the week, holidays, and influenza. The effects of temperature were handled in a very complex fashion in which death rates were adjusted for seasonal cycles, extreme heat, and daily and weekly temperature differences. After regression analysis and serial elimination of the other variables, sulfur dioxide was found to be highly correlated with the residual mortality. Mortality was 2 percent more than expected on days when sulfur dioxide concentrations were above 500 ug/m3 (0.19 ppm), and 1.5 percent less than expected on days when sulfur dioxide concentrations were less than 30 ug/m3 (0.01 ppm). Graphic portrayal shows a tendency toward a stepwise progression in mortality with increasing sulfur dioxide concentration and gives the impression that there is no appreciable threshold for this effect. However, the differences at the lower concentrations of sulfur dioxide are not statis-
tically significant. The authors state that particles do as well as sulfur dioxide in dieting death and that a similar but weaker effect was observed in the Philadelphia area. However, the data are not presented.
Schimmel and Greenburg (1972) reported a much higher estimate of deaths associated with sulfur dioxide and smoke shade. Their study used data from the same monitoring station as that of Buechley et al. (1973), but was limited to deaths in 1963–1968 solely within New York City. They also considered the effect of pollutant concentrations on the days preceding death, as well as on the day of death, and included the cause of death in their analysis. The highest estimate of deaths due to smoke shade and sulfur dioxide were obtained when the regression was performed for pollution alone. This estimate was lower after adjustment for other variables, including mean daily temperature, seasonal and annual trends, and day of the week. Estimates of the percentage of deaths immediately related to air pollution depended on the analysis and ranged from 8 to 16 percent. The authors discuss why the various approaches might overestimate or underestimate the true effects and conclude that 12 percent is a reasonable assumption. Mortality from all causes, except diseases of infants, was related to pollution. When the excess deaths were partitioned between sulfur dioxide and smoke shade, 80 percent of them appeared to be associated with smoke shade.
The reasons for the large contrast between these two papers are difficult to disentangle. The much lower association observed by Buechley et al. may be due to more intensive adjustment for temperature variables and to the consideration of the effect of influenza. The higher estimate in the Schimmel and Greenburg paper might be related to their consideration of the contribution of pollutant concentrations on the days preceding the day of death. However, Lebowitz (1973), using a different statistical approach, found an almost immediate effect of pollution on mortality in New York and other cities. To the extent that it is inappropriate to use one monitoring station to characterize a large area, the approach of Buechley et al. is
more vulnerable, in that they used mortality data from the entire metropolitan area, rather than New York City alone. In this respect, the study of Blade and Ferrand (1969) showed a reasonably good correlation between the many New York monitoring stations. However, a report evaluating more recent data from the same network did not find as close a relationship (Goldstein et al. 1974). Another pertinent point is that, if, in fact, 12 percent of New York City residents had their life expectancy decreased by the short-term effect of pollution in the middle of the last decade, then air pollution was a far more serious public health hazard than most people believed.
Despite their individual differences, the four studies of New York City mortality in relation to daily pollution concentrations have relatively similar overall findings. Each has found that, before the institution of recent control measures, air pollution in New York City was associated with an increase in daily mortality. In addition, there is the suggestion that this effect may not have an appreciable threshold. The lack of agreement as to whether particles or sulfur dioxide correlated best with mortality may constitute indirect evidence that the measurements are only indicators of the pollutants, related or unrelated, that are actually responsible for toxicity.
These studies also illustrate that epidemiology is a relatively imprecise science. An observed association becomes far more credible when it is replicated by different scientists using different approaches, particularly in a field as complex as the health effects of air pollution. Although the results are in the same direction, the fact that they vary widely in magnitude indicates further the difficulty in determining precisely what degree of air pollution produces how much illness in how many people.
Both Buechley and Schimmel are extending their observations to more recent years, in which sulfur dioxide concentrations have been greatly reduced. This reduction has been caused by the use of low-sulfur fuel, but it has been associated with only a relatively small decrease
in particle concentrations. A tentative and incomplete analysis of the more recent mortality data has been presented by Schimmel et al. (1974); there appears to be no change in the finding that 12 percent of deaths are associated with air pollution. If that is true, it implies that control measures have thus far had little effect. However, this finding must be approached with caution, until both groups have had a chance to complete their analyses and there is an opportunity to review their results in detail.
It is reasonable to assume that, for every person who dies during an air pollution episode, many more will be made sick. Furthermore, relatively minor daily variations in atmospheric pollution would be expected to have a greater effect on morbidity than on the mortality of the population at risk. Accordingly, one would predict that morbidity would be a better indicator of air pollution effects than would mortality. However, it is apparent from the studies to be described that the evidence of an association of relatively low pollutant concentrations with respiratory tract morbidity is at most slightly better than that for mortality. This may be a function of the measurement of response. Death is a readily quantifiable all-or-none phenomenon; the gradation between health and illness can be very subtle, particularly when large populations are evaluated. Epidemiologic studies of respiratory tract morbidity have used a number of measuring devices, including daily diaries, questionnaires, work and school absence rates, hospitalization rates, clinic visits, and the testing of pulmonary function. All these have some difficulties that might obscure an association with air pollution. In addition, as discussed earlier, some variables, such as meteorologic factors, are related to pollutant concentrations and have independent effects on respiratory disease. As is the case with air pollution, such a factor as temperature would be
expected to have more subtle effects on morbidity than on mortality. It is therefore necessary to assess carefully these possibly confounding variables in the study of the relationship of respiratory disease to air pollution.
Many of the studies that have suggested an association of air pollution with chronic respiratory disease are based on the higher prevalence rates in urban, compared with rural, areas. Although the increased prevalence of chronic respiratory disease in urban adults is conceivably due in part to the population density and greater mobility—leading to a higher incidence of endemic and epidemic respiratory tract infections, compared with that in more isolated rural areas—this would not explain the major differences observed. Furthermore, comparisons of cities with similar population densities but different degrees of air pollution have tended to confirm an association of air pollution with chronic respiratory disease. As discussed earlier, studies that compare prevalence rates of chronic respiratory disease among different areas are of value only if careful attention is paid to standardization of observers, observation methods, and the populations at risk.
Higgins et al. (1958, 1956) conducted a series of studies in rural areas of Scotland and Wales and the industrial town of Leigh, in which the prevalence of respiratory symptoms and the forced expiratory volume (0.75 sec) were measured in a random sample of men and women 55–64 years old. Slight changes consistent with an urban effect were observed, but these were minor, compared with the effect of a past or present history of working in coal mines. Reid and Fairbairn (1958) studied about 500 British postmen who had retired because of chronic bronchitis. They noted that those over 44 years old living in more polluted areas had a higher attack rate of illness and that, after treatment, those living in more polluted areas died of their disease faster. Air monitoring data are not given for these studies, which were conducted in the 1950’s. In 1960–1961, Holland and Reid (1965) noted an increase in the
frequency of respiratory symptoms and a decrease in pulmonary function in workmen living in London, compared with those in more rural areas of southern England. A comprehensive study by the College of General Practitioners (1961) in Great Britain confirmed the presence of a significant urban-rural difference in bronchitis rates. A comparative study of England and the United States has been reported by Holland et al. (1965).
Fairbairn and Reid (1958) have also evaluated sickness absence rates and retirements because of bronchitis in British civil servants in relation to an indirect measure of air pollution. In 1948–1954, total sickness rates in postmen correlated significantly with both population density and pollution; however, bronchitis disability was significantly related only to pollution. The distribution of bronchitis disability was similar to that of bronchitis mortality for the entire British population. In a 3 percent sample of the total civil service during 1946–1953, the sickness absence rates because of various respiratory tract illnesses were calculated for postmen, men working indoors, and women working indoors. In all three groups, after standardization for population density and domestic crowding, there was a positive correlation of pollution with bronchitis that approached statistical significance. Upper respiratory tract infections and influenza did not correlate with polution, although influenza in men was strongly associated with crowding.
Sickness absence rates due to bronchitis were also evaluated by Cornwall and Raffle (1961) in London transport workers in 1952–1956. Absences of 4 days or longer were related to the area in or around London in which they worked, largely in buses or trolleys. The incidence of bronchitis in the total group correlated closely with dense London fogs. Those working in the more rural areas around London had lower bronchitis absence rates than those within London. When the bronchitis rates in those working in different areas of the countryside around London were compared, the highest rates were observed in the direction in which
prevailing winds would be expected to transport London air pollution. Reid reported a similar observation in London postmen in a more restricted periurban area (1956).
The concept of an interaction between cigarette-smoking and air pollution effects is supported by the study of Lambert and Reid (1970), a postal survey of nearly 10,000 britons 35–69 years old. In nonsmokers, the prevalence rates of respiratory symptoms were relatively unaffected by air pollution. However, air pollution had a definite and independent effect on prevalence rates in smokers. The authors constructed symptom prevalence ratios standardized for age and smoking in relation to atmospheric smoke and sulfur dioxide concentrations. Men residing in areas with mean annual smoke concentrations of less than 100 ug/m3 had symptom prevalence ratios of 97, compared with 112 for those residing in areas with smoke concentrations of 100–150 ug/m3. Higher smoke concentrations were associated with greater increases in prevalence ratios. The data on men for sulfur dioxide were similar but not as dramatic. When annual mean sulfur dioxide concentration was less than 100 ug/m3, the symptom prevalence ratio was 87; at 100150 ug/m3, it was 96. However, there were only 11 male responders in the areas with low sulfur dioxide. For women, the trends were smaller and less consistent, in keeping with the smaller urban-rural differences for chronic bronchitis mortality and morbidity in women. The data as a whole further support the dominant influence of cigarette-smoking, compared with air pollution, on respiratory disease.
A study that apparently had a significant impact on the original U.S. air quality standard for sulfur dioxide (0.03 ppm, annual arithmetic mean) was performed in Genoa by Petrilli et al. (1966). The frequency of respiratory disease, as measured by an undescribed slight modification of the British Medical Research Council questionnaire, was determined in seven districts of Genoa in an indigent population receiving free medical care and in non-smoking women over 60 years old who were said to be long-time residents of the areas. Sulfur dioxide was
measured by a volumetric procedure, which is unfortunately not detailed. Total dustfall, suspended particles, and sulfation rate (by the lead peroxide candle method) were also measured in each district. Chronic bronchitis, tonsillitis, rhinitis, and influenza tended to be increased in the polluted areas, but were not as linearly related to sulfur dioxide as was the bronchitis rate. Mean temperatures were somewhat lower in the more polluted areas, but this did not totally explain the observed effect on bronchitis.
There are some points about the data that are unclear, including the rationale for arithmetically averaging the bronchitis rates of the groups 15–64 years old and 65 and over, whether the data were corrected for the ages of the subjects examined, and whether there were differences in cigarette consumption.
One point of interest in the study of Petrilli et al. (1966) concerns the three least polluted districts, all of which had annual average sulfur dioxide concentrations of 0.025 ppm. One of the districts, Molo, is reported as having a sulfation rate of 0.68 mg of sulfur trioxide per 100 cm2 per day; the other two districts both had rates of only 0.17 mg/100 cm2 per day. Molo does not significantly differ in suspended matter, total dustfall, or mean winter temperature, and its influenza rate is intermediate between those of the other two districts low in sulfur dioxide. However, this district, with a fourfold higher sulfation rate, had a substantially higher bronchitis prevalence rate (6.0 percent vs. 2.1 percent and 3.1 percent) and chronic bronchitis rate (9.8 percent vs. 2.1 percent and 2.5 percent) than the other two districts. This increase does not appear to be accounted for by the somewhat greater number of older people examined in Molo.
These findings could be interpreted as indicating that other atmospheric sulfur compounds (in addition to sulfur dioxide) that were measured by the lead peroxide candle method were in part responsible for the observed differences. However, the earlier volumetric sulfur dioxide measurement methods were relatively inaccurate at low concentrations, and it
is conceivable that these three communities differed in sulfur dioxide concentration. With the conversion factor obtained in the Nashville study (Zeidberg et al. 1964), the sulfur dioxide concentrations based on the sulfation rate would be close to the 0.025 ppm reported for Molo, but would be lower for the other two districts. This could indicate the possibility of a geographically related difference in respiratory morbidity associated with sulfur dioxide concentrations below the current U.S. standard. In view of the difficulties with the study, of Petrilli et al., such an interpretation must be viewed with caution.
The Nashville study described above analyzed morbidity in relation to air pollution. A questionnaire was given to over 3,000 domiciles; the housewife was usually the respondent for the entire family. Illness rates were inversely correlated with socioeconomic class. When the middle class was evaluated, a direct relation between all illnesses and pollution, as measured by sulfur dioxide and soiling index, was observed for persons 55 years old or older, but not for younger people. Total illness rates of nonworking females, who presumably spent more time in the air pollution category to which they were assigned by area of residence, correlated better with air pollution than did the illness rates of more mobile working women. Problems with the study include the broad definition of the middle class, a lack of relation of air pollution to respiratory illness, and the absence of information concerning cigarette-smoking. Again, it should be emphasized that the Nashville area was relatively unpolluted at the time of study.
Ishikawa et al. (1969) evaluated 600 lungs obtained through autopsy in Winnipeg and St. Louis in 1960–1966. On the basis of emission data, St. Louis was clearly more polluted than Winnipeg; however, the autopsy sets were reasonably well matched in terms of sex, age, and race. Lungs from people with known histories of occupational exposure were excluded. There was a marked increase in emphysema in St. Louis in all smoking categories of males, but not females. The authors report
that cigarette-smoking and air pollution acted synergistically in the production of severe grades of emphysema. However, review of the data shows that the relative amounts of total emphysema and mild and moderate grades of emphysema fit an additive model more closely than a synergistic model.
A series of studies performed by Ferris and his colleagues (Ferris and Anderson 1962) have evaluated respiratory disease prevalence in Berlin, New Hampshire, at different times and in comparison with another small city, Chilliwack. British Columbia. At the time of their original study in Berlin in 1961, the sulfur dioxide concentrations were probably about the current standard, in that the mean lead peroxide candle sulfation rate was recorded as 0.731 mg of sulfur trioxide per 100 cm2 per day. However, the mean 24-hr total suspended particles were 180 ug/m3 or, as indicated by the authors, perhaps somewhat higher. This study demonstrated that cigarette-smoking and aging were the major determinants of chronic respiratory disease prevalence and of pulmonary function. The possibility that air pollution might have some effect was suggested by an almost twofold increase in prevalence in each disease category in nonsmoking men resident in the most polluted areas of Berlin. However, this difference was not statistically significant and, as pointed out by the authors, the possible influences of ethnic, social, and economic differences could not be established.
In 1963, the same investigators (Ferris and Anderson 1964) performed a similar study, although with a slightly different questionnaire, in Chilliwack, British Columbia, a community with essentially clean air, and compared the results with those from Berlin. Using expected age-specific prevalence rates for chronic bronchitis and irreversible chronic obstructive lung disease calculated for both populations combined, it was found that nonsmoking females in Chilliwack had about a 6–8 percent decrease in prevalence of chronic respiratory disease. The prevalence rates for nonsmoking men were the same in both communities. From the Berlin data, multiple regression equa-
tions were calculated for forced expiratory volume (1 sec) and peak expiratory flow rate. Applying these equations to the Chilliwack data revealed that in all smoking categories the pulmonary function was about 8 percent higher than predicted in Chilliwack. Although these findings are consistent with an effect of air pollution, ethnic differences or subtle variations in life style might also explain the results.
A further study in Berlin was performed in 1967 (Ferris et al. 1973). At that time, there had been a decrease in sulfation rate to 0.469 mg of sulfur trioxide per 100 cm2 per day and a decrease in particle concentration to 131 ug/m3. When the same subjects were reevaluated, there was a lower prevalence of chronic nonspecific respiratory disease and better pulmonary function than expected after taking into account the effect of aging and changes in cigarette-smoking. On the basis of prediction equations derived from the 1967 Berlin population, the 1961 population had about a 5 percent decrease in forced vital capacity and peak expiratory flow rate in men and a 5 percent decrease in forced vital capacity in women, all of which were statistically significant. No difference in forced expiratory volume was observed. This improvement in respiratory function, which is consistent with a beneficial effect of air pollution control, is not as great as the observed beneficial effects of cessation of cigarette-smoking in the same study.
Stebbings (1971), in a series of studies of chronic respiratory disease in Hagerstown, Maryland, has evaluated the effects of past urban residence on the peak expiratory flow rate and forced expiratory volume (1 sec) of over 400 white nonsmoking men 35–64 years old. None of these men had lived in Hagerstown during the preceding 20 years or more. A positive association of childhood urban residence with peak expiratory flow rate was observed, and this effect persisted until about the age of 28. In contrast, those who had lived for longer than their first 28 years in an urban area had a relative decrease in peak expiratory flow rate. No consistent effect on forced expiratory volume
was observed. The data were not explainable on the basis of socioeconomic factors, and there were too few men with significant chronic respiratory disease to suggest that selective migration was a factor. The prevalence of respiratory symptoms was positively correlated with long-term urban residence, although the numbers were small. The author’s tentative explanation for the increase in peak expiratory flow rate observed in nonsmokers who had spent their childhood in urban areas is that an urban factor, perhaps air pollution, might lead to a compensatory increase in pulmonary function. However, if such an exposure continues long enough, a decrement in function will occur. If, in fact, childhood exposure to air pollution is the factor that leads to an increased peak expiratory flow rate, this would tend to contradict the results of a number of shorter-term studies described above.
Intercommunity differences in the prevalence of respiratory disease have also been assessed as part of the CHESS program (Goldberg et al. 1974, Hayes et al. 1974, House et al. 1974). Studies in the Salt Lake Basin, Rocky Mountain, and New York areas were based on questionnaires filled out generally by the mothers of schoolchildren concerning the health of family members. The format of the studies and the pollution concentrations of the various communities have already been described in some detail above. The prevalence rates of bronchitis (defined as cough or phlegm on most days for at least 3 months each year) were calculated independently for smokers, ex-smokers, and nonsmokers among mothers and fathers who had lived in the area for 2 years or more and who were not occupationally exposed to presumed respiratory pathogens. In the Salt Lake Basin area (House et al. 1974), the high-pollution community had the highest bronchitis prevalence rates in all six categories tested, and the difference was statistically significant. A tendency toward an increased prevalence rate was also noted in the second-most-polluted community, compared with the other two, but this was not statistically significant. The bronchitis prevalence rates were about 100 percent
higher in nonsmokers and about 40 percent higher in smokers in the high-pollution community, compared with the other communities. In the Rocky Mountain study (Hayes et al. 1974), an increased prevalence of bronchitis was again noted in the high-pollution communities in each smoking category. However, the data were not as clearcut, and the differences were relatively small, except for the nonsmoking group in which the prevalence rate was greater by twofold to threefold in the high-pollution communities. Socioeconomic factors may have been a problem in this area. In the Rocky Mountain and Salt Lake areas, studies of subjects who were occupationally exposed demonstrated that this factor had a substantially greater effect on bronchitis prevalence than did air pollution. However, the effects of cigarette-smoking were even greater and ranged up to 10 times that attributed to air pollution.
Studies in the New York area (Goldberg et al. 1974) again demonstrated a higher bronchitis prevalence rate in the two intermediate communities than in the low-pollution community, and in general the gradient was steeper than that observed in the Salt Lake Basin and Rocky Mountain areas. Cigarette-smoking was again the major factor in bronchitis prevalence rates.
Although these studies have been criticized on the grounds of anomalous data in each area and among the various areas and on the basis of possible biases involved in self-administered questionnaires, the studies taken together do tend to support an effect of air pollution on chronic bronchitis prevalence rates. In addition, it should be noted that the subjects of these studies do not represent a particularly susceptible population group. However, in terms of extrapolating these data to questions concerning the appropriateness of present air quality standards, the reported increases in chronic bronchitis prevalence rates presumably reflect in part past exposure to air pollution, and all the high-pollution communities in the New York study (Goldberg et al. 1974) had previously been well in excess of the air quality standards. It is hoped that these studies will serve as a baseline for the future evaluation of
whether, and to what extent, present emission controls have produced an amelioration of chronic bronchitis rates.
An additional respiratory disease prevalence study, performed by the CHESS (Finklea et al. 1974) group in young military recruits undergoing examination in the Chicago induction center, found only a small and inconsistent relation of respiratory symptoms with area of origin, which, although tending to be in the direction expected for an effect of air pollution, was not statistically significant.
Among the studies that have purported to demonstrate an association of morbidity with sulfur dioxide concentrations below the current standard is the work of Sterling et al. (1969), which studied hospitalization rates and length of hospital stay in Los Angeles from March to October 1961. After day of the week was taken into account, various pollutants, including sulfur dioxide and ozone, were found to correlate with hospital admission for diseases thought to be related to air pollution. Comparison of the one-third of the days with highest sulfur dioxide concentrations with the one-third of the days with lowest sulfur dioxide concentrations showed that the former had 13 percent more admissions for infectious disease, 10 percent more for bronchities, and 10 percent more for acute upper respiratory infections. Little effect was observed on diseases not believed to be related to air pollution. A slight positive correlation of sulfur dioxide concentration with length of hospital admission for relevant diseases was also noted. Detailed air monitoring data are not reported; however, the mean daily sufur dioxide concentrations for the period was about 0.013 ppm, in keeping with the generally low concentrations observed in southern California. It appears unlikely that sulfur dioxide was the sole pollutant responsible for the observed findings, which, if valid, presumably reflect the role of sulfur dioxide as an indicator of specific meteorologic conditions associated with the buildup of pollutants.
Gregory (1970) evaluated records of sickness absence because of bronchities in workmen with
chronic bronchitis employed in an urban steel factor for the period 1955–1961 in England. With multiple regression analysis, the monthly bronchitis incidence rates and prevalence rates were found to correlate best with temperature (r =0.75). Positive correlations with smoke and sulfur dioxide were not as great and may have been temperature-dependent. Because the winter of 1957–58 was noted to have particularly high bronchitis absence rates, this period was chosen for further study. When weekly averages were computed for bronchitis incidence, prevalance, pollution, and meteorologic factors, a slight nonsignificant correlation was noted among the various illness and environmental factors in the same week. However, bronchitis incidence was significantly correlated (r=0.48) with the mean temperature (r=0.11) and sulfur dioxide concentration (r=0.34) of the preceding week. In contrast, the bronchitis prevalence rate correlated best with temperature (r=0.41) and only minimally with mean pollution concentrations of the preceding week. When maximal weekly meteorologic and pollutant data were evaluated, the only statistically significant association was between maximal smoke concentrations and the bronchities incidence rate of the following week (r=0.50). The author points out that the delay in the increased incidence of bronchitis may be due to the lack of work absence data for Saturdays and Sundays and the tendency of workmen to finish out the week before going off sick. The greater effect of temperature on prevalence rates may reflect the reluctance of recuperating people to return to work on a colder day. From a graph of the data, it appears that a 100-ug/m3 increase in mean weekly smoke concentration would be associated with approximately a 0.6 percent absolute increase in the incidence of bronchities in workers already identified as having chronic bronchitis. With respect to extrapolation of the findings, it should be emphasized that these workmen represented less than 10 percent of the total work force and that these data are for only one winter of six.
Another approach to evaluating the effects of pollution on chronic respiratory disease is
to follow a cohort of people. Lawther and colleagues (1970) have presented a series of studies in which bronchitic patients attending chest clinics have been asked to fill out diaries in terms of whether they felt better, the same, or worse on any given day. In their original study, about 180 London patients were followed during the winter of 1955–1956, and a significant correlation of worsening of symptoms with smoke and sulfur dioxide was observed. An increase in illness appeared to be related to an increase in pollution, rather than to an absolute measure of pollution. Meteorologic factors had relatively small and insignificant effects on illness rates. A further study of 248 bronchitic patients in the London area in the winter of 1957–1958 also showed a correlation between pollution episodes and illness. Again, little relation to temperature or humidity was observed; however, it was noted that the patients tended to become more symptomatic as the winter progressed. A similar relation of pollution to bronchitis was observed in the immobile populations, but not in bronchitics living in unpolluted areas.
A larger study was performed in the winter of 1959–1960 in over 1,000 chest-clinic patients, with a slightly modified questionnaire. A worsening of symptoms was observed each time either smoke or sulfur dioxide exceeded 1,000 ug/m3. The lowest pollutant concentration associated with any definite decrease in well-being was about 600 ug/m3. At the time of the next large study by the same group, in 1964–1965, there had been a significant abatement in London smoke concentrations, with little change in sulfur dioxide. The mean winter concentrations of smoke were 342 ug/m3 in 1959–1960 and 129 ug/m3 in 1964–1965; those of sulfur dioxide were 296 ug/m3 in 1959–1960 and 264 ug/m3 in 1964–1965. A mean symptom score was calculated by assigning one, two, or three points to the subject’s daily description of whether he felt better, the same, or worse. When these were tabulated for individual winter months and correlated with monthly pollutant concentrations, statistically significant associations were observed with both
smoke and sulfur dioxide for the 1959–1960 period. However, in 1964–1965, the positive correlations that were still observed tended not to be statistically significant. When pollution episodes for both periods were evaluated in reference to days with peak mean symptom scores, definite relationships were obseved, although occasionally these were out of phase by a day. The minimal daily pollution concentrations leading to a significant response appeared to be about 500 ug/m3 for sulfur dioxide in conjunction with about 250 ug/m3 for particles.
The authors identified 87 people who in 1964–1965 were the most sensitive to changes in the degree of pollution, and 50 of these presumably susceptible people were restudied in 1967–1968, by which time mean winter smoke concentration had decreased to 68 ug/m3 and mean winter sulfur dioxide concentration was somewhat lower, at 204 ug/m3. The correlations of mean symptom scores for this group of subjects in 1964–1965 were 0.39 with smoke and with sulfur dioxide; in 1967–1968, the correlation with smoke was 0.31, and that with sulfur dioxide was 0.28. Although the correlations in 1967–1968 were somewhat lower, they were still statistically significant. Also statistically significant was a negative correlation with temperature in both periods, and, although the correlations were lower than those with the pollutants, the data do not appear to have been adjusted for this meteorologic variable. Of great interest is the finding that sulfuric acid concentration in 1964–1965 had a high correlation of 0.51 with mean symptom score; but in 1967–1968, a correlation of only 0.26.
The authors note that their findings may perhaps be best associated with peak pollutant concentrations during the day, rather than average 24-hr concentrations, although data to support this assertion are not presented. Also noted is that daily pollution concentrations appear to have more of an effect than daily temperature, particularly early in the study, when relatively severe pollution episodes were frequent. Of further interest is the repeated observation that, as the winter progressed, the patients appeared to be less responsive to
similar pollution episodes. The possibility of individual adaptation that this suggests has been discussed in some detail above.
Lawther et al. (1974), have also recently reported a series of studies in which pulmonary function in a small group of normal subjects and two bronchitics in the same hospital laboratory in London was measured frequently. The results were highly variable, and, although a relationship with daily and hourly sulfur dioxide concentrations was observed in some subjects, the major determinant appeared to be respiratory infection.
An additional study that suggests that pollution control measures in the London area have led to a smaller association of respiratory dysfunction with air pollution was reproted by Emerson (1973). Eighteen patients with various degrees of chronic bronchitis and asthma living relatively close to an air monitoring station were repetitively studied with a battery of pulmonary-function tests for up to 82 weeks, beginning in November 1969. Pulmonary function was correlated with a 5-day average of smoke and sulfur dioxide concentrations, including the day of testing and the 4 preceding days. A statistically significant correlation, presumably negative, between sulfur dioxide concentration and forced expiratory volume (1 sec) was observed in only one patient, and between sulfur dioxide concentration and maximal expiratory flow rate in only two patients. In no case was a significant correlation with smoke concentration reported; however, more frequent significant correlations with meterologic factors were observed. Mean concentrations in 1969–1970 were 193 ug/m3 for sulfur dioxide and 44 ug/m3 for smoke; those in 1970–1971 were 187 ug/m3 for sulfur dioxide and 41 ug/m3 for smoke. The rationale for the use of a 5-day average for pollutants is not given, nor is it clear to what extent disability may have kept these patients indoors. Fletcher et al. (1968) have also reported a general decline in sputum production of bronchitics in association with a decrease in London pollution. This was not as great as that observed in patients who had discontinued smoking. More recently, Howard (1974) noted
that patients with obstructive airway disease studied in Sheffield between 1966–1972 had less respiratory dysfunction than a group of the same age and smoking habits studied between 1960–65 when pollution levels had been higher.
The applicability to the United States of the recent relative inability of British investigators to detect an effect of air pollution, compared with the past, appears worthy of further comment. British pollution abatement measures have let to a considerable reduction in concentrations of particles, with relatively less change in sulfur dioxide. In contrast, the major effect of air pollution control measures in the United States has been to decrease sulfur dioxide, rather than particles. This raises the possibility that respirable particles are more of a health hazard than is sulfur dioxide. Although this may be true, it is a somewhat facile explanation and definitely cannot be used as an argument against the control of sulfur dioxide. A number of differences between the British experience and ours should be kept in mind: The content of particles in London differed greatly from that usually observed in American cities and may have played a role in the reported health effects. This may be particularly important with respect to acid sulfates; if the data are available, a comparison would be of interest. Furthermore, it is conceivable that the British have adapted to their high particle concentrations and that further effects will not be observed until concentrations have stabilized again. Another point is that there appears to have been a much smaller decrease in particulate sulfate in U.S. urban areas than in sulfur dioxide, possibly because of vagaries of the oxidation process within urban atmospheres. However, the reduction in sulfur dioxide emission in the cities might still lead to a decrease in sulfate in the countryside. It is not clear whether the kinetics in the air of British urban areas is similar.
Two studies in Chicago have evaluated the symptoms of patients with chronic respiratory disease with refernce to daily environmental factors. Burrows et al. (1968) used diaries to
study 115 Chicago area clinic patients for the 2-year period 1963–1964. Data on symptoms, which were available for about 50 percent of the days from all patients, were compared with various pollutant measurements (excluding particles) obtained in the Chicago Loop and with meteorologic information. When a symptom severity score was calculated from data on cough, sputum production, and shortness of breath, the correlation with daily sulfur dioxide concentrations was a relatively high 0.55. However, a better correlation with mean daily temperature was observed (r=0.07). Furthermore, when the data were calculated solely for the months of December, January, and February, no relation between symptom severity and sulfur dioxide was obsered. In fact, multiple regression analysis revealed that, after temperature was held constant, there was a statistically significant negative partial correlation (r=0.20) between symptoms and sulfur dioxide during the winter months. Introduction of lag periods of up to 5 days did not result in any significant correlations with sulfur dioxide. Selection of 7 days when there was considerable variability in suspended particle concentration in different areas of Chicago and analysis of symptom severity by area of residence resulted in a slightly negative correlation with particle concentration. Mean pollutant data are not given, but apparently the peak daily sulfur dioxide concentration was around 0.8 ppm, and Chicago undoubtedly exceeded current U.S. air quality standards during this period. The data indicate that, for this group of patients, low temperature is the dominant environmental factor in the severity of chronic respiratory disease during a Chicago winter. In view of the high positive correlation with sulfur dioxide for the entire year, one wonders whether an air pollution effect would have been observed in a detailed analysis during a period of milder weather. This possibility will be discussed in more detail later.
Another study in Chicago used a similar approach and found a correlation of pollution concentrations on the same or previous day with the morbidity of patients with chronic
respiratory disease who were 55 years old or older. Carnow (Carnow et al. 1969) evaluated over 500 patients throughout Chicago who were part of a bronchopulmonary disease registry with a diary in which was recorded dialy the presence or absence of chest illness defined in terms of the patinet’s usual status. The data were subdivided by an age classification and by the degree of bronchitis. The days of acute respiratory illness were related in each of these groups to sulfur dioxide concentrations by area of residence determined in a network of monitoring stations. In patients with greater degrees of bronchitis, there appeared to be a gradient of illness in relation to daily sulfur dioxide concentration that was present for all age groups and was also noted for 1- or 2-day lags of the pollution concentration. The effect on acute illness was most marked in those 55 years old or older a day after exposure. For this group the chest illness rates were 26.5 percent a day after a sulfur dioxide concentration of more than 0.3 ppm and 13.6 percent a day after a concentration of 0.0–0.04 ppm. In those with lesser degrees of bronchitis, no effect was observed in the older group, but there was a slight tendency toward a response in the younger group. A further analysis was performed for October to December 1967, with each patient as his own control; a comparison was made of the sulfur dioxide concentrations on the days when the patient reported illness or no illness, or on the previous days. Again, the best correlations were with sulfur dioxide concentrations on the days preceding illness for those with more severe grades of bronchitis who were 55 years old or older.
It is of interest to contrast these two Chicago area studies, which have reported opposite results. The analysis of Carnow et al. (1969) appears to be more likely to detect an effect of air pollution on the morbidity of patients with respiratory disease, in that the population was subdivided, allowing detection of a particularly susceptible group, and the sulfur dioxide concentrations were evaluated in relation to an extensive monitoring network, rather than an individual station. However,
these advantages seem to be more than overshadowed by the lack of assessment of meteorologic factors, which were shown by Burrows et al. (1968) as well as other investigators, to have a significant effect on respiratory tract morbidity.
Another point can be made that is speculative, but nevertheless intriguing. The Carnow et al. analysis was performed for October–December, whereas that of Borrows et al. evaluated the colder months of December–February. It is possible that increases in sulfur dioxide in the fall are associated with more respiratory tract effects than similar increases occuring in the winter or early spring. This is suggested by the sutdies of Lawther at al. (1970) discussed earlier and by the data of Buechley at al. (1972), in which sulfur dioxide correlated well with New York City area mortality in the fall, but not in the winter. Although these are likely to be random observations of no real significance, three possible explanations can be suggested: (1) An overwhelming effect of low temperature makes it technically difficult to detect lesser effects due to air pollution. (2) People with chronic bronchitis may spend more of their time indoors during the colder winter months and therefore be somewhat protected from ambient pollution. (3) Adaption to the effects of sulfur dioxide or other pollutants occurs, whereby initial peaks early in the home heating season result in more of an acute effect than do similar or higher peaks later in the winter. The possibility of adapation to short-term effects of sulfur dioxide has been suggested in animal and human controlled exposure experiments, and relatively long-term adaption appears to occur in occupationally exposed people. Whether such an effect occurs over a period of months in usual ambient conditions is, of course, unknown. Furthermore, adaption to the acute effects of a toxic agent does not necessarily imply the prevention of chronic long-term effects.
Spicer and Kerr (1966) evaluated selected groups of patients with moderate degrees of obstructive airway disease who lived near an air monitoring station in Baltimore. In their first
study, airway resistance was measured in seven patients 5 days/week for 14 weeks; in their second study, 14 patients were evaluated for 47 consecutive days. In each study, it was observed that the airway resistance of each patient tended to rise and fall together, implying the existence of an environmental factor, although it was not possible to separate an individual pollutant or meteorologic variable. During the course of the work, 24-hr particle concentrations were as high as 500 ug/m3, and 2-hr sulfur dioxide concentrations were as high as about 0.13 ppm. However, detailed air monitoring data are not given. A further serial study by these authors (1970) on healthy students revealed little correlation of respiratory function with air pollution.
Winkelstein and Kantor (1969) evaluated respiratory symptoms reported in a questionnaire of white women in the Buffalo area in 1961–1963. Unfortunately, the questionnaire had not been designed for the study of respiratory disease, and there was poor reproducibility of results when a small subsample was retested. With the same air pollution districts as in the Erie County study described before, it was found that cough and phlegm in nonsmokers over 45 years old correlated with particle concentration, although the results were not statistically significant. No gradient for sulfur dioxide was observed. Some influence of residential mobility on the results for smokers was discerned.
The CHESS program evaluated panels of elderly people with and without cardiopulmonary symptoms in the New York area (Goldberg et al. 1974). In general, this was the least successful of the CHESS efforts. Among the problems were a very low participation rate and a high dropout rate during the course of the study, which introduced frequent interactions with the staff and a distinct possibility of bias. Furthermore, members of the panel in the low-pollution community were healthier than those in the higher-pollution communities, although this problem was avoided somewhat by using each subject as his own control. The analyzed data show an association of morbidity with pollutants. Suspended sulfates appear to
have the strongest effect. However, the additional sophisticated analyses reported in the study appear unwarranted, in view of the difficulties described.
Although most of the studies cited have noted an association of air pollution with respiratory disease, this is not always the case. In a series of three related studies, Comstock et al. (1973) were unable to detect an effect of air pollution on pulmonary function or respiratory symptoms of American and Japanese male telephone workers. The first and second studies were performed in 1962–1963 and 1967–1969 in four locations in the United States: Washington, Baltimore, Manhattan (New York City), and a rural part of Westchester County. New York. The third study was performed in Japanese working in Tokyo, but living in areas with differing pollution concentrations. A standardized questionnaire and 1-sec forced expiratory volume were the source of the data, which were analyzed in relation to cigarette-smoking, place of birth, areas of past and present residence, and area of workplace. There was a clearcut effect of age and cigarette-smoking, but no effect of area consistent with a response to air pollution was observed. The American data can be criticized, in that only Manhattan would be expected to have appreciable air pollution concentrations, and the cooperation rates were lowest in this gorup, which was also tested at periods somewhat different from those of the other areas. However, the data largely support an absence of an appreciable response to air pollution in healthy people working in a rather strenuous occupation. The findings are, of course, not pertinent to more susceptible population groups.
Another study that failed to show an effect of air pollution is that of Hrubec et al. (1973) who analyzed over 4,000 pairs of male twins 41–51 years old by means of a mailed questionnaire. The air pollution data for the area of residence are not fully described, but were apparently calculated from U.S. air monitoring and emission data, as well as from meteorologic factors. These were used to obtain estimates of suflur dioxide, particles, and carbon monoxide,
which were then averaged together. Comparison of twin pairs revealed that cigarette-smoking and alcohol consumption were directly related to bronchitis and prolonged cough. A slight relation with urban residence was also present, which had previously been reported in a study of twins in Sweden, (Cederlof 1966), but there was no association with the estimates of air pollution. The major question concerning the study of Hrubec et al. is the validity of the air monitoring data, particularly in view of the use of carbon monoxide in the estimate.
Briersteker et al. (1969) were unable to observe any relation between time of residence in the polluted city of Rotterdam and respiratory symptoms or pulmonary function in a study of municipal employees.
In summary, an effect of suflur oxides and particles on the prevalence rate, morbidity, and mortality of chronic bronchitis and emphysema is apparent and will almost certainly occur at pollutant concentrations only somewhat above present U.S. air quality standards.
Determination of the lower limits of this effect will require continued epidemiologic study, with measurements of sulfuric acid and individual particulate sulfates, as well as other repirable particles. This will be greatly aided by animal studies aimed at determining which of the sulfur oxides, alone or in combination, is responsbile for health effects. It appears that a particularly crucial subject for epidemiologic study is the extent of mortality associated with daily variations in sulfur oxides and particles, including evaluation of the suggestion that there is no threshold for this effect. If this is, in fact, true, or if a relatively high fraction of daily mortality is associated with present pollutant concentrations, then it is likely that the morbidity data presented here substantially underestimate the effects of suflur oxides and particles.
Respiratory Tract Infections
Infections of the respiratory tract are among the most common diseases in man,
accounting for a significant part of total morbidity and mortality in the general population. Respiratory tract infections account for a very high percentage of time lost from work or school, and their economic impact includes substantial costs for drugs, doctors’ fees, and hospitalization.
These infections can be conveniently divided by anatomic location. Those affecting the upper respiratory tract—which is usually considered to include the nose, mouth, pharynx, and larynx—tend to have less severe health consequences to normal adults, particularly in this antibiotic era; however, they have an enormous economic impact on society as a whole. Those affecting the lower respiratory tract, including bronchitis and pneumonia, generally have more immediate and longer-term health consequences. Respiratory tract infections may also be classified by etiologic agent. Viral infections are very common and include mild upper respiratory tract infections usually referred to as colds. However, influenza can have severe consequences, particularly in the aged and those with preexisting cadiopulmonary disease; and viral pneumonias do occur. Acute bacterial infections of the lower respiratory tract tend to have more serious implications, particularly because they may leave residual damage, which acts as a focus for recurrent disease. Other microbiologic agents producing diseases such as fungi, Mycobacterium tuberculosis, and Mycoplasma—will not be discussed here, because they do not appear to be related to air pollution. It should be stressed that the division between upper and lower respiratory tract infections and between viral and bacterial agents is somewhat arbitrary, particularly inasmuch as lower respiratory bacterial infection is often a sequelae of acute viral upper respiratory infections.
Many of the studies that have evaluated the daily well-being of people with chronic respiratory disease in relation to pollutant concentrations can be considered to have indirectly assessed respiratory tract infections, in that these play a major role in the progression of chronic bronchitis. What
would be a minor respiratory tract infection to an otherwise healthy person may have serious consequences in someone with underlying lung disease. Such people may also be at more risk of development of pulmonary disability.
Most of the evidence associating respiratory tract infections with products of stationary fossil-fuel combustion has been obtained in studies of children, which were described earlier. To summarize, there is reasonably good evidence that concentrations of sulfur dioxide and particles above U.S. air quality standards are associated with an increased incidence of lower respiratory tract infection, particularly croup and bronchitis, in children. The findings have also suggested a possible role for atmospheric suspended sulfates. The association with pneumonia is inconsistent and probably not real. In addition, there is little evidence that upper respiratory infections in childhood are related to sulfur dioxide and particle concentrations. A variable association of pullution with ear infections, which are often sequelae of upper respiratory tract infections in childhood, has been reproted.
The following discussion will evaluate mainly respiratory tract infections in adults not identified as having chronic lung disease and will also describe animal studies related to this topic.
Fairchild and his colleagues (1972) used a mouse influenza model to study the effects of sulfur dioxide. Combined exposure to relatively high concentrations of sulfur dioxide and to influenza virus was found to produce a higher incidence of pneumonia at higher concentrations but less pneumonia at lower concentrations than was observed in control animals.
In addition to producing an increase in the incidence of infection, it is conceivable that pollutants increase the morbidity of a preexisting infection, perhaps by interfering with the mechanisms by which the respiratory tract acts to contain and combat infectious foci. This was studied in mice exposed to sulfur dioxide at 20 ppm for a week after inhaling an infective dose of influenza virus. These animals developed more evidence of
pneumonia than mice that received the same viral dose but were not exposed to sulfur dioxide (Fairchild et al. 1972). The results were similar when sulfur dioxide exposure (25 ppm) preceded the viral infection. However, if the mice were exposed to sulfur dioxide at 2–5 ppm for a week after the influenza dose, a decrease in the extent of pneumonia was observed. Sulfur dioxide exposure did not appear to affect the growth kinetics of influenza virus. Not was it clear whether the observed pneumonia represented viral infection of the lung or a secondary bacterial process. These results may perhaps be explained by studies that indicate that lower doses or shorter exposures to sulfur dioxide tend to increase mucociliary clearance, whereas higher doses or longer exposures inhibit mucociliary flow (Ferin and Leach 1973, Holma 1967). The authors also mention unpublished findings that sulfur dioxide at 6–20 ppm results in inhibition of influenza viral growth in the nasal cavities of mice.
In another study of mice, Giddens and Fairchild noted that inhalation of sulfur dioxide at 10 ppm for 24–72 hr had much greater pathologic effects on the nasal mucosa of mice with mild upper respiratory tract disease than on those of a disease-free group (Giddens 1972). This could also be interpreted as indicating potentiation of a respiratory tract infection by sulfur dioxide, but the converse is equally possible. The basic mechanisms postulated for either assumption are similar, in that any insult to the respiratory tract is liable to interfere with the normal defense against other insults.
Studies that evaluated the effects of air pollutants on the pulmonary clearance of bacteria were reported by Rylander (1969). After inhalation of either live or dead Escherichia coli, groups of guinea pigs were exposed to sulfur dioxide at 5–10 ppm, to manganese dioxide aerosol at 5,900 ug/m3 (90 percent of particles smaller than 0.5 um), or to both for 3 hr (Rylander et al. 1971).
Negligible effects were observed with either manganese dioxide or sulfur dioxide alone. However, combined exposure led to a
statistically significant decrease in the removal of either the live or dead bacteria from the lung. It should be noted that removal of dead bacteria presumably reflects mucociliary clearance, whereas removal of live bacteria also measures lung bacteriacidal capability. Also of interest in this study is that manganese dioxide is relatively insoluble, and earlier studies by Amdur and Underhill had failed to show a synergistic effect of sulfur dioxide and manganese dioxide on guinea pig bronchoconstriction (Amdur and Underhill 1968). Rylander et al. suggest that the combination of these two agents produces a decrease in pH that accounts for the biologic effects. However, previous studies by Tylander had similarly demonstrated a synergistic effect of suflur dioxide and coal dust in this same system, and it is not clear whether this could be due to pH (Rylander 1970, 1969). It is of interest that viral infections have been shown to retard the clearance of dust particles; this suggests that infectious disease might potentiate an effect of atmospheric particles on lung clearance, leading in a sense to a vicious circle (Creasis et al. 1973).
Battigelli et al. (1969) were unable to demonstrate any effect of sulfur dioxide in combination with graphite dust on the bacterial microflora of rats. Animals were exposed to graphite dust at 1,000 ug/m3 or to graphite dust and sulfur dioxide at 1 ppm for 12 hr/day for 4 months and compared with nonexposed controls. Bacterial samples form the nasal turbinates, the main stem bronchi, and the lungs at weekly intervals revealed no significant differences among the three groups.
A number of studies have also suggested that prolonged exposure to sulfur dioxide results in an alteration of immunologic response (Ardelean et al. 1966, Zarkower 1972, Zavrotskii 1959). Antibody formation and cellular immunity play a role in preventing lung infection, so any decrement in these responses would presumably potentiate a deleterious response to microorganisms. A study by Goldring (1967) in which hamsters were repetitively exposed to sulfur dioxide at 650 ppm showed no additive effect of influenza virus. There was, in fact.
some evidence that this concentration of sulfur dioxide may have killed the virus. A recent sudy by Zarkower has evaluated a number of characteristics of immune response in mice exposed to sulfur dixide at 2.0 ppm, to carbon particles at 558 ug/m3 (particle diamter, 1.8–2.2 um), or to both for up to 200 days (Zarkower 1972). Variable responses, depending on the duration of exposure, were observed; but, by the end of the experimental period, the animals exposed to sulfur dioxide or carbon alone had a reduction in serum hemagglutination titers to killed Escherichia coli administered as an aerosol. Combined exposure to sulfur dioxide and carbon produced less than an additive response. In contrast, there was an enhancement of the number of antibody-forming cells in the mediastinal lymph nodes with either carbon or sulfur dioxide after 135 days of exposure that was no longer observed after 192 days of exposure. Mice exposed to both agents had a synergistic increase in mediastinal lymph node antibody production after 135 days that was still present after 192 days. The major implication of these findings is that long exposure to relatively low concentrations of sulfur dioxide produces a lateration in the immune system of the mouse. As pointed out by the author, the mechanism of this effect is puzzling. Further studies are indicated before these results can be extrapolated to humans breathing ambient polluted air, particularly because infectious disease has not been noted as a problem in humans occupationally exposed to the sulfur dioxide concentrations studied or to higher concentrations.
An interesting in vitro study that has apparently not been folowed up is that of Lawther et al. (1969). They noted that aqueous extracts of particles collected from London air had a stimulatory effect on the growth of Haemophilus influenzae, a bacteria that has been implicated in the progression of chronic bronchitis and often recovered from the sputum of chronic bronchitis patients.
Many of the epidemiologic studies of the association of respiratory tract illness with air pollution have evaluated illness absences
among large populations of workers. Angel et al. studied the weekly attack rate and prevalence of respiratory illness in men working in a post office savings bank and an engineering works in London who lived within 2 miles of an air monitoring station (Angel et al. 1965). The group consisted of 85 men, representing about one-fourth of the work population, who were apparently selected to some extent on the basis of frequency of chest illness. They were seen by a physician at least once every 3 weeks from October 1962 to May 1963. The attack rate of minor respiratory illness was associated equally with weekly means smoke and sulfur dioxide concentrations. After standardization for pollutant effects, no correlation with temperature was observed. The prevalence rate was found to be more strongly associated with smoke than with either sulfur dioxide or temperature. These results are somewhat different from those reported by Gregory for bronchitics (discussed above). This may be due in part to differences in the extent of underlying illness, although it is not clear from the data of Angel et al. (1965) whether their population group contained subjects with chronic bronchitis.
Dohan and Taylor assessed the incidence of illness absences of women working in manufacturing plants of a large U.S. corporation during 1955, 1957, and 1958 (Dohan 1961, Dohan and Taylor 1960). Mean annual monitoring data for the eight eastern areas that had plants with more than 900 women workers were correlated with respiratory illness absences lasting more than 7 consecutive days. There was a fivefold difference in the incidence of respiratory illness between the factories with the most and the fewest illnesses. A remarkably high correlation (r=.964; p≤0.001) was observed with the mean annual suspended particulate sulfate concentration, and the rank order of the eight plants was consistent in each of the 3 years studied. Furthermore, in the year of a major influenza epidemic, the areas with higher particulate sulfate concentrations had greater increases in respiratory illness absence rates. The four areas with the highest illness absence
rates had mean annual suspended sulfate concentrations of 13.2–19.8 ug/m3. Of the four lowest areas, sulfate data were available for only one (7.4 ug/m3), but sulfate concentrations were estimated to be very low in another. The communities with the two highest respiratory illness absence rates had the two highest concentrations of total suspended particles (173 and 188 ug/m3); however, the gradient for this pollutant was otherwise unrelated to respiratory illness. Some tendency toward as association of airbone copper, nickel, and vanadium was also observed. When the data were evaluated for types of respiratory disease, an association with suspended sulfates was observed for influenza and bronchitis, but not for pneumonia. These findings did not appear to be related to interplant differences in age, weather, crowding, occupational exposures, or the number of children at home. As pointed out by Dohan, the observed effect may have been due to a prolongation of the duration of respiratory tract illness to 8 days, rather than to an increase in the incidence of disease. One problem with the study is that mean annual sulfate concentrations were based on only 21–25 determinations in four of the five areas for which these data are available. Nevertheless, the observed correlation is remarkably high for a study of this sort and strongly suggests an effect of suspended sulfates.
Ipsen et al. (1969) evaluated the relationship between industrial absences, air pollution, and meteorologic factors in plants in Philadelphia and Camden, New Jersey, in 1960–1963. Total suspended particles, particulate sulfate, and soiling index were measured. Morbidity, defined as incidence and prevalence of respiratory disease, was associated with weather factors and with pollutants. Of the pollutants measured, the immediate correlation with suspended sulfates was the strongest. However, this almost disappeared when partial correlation coefficients were calculated in which each variable was adjusted for the others. This analysis demonstrated that weather had the major effect on respiratory morbidity, although there was a significant positive correaltion of
an additive index of all three pollutants with the prevalance of respiratory disease on the same day or a week later. The actual monitoring data are not presented and presumably are rather limited, with respect to the number of sites available. The place of residence of the workers is also not taken into consideration.
Verma et al. studied respiratory and nonrespiratory illness absence data for 1965–1967 on white-collar workers, 16–64 years old and employed at a New York City insurance company (Verma et al. 1969). Respiratory disease absence rates per 1,000 employees per day were calculated, and the data were expressed as deviations from the average respiratory disease absence rate in relation to daily air pollution concentrations. On days when the temperature was in the 16–50 range, there were 4.50 more respiratory disease absences per 1,000 employees than average when the 24-hr sulfur dioxide concentration was 0.25 ppm or greater and 0.65 more per 1,000 employees when the concentration was less than 0.25 ppm. Again, with sulfur dioxide at 0.25 ppm as the dividing line, smaller differences in the respiratory disease absence rates were observed at higher temperatures. When the data were calculated for smoke shade, with 1.6 COHS as the dividing line, the gradient was not as steep in the temperture ranges of 16–50 F and 77–103 F, but was greater than that for sulfur dioxide in the temperature range of 51–76 F. No consistent effect of carbon monoxide was observed, and nonrespiratory illnesses did not correalte well with pollution.
Further analysis revealed a close association of respiratory illness with pollution and meteorologic factors for lag periods as long as 7 days. The data were strongly influenced by seasonal cycles, and removal of time trends greatly decreased the positive relationship between respiratory disease illness absences and pollution. A linear air pollution model was found to account for about 20 percent of the observed variability in illness absence rates. The authors conclude that, although no causal relation can be inferred, there is an association between air pollution, meteorologic variables, and
respiratory illness absences from one period to the next. It should be noted that New York City at present rarely exceeds a 24-hr sulfur dioxide concentration of 0.25 ppm, and it is not clear from this paper whether an effect might be observed at lower sulfur dioxide concentrations. A similar study in the New York area with more extensive air monitoring data would be valuable.
A number of studies have used cough to assess the effects of air pollution. Coughing is, of course, a nonspecific respiratory tract response. However, in the absence of chronic respiratory disease or an obvious atmospheric irritant, cough is usually ascribed to acute respiratory infections.
Loudon et al. (1969) assessed prescription rates for exempt narcotic anticough medicines in relation to environmental factors in Dallas. A negative correlation with temperature, but little (if any) effect of air pollution was observed. Monitoring data are not given.
McCarroll et al. (1967), as part of a series of extensive studies of a New York City population living close to a monitoring station, assessed cough and eye irritation, but a distinct difference was noted when lag periods were studied. The pollutant effect on eye irritation represented by suflur dioxide concentration was almost immediate, whereas the maximal effect on cough occurred 1 or 2 days later. Particles were not consistently related to eye irritation, but were correlated to some extent with cough. There is some periodicity of the data that is not explained. The air monitoring data are not described, and meteorologic conditions were apparently not examined.
The same group of investigators also noted some correlation of respiatory tract illnesses with air pollution episodes. Of interest was an analysis of their data that attempted to define a subpopulation of persons who were particularly sensitve to environmental conditions and could therefore be used as monitors (Lebowitz et al. 1972). A specific subset of people were identified who appeared to develop a higher incidence of upper respiratory tract infection when subjected to meteorologic extremes or high
pollution concentrations. An additional analysis of this group focused on the complex interactions of weather and pollution with regard to symtoms (Cassell et al. 1969). An increased incidence of upper respiratory infection was also observed in four New York City old-age homes during a 1962 pollution episode in which there was no apparent effect on mortality or hospital admit visits for upper respiratory infection or asthma (Greenburg et al. 1963).
Prospective studies of respiratory tract illness in the general community have also been performed as part of the CHESS studies in New York and Chicago (Finklea et al. 1974, Love et al. 1974). These have already been described. In both areas, an increased incidence of lower respiratory tract infection was obseved in mothers and fathers living in the more polluted communities. In Chicago, there was a slight tendency toward an association of upper respiratory tract infection with pollution, but the opposite was observed in New York. In all communities, mothers had higher illness rates than fathers; this probably represents a bias due to the mothers’ filling out the questionnaire. The data were interpreted by the authors as indicating that air pollution in the two New York City communities might be responsible for 5 extra days of restricted activity and one extra physician visit a year for an average family of four. The findings must be interpreted cautiously, particularly in view of some inconsistencies in the data, the possible effects of extraneous variables (such as indoor pollution), and the rather low questionnaire response rates. However, by and large, these studies support the conclusions discussed below.
The data cited indicate relatively clearly an effect of products of stationary fossil-fuel combustion on the incidence of lower respiratory tract infections (not including pneumonia). The evidence does not support an association of these pollutants with upper respiratory tract infection, except perhaps in a particularly susceptible population. A no-effect concentration has not been established and may
be below the pollution concentrations associated with the present air quality standards for sulfur dioxide and particles. However, the no-effect concentration appears more likely to be at or somewhat above the present standards. A role of suspended particulates in the production of lower respiratory tract illness is strongly suggested, but not proved. This association with suspended sulfates clearly deserves further evaluation, which may result in the establishment of an air quality standard more directly related to protecting the public against pollutant-induced lower respiratory tract infection.
There is no substantial evidence that directly implicates sulfur oxides in the causation of lung cancer. However, some observations indirectly suggest a relationship and clearly indicate that more study of this subject is required.
In vitro studies have indicated that sulfur dioxide can react with the deoxyribonucleic acid (DNA) cytosine, a component of chromosomes, which carry genetic information. Incubation of cytosine with bisulfite, a hydrated form of sulfur dioxide, results in the formation of the unstable intermediate dihydrocytosine-6-sulfonate, which deaminates to form uracil (Hayatsu et al. 1970, 1970, Shapiro et al. 1970). The conversion of cytosine to uracil after incubation with bisulfite has been observed in viral and bacterial DNA, yeast ribonucleic acid (RNA), and synthetic nucleic acid polymers.
Theoretically, a modification of nucleic acid constituents in a molecule containing genetic information is potentially mutagenic. An increased frequency of reversion of transition mutants of Escherichia coli consistent with mutagenesis has been observed by Mukai et al. (1970), and two scientific groups have observed bisulfite mutagenesis in bacteriophage (Summers and Drake 1971, Hayatsu and Miura 1970).
However, it should be noted that optimal conversion of cytosine to uracil occurs at a pH of 5.5, with little or no reaction at the usual
body pH of 7.4. All three studies of bisulfite microorganism mutagenesis detected results at low pH; in the study of Mukai at al. (1970), no effect was observed in the physiologic pH range. An in vitro study in which phytohemagglutinin-stimulated human lymphocyte cultures were bubbled with 100 ml of sulfur dioxide at 5.7 ppm demonstrated chromosomal abnormalities, as well as a decrease in DNA synthesis and mitosis (Schneider and Clakins 1970). Chromosomal abnormalities have been observed in pollen exposed to less than 0.1 ppm sulfur dioxide (ma et al. 1973). A lethal effect of sulfur dioxide (25 ppm) on tissue-culture cell lines has also been reported. Of interest in this study is that sulfite salts were more toxic to cell cultures than were equivalent concentrations of sulfate (Thompson and Pace 1962). An alternative mechanism of sulfite-induced damage to DNA might occur in which free radicals, developed during sulfite oxidation at physiologic pH, alter nucleic acid constituents in a manner presumably similar to that of radiation. Again, there is no evidence that any of these reactions occur in vivo after inhalation of sulfur oxides.
The epidemiologic evidence suggesting an association of sulfur oxides with cancer is at best indirect. For the most part, it is based on the generally observed higher lung cancer incidence in urban than in rural areas, which appears to be unrelated to cigarette-smoking. This urban effect is still open to question, as is its relation to sulfur oxides. Stocks (1960) and Burn and Pemberton (1963) have found positive correlations of smoke pollution and lung cancer. However, Ashley (1967) reported slight negative correlations of both smoke and sulfur dioxide with lung cancer, despite high positive correlations of these two pollutants with bronchitis mortality in residential areas of Great Britain. If there is an urban effect and it is related to air pollution, aromatic hydrocarbons are more likely to be causative pollutants (Carnow and Meier 1973, Stocks 1960). Higgins (1974) has noted a decrease in the trend of lung cancer in Britain in recent years that cannot be totally accounted for by changes in
cigarette-smoking and that appears to follow the decrease in particulate air pollution. Studies in Nashville (Hagstrom and Sprague 1967) and in Erie County, New York (Winkelstein and Kantor 1969), which evaluated the relation of cancer rates within the same urban area to different degrees of air pollution, have found some association of sulfur dioxide or total suspended particles with some nonpulmonary tumors, but none with cancer of the lung, which would be the presumed site of action of inhaled sulfur oxide irritants.
Lee and Fraumeni demonstrated a greatly increased risk of lung cancer in smelter workers exposed to arsenic in the presence of relatively high concentrations of sulfur dioxide (Lee and Fraumeni 1969). A smaller lung cancer gradient for sulfur dioxide exposure was observed, and it was technically difficult to separate the effects of these two agents. Although an independent role of sulfur dioxide is possible, the data are probably best interpretable as representing a promoting action by sulfur dioxide on arsenic carcinogenesis, perhaps analoguous to the findings of Laskin et al. (1970) discussed below.
Some of the most impressive evidence consistent with the possibility that sulfur oxides are at least partly responsible for an increased incidence of urban lung cancer has been obtained in animal studies. Peacock and Spence (1967) exposed a strain of mice that has a high incidence of spontaneous pulmonary adenoma to sulfur dioxide at 500 ppm for 5 hr/day, for 300 or more days. An increase in adenomas and what is described as carcinoma was noted in the sulfur dioxide-exposed group. In the ongoing sutdies of Laskin et al. (1970), animals have been exposed individually, simultaneously, and sequentially to benzopyrene, and aromatic hydrocarbon air pollutant, and to sulfur dioxide (3.5 ppm). Lung squamous cell carcinomas have been found in the groups inhaling both benzopyrene and sulfur dioxide. Although benzopyrene is a highly potent carcinogen in many systems, lung cancer had previously been observed only after tracheal instillation of this agent, and not during
inhalation. These interesting findings must be interpreted with caution, especially because high pollutant concentrations were used in the initial study. In addition, it is not clear whether the findings represent an independent carcinogenic effect of sulfur dioxide in addition to benzopyrene or a potentiation of benzopyrene carcinogenesis by an otherwise unrelated consequence of sulfur dioxide exposure. Recent preliminary studies by this group appear to indicate that combined exposure to nitrogen dioxide and benzopyrene also results in lung carcinogenesis. If this is confirmed, it would tend to support the hypothesis that sulfur dioxide promotes benzopyrene carcinogenesis through its action as a nospecific irritant. However, whatever biomedical mechanisms are involved, further animal inhalation studies with lower pollutant concentrations are definitely warranted.
Despite the biochemical and animal inhalation studies cited, there appears to be insufficient epidemiologic evidence to assign a definite risk to the possibility that ambient sulfur oxides are a factor in the production of human lung cancer.
There have been a number of attempts to quantify the damage caused by air pollutants. To do so, it is necessary to assign some numerical value to the expected health effects in relation to given degrees of air pollution. In the preceding sections of this review, where permitted by the data, quantitative estimates of morbidity and mortality in association with air pollution have been cited from individual papers. It would be possible to graph these estimates and analyze them statistically to arrive at some quantitative estimate of the amount of morbidity and mortality associated with measured concentrations of individual pollutants. However, such an exercise would be grossly misleading and would undoubtedly lead to erroneous conclusions. Each of the studies cited earlier must be considered in relation to
the population at risk, the nature of the measured and unmeasured pollutants present, and the limitations in the gathering and analysis of data.
Furthermore, it should be clearly understood that the assessment of dollar costs related to air pollution health effects is a numbers game. As in any game, there are some basic rules that must be accepted. The major rule in this game is that illness can be fully quantified in terms of dollars. That this premise is unacceptable and perhaps unethical must be kept in mind during any discussion of this topic.
A major problem in any quantitative approach to air pollution health effects is in defining a completely safe level of exposure; so-called threshold or no-effect levels. The difficulties with this concept have been ably discussed by different authors in the recent National Academy of Sciences report on “Air Quality and Automobile Emission Control” (NAS 1974). The last paragraph of the statement prepared by Palmes for the NAS-NRC Committee on Sulfur Oxides is as follows:
It should be recognized at the outset that there is no value other than zero that will carry with it assurance of obsolute safety, or zero risk. There are, however, finite concentrations that, in the light of present understanding, would reasonably be expected to produce a very small risk of adverse effects. These adverse effects can range from minor and transient irritation to serious chronic diseases, such as emphysema. Depending on the benefits of the process(es) that introduces the contaminant into the environment, this risk could be judged acceptable or unacceptable. Obviously, as the toxicologic data base is increased, the calculated risk should be changed accordingly. Thus, a given concentration of a specific material could be acceptable at one time and not acceptable later. Similarly, the benefits would necessarily be reevaluated as the technology changes. In summary, the acceptability of a degree of contamination would depend on the risk-benefit appraisal at a particular time.
An interesting introduction to the methodology for quantifying air pollution costs is given in a symposium edited by Wolozin (1966). In general, the participants point out the difficulties in applying economic approaches to this field and apperar rather dubious about obtaining reasonably accurate estimates. Ridker (1967), however, has described a number of methods to evaluate air pollution costs. He estimated the cost of air pollution in 1958 at $360–400 million of the total $2 billion cost of respiratory disease. The figure of 18–20 percent of pollution costs due to air pollution is derived from studies of urban-rural differences in respiratory and lung cancer mortality rates.
A thorough analysis of pollution costs due to disease is presented by Lave and Sesking (1970). They derive their estimate of the impact of air pollution on various diseases by extrapolation form, the literature and by extensive analysis of the urban factor in disease. Multiple regression analysis is used for such factors as population density, race, sex, and socioeconomic and age variables, as well as air pollution. They conclude that a 50 percent reduction in urban air pollution would account for 25–50 percent of the excess urban mortality and morbidity from bronchitis, 25 percent of lung cancers, 25 percent of respiratory disease, 10 percent of cardiovascular morbidity and mortality, and 15 percent of cancer in general. On the basis of these figures, a total savings of $2.08 billion in health costs would be associated with a reduction in air pollution by 50 percent. This reduction would bring more polluted cities into the category of urban areas with relatively clean air. They further estimate that such an abatement would lead to a 4.5 percent reduction in the economic costs associated with all morbidity and mortality.
Waddell (1973) has reevaluated these data to assess the amount of money to be saved if the reduction in air pollution reached 1970 standards and has derived a figure of $3.73 billion in 1970. He also discusses an EPA analysis in progress that used data from the
CHESS studies to derive an estimate of the health costs of sulfur oxides and particles of $0.9–3.2 billion. Barrett and Waddell (1973) also reevaluated the Lave and Sesking data to take into account indirect costs not included in the original analysis; by using the figure of 4.5 percent of total health costs due to air pollution, they arrive at a figure of $4.3 billion.
Many of the more recent studies of air pollution health costs have used Lave and Seskin’s data (1970) as the baseline for further analysis and have generally derived much higher figures, ranging up to $15 billion, although this is due partially to inflation. Some of these studies have been reviewed by Waddell (1973), Babcock and Nagda (1973), and Williams and Justus (1974). The later authors are highly critical of other studies of this subject and in their own analysis report the figure of $62–311 million as the yearly cost of air pollution to health. Their major objections to the higher figures are that these are based on overestimates of the contribution of air pollution to urban respiratory disease and that there has been a misinterpretation of the Lave and Seskin data to which the additional costs have been added. The first point is discussed below and seems to constitute a valid objection. The second point appears to be partly correct, in that Lave and Seskin were evaluating the major part of the urban air pollution effect and that analyses that have restricted the Lave and Seskin data to sulfur oxides and particles and then added costs for other pollutants have therefore been counting effects twice. However, although the analysis of the air pollutant contribution to urban disease by Lave and Seskin probably did include the effects of nitrogen oxides, it did not consider problems usually associated with carbon monoxide. The criticism by Williams and Justus (1974), concerning the doubling of Lave and Seskin’s estimate of $2.08 billion to derive a figure for the total costs of air pollution is probably inaccurate, in that other invetigators appera to be using the $4.3 billion estimate of Barrett and Waddell (1973). In addition, the Williams and Justus analysis
probably is in error, in that they assert that cigarette-smoking and air pollution have synergistic effects; that is contrary to most studies, which show an additive relation.
In an interesting report by Chapman et al. (1970), projected emission data are used to estimate the excess adverse affects to be expected if standards are not met in the future. A preliminary assessment of the same areas has also been presented by the Brookhaven National Laboratory (Hamilton, Ed. 1974). Recently, Jaksch and Stoevener (1974) reported a study of outpatient medical costs in relation to air pollution in Portland, Oregon, in which it was estimated that an increase in total suspended particles from 60 ug/m3 to 80 ug/m3 would result in a 3.5 percent increase in outpatient medical costs per contact with the medical system for respiratory disease.
The Ford Energy Policy Project has also evaluated the health costs of stationary fossil-fuel combustion, but its model is concerned mostly with factors not related to community air pollution. However, a panel of the American Public Health Association (APHA) estimated health effects associated with energy use as part of the input into the Ford Energy Policy Project. The original APHA document developed a model to determine numerically the adverse health consequences expected from a partial conversion of energy souces from oil to coal. The authors strongly biased their results by selecting from among the most apparent examples of air pollution health effects in the literature and then overinterpreted the specific findings. This resulted in an extrapolation that indicated that the partial conversion of energy sources from oil to coal would result in severe health effects to a large population. Following a review process, the document was revised, and the results were restricted to more limited circumstances with less of an impact (Carnow et al. 1974). Unfortunately, the original unpublished extrapolations were included in a press release from the American Public Health Association which was widely reported and is still being quoted.
The above discussion does not include non-disease costs of air pollution. These are considered in some detail in a number of the references, some of these costs are more or less quantifiable, including effects on agriculture, damage to materials, and loss in property values. Others, such as aesthetic effects and annoyance, cannot readily be expressed in numbers. Even the quantifiable effects may have hidden values not easily put into dollar terms. For instance, the monetary costs of covering up the rapidly deteriorating marble facade of New York’s City hall is a matter of record.. But one cannot place a number on the resulting cost to the eye of the casual stroller.
It must be emphasized that it is inappropriate merely to balance the health dollar costs with the price of air pollution control. There is an increment above the economic costs that each person would be willing to pay to avoid being ill. Obviously, this increment will vary with the degree of suffering or life-shortening involved, the absolute dollar costs, and financial circumstances of the individual. Most people, for example, would be willing to pay 25 cents if they could somehow magically avoid a painful cut for which the sole economic cost is 1 cent in bandages. Few would be willing or able to pay $25,000 to avoid an appendectomy costing $1,000.
Although it would seem reasonable to approach a cost-benefit analysis by dividing the air pollution control costs on a per capita basis, this may not be appropriate for the benefits. That is because of the marked variability in individual response to pollution and because most members of the population do not now know whether they belong to a hypersusceptible group that will in the future be severely affected by pollution. A more valid economic approach might be to inquire whether the per capita air pollution control cost is a reasonable price for each individual to pay as a form of insurance against the possibility of being significantly and adversely affected by the absence of air pollution control.
The following estimation of the health costs of sulfur oxides is presented with great reluctance due to reservations concerning its validity and usefulness. The analysis is restricted to the effects of sulfur oxides that appear to be reasonably justified on the basis of the foregoing review and is related to estimated health effects within a reasonable range of present pollution conditions. The goal is to provide judgment estimates of possible use to economists interested in costing out the health effects of sulfur oxides. The inexactitude of both the health effects and the economic data appears to justify the use of round numbers and broad estimates. Within these contraints, the bias will be to overestimate the effects of sulfur oxides, and the figures can be considered as upper limits based on available information.
The most apparent effect of sulfur oxide air pollutants is on increasing the morbidity and mortality associated with chronic respiratory disease, particularly chronic bronchitis and emphysema. One approach to assessing the dollar costs for this effect is to estimate the fraction due to air pollution nationwide. Review of the literature reveals that, in addition to air pollution, there are a number of factors associated with the prevalence of chronic respiratory disease, including cigarette-smoking, occupational exposure, constitutional characteristics, and the vicissitudes of aging. Meteorologic factors, particularly low temperature, play an improtant role in acute exacerbations of disease and in mortality. Cigarette-smoking is undoubtedly the major factor in causation of disease, so it would be useful to compare its effects with those of air pollution. This can probably best be done by use of the CHESS studies (EPA 1974), which have carefully and consistently looked at this problem in a number of communities, and which are unlikely to have underestimated the effects of air pollution. In the CHESS summary (Finklea et al. 1974), it is stated that the relative contribution of air pollution to chronic bronchitis prevalence is one-third to one-seventh as strong as that of cigarette-
smoking, except for males in New York City, in whom the contribution of air pollution was slightly larger than that of smoking. This is due to the remarkably high prevalence of bronchitis in nonsmokers in New York, ranging up to 5 times as high as that observed for males in other polluted CHESS communities. As pointed out by the CHESS investigators, this is “a finding difficult to accept in the light of other evidence.” Furthermore, the relative effect of air pollution was only one-eleventh that of cigarette-smoking in the Chicago military recruit study. The data of Lamber and Reid (1970), obtained during periods of very high pollution in Great Britain, also suggest that air pollution has at most one-third of the effect of cigarettes.
Accordingly, it seems that a reasonable estimate is that air pollution is responsible for at most one-fourth of the effect of cigarette-smoking on bronchitis prevalence, and presumably eventual bronchities mortality, among those who both smoke and live in urban areas. However, assuming that 20 percent of chronic respiratory disease is due to air pollution nationwide is inappropriate, in that not everyone is a cigarette-smoker and some fraction of the problem is related to constitutional factors and occupational exposure. An even greater dilution will occur when a factor is added for the fraction of the population exposed to significant concentrations of products of stationary fossil-fuel combustion. In addition, some degree of chronic bronchitis prevalence and mortality may be related to nitrogen oxides, which are only partially derived from this source. Thus, it seems reasonable to assign no more than 10 percent of chronic bronchitis prevalence in the general population to the effects of sulfur oxides.
Alternatively, if one accepts the figure of 70 percent as the amount that cigarette-smoking contributes to chronic respiratory disease, a figure of 10 percent for sulfur oxides appears reasonable after the effects of occupational exposure, constitutional factors, etc., are considered.
With respect to acute morbidity occuring during the course of chronic respiratory disease, two major factors are the community incidence of upper respiratory infections and temperature variations. After consideration of the dilution factors mentioned above and the epidemiologic observations of this problem in relation to current air pollution, it again appears reasonable to attribute to sulfur oxides no more than 10 percent of the acute morbidity in patients with chronic respiratory disease.
The effect of air pollution on acute respiratory infection is difficult to estimate. There is little evidence of any outstanding effect of sulfur oxides on the incidence of upper respiratory infections. However, in view of some findings that suggest such an effect, particularly in susceptible populations, it seems appropriate to set a figure of 1 percent for the effect of sulfur oxides nationwide. There is much better evidence of an association with lower respiratory tract infections. One approach to assessing the economic costs is to use the figures provided in the CHESS New York City (Love et al. 1974) study, which showed a substantial effect of pollution on lower respiratory tract infections. It was estimated that the average family of four would expect to have 5 extra days of restricted activity and one extra physician visit per year due to air pollution. Because no work time is lost by children, not all fathers and mothers are employed, and people do not work every day, the activity-restricting effect could be roughly translated into 1–2 working days lost per year per employed person in the population at risk as a result of sulfur oxides. However, until this CHESS study is replicated, these figures should be viewed with caution.
Estimates of the effects of sulfur oxides and particles on asthma attack rate have also been provided by the CHESS document. Specific risks appear to increase by 10–50 percent on days with increased pollution and in conjunction with specific meteorologic factors. Making a rough attempt to account for days when the air is clean or the climate is not conducive again suggests that a reasonable estimate from the
data might be a 10 percent yearly increase in attack rate in polluted areas, or perhaps 5 percent nationwide.
As discussed earlier, there is insufficient evidence that sulfur oxides participate in the causation of lung cancer or other cancers to assign any risk to this problem.
Separate estimation of mortality due to air pollution is difficult inasmuch as this is due mainly to chronic respiratory disease, which has already been considered. However, one can use the Buechley data (Buechley et al. 1973) for the New York area, which indicate that 2 percent of deaths in 1962–1966 were associated with sulfur dioxide and particles and then arbitrarily extrapolate from the number of deaths for chronic pulmonary disease at that time to assess the total nonrespiratory deaths.
A factor for increased morbidity in patients with cardiopulmonary disease should also be used. However, the bulk of the effects in chronic bronchitis has already been considered. The effects of air pollution in patients with cardiac disease can be roughly estimated from the CHESS (Goldberg et al. 1974) study as being in the range of 10–30 percent reporting more symptoms. The extrapolation of this figure to medical care costs is difficult.
A number of points deserve emphasis. The estimated health costs given above are based on the assumption that the major question concerns the benefits of air pollution control measures in addition to those already in use. The figures are not applicable to discussion of the relaxation of currently operative controls. Although no firm dose-response curves can be given, it is clear that an increase in sulfur oxides above the present concentrations would produce more adverse health effects than would be prevented by a decrease in pollutant concentrations of an equivalent amount. A possible source of underestimation of the health costs is the imprecision of current pollutant monitors. It is conceivable that improved quantification of sulfuric acid or a particular respirable sulfate would result in the observation of a much greater association of sulfur oxides with health effects than is now evident.
In response to the request of the U.S. Senate Committee on Public Works, a panel of the National Academy of Sciences (NAS) is endeavoring to delineate the effects of various control strategies on atmospheric sulfate concentrations in relation to their monetary costs. To quantify the potential benefits of air pollution control measures, it would be extremely useful to have available dose-response curves indicating the extent of adverse health effects produced by given concentrations of a specific pollutant. On the basis of the CHESS studies, the EPA has estimated dose-response curves for suspended sulfates. As pointed out by the CHESS investigators, their data represent first approximations that require further replication. The dose-response curves provided by CHESS may have underestimated the true effects by a factor of 2 or overestimated them by a factor of 10. This judgment is provided solely in the interest of suggesting a framework for the NAS analysis of the impact of various control strategies and in recognition of the urgency of making decisions concerning these strategies.
It must be kept in mind that suspended sulfates are merely an indicator of the health effects of sulfur oxides. Although, on the basis of the scientific literature, it is reasonable to assume that suspended sulfates are a better indicator of sulfur oxide toxicity than is sulfur dioxide, there is clearly a difference in relative potency between various forms of sulfate, and there is little likelihood that one oxide of sulfur is solely responsible for the observed health effects of all oxides of sulfur. The use of suspended sulfates as the basis for an analysis of control strategies has the advantage of indicating the importance of the atmospheric oxidation of sulfur dioxide. However, because the relative potencies of the various sulfur oxides in polluted air have not been ascertained, it might be preferable to relate health effects to units of sulfur emitted into the atmosphere. Furthermore, in view of the uncertainties and possibly inappropriateness of presenting human suffering in terms of dollar costs, a numerical estimation of illnesses might
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