Document mBMn0LLw5BmaRGbZb8q3Y9514

Environmental Health Perspectives Vol. il. pp. 255-176, 1981 Assessment of the Health Effects of Atmospheric Sulfur Oxides and Particulate Matter: Evidence from Observational Studies by James H. Ware,* Lawrence A. Thibodeau,* Frank E. Speizer,** Steven Colome* and Benjamin G. Ferris, Jr.* Steadily ri*ing*nrgy coctt have increased the need for reliable information on the health effects of atmospheric sulfur oxides and particulate matter. Because ethical and practical consider* ations limit studies of this question under controlled conditions, observational studies provide an important part of the relevant information. This paper examines the currently available epidemiologic evidence from population studies of the health effects of these pollutants. Nonexperimental studies also have important limitations, including the inability to measure accurately the exposure burden of free living individuals, and the potential for aerious confounding by other factors affecting health. We begin with a discussion of some of these methodologic issues. The evidence is then reviewed, first in association with fluctuations in 24 hr mean concentration of sulfur oxides and particulate matter, and then in association with differences in mean annual concentration. In the last section, this evidence is summarized and used to approximate the exposure-response relationship linking pollutant concentrations with mortality and morbidity levels. Introduction In view of the potential for adverse health effects of air pollution, and the expense of control mea sures, reliable assessment of the health effects of different air pollutants is an important public health This work was supported in part by contracts funded by the Environmental Protection Agency in conjunction with prepara tion of the Air Quality Criteria Document for Particulate Matter and Sulfur Oxides and by grant ES0U06 from the National Ins'.itute of Environmental Health Sciences and Electric Power Research Institute Contract No. RP 1001 EPRI. The opinions expressed are those of the authors and may not reflect the position of the Environmental Protection Agency. `Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115. ?Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital. October 1981 problem. Lowrance (J) has defined four tasks in this assessment: identifying the health effects; quantifying these effects at various ambient concentrations; estimating how many people are exposed at these levels; and calculating the overall health risk associated with a given degree of air quality. This paper addresses the quantification of the health effects of sulfur oxides and particulate matter, especially at ambient concentrations near the present air quality standards. The health effects of these air pollutants can be studied to some extent in controlled conditions. Laboratory studies of animals allow careful control of the concentration of individual pollutants and conditions of exposure, as well as detailed study of the effects on study animals. These studies have been useful for identifying possible mechanisms of action and potential health effects. However, it is 255 UCC 084321 a difficult to use animal studies to quantify these and effect, rather we infer causality based on the effects in human populations, primarily because the precepts proposed by the Surgeon General's Advi basis for extrapolating from animal to man is sory Committee on Smoking and Health (2) and bv a uncertain. The uncertainty of such extrapolation is Hill (3): the strength of the association, the consis increased by significant interspecies variability in tency of the data, the specificity of the results, the the response to pollutants. temporality of the observations, the demonstration Laboratory studies with human subjects avoid of a biological gradient and the plausibility and extrapolation from animal to man but raise other coherence of the results. Ideally, findings will be concerns, such'as ethical considerations and practi replicable by specific experimentation, and conclu a cal difficulties in studying long-term exposures. In sions will be further strengthened when different addition, laboratory studies cannot duplicate the approaches or methods yield similar results. activity patterns and pollutant mixture experienced The next section of this paper briefly sum by free living populations. Within these constraints, marizes the methodological issues which should be studies involving human subjects can be used to considered in evaluating nonexperimental studies establish the response to short-term exposure. of the effects on health of exposure to atmospheric Studies of occupational groups have been sug Bulfur oxides and particulate matter. We then gested as another source of information. Although review the evidence from selected studies of the these studies may provide good estimates of expo association between mortality and morbidity levels sure, the mix of pollutants and concentrations is and 24*hr mean concentration of sulfur oxides and usually different from ambient air. Exposures are particulate matter the evidence linking mortality for 8 hr or less rather than on a more continuous and morbidity levels to annual mean concentra basis. Temperature and humidity conditions are tions. The evidence is summarized in the final t also likely to differ from those experienced by the general population. Furthermore, the working popu section. lation differs fronrthe general population in impor tant ways. The very young, elderly and ill persons Methodological Issues in are not included. There is considerable selection by the employer and self-selection by the worker, so Observational Studies that those with current disease or who are more Observational (nonexperimental) studies of the sensitive or susceptible are not as well represented association between health and air pollution are as in the general population. As a result, one cannot sometimes viewed as natural experiments in which conclude from a negative study in an occupational the exposure to pollutants varies over groups or group that the same exposure is safe for the general time. However, this view ignores several special population. If an association between an air pollu characteristics of observational studies of air pollu tant and a health effect is found in an occupational tion. One of the most important is inaccurate setting, there may be a greater association in measurement of the exposure burden of individu general populations. als. Pollution data are usually obtained from one or Because of the limitations of each of these several outdoor monitoring stations, but the expo types of investigation, epidemiologic studies in sure burden can vary greatly between individual- general population groups provide much of the living in the same neighborhood because of special relevant information about the health effects of features of the outdoor micrometeorology and the sulfur oxides and particulate matter at levels of indoor environment (4-6). The effects of errors in exposure near present ambient standards. Here, the independent variable on the estimated associa too, there are limitations with respect to estimating tions between air pollution and health effects de exposure and measuring effects. Other risk factors, pends on both the size and expectation of the such as cigarette smoldng and occupational expo errors. Many health endpoints, including lung func sures, must be considered, and confounding fac tion, hospital admission and frequency of symp tors, such as socioeconomic status, race and weather toms, also are measured with substantial variabili must also be evaluated. In these studies, exposures ty. When an association between air pollution and are not subject to manipulation, though ambient health is found, collinearity (high correlation) of levels can change during the course of a study. This sulfur oxide and particulate concentrations (?) and makes it difficult to determine whether mean con the possibility of complex chemical interaction- centration, peak concentration, variability, or some reported from laboratory studies (8. 9) frequent!) other aspect of air pollution concentration is the make it difficult to associate the effect with either most important determinant of health effects. pollutant alone (10). Observational studies cannot demonstrate cause Observational studies of respiratory disease or 256 Environmental Health Perspective? UCC 084322 a Iby |sis- the tion and 1 be clu- a'ent urn* i be dies eric .hen the *vels and tlity traina] 1 the ' or cial illuate idua or ^po* jals cial the s in ciadethe inempoiiiand i of and ons ltly her or lung function must consider a host of confounding variables (11), many of which have greater health efTects than air pollution. When these variables are ignored or inadequately measured, resulting bias can easily be greater than the association of inter est. In addition, many observational studies use linear or other simple models to summarize com plex data sets without assessing the adequacy of the model. Unless data displays, simple groupings or other analyses are used to show that these models are properly summarizing the data, one can only have limited confidence in the results. These factors, taken together, create additional uncertainty in interpreting observational studies in comparison with laboratory experiments. The most difficult problem in interpreting the evidence from a group of observational studies is determining how effectively these potential problems have been addressed in each study. There is an unavoidable element of subjectivity in the assessment of evidence. In an effort to reduce that subjectivity we have included in the assessment those studies which satisfy five criteria. (1) They have been reported in the open litera ture. (2) Concentrations of both 'sulfur dioxide and particulate matter were reported. (3) Major confounding factors were controlled, particularly temperature in studies of acute expo sure. and smoking, race and socioeconomic status in studies of chronic exposure. (4) The findings pertain to concentrations less than 1000 pm/m3 for both sulfur dioxide and particu late matter. (5) The data collection, analysis and interpreta tion were free of error or potential bias which could be reasonably expected to substantially affect the results. Studies failing to meet one or more of these criteria were also included when discussion of their validity and significance was seen as an important part of assessing the evidence from observational studies. Health Effects of Acute Exposure to Sulfur Oxides and Particulates The earliest studies of the acute health effects of air pollution focused on dramatic episodes of severe air pollution (12-18). The sudden increases in mor tality and morbidity that accompanied these epi sodes and the frequency and severity of respiratory complaints left little doubt that air pollution was, at least in part, the cause of the adverse health effects. Investigators also recognized that weather, October 1981 particularly extreme temperatures, could influence mortality and morbidity rates. A substantial reduction in ambient sulfur oxide and particulate concentrations, achieved in most English and American cities by the 1970's, pro duced a gradual decline in severity and eventual disappearance of episodes in which either sulfur dioxide or particulate matter exceeded 1000 p.g/m3 (measuring particulate matter either by the British Black Smoke method or as Total Suspended Particu lates). Episode studies-were gradually supplanted by studies of fluctuations in daily mortality over extended periods, and investigations of potentially more sensitive indices of health effects, including lung function and respiratory disorders. Sensitive population subgroups, such as asthmatics and chil dren, have also been studied. The pollution concen trations in studies of acute exposure have typically been measured by 24-hr mean concentrations, though high level exposures for shorter periods might be important. Counts of total daily mortality show a seasonal pattern with a peak in winter, and rates on succes sive days are interdependent. Early studies used the deviation of daily mortality from the 15-day moving average to eliminate seasonal effects. More recently, investigators have used sophisticated time-series-analysis techniques in an effort to elim inate seasonal effects and other long-term trends affecting daily mortality. Elimination of seasonal effects by these methods may be incomplete, and this becomes especially important when investiga tors attempt to identify pollution effects that are small relative to effects of temperature, season and even day of the week. We will return to this issue in the discussion of individual studies. Morbidity data are more difficult to gather than daily mortality figures. For that reason, investiga tions of morbidity effects of acute exposure to sulfur oxides and particulate matter have usually been small, permitting relatively simple analysis. These studies would be unlikely to detect small increases in morbidity at relatively low air pollution concentrations. Studies reported in this section used three sepa rate measures of particulate pollution. The British studies used the British Black Smoke method and reported particulate levels in ng;m3 (BS). Some American studies used the filter soiling method and reported particulate concentrations in units of Coefficient of Haze (CoHs). Other American studies measured Total Suspended Particulates (TSP) by the high-volume sampler method. Results are re ported for each study in the original units, and the relationship between the different measures is considered when summarizing the evidence. 257 L ucc 084323 Ii Mortality Effects of Acute Exposure to ship between differences in pollution concentration Sulfur Oxides and Particulate Matter and differences in death rate on successive days, I their paper provided total deaths, smoke concen In this section, we examine studies of the associ tration and S02 concentration from November 1, ation between daily mortality rate, as measured by 1958 to February 28, 1959. We have re-examined the recorded number of deaths, and 24-hr average their data after excluding the month of February', concentration of sulfur dioxide and particulate mat as an epidemic of Type A influenza had a significant ter. The clearest evidence comes from studies of influence on daily mortality in that month. I relatively high pollution concentrations, while stud ies of lower concentrations have been equivocal, For the remaining 92 days, the deviation of each day's total mortality from the 15-day moving aver primarily because collinearity of temperature and age (truncated at each end of the series) was other weather variables with pollution concentra computed. The average deviation is given far tions have made it difficult to interpret associations intervals of BS concentration in Table 1 and SO2 between daily mortality and air pollutant concen concentration in Table 2. trations. Although Lawther (21) has suggested that the I Studieo of Daily Mortality in London. Two number of deaths increased significantly when important British studies bearing on mortality BS rose above 750 ug/ms and S02 concentrations effects ofacute exposure to S02 and particulate matter exceeded 710 itg/nr, these tables do not suggest at concentrations near present 24-hr air quality stan those values. If one begins with a threshold hy dards were reported by Martin and Bradley 09) pothesis, that mortality is not affected until air and Martin (20). Martin and Bradley related daily pollution concentrations exceed threshold levels, mortality from all causes (and from bronchitis and one might choose threshold values of 500 ng/ms of pneumonia) to the concentrations of S02 and black BS and 300 p.g/m3 of S02 from these data. However, smoke (BS) in I^qndon during the winter of 1938-59. the data are also consistent with a monotonic The authors found a considerable number of coinci exposure-response hypothesis, that mortality level dent peaks in pollution concentration and daily increases with air pollution concentration over a mortality. The correlation of mortality from all broad range of values, including those just cited. causes with air pollutant concentration, measured A similar analysis was carried out by Martin far on the log scale, was 0.61 for BS and 0.52 the winter of 1959-60 (20). That winter had fewer for S02. The correlation between mortality and incidents of high pollution. The significant positive mean daily temperature was -0.03 (not significant), correlation between mortality and pollution was while the correlation of mortality with humidity still present, although the author reported that the was 0.19 (significant at the 0.05 level). The authors correlation coefficients were somewhat lower than noted that about two-thirds of the air pollution in the previous year. Tables 3 and 4 show Martin's episodes were accompanied by thick fog, and the results combining high pollution days from 1958-59 correlation between mortality and visibility was and 1959-60, excluding days with pollution concen found to be -0.55. Visibility is influenced both by fog trations lower than the previous day. The mean and particulate pollution. deviation is positive in every group reported. Although the authors emphasized the relation- Bronchitis mortality w*as also found to be significant!}'. ! though less strongly, correlated with pollution level. Pneumonia mortality was not found to be Table 1. Averse* deviation of daily mortality from 15-day moving average, by concentration of amoke (London. Nov. 1, correlated with pollution. 1958, to Jan. 31. 1959).* Smoke concentration, 114/m* (BS) 100-199 200-299 300-399 400-199 500-599 600-699 700-799 800-1199 1200 + Number of days 6 12 18 19 9 6 7 10 5 Mean deviation -20.82 -13.65 -10.80 -7.15 10.89 19.72 4.17 21.49 38.36 Table Z. Average deviation of daily mortality from 15-day moving average, by concentration of SO; (London. Nov. 1, 1958, to Jan. 31, 1959).* Smoke concentration, iig/m' Number of days Mean deviation 100-199 200-299 300-399 400-499 500+ 17 -13.01 29 -12.16 22 6.87 11 9.32 13 27.21 'Data of Martin and Bradley (19). 258 Data of Martin and Bradley U9). Environmental Health Perspectives UCC 084324 A*. len-rl. ined ary. cant fieh Tver- was for SO* the then tiong -gest 1 hv1 air vels, f or ver. tonic level er j ed. for IV* was t the than tin's '>8-59 -ennean rted, ntly, ition o be -day *v. i j i 7 9 1 ^ec Tabic S. Average deviation of daily mortality from 15-day oring averag*. by concentration of amoke (BS) (London, 195840).* Smoke concentration, pf/m1 (BS) GOO-599 600-699 700-799 800-1099 1100+ Number of days 9 6 9 8 7 Mean deviation 5.2 13.0 9.2 15.6 40.0 I *QaU of Martin (tO). These two studies represent an important part of the evidence for mortality effects of short-term elevations in S02 and particulate pollution. Al though temperature was not an important con founding factor in the two winters studied, fog was an important factor in many air pollution episodes, especially in the winter of 1958-59. Reported analy ses have not adequately controlled for the effects of fog on mortality. During this period, daily mean concentrations of S02 and BS were highly corre lated (r = 0.89 for the winter pf 1958-59). Conse quently, these associations cannot be attributed to either pollutant individually. Additional evidence for acute effects of short term elevations in sulfur dioxide and particulate matter concentrations was provided by the analysis of a pollution episode in London in December, 1975 (22.22). Maximum 24-hr concentrations of 994 jxg/m3 (SOj' and 546 p.g'm3 (BS) were reported, and an increase of 100 to 200 deaths above expected totals was observed during the week in which the episode occurred. A doctors' strike in the period immedi ately prior to this episode had an unknown impact on the mortality data. Studies ofDaily Mortality in Sew York City. The other principal source of information on variation in daily mortality comes from a series of studies in New York City. This information includes reports Table $. Average deviation of daily mortality from normal, by level of smoke shade (CoHs) (New York, 196044, October through March).* Smoke shade level (CoH) Number of days Mean deviation (SE) <1.0 1.0-1.9 2.0-2.9 8.0-3.9 4.0-4.9 5.0-5.9 6.0+ 26 -2.8 (3.5) 160 -1.6 (1.4) 318 -2.4 (1.0) 239 1.5 (1.2) 83 2.5 (2.3) 19 18.8 (4.3) 9 17.2 (7.8) *DaU of Glasser and Greenberg (7). October 1981 Table 4. Average deviation of daily mortality from 15-day movint average, by concentration of SO, (London. 195840).'* SO, concentration, Number of days Mean deviation 400-499 500-599 600-799 800-899 900+ . 9 9.0 6 11.6 9 16.0 6 19.2 5 39.6 Data of Martin (SO). (24-26) of several air pollution episodes not dis cussed here, since pollutant concentrations were too high to contribute significantly to our assess ment. However, Glasser and Greenburg (27) car ried out an analysis of daily mortality in New York City during the five-year period 1960-64, using only data from the months October through March. The 24-hr average pollution concentrations were based on hourly S02 and bihourly smoke shade (CoHs) readings from a single monitoring station. Death rates were analyzed both as deviations from a 15-day moving average and as deviations from the five-year average for that day. The two analyses were said to have qualitatively similar results. In cross-tabulation of daily mortality by S02 and smoke shade level, S02 appeared to be more strongly related to mortality and was used as an index of pollution in some analyses. Multiple re gression analysis showed a stronger association of mortality with S02 than with either temperature or rainfall. Tables 5 and 6 summarize the analysis by Glasser and Greenburg. These results have been inter preted as showing a mortality effect for smoke shade above 5 CoHs and S02 above 786 ng'ni3, though they are again supportive of a monotonic exposure response relationship. Although the ob servations of daily mortality are correlated, Glasser and Greenburg computed standard errors for the mean deviations by assuming independence. Most Table 6. Averafe deviation of daily mortality from normal, by level of SO, (New York. 196044, October through March).* SO, concentration, ngftn* Number of days Mean deviation (SE) <262 112 -3.5 (1.6) 262-524 311 -3.1 (1.0) 525-786 172 1.8 (1.4) 787-1048 66 9.4 (2.0) >1048 80 11.9 (2.5) *Data of Glaaser and Greenberg (f7). 259 UCC 084325 4 of these standard errors were near 2.0, though the from zero. Since the percentage of excess deaths entry 18.8 in Table 5 had a quoted standard error of attributed to air pollution differed little in periods 4 4.3. The authors also stratified days by tempera* with three-fold differences in S02 concentration, ture into three groups: those more than five de they concluded that S02 concentration is merely an grees below normal, within five degrees of normal, index variable for other unmeasured extraneous and more than five degrees above normal. The variables and not a cause of adverse health effects result of the stratified analysis differed little from at these levels. the unadjusted analysis. However, this simplified Schimmel (30) continued his analysis of these i approach to covariance adjustment may not elimi data by utilizing time series techniques to eliminate nate the confounding effects due to temperature. any seasonal or other cyclical effects contributing to Multivariate analyses of the New York data de associations between pollution and .mortality, b scribed below suggest that more careful control for this analysis, the regression of mortality on S02 temperature and other meteorologic factors has a was not significant and negative coefficients were substantial effect on the results. obtained in some regressions. To analyze possible mortality effects of even Buechley (31, 32) also sought to identify major t lower levels of pollution, the 15-day moving aver nonpollutant variables influencing daily mortality age method is not sufficiently sensitive. Further and found that mortality was affected by the annual more, some authors have argued that more sophis cycle, summer heat waves, influenza epidemics and ticated adjustment techniques are necessary to a temperature variable. These four variables ex ensure that seasonal and temperature effects are plained 78% of the variation in daily mortality eliminated in the adjusted analysis. To achieve that during the 11-year period 1962-72 in New York i objective, Schimmel and coworkers {28-30) have reported three analyses of mortality data from New City. Although S02 concentration and particulate level also entered significantly into the regression York City in whiotethe adjustment methodology equation, Buechley found that the coefficient for was refined over time. Buechley et al. (31) and S02 concentration in regression analysis of daily Buechley (32) have also analyzed some of the same mortality during the winter of 1971-72 was slightly data. higher than the corresponding coefficient for the Schimmel and Murawski (29) emphasized the winter of 1967-68, even though the mean SO2 common seasonal trends in mortality, pollution and concentration in the second winter was only 10% of temperature in New York City, and the possibility that in the earlier period. that nonlinear relationships would make linear Both Schimmel (30) and Buechley (32) concluded regression unsatisfactory as an adjustment tech that the associations they found between mortality nique. They eliminated periods associated with and air pollution could be explained by joint associ heat waves and analyzed the remaining data in ation with temperature and other weather vari three time periods, 1963-66, 1967-69 and 1970-72. ables. Their work highlights the limitations of While smoke shade level varied little over the three observational studies when the study objective is periods, the average SO2 level declined dramatical accurate estimation of-small primary relationships ly, as shown in Table 7. when other independent variables are more strongly Schimmel and Murawski estimated the percent associated with mortality. These other variables age of premature deaths due to air pollution to be influence the estimate of the primary relationship, 2.78, 2.48 and 3.20, based on regression analysis of and the proper method of adjustment is unknown. the three periods using a model with no lag Thus, it will be difficult to reliably quantify small effects. The percentage attributed to SO2 was 0.58, mortality effects of fluctuations in ambient pollution 1.22 and 0.62, values not significantly different concentrations by analyzing observational data. Table 7. Average pollution level* during three time period* analyzed by Schimmel and Murawiki.1 Time period SO? level, M*'m5 CoH* level 1963-66 1967-69 1970-72 112 2.07 359 2.27 155 2.13 *DU of Schimmel and Murawski (SS). 260 Morbidity Effects of Acute Exposure to Sulfur Oxides and Particulate Matter Levels of air pollution which acutely affect mor tality rates should affect other health indices, including incidence and prevalence of respiratory disease as measured by emergency room visits or hospital admissions, prevalence and severity of respiratory symptoms as measured by question- Environmental Health Perspectives ucc 084326 * ( 0hs lion, >an eous fects hese mate ngto In S02 were i^jor .alitv mual land s ex- jlitv York ulate ssion i for "daily g^itly r the SO, 0%of tality SSOCivarins of ive is ships ongly ables whip, town, small iution i. to ar moriices. atory its or ty of stion- naire during regular contact with a panel of partici pants, or changes in various aspects of lung func tion. Unlike mortality rates, these health data must often be specially obtained by the investigator. This has limited the size of morbidity studies. Many studies have used the diary or panel method, in which a group of participants regularly record or report symptoms. Substantial nonparticipation rates have been a problem in many of these studies, and nuke it difficult to interpret the symptom reports by those from whom observations are obtained. lilness data were obtained in many of the early severe pollution episodes OS, IS, SS). This informa tion did little more than confirm the mortality results, though there was some evidence that the increase in illness was not as large in percentage terms as the increase in deaths, and the effects were not so sudden. Martin (20) examined hospital admissions for the winters of 1958-59 and 1959-60 and found, after adjustment for day of the week and correction for 15-day moving average, significant correlations for both cardiovascular and respiratory conditions with BS and sulfur dioxide. The average deviations by pollution concentration, given in Tables 8 and 9, show more irregularity than the mortality data. 4s Table S. Average deviation of reipiratory and cardiac morbid ity from 15-day moving average, by smoke concentration (BS) (London, 1958-60).* Smoke concentration, vugW (BS) 500-599 600-699 700-799 800-1099 1100 + `Data of Martin (fO). Number of day* 9 6 9 8 7 Mean deviation 3.2 -0.7 2.4 4.9 12.9 Table 9. Average deviation of respiratory' and cardiac morbid ity from 15-day moving average, by S02 concentration (Lon don. 1958-60).* SOj concentration, Hg/m1 400-199 500-599 600-799 800-899 900+ `Data of Martin (SO). October 1981 Number of day* 9 6 9 6 5 Mean deviation 2.2 5.1 6.9 12.8 12.8 In a second important British study, Lawther et al. (Si, SS) collected daily self-reported health status from 194 persons with chronic respiratory disease during the winters of 1959-60 and 1964-65. Health status was reported relative to the previous day, and worsening of health status by self-evaluation was clearly associated with increases in air pollu tion. The authors reported that this effect could be seen on days when the 24-hr average level of SOg exceeded 500 p-g/m3 and smoke exceeded 250 p.g/m3 (BS). The strength of this response declined as the winter progressed and there was some evidence for an adaptation or desensitization effect or even loss of interest by participants. Lawther et al. commented that these responses could have resulted from brief exposure to maximum concen trations several times the 24-hr average. Studies ofBronchial Asthma. Some studies of pollution and asthma have reported negative or equivocal results (SS, ST). However, Cohen et al. (SS) found a weak association between air pollution and the frequency of asthma attacks in a study of patients living near a coal-fueled pow'er plant in West Virginia. Temperature was most strongly correlated with frequency of attacks among 20 patients having at least one attack during the study. In a multiple regression analysis, either S02 or TSP concentration was significantly correlated with attack rate after adjustment for temperature (p < 0.01). When days were classified as high and lowparticulate concentration (above or below 150 pg^m3 TSP), or as high and low S02 concentration (above or below 200 pg'm3), -symptom prevalence was significantly higher on the high pollution days. These values should not be interpreted as thresh old values, since the dividing line seems arbitrary and the table comparing the two groups of days does not seem to be temperature adjusted. The authors provide little information about changes in panel membership over time, and also give insufficient information about their data analysis methods. In particular, they combined data from children and adults participating in the study. The sensitivity of asthmatics to exogenous allergens, respiratory' in fections, dust, animals, smoking, cold weather and psychological factors also suggests caution in attributing changes in symptom prevalence to changes in air pollution concentration. Studies of Acute Respiratory Disease. Few studies relating acute exposure to moderate levels of air pollution to increased incidence of acute respiratory disease have been published. Although early studies by Dohan and Taylor (S9) and Dohan (i0) found an association between the level of suspended sulfates and work absences for respiratory disease among outdoor telephone workers, ipsen et 261 UCC 084327 i I al. Ul) conducted a near replication of their study these results do not provide sound evidence for and found that apparent associations between ab health effects of air pollution at the levels reported. I senteeism and air pollution were eliminated by adjustment for temperature, humidity and wind velocity. Health Effects of Chronic StudieaofPulmonaryFunction. VanderLende Exposure to Sulfur Oxides and et al. US) obtained results in a study of respiratory symptoms and lung function in the Netherlands Particulate Matter which could represent an acute effect of air pollu Studies of health effects of chronic exposure to 4 tion. Examination of a large general population air pollutants are typically cross-sectional, compar group in 1969 and again in 1972 failed to show the ing mortality or morbidity rates within or among a expected small decrease in levels of Forced Vital number of communities. The possibility that the Capacity (FVC) and Forced Expiratory Volume in estimates of air pollution effects will be biased by one second (FEVt), but rather small significant other community differences related to health is increases. The authors suggested that this could be particularly great in these studies. Concentrations % attributed to improvement in air quality, from of air pollutants are usually higher in urban than in reported maximum 24-hr smoke level of 160 p-g/m3 rural areas, and many authors have noted that (BS) and S02 concentration of 300 pg/m3 in 1969 to smoking patterns, family size, age distribution, 40 jig/tn3 (BS) and 100 pg/m3 (S02) in 1972. [This occupation, domestic crowding, nutrition, physical and some other continental European studies used activity and other characteristics of the population OECD calibration curves to express Black Smoke in can differ between rural and urban areas. Although pg/m3. Some reviewers have suggested that the some studies have sought to match communities on reported values should be increased, perhaps by a important characteristics or use multivariate ad factor of 2, to be pomparable with the British Black justment techniques to control for the effects of Smoke method U2).) these factors, their effectiveness is typically un Expected decreases in pulmonary function were known. This is especially true when complex re seen in a rural area measured at the same times. gression models are used for adjustment, for the The authors explored possible sources of bias in the adjustment is limited by the degree to which the study but were unable to explain their results on model correctly specifies the relation between these that basis. If real, these changes are most reasona factors and the outcome under study. bly interpreted as an acute, reversible response to elevated concentrations of air pollution. Stebbings et al. Ui) studied pulmonary function in 272 children during and after an air pollution Mortality Effects of Chronic Exposure to Sulfur Oxides and Particulate Matter alert in Pittsburgh in 1975. The 24-hr average S02 The study of Buck and Brown U6) was one of the concentration reached 350 pg'm3 and the 24-hr TSP first to show an association between annual average level reached 770 pg/m3. The mean FEV0,5 and concentration of S02 and Black Smoke and mortality FVC values, instead of increasing as hypothesized, rate across communities in Great Britain. Howev declined throughout the six-day period. Because er, mortality data were obtained in 1955-59 and the investigators did not have a pre-alert lung pollution was measured in 1962. Pollution levels function measurement, the values obtained during were falling during this period. Although it has the alert days could not be compared to "normal" been argued that mortality effects were seen in lung function values. Since the children were fol boroughs where Black Smoke and S02 levels exceeded lowed for only the week, the possibility of a later 200 tig/m3, it is likely that exposures prior to and increase in lung function values could not be excluded. during 1955-59 were somewhat higher than in 1962. In a later report, Stebbings et al. U5) identified a Wicken and Buck U~) also found differences in lung group of children whose lung functions showed cancer and bronchitis mortality rates between areas large increases after the alert. Since the proportion of high and low pollution after adjusting for age. of such children was significantly greater in the smoking habits and social class. However, this alert than in a control area, they concluded that study was also limited by unavailability of concur the alert had been associated with reduced lung rent air pollution measurements in most of the function. Since the analysis was selected in re communities studied. sponse to the data, was based on unvalidated More recently, several investigators have used methodology, and failed to explain the anomalous multivariate regression techniques to analyze mor finding of an excess of children in the alert area tality data obtained from vital statistics sources. whose lung function declined during the study, The following sections discuss these investigations 262 Environmental Health Perspectives UCC 084328 I I d ire to mpar* long* *t the ed by ilth is ations hanin i that ition, tysical ilation hough :ies on te adcts of *y unex reor the ch the ithese vure itter of the ^erage rtality owev>9 and levels it has een in ceeded +0 and il962. in lung : areas <t age. r, this oncurrf the e used e morjurces. ations. rtfves Analyses of Total Mortality Rates As noted above, there are many reasons why mortality rates vary among communities. There fore. study units should be selected to minimize variation due to factors other than air pollution. On the other hand, study units must be selected to conform with the available data. For mortality studies. Standard Metropolitan Statistical Areas (SMSA's) and cities meet this condition but present several difficulties. Investigators, recogniz ing that the study units differ with respect to factors other than air pollution, attempt to adjust for these differences by including socioeconomic and demographic variables in their analysis. Nev ertheless, it is likely that the effects of variables such as personal habits, occupational exposure, and medical care cannot be fully quantified and elimi nated in this way. If any of these factors covaries with air pollution levels, a spuriously large effect will be attributed to air pollution. The evidence in a multiple regression analysis relating mortality to pollution can be expressed through the coefficients of the pollutants and their standard errors. Comparison of the results of regression analyses from major studies relating mortality rates to pollution "levels across communi ties illustrates the problems that arise in inter preting these studies. The four regression equations summarized in Table 10 are taken from the work of Lave and Seskin (48). TSP represents the average of 26 biweekly measurements of24-hr TSP in each SMSA, while S04 is the lowest sulfate determination from these 26 observations. Regressions LSI and LS2 were both obtained from the analysis of 1960 mortality data for 117 SMSA's. The two regression equations differ only in that the second contains one additional adjustment variable, home heating fuel. Adding this variable reduces the coefficients of the air pollutants by a factor of three and they are not significant in LS2. Lave and Seskin argue that this occurs because home heating fuels are a major pollution source, home heating fuels and pollutants are highly correlated. This contrast illustrates one effect of collinearity on the regression coefficients. Regression LS3 results from fitting the model from regression LSI to 1961 data. Mortality and pollu tion values were about the same in the two years, and the coefficients are quite similar also. When the same model is fitted to the 1969 data (regression LS4), the estimated effects are larger even though mean TSP level declined from 118 ng/m3 to 96 M-g'm3 and the average SO* level declined from 4.72 ng/m3 to 3.46 M-g/m8. These comparisons show how sensi tive these multiple regression analyses are to variable selection, and also raise questions of con sistency. Table 10. Coefficient! of TSP end SO, in four regressions reported by Lave and Sekin.* Repression Source Coefficient (SE) TSP SO, Other variables11 LSI Data from 117 U.S. SMSA's in 1960 LS2 Data from 117 U.S. SMSA's in 1960 LS3 Data from 117 U.S. SMSA's in 1961 LS4 Data from 117 U.S. SMSA's in 1969 0.452 (0.169) 0.171 (0.158) 0.516 (0.178) 0.818 (0.241) 6.31 (2.33) 1.84 (2.16) 4.56 (2.49) 7.74 (3.67) D. A. R. I. P D. A. R. I. P, HHF D. A, R, I. P D. A. R. I. P Data of Lave and Seskin US). ^Symbols used in this column are defined in Table 12. Table 11. Coefficient* of TSP and SO, in regressions analysis by Lipfert and Crocker et al. Regression Source Coefficient TSP SO, Other variables* LI Data from 60 U.S. SMSA's in 1969b L2 Data from 60 U.S. cities in 1969b L3 Data from 136 U.S. cities in 1969b L4 Data from 181 U.S. cities in 1969b Cl Data from 60 U.S. cities in I9601 0.73 5.4 D. A. R. 1 0.78 8.2 D. A, R. I 1.00 -2.0 A. R. 1. H. B 0.72 -4.3 A. R. I, H. B. C, log D 0.11 -0.31d MD. Ml, E. CH. C. CT. R. MA, DF 'Symbols used in this column are defined in Table 12. bData of Lipfen US, 50). 'Data of Crocker et al. (5J). ^Coefficient of SO*. October 1981 263 UCC 084329 i I Results of four regression analyses reported by average value of that pollutant in the data set, Lipfert U9, 50) are shown in Table 11. The first adding these quantities for all pollutants, and ( (LI) is based on analysis of 1969 mortality data dividing by the average mortality over study units. from 60 U.S. SMSA's, using a model much like So long as the set of pollution variables chosen regression LS4 in Table 10. Very similar coefficients contains variables capturing the total association are obtained. The first two models in Table 11 differ between all air pollutants and mortality, the elastic only in that the first uses mortality data from 60 ity will be relatively insensitive to the choice of a SMSA's while the second uses mortality data from subset of these highly collinear pollutant variables. 60 U.S. cities. The coefficient of S04 is larger in the Thus, the elasticities can be viewed, at least I second regression using smaller geographic areas. approximately, as measuring the total mortality Model L3 differs from L2 in that more cities are effect of all pollutants included. included and age of housing and birth rate are Table 13 gives elasticities for the nine regression added as independent variables, while cigarette analyses summarized in Tables 10 and 11. Regres consumption is added in L4. Though the coefficient sions LSI, LS3, and LS4 were the simplest models of TSP changes very little, the coefficient of S04 is used by Lave and Seskin and had the largest i negative in these regressions. elasticity. In regressions using more variables, The final regression in Table 11 is taken from an such as home heating fuel in regression LS2, analysis of 60 U.S. cities in 1970 by Crocker et al. smaller elasticities were obtained. (When occupa (57). In addition to variables used by other investi tion was added to the model for regression LSI, gators, this model includes variables for climate, elasticity declined to 0.05). Regressions LI and L2 education, availability of medical care and nutritional included population density, percentage above 65, habits. Although Crocker uses SO2 and not S04 as a percentage nonwhite and percentage with income 4 pollution variable, neither pollutant contributes below $3,000 as independent variables. When birth significantly to the regression. Crocker et al. report rate and age of homes were added (L3) or cigarette a correlation between SO2 and S04 of 0.74. smoking (L4), elasticity declined to 0.06 and 0.04, The association between air pollutant concentra respectively. The effect of cigarette smoking should tion and mortality rates in different analyses can be especially be noted. Finally, in the analysis by summarized by the elasticity. An elasticity is a Crocker et al. (57) using several other added dimensionless number that represents the expected independent variables (Cl), the elasticity was nearly percent change in the dependent variable, mortali zero. These variables included measures of medical ty, associated with a 100* increase from the mean care, diet, climate and cigarette consumption and value in each of the pollutant variables in the could easily be defended as critically important in regression. Elasticity is computed by multiplying any analysis controlling for other factors expected each air pollutant regression coefficient by the to influence mortality. Though it has sometimes been argued that smok Table 12. Definitioni of other independent variable! used in multiple regressions in Tables 10 and 11. ing is not associated with air pollution concentra tion, Crocker et al. report a correlation of 0.23 between cigarette consumption and sulfur dioxide Variable Definition in the 60 cities in their study. Certainly the two D Population density in person/mile: A Percentage of population 65 or older R Percentage of population nonwhite variables are not causally related, but both may reflect other characteristics of the population. Schwing and McDonald (52) report on a study of I Percentage of population with income P HHF below S3000'year Log arithm of SMSA population Percentage of homes using esch of several Table 13. Elasticities for air pollutants in nine regression analyses of mortality. home heating fiiels H Percentages of housing units built before 1960 Regression Elasticity B Births'lOOO population/year MD No. of physicians per capita MI Median income E Percentage of persons 25 or older with high school diploma CH Percentage of persons living in homes with more than 1.5 persons per room C No. of cigarette packs purchased per capita CT No. of days with temperature below 0C MA Median age LSI LS2 LS3 LS4 LI L2 L3 L4 Cl 0.09 0.03 0.09 0.12 0.10 0.09 006 0.0-; 0.O-'4 264 Environmental Health Perspective* UCC 084330 I its. f*n Son ticjf a les. -*ast i't.v I. 'ion resdels eest les, -S2, ipa* -SI, 1 L2 ' 65. ome lirth Jp'.le 3.04. lould s by deled nt in iCted nokrrtra0.23 xide two may dy of Mion 46 SMSA's (1959-61) in which 23 explanatory vari ables are used, including climate, socioeconomic, occupational and smoking variables and eight air pollutants. This study differs from those summa rized in Tables 10 and 11 in that the investigators included all 23 variables in their models. To counter revere collinearity, the authors used two methods of analysis, ridge regression and constrained least squares, rather than ordinary least squares. (The previously reported studies all used ordinary least squares.) Ridge regression is a numerical method for stabi lizing estimates of regression coefficients from a data set that has collinear explanatory variables. While the method does achieve stability, it does so by selecting an arbitrary constant that has the effect of shrinking each estimated coefficient to ward zero. Though ridge regression leads to smaller I standard errors for the estimated coefficients, these coefficients are no longer interpretable as partial j regression coefficients, that is, measures*of the effects of changes in a single variable while the other variables are held fixed. As emphasized throughout this presentation, collinear data sets are fundamentally insufficient to allow assignment of mortality effects to individual members of a group <>f collinear explanatory* Variables. Schv ing and McDonald also use constrained least squares, constraining the air pollution coefficients to positive values. This may be unreasonable when eight air pollutants are studied simultaneously. Thur ston e; al. (53) report that respirable sulfate as a fraction of total sulfate is not constant over differ ent lev els of air quality. They note that in "dirty" cities the fraction is 0.6 to 0.7 while in "clean" cities the fraction is 0.8 to 0.9. Thus, if the respirable sulfate affects mortality, an indicator of overall air quality such as TSP could take a negative sign, when both TSP and respirable sulfates are included in the model, to account for the difference in the respi) able sulfate fraction between cities, Schwing and McDonald report an elasticity of 0.22 from ridge regression and an elasticity of 0.045 from constrained least squares. These values are still an order of magnitude larger than that re ported by Crocker et al. (0.004). This discussion has been provided to illustrate the limitations of multiple regression analyses of vital statistics data, using explanatory variables defined by data availability rather than intrinsic interest, and complicated by severe collinearity of pollutant and other explanatory variables. The model can only be approximately correct, the surrogate explanatory variables can never lead to an ade quate adjusted analysis, and it is impossible to separate associations of mortality rate with pollu- October 1981 tant and confounding variables. This group of stud ies, in our opinion, provides no reliable evidence for assessing the health effects of sulfur dioxide and particulate matter. Morbidity Effects of Chronic Exposure to Sulfur Oxides and Particulate Matter This section focuses on those studies that provide the air pollution and health-status data necessary to assess the morbidity effects of chronic exposure to sulfur oxides or particulates. These studies most commonly represent the cumulative exposure to air pollutants as an arithmetic average concentration of sulfur compounds and participates during an interval including the study period. Since chronic exposure may refer to the lifetime of an individual, this measure of exposure may be misleading when pollution concentrations have changed substantially during the years preceding the study. Morbidity outcomes are generally limited to respiratory symp toms and measured lung function. Respiratory symp toms are roost commonly assessed with self- or interviewer-administered questionnaires. The stan dard questionnaire developed by the British Medi cal Research Council (54) has been used typically, with modifications or additions. [A standard ques tionnaire has recently been developed under the joint sponsorship of the American Thoracic Society and the Division of Lung Diseases, National Heart, Lung and Blood Institute, and is recommended for all U.S. population studies (55).] Lung function is generally measured by spirometry from which both forced expiratory volume and flow rates can be determined.. Relationships between air pollution and nonrespiratory or systemic morbidity are usu ally not explored. Most of the studies reviewed are cross-sectional investigations of morbidity prevalence. Many of the difficulties of inferring a cause-effect relationship between air pollution and health outcome in such studies have been discussed above. Typically, a few cities or areas with different air pollution concen trations are compared. The study populations are either matched on, or analyses standardized for, differences in variables such as age distribution, race, socioeconomic characteristics, occupational cate gories, and smoking habits. Often only two cities or areas with contrasting air quality are compared. Rarely are more than half a dozen areas compared. The effect of limited observations at differing air pollution levels is partially mitigated by the ability to gather extensive information on outcome vari ables such as ventilatory function and symptom 265 UCC 084331 prevalence and on potentially confounding factors \Lg/m3 (BS) and 123 M-g/ni3 (S02) in the clean area such as cigarette smoking and occupation. Never and averaged about 140 p.g/m3 (BS) and 200 jig/m3 theless, when only a few observations have been (S02) in the dirty areas. I made at different air pollution levels, it is difficult Douglas and Waller (55) reported on a study of a to construct generalizable quantitative dose-response sample of children born during one week in March relationships. 1946. Air pollution was assessed by creating an The major studies suggesting morbidity effects index based on coal consumption. The authors cre of exposure to elevated concentrations of particu ated four pollution categories, and found that the late matter and/or sulfur oxides have been reported prevalence of lower respiratory disease, but not from three countries; Great Britain, Poland and the upper respiratory disease increased with increasing I Unites States. pollution wherLthe children were studied at ages 6, BritUh Studies. Lunn et al. (56, 57) studied 7,11 and 15. schoolchildren living in four areas of Sheffield, En Comparison of the index to measured BS and S02 gland with different air pollution concentrations. concentrations in 1962 established a gradient of These concentrations are shown in Table 14 for the mean annual pollutant concentrations across the two winters studied. Questionnaires were answered four pollution categories. The lowest pollutant con 1 by parents and the investigators found substan centrations in 1962 among the categories with in tially higher prevalence of symptoms of respiratory creased morbidity were 130 M.g/nr(BS) and 130 disease in the three more polluted areas than in the fig/m3 (S02). Colley et al. (59) followed this cohort less polluted area (Table 15). These children were at age 20, and Kiernan et al. (60) followed it again at followed up in 1967-69 when they were nine years age 25. Neither investigation found an association old (57). As a result of the institution of smoke of respiratory disease symptom with previous air control, smoke levels were reduced to about half pollution exposure, although at age 20 the preva their former levels. When children from the three lence of respiratory symptoms was slightly higher dirtier areas wqi pooled and compared to children among those who had lived in high pollution areas from the clean area in the second study, there were (11.5%) than among those from low pollution areas no differences in symptom prevalence rates. Pollu (10.2%), and a similar relationship was found at age tion concentrations in the later period were 48 25. Respiratory symptom prevalence was associ- Tsble 14. Air pollution concentrations in communities studied by Lunn et al.* Greenhill Winter 1964 196566 Concentration (24-hr average), ug'm3 ________ Longley Park Winter Winter - 1964 1965-66 1964 1965-66 Attercliffe Winter 1964 1965-66 BS 97 (70-78) 230 177 262 220 301 249 SO, 123 (109-134) 181 194 219 241 275 301 *Data of Lunn et al. (55). Table IS. Symptoms by area in the study of Lunn et al.1 Symptom Nasal discharge 3 colds Eardrum finding Frequent cough Cold going to chest Lower respiratory infection Greenhill Nb P* SE< 408 6.4 l.S! 413 34.4 2.3 381 9.4 1.5 411 22.9 2.)1 412 34.7 2.4 413 23.0 4.3 Longley NP 192 5.2 194 43.8 178 10.7 194 36.1 194 42.8 192 36.0 SE 1.6 3.4 2.3 3.4 3.6 5.8 Park NP 130 15.4 130 48.5 125 14.4 130 34.6 130 40.0 127 35.0 SE 3.2 4.4 3.1 4.2 4.3 7.1 Attercliffe N P SE 82 14.6 3.9 82 46.3 5.5 75 17.2 4.4 82 50.0 5.5 82 63.7 6.5 82 30.0 9.2 Data of Lunn et al. (50. hThe number of responses obtained. The percentage of positive responses. *The estimated standard error of the observed percentage. 266 Environmental Health Perspectives Ucc 084332 dean area stuay of a a in March eating an ithors ere* i that the u but not increasing at ages 6, I S and SO* adient of cross the Jtant con 's with in* and 130 s cohort :t again at ssodation `vious air te prevaly higher gin areas ion areas nd at age s associ- Vinter 965-66 249 901 EE 3.9 5.5 4.4 5.5 5.5 8.2 ectives ned with cigarette smoking at these ages. Because oolhition concentrations in 1962 were presumably inuch lower than those in earlier years, the concen trations cited probably understate the exposure of study participants. We note that exposure during childhood to air pollution concentrations in excess of 130 gg/m3 (BS) and 130 M-g/m3 (S02) resulted in no significant increase in respiratory illness by adult hood compared to those exposed to lower air pollu tion concentrations. Lambert and Reid (61) mailed self-administered questionnaires to 18,379 men and women in Britain to assess the relationship of smoking and air pollu tion to bronchitis symptoms. The reply rate was 749 from the 35-69 year-old age group studied, from the 9,975 replies analyzed, the authors con clude that the prevalence of respiratory symptoms increased with pollution levels independently of cigarette smoking. Air pollution was found to have a greater effect on the symptoms of smokers than nonsmokers, in terms of the absolute difference in svmpi om prevalence rates. The exposure levels in this study are approxi mate. since only 30# of the population surveyed mas covered by actual air pollution measurements. The pollutants measured, BS and S02, were taken from 1965 data of the British National Air Pollution Survey. The balance of the population was assigned to exposure categories based on the DouglasWalk-r (58) index which was developed from 1952 domestic coal consumption. A comparison of symp tom-prevalence ratios from measurements of BS, SO.), and index values shows similar ratios and fimi'ar gradients for symptoms with increasing pol lution. The lack of complete air pollution data adds unct rtainty to the exposure estimates, but in those ares? where BS and S02 measurements were avail able, increased prevalence of symptoms was found in association with BS and S02 levels between 100 and 150 ngtat3, as an annual average. Polish Studies. A study of two areas of con trasting air quality in Cracow, Poland, was con ducted by Sauicki. The study began with a cross sectional survey in 1968 and continued with a pro spective study until 1973 (62). Annual average Darticulate values in 1968 w'ere 90 and 170 ug/nr. In 1968, chronic bronchitis prevalence was greater in the more polluted area for men, but not for women. The difference was statistically significant for men .who were nonsmokers or present smokers. These data are given in Table 16. Asthmatic disease prev alence was also greater among smokers living in the more polluted area and FEVj as a percentage of FVC was lower for most age-sex-smoking-history groups. Between 1968 and 1973, the annual mean concen tration of S02 and BS declined slightly for Cracow as a whole but increased slightly at the sites close to the homes of most study participants. In 1973, respiratory disease was again more prevalent among those living in the areas of high pollution for many, but not all of the age, race, and sex groups studied. Mean FEV, level was not significantly different in the two areas. The prevalence of obstructive dis ease was higher in the more polluted area only for present smokers. The authors concluded that smok ing and, to a lesser extent, occupational exposure and age had the greatest effect on respiratory illness prevalence, while air pollution at the place of residence was listed as one of several factors having a smaller effect on respiratory illness. Rudnik et al. (63) reported extensively on the early phase (1970-1976) of a long-term study of the factors which influence development of childhood Tabic 16. Prevalence of chronic bronchitii by aex and Knotting ctatui in 1968.* Smoking statu* Total Kor.tmokera Ex-?mokera Present amokera Ptr.jd of amoking 1-10 year* 11-20 year* > 21 year* Low pollution ana Men Women Nb P* SE* N P S High pollution Area Men Women N P SE N P 323 11* 1.7 362 4 1.0 262 19* 2.4 396 5 56 4 2.6 266 2 0.9 58 7 3.4 264 3 46 4 2.9 18 11 7.4 40 5 3.4 34 6 221 14* 2.3 78 10 3.4 164 27* 3.5 98 10 56 5 2.9 39 9* 3.0 76 28 5.2 41 7 4.0 21 14 7.6 16 13 8.4 42 7 3.9 38 29* 7.4 84 36 5.2 42 5 18 6 38 18 'Data of Sawicki (S3). 'Number of persona studied. 'Prevalence of chronic bronchitic. 'Standard error of the observed rate. 'Rates which are significantly different at the 0.05 level. October 1981 SE 1.1 1.0 4.1 3.0 3.4 5.6 6.2 267 UCC 084333 4 0' 4 i are to mpar^onga at the ed by ilth is ations han in 1 that jition, tysicaJ ilation hough ;ie? on te ad ds of <y unex re ar the ch the i these Analyses of Total Mortality Rates As noted above, there are many reasons why mortality rates vary among communities. There fore, study units should be selected to minimize variation due to factors other than air pollution. On the other hand, study units must be selected to conform with the available data. For mortality studies. Standard Metropolitan Statistical Areas iSMSA's) and cities meet this condition but present several difficulties. Investigators, recogniz ing that the study units differ with respect to factors other than air pollution, attempt to adjust : for these differences by including socioeconomic and demographic variables in their analysis. Nev ertheless, it is likely that the effects of variables such as personal habits, occupational exposure, and medical care cannot be fully quantified and elimi nated in this way. If any of these factors covaries with air pollution levels, a spuriously large effect rill be attributed to air pollution. The evidence in a multiple regression analysis relating mortality to pollution can be expressed through the coefficients of the pollutants and their standard errors. Comparison of the results of regression analyses from major studies relating mortality rates to pollution levels across communi ties illustrates the problems that arise in interi preting these studies. The four regression equations summarized in Table 10 are taken from the work of Lave and Seskin H8). TSP represents the average of 26 biweekly measurements of 24-hr TSP in each SMSA, while S04 is the lowest sulfate determination from these 26 observations. Regressions LSI and LS2 were both obtained from the analysis of 1960 mortality data for 117 SMSA's. The two regression equations differ only in that the second contains one additional adjustment variable, home heating fuel. Adding this variable reduces the coefficients of the air pollutants by a factor of three and they are not significant in LS2. Lave and Seskin argue that this occurs because home heating fuels are a major pollution source, home heating fuels and pollutants are highly correlated. This contrast illustrates one effect of collinearity on the regression coefficients. Regression LS3 results from fitting the model from regression LSI to 1961 data. Mortality and pollu tion values were about the same in the two years, and the coefficients are quite similar also. When the same model is fitted to the 1969 data (regression LS4), the estimated effects are larger even though mean TSP level declined from 118 p.g/m3 to 96 jig/m3 and the average S04 level declined from 4.72 ng/m3 to 3.46 p.g/m3. These comparisons show how sensi tive these multiple regression analyses are to variable selection, and also raise questions of con sistency. Ture itter of the /erage rtalitv owev59 and levels it has een in ceeded to and 11962. m lung i areas >r age. r, this oncuraf the e used e morjurces. ations. dlvts Tabic 10. CocfHcicnti of TSP end SO, in four regressions reported by Lave and Seskin." Regression Source Coefficient (SE) TSP SO, Other variables" LSI Data from 117 U.S. SMSA's in 1960 LS2 Data from 117 U.S. SMSA's in 1960 LS3 Data from 117 U.S. SMSA't in 1961 LS4 Data from 117 U.S. SMSA's in 1969 0.452 (0.169) 0.171 (0.158) 0.516 (0.178) 0.818 (0.241) 6.31 (2.33) 1.84 (2.16) 4.56 (2.49) 7.74 (3.67) D. A. R. I, P D. A. R, I, P. HHF D. A. R. I. P D. A. R, I, P Data of Lave and Seskin US). "Symbols used in this column are defined in Table 12. Table 11. Coefficients of TSP and SO, in regressions analysis by Lipfert and Crocker et al. Regression Source Coefficient TSP SO, Other variables* LI Data from 60 U.S. SMSA's in 1969" L2 Data from 60 U.S. cities in 1969" L3 Data from 136 U.S. cities in 1969" U Data from 161 U.S. cities in 1969" Cl Data from 60 U.S. cities in 1960" 0.73 5.4 D, A, R. I 0.78 8.2 D, A. R. 1 1.00 -2.0 A, R, I. H, B 0.72 -4.3 A. R. I, H. B, C. log D 0.11 -0.31d MD. MI, E. CH, C, CT, R. MA. DF Symbols used in this column are defined in Table 12. "Dsta of Lipfert 09, SO). Data of Crocker et el. (51). dCoefficient of SO*. October 1981 263 UCC 084334 i a Results of four regression analyses reported by average value of that pollutant in the data set, Lipfert (49, 50) are shown in Table 11. The first adding these quantities for all pollutants, and a (LI) is based on analysis of 1969 mortality data dividing by the average mortality over study units. from 60 U.S. SMSA's, using a model much like So long as the set of pollution variables chosen regression LS4 in Table 10. Very similar coefficients contains variables capturing the total assnmation are obtained. The first two models in Table 11 differ between all air pollutants and mortality, the elastic only in that the first uses mortality data from 60 ity will be relatively insensitive to the choice of a SMSA's while the second uses mortality data from subset of these highly collinear pollutant variables. 60 U.S. cities. The coefficient of SO* is larger in the Thus, the elasticities can be viewed, at least second regression using smaller geographic areas. approximately, as measuring the total mortality Model L3 differs from L2 in that more cities are effect of all pollutants included. included and age of housing and birth rate are Table 13 gives elasticities for the nine regression added as independent variables, while cigarette analyses summarized in Tables 10 and 11. Regres consumption is added in L4. Though the coefficient sions LSI, LS3, and LS4 were the simplest models of TSP changes very little, the coefficient of SO* is used by Lave and Seskin and had the largest negative in these regressions. elasticity. In regressions using more variables, The final regression in Table 11 is taken from an such as home heating fuel in regression LS2, analysis of 60 U.S. cities in 1970 by Crocker et al. smaller elasticities w'ere obtained. (When occupa (51). In addition to variables used by other investi tion was added to the model for regression LSI, gators, this model includes variables for climate, elasticity declined to 0.05). Regressions Ll and L2 education, availability of medical care and nutritional included population density, percentage above 65, habits. Although Crocker uses S02 and not SO* as a percentage nonwhite and percentage with income pollution variable, neither pollutant contributes below $3,000 as independent variables. When birth significantly to the regression. Crocker et al. report rate and age of homes were added (L3) or cigarette a correlation between S02 and SO* of 0.74. smoking (L4), elasticity declined to 0.06 and 0.04, The association between air pollutant concentra respectively. The effect of cigarette smoking should tion and mortality rates in different analyses can be especially be noted. Finally, in the analysis by summarized by the elasticity. An elasticity is a Crocker et al. (51) using several other added dimensionless number that represents the expected independent variables (Cl), the elasticity was nearly percent change in the dependent variable, mortali zero. These variables included measures of medical ty, associated with a 100% increase from the mean care, diet, climate and cigarette consumption and value in each of the pollutant variables in the could easily be defended as critically important in regression. Elasticity is computed by multiplying any analysis controlling for other factors expected each air pollutant regression coefficient by the to influence mortality. Though it has sometimes been argued that smok Table 12. Definitions of other independent variable* uaed in multiple recreation* in Table* 10 and 11. ing is not associated with air pollution concentra tion, Crocker et al. report a correlation of 0.23 between cigarette consumption and sulfur dioxide Variable Definition in the 60 cities in their study. Certainly the two D Population density in person/mile2 A Percentage of population 65 or older R Percentage of population nonwhite variables are not causally related, but both may reflect other characteristics of the population. Schwing and McDonald (52) report on a study of I Percentage of population with income below S3000/year P Log arithm of SMSA population Tabic 13. Elasticity* for air pollutant* in nine regression HHF Percentage of homes using each of several analyse* of mortality. home heating Aiels H Percentage* of housing units built before 1960 Regression Elasticity B Births/1000 population/year MD No. of physicians per capita MI Median income E Percentage of persons 25 or older with high school diploma CH Percentage of persons living in homes with LSI LS2 LS3 LS4 Ll 0.09 0.03 0.09 0.12 0.10 more than 1.5 persons per room L2 0.09 C No. of cigarette packs purchased per capita CT No. of days with temperature below 0*C MA Median age L3 L4 Cl 0.06 0.01 0.001 264 Environmental Health Perspective* UCC 084335 its. en 'tan tic- jf a les. .ast -lity -ion m- (iek ?est >les, S2, *pa-Si. i L2 65. ome urth ?tte 3.04. iould s by dded early nt in ected nokntra0.23 xide two may dy of *ion es 46 SMSA's (1959-61) in which 23 explanatory vari ables are used, including climate, socioeconomic, occupational and smoking variables and eight air pollutants. This study differs from those summa rized in Tables 10 and 11 in that the investigators included all 23 variables in their models. To counter severe collinearity, the authors used two methods of analysis, ridge regression and constrained least squares, rather than ordinary least squares. (The previously reported studies all used ordinary least squares.) Ridge regression is a numerical method for stabi lizing estimates of regression coefficients from a data set that has collinear explanatory variables. While the method does achieve stability, it does so by selecting an arbitrary constant that has the effect of shrinking each estimated coefficient to ward zero. Though ridge regression leads to smaller I standard errors for the estimated coefficients, these coefficients are no longer interpretable as partial ; regression coefficients, that is, measures of the I effects of changes in a single variable while the other \ariables are held fixed. As emphasized throughout this presentation, collinear data sets are fundamentally insufficient to allow assignment of mortality effects to individual members of a group of collinear explanatory* Variables. Schving and McDonald also use constrained least squares. constraining the air pollution coefficients to positive values. This may be unreasonable when eight air pollutants are studied simultaneously. Thur ston et al. (53) report that respirable sulfate as a fraction of total sulfate is not constant over differ ent let els of air quality. They note that in "dirty" cities the fraction is 0.6 to 0.7 while in "clean" cities the fraction is 0.8 to 0.9. Thus, if the respirable sulfate affects mortality, an indicator of overall air quality such as TSP could take a negative sign, when both TSP and respirable sulfates are included in the model, to account for the difference in the respirable sulfate fraction between cities. Schving and McDonald report an elasticity of 0.22 from ridge regression and an elasticity of 0.045 from constrained least squares. These values are still an order of magnitude larger than that re ported by Crocker et al. (0.004). This discussion has been provided to illustrate the limitations of multiple regression analyses of vital statistics data, using explanatory variables defined by data availability rather than intrinsic interest, and complicated by severe collinearity of pollir ant and other explanatory' variables. The model can i inly be approximately correct, the surrogate explanatory variables can never lead to an ade quate adjusted analysis, and it is impossible to separate associations of mortality rate with pollu- October 1981 tant and confounding variables. This group of stud ies, in our opinion, provides no reliable evidence for assessing the health effects of sulfur dioxide and particulate matter. Morbidity Effects of Chronic Exposure to Sulfur Oxides and Particulate Matter This section focuses on those studies that provide the air pollution and health-status data necessary to assess the morbidity effects of chronic exposure to sulfur oxides or particulates. These studies most commonly represent the cumulative exposure to air pollutants as an arithmetic average concentration of sulfur compounds and particulates during an interval including the study period. Since chronic exposure may refer to the lifetime of an individual, this measure of exposure may be misleading when pollution concentrations have changed substantially during the years preceding the study. Morbidity outcomes are generally limited to respiratory symp toms and measured lung function. Respiratory symp toms are most commonly assessed with Belf- or interviewer-administered questionnaires. The stan dard questionnaire developed by the British Medi cal Research Council (54) has been used typically, with modifications or additions. [A standard ques tionnaire has recently been developed under the joint sponsorship of the American Thoracic Society and the Division of Lung Diseases, National Heart, Lung and Blood Institute, and is recommended for all U.S. population studies (55).] Lung function is generally measured by spirometry from which both forced expiratory volume and flow rates can be determined. Relationships between air pollution and nonrespiratory or systemic morbidity are usu ally not explored. Most of the studies reviewed are cross-sectional investigations of morbidity prevalence. Many of the difficulties of inferring a cause-effect relationship between air pollution and health outcome in such studies have been discussed above. Typically, a few cities or areas with different air pollution concen trations are compared. The study populations are either matched on, or analyses standardized for, differences in variables such as age distribution, race, socioeconomic characteristics, occupational cate gories, and smoking habits. Often only two cities or areas with contrasting air quality are compared. Rarely are more than half a dozen areas compared. The effect of limited observations at differing air pollution levels is partially mitigated by the ability to gather extensive information on outcome vari ables such as ventilatory function and symptom 265 UCC 084336 prevalence and on potentially confounding factors such as cigarette smoking and occupation. Never theless, when only a few observations have been made at different air pollution levels, it is difficult to construct generalizable quantitative dose-response relationships. The major studies suggesting morbidity effects of exposure to elevated concentrations of particu late matter and/or sulfur oxides have been reported from three countries; Great Britain, Poland and the Unites States. British Studies. Lunn et al. (56, 57) studied schoolchildren living in four areas of Sheffield, En gland with different air pollution concentrations. These concentrations are shown in Table 14 for the two winters studied. Questionnaires were answered by parents and the investigators found substan tially higher prevalence of symptoms of respiratory disease in the three more polluted areas than in the less polluted area (Table 15). These children were followed up in 1967-69 when they were nine years old (57). As a result of the institution of smoke control, smoke levels were reduced to about half their former levels. When children from the three dirtier areas wqi$ pooled and compared to children from the clean area in the second study, there were no differences in symptom prevalence rates. Pollu tion concentrations in the later period were 48 Ug/m3 (BS) and 123 jig/m3 (S02) in the clean area and averaged about 140 jxg/m3 (BS) and 200 ng/m3 (S02) in the dirty areas. Douglas and Waller (58) reported on a study of a sample of children bom during one week in March 1946. Air pollution was assessed by creating an index based on coal consumption. The authors cre ated four pollution categories, and found that the prevalence of lower respiratory disease, but not upper respiratory disease increased with increasing pollution when the children were studied at ages 6, 7, 11 and 15. Comparison of the index to measured BS and S02 concentrations in 1962 established a gradient of mean annual pollutant concentrations across the four pollution categories. The lowest pollutant con centrations in 1962 among the categories with in creased morbidity were 130 M.g/nr(BS) and 130 ug/m3 (S02). Colley et al. (59) followed this cohort at age 20, and Kieraan et al. (60) followed it again at age 25. Neither investigation found an association of respiratory disease symptom with previous air pollution exposure, although at age 20 the preva lence of respiratory symptoms was slightly higher among those who had lived in high pollution areas (11.5%) than among those from low pollution areas (10.2%), and a similar relationship was found at age 25. Respiratory symptom prevalence was assod- Table 14. Air pollution concentration* in communities ftudied by Lunn et al.* Greenhill Winter 1964 1965-66 Concentration (24-hr average), (igTn* Longley Park Winter Winter 1964 1965-66 1964 1965-66 Attercliffe Winter 1964 1965-66 BS 97 (70-78) 230 177 262 220 301 249 S02 123 (109-134) 181 194 219 241 275 301 'Data of Lunn et al. (56). Table IS. Symptom* by area in the study of Lunn et al.* Symptom Greenhill Nb F* SE4 Longley N P SE Park Attercliffe N P SE N P SE Nasal discharge 408 6.4 1.2 192 5.2 1.6 130 15.4 3.2 82 14.6 3.9 8 colds 413 34.4 2.3 194 43.8 3.4 130 48.5 4.4 82 46.3 5.5 Eardrum finding 381 9.4 1.5 178 10.7 2.3 125 14.4 3.1 75 17.2 4.4 Frequent cough 411 22.9 2.1 194 36.1 3.4 130 34.6 4.2 82 50.0 5.5 Cold going to chest 412 34.7 2.4 194 42.8 3.6 130 40.0 4.3 82 53.7 5.5 Lower respiratory 413 23.0 4.3 192 36.0 5.8 127 35.0 7.1 82 30.0 9.2 infection 'Data of Lunn et al. {56). 'The number of response* obtained. The percentage of positive responses. *The estimated standard error of the observed percentage. 266 Environmental Health Perspectives ucc 084337 dean area ^00 ug m'1 ^^uav of a in March ^eating an ithors cre4 that the but not increasing at ages 6, S and SO* adient of cross the jtant tons with in' and 130 4is cohort t again at ssociation vious air le prevaly higher on areas ton areas nd at age s assoti- Vinter 965-66 249 901 SE 3.9 5.5 4.4 5.5 5.5 B2 ectives ated with cigarette smoking at these ages. Because oollution concentrations in 1962 were presumably much lower than those in earlier years, the concen trations cited probably understate the exposure of study participants. We note that exposure during childhood to air pollution concentrations in excess of 130 gg/m3 (BS) and 130 gg/m3 (S02) resulted in no significant increase in respiratory illness by adult hood compared to those exposed to lower air pollu tion concentrations. Lambert and Reid (61) mailed self-administered questionnaires to 18,379 men and women in Britain to assess the relationship of smoking and air pollu tion to bronchitis symptoms. The reply rate was 74^ from the 35-69 year-old age group studied. From the 9,975 replies analyzed, the authors con clude that the prevalence of respiratory symptoms increased with pollution levels independently of cigarette smoking. Air pollution was found to have ' a greater effect on the symptoms of smokers than nonsmokers, in terms of the absolute difference in symptom prevalence rates. The exposure levels in this study are approxi mate. since only 307c of the population surveyed was covered by actual air pollution measurements. The pollutants measured, BS and S02, were taken from 1965 data of the British National Air Pollution Survey. The balance of the population was assigned to exposure categories based on the DouglasWaller (58) index which was developed from 1952 domestic coal consumption. A comparison of symp tom-prevalence ratios from measurements of BS, S02. and index values shows similar ratios and simi'ar gradients for symptoms with increasing pol lution. The lack of complete air pollution data adds -unct rtainty to the exposure estimates, but in those areas where BS and S02 measurements were avail able, increased prevalence of symptoms was found in association with BS and S02 levels between 100 and 150 gg/m3, as an annual average. Polish Studies. A study of two areas of con trasting air quality in Cracow, Poland, was con ducted by Sawicki. The study began with a cross sectional survey in 1968 and continued with a pro spective study until 1973 (62). Annual average par ticulate values in 1968 were 90 and 170 gg/m . In 1968, chronic bronchitis prevalence was greater in the more polluted area for men, but not for women. The difference was statistically significant for men who were nonsmokers or present smokers. These data are given in Table 16. Asthmatic disease prev alence was also greater among smokers living in the more polluted area and FEV, as a percentage of FVC was lower for most age-sex-smoking-history groups. Between 1968 and 1973, the annual mean concen tration of S02 and BS declined slightly for Cracow as a whole but increased slightly at the sites dose to the homes of most study participants. In 1973, respiratory disease was again more prevalent among those living in the areas of high pollution for many, but not all of the age, race, and sex groups studied. Mean FEVj level was not significantly different in the two areas. The prevalence of obstructive dis ease was higher in the more polluted area only for present smokers. The authors concluded that smok ing and, to a lesser extent, occupational exposure and age had the greatest effect on respiratory illness prevalence, while air pollution at the place of residence was listed as one of several factors having a smaller effect on respiratory- illness. Rudnik et al. (63) reported extensively on the early phase (1970-1976) of a long-term study of the factors which influence development of childhood Table 16. Prevalence of chronic bronchitii by cex and smoking itatui in 1968.* Smoking status Low pollution area Men Women Nb Pc SEd N P SE High pollution area Men Women N P SE N P Total Non-moken 323 11* 1.7 362 56 4 2.6 AMge) 4 1.0 262 19* 2.4 396 2 0.9 58 7 3.4 264 5 3 Ex-.-mokers Pre-ent smokers 46 4 2.9 221 14* 2.3 18 11 7.4 40 5 3.4 78 10 3.4 164 27* 3.5 34 6 98 10 Period of smoking M0 yean 11 -20 yean > 21 yean G6 5 2.9 41 7 4.0 89 9* 3.0 21 14 7.6 76 28 5.2 16 13 8.4 42 7 3.9 38 29* 7.4 84 36 5.2 42 5 18 6 38 18 'Data of Sawicki (82). ` N'umber of persons studied. 'Prevalence of chronic bronchitis. 'Standard error of the observed rate. 'Rates which are significantly different at the 0.05 level. October 1981 SE 1.1 1.0 4.1 3.0 3.4 5.6 6.2 267 ucc 084338 chronic nonspecific respiratory disease (CNSRD). The authors discussed an early pilot study that was used to test and develop the design and instru ments for the main study. The main study, sched uled for completion in 1982, compares 3805 eight to ten year olds, on respiratory symptoms, illness, and lung Sanction (PEFR), in the Polish communi ties of Cracow (two areas), Nowy Targ, and Limanowa. The arithmetic mean air pollution val ues for each of two years in these communities are shown in Table 17. The authors provide detailed information on the distribution and seasonal pat tern of the air pollution observations. Most of the symptoms analyzed and past respira tory illness were less prevalent in the cleaner com munities of Nowy Targ and Limanowa than in the two areas in Cracow. There was some indication that symptom rates were lower in the cleanest city of Limanowa than in Nowy Targ. Peak expiratory flow rate (PEFR) was lower in Cracow. In fact, PEFR of children without symptoms in Cracow* was lower than in symptom-positive children in the cleaner areas. The authors concluded that living in the more polluted ^community had a deleterious effect on respiratory symptoms, illness, and lung function. The effect of living in Cracow was greater than the other social, economic and environmental factors investigated by the authors. Unfortunately, PEFR as measured with Wright peak flow meters is subject to considerable variation due to variabil ity between machines. It is not clear from these reports how this phenomenon was controlled. U.S. Studies. A series of studies conducted in a New Hampshire pulp mill town, beginning in 1961, Table 17. Two-year mean air pollution value*.* SO, u/ms_____ 1974 1976 BS. wrftn3 1974 1975 Cracow-1 Cracow-2 Nowy T*rg Limanowa 111.4 138.2 57.1 41.5 108.1 148.5 66.8 64.3 169.7 204.9 82.0 53.4 160.9 227.4 79.8 49.2 Data of Rudnick et al. (6J). represent some of the earliest work on the health effects of chronic exposure to sulfur oxides and particulates in this country. In the initial study, Ferris and his colleagues (61, 65) compared symp tom prevalence and lung function in three areas with different pollution levels within Berlin, New Hampshire and found no associations after control for cigarette smoking. In a subsequent study (tiff), a random survey was carried out in the relatively clean city of Chilliwack, British Columbia. Though the pollution levels were considerably lower than those in Berlin, the prevalence of chronic respira tory disease was not significantly different in the two towns after adjustment for age and smoking habits. The average values of FEVt and peak expiratory flow rate (PEFR) were higher in Chilliwack than in Berlin for 30 of 32 subgroups defined by sex and smoking history after controlling for age and height. The authors suggested that differences in ethnicity, weather, medical facilities and other factors may have confounded the examination of the effect of air pollution. The Berlin, New Hampshire population was fol lowed up in 1967 and again in 1973 (67-69). During the period between 1961 and 1967, all measured indicators of air pollution fell. In the 1973 follow-up, sulfation rates nearly doubled from the 1967 level (0.469 to 0.901 mg SO3/100 cm2/day) while TSP values fell from 131 to 80 p.g/m3 (Table 18). Concen trations of SO2 were estimated by assuming that all atmospheric sulfur was in the form of S02. For all three periods, concentrations of S02 at these sites were below the present annual ambient air stan dard. During the 1961 to 1967 period, standardized respiratory symptom rates decreased and there was an indication that lung function also improved. Thus, the higher pollution concentrations seen in 1961 were judged to be associated with increased incidence of respiratory symptoms and impairment of lung function. Between 1967 and 1973, age-sex standardized respiratory symptom rates and agesex-height standardized pulmonary function levels were unchanged. The authors concluded that either Table 18. Pollution level*, Berlin, New Hampchire, during three study period*. Year () Total dustfall, g/m*/30 day* TSP, MgOn* Sulfation Oead peroxide), mg SOj/100 cma/d*y Sulfation converted to SO*, ng m* 1961 1966-67 1973 18.4 14.3 -- 180 -131 80 0.731 0.469 0.901 55 37 66 Assuming *11 sulfur in the form of SO*. 268 Environmental Health Perspective* UCC 084339 4 i *A a y ;h d ie :y in U it. y, ay lir M`"8 ed >P. el SP .es m- ed re J. in ed *nt ex leals ier ve* the change in air pollution concentration during the latter period was not associated with a change in respiratory health or that the study was too small to detect an effect. The comparison of health status between 1961 and 1967 suggests morbidity effects at 180 (xg/m3 (TSP) and 55 M-g/m3 (S02). These effects could represent a combination of transient (acute) and irreversible (chronic) effects of air pol lution exposure. The TSP value of 180 jig/m3 was based on sampling during the summer months and probably underestimated the annual average con centration. The comparison of 1967 to 1973 is unin formative because of offsetting changes in pollution concentrations, although S02 concentrations were below present ambient standards in both periods. Mostardi and Leonard (70) compared the results of pulmonary function testing in 42 high school students from an urban area with pollution concen trations of 100 ng/m3 (S02) and 109 ng/m3 (TSP) and 50 students from a rural area with pollution concen trations of 72 jxg/m3 (S02) and 83 \Lg/m3 (TSP) (maximum annual average over five years). This study was flawed by failure to consider smoking effects. Subsequently, Mostardi and Martell (71) reported on 173 and 161 students respectively from the same urban and rural areas. They tested FVC and FEV0 75 on subjects residing for 4 years or more in the areas. The groups were analyzed separately by sex and nonsmoking males were separately considered. The two groups had similar anthropometric charac teristics. Approximately 207c lower values of FEV0 75 and 10% lower values of FVC were reported in the more polluted area for the total group, for males, females, and for non-smoking males. While a higher proportion of smokers was found in the urban area (127c vs. 6% in the rural area) the authors claim this did not influence their results. They did not men tion race in this study. In the first report (70) the authors found that the lung function differences persisted after exclusion of the three black students in the urban area. The observed differences of 20% for FEV0 75 and 10% for FVC in two communities with relatively small differences in ambient concentrations of S02 and TSP are striking. Other studies discussed here suggest that air pollution at these levels would not have this large an impact on lung function. This implies that other community differences such as racial composition or socioeconomic status may have contributed to the intercommunity differences. The observed differences cannot be reliably attributed to differences in air pollution concentrations. The remainder of the evidence for health effects of sulfur oxides and particulate matter comes from the Community Health and Environment Surveil* October 1981 lance System (CHESS) program, sponsored by the Environmental Protection Agency during the late 1960's and early 1970's. Much of this work was published in a monograph (72) and subsequently summarized in three brief papers (73-75). These studies have been severely criticized. The most important criticism is that methodology and quality control for aerometric measurements was seriously flawed. In particular, spills of reagent and other errors in handling measuring equipment led to un derreporting of S02 values by 50 to 100%, while smaller biases were identified in the procedures for particulate measurement, resulting in underreport ing by an estimated 10 to 30%. A number of other problems of study design, participant follow-up and data quality control were detected, raising doubts about the accuracy and proper interpretation of reported results. Ultimately, the CHESS studies were the subject of a special Congressional hearing (76) and an investigation by an expert panel con vened by a Committee of the U.S. House of Repre sentatives (77). The principal criticism ofthe CHESS report arising from this review was that the data had been overinterpreted in the CHESS monograph. As we have indicated, observational studies of the health effects of air pollution are particularly difficult to conduct because individual exposure is poorly measured and populations may not be com parable in ways related to respiratory health. In view of the special problems occurring in the stud ies published in the CHESS monograph and the failure of subsequent publications to meet these criticisms, we believe that these studies cannot be used to assess the exposure response relationship between sulfur oxide and particulate concentrations and morbidity. This decision substantially reduces the evidence for morbidity effects of chronic expo sure to particulates and S02 at levels near present air quality standards, in that most of these studies reported health effects in association with pollutant concentrations near these standards. A more ex tensive discussion of this controversy can be found in the above cited congressional reports and a re cent review article (78). Two studies which were part of the CHESS program were published separately (79, 80). Infor mation in these articles addresses some of the criti cisms of the CHESS program. Hammer et al. (79) surveyed children in four metropolitan New York communities chosen for socioeconomic similarity. Some of the aerometric data used in Hammer's analysis are shown in Table 19. The TSP values for 1968-70 were obtained by extrapolating from the TSP values at the Manhattan station using dustfall values in each borough and the ratio of dustfall to TSP at the Manhattan station. Values of S02 in 269 UCC 084340 iI Tabic 19. Approximate air pollution concentrations.1 munities had very low S02 concentrations. Howev Air pollution concentration, ne'm3 er, the TSP concentrations cited are approximate. Hammer found that lower respiratory disease Pollutant 1968-1970 1971 1972 morbidity was less prevalent for children in the SO* Riverhead Queens Bronx N/Ab 23 22 cleaner community (Table 21). A separate analysis 176 51 50 of children with bronchial asthma produced more 250 51 38 equivocal findings. TSP Riverhead Queens Bronx N/Ab 34 36 Among asthmatics, morbidity rates in the more 85 63 89 polluted community were greater for only about no 86 60 half of the comparisons made. In the case of asth *Data of Hammer et al. (79). bNot available. matic blacks, bronchitis rates were greater in the cleaner community. On the whole, this study showed an association between TSP concentration and mor bidity level. Queens and Bronx were obtained from stations in Among the remaining studies in the CHESS * the boroughs. Data for Riverhead were provided program, the study of chronic respiratory disease by Suffolk County (New York). The fourth commu prevalence in the Salt Lake Basin (Si) is deserving nity, Sheepshead, was geographically contiguous to of fiirther attention. Although large and statisti the area studied in Queens, and was assumed to cally significant differences were found in disease have similar pollution values. All data for 1971 and prevalence between communities with high and low 1972 were obtained from the CHESS monitoring levels of S02 and sulfates, these pollutants were network. Although Riverhead unquestionably had among those found to be especially inaccurately substantially less air pollution than the other three communities,'Both historically and during the study, the values cited can be regarded only as approxima tions to the ambient concentrations in the study measured by the CHESS aerometric network, and Utah State Aerometric was incomplete for the rel evant years. Nevertheless, the health data have not been convincingly criticized, and an air pollu communities. Questions on respiratory disease were tion gradient was recognized to exist across the answered retrospectively by parents. Significant differences were found in rates of lower respiratory disease in the low pollution community compared to the three high pollution communities for all ages from 1 to 12. Sex and education of head of house study communities, despite problems of precise measurement. Further work with these data may increase the acceptance of this study. At the August 1980 meeting of the Clean Air Scientific Advisory Committee, EPA officials re hold were considered in the analysis. Although smoking may have been a factor in older children, this study suggests morbidity effects at pollution concentrations of about 175 pg/m3 (S02) and 85 fig/m3 (TSP), using the average of the annual expo sures over the years 1968 to 1970. Interpretation of this study is complicated by a 10-fold decline in S02 and 3-fold decline in TSP over ported that unacceptably high data entry error rates had been detected in some CHESS data sets, and that data sets for the major CHESS studies would be reentered and reanalyzed to establish the validity of earlier results reported from the CHESS program. Unfortunately, this report further weak ens the credibility of CHESS results. Although we cite results from two CHESS studies, continued the 12 year period and by the lack of direct local use of these findings is contingent upon successful measurement of air pollution concentration. More validation of the data sets by the staff of the EPA. detailed information might improve exposure esti The studies that have been reviewed in this mation for each child by age and period of exposure. section provide the observational evidence for morHammer (SO) also conducted a retrospective study, using parent-answered questionnaires covering four years recall of acute lower respiratory disease in 10,000 children aged 1 to 12 years. The two com Table 20. Approximate air pollution values for Birmingham and Charlotte, 1968-71 average.* munities chosen for comparison differed in particu Air pollu'.ii'n values, ttgm* late air pollution concentration but had low S02 concentrations (Table 20). The values for 1968-1970 cited in Table 20 were obtained by fitting trend lines to a few data points. As with the New York study, we can be confident that the cleaner community (Charlotte) had lower Pollutant City TSP SO* Charlotte Birmingham Charlotte Birmingham 1968-70 <25 <25 81 141 1971 <25 <25 74 133 TSP concentrations, while in this study both corn- *Data of Hammer (80). 270 Environmental Health Perspective* UCC 084341 'u tne <Jysis more more about ' asthJn the nowed J mor- HESS disease erving 4itistilisease nd low were ;ratel,v k, and ie relf have polluss the >recise a may error i sets, tudies sh the HESS ^eakgh we :inued essful EPA. n this mor- nfham <71 25" 25 74 38 lives Table 21. Afe-adjusted rate* (%) of one or more episodes of lower respiratory ditease, by race and age interval.* Race Age, yr Any lower respiratory Disease, Charlotte Birmingham Bronchitis. ft Charlotte Birmingham White Black 1-4 5-8 9-12 1-4 5-8 9-12 35.0 38.9 23.1 27.7 29.9 36.3 20.4 26.2 22.0 26.4 14.9 18.6 27.8 24.0 13.7 10.6 16.4 20.6 7.8 7.9 12.7 15.9 6.3 6.9 `Data of Hammer (80). bidity effects of chronic exposure to SO2 and partic ulate matter. In the next section, we summarize and interpret all of the evidence for health effects of acute and chronic exposure. Summary and Conclusions Individual studies providing evidence on the as sociation between health effects and the ambient concentration of sulfur oxides and particulate mat ter have been described in preceding pages. This section is devoted to a summary of that evidence in an effort to present a perspective on using the available data to establish concentrations for both acute and chronic exposure associated with increased morbidity or mortality. The analysis in this section has been influenced by the many thoughtful re views published in recent years (78, 82-89). For the purposes of this discussion, acute expo sure is measured by the 24-hr average concentra tion of each pollutant. Current National Ambient Air Quality Standards for maximum 24-hr average concentration are 260 p-g/m3 for TSP and 365 ng/m3 for S02. Exposures over shorter periods may be important, perhaps as measured by the peak hourly concentration in each 24-hr period. Exposures cal culated from different short term averaging periods arc highly correlated in most situations. The choice of method for measuring chronic expO'Ure is less straightforward, and can have a significant influence on the determination of con centrations associated with health effects. Most studies reported arithmetic average concentrations of each pollutant over some sampling period includ ing the study period. Although the sampling period did not cover an entire year in every instance, we express the values reported in the various studies as an annual mean concentration. Current National Ambient Air Quality Standards for annual mean concentration are 75 pg/m3 for TSP (computed as the geometric mean of 24-hr samples) and 80 pg m3 for SO2 (arithmetic mean). Since arithmetic October 1981 means were used almost exclusively for reporting particulate and sulfur oxide concentrations in the studies of chronic exposure, these values have been used in summarizing the evidence. Differences be tween geometric and arithmetic means are usually unimportant compared to other sources of uncer tainty in measuring exposure. Many of the studies cited failed to obtain concur rent aerometric data. When available, those data were collected at one or a few sites distant from the homes of study participants. The air monitoring techniques were often primitive by current stan dards, with a resulting potential for substantial bias or variability in measuring concentration. Even when ambient concentrations are optimally mea sured, the implications for individual exposure are uncertain. Consequently, very great uncertainties about the actual air pollution exposures of study participants in most of the studies discussed weaken analyses of the relationship between exposure and health effect response. For studies using Black Smoke (BS) to measure particulate concentrations, the conversion to TSP values is highly uncertain and depends upon condi tions in the study environment. We convert BS to TSP values using the results of Commins and Wal ler (89). Since their study was conducted in London between 1955 and 1963, the applicability to other sites or times is unknown. Although we use their conversion to unify the discussion, this introduces additional uncertainty. For the one New York study using Coefficient of Haze (CoHs), we use the con version developed in New York by Ingram and Golden (90). They equate 5 CoHs to 580 ng/m3 (TSP). Some studies have reported sulfate concentra tions, and there has been considerable interest in the fine particulate fraction (91). However, the correlation between TSP concentrations and its components has been consistently high in observa tional studies. Thus, these studies provide no basis for separately assessing the health effects of differ ent fractions by size or chemistry of ambient par 271 UCC 084342 A ticulate matter. Further understanding ofthe proper measure of particulate concentration in terms of health significance will come from advances in un* derstanding of lung physiology and from exposure studies with animals. Assessing causal relationships from studies of association is a familiar problem for epidemiolo gists, and the problem is especially difficult in air pollution research. When exposures are near pres ent air quality standards, the health effects of air pollution exposure are likely to be small. Many other individual characteristics influence lung func tion and the risk of respiratory disease. Some of these, like smoking, occupational differences, and socioeconomic status, are well known but difficult to measure, others like passive smoking have been recognized only recently. The association of lung function and respiratory disease with these charac teristics is often much greater than the likely ef fects of air pollution. The possibility in any observa tional study that these factors have been inadequately controlled adds additional uncertainty to the inter pretation of the nonexperimental studies. Thus, the determination of concentrations associated with ad verse effects is tempered by recognition of these potential nonsampling errors. For all of these reasons, the epidemiologic data base is extremely weak. In particular, it is insufficient to distinguish between a threshold hypothesis, that health effects are seen only above certain concen trations, and a monotonic exposure-response hy pothesis, that health effects increase (perhaps very slightly) with air pollution concentration over a very wide range. Although we favor the latter hypothesis as more physiologically plausible, we have chosen to interpret the evidence in terms of concentrations at which health effects have been detected. These values should not be interpreted as threshold values. Finally, S02 and particulate con centrations were highly correlated in many of the studies cited. Thus we cite concentrations jointly of SO2 and TSP at which health effects have been detected, and then discuss the evidence for health effects of the individual pollutants. Health Effects of Acute Exposure to S02 and Particulate Matter The studies providing evidence for health effects resulting from acute exposure to S02 and particu late matter are summarized in Table 22. The selec tion criteria excluded studies of S02 or TSP expo sures above 1000 pg/m3, and the list is strikingly short. The tw*o mortality studies cited (from the same group) found increased mortality associated with TSP concentrations of 500-600 pg m3 in con junction with SO2 concentrations of 300-400 pg/m3. These studies summarize a relatively small body of data from two winters in London. The individual studies do not suggest a threshold phenomenon. Although there is some suggestion of an association at lower concentrations, the evidence is very' scanty. For all of the reasons discussed above, this inter pretation is subject to considerable uncertainty, and this explains in part the divergent views ex pressed by different reviewers. Time series analy ses of daily mortality records over several years have sometimes suggested small mortality effects of air pollution concentrations at much lower con centrations, particularly in association with particu late concentration in the New York studies, but the results have been highly dependent on model selec tion and are internally inconsistent. Only two reports of associations betw een morbid ity and 24 hour average pollutant concentrations are cited in Table 22, and one of these is again the study by Martin. Thus, the acceptable epidemiologic evidence for health effects in association with acute elevations of SO2 or TSP concentrations below 1000 pg/m3 consists of only two studies. Other reports, including those of Cohen (38), Van der Lende US), and Glasser and Greenberg (27) are suggestive but subject to numerous ambiguities related to meth- Table 22. Summary of evidence for health effect* of acute exposure to SO] and particulate matter. Type of etudy Reference Effects observed 24-hr average pollutant levels at which effects were detected. ue'm3 TSP SO* Mortality Morbidity Martin and Bradley (iff) Martin (0) Martin (0) Lawther et al. (4, 35) Increases in daily total mortality above the 15-day moving average Increases in daily total mortality above the 15~day moving average Increases in hospital admissions for cardiac or respiratory illness Worsening of health status among 195 bronchitics 600 600 600 350 300 400 400 500 272 Environmental Health Perspectives UCC 084343 f alih eels :icuilec> >P<>ngly the ated con'm3. lv of aual non. ttion nty. lternty, exI'alyears ects con:icu: t*" bidions the ogic 'Ute .000 rts, 13), but eth- ei* ed. -- odology and interpretation. Although severe air pollution episodes have frequently been associated with excess mortality and morbidity, there is only a small body of evidence to document such effects at concentrations below 1000 p-g/m3. Health Effects Associated with Chronic Exposure to S02 and Particulate Matter As noted above, the evidence for mortality ef fects of chronic exposure to S02 or particulate matter is inconclusive. Though several studies have found associations, the methodological uncertain ties are so great as to make these studies essen tially valueless for quantifying the exposure-response relationship. The morbidity studies that have found differences in levels of health effects in association with differences in pollutant concentrations are sum marized in Table 23, and displayed in Figure 1. In these studies, upper and lower respiratory symp toms, chronic bronchitis and reduced pulmonary function were observed in association with TSP concentrations in excess of about 180 pg/m3. In one study, acute respiratory disease was increased in association with reported T^P concentration of 135 pg m3 though these values were estimated from relatively weak aerometrie data. As with the stud ies of acute effects, most of these studies could be interpreted as demonstrating that the prevalence of adverse health effects increases monotonically with exposure over the entire range of exposure studied. These studies provide little evidence to assess the health effects associated with elevated SOa concentrations along with moderate particulate concentrations. Although Hammer (79) and the Salt Lake Studies (72) did report such associations, the problems with methodology and aerometrie mea surement in those studies limit their value in this assessment. Though exposure to these pollutants at concentrations below those cited may imply some increase in risks, it will be difficult to resolve this question in an observational setting, because health effects of pollutants at these concentrations are likely to be small relative to effects of other factors which vary over communities. MO wwcwirt* UM 3M SB B 63 100 SI so GH-ffi U1O U0!--- M0I >wn TOO vnvvfttratlan Figure 1. Plot of studies in which increased levels of adverse health effects were associated with chronic exposure to higher concentrations of TSP and SOg. Studies are plotted at the lowest concentrations at which increases were seen and by the reference numbers in the bibliography. The dashed lines correspond to the current National Ambient Air Quality Standards for annual mean concentration. #-S7 Table 23. Summary of evidence for health effects of chronic exposure to SOg and particulate matter. Type of study Reference Effects observed Annual average poll levels at which eff noted, ug'm3 TSP SO, Cross-sectional (four areas) Cross-sectional study across Britain Cross-sectional (two areas) Cross-sectional (four areas) Longitudinal and cross-sectional Cross-sectional (two areas) Lunn et al. (56, 57) Lambert and Reid (61) Sawidd (61) Rudnik et al. (63) Ferris et al. Hammer (SO) Increased frequency of respiratory symptoms; decreased lung function in five-year-olds Increased prevalence of respiratory symptoms More chronic bronchitis, asthmatic disease in smokers; reduced FEVft Increased history and symptoms of respiratory illness Higher rate of respiratory symptoms; and decreased Jung function Increased frequency of acute lower respiratory disease 360 200 270 285 180 135 225 100 125 125 55 <25 October 1981 273 UCC 084344 i Summary The studies summarized in Table 22 indicate that increased mortality and morbidity are associated with exposure to 24-hr average TSP concentrations of 500-600 jig/m3 and S02 concentrations of 300-400 M.g/m3 and a temporary decrease in lung function has been associated with a TSP concentration of 250 M-g/m3 and a S02 concentration of 300 ug/m3. This conclusion is based on only two independent stud ies. There is little evidence concerning health ef fects of short term exposure to only one of these pollutants. Various studies not accepted in this assessment have reported health effects at lower pollutant concentrations, but we believe that the evidence from these studies is inconclusive. The studies summarized in Table 23 indicate that increased morbidity is associated with chronic ex posure to TSP concentrations exceeding 180 ug/m3 (annual average). Though effects were found both with and without parallel increases in S02 concen tration, there is no basis in these studies for evalu ating the effects of elevated S02 concentrations without increased particulate pollution. Once again, one cited study (80) and several studies not ac cepted for this assessment have reported health effects at lower concentrations and with elevated S02 concentrations, particularly the studies in the CHESS program. In our opinion, the evidence for health effects at these lower concentrations is in conclusive, but should be the subject of continuing investigation. Though we have focused on the evi dence from observational studies, the evidence from animal studies and controlled studies of human exposure must also be considered, particularly in relation to the less severe effects of short-term high exposures. These studies will also play an impor tant role in future efforts to link health effects with chemical or size fractions of the S02-TSP pollution complex. Nonexperimental studies provide little information on this issue because of the collinearity of the components of interest. This will be espe cially important in studying fine particulates. Although we have given single numbers as con centrations above which various health effects occur, these numbers are based on very sparse data from studies not designed to establish such values. Thus, the numbers are subject to uncertainty which is difficult to quantify. In view of the limitations of studies based on multivariate analysis of data obtained from sources not oriented to air pollution research, future stud ies will be most informative if they involve thor ough and detailed investigation of well defined pop ulations. Direct measurement and careful control of poten 274 tial confounding factors will be especially impor tant, as will improved measurement of the air pol lution exposure of individuals. 1116 need for such research may grow as energy usage patterns shift in response to limited availability of oil and natural gas. The public health significance of this question is sufficient to justify the commitment of additional resources to improving the data base on health effects of sulfur oxides and particulate matter. Many colleague* and associates have made helpful suggestions and constructive criticisms of earlier drafts of this paper. 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E., Knowelden, J., and Handyside, A. J. Patterns of respiratory illness in Sheffield infant school-children. Brit. J. Prev. Soc. Med. 21: 7 (1967). S7. Lunn, J. E., Knowelden, J., and Roe, J. W. Patterns of respiratory illness in Sheffield junior school-children: a follow-up study. Brit. J. Prev. Soc. Med. 24: 223 (1970). 68. Douglas, J. W. B., and Waller, R. E. Air pollution and respiratory infection in children. Brit. J. Prev. Soc. Med. 20: 1 (1966). 59. Colley, J. R. T., Douglas, J. W. B., and Reid, D. D. Respiratory disease in young adults: influence of early childhood lower respiratory tract illness, social class, air pollution, and smoking. Brit. Med. J. 3:195 (1973). 60. Kiernan, K. E., Colley, J. R. T,, Douglas, J. W. B., and Reid, D. D. Chronic cough in young adults in relation to smoking habits, childhood environment, and chest illness. Respiration 33: 236 (1976). 61. Lambert, P. M., and Reid, D. D. Smoking, air pollution and bronchitis in Britain. Lancet i: 853 (1970). 62. 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Ferris, B. G., Jr., Higgins, I. T. T,, Higgins, M. W., and Peters, J. M. Sulfur oxides and suspended particulates: possible effects of chronic exposure. Arch. Environ. Health 27: 179 (1973). 69. Ferris, B. G., Jr., Chen, H., Puleo, S., and Murphy,''R. L. H., Jr. Chronic non-specific respiratory disease in Berlin, New Hampshire, 1967-1973. Am. Rev. Resp. Dis. 113: 475 (1976). 70. Mostardi, R., and Leonard, D. Air pollution and cardiopul monary functions. Arch. Environ. Health 29: 325 (1974). 71. Mostardi, R. A., and Martell, R. The effects of air pollution on pulmonary functions in adolescents. Ohio J. Sd. 75: 65 (1975). 72. U.S. Environmental Protection Agency. Health Conse quences of Sulfur Oxides: A report from CHESS, 1970-1971. ORD, NERC, Research Triangle Park, N.C., EPA 650/1-74-004. 73. Shy, C. M., Hasselblad, V., Burton, R. M., Nelson, C. J., and Cohen, A. Air pollution effects on ventilatory function of U.S. school children. 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U.S. House of Representatives, U November. U.S. Government Printing Office. Washington, D.C. (1976). 78. Bennett, A. E., Cameron, J. R., duV. Florey. C., Holland, W. W,, Leader, J. R,, Schilling, R. S. F., Swan, A. V,, and Waller, R. E. Health effects of particulate pollution. Reap praising the evidence. Am. J. Epid, 110: 525 (1979). 79. Hammer, D. I., Miller, F. J., Stead, A. G., and Hayes. C. G. Air pollution and childhood lower respiratory disease, L Exposure to sulfur oxides and particulate matter in New York, 1972. In: Clinical Implications of Air Pollution Re search. A. J. Finkel and W. C. Duel, Eds.. Publishing Sciences Group, Acton, Mass., 1976. 80. Hammer, D. I. Frequency of lower respiratory disease in two southeastern communities, 1968-1971. Sc.D. Disserta tion, Harvard University, 1976. 81. Hertz, M. B,, Truppi, L. A., English, T. D., Sovocod, G. W., Burton, R. M., Heiderscheit, L. T., and Hunton, D. 0. 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I. in Mew lotion RePublishing ,'iseise in Diatena- vocool, G. -on, D. 0. he Basin 0/1-74-04, Vol. 41, pp. 277-289, J981 Mathematical Models of the Uptake of Carbon Monoxide on Hemoglobin at Low Carbon Monoxide Levels by Robert Joumard,* Mireille Chiron,* Robert Vidon, Michel Maurin* and Jean-Marc Rouzioux* Cobum's differential equation for the uptake of carbon monoxide by hemoglobin and two particular types of solution of this equation were considered and the solutions verified for a group of healthy adults consisting of 73 nonsmoking pedestrians or car passengers exposed to low levels of carbon monoxide as experienced in the city of Lyon. The CO levels at the breathing level and the walking speed of the subjects was continually measured, and the carboxyhemoglobin levels determined artfie beginning and the end of each test journey. The values of all the other relevant parameters were alto determined. The half-life of carboxyhemoglobin was studied as a function of the degree of activity, the age, the sex and the height of the subjects. Finally a mathematical model was set up to represent a periodic uptake of CO which made it possible to estimate the variations in the carboxyhemoglobin level for any subject during a period of a day or a week without any need to know the initial level. n Control 'eminent fare. Air Pollution -S. Gov- tspended 8. World Vaahingdemy of llution. levels of ir Poll. from a -ondan. `ion. J. R. ., rations J. Air es There is normally a very small concentration of CO in the air as a result of natural phenomena, its level being between 0.01 and 1 ppm. Measurements canned out on the Isle of Sark (I), where motor vehicle traffic is prohibited, confirmed that the CO levels were always less than 1 ppm. Measurements j marie in urban areas in various places in the world over many years have resulted in a considerable quantity of information on CO levels. The exact j location where the measurements are made is I important, since the highest concentrations are I found in the midst of a stream motor vehicles and j also inside such vehicles, as confirmed by this I in\ estigation. Pedestrians walking along the sidej walks are exposed to a lesser concentration of CO * than are motorists. People who are obliged to j remain at certain critical locations such as toll Institut de Recherche dee Transports, Centre devaluation et de Recherche des Nuisances et de l'Energie, BP 75, 69672 Bron Cedex, France. Facuhe de Medeane Alexis Cartel, Leboratoire de MAderine Legale et Toxicologie' Rue Guillaume Poradin, 69008 Lyon, France. October 1981 booths, garages or in traffic jam in enclosed and poorly ventilated streets are exposed to high CO levels due to road traffic (2,3). In order to obtain some idea of the conditions, a person moving within a city will experience CO levels having an average level for the hour in excess of 30 ppm U). American standards for permissible levels to which the public may be exposed are in fact sometimes exceeded (5,5). Dangerous HbCO Level and Particularly Vulnerable Subjects The effect of carbon monoxide is to reduce oxygenation of the tissues and this effect may be experienced immediately or after a longer period of time. Any increase above the endogenous level can in theory be harmful for a person having an extreme requirement for oxygen, and w-ho cannot compensate a reduced supply of oxygen by physio logical means. Such subjects consist mainly of people suffering from coronary atheromatic ischaemia or from cerebral vascular deficiencies. Also at risk 277 UCC 084348 4 here are people suffering from pernicious anaemia 13.3 kPa (100 mm Hg) and 6.3 kPa (47.5 mm Hg), or from respiratory deficiencies, patients recovering respectively. 4 from major surgery or premature babies. Aronow The value of Pw is directly related to that of C and Isbell (7) refers to a "critical" carboxyhemoglobin by the equation: Pico * PB x HrC. We also level of between 0.025 and 0.030 for angina pectoris assumed that y * HbCO = 17 [CO]/[Hb], (or 1000 sufferers, such a level giving rise to an appreciable [CO]/1.316 [Hb], if [CO] and [Hb] are in ml/100 ml reduction in the time elapsing before the onset and g/100 ml of blood, respectively), and similarly of a painful attack following a given physical ef that HbX 17 [X]/[Hb]. The value of DL is related fort. The World Health Organization (5) estimates to the height and body surface of the subject and 4 that the level-for the population exposed to atmo the value decreases with age. A number of relation spheric pollution should not exceed these limits. In ships have been proposed, and the resulting calcu the case of our sample, the 0.025 level was exceeded lated values may. differ 20 to 30% for the same for 19 out of the 73 subjects (pedestrians or car subject. We used the following relationships (9): passengers) as a result of their displacement in the For a man aged 18 or more: city. However this level can in theory easily be Dh - 0.329# - 0.000135Y - 0.318 4 exceeded for subjects remaining in heavily polluted For a woman aged 18 or more: localities. The 0.025 carboxyhemoglobin level would Dl - 0.119# - 0.000087y - 0.015 result from an exposure to a 13 ppm CO concentra For a child: tion for more than 24 hr. Dl - 0.117A-0.022 The value of Vb for adults depends on the sex of Kinetics of the Uptake and Elimination of Carbon Monoxide the subject and we assumed values of m/13 and m/15 for male and female subjects, respectively. For children we assumed values of 0.071m, 0.075m and Symbols and urtits used are summarized in Table 1. We used SI units, but for CO concentration used ppm because it is independent of the temperature. 0.080m for 15, 10 and 1-6 year old subjects respec tively (JO). The value of Vco for a standard male subject has been given as 5.2 x 10-6 mmole/sec (0.007 ml/min) (5). We assumed that the value varied with the Differential Equation total hemoglobin level Vb[Hb] (for a standard male Cobum et al. (3) have proposed the following subject, Vb - 5 liters and [Hb] = 155 g/l blood), giving differential equation (1) for carboxyhemoglobin level as a function of time: Vco * 5.2 x 1(H Vb[Hb]/5(155) Vb MlOJ/Pc^ (1/Dl + PB- Ph2o/Va> dlCOVdt + [CO] - Pico MO*]/Pc0i + Vco M[02]/Pc0j The degree of alveolar ventilation is proportional (jj) to the oxygen consumption VA = 19.63V<j2, and this consumption depends in turn on the power expended by the subject (12). Thus we have: (1/Z?L + P " PH2c/^a) ^ VA - 4.33 x 10-* P Numerical Values of the Different Parameters The values given below are statistical averages for subjects in good health and very different values can apply in individual cases, particularly in the case of subjects suffering from certain diseases. The value of M can vary from 185 to more than 250, and we assumed a value ofM = 250. [02] was given a value such that: [02] + [CO] + [X] * 8.92 mmole/ liter of blood (200 ml/1.) PB was assumed to have a value of 99.3 kPa (745 mm Hg) for the town of Lyon, which is at an altitude of 120 m above sea level. Pcog and Phzo were assumed to have values of 278 Power Expended The power expended is the sum of the basal metabolism, the muscular power and the specific dynamic action of the foods: P * MB + PM + SDA. The basal metabolism is proportional to the surface area of the body: MB Ax. Pandolf et al. (IS) have established an equation giving the rate of energy expenditure for a subject when standing or when walking at different speeds and when carrying or not carrying a load. P (SDA - 0) - 1.5m + 2(m + m') (m'/mf + e(m + m') (1.5V* + 0.35aV) Environmental Health Perspectives UCC 084349 also d'000 X) ml larlv lated and tiontlcu1/irne 9): < ;x of m/15 For and oeci has min) the nale ^r- >nal and A'er isal fic >A. ace ion ect xie Symbol .4 all) HU C (CO] d Dt ni u H [Hbl HbCO HbO: HbX HEL t K Xo X, Kt m m' SI MB to,] P, *CO Pc0 P2 P?2 piS sda SDA V V. V,," U2 rr 7 (X) y V tit) Vo t\m V*. a l T Unit m* ppm mmole/1. of blood mmole/sec/kPa m g/1. of blood fraction fraction fraction fraction fraction/ppm fraction/ppm/sec fraction fraction/sec fraction*/sec kg kg W mmole/1. of blood W kPa kPa kPa kPa kPa W W W m/s mmole/sec liters mmole/sec mmole kJ/kg W/m* mmole/1. of blood years fraction fraction fraction fraction fraction per cent sec sec + O * October 1981 Table 1. Symbol* and unite used. Definition Body surface area Other form of the coefficient in Coburn's equation Other form of the coefficient in Cobum's equation Carbon monoxide concentration in air CO level in blood A coefficient depending on the type of meal Pulmonary CO diffusion capacity A coefficient depending on the condition of ground surface Function used for resolving Cobum's equation Function used for resolving Cobum's equation Height of subject Hemoglobin level Carboxyhemoglobin level with respect to the total hemoglobin Oxyhemoglobin level with respect to the total hemoglobin X hemoglobin level with respect to the total hemoglobin (e.g., nitrosylhemoglobin) Limit endogeneous carboxyhemoglobin level with respect to the total haemoglobin A constant for carboxyhemoglobin level Rate constant for carboxyhemoglobin formation A coefficient employed in step-by-step calculation: carboxyhemoglobin and oxyhemoglo bin levels Coefficient employed in step-by-atep calculation: partial rate constant for CO uptake Coefficient employed in step-by-step calculation: partial rate constant for CO uptake Weight of subject Load carried by subject Haldane's constant Basal metabolism Oxygen level in the pulmonary capillaries Fraction of the daily energy allowance for one meal Total power expended by the subject Barometric pressure Average partial CO pressure in the pulmonary capillaries Average partial oxygen pressure in the pulmonary capillaries Vapor pressure of water Partial CO pressure in inspired air Muscular power (expended) Instantaneous specific dynamic action per 1 kJ of food ingested at last meal Specific dynamic action of foods Walking speed Alveolar ventilation rate Blood volume Rate of endogeneous CO production Volume of oxygen consumed Heat production to food/kg of body weight Basal metabolism per unit body surface area Possible gas level other than Oj and CO in the pulmonary capillaries (e.g. nitric derivatives) Age of subject ( HbCO): proportion of carboxyhemoglobin withrespect to total hemoglobin particular periodic solution of Cobum's equation value of y at time to Initial measured value of HbCO Final calculated value of HbCO Final measured value of HbCO Inclination Kronecker symbol (1 - standing, 0 other eases) Time constant Half-life 279 UCC 084350 i 4 The validity of this equation has been verified for and SDA of 78, 13 and 17, respectively. Thus the young male subjects of average height and weight SDA is approximately 20. It represents nearly a (1.75 m, 78.2 kg). The equation gives the value of quarter of the basal metabolism to which we need 4 the total power expended, including the basal to add the muscular work rate which can be greater metabolism, but for a zero SDA value. than the basal metabolism. Thus the SDA is not We also considered Scherrer's findings (IS); he negligible. stated that the power expenditure amounts to 1.2 times the basal metabolism for a standing subject and to 1.1 times the same basal metabolism when Solving the Differential Equation the subject is sitting and at rest (and 0.9 times Three methods of solving Coburn's equation are 4 when the subject is asleep). We made use of a considered. coefficient d to allow for these factors. Certain First Method: Step-by-Step Solution. Let y, authors have shown that a female or an overweight and y2 be the carboxyhemoglobin levels at times tj subject expends less energy when at rest as a result and tg, respectively; if C remains unchanged from of a smaller proportion of muscular tissue which time ti to time tg we can write: 4 accounts for the difference in metabolism with effort. The additional expenditure of energy as a result of performing work PM is the same (U). If Vz - Vi + 2 - <i) { Aj - lKg/(K0 - yj)l } we wish to apply the above equation for a subject of where either sex then the first term (1.5m) in the expres sion must be a function of the sex. We accordingly Ao 17(8.92 - rXD replaced the first term by Adz, where x is a [Hb] ) function of both age and sex (15) and the second 4 term appears only for a stationary, standing sub 17 ject. We then have: VJHb] P(SDA * 0) * Adx + 26(m + m') (m'/mf + e (m + m') (1.5V2 + 0.35aV) (1) r fS + MP* X 1(HC y1 {(1 IDO + [(PB - P,,2o)/Va] }+ C0 J The SDA or additional postprandial heat is de fined as the increase in the rate of energy ex penditure resulting from the ingestion of a meal, the other conditions being basal. This specific dynamic action varies with time and it rises to a maximum value some 2 hr after the ingestion of a meal (Iff). Furthermore it should be noted that the SDA value depends on the type of food consumed and it can be assumed, as a first approximation, that it is a function of the energy value of the meal, this latter being a function of the age and sex of the subject. It is also proportional to the weight of the individual and we can accordingly refer to wr, the heat allowance per kilo of weight of the subject. We therefore have: SDA * mwT (Y, sex)pr sda where sda is the SDA for 1 kJ of food and pT is the fraction of the daily energy allowance for each meal. What is the relative importance of MB, PM and SDA? With our mixed group of subjects made up half of pedestrians and half of car passengers we had values of MB * 91, PM = 80 and SDA - 23. On considering a theoretical subject over a period of one week we obtained average values of MB, PM (2) & [ ](8.92 - [X])Pc0 MVb { (1/Dl) + [(PB - P^/VJ ) J (3) The advantage of this method of solving the equation in comparison with the other two methods considered below is that no assumptions need to be made. The disadvantage is that an error is intro duced, since no distinction is made between the tangent to the curve and the curve itself at each point. Second Method: Analytical Solution. If we ignore [CO] (and [X] but it is not strictly necessary) with regard to [02], then the basic equation can be put into the form of a linear first order differential equation: (k/IQdy/dt + y - kC + HEL (4) This is also the form of equation proposed by Chovin and Richalet (17) except for the inclusion of 280 Environmental Health Perspectives UCC 084351 * This the Utr>v a id greater 4. is not don are 'Let yt times ti id from ]} (1) m ] (3) g the ithod6 1 to be intron the . each If we ssary) -an be ential (4) id by ion of tives the HEL term, which was based on the results of the experimental investigation by Hanks and Fanjuhar (18). Peterson and Steward (19) have verified it for constant concentrations (50 to 200 ppm) in industrial conditions on the whole. If, in addition, C can be regarded as a linear function of time (C * at + CO then the analytical solution to the equation becomes: y - HEL + K{a[t-ik/K) + CO + to - * [a (k/K) - CO - HEL} e** where 17 x 8.92MPt x lfr* *VHb] K= 17P. x lfr B Vb[Hb] [(1IDl) + UP.-Ph^J HEL 17 x 8.92MV,co Pc02[Hb] [(1/Z>L) + [(P.-Ph.oWJ The time constant k/K is then given by: T- 8.92M fe ---------- V. Pcn v2 )P.-PH,0 The constant k is such that the HbCO level follow ing an infinite time of exposure to a concentration C a ill be kC + HEL. In particular, the value of k is a function of the hemoglobin level and is independent of the level of activity. The value of the factor K, wnich defines the rate of uptake of CO by the ht-moglobin, increases with the degree of alveolar ventilation and hence with physical activity. Stan dard values of k and K are listed in Table 3 below. The limit endogeneous carboxyhemoglobin level HEL al'O increases with the amount of physical activity, but the level remains very low (< 0.002). This analytical method of solving the equation enables us to determine any HbCO level, if the initial level is known, provided the variation of C is linear and K remains constant during the interval concerned, which are not unreasonable assumptions. Third Method: Periodic Solution. The two methods of solving the differential equation described above depend on a knowledge of the initial HbCO October 1981 level. This well-established disadvantage can dis appear if we ignore [CO] with regard to t02] and if the parameters K, C and HEL are periodic func tions of time (k being constant for a given subject). It is possible to find a periodic solution by using some analytical properties. For convenience, we use a more mathematical language in this section. If we rewrite the equation dy/dt + a(t)y * 6(f) with a(f) K(t)/k bit) - K(t) C(t) + Kit) HEUt)/k this is a linear differential equation of the first order, whose general solution is V(t) * VoM + g(D with the new functions (0) At) * exp {- f a(u)du) A0) 1 *o and fgit) * At) biuVAu) du gi0) * o */o If a(t) and 6ft) are periodic functions of period T and if aft) a 0, it may be easily shown that m - gimtm-am + git) is a particular solution which is periodic (of period T), and every general solution y0 At) + g(t) con verges towards yft) as t is increasing (f * 3 or 47) i2l). Then the yft) function is a convenient analyti cal tool to describe the actual variations of the carboxyhemoglobin level yft) if the data used K,C,HEL are periodic functions of time. So we make the realistic assumption that these data rep resentative of the activity and CO exposure of a person are periodic over a period of 24 hr, or, better, over 7 days; moreover, since these varia tions are known, it is no longer necessary to mea sure or to choose arbitrarily the initial HbCO level to describe the variations of the HbCO level in any time interval. In practice, we obtain the values of K, HEL and C every* 15 min (during 24 hr or 7 days) and calculate the basal integrals At), g(t) at the same moments by numerical methods on a comput er. 281 UCC 084352 i For the second and third methods, we ignore [CO] with regard to [02]: the greater the value for HbCO, the more k and HEL are overestimated. We can give [02] its initial value [8.92 - (Hb/17) yj or its mean value. Besides, if we do not ignore [X] when we can estimate it, we must replace 8.92 by 8.92 -IX]. Experimental Verification In order to validate the theoretical analysis, we carried out tests with a total of 73 subjects whose ages varied from 18 to 60 years and who all stated that they were nonsmokers. This sample was divided into two groups of subjects: one group consisting of car passengers who remained seated in each case for the duration of a test journey within and around the town, and a second group consisting of pedestrians who walked at a nearly constant speed in each case in the actual polluted atmos phere existing in certain streets of the city of Lyon. The pedestrians were accompanied by a technician who ensured that the walking speed was main tained throughdiit each test journey on making measurements at intervals of 3 to 4 min (the mean speed is 1.09 m/sec). Samples of blood were taken at the beginning and end of each journey and these samples analyzed in order to obtain values of [Hb]; yim and y^. The analysis of the blood samples was based on the method developed by Boudene, Godin and Roussel (22), where the proportions of hemoglobin and CO in the blood were determined by means of infrared spectroscopy. The carbon monoxide levels in the atmosphere were measured on a continuous basis by means of a polarography technique by using a portable Ecolyser and a paper recorder. For each of the subjects we had in addition to our knowledge of the values of [Hb], ylm, y2m and C, information concerning the sex, weight, height and age of the subject, the load carried by the subject, the time of day when the subject undertook the test journey and continuous information on the walking | j , j i .) i | , t Table 2. Aert|t value* of the different parameters for the ample aubjecta. Parameter Men Women n Age (Hb], g/1 m, kg m', kg H, m C, ppm V, m/aec Duration, min D,, mmole/aee/kPa A, m* K, litem Vqq x 10"*, mmole/aec ?2m >*. . mm Activity A Activity B 37 32 147 71 3 1.75 13.9 0.70 126 0.190 1.85 5.46 5.55 0.019 0.007 0.023 0.008 236 140 36 32 133 57 3 1.62 13.7 0.64 123 0.175 1.59 3.78 3.49 0.018 0.006 0.021 0.006 208 117 282 Environmental Health Perspective* UCC 084353 I - the fjour .dC, t and >ject, test king i r the len 3 f >4 175 1,9 T8 19 >18 106 >21 06 jv-* speed of the pedestrians. Knowing the initial level in each case we calculated the successive carboxyhemoglobin levels throughout the duration of the test and the final level y^ for each subject. An example of the results obtained as a result of mak ing these calculations is given in Figure 1. The calculations were made on using the analytical method without approximate rectification of [02] to solve the differential equation and also on using the step by step method on estimating HbX = 0 or HbX 0.010. In Table 2 we list with respect to the sex of the subjects, average values of the different pa rameters for the sample subjects: age, [Hb], m,m\ H, CO concentration, V, duration of the tests, Z>L, A, Vb, VcO, ylrn, y2m and the half-life for the subjects when at rest (A) and when walking at a speed of 4 km/hr (B). As a verification of the validity of the theoretical calculations we compared the final measured levels with the different calculated values. We applied statistical tests to the pairs of values (ylm, y2,,), (^m. Vic) and (y2Jylm, y^yiTM) in order to ascer tain if there were any significant differences be tween them (at 5%) for different subsamples as regards the sex and the type of activity. As a result of this it was found that th^initial and final mea sured levels wlm and y2m were significantly differ ent (p - 10-7). The method of calculation employed did not have any effect on the results; the differ ences in the levels determined by each method were not significantly different from one another. There was no significant difference between the calculated and measured levels either for the whole sample of subjects or, except for the case of male pedestrians, for any subsample. This was found for both the (y2m, y2e) and the (y2Jyim, y^y>m) pairs of values. We calculated also A = [sign of(y2m-ylm)] (j/2c yzmVyim, which is positive when the calcu lated change is too great. Mean A showed that the calculated changes were generally lightly too small and in the case of male pedestrians clearly too small. The calculated results as a whole were very satisfactory for all subjects and particularly so in the case of female pedestrians. Thus we can con clude that the two method (analytical or step-by stop solutions) were equally valid, at least when the level of HbX + HbCO is low. The analytical solu tion is therefore to be preferred for environmental pollution since it is easier to use; we can give if necessary to [02] its initial or mean value. The differential equation for the uptake-elimination of carbon monoxide by hemoglobin and the use of the selected parameter values to model the phenomena is generally valid, although it would appear that the changes in the HbCO levels are underestimated for October 1981 male pedestrians (the degree of alveolar ventilation is no doubt insufficient in the model). Applications Effects on a Particular Subject The procedure employed to verify the validity of the theoretical approach can also be applied to real life cases. This requires measuring or estimating the CO concentrations throughout the period of time being considered and assuming an initial HbCO level. We can then determine the effects of the changing environment on a real or imaginary subject. However, it is often difficult, if not impossible, to obtain information on the CO concentration in the air and on the level of activity of the subject at each instant. We must therefore ask what error would be introduced on using average values of CO con centration and/or of the level of activity of the subject? To answer this question let us consider a female subject exposed to an average CO concen tration of 15 ppm and walking along at an average speed of 1 m/sec, with both these values varying from zero to twice the average level. The initial level of HbCO is assumed to amount to either 0.010 or 0.050. When calculating the results for this case it was found that no errors are introduced when assuming these average values despite the random variations in the instantaneous values of CO con centration and the level of the subject's activity. In general it was found that only a small error is introduced by assuming an average value for the level of activity but that a significant error can result when assuming an average value for the CO concentration and the period of integration involved is greater than the half-life (see below). The error, however, becomes negligible for periods of integra tion which are less than the half-life by an order of magnitude or more. Graphs for Determining the Uptake and Elimination of CO Under Different Conditions A desk calculator has to be employed to obtain analytical solutions of the differential equation, and we have therefore produced a series of graphs resulting from theoretical calculations which show the way in which CO is taken up or eliminated from hemoglobin for CO concentrations of 0, 10, 30, 50 283 UCC 084354 4 and 100 ppm for an average (French) women (1.60 continuously varying concentrations of CO in the m high, 55 kg in weight): atmosphere and of levels of activity of the subject. 4 . Level of activity A: Subject seated and at rest. VA - 4.06 mmole/ sec - 5460 ml/min The graphs include curves for each of the three levels of activity for each of the CO concentrations. Level of activity B: Subject walking along at a As an example of the use of these graphs we can speed of4 km/hr. VA -- 8.87 mmole/sec * (11930 ml/ consider (see Fig. 2) the case of an average female min) subject having an initial HbCO level of 0.020 who is Level of activity C: Subject involved in some successively exposed to different CO concentra strenuous physical or sporting activity such as cy- tions as follows: 30 ppm for 1 hr while at rest, 4 cling (at a speed of 15 to 20 km/hr), football or HbCO * 0.028; 50 ppm fori hrwhile walkingalongat swimming, resulting in a doubling in the value of a speed of 4 km/hr, HbCO * 0.049; 0 ppm for 1.5 hr VA compared to the value for activity B: VA * while at rest, HbCO * 0.037; 100 ppm for 1 hr while 17.74 mmole/sec 23860 ml/min at rest. On referring to the appropriate graphs for Two sets of curves are shown on each of these these exposures it will be found that the final HbCO graphs for the different CO concentrations and level for the subject amounts to 0.067. levels of activity, one set originating from a zero * and the other set from a 0.100 HbCO level. Reference can be made to this graph in determin Model of Periodic Conditions ing the approximate fixation-elimination of CO for a subject for a given initial level of HbCO and for Ott and Mage (23) used a simplified point-by point determination of the HbCO level, CO concen- Figuke 2. Graphs of the uptake-elimination of CO for an average woman, with constant concentration and activity and example of use. 284 Environmental Health Perspectives ucc 084355 I 'ns. can nale no is itraest, igat />hr 7'hile 5 for bCO tration being known hour by hour and the physical activity being constant. For a more precise calcula tion, a point-by-point determination is only possible in the case of relatively short periods of time. For longer periods of time and in cases where the CO concentrations and the levels of activity of the subject vary in a periodic manner it is better if we make use of the periodic method of solving the differential equation. We employed this method for solving the differential equation for two different cases, the time base being a quarter of an hour and the most significant period for the calculations being 1 week. The details of these two cases and the results of the calculations were as follows. First Case. A customs officer whose place of work was at the side of the road near the FrenchSwiss frontier lived in the surrounding countryside. The CO concentration at the place of work was measured during the winter of 1978. It was found that the carboxyhemoglobin level varied from 0.002 to 0.033. The level exceeded 0.025 for 3.3% of the total time (corresponding to 14% of the working time) and the average CO concentration (working and rest periods combined) amounted to 3.7 ppm. Second Cate. A saleswoman lived on the outskirts of a large town and worked in a shop located in the main street and in the vicinity of road traffic from Tuesday to Saturday. She travelled to work by bus and spent a part of the weekend in the country. The CO concentrations taken into account were those actually measured at the side-walk of the main street. The CO concentrations in the other locations and the levels of activity taken into account were as estimated. On assuming the sub ject to be a nonsmoker, it was found that the HbCO level oscillated between values of 0.002 and 0.022. The average CO concentration amounted to 4.7 ppm (Fig. 3). In order to have some idea of the effects of pollution due to motor vehicle traffic in comparison with the effects of smoking cigarettes (assuming 10 inhalations of 30 ml at 4% CO concentration per Tipte of Ficl-re 3. Simulation of the periodic variation in HbCO level for a nonsmoking saleswoman and for a subject smoking a total of 103 cigarettes per week. October 1981 285 UCC 084356 cigarette) we also considered the case of the same saleswoman smoking at the rate of one cigarette per hour (103 cigarettes per week). The results of the calculations for this case are also shown on Figure 3. The HbCO level oscillated between values of 0.017 and 0.087, while the average CO concentration due to both the motor vehicle traffic and the smoking amounted to 18.3 ppm. The HbCO level exceeded 0.025 for 97% and 0.040 for 79% of the time. The levels were in general some four times greater for the cigarette smoking than for the nonsmoking subject. The simulation of periodic variations in carboxyhemoglobin levels would appear to be a very useful technique in assessing the effects of carbon monox ide pollution of the atmosphere and of the varia tions in the actual CO concentration. The calculated HbCO levels given in the examples above are quite consistent with the HbCO levels quoted in the literature (24-28). It is necessary, however, to have information on the behavior of the subject on a quarter of an hour to quarter of an hour basis, but there are no problems in making assumptions concerning the bdfiavior of a subject over certain very long periods of time (nighttime and rest periods). It is accordingly possible to determine the effects of any particular variations in CO concentra tions during specific periods of time (e.g., during working hours or when travelling). Thus this tech nique has many potential applications. Half-life of the Carboxyhemoglobin Given a constant CO concentration in the air, the time involved for the HbCO level to change from level y} to level y2 is given by: AI -Tlog ft-H?1--1*? y2 - HEL - kC If the atmosphere is unpolluted (C = 0) then At is the period of time during which the HbCO level decreases from yx to y2. Thus we can determine, for example, the time needed for the HbCO level to fell from 0.200 to 0.010 and from 0.50 to 0.10 for the three standard subjects (male, female and child) and for the previously defined levels of activity A, B and C (Table 3). If we neglect HEL in the equation for the value of At (HEL is always small and is a function of the level of activity of the subject), it then becomes a simple matter to determine the periods of time for the initial HbCO levels to be halved. The times At are then independent of the initial and final HbCO levels, and they depend only on the levels of activity of the subjects and the physiological factors involved. Thus we can determine the half-life (t^ > t log 2) in each case, this being the period of tune for the HbCO level to fall to half of any given value in an unpolluted atmosphere (Table 3). The real half-life is a little lower because we ignore [CO) with regard to [OJ. The lower the value of th, the faster will any HbCO level be reduced to one half in an unpolluted atmosphere, and conversely the faster will the new level be doubled in the case of a constant concentra tion of CO, given that At is proportional to t for such changes in level. The time taken for the HbCO level to double will in fact be proportional to t (or to ti/j) the value ofthis time constant in turn depending essentially on. the value of y2 with respect to the absolute maximum level kC. Thus it would be important to have a good knowledge of half-life. It is interesting to consider what are the population groups (healthy subjects) that are most sensitive to CO pollution in terms of half-life values. The results of the calculations for our sample subjects showed that the standard deviation for the half-life values for either sex amounted to 8%. Thus calculated individual half-life values will deviate appreciable Table 3. "Standard" value*, for 30 year-old men and women and for 6 year*-old children, of the conitant k, the alveolar ventilation rate V., the rate conitant for HbCO formation K, the half-life, the time need for the HbCO level to fall from 0.200 to 0.010 and from O.OsO to 0.010 in unpolluted air, for the leveli of phydeal activity A (at reit-dtting), B (walking 4 km/hour) and C (itrenuoui or (porting activity). Men, k - 0.00183/ppm Activity level A Activity level B Activity level C Women, k - 0.00202/ppmChildren, k - 0.00223 ppm Activity level A Activity level B Activity level C Activity level A Activity level B Activitylevel C V., mmole/aec k x Hr7. fraetion/ppm/iee Half-life v^, min t (0.20-*0/01), min t (0.06-- 0.01), min 5.17 2203.95 1030 575 10.88 1.61 131 587 321 21.77 2.35 90 402 220 4.06 1.11 210 973 543 8.87 1.91 122 546 299 17.74 2.75 85 379 207 3.23 1.69 152 706 494 5.12 2.15 120 535 293 10.25 2.81 92 410 224 286 Environmental Health Perspectives UCC 084357 n At is > level or uie .diild) ity A, value of the mes a ne for wes At ^bCO sis of actors <T*" fume value I real [CO] II any ihited - new . itrat for IbCO (or to nding o the ation veto -suits owed alues ated iable eolar 00 to ndC ity C i5 ives HbCO half-life. from the average and the actual deviation will be even greater in the case of the actual population. The half-life increases with age, the increase being rapid up to the age of 20 years, after which the increase with age slows down (Fig. 4). Age has a greater effect on the half-life than does the sex of the subject. Thus it may be seen from Figure 4 that the half-life for subjects at rest doubles as the age increases from 2 to 70 years, whereas the difference in half-life between male and female subjects does not exceed 6%. The half-life decreases with physical activity, the effect here being about the same for both male and female subjects but less pronounced for children where the muscular power expended is a small proportion of the total power expended. The degree of variation in the half-life with age or the sex of the subject decreases as the level of activity increases. We also studied the effect of the height on the half-life in the case of healthy subjects whose weight was an optimum with respect to height according to the relationship: m - 75H + 0.25F -67.5 for a male subject, the weight being assumed to be 5 to 10% less for a female (29). Height had only a slight effect on half-life in the case of female subjects involved in a low level of activity, when was found to increase with height. October 1981 C nclusi ns The uptake-elimination of carbon monoxide by hemoglobin, i.e., the variation in the level of carboxyhemoglobin (HbCO) of a subject, can be defined by a fairly complex differential equation which involves a number of physiological parame ters. We verified the validity of this equation on a sample of 73 subjects made up of persons of both sexes, and for different levels of physical activity and low carbon monoxide levels. As a result of our tests on these sample subjects we established the validity of two methods of simulating the uptakeelimination of carbon monoxide which take account of the nonpathologic variations for individual sub jects. Thus the HbCO levels at each instant of a given period of time (day, week, etc.) can be predicted with reference to initial level and on taking account of the applicable conditions as a result of an analytical method of solving the differ ential equation (actual calculations in each case or use of an existing Bet of graphs based on previous calculations). This can be done better by a mathematically based simulation of the periodic variations in HbCO levels without reference' to initial level. The HbCO levels depend first of all on the CO concentration in the atmosphere and then on the level of physical activity, the age (the half-life increasing with age) and finally on the sex (the half-life is a little shorter for the female sex) of the subject. It would appear that the HbCO levels predicted by the periodic simulation are a function of the HbCO half-life (as determined by a fairly simple calculation) but this matter should be the subject of a more systematic statistically based study. Although we did not study the matter in any detail, it appears that subjects suffering from certain ailments and in particular from respiratory deficiencies for whom certain physiological vari ables deviate appreciable from the normal values can have carboxyhemoglobin levels that are signi ficantly different from those encountered in the course of this investigation. We need more detailed information for such cases. It is difficult to reach any conclusion with regard to the short-term and long-term effects of the low carboxyhemoglobin levels that have been observed in a nonsmoking population. With the exception of people who are exposed to the atmospheric pollu tion due to road vehicle traffic, in particular be cause of their occupation, it appears however that there are no effects on either the alertness or sensory perception of pedestrians or car passengers making journeys of short duration in the city of Lyon. For the car passengers in our sample, who 287 UCC 084358 1 were the subjects exposed to the highest level of tion. Poll. Atm. 72:313-319 (1976). atmospheric pollution, the HbCO level amounted to 5. World Health Organization. Environmental Health Criteria. 4 0.027, on the average, at the end of their test journey. The levels of atmospheric pollution nor 13. Carbon monoxide, WHO, Geneva, 1979. 6. Joumard R., and Vidon R. Disperaon dans une rue en U. 3: rtsultata statistiques des teneurs et trafics. IRT-CERNE mally encountered can however have effects on report, Bron, France, 1980. advent of arteriosclerotic lesions. Thus such levels 7. Aronow, W. S., and Isbell, M. W. Carbon monoxide effect are sufficient to result in the occurrence or an on exercise induced angina pectoris. Ann. lnt. Med., 79: increase in the seriousness of acute ischaemic 392-395 (1973). 8. Coburn, R. F,, Forster, R. E. and Kane P. B. Considera incidents in subjects who already suffer from artery tions of the physiological variables that determine the blood * deficiencies. carboxyhemoglobin concentration in man. J. Clin. Invest. Apart from being useful in establishing carbon monoxide atmospheric pollution indices, the results of this study may also contribute to the establish ment of the standards for acceptable carbon monox 44: 1899-1910 (1965). 9. Giammona, S. T. J., and Daly, W. J. Pulmonary diffusing capacity in normal children ages 4 to 13. Am. J. Dis. Child. 110:144-151 (1965). 10. Osgood E. E. Pediatrics 15: 000 (1955). ide concentrations on the basis of the following 11. Galetti, P. M. Les dchanges respiratoires pendant approach: establish the carboxyhemoglobin levels that must not be exceeded for both healthy and pathological subjects; determine the CO concentra tions that are in agreement with these carboxy l'exerdce musculaire. (Respiratory exchanges during muscular effort). Helv. Physiol. Acta 17: 34-61 (1959). 12. Schemer, J. Phyaiologie du Travail (Physiology of work), Vol. 1. Masson, Paris, 1967. 13. Pandolf, K. B., Givoni, B., and Goldman, R. F. Predicting hemoglobin levels by simulating the cyclic varia tions as well as employing other techniques. In making this approach, it must be understood that there is no such thing as a population of energy expenditure with loads while standing or walking very slowly. J. Appl. Physiol., 43: 577-581 (1977). 14. Gehlaen, G. M., and Dill D. B. Comparative performance of men and women in grade walking. Human Biol. 49:381-388 (1977). average subjects, but the physiological characteris 15. Keele and Neil. Sampson Wright's Applied Physiology, 12th tics and hence the sensitivity to the effects of carbon monoxide vary in accordance with a Gaussian distribution about the mean values that we have Ed., Oxford University Press, 1971. 16. Apfelbaum, M., Bostsarron, J., and Duret F. Physiologic. Vol. 2, Vigot Frtres, Paris, 1972. 17. Chovin, P,, and Richalet, J. Etude theorique de la considered here for healthy subjects. There is also rinStique de la fixation du monoxyde de carbone sur the fact that there are pathological variations of physiological data for a significant proportion of the population. More generally, the results of the study can be of l'himoglobine du sang. (Theoretical study of the kinet ics of the fixation of carbon monoxide on the haemoglobin of the blood.) Ann. Fals. Exp. Chim., 710: 1TT-194 (1973). 18. Hanks, T. G., and Farquhar, R. D. Final report PH use whenever it appears to be necessary to give 22-68-31, National Air Control Administration. Durham, proper attention to certain periods of time that are being studied out of their normal context (e.g., in the case of industrial medicine studies periods of N.C.. 1969. 19. Peterson, J. ., and Steward. R. D. Predicting the carboxyhemoglobin levels resulting from carbon monox ide exposures. Report CRC APRAC CAPM-368 time, other than the concerned with work high MC0W-ENVM-C0-731, 1973. carbon monoxide concentration considered periods, could affect carboxyhemoglobin levels), first for low pollution, because the precision of certain methods is a good as low is HbCO level. 20. Goursat, E. Coura d'Analyse, Vol. 2. Gauthiers. Villan, Paris, 1925. 21. Maurin M. Impact du monoxyde de carbone sur les individus. IRT-CERNE report, Bron. France. 1978. 22. Boudene C., Godin, J., and Roussel, A. Methods de dosage This study has been the subject of an internal report (SO). de l'oxyde de carbone dans le sang sans extraction separie prSalable par absorption selective dans l'imrarouge. Arch. Malad. Prof. Mid. Trav. Sec. Soc. (Paris) 34:449-456 (1973). 23. Ott, W. R., and Mage D. T. Interpreting urban carbon REFERENCES 1. Cole, P. V. Comparative effects of atmospheric pollution monoxide concentrations by means of a computerized blood COHb model. J. Air Poll. Control Assoc. 28: 11-916 (1978). 24. Grisler, R,, Gobbi, A,, Giavardi, C., Gaimmi. G., Soverini, and cigarette smoking on carboxyhaemoglobin levels in R., and Botta, A. Valori di HbCO rilevati in 1<*K) abitanti di man. Nature 255: 699-701 (1975). Milano non esposti all'assorbimento professional di CO. 2. Burgess, W. M. A., Diberardinis, L., and Speizer F. E. Med. Lav. 66: 34-47 (1975). Health effects of exposure to automobile exhaust. 5. Expo 25. Kahn, A., Rutledge, R. B., Davis, G. L.. Altes, J. A,, sure of toll booth operators to automobile exhaust. Am. Ind. Ganter, G. E., Thornton, C. A., and Wallace, N. D. Hyg. Assoc. J. 38: 184-191 (1977). Carboxyhemoglobin sources in the metropolitan St. Louis 3. Kohl, U., and Lob, M. Risque* d'oxycarbonisme chronique Population. Arch. Environ. Health, 29:127-135 (1974). dans les garages. Schweiz Med- Wochenschr. 105: 50-56 26. Seppanen, A., Kakkinen, V., and Tenkku. M. Effect of (1975). gradually increasing carboxyhaemoglobin saturation on vi 4. Delsey, J., Joumard, R., and Vidon R. Pollution par le sual perception and psychomotor performance of smoking monoxyde de carbone a 1'interieur d'une voiture en drcula- and non-smoking subjects. Ann. Clin. Res. 9:314-319 (1977). 288 Environmental Health Perspectives UCC 084359 T k'i. RNE < ffect . TSt lera>lood vest edng hild. dant iring ?rk), 4 :ting Jdng eeof 12th 4 * la sur :netobin -LQ4 .am, the nox3-68 lea *8* Arte rch. 73). bon lood 78L rini, tidi CO. A., D. ouia t of i vi-ring m 27. Torbati, I. D., Har-Kedar, I., and Ben-David, A. Carboxyhaemoglobin levels in blood donors in relation to cigarette smoking and to occupational exposure to carbon monoxide. Israel J. Med. Sci., 10: 241-244 (1974). 28. Billiet, L., Baisier, N., and Naedts, J. P. Effet de la taille, du sexe et de l'ige sur la capacite de diffusion pulmonaire de l'adulte normal. (Effects of the height, sex and age on the pulmonary diffusion capacity of a normal adult.) J. Physiol. (Paris), 55:199 (1963). 29. Lecoq R. Manuel d'Analyses Medicates et de Biolope Clinique. (Manual of Medical and Clinical Biology Analyses.) Beaancon, France, 1967. 30. Joumard, R., Chiron, M., and Vidon, R. La fixation du monoxyde de earbone sur ITiCmoglobine et sea effets sur lTiomme. (Uptake of carbon monoxide on haemoglobin and the effects on man.) IRT-CERNE report, Bron, France, 1979. October 1981 289 UCC 084360 Environmental Health Perspectives Vol. hi, pp. t91-309, 1981 Noise and Stress: A Comprehensive Approach by Jack C. Westman* and James R. Walterst The AindamenUl purpoeei of hearing are to alert and to warn. As a mult eound directly evoke* emotion* and action*. The processing of sound by the brain is outlined to provide a biological and psychological basis for understanding the way in which sound can become a human stressor. The auditory orienting response, startle reflex and defensive response translate sound stimuli into action and sometimes into stress induced bodily changes through "fight or flight" neural mechanisms. The literature on the health and mental health effects of noise then is reviewed in the context of an integrated model that offer* a holistic approach to noise research and public policy formulation. The thesis of this paper is that research upon, and efforts to prevent or minimize the harmful effects of noise have suffered from the lack of a full appreciation of the ways in which humans process and react to sound. 4S Introduction The damaging effects of noise usually are re garded as limited to the structures of the ear through impairing one's ability to hear sounds such as speech and music. Often unappreciated is the fact that noise has more pervasive physiological effects (J, 2). In the course of evolution, certain fishes devel oped organs of hearing to orient themselves in space. In amphibians, vision provided the ability to locate prey but was not sufficient in terrestial environments to warn of other predators. Hearing accordingly developed as an organ for perceiving and responding to danger (J). Hearing also has played a role in sexual mating behaviors in mam mals and even insects. These primitive functions exist in humans as well. From the outset sound has evoked emotions and actions through the inner ear's direct connections to "fight or flight" neural mechanisms via the auto nomic nervous system. Because of this defensive Department of Psychiatry, University of Wisconsin, Clinical Science Center, 600 Highland Avenue, Madison, Wisconsin 38792. Office of Noise Abatement, Environmental Protection Agen cy, Washington, D. C. 20460. October 1981 purpose, hearing also cannot be turned off, and sound registers in the brain even during sleep. Only later in primate evolution did the auditory system include higher cerebral centers permitting the appearance of spoken language. The current usage of the terms "nonauditory" or "extraauditory" is unfortunate. This distinction designates as nonauditory the auditory system's original, primitive influence upon wakefulness and body activity. The auditory system and physiologi cal responses to sound are inseparably connected. Therefore, all of the effects of noise on the body mediated by the ears are "auditory" effects. More precisely, the effects of sound on the body through vibration of structures other than those of the auditory system are "non-auditory" or "extraauditory." Another basic consideration in understanding the functioning of the auditory system merits empha sis. The human auditory system was designed to process the frequencies and intensities relevant to survival in the sound environments of nature. The evolutionary process has not allowed humans enough time to adapt hearing to sounds generated by loud modern noise sources. This means that the auditory apparatus is not prepared to cope with commonly encountered urban and industrial noise. Conse quently, we find ourselves exposed to sound envi- 291 UCC 084361 ronments that overload the auditory system. An Neuroanatomy of the analogous situation would occur in the visual sys tem if we were forced to look at the sun and thereby Auditory System 1 damage the retina. An appreciation of the structural basis for physio The fundamental relationships of hearing to emo logical and behavioral responses to sound can be tion and action and the auditory system's vulnera gained fropi knowledge of the neuroanatomy of the bility to modem sounds are not appreciated auditory system (Fig. 1). The auditory pathways of sufficiently by the public. Research also has suf the central nervous system consist of direct path fered from a lack of breadth and depth in conception ways from the inner ear to the auditory cortex and t resulting in contradictory findings. For example, indirect pathways to the reticular activating sys laboratory studies of healthy young people have tem which connect to the limbic system and other concluded that noise has no harmful psychophysio- parts of the brain, the autonomic nervous system logical effects on humans. At the other extreme are and the neuroendocrine system U). reports that jet aircraft noise increases psychiatric The direct auditory connections consist of ascend hospital admissions. ing pathways which carry impulses excited by We lack a comprehensive model to ensure that sounds from the receptor cells in the organ of Corti t research on sound includes the critical variables to the auditory centers in the cerebral cortex. that make it a significant source of human stress. These pathways end in the temporal lobe where the Much of the research cited in this paper suffers sum of incoming impulses are consciously perceived from methodological inadequacies because noise is and interpreted. The ascending auditory pathways but one of a number of variables affecting complex travel along the auditory nerve via the cochlear human beings. Before delineating the system levels nucleus, superior olivary complex, inferior colliculus, involved in bodily responses to sound, we first will nuclei of the lateral lemniscus and geniculate body outline the neuroanatomy and physiology of the to a number of areas in the auditory cortex which in central processing metfianism of sound. turn are connected to other cortical areas that Figure 1. Processing of sound by the brain. 292 Environmental Health Perspectives UCC 084362 > be the *s of athand systher em end- by 'orti tex. the */ed ays lear ilus, ody hin 'hat ves receive inputs from the other sensory organs as well. There also are descending pathways from the temporal cerebral cortex to the dorsal cochlear nucleus via the inferior colliculus and to the organ of Corti via the medial geniculate body, inferior colliculus and lateral lemniscus through the olivo cochlear bundle. These descending pathways have inhibitory and, to a minor degree, excitatory influences. In addition to these direct pathways to and from cerebral cortex, there are a variety of indirect connections from the inner ear to the brain centers that control basic physiological, emotional and be havioral responses of the body. Nerve fibers branch out from the various synaptic junctions along the direct auditory pathways to motor cell nuclei subserving reflexes within the brainstem and to the reticular activating system in the midbrain. Impulses reaching the reticular activating sys tem excite still other impulses that spread to higher cerebral centers that control alertness, cognition and motor performance. At the same time the reticular activating system conveys impulses to hypothalamic autonomic nervous system centers which are linked to the sympathetic-adrenal neuro endocrine system and thereby regulate the secre tion of the catecholamines, adrenaline (epinephrine) and noradrenaline (norepinephrine). Impulses con veyed by the reticular activating system also are transmitted to the pituitary-adrenal neuroendocrine system which secretes corticosteroids (cortisol). The catecholamines play an important role in mobi lizing immediate adaptive resources of the body, and the corticosteroids provide for more enduring adaptation to prolonged stress (5). Thus, the audi tory apparatus is connected to the entire central nervous system and the neuroendocrine system as well. Physiology of Sound In conjunction with the other special senses, the auditory system serves to maintain the arousal of the brain projections to the temporal cortex and the reticular activating system via the limbic system and the hypothalamus. In this way cognitive pro cesses and emotions interplay with sound stimuli in influencing the state of consciousness. The cerebral cortex requires a certain level of arousal to make optimum use of incoming sensory information upon which efficient behavior and phys iological functioning depend (6). Neither underarousal nor overarousal is conducive to effective perfor mance of physiological functioning (7). Sound can improve performance on tasks which are inherently underarousing, repetitive, and monotonous. Con versely, sound can impair performance on tasks demanding concentration and complicated responses (8). Sound contributes to the homeostasis of the central nervous system and consequently influences the physiological homeostasis of the body through the autonomic and neuroendocrine centers of the hypothalamus. The arousal level of the central nervous system depends upon the intensity, complexity, variability, predictability and meaning of sound stimuli. The auditory system responds most to changes in the timing of sound stimuli. Therefore, a transient increase in the firing of auditory neurons may be produced by the termination of a sound as well as by its inception. Some neurons in the auditory system respond to stimulus onset with a high rate of impulse discharge, quickly cease firing, remain silent while the stimulus is continued, and dis charge a second burst of impulses when the stimu lus stops. However, in a much larger number of neurons, the rate of firing declines to a lower level of activity shortly after the initial high frequency discharge and then is tonically maintained during long periods of continued stimulation. These sound stimulus-induced alterations persist after the stim ulation ceases (9). The direct effects of certain sounds on emotions and attitudes is illustrated by the fact that chalk scraping on a blackboard can cause chill sensations in a listener. Musical rhythm, tempo and melody can evoke moods ranging from calmness to excita tion or elation. Music also can promote positive attitudes toward work. The further influence of higher cerebral cortical centers on the emotional reaction to sound stimuli is illustrated by a study of sound in hospitals in which one source of annoyance was staff conversations in the halls, not because of undue loudness but because of the discussion of patients (10). Sound stimuli also influence the other sensory systems. For example, sound input overload can induce visual changes in color perception, cause nystagmus and vertigo and even act as an analgesic (11). In summary, sound stimuli play a vital role in maintaining arousal of the brain and thereby influence the basic physiological functioning of the body. Sound may influence the body after cessation of the stimulus through reverberating neural circuits within lower and higher brain centers. In this way sound can produce physiological reactions that develop a momentum of their own independent of the original stimulus. October 1981 293 UCC 084363 Fundamental Auditory Responses Orienting Response (Novelty Reflex) The basic behavioral response to all sound stimuli is the orientation reflex, which involves ascending and descending auditory cortical pathways and is reflected by an arousal pattern in the electroen cephalogram, The response orients the head and eyes toward the source of a sound in order to ready the organism to receive and respond to the sound stimulus situation. There is an associated decrease in auditory threshold and increased attention to the sound stimulus. The orienting response occurs to sounds of low or moderate intensity and significance. The person's cognitive appraisal of the sound stimulus deter mines the intensity and duration of the orienting response. It extinguishes, or habituates, after var ying repetitions so that the individual can accom modate to familiar and insignificant sounds with relative ease and concentrate on a preferred activi ty. If an appreciable amount of time passes be tween repetitions of specific sound, habituation disappears and repetition of the same sound again evokes an orientation response. Habituation usu ally does not occur if attention to a sound is volun tarily sustained or if a sound has special significance, either positive or negative. Sounds of close to hear ing threshold intensity do not easily habituate, probably because of the auditory system's difficulty in assessing their significance. Even after behavioral habituation has occurred, sound stimuli continue to activate both cortical and subcortical areas of the brain (9). This is in part because excitation transmitted by the reticular ac tivating system continues to arrive in the cerebral cortex after that transmission directly ceases. When the decision is made not to orient to a sound, descending cortical excitation actively restrains, but does not eliminate, the reticular activating sys tem's excitation from spreading to higher areas of the brain. After the orienting response to sound habituates, there may be no change or an increase in the amplitude of the electrical responses evoked in the cerebral cortex and the medial geniculate body. The reticular activating system and the struc tures that it influences continue to be affected by sound even after behavioral habituation has occurred. This is not surprising because the organism's sur vival would be threatened by decreased altertness to danger if unattended stimuli were excluded from cognitive appraisal. 294 Startle Reflex The second basic auditory response is the startle reflex which is evoked by sounds of sudden, in tense, or frightening significance. The reflex has a series of components. First, the middle ear muscle reflexes via the superior olive to the tensor tympani through the fifth cranial nerve and to the stapedius muscle through the seventh cranial nerve provide a small degree of protection against sounds of ex tremely high intensity. The auropalpebral reflex via the superior olive and the sixth cranial nerve produces eye blinking. There also is opening of the mouth and flexion of the neck via the seventh and eleventh cranial nerves. More generally, there is flexion of most muscle groups in a "freezing" pos ture with raising of the shoulders, abduction of the arms, flexion of the fingers, contraction of the ab domen, and bending of the knees mediated by the ascending auditory and descending cerebral cortical motor pathways. The typical reflex is completed in less than one second. Those components of the startle reflex that reflect cerebral cortex activity are subject to habituation or enhancement, however, those involving lower centers in the brainstem are not. The startle reflex accordingly can be decreased by anticipation, in creased by background sound levels and exaggerated by emotional states such as fear. The Defensive Response ("N" Response) Although usually an extension of the orienting or startle responses, the defensive response merits separate consideration because it can occur inde pendently of them and does not require sounds of high intensity. This response is produced by sounds of sufficient intensity, significance or duration to be perceived as threatening and to mobilize a "fight or flight" reaction. The response includes alerting of the cerebral cortex, emotional arousal, and prepa ration of the body for action (J2). Sounds in the range of 70 to 120 dB can produce the defensive response which appears first in the form of skeletal muscle tension that quickly reaches its peak and decays within a few seconds. Next there is a decrease in skin electrogalvanic resis tance which changes more gradually than the skele tal muscle tension. Pupillary dilation occurs as well. A variety of circulatory responses are next in order first an acceleration of pulse rate and decrease in pulse pressure, then a constriction of the finger and dilation of the chin blood vessels, followed by a slowing of pulse rate and an increase in pulse pres sure. Finally in the series comes a shift to slower, Environmental Health Perspectives UCC 084364 m -- i*.,as a uscle ipani adius idea f exeflex ^rve fthe and re is posf the abTthe tical ;d in fleet ition . ver 'flex . inated g or rits ldes of ids )be t or % of "pa- uce ..he hes ext sisaleell -an ; in and va eser. et deeper breathing. The defensive response also in cludes a reduction in salivary and gastric secretions and slowing of digestive processes C4). The defensive response largely involves the sym pathetic nervous system but has some parasympa thetic aspects. This response is not limited to a single organ system or structural division of the nervous system. It occurs independent of emotional response on the part of the subject. It is altered by sound intensity and band width in a dose-dependent fashion. It does not completely habituate (IS), al though under laboratory experimental conditions, substantial apparent physiological habituation has been reported (14). It also may be elicited by low levels of sound with special significance (15). Under actual working conditions, the physiological effects of the defensive response were found in sawyers exposed to bandsaw noise (16). Another laboratory study noted a decrease in blood eosinophile level reflecting a stress response after 25 min exposure to 85 dB level noise (17). The defensive response can become the stress that leads to the General Adaptation Syndrome that will be described more fiilly later with its alarm, resistance, and exhaustion stages if the sound stressor is of sufficient duration, quantity, and qual ity (IS). When this takes place the hypothalamicpituitary-adrenal axis is mobilized with resulting increase in adrenal cortisol and epinephrine output. During prolonged exposure to intense sounds, these endocrine effects may produce gastroduodenal ul cers and renal changes in laboratory animals (1). Next we will enumerate the critical variables that determine whether or not sound stimuli be come stressors that produce human stress. Sound as a Stressor Modem urbanization, crowding, the mass media, information technology, conditions of work and noise are overloading the human sensory environment (19). Of these stimuli our interest is in sound, particularly noise, although sound with meaning, such as speech, also can contribute to overloading an individual's processing capabilities. The progres sive increase in noise from industrial, traffic and home sources, both machine and human generated, has reached offensive proportions in the United States (20, 21). Noise essentially is unwanted sound. As such, subjectively experienced noise is any sound that produces annoyance or communication or task per formance interference. The same sound stimulus may be perceived subjectively as noise by some and not by others. For this reason it is useful to define objectively experienced noise as sound that pro October 1981 duces harmful bodily effects, which may or may not be subjectively perceived. This point is important because noise can be subjectively or objectively stressful, or both. In information processing terms, noise is sound that overloads the central nervous system's prothis state can be detected by changes in the electro encephalogram (27). The reception of a stimulus is influenced by two kinds of cognitive state charac teristics, current transient influences and enduring qualities of the individual. The first characteristics are transient influences that are more evident and easily measured than the second type. They include level of mental arousal, from sleep through alertness to anxiety; the con text of sensory stimuli arriving through the other special senses; the motor context which includes ongoing task performance, the activities of the in dividual; the meaning of the stimulus evoked by associations from cerebral cortical memory areas; the degree of perceived control of the stimulus, whether one is able to control the situation is help less or expects failures (25) and social values and attitudes toward the stimulus sources. The level of mental arousal is influenced whether or not a sound stimulus is consciously perceived as a stressor. During the stage of early sleep, for exam ple, sound can produce orienting and defensive responses and alter the quality of sleep without causing awakening. At the other extreme, an anx ious individual can experience heightened sensitiv ity to a sound stimulus. For example, a study of college age males rated on an anxiety scale dis closed that for subjects rated high on anxiety, household noise levels were stressors as manifested by impaired task performance and subjective frus tration (28). The interaction of sound stimuli with other sen sory stimuli may be significant. For example, re lated visual stimuli enhance the effect of sound. Clinically, sound can have an analgesic effect when certain intensities and frequencies occur in the pres ence of pain as is known in the practice of dentistry. The ongoing motor activity of an individual influences cognitive state with higher levels of arousal by sound stimuli occurring while complex tasks are being performed and lower levels of arousal occur ring when routine, monotonous activities are taking place. For obvious reasons related to survival at a prim itive level the meaning of sound is one of the most important factors that determines an organism's response. Threatening sounds of any kind portend potential danger, however, certain sounds acquire particular significance because of their symbolic meaning to the individual. Conversely, familiar, 295 UCC 084365 1 I repetitive sounds of moderate intensity cease to animals, for example, it is used as a stressor to attract attention. Meaning connoting potential dan* produce lesions in the renal, reproductive and car t c 4 ger, then is related to unfamiliarity, rapid changes diovascular systems (23). i< in intensity, or learned associations. For example, a Another illustration of the use of sound is in study of evoked auditory potentials in the brain stress studies such as the one by Cantrell, who c demonstrated that quickly changing acoustical events exposed healthy young male volunteers to intermit ii produce prominent cerebral excitation. The study tent noise for several weeks (24). He found significant also showed that sounds with symbolic meaning increases in plasma cortisol and blood cholesterol P ft were perceived as more annoying than meaningless levels in addition to associated annoyance and sleep c< 4 sounds of the same intensity and also produced disturbance effects during prolonged exposure to re larger evoked cerebral potentials (29), bursts of 85 to 90 decibel noise. if Of particular importance is the fact that habitua We can use current approaches in stress research tt tion does not occur to repeated novel laboratory to facilitate our understanding of sound as a stressor tc stimuli that imply conflict or are coupled with an (22,25). In stress research the environmental condi instruction to pay attention to that stimulus. Even tions and the intervening bodily structures and I* in i covert associations with sound stimuli, such as a processes that determine when and in what forms subject's attitude toward the experimenter, may stress reactions occur are taken into account (26). st Pi decrease habituation (8). In addition, the symbolic The work of Rahe, although encompassing life Wi meaning of a sound stimulus can evoke irrational change in addition to sensory stressors, is particu re responses, adding unconscious determinants of mean larly useful in identifying specific variables that ing (SO, SI). should be taken into account in research on the pe In addition to the meaning of the sound stimulus, human effects of noise. Rahe developed a life stress re i a sound's predictability is an important determi and illness model which identifies the key steps to nant of response. In one s^qdy, unpredictable noise along a pathway extending from a person's expo je< resulted in lower tolerance for frustration and greater sure to a stressor to the eventual reporting of an th. impairment of performance efficiency than predict illness (25). Rahe's model (Fig. 2) utilizes the anal th able noise (32). Furthermore, those investigators ogy of a series of optical lenses and filters in which ex found that an individual's ability to control the noise stressors are depicted by a series of "light rays" of fee source, and even the belief that one could, reduced different stimulus characteristics. Ra the adverse impact of unpredictable noise (8). They The influence of a person's perceptual state in ex; postulated that the deleterious effects of noise were altering the experience of a stressor is represented a function of unpredictability and the belief that one by a "polarizing filter" shown in step 1. Possible cessing capacity because it is too great in quantity, sensitization, or desensitization, of a person to a Ct appears too rapidly or is dissonant in meaning or stressor is indicated by changes in the "light rays" pattern. Noise is a commonly used standardized stressor in laboratory testing designed to evaluate human responses to stress (5, 22). In laboratory as they pass through the filter. The psychological defense mechanisms which appear to be capable of "diffracting away" a stressoFs impact are depicted che firs cog thi ele lus cha SOUND STIMULI enc 7 tha sec froi tex spe ong indi ass< REGULATION DYSFUNCTION. ILLNESS BEHAVIOR CMSEASE ILLNESS MEASUREMENT the whe help and Figure 2. Rahe model of life stress end illness (tSi. T 296 Environmental Health Perspectives Octc UCC 084366 i m by the negative lens in step 2. Stimuli not so diffracted pass on to produce a variety of physiolog or not a sound stimulus is consciously perceived as a Btressor. During the stage of early sleep, for ical reactions represented by the "black box" in example, sound can produce orienting and defen in Step 3. The wavy lines emerging from the black box sive responses and alter the quality of sleep without vho cease to represent specific stressors and begin to causing awakening. At the other extreme, an nit- indicate various psychophysiological responses to anxious individual can experience heightened ant perceived and "undefended" stressors. Next a "color sensitivity to a sound stimulus. For example, a .*rol filter" shown in step 4 depicts how a person may study of college age males rated on an anxiety scale eep cope with or absorb certain of these physiological disclosed that for subjects rated high on anxiety, to reactions. Prolonged psychophysiological activations, household noise levels were stressors as manifested if unabsorbed, lead to organ dysfunction and even by impaired task performance and subjective frus rch tually to psychological and bodily symptoms. Symp tration (28). sor tomatic individuals may then seek medical care. A The interaction of sound stimuli with other sen ldi- person's "focusing" of attention on symptoms is sory stimuli may be significant. For example, ind indicated by the illness behavior "positive lens" in related visual stimuli enhance the effect of sound. ms step 5. If these symptoms are reported to health Clinically, sound can have an analgesic effect when personnel, the person receives a medical diagnosis certain intensities and frequencies occur in the which then can be used as a measure of illness as presence of pain as is known in the practice of cu- represented in Step 6. dentistry. hat The value of Rahe's model is that it incorporates The ongoing motor activity of an individual the pertinent system levels in conceptualizing human influences cognitive state with higher levels of ess responses to stressors, ranging from organ system arousal by sound stimuli occurring while complex eps to societal levels. It permits inclusion of both sub tasks are being performed and lower levels of JO- jective and objective data as well. Furthermore, arousal occurring when routine, monotonous activi an the model reflects clinical ^realities by recognizing ties are taking place. iai- the social factors that influence whether or not For obvious reasons related to survival at a ich experienced dysfunctions become labeled as mani primitive level the meaning of sound is one of the ' of festations of illness. For these reasons, we will use most important factors that determines an organ Rahe's model to elucidate key variables in the human ism's response. Threatening sounds of any kind experience of sound as a stressor. portend potential danger, however, certain sounds acquire particular significance because of their ble )a Cognitive State symbolic meaning to the individual. Conversely, familiar, repetitive sounds of moderate intensity vs" Bearing in mind the preceding discussion of the cease to attract attention. Meaning connoting po cal characteristics of sound experienced as noise, the tential danger, then is related to unfamiliarity, of first step in processing a sound stimulus is the rapid changes in intensity, or learned associations. ed cognitive state of the individual. Some variations in For example, a study of evoked auditory potentials this state can be detected by changes in the in the brain demonstrated that quickly changing electroencephalogram (27). The reception of a stimu acoustical events produce prominent cerebral exci lus is influenced by two kinds of cognitive state tation. The study also showed that sounds with characteristics, current transient influences and symbolic meaning were perceived as more annoy enduring qualities of the individual. ing than meaningless sounds of the same intensity The first characteristics are transient influences and also produced larger evoked cerebral potentials that are more evident and easily measured than the (29). second type. They include level of mental arousal, Of particular importance is the fact that habitua from sleep through alertness to anxiety; the con tion does not occur to repeated novel laboratory text of sensory stimuli arriving through the other stimuli that imply conflict or are coupled with an special senses; the motor context which includes instruction to pay attention to that stimulus. Even ongoing task performance, the activities of the covert associations with sound stimuli, such as a individual; the meaning of the stimulus evoked by subject's attitude toward the experimenter, may associations from cerebral cortical memory areas; decrease habituation (8). In addition, the symbolic the degree of perceived control of the stimulus, meaning of a sound stimulus can evoke irrational whether one is able to control the situation is responses, adding unconscious determinants of mean helpless or expects failures (25) and social values ing (30, 31). and attitudes toward the stimulus sources. In addition to the meaning of the sound stimulus, The level of mental arousal is influenced whether a sound's predictability is an important determi- October 1981 297 UCC 084367 I nant of response. In one study, unpredictable noise resulted in lower tolerance for frustration and greater impairment of performance efficiency than predictable noise (32). Furthermore, those investi gators found that an individual's ability to control the noise source, and even the belief that one could, reduced the adverse impact of unpredictable noise (8). They postulated that the deleterious effects of noise were a function of unpredictability and the belief that one had little or no control over the noise source. A laboratory study of rhesus monkeys exposed to noise disclosed that plasma cortisol levels were significantly higher in animals with no control over the noise source than in those with control (33). Similar findings resulted from an experimental study of humans performing mental arithmetic problems under noise exposure (34). The importance of attitude toward the noise source is illustrated by another study in which a positive or negative attitude toward all aspects of one's com munity consistently influenced the reporting of per ceived annoyance by noise positively or negatively (35). In the same vein, a Swedish study disclosed that propaganda promoting the importance of the air force diminished the reported annoyance levels in a community exposed to military aircraft noise (36). The second kind of variables that influence the cognitive state of an individual are enduring back ground characteristics in the form of individual differences in temperament and cognitive styles, organic disease processes and mental illness. Individual variations have been demonstrated in the ways that sensory stimuli are processed. Some individuals reduce and some augment the intensity of stimuli, leading to low or high sensitivity to a particular stimulus (19). Sensitivity to noise also is correlated with empathic, creative, intellectually oriented personality traits, confirming Schopenhauer's comment that "noise is a torture to people, of great intellect" (37). Extraverted children may have a higher level of noise tolerance than introverted children (38). Moreover, individuals who express criticism tend to report annoyance by noise (55). Further evidence of individual differences in sensi tivity to noise is reflected by the finding that some people thrive on noise which tends to synchronize their electroencephalograms while most people show electroencephalographic desynchronization (39, 40), At the other extreme, it is likely that 4 to 6 % of the normal population is "noise sensitive," in the sense that they do not adapt to noise at all (8). For all of these types of individuals, noise has implications detrimental to their mental health. As an illustration of other background illness characteristics, one study showed that cardiac in- farction and schizophrenic patients showed greater stress responses to noise as measured by cortisol and urinary catecholamine levels than did normal subjects (41). Similarly, persons with cerebral vas cular disease were found to be more susceptible to the detrimental effects of noise than normal sub jects (42). Another unique group of patients harmed by sound are those susceptible to audiogenic sei zures. Some are affected by sounds that produce the startle response and others by. sounds such as music (43). The role of psychiatric status in sensitivity to sound was suggested in a study in w hich normal subjects and patients with specific phobias showed habituation of physiological responses to noise while hysterical patients did not. Moreover, patients with diffuse phobias, anxiety neuroses and agitated de pressions all habituated more slowly than normals (44). In a general sense, another survey found that psychiatric patients were more annoyed by noise than normal subjects (45). Defense Mechanisms The next cluster of variables that influence an individual's response to sound stressors are inter nal defense mechanisms noted in step 2 of Rahe's model. In contrast with coping techniques which are directed toward changing the stimulus envi ronment, the defense mechanisms are devoted to maintaining homeostasis or internal equilibria, within the person. The defense mechanisms operate automatically and unconsciously. The most primitive is the acous tic reflect which offers a small degree of protection from high intensity sounds. Another example of a physiological defense is cerebral cortical inhibition such as was demonstrated in a study of laboratory animals exposed to extreme sound which ultimately produced convulsive seizures and lethal cerebral hemorrhages. This study found that a seizure pro ducing epileptogenic focus of excitation arising in the medulla was actively inhibited by the cerebral cortex. When this inhibitory process was exhaust ed, seizures occurred (46). In addition to these physiological defenses, psy chological defenses shield the individual from phys iological arousal and also play a significant role in reducing sensitivity to sound. For example, the psychological defenses of repression and denial can minimize physiological responses as was found in a study of patients in a coronary intensive care unit (25). 298 Environmental Health Perspectives ucc 084368 ,'sol Wi vase to submod sei-ice i as ' to mal wed bile ftth denals :hat oise an terne's I to `.bin ally ms'on of a tion :ory tely bral pro- in bral ust- osyiya* in the can in a unit a Psychophysiological Responses The next level, step 3 in the model, comprises psychophysiological responses to sound stressors. The psychophysiological responses can be divided into two categories. First are responses within the awareness of the individual, such as sweating, change in heart rate and muscle tension. Second are those responses which occur outside of one's direct aware ness, such as changes in serum lipids, cortisol, blood pressure and blood sugar levels. The psychophysiological responses are manifes tations of the defensive response to sound, can be immediate or delayed, and occur in interactional patterns. Thus, studies of single physiological re sponses oversimplify the mixture of responses. An example of an immediate psychophysiological re sponse to noise is the finding of elevated diastolic and systolic blood pressures and urinary excretion of norepinephrine metabolites in brewery workers on days in which they deliberately did not wear hearing protective devices US). Genetic and constitutional individual differences may increase the likelihood that a particular organ system will respond to stressors more than others and over time lead to disease. There also may be a critical period during infancy in which visceral learn ing takes place, adding conditioning of an individu al's disposition to the physiological responsiveness through a specific "target" organ system U9). For example, in certain predisposed individuals, the target organ is the cardiovascular system, and sound stimuli produce intermittent increases in blood pres sure which may eventually cause structural changes in blood vessels leading to permanent hypertension (50). Stimulus and Response Regulation The next cluster of variables are stimulus and response reduction mechanisms. These coping tech niques may deal with the stressor itself or with the physiological and emotional responses to it (51,52). Using ear protective devices is an example of deal ing with the stressor itself by reducing the recep tion of the sound stimulus. If one becomes aware of the psychophysiological responses, particularly if they are seen as threats to health, deliberate response management tech niques can be employed. For example, muscle re laxation may "absorb" the muscle tension that con tributes to elevation in blood pressure. In a broader social sense, stimulus regulation can be achieved through an individual's participation in community, industrial and consumer efforts to acous tically condition home and working environments and manufactured products. Dysfunction: Illness Behavior In step 5 in the model, the lack or failure of defense mechanisms and regulation techniques play important roles in producing dysfunction. The con cept of sensory and information input overload is useful in understanding how the central nervous system responds when defense mechanisms and regulation techniques fail to adequately screen in coming stimuli. In this conception sensory inputs are the sound stimuli and information inputs are sounds with symbolic, message containing mean ing. Overload results from an excess of the number or rate of sensory or symbolic stimuli or both. Human experiments have shown the disorganiz ing and psychotogenic effects of sensory overload. Experimental exposure to intense visual and audi tory sensory overload produces dramatic effects in the form of heightened and sustained arousal, mood changes, illusions, hallucinations, and body image distortions (19). Sensory and informational sound overload also are commonplace in modem, urban living (53). Jets, air compressors, sirens, rock and roll music and road traffic are generally unpredictable and often uncontrollable sources of stimulation that contrib ute to making the sound of our environment inimi cal to mental well being. Low frequency noises have effects similar to the more familiar piercing high frequency sounds (54, 55). A typical household vignette illustrates the un recognized importance of sound sensory and infor mational overload in our lives. The washing ma chine provides a steady hum, the clothes dryer suddenly begins to vibrate; then the telephone jan gles while the delivery boy rings the doorbell; a jet aircraft rumbles overhead and automobile horns are heard, a television set blares in the background; and amidst this confusion, children begin to fight, cry and scream. The overall noise level is not high by hearing damage risk criteria, but a homemaker can attest to the resulting frustration, irritability and even anger. Over time, one manages to adapt to this noise routine. However, one makes errors in balancing the checkbooks, screams at the children for minor transgressions, is irritable with one's spouse, and generally shows symptoms of stress by the end of the day. Furthermore, when one be comes resigned to a lack of control over one's envi ronment,the resulting "learned helplessness" itself may become a stressor and contribute to additional symptoms of depression (10, 56). October 1981 299 UCC 084369 Selye's classic work on stress provides a frame work for understanding the body's responses to sensory and information input overload (18). His terms stressor and stress are comparable to stress and strain in physics. In his view stressors produce two types of changes in the body. The first is a primary nonspecific change in an organ system called the "Local Adaptation Syndrome." This local adaptation occurs repeatedly in normal living. For example, running produces stress in the musculo skeletal and cardiovascular systems. The resulting exhaustion is reversible through rest. The second change is the "General Adaptation Syndrome" which is activated by intense and per sistent stressors that produce a specific effect on the adrenal glands, thymus and stomach. The fully developed general adaptation syndrome consists of three stages; an alarm reaction, a stage of resis tance and an ultimate stage of exhaustion. Extremely severe stress can lead rapidly to exhaustion and death. Stressors, then, set in motion adaptive responses which maintain biological and psychological homeo stasis. In addition to specific organ system respons es, a relatively stereotyped set of neuroendocrine reactions contribute to the development of the gen eral adaptation syndrome. Most prominent are in creased secretion of the adrenal cortical hormone, cortisol, and increased activity of the sympathetic nervous system, including increased secretion of epinephrine by the adrenal medulla. The increase in sympathetic nervous system activity prepares the individual for "fight or flight." The net effect of, these responses is to mobilize nutrients, such as glucose from the liver and fatty acids from fat tissue, to "arouse" the central nervous system, to provide more oxygen and nutrients to skeletal mus cles, to increase contractibUity of skeletal muscles and to increase coagulability of the blood. When these responses are persistent, the sustained ef fects of cortisol may appear in the form of gastric ulceration, inhibition of immune responses, hyper tension, atherosclerosis, sterility and personality changes (57). Most stressors act for a limited time and produce changes corresponding to the first and second stages of Selye's syndrome. The complete general adaptation syndrome results in a specific set of physical changes: enlargement of the adre nals, shrinkage of the thymus and lymph nodes and ulceration of the stomach. Selye's conception helps to explain that subjec tive experience and physiological responses to stressors can appear to have returned to normal or pre-stressor levels during the second stage of resis tance. This point is essentia] in understanding the phenomenon of habituation which has been repeat 300 edly observed in experimental studies of human responses to sound as a stressor (8, li). Habitua tion may reflect the completion of a local adaptation syndrome cycle with restoration of normal bodily functioning. On the other hand, it may reflect a stage of resistance during which the body is moving into the full general adaptation syndrome which gains a momentum of its own and exacts a physio logical cost through the development of dysfunction of the various organ systems. A stimulus appraised as threatening gradually loses its capacity to arouse an emotional response if it is reappraised on repetition as less harmful and results in adaptation (26). This surface adaptation may be deceptive, however, and continued expo sure to the stressor may produce cumulative effects that appear after stimulation is terminated. This may be in the form of strain induced by the adap tive responses themselves. In spite of adaptation, then, stressors may cause biological and behavioral aftereffects following cessation of the stimulus (8). Laboratory studies of the physiological knd be havioral reactions to noise indicate that adaptation (habituation) generally takes place in healthy sub jects. There is laboratory evidence, however, which suggests that some components of physiological responses to noise do not habituate completely (58), although this work has been questioned (U). It is important to distinguish between the tension re sponse of an organism to stressors and stress which is a dangerous condition resulting from failure to manage tension effectively (59). Another factor should be taken into account. More than lower animals, human reactions to stressors not only depend upon the direct impact of stimuli themselves but also on associated cues that signify the meaning and consequences of the stimu li. Human stress, therefore, must be defined in terms of transactions between a stimulus and an individual's reaction to the situation. The fact that sound stimuli are processed cogni tively, therefore, introduces the important concep tion that psychological stressors, such as the antici pation of harm, can strongly influence human responses to sound stressors (52). Activation of the neuroendocrine system usually depends upon the individual's recognition of a stressor as a threat. The auditory system, however, like heat or cold stressors, automatically activate the reticular acti vating system and thence can evoke autonomicneuroendocrine responses. Dysfunction resulting from sound stressors, then, may be the direct result of the sound stressor situation or may indirectly result from the activa tion and progress of the general adaptation syn drome. Dysfunction may be subjectively experienced Environmental Health Perspectives UCC 084370 * man ving hich /sio* tion "ally eif and tion xpo* ects rhis 'aplon, oral (8). betion >ub,:ch ical 58), t is re- lich int. to tof hat nuin an miepiciian .ie the at. old :tido- c:n, ior vaVTled as symptoms, for example, annoyance and tinnitus, or be objectively demonstrable as physical signs, for example, elevated blood pressure and hearing loss. At the same time subjective reports of inter ference with task performance and speech commu nication also can be accompanied by objective changes in cerebral responses on the electroencephalogram (*7). Human dysfunction can be categorized according to the influence of noise on five basic, interrelated functions that influence the well being, or mental health, of an individual: (1) hearing, (2) sleep, (3) task performance, (4) speech communication and (5) emotional state. Hearing. The effects of noise on hearing in the form of temporary and permanent threshold shifts and progressive deafness are well documented (60-62). There are three levels of hearing at which loss of acuity can occur the primitive, warning, and sym bolic (63). The primitive level includes the familiar back ground sounds of one's every day environment. Loss at this level constitutes a form of sensory deprivation and may lead to a sense of isolation. Loss of hearing at the warning level contributes to a sense of insecurity and physical vulnerability in the environment. Loss at the symbolic level inter feres with interpersonal communication and may result in social isolation, withdrawal and depres sion. Overlap between levels of hearing loss magnifies the psychological impact on the affected individual. In addition* the need to wear a hearing aid in itself may cause self-consciousness and undermine self esteem. The emotional and psychological reactions to hearing loss accordingly are threats to an indi vidual's mental health (13, 64, 65). In a more general vein, the loss of hearing with aging (prebycusis) has been related in part to noise exposure in urbanized societies (66, 67). Sleep. Chronic sleep disorders detrimentally af fect health and well-being. A major portion of com plaints about noise arise from disturbance of rest and sleep (31). The Environmental Protection Agency Urban Noise survey found that 28% of the sampled population experienced sleep disturbance which also was rated as the most annoying effect of noise (20). Similar findings have been reported by other sur veys (68-71). The electrophysiological response to noise tends to decrease during exposure to noise during sleep, however, autonomic responses do not (31, 72). This has been shown in a study in which cardiovascular responses did not habituate to traffic noise experi enced by sleeping subjects (73). In sleep, noise evokes the same orienting response in the form of EEG arousal and changes in heart rate, GSR and October 1981 finger vasoconstriction as during waking without its voluntary motor component (31). The evidence also is clear that noise exposure during sleep lightens the level of sleep, especially for subjects of an anxiety-introversion personality type (27, 70, 74). Sleep disturbances have been reported in response to low frequency noise in the 20-1000 Hz range (55). Intermittent noise above the mean background level has a greater effect than louder, more continuous noise on vegetative func tions (75). Age and sex in addition to sleep stage are critical factors in determining the physiological responses of noise sensitive individuals. Older sub jects and women are more sensitive than younger subjects and men. Moreover, sounds with meaning tend to awaken subjects at lower intensities than those without meaning (76). A study devoted to the next day effects of noise-exposed interrupted sleep showed impaired performance of tasks affected by the lack of sleep. There also is suggestive evidence that noise experi enced during the waking hours may reduce the duration of sleep of susceptible persons (77). All of these findings suggest that susceptible persons may be affected by noise occurring during sleep as well as during the waking state. For night workers, mothers with babies and elderly persons, day and nighttime noise can be a significant prob lem (31). Task Performance. There is little evidence that significant performance impairment on simple tasks occurs under continuous noise below* 80 to 90 dB (77). Unpredictable or intermittent noise, however, does affect performance at even lower levels (78). It is well established that noise has a negative effect on work tasks that involve listening or conversing (79). Adverse effects occur with complex, multicomponent tasks that require prolonged vigilence or continuous performance and those in which information content is high. Under these circum stances, impairment of task performance persisting after exposure to noisy environments has been reported (80, 81). Evidence has accumulated regarding noise inter ference in the school performance of children When children are involved in complex activities requir ing precise movements and intense concentration, noise produces inattention and impaired task per formance (82, 83). A study of the effects of noise generated by expressway traffic in homes showed higher reading achievement for children exposed to lower ambient noise levels (84). Another study suggests poorer task performance by young children from noisy than quiet homes (85). A study compared children from schools and 301 UCC 084371 homes with noise levels of 87-99 dBA with those of 48-65 dBA levels. The children in the noisy envi ronments showed increased distractibility and im paired achievement in school. Over a period of four years they became more distractible, indicating increased sensitivity to noise with the passage of time (86, 87). Children exposed to high noise levels in schools also attain lower reading achievement Uian those with low noise levels (88-90). One study of preschool children found that reflex motor reactions to sound and light stimuli were delayed in those exposed to moderate background levels. The children with the higher noise level required more time in task performance as well (91). All of these performance effects influence an individual's attitude toward work and may consti tute additional stressors in themselves, contribut ing to frustration and stress reactions. Speech Communication. Interference with com munication through speech not only creates per sonal frustration but has consequences in social interaction. Individuals react to noise levels that do not completely interfere with intelligibility. Noise accordingly may reduce efforts to converse, lead to repeated speech, and ultimately to withdrawal (92). The hearing unpaired are particularly susceptible to these reactions (93). Interference with communi cation between teachers and children in air traffic exposed schools also has been found (94). Children's speech acquisition and language de velopment may be impaired since the repetition of speech needed to develop these skills is reduced as background noise level increases. Noise accord ingly may interfere with the perception of speech by young children and affect the acquisition of language. More than adults, children depend upon the clear perception and repetition of speech sounds during early learning periods (61). Emotional State. The most prominent subjec tive emotional response to noise is annoyance, a commonly reported but difficult to describe and quantify emotional state. Research on annoyance is hampered by the ambiguity of the term and the fact that one can be annoyed by noise itself or by its symptomatic and behavioral consequences. Arhlin relates annoyance to the direct effects, such as hearing loss, sleep, task performance and speech interference, and the indirect effects of noise, such as blood pressure elevation, headaches, fatigabili ty, anxiety, depression and accident risk (95). A standardized definition of annoyance is needed because each study tends to report annoyance in a different way. In its most specific sense annoyance is an emotion with a protective fiinction. It moti vates an individual to try to avoid or influence the 302 sound stressor. Like discomforts such as pain, chill and warmth, annoyance serves to warn an individ ual of unpleasant or harmful environmental condi tions. Annoyance also can be produced by interfer ence with task performance sleep and somatic symptoms. The direct experience of annoyance by noise itself differs from indirect annoyance because of a headache. Annoyance directly related to noise, then, is an unpleasant emotion experienced as irritability and is a form of anger or hostility related to the state of the individual in a particular social and environ mental context. For example, the sound of the barking of one's own dog may be less annoying than the barking of a neighbor's dog. In another vein, some experimental subjects refused to continue in a noise study because they perceived it as unpleasant (8). There also is a tendency to regard sound as noise at work more than at home (96). Because of this relationship to the peculiarities of the context, annoyance can be expected to vary in its occurrence and reporting. Annoyance is heightened when noise is perceived as unnecessary; when those responsible for the noise are perceived as unconcerned about the exposed population's welfare; when other aspects of the environment are disliked; when noise is be lieved to be harmful to health, and when noise is associated with fear (10). Although defined differently from study to study, annoyance is a commonly used concept in surveys of community responses to noise. The tendency is to define annoyance of the respondents in terms of physiological responses, although a scale has been developed that excludes somatic symptoms (45). It can be inferred then that the more annoyed a respondent the greater the physiological reactions the person is experiencing. Direct physiological measurements would be preferable to subjective reports, however, the stage of this research is not sufficiently advanced to permit the specific mea surement of noise induced stress isolated from other environmental stressors. The evaluation of annoyance is further compli cated. Not only is it an ambiguous concept, but respondents are influenced by the questions they are asked. For example, more positive responses were obtained when people were asked if aircraft noise produced specific symptoms than if asked about symptoms without suggesting a connection to aircraft noise (97, 98). When annoyance was ana lyzed according to attitude, activity interference and symptoms, McKennel found that 65ft of his sample reported feeling annoyed, 35ft reported interference with activities and 5% reported symp toms (99). Environmental Health Perspectives ucc 084372 4 chill fid- rffe*siatic e by ause is an and teof the than 'ein, ina sant ext, ence ived the 4 the :sof bee is of den .It 1a one .al ive not earom oli jut hey see -aft -ted ito "la nce his ted np- * V, Although methodological problems are important in assessing studies of reported annoyance due to noise, a number of surveys suggest that between 30$ and 40$ of urban dwellers are regularly annoyed by noise (20,21, Si, 96,100). In the flight pattern of Heathrow airport in London, 65$ re ported annoyance (99). Noise in industrial situations also may induce what has been described as an "astheno-vegetative syndrome" in the form of increased fatigability, decreased capacity for focusing attention and slow ing of motor reactions' (101). Disease: Illness Measurement In step 6 of the model, whether or not people deflne themselves as ill depends upon individual and cultural attitudes toward assuming the patient role. These personal and social factors influence whether or not an individual minimizes or exagger ates symptoms and adopts "sick" behaviors such as missing work and seeking health care. The critical step for defining illness, then, occurs when health care is sought and a diagnosis is established. This point is the entree for measuring illness resulting from sound induced stress There is an inevitable gap between laboratory studies of the immediate and delayed effects of noise on health. Still, some investigators regard noise pollution in densely populated areas as a social danger comparable to that of known ingested carcinogens and air pollutants (102). Imposing prob lems, however, stand in the way of proving this thesis as illustrated by methodological criticisms of a study which found that people residing near the Los Angeles International Airport had a higher death rate from stress related diseases than a con trol population (103). More specifically, European research on indus trial noise has identified a cluster of symptoms encountered by physicians and referred to as "noise sickness" (31,104). This syndrome is manifested by tinnitus, increased sensitivity to noise, fatigability, lowering of general resistance to illness, headaches, irritability, sleep interference, "heart pains," weight loss, tremors, digestive disorders and ultimately hearing loss. These symptoms are based upon the stress responses of the auditory, autonomic, car diovascular, endocrine, and gastrointestinal systems and precede the actual loss of hearing. Although short-term studies show that work per formance can be maintained under noisy conditions, the more important consideration is the long-range effect of noise on health. The European data appear to show that complete physiological and psychologi cal adaptation to prolonged noise exposure does not October 1981 occur. The person reacts unfavorably to noise from the beginning, and adverse reactions progressively increase with the passage of time. This is most evident in work requiring complex task performance. Because of the cumulative negative effect on one's state of health, the adaptation of many individuals working in noisy environments exacts a health cost (101). For convenience we will briefly summarize the relationship between noise exposure and (1) men tal illness, (2) cardiovascular disorders, (3) gastro intestinal disorders, (4) neurological disorders and (5) fetal abnormalities. Noise and Mental Illness. The role of noise in mental illness is most difficult to assess. Several studies of mental hospitals in the vicinity of Heathrow Airport in London disclosed a small but significantly higher admission rate than those in less noisy areas (105-107). Another piece of evidence relating a form of mental illness to noise is through an indirect rela tionship between noise induced hearing loss and mental illness. Acquired deafness forces a change in life style toward greater social isolation and leads to an over-representation of mental illness in deaf people of all ages. One study found that 46$ of a group of elderly deaf persons were paranoid and 21$ had affective disorders (65). On the other hand, noise-related annoyance in itself probably is not a cause of mental illness, although psychiatric patients do constitute a vul nerable group to the adverse effects of noise. So matic and emotional symptoms associated with an noyance by noise are significant, however (45). The consumption of tranquilizers and sedatives has been used as an index of these symptoms resulting from noise exposure. Greater usage of these medications have been found in air and road traffic areas ex posed to high levels of noise (69, 99, 108, 109). Noise and Cardiovascular Disorders. There is a consistent correlation between prolonged expo sure to high intensity industrial noise and an in creased prevalance of hypertension, as demonstrated by over 40 studies (110). The risk increases with advancing age and increasing years of employment for both men and women. TTie risk also is greater under circumstances of intermittent impulse or im pact sound than continuous or relatively steady sound. There is significant confirmation under actual living and laboratory conditions of the association between high intensity sound and cardiovascular disorders in children and adults (10, 69, ill, 112. More specifically, prolonged noise exposure pro duced sustained elevations in blood pressure in a controlled experimental study of Rhesus monkeys. A carefully designed and monitored study of mon- 303 UCC 084373 14 keys exposed for nine months to a continuous noise In experimental animals, maternal and fetal ab environment simulating that of urban factory work normalities have been Unked to noise (116). At this ers disclosed significant, sustained elevations in time, however, the evidence of the adverse effect of blood pressure levels and alterations in diurnal noise on the human fetus is suggestive but not blood pressure rhythms (113). These changes per established (117,118). sisted after discontinuing exposure to the noise In summary, the data on the health effects of environment, suggesting a basis for long-term noise noise indicate that sound exposure of more than 3 to effects on the cardiovascular system in humans. 5 years with intensity levels of 85 dBA to 90 dBA is Since Borg's study disclosed that lifelong exposure associated with increased health risk. Furthermore, to high noise levels did not produce hypertension in the adverse physiological effects of noise surface \ rats (Hi), this study of primates is important be before damage to hearing appears suggesting that cause it bears a closer relationship to the human attention to the physiological effects of noise may situation. well enhance the prevention of noise induced hear The fact that all persons exposed to noise do not ing loss. ( 4 show cardiovascular disorders is consistent with The effects of noise on children deserve special i the likelihood that noise affects the health of sus attention because children do not spontaneously r ceptible individuals when combined with other report them, have little aw'areness of their significance r stressors, such as work pressure and population and cannot significantly influence their environments. n density. Furthermore, environmental stressors are The evidence is that children may be particularly t. most likely to affect people who are unable to susceptible to noise-induced development^ and learn t; control them. Thus, people in institutions, with low ing impairment which have long-range implications a incomes and low levels of Question and children for later life (JO). c; are especially likely to show adverse reactions from For those who choose to question the health ir noise exposure (10). implications of noise, we must recognize that posi fi. Noise and Gastrointestinal Disorders. The data tive proof of cause and effect between a stimulus T presently available are insufficient to justify judg and human disease can never be established in the at ments about the role of long term noise exposure in strictest experimental sense because of the multi I gastrointestinal disorders (110). The European lit tude of intervening variables. Research in the health erature on industrial noise, however, strongly sug sciences differs fundamentally from that of the phys nc gests such a relationship (10,101). ical sciences. In even the most sophisticated epide in Noise and Neurological Disorders. A number miological survey, a correlation remains a correla cc of investigators report neurological changes associ tion. Species differences always exist and must be nc ated with long-term occupational noise exposure considered in even the most convincing animal study. ec (110). The principal signs include: autonomic imbal For ethical reasons these are the only kinds of th ance such as dematographism, hyperreflexia, hy* research evidence we are likely to have. We need perhydrosis, and hand and eyelid tremors; an al further research to illuminate specifics but not to th tered sense of balance; decreased tactile sensitivity prove that noise is a significant threat to human ne of the hands and feet; decreased stimulus reaction health. th time; a decreased reactivity to visual stimuli; and frt obscuring of regional activity in the electroencepha logram. Implications it} aff An uncommon neurological disorder that is di Our thesis is that research on, and efforts to rectly affected by auditory stimulation is the audio prevent or minimize, the harmful effects of noise cor genic seizure syndrome (43). In individuals with have suffered from the lack of a full appreciation of tar this disorder seizures are precipitated by certain the ways in which humans process and react to late sounds. sound. In an effort to stimulate more comprehen Mo Noise and Fetal Abnormalities. The human sive approaches, we have described an integrated vot fetus perceives and responds to environmental sound model of the auditory processing of sound based in utero as reflected in motor activity and heart rate upon current knowledge of neuroanatomy, neuro ten tivi change. In the last trimester of pregnancy, the physiology, neuroendocrinology and human stress. oth fetus can be conditioned by external sound stimuli. Piecemeal research on narrow aspects of noise- poii Maternal anxiety related to noise can produce in related problems has led to conflicting conclusions creased fetal activity. A possible subtle prenatal that either minimize or exaggerate the significance sen wor effect of maternal anxiety induced by noise expo sure could be infants who are hyperactive and have dysrhythmic temperaments (115). of noise for physical and mental health. The desig nation of the general physiological effects of sound as "nonauditory" has been particularly misleading K othc char 304 Environmental Health Perspectives Oct UCC 084374 I tal ab_\t this ir` r *cts of in 3 to BA is more, irface ,r that 4 may hear- >ecial ously :ance ents. 4arjy earntions ?alth >osi;ilus the ultialth lyside- of jed to lan to se of o n?d d > .8 e d g s to the general public. Because of this fragmentation and ambiguity, definitive action has been stymied by misunderstanding of the economic, social, and personal costs of noise control efforts. Underlying the confusion is the failure to appreciate that, beyond human communication, sound plays a vital role in the physiological functioning of the body. As is true with other human problems, additional inevitable resistances to facing and remediating the untoward effects of noise have been encountered. This is particularly because the root causes of noise pollution are the imposition of modern technology and population pressures on natural human living conditions. Solutions accordingly require adjustments in styles of behavior and living. Even though short range inconveniences may lead to long range be nefits, the human tendency is to resist change and maintain the status quo. Workers fail to wear pro tective hearing devices, manufacturers do not acous tically condition products and government does not adequately enforce standards. Moreover, the human capacity to adapt to noisy environments masks the magnitude of the problem. Hearing loss in itself further may reduce awareness of noxious sounds. These resistances are important determinants of ambiguities in the measurement of community re sponses to noise (119). We believe that the paralysis of effective action is not a result of lack of knowledge but of a failure to integrate and articulate existing knowledge so that compelling reasons can stimulate the motivation needed to implement changes. For this reason, education of the public and workers in the field is the most important need today. The compelling reasons for action are the facts that substantial groups of the population are vul nerable to adverse health effects from noise, that the quality of life is generally eroded by annoyance from noise, that sleep is disrupted, that productiv ity is reduced, and that the education of children is affected by noisy environments. Without question noise can be a stressor and consequently an important underestimated pollu tant of modern society as are chemicals and particu late matter that pollute the air, water, and food. Moreover, noise significantly affects the human ner vous and endocrine systems. Because these sys tems are capable of sophisticated short range adap tive maneuvers, the harmful effects of noise, like other pollutants, usually become evident at later points in time. Noise is one of the main sources of sensory overload for city dwellers and industrial workers (19). More than other pollutants noise interacts with other sensory stressors, population density, life change and life circumstances. Thus, noise plays an October 1981 aggravating role in addition to stress generated by environmental conditions and attitudes toward them. These complex interactions have led to despair in ferreting out the exact role of noise in stress in duced dysfunctions. When seen in the context of all of these factors, however, noise often emerges as the one most accessible to preventive and remedial action. This is reflected in the already existing federal, state, and local noise control measures. Actually, there is little more that needs to be known. The problem lies in the lack of coordination between acoustical engineering, urban planning, health, architecture, audiology, and other related professional disciplines. There are essentially three points of intervention in noise control: reducing sound emission from the source, blocking sound transmission from the source to the ear, and protecting the ear itself from receiv ing the sound. Practical considerations limit the reduction of sound emission from industrial, traffic and aircraft sources. Still, acoustical conditioning of working and living environments can effectively reduce transmitted sound. Finally, sound can be effectively blocked at the level of the ear through protective hearing devices. By intervening at any or all of these levels there are few noise problems that cannot be effectively managed today. Thus, the problem is not that remedies are unavailable or too costly, but that the least expensive ones are not being used. The multifaceted nature of solutions to the noise problem involves the cooperation of those who gen erate and those who are affected by noise. We cannot realistically expect dramatic reductions in the sources of noise pollution (120). Unlike other forms of environmental pollution, however, indi viduals can minimize the adverse effects of noise upon them. To the extent of economic feasibility industry should more actively reduce noise emis sion at the source by machines, vehicles, and appli ances. Beyond that point, individuals can and should protect themselves from harmful sounds through acoustical conditioning and sound occluding ear de vices. The fundamental problem is one of attitude at the levels of government, industry, consumers, and health care workers. Noise already has been identified as a national hazard by Congress in the form of the Noise Control Act of 1972 and the Quiet Communi ties Act of 1978. Federal standards for new product noise emission, labeling requirements, and state and local regulations are being promulgated (121123). Yet unachieved, however, is public awareness of the significance of noise pollution. An attitude of helplessness prevails leading to either resignation to the existence of noise or escape from it by 305 UCC 084375 4 moving out the urban areas or changing jobs. Un intestinal disorders; and possibly aggravated men appreciated is the fact that citizen initiatives, com tal illness and fetal abnormalities. 4 munity organization, labor union bargaining, con Noise is a stressor and an important, largely sumer demand, and personal efforts can create a unrecognized, pollutant of our environment. Our climate in which an attitude of mastery over noise quality of life generally is eroded by annoyance rather than helplessness can be achieved. from noise, and substantial segments of the popula The basis now exists for public, consumer and tion are vulnerable to its adverse health effects. labor expectations that acoustical conditioning be More specifically, sleep is disrupted, productivity is given priority equivalent to air conditioning in hous reduced and the education and development of 4 ing and industrial construction and in machine and children is affected by noisy environments. appliance manufacturing. The problem lies simply The prevention and reduction of noise pollution in a lack of awareness of the importance of these need not await further knowledge. The technology factors. People have become accustomed to accom for reducing noise emission, acoustically condition modating to noise through bodily defense mecha ing environments and protecting hearing now ex nisms and lack an understanding of the personal ists. The problem is the lack of public awareness of and governmental resources available to them. Cit the significance of noise pollution and solutions to it. izens do not fully appreciate that, negative research The challenge is to convert through education a findings and preoccupation with the details of meas public attitude of helplessness to one of mastery uring community annoyance notwithstanding, they through citizen initiatives, labor union bargaining, have the right to determine the quality of their consumer demands and personal efforts to adopt lives and to be free from the harrassment of noise the most feasible noise and noise response control generated by industrial, vehicular, office, airport, measures. and household appliance sources. f* l l I! 2t Summary The fundamental purposes of hearing are to alert and to warn. The auditory orienting response, star tle reflex and defensive response translate sound stimuli into action and sometimes into stress in duced bodily changes. In the course of human evo lution the additional purposes of communication and entertainment developed as sound assumed symbolic meaning. The brain's processing of sound has been outlined as the biological and psychological basis for the effects of sound on the body. An integrated model then was presented for analyzing the impact of sound as a stressor on the body and for identifying key variables for research on the health effects of noise. In addition to the characteristics of the sound stimulus, a variety of personal and social factors determine whether or not noise becomes a stressor. The cognitive state, defense mechanisms, psychophysiological responses and stimulus and response regulation techniques of the individual person play vital roles. When the tension induced by sound persistently alters the homeostasis of the neuroen docrine system, a state of stress results with ac companying dysfunction in hearing, sleep, task per formance, speech communication, and emotional state. 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