# ·Chronic Obstructive Pulmonary Disease Symptom'Effects

of Long-Term Cumulative Exposure toAmbient Levels of

Total Oxidants and Nitrogen Dioxide in California Seventh-day Adventist Residents

# *

JOHN E. HODGKIN, M.D. Clinical ProfessorofMedicine Health Department UniversityofCalifornia, Davis California Centerfor Health Promotion and Rehabilitation RespiratoryCareand Pulmonary Rehabilitation E. ABBEY, Ph.D. St. Helena Hospitaland HealthCenter Deer Park, California IItImntsofBiostatistics and PreventiveMedicine University ALLAN R. MAGIE, Ph.D. linda, California Administrator Early DiseaseDiagnosticCenter

ABSTRACT. To assess theriskofchronicobstructivepulmonarydiseasesymptomsdueto long-termexposuretoambientlevels oftotaloxidants and nitrogen dioxide (NO.), symptoms wereascertained usingtheNational Heart, Lung, and Blood Institute (NHLBI) respiratory symptomsquestionnaire. Atotalof7,445 Seventh-dayAdventist (SDA) nonsmokerswhowere25yrofageorolderandhad residedatleast 11 yrinareasofCaliforniawith hightolow photochemicalairpollutionwereincludedinthisstudy.Cumulativeexposures toeach pollutant in excess offourthresholds wereestimated for each participant, using zipcodesfor monthsofresidenceandinterpolateddosagesfrom stateair-monitoringstations. Multiple logistic regression analyses were conducted individually and together for pollutantsandincludedeightcovariables, includingpassivesmoking.Astatisticallysignificantassociation with chronic symptomswas seen for total oxidantsabove 10 pphm (196 mcglm') (p

### < .004, relative risk of 1.20for 750 hr/yr). Chronic respiratory diseasesymptomswerenotassociatedwith relativelylow NO.exposurelevelsin thispopulation.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). ExposuretoTSPiseithermorestronglyassociatedwith symptomsof chronic obstructivepulmonary disease than theother measured exposures oris thebest single surrogaterepresentingthemixofpollutantspresent.

"This study was performed at the Department of Biostatistics and Epidemiology, School of Public Health, Loma Linda University, Loma Linda, California,

279TOXIC EFFECTS on lungs and upperairways 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 respiratory 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 toanother.

In this study we seek to isolate the effects ofspecific 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 ofcapowas 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 paperwe report the effects ofexposure tototal oxidants and N01

. In addition, wediscuss 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 awide 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 ofTSP, and other pollutant levels at these monitoringstations.

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 centrations 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 milesfor N01• Service Corporation (TSC) of Santa Monica, incorporated these distances and determ

. codes of areas where relatively reliable estimates could be obtained.62 

### Ofthe A lation (excluding the small sample of 862

. areas), 99% and 92% livedwithinthe 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

280were 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 priorto 1966 were too scarce to iitefoolatlCm.) Analyses on both sets ofdata 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 ofthe fit of the model to

was performed using achi-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 ofthese eight co-variates
were not altered significantly by any ofthe ambient exposure variables studied individually or in combination. For further discussion of the co-variates, please refertothe previousreport.59

Table 1.-ConcentrationThreshold 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) (1st 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-hrstandard for 50, has since been revised upward to 5pphm (131 mcglm').

Table2.-lndependentEstimatesofChronicObstructivePulmonaryDiseaseSymptom Risk forSelected Exposureand DemographicVariables byMultipleLogistic Analysis: California SDA Residents25 YrofAgeandOlder, 1966-1976

Relative Logistic risk Variable coefficient' Increment estimate Pvalue

Hours OX(IO) exposure 0.00007 750 hr/yrt 1.20 <.004 Occupational exposure 0.22547 (no;yes) 1.20 .18 Years livedwith smoker 0.00789 10 yr 1.07 .007 Years workedwith smoker 0.01158 10yr 1.10 <.001 Past smoker 0.14845 (no;yes) 1.13 .09 Sex 0.7483 (female;male) 1.07 .36 Age 0.00397 30yr 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. 'Perone unit, i.e., 1 hror 1yr. tSpanning4yr (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. Toensure this was not astatistical artifact due tocorrelations between thresholds, hours ofexposure 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 ofexposure above the upperthreshold.

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 variabilityduetosmaller 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 ofoxidants 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 ofCOPO. A large portion ofthe population had considerable exposure to levels in excess of the lowest threshold of 5 pphm; 80% were exposed for at least 1,500 hr/yrand 20% wereexposed for4,900 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 top20%
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 ofchronic 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 athreshold of 25 pphm and again withathreshold of5pphm intoone 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" ofthe model for this
was 60. This compares to likelihood**r2tl,"'~.",** 

### 502

### (4) alone of45, 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 predictorofCOPO datedwith exposure tothe air polilTarulTln

... sidered.

. To assess possible synergistic effects, termsweredeveloped bytakingthe.product,
excess of a threshold for all possible two pollutants. Each combination was tried in the logistic regression equation with pollutant/thresholds. J

### n no case did 

### the term improvethe 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 bythe 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 ofarea 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 ifexposure 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

Archivesof**En\liroll~** 282

### ofthe two pollutants. Since 1983, the California ler 

### rces Board has separately measured twocomofTSP: coarse (10to2.5 II) 

### and fine «2.5II). 

### 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 ofthe following: lower statis­

,...........,..."
, smaller percentage ofthe 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 totime 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 ofother pollutants bealso occurs in the presence of other pollu­

:a,.,rn•.,.,ir.n

### toareview 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 tofinding no effects in healthy adults from acute exposure to levels as high as 100 pphm. Onestudy!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 ofAHSMOG participants ranged only as high as 13.0 pphm. The
mean ofthe 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 ofgas 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 ofTSP(200), OX(lO)' and SOl(4) were studied simultaneously in one logistic regression analysis, onlyTSP 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

Table3.-lndependentEstimateofChronicObstnlctivePulmonary DiseaseSymptom Riskfor HourThresholdsbyMuhiplelogisticAnalysis: Califomia SDA Residents25 YrofAgeand Older, 1966-1976

Percentage Relativet Hours oxidant population Increment risk exposure exposed size estimate p value;

Above 10ppnm 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, 1973-1976air monitoringdata was used forthe analyses represented in this Table. See text for rationale. tThe relative risk estimate is afunction ofthe regression coefficient and the increment size. *Thep 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 ofthe 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 overthe 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·

fect of ambient levels of ozone on monkeys. Federation Proceedings 34:1670-1974. 2. Sielczak, M. W.; Denas, S. M.; and Abraham, W. M. 1983. Airway cell changes in tracheal lavage of sheep after ozone exposure. JToxicol 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 ofthe lung periphery to ozone and histamine. JAppl 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 RespirDis 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,

on immune responses in pulmonary lymphofsheep. I7oxicolEn­ viron Health 10:341-48. 10. Fujimaki, H.; Shimizu, F.; and Kubota, K. 1982. Effect ofsubacute exposure to NO, on lymphocytes required for antibody responses. 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. JAppl 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. JToxical Environ Health 11:405-14. 14. Dawson, S. V. and Schenker, M. B. 1979. Healtheffects ofinhalation 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 J44:14-20. 16. Whittemore, A. S. and Korn, E. L. 1980. Asthma in the Los Angeles area. Am JPublic 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 Lung Association. 1978. American Medical Section: Health Effects ofAir 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 RespirDis 20. Cohen,C. A.; Hudson, A. R.; Clausen, J. L.; 1972. Respiratory symptoms, spirometry, and tion in nonsmoking adults. Am Rev RespirDis 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 ofchronic obstructive respiratory Rev RespirDis 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 RespirDis 128:890-93. 29. Stebbings, J. H. and Fogleman, D. G. 1979. Ilrl",nflilvir

... ble subgroup: Effects ofthe Pittsburgh air pollution schoolchildren. Am JEpidemiol 110:27-40. 30. Higgins, M. and Keller, J. 1975: Familial occurrence respiratory disease and familial resemblance in capacity. JChron 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 RespirDis 114:485-92. 32. Lebowitz, M. D. and Burrows, B. 1977. The ml·,';r."<1""" respiratory illness history to the prevalence and structive lungdisorders. Am JEpidemiol 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 RespirDis 127:508-523. 34. Beck, G. 

### J.; Doyle, C. A.; and Schachter, E. N. 1982. tudinal study of respiratory health in a rural community. Re5pirDis 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 JMed 291 :755-58. 37. Buist, A. S.; Nagy, J. M.; and Sexton, G. J. 1979. The smoking cessation on pulmonary function: A 3D-month oftwo smoking cessation clinics. Am Rev RespirDis 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. RespirDis 119:695-705.

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

ArchivesofEn1 vin)nrnetdal'll! 284and morphometric effeds of prolonged cigarette smoksmall airways. Am Rev Respir Dis 122:265-71. M.'D. 1982. Multivariate analysis ofsmokingand 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 JEpidemiol 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.; andOriol, P. 1983. Adult passive smokhome environment: A risk fador for chronic airflow Am JEpidemiol 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 ofTecumseh. 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 RespirDis 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 ofworkers in an aluminum smelter in Am Rev RespirDis 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 studyof 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 CoastAil 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. Indoorair pollution and respiratory health. RespiratoryCare 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 ofozone and their relation to establishing clean indoor air. Environ Sci Technol 7:347-53.

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