· Chronic Obstructive Pulmonary Disease Symptom 'Effects 

of Long-Term Cumulative Exposure to Ambient Levels of 

Total Oxidants and Nitrogen Dioxide in California 

Seventh-day Adventist Residents * 

JOHN E. HODGKIN, M.D. 

Clinical Professor of Medicine 

Health Department University of California, Davis 

California Center for Health Promotion and Rehabilitation 

Respiratory Care and Pulmonary Rehabilitation E. ABBEY, Ph.D. 

St. Helena Hospital and Health Center 

Deer Park, California IItImnts of Biostatistics and Preventive Medicine 

University ALLAN R. MAGIE, Ph.D. 

linda, California Administrator 

Early Disease Diagnostic Center 

ABSTRACT. To assess the risk of chronic obstructive pulmonary disease symptoms due to 

long-term exposure to ambient levels of total oxidants and nitrogen dioxide (NO.), symptoms were ascertained using the National Heart, Lung, and Blood Institute (NHLBI) respiratory symptoms questionnaire. A total of 7,445 Seventh-day Adventist (SDA) nonsmokers who were 25 yr of age or older and had resided at least 11 yr in areas of California with 

high to low photochemical air pollution were included in this study. Cumulative exposures 

to each pollutant in excess of four thresholds were estimated for each participant, using 

zip codes for months of residence and interpolated dosages from state air-monitoring stations. Multiple logistic regression analyses were conducted individually and together for 

pollutants and included eight covariables, including passive smoking. A statistically significant association with chronic symptoms was seen for total oxidants above 10 pphm (196 

mcglm') (p < .004, relative risk of 1.20 for 750 hr/yr). Chronic respiratory disease symptoms were not associated with relatively low NO. exposure levels in this population. When 

these pollutant exposures were studied with exposures to total suspended particulates 

(TSP) and sulfur dioxide (SO.), only TSP exposure above 200 mcglm' showed statistical 

significance (p < .01). Exposure to TSP is either more strongly associated with symptoms of 

chronic obstructive pulmonary disease than the other measured exposures or is the best 

single surrogate representing the mix of pollutants present. 

"This study was performed at the Department of Biostatistics and Epidemiology, School of Public 

Health, Loma Linda University, Loma Linda, California, 

279 
TOXIC EFFECTS on lungs and upper airways resulting 

from inhalation of total oxidants (OX)I-8 and nitrogen 

dioxide (NOz)9-15 have been demonstrated by experimental studies. To date, however, epidemiological 

studies have not consistently demonstrated or quantified the risk of impairment of otherwise normal subjects, due to long-term exposure to these pollutants at 

14 29 concentrations seen in urbanized areas. - Possibly 

respiratory health in the adult is determined by many 

factors more influential than ambient air pollution exposure, e.g., genetic make_up,30,31 infant and childhood 

respi ratory infections,32,33 active and passive tobacco 

smoke exposure,31-49 and occupationalso,51 and indoor 

pollution exposures. 14,52-56. 

To date, studies have not determined minimum safe 

levels of individual ambient pollutants at which no significant adverse health effects would occur in individuals who have experienced many years of exposure. 

Consequently, ambient air quality standards have been 

set without substantial supporting evidence.57 Neither 

have published studies distinguished adverse respiratory effects related to one pollutant from those related 

to another. 

In this study we seek to isolate the effects of specific 

pollutants and to quantify long-term cumulative exposures to these pollutants in such a way as to be useful 

for standards setting. The approach uses the existing 

monitoring station network throughout California and 

illustrates a method which could be useful for largescale epidemiological studies. 

In a previous report, comparisons were made between geographic basins58 for prevalence of individual 

respiratory symptoms and a complex of chronic respiratory symptoms defined as "definite" chronic obstructive pulmonary disease (CaPO). A total of 4,379 

nonsmoking individuals who had resided in a high-pollution area for at least 10 yr were compared to 2,287 

residents of low-pollution areas. After adjustment for 

age, sex, race, education, occupational exposure, and 

past smoking history, the risk of capo was 15% higher 

in the high-pollution area (p = .03). 

Recently we reported an association between capo 

symptoms and exposure to total suspended particulates (TSP).59 An association was also seen for exposure 

to sulfur dioxide (Sal). We adjusted for the same 

covariables as listed above with the addition of "years 

working with a smoker" and "years living with a 

smoker." The methods illustrated that long-term cumulative exposure to a specific air pollutant can be estimated relative to state air quality standards. This is accomplished by determining the number of hours per 

year, e.g., that an air pollutant at the respondent's residence was above a threshold. We referred to this as 

"exceedance hours." 

In this paper we report the effects of exposure to total 

oxidants and N01 . In addition, we discuss the results of 

a combined analysis of all four pollutants and their interaction terms. 

Methods 

In 1974 the Adventist Health Study (AHS), funded by 

the National Cancer Institute, enrolled 36,805 individuals of Seventh-day Adventist (SOA) 


fornia. This database has been used to 


tively a wide variety of health effects 


the SOA lifestyle. For this air pollution 


viduals who were at least 25 yr old and 


in their 1977 residential area for 10 yr 


chosen from the greater metropolitan 


geles and border counties, San F 


ego. In addition, 862 members were 


ically from rural areas of California. 


cerning geographic distribution and 


scription, see a previous report. 58 ~rclCeldul~ 

tical methodology utilized to survey the 


als in this population and to measure 


exposure have been described recently. 


invited to peruse that report prior to 


one. What follows provides additional 


total oxidants, NOz, and combined 


The Adventist, Health, and Smog 


population resides in a geographic area 


the California Air Resources Board (ARB) 


database from more than 70 air quality 


tions operated by local air pollution 


averages of total oxidants (OX), N01, ~" 

averages of TSP, and other pollutant levels 


at these monitoring stations. 


To determine respiratory health effects 

long-term exposure to concentrations of 

ent air pollutants comparable to the 

standards, we estimated each 

exposure to pollutant concentrations 

each threshold shown in Table 1. Four 

cent rations were chosen for each pollutant 

occurring ambient levels to include at 

standard. The World Health Organization 

mended that maximum 1-hr mean levels 

once per month 120 mcg/mJ for 

idants and 190 mcg/mJ-320 mcg/m3 for 

United States Environmental Protection. 

national primary standard for maximum 1 

for ozone (the major component of total. 

235 mcg/mJ, and their maximum 

average for NOz is 100 mcg/mJ. 

The distance from a monitoring station foF. 

measured concentration would be 

been determined by EPA. 61 For oxidants, this 

up to 20 miles and up to 10 miles for N01 • 

Service Corporation (TSC) of Santa Monica, 

incorporated these distances and determ . 

codes of areas where relatively reliable 

estimates could be obtained.62 Of the A 

lation (excluding the small sample of 862 . 

areas), 99% and 92% lived within the areas of: 

reliable concentration estimates for oxidants ' 

respectively. 

USing the ll-yr monthly residential zip 

provided by each respondent and monthly: 

lated pollution concentrations for each 

individual's ll-yr cumulative hours and 

each threshold were calculated for each 

shown in Table 1. Because of the high rn.".... 

tween hours and dosage and because the 

280 
were more easily interpretable for hours, only 

are reported here. Key analyses were reexcess dosage and were similar to those 

rs below. Values since 1973 were 

to be more accurate because a much larger 

of monitoring stations became operational 

Each participant's total oxidants exposure 

for each time period, Le., 1966-1976 

(Data prior to 1966 were too scarce to 

iitefoolatlCm.) Analyses on both sets of data were 

..tt,·.,.,.,m"'nt. To conserve space, results for only 

period are presented here. 

logistic regression analyses were conducted, 

for confounding factors and co-variate effects 

assessment of the singular effects of each exvariable. Assessment of the fit of the model to 

was performed using a chi-square test for each 

decile of risk. 63 There were no statistically significant 

differences between observed frequencies and those 

predicted by the regression equations. For those that 

contained NO] as the single ambient exposure variable, p values ranged from .40 to .87, and for the oxidant regressions p values ranged from .31 to .77. 

Results 

In Table 2 the effects of total oxidant exposure-in 

number of hours per year at concentrations above 10 

ppm (196 mcglm3)-and the eight co-variates determined 

to be the most important of those measured in this 

study are shown. Coefficients of these eight co-variates 

were not altered significantly by any of the ambient exposure variables studied individually or in combination. For further discussion of the co-variates, please 

refer to the previous report. 59 

Table 1.-Concentration Threshold Levels 

Concentration threshold 

Pollutant 	 1st level 2nd level 3rd level 4th level 

OX 	 10 pphm 15 pphm 20 pphm 25 pphm 

(196 mcglm') (294 mcglm') (392 mcglm') (490 mcglm') 

(Calif. standard) (1 st stage alert) 

NO, 	 5 pphm 15 pphm 20 pphm 25 pphm 

(94 mcglml) (282 mcglm') (376 mcglm') (469 mcglm') 

(primary 1-yr (Calif. 1-hr 

standard) 	 standard) 

SO, 2 pphm 4 pphm' 8 pphm 14 pphm 

(52 mcglm') (105 mcglm') (209 mcglm') (365 mcglm') 

(Calif. 24-hr (primary 24-hr 

standard) standard) 

T5P 60 mcglm' 100 mcglm' 150 mcglm' 200 mcglm' 

(Calif. 1-yr (Calif. 24-hr (secondary 1-yr 

standard) standard) standard) 

"The Calif. 24-hr standard for 50, has since been revised upward to 5 pphm (131 mcglm'). 

Table 2.-lndependent Estimates of Chronic Obstructive Pulmonary Disease Symptom Risk 

for Selected Exposure and Demographic Variables by Multiple Logistic Analysis: California 

SDA Residents 25 Yr of Age and Older, 1966-1976 

Relative 

Logistic risk 

Variable coefficient' Increment estimate P value 

Hours OX(IO) exposure 0.00007 750 hr/yrt 1.20 <.004 

Occupational exposure 0.22547 (no;yes) 1.20 .18 

Years lived with smoker 0.00789 10 yr 1.07 .007 

Years worked with smoker 0.01158 10 yr 1.10 <.001 

Past smoker 0.14845 (no;yes) 1.13 .09 

Sex 0.7483 (female;male) 1.07 .36 

Age 0.00397 30 yr 1.10 .13 

Race 0.17633 (non-white;white) 1.17 .13 

Education 0.01358 4 yr 1.04 >.50 

Notes: N - 6,482, cases ~ 1,026. 

'Per one unit, i.e., 1 hr or 1 yr. 

tSpanning 4 yr (1973-1976). 

281 
In Table 3, exposure' above the lowest threshold of 

oxidant concentration (10 pphm) is the most significantly associated with chronic obstructive pulmonary 

disease symptom prevalence, which suggests that statistically significant effects begin at or below 10 pphm. 

To ensure this was not a statistical artifact due to correlations between thresholds, hours of exposure between 

the thresholds of 10 and 15 pphm were entered together into the same logistic regression equation with 

hours above 15 pphm. This was repeated for hours between 10 and 20 pphm with hours above 20 pphm and 

again for hours between 10 and 25 pphm with hours 

above 25 pphm. In each regression equation, hours between 10 and the upper threshold showed a more significant association with COPO symptoms than hours 

of exposure above the upper threshold. 

As the concentration threshold increases in Table 3, 

less and less hours per year are needed to increase the 

risk. The relative risk estimate of 1.07, for example, requires 250 hr/yr exposure above 10 pphm. Above 15 

pphm only 125 hr/yr are needed; above 20 pphm, 48 

hr/yr; and above 25 pphm, 25 hr/yr. Also, as threshold 

concentrations increase, exposure above those levels 

become less statistically significant because of higher 

variability due to smaller numbers at risk. The margin of 

error in the estimation of individual exposures has a 

much greater dilution effect on the individual estimates 

of hours per year above the threshold of 25 pphm 

(above which 45% of the population are exposed for 

only 6 hr/yr) than above 10 pphm (above which 43% 

are exposed for 500 hr/yr). This lack of sufficient exposure in our population to higher levels of oxidants is 

probably causing the reduced statistical significance for 

the higher thresholds. 

A table depicting results of our multiple logistic regression analyses on ambient N02 exposure has not 

been included because we found no statisticaly significant association between hours of N02 exposure 

above any of the four threshold concentrations and 

symptoms of COPO. A large portion of the population 

had considerable exposure to levels in excess of the 

lowest threshold of 5 pphm; 80% were exposed for at 

least 1,500 hr/yr and 20% were exposed for 4,900 hr/yr. 

For the next higher threshold of 15 pphm, exposure 

plummeted to where only the top 20% were exposed 

for 350 hr/yr or more. For higher thresholds there was 

even less exposure; above 20 pphm the top 20% were 

exposed for 115 hr/yr and above 25 pphm the top 20% 

were exposed for only 25 hr/yr or more. Perhaps too 

few individuals in our population experienced sufficient exposure to N02 to detect statistically significant 

associations with symptoms of chronic obstructive pulmonary disease. 

The pollutant/threshold above which exposure was 

found to be most significantly associated with COPD 

symptoms were T5P above 200 mcg/mJ , T5P(200); oxidants above 10 pphm, OX(lO); and 502 above 4 pphm, 

502(4). These were entered with N02 at a threshold of 

25 pphm and again with a threshold of 5 pphm into one 

multiple logistic regression analysis incorporating the 

eight co-variates shown in Table 2. In these combined 

regression equations, N02 again was not found to contribute in any consistent or significant 


quently, N02 was excluded from 


analyses. 


In the three pollutant combined 

exposure effects overshadowed the 

and 502 (4); T5P(200) was the only J,JUIIUliln 

where significant association with 

was seen (p - .008). The likelihood ratio 

can be used as a relative measure of 

power or "fit" of the model for this 

was 60. This compares to likelihood r2tl,"'~.", 

502 (4) alone of 45, for OX(10) alone of 5i 

and OX(lO) together of 53. However, ' 

ratio statistic was the highest (63) when 

entered alone. This may indicate that for' 

T5P(200) is the best predictor of COPO 

dated with exposure to the air polilTarulTln ... 

sidered. 

. To assess possible synergistic effects, 

terms were developed by taking the. product, 

excess of a threshold for all possible 

two pollutants. Each combination was tried 

in the logistic regression equation with 

pollutant/thresholds. Jn no case did the 

term improve the likelihood ratio statistic . 

one, indicating no significant imnrrk\'"'''''''''' 

model. Neither did any of the terms 

coefficients that approached statistical. Sllll11111"2 

Because of the potential problems 

ity in the above regression, multiple r"'ar.."cj .... ~., 

were performed to determine what n.:>r.r..n,f.. 

variation in each ambient pollutant thr'""c~"'J. 

[T5P(200), OX(10), 502 (4), or N02 (25)] 

by the other three pollutant threshold 

cated by the multiple R2. It was found 

and 49% of the variation in T5P (200), 

502 (4), respectively, were explained by the 

pollutant threshold variables. This may 

T5P(200) is presently the single best 'rrr....,.t·A 

of overall ambient air pollution exposure 

COPD symptoms in this population. 

Discussion 

The Los Angeles area has the most severe 

bient air pollution in the United 5tates. 19 Thus, 

cent air pollution epidemiologic studies of area 

have compared groups of people living in 

relatively high levels to those living at low 

dant exposure. 19-22.58 Chronic respiratory 

were not linked to increased oxidant exposure 

studies,l9-21.58 but an association was seen in ' 

Our strongest statistical association between 

posure and COPO symptoms was at the 

pphm) oxidant threshold studied. We will . 

to determine if exposure at lower threshold is 

COPO symptoms. 

I n each of the studies mentioned above, 

population was located in a geographic 

higher oxidant levels and higher particulate 

found a correlation of 0.79 between 

(200) levels in the AHSMOG population.. 

this high correlation, we cannot definitely 

282 Archives of En\liroll~ 
of the two pollutants. Since 1983, the California 

ler rces Board has separately measured two comof TSP: coarse (10 to 2.5 II) and fine «2.5 II). If 

..."..,u,,:mon of either component with oxidants is 

separation of the effects may be possible for 

studies. 

the results of the pollutant-specific 

regression analyses reported previously, 59 OX is 

but possibly secondary importance to TSP. 

rent because of the following: lower statis­

,...........,..." , smaller percentage of the population 

relative risks, and fewer hours of exposure 

the state standards. Sulfur dioxide is much less 

and NOl is not statistically significant. 

",....JI",,,,·ng for passive smoking, we may have conthe major indoor source of SOl and TSP air 

64.&5 However, because oxidant levels are 

higher outside than indoors,&&·67 exposure to 

as approximated by ambient residential levels 

be less accurate for the individual who spent 

indoors. The fewer hours per year individuto residential oxidant levels above a 

the greater will be the resulting increased 

in related exposure effects due to time spent 

This phenomenon, along with the greater iminterpolation error at higher threshold levels 

. low hours of exposure, may explain the trend 

,decreasing statistical significance associated 

oxidant thresholds (Table 3). 

has been difficult to separate ambient 

effects from those of other pollutants bealso occurs in the presence of other pollu­

:a,.,rn•.,.,ir.n to a review by Dawson and Schenker, 14 

report respiratory effects of NOl exposure 

range from implicating mean concentrations as low as 

5 pphm in children and 10 pphm in asthmatics to finding no effects in healthy adults from acute exposure to 

levels as high as 100 pphm. One study!7 found a reduction in acute respiratory illness rates associated with a 

drop in mean NOl concentrations. We are not aware 

of any studies that have reported adverse respiratory 

health effects in adults due to long-term exposure to 

commonly experienced ambient levels of NOlI i.e., 

mean levels" SO pphm. 

Yearly mean levels in residential areas of AHSMOG 

participants ranged only as high as 13.0 pphm. The 

mean of the station yearly mean levels was 5.2 pphm 

(standard deviation [SO] = 4.3 pphm). We found no 

evidence in our population to support a link between 

this level of long-term exposure to NOl and COPD 

symptoms. Most likely these relatively low ambient 

NOl levels in California do not directly contribute 

toward increased risk of development of these symptoms. However, we did not adjust for indoor NOl levels, which may often be significantly elevated due to 

the use of gas cooking stoves and which have been reportedly associated in several studies with increased 

respiratory disease symptoms in children. 14 Childhood 

respiratory symptoms, in turn, have been associated 

with increased COPD in adulthoodY·33 Ongoing investigations will measure and adjust for these factors . 

When the exposure effects of TSP(200), OX(lO)' and 

SOl(4) were studied simultaneously in one logistic 

regression analysis, only TSP exposure was found to be 

significantly associated with COPD symptoms (p < 

.01). This finding does not necessarily weaken the 

association seen between oxidant(lO) exposure and 

COPD symptoms. Oxidant and TSP levels are highly 

Table 3.-lndependent Estimate of Chronic Obstnlctive Pulmonary Disease Symptom 

Risk for Hour Thresholds by Muhiple logistic Analysis: Califomia SDA Residents 25 

Yr of Age and Older, 1966-1976 

Percentage Relativet 

Hours oxidant population Increment risk 

exposure exposed size estimate p value; 

Above 10 ppnm 18 750 nr/yr 1.20 <.004 

43 500 nr/yr 1.13 

50 250 nr/yr 1.07 

Above 15 ppnm 23 250 nr/yr 1.15 <.005 

45 125 nr/yr 1.07 

49 75 nr/yr 1.04 

Above 20 ppnm 16 96 nr/yr 1.13 <.02 

40 48 nr/yr 1.07 

45 24 nr/yr 1.03 

Above 25 ppnm 16 24 hr/yr 1.07 .11 

33 12 nr/yr 1.03 

45 6 nr/yr 1.02 

Notes: N - 6.482, cases - 1,026. 

"Exposure time period was 1966-1976, nowever, 1973-1976 air monitoring data was 

used for the analyses represented in this Table. See text for rationale. 

tThe relative risk estimate is a function of the regression coefficient and the increment 

size. 

*The p value is determined by the regression coefficient and is the same for all relative 

risk estimates for a given threshold. 

! 

I 

283 
•••••••••• 

•••••••••• 

correlated. Both may be highly correlated with a third 

factor or combination of factors which is/are directly 

related to COPO symptoms. TSP(200) may well be the 

best single readily available indicator of the impact on 

COPO symptoms from exposure to the photochemical 

air pollution in Southern California. 

The study limitations were discussed in a recent report. 59 One limitation is the basic design. A cross-sectional study has inherent biases not present in a prospective study. We have maintained current files on this 

population so that future surveys will compare changes 

in COPO symptoms and changes in ambient pollution 

exposure levels over the next decade. 

This study was supported by the following: Environmental Protection Agency (R804603), California Air Resources Board (A013032, 

A7·176-30, A8-147·31), and American Respiratory Therapy Founda· 

tion Lifemark Research Grant (1983). 

Submitted for publication June 25, 1987; revised; accepted for publication February 25, 1988. 

Requests for reprints should be sent to: Gary Euler, Dr.P.H., Kern 

County Health Department, Bakersfield, CA 93305·4198. 

References 

1. 	 Dungworth, D. L.; Castleman, W. L.; and Chow, C. K. 1975. Ef· 

2. 	

ceedings 

Sielczak, 

fect of ambient 

34: 

M. 

1670-1974. 

W.; 

levels 

Denas, 

of 

S. 

ozone 

M.; and 

on 

Abraham, 

monkeys. 

W. 

Federation 

M. 1983. 

ProAirway cell changes in tracheal lavage of sheep after ozone exposure. J Toxicol Environ Health 11 :545-53. 

3. 	 Boatman, E. S.; Sato, S.; and Frank, R. 1974. Acute effects of 

ozone on cat lungs. Am Rev Respir Dis 110: 1157-69. 

4. 	 Stephens, R. J.; Sloan, M. F.; Evans, M. J.; and Freeman, G. 1973. 

Early response of lung to low levels of ozone. Am J Pathol 

74:31-58. 

5. 	 Hu, P. c.; Miller, F. J.; and Daniels, M. J. 1982. Protein accumulation in lung lavage fluid following ozone exposure. Environ Res 

29:377-88. 

6. 	 Gertner, A.; Bromberger-Barnea, B.; Traystman, R.; Berzon, D.; 

and Menkes, H. 1983. Responses of the lung periphery to ozone 

and histamine. J Appl Physiol 54:640-46. 

7. 	 Golden, J. A.; Nadel, J. A.; and Boushey, H. A. 1978. Bronchial 

hyperirritability in healthy subiects after exposure to ozone. Am 

Rev Respir Dis 118:287-94. 

8. 	 Avo!, E. L.; Linn, W. S.; and Venet, T. G. 1983. A comparison of 

ambient oxidant effects to ozone dose-response relationships. 

Southern California Edison. Research and Development Series: 

83-RD-29. 

9. 	 Joel, D. D., Chandra, P.; and Chanana, A. D. 1982. Effects of NO, 

10. 	

exposure 

on 

viron 

Fujimaki, 

immune 

Health 

H.; 

to 

responses 

10:341-48. 

Shimizu, 

NO, on 

in 

F.; 

lymphocytes 

pulmonary 

and Kubota, 

lymph 

required 

K. 1982. 

of sheep. 

Effect 

for antibody 

I 

of 

7oxicol 

subacute 

En­responses. Environ Res 29:280-86. 

11. 	 Case, B. W.; Gordon, R. E.; and Kleinerman, J. 1982. Acute bron· 

chiolar injury following nitrogen dioxide exposure: A freeze fracture study. Environ Res 29:399-413. 

12. 	 Hazucha, M. J.; Ginsberg, J. F.; and McDonnell, W. F. 1983. Effects of 0.1 ppm nitrogen dioxide on airways of normal and 

asthmatic subjects. J Appl Physiol 54:730-39. 

13. 	 Gregory, R. E.; Pickrell, J. A.; Hahn, F. F.; and Hobbs, C. H. 1983. 

Pulmonary effects of intermittent subacute exposure to low-level 

nitrogen dioxide. J Toxical Environ Health 11 :405-14. 

14. 	 Dawson, S. V. and Schenker, M. B. 1979. Health effects of inhalation of ambient concentrations of nitrogen dioxide. Am Rev 

Respir Dis 120:281-92. 

15. 	 Kagawa, J. 1983. Respiratory effects of two-hour exposure with 

intermittent exercise to ozone, sulfur dioxide and nitrogen dioxide alone and in combination in normal 'U"I~DC' 

Assoc J 44:14-20. 

16. 	Whittemore, A. S. and Korn, E. L. 1980. Asthma 


in the Los Angeles area. Am J Public Health 


17. 	 Love, G. J.; Lan, S.; Shy, C. M.; and 


respiratory illness in families exposed to n 


bient air pollution in Chattanooga, Tennessee. 


Health 37:75-80. 

18. 	 American Lu ng Association. 1978. American 


Medical Section: Health Effects of Air 


American Lung Association. 

19. 	 Linn, W. S.; Hackney, J. D.; and Pedersen, E. E. 1 


function and symptoms in urban office workers 


dant air pollution exposure. Am Rev Respir Dis 


20. Cohen, 	C. A.; Hudson, A. R.; Clausen, J. L.; 


1972. Respiratory symptoms, spirometry, and 


tion in nonsmoking adults. Am Rev Respir Dis 


21. 	 Detels, R.; Rokow, S. N.; Coulson, A. H.; Tash 


W.; and Massey, F. J. 1979. The UCLA 


chronic obstructive respiratory disease. I. MF'fh,vin,l~ 

parison of lung function in areas of high and low 


Epidemiol 109:33-58. 

22. 	 Rokaw, S. N.; Detels, R.; Coulson, A. H. 1980. 'rhe 


tion studies of chronic obstructive respiratory 


78:252-62. 


23. 	 Detels, R.; Sayre, J. W.; and Coulson, A. H. 1 


population studies of chronic obstructive respiratory 


Rev Respir Dis 124:673-80. " 


24. 	 Aubry, F.; Gibbs, G. W.; and Becklake, M. R. 1979. 


and health in three urban communities. Arch 


34:360-68. 


25. 	 Bouhuys, A.; Beck, G. J.; and Schoenberg, 


Epidemiology of environmental lung disease. Yale' 


52:191-210. 


26. 	 Dodge, R. 1983. The respiratory health and lung 


Anglo-American children in a smelter town. Am Rev 


127: 158-61. 

27. 	 Neri, L. c.; Mandel, J. S.; Hewitt, D.; and 


Chronic obstructive pulmonary disease in two 


trasting air quality. CMA J 113: 1 043-46. 


23. 	 Harkonen, H.; Nordman, H.; Korhonen, 0.; 


1983. Long-term effects of exposure to sulfur 


Respir Dis 128:890-93. 

29. 	 Stebbings, J. H. and Fogleman, D. G. 1979. Ilrl",nflilvir... 

ble subgroup: Effects of the Pittsburgh air pollution 

schoolchildren. Am J Epidemiol 110:27-40. 

30. 	 Higgins, M. and Keller, J. 1975: Familial occurrence 

respiratory disease and familial resemblance in 

capacity. J Chron Dis 28:239-51. 

31. 	 Tager, I. B.; Rosner, B.; Tishler, P. V.; Speizer, F. E.; 

H. 1976. Household aggregation of pulmonary 

chronic bronchitis. Am Rev Respir Dis 114:485-92. 

32. 	 Lebowitz, M. D. and Burrows, B. 1977. The ml·,';r."<1""" 

respiratory illness history to the prevalence and 

structive lung disorders. Am J Epidemiol 105:544-54. 

33. 	 Samet, J. M.; Tager, I. B.; and Speizer, F. E. 1983. The 

between respiratory illness in childhood and chronic 

struction in adulthood. Am Rev Respir Dis 127:508-523. 

34. 	 Beck, G. J.; Doyle, C. A.; and Schachter, E. N. 1982. 

tudinal study of respiratory health in a rural community. 

Re5pir Dis 125:375-81. 

35. 	 Beck, G. J.; Doyle, C. A.; and Schachter, E. N. 1981. 

and lung function. Am Rev Respir Dis 123: 149-55. 

36. 	 Neiwoehner, D. E.; Kleinerman, J.; and Rice, D. 

Pathologic changes in the peripheral airways of young 

smokers. N Engl J Med 291 :755-58. 

37. 	 Buist, A. S.; Nagy, J. M.; and Sexton, G. J. 1979. The 

smoking cessation on pulmonary function: A 3D-month 

of two smoking cessation clinics. Am Rev Respir Dis 1 

38. 	 Buist, A. S.; Sexton, G. J.; Nagy, J. M.; and Ross, B. B. 

effect of smoking cessation and modification on lung 

Am Rev Respir Dis 114: 115-22. 

39. 	 Berend, N.; Woolcock, A. J.; and Marlin, G. E. 1979. 

between the function and structure of lung in smokers. 

Respir Dis 119:695-705. . 

40. 	 Cosio, M. G.; Hale, K. A.; and Niewoehner, D. E. 1 

284 Archives of En1vin)nrnetdal'll! 
and morphometric effeds of prolonged cigarette smoksmall airways. Am Rev Respir Dis 122:265-71. 

M.'D. 1982. Multivariate analysis of smoking and other 

for obstrudive lung diseases and related symptoms. J 

. 35:751-58. 

R. S. F.; letai, A. D.; Hui, S. l.; Beck, G. J.; Schoenberg, 

Bouhuys, A. 1977. lung fundion, respiratory disease, 

in families. Am J Epidemiol 106:274-83. 

U, R. 1972. Cigarette smoke in closed spaces, Environ 

Perspect 1: 117-28. 

A.; Jermini, c.; and Grandjean, E. 1976. Irritating effects 

of air pollution due to cigarette smoke. Am J Public 

66:672-76, 

, F,; Tessier, J.; and Oriol, P. 1983. Adult passive smokhome environment: A risk fador for chronic airflow 

Am J Epidemiol 117:269-80. 

R. 	and Froeb, H. F. 1980. Small-airways dysfundion in 

chronically exposed to tobacco smoke. N Engl J 

. M.; Howatt, W. F.; Keller, 1. B.; Butler, W. J.; Hig· 

T.; and Higgins, M. W. 1983. Passive smoking, 

symptoms and pulmonary fundion in the pediatric 

ID\)IJlatlon of Tecumseh. Am Rev Respir Dis 127:156. 

D. 	 P.; Clark, V.; and Coulson, A. 1983. Effed of exparental smoking on lung function of children 7-17 

age. Am Rev Respir Dis 127: 157. 

M_ and Melville, G. N. 1983. Effeds of parental smoking 

""",til,.tn,,,, fundion in children. Am Rev Respir Di.1 127:187. 

D. 1977. Occupational Exposures in relation to 

mn~nrn"t(}Ir,,,v and lung function in a community population. 

4:59-67. 

M.; Wong, R.; and Maclean, l. 1983. 

,w'min(r'l1i,c health study of workers in an aluminum smelter in 

Am Rev Respir Dis 127:465-69. 

D. 1976. Aerosol usage and respiratory symptoms. 

Health 31 :83-86. 

M. D. 1983, Health effeds of indoor pollutants. Ann 

Health 4:203-21. 

H.; Glovsky, M. M.; Newcomb, R. l.; and Easton, J. G. 

multifadorial study 	of patients with asthma. Part 2. Air 

animal dander and asthma symptoms. Annals Allergy 

55. 	 Repace. J. l. and lowrey, A. H. 1980. Indoor air pollution, tobacco smoke, and public health. Science 208:464-72. 

56. 	 Dodge, R. 1982. The effeds of indoor pollution on Arizona chil· 

dren. Arch Environ Health 37:151-55. 

57. 	 Holland, W. W.; Bennett, A. E.; and Cameron, I. R. 1979. Health 

effects of particulate pollution: Reappraising the evidence. Am J 

Epidemiol 110:527-659. 

58. 	 Hodgkin, J, E.; Abbey, D. E.; Euler, G. l.; and Magie. A. R. 1984. 

Comparison of chronic obstrudive pulmonary disease preva· 

lence in nonsmokers in high and low air pollution areas. Chest 

86:830-38. 

59. 	 Euler, G. l.; Abbey, D. E.; Hodgkin, J. E.; and Magie, A. R. 1987. 

Chronic obstructive pulmonary disease symptom effeds of longterm cumulative exposure to ambient levels of total suspended 

particulates and sulfur dioxide in California Seventh·Day Adven· 

tist Residents. Arch Environ Health 42;213-22. 

60. 	 Euler. G. L 1986. Chronic Respiratory Disease Symptom Effecrs of 

Long-Term Cumulative Exposure to Pass/vI' Tobacco Smoke and 

to Ambient Levels of TSP, OXidanrs. 50, and NO, in Southern 

California (Doctoral dissertation). Ann Arbor, MI; University Microfilms International. 

61. 	 U.S. Environmental Protection Agency. 1977. Guideline on Pro· 

cedures for Constructing Air AnalySIS, EPA·45012·77-024a (OA· 

QPS No. 1.2-083). Research Triangle Park, NC: U.S. Environmental Protedion Agency. 

62. 	Technology Service Corporation. 1979. Development of Datil 

Base for Human Exposure to Air Pollution in the South Coast Ail 

Basin. California Air Resources Board, Contrad A7-163-30. 

63. 	 Hosmer, D. and lemeshow. 1980. Goodness of fit tests for the 

multiple logistic regressions models_ Communications in Statistics 

A9:1043-69_ 

64. 	 Committee on Indoor Pollutants, National Research Council. 

1981. Indoor Pollutanrs. Washington, DC: National Academy 

Press. 

65. 	 Witek, T. J.; Schachter, E. N,; and Leaderer, B. P. 1984. Indoor air 

pollution and respiratory health. Respiratory Care 29:147-54. 

66. Thompson, 	C. R.; Hensel, E. G,; and Kats, G. 1973. Outdoor-in· 

door levels of six air pollutants. I Air Poilu! Control Assoc 

23:881-86. 

67. 	 Sabersky, R. H,; Sinema, D, A.; and Shair, F. H. 1973. Concentra· 

tions, decay rates, and removal of ozone and their relation to establishing clean indoor air. Environ Sci Technol 7:347-53. 

285