Effects of Ambient Air Pollution on Pulmonary Function among Schoolchildren

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InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx

1

ContentslistsavailableatScienceDirect

International

Journal

of

Hygiene

and

Environmental

Health

jou rn a l h o m e p a g e :w w w . e l s e v i e r . d e / i j h e h

Original

article

1

Effects

of

ambient

air

pollution

on

pulmonary

function

among

schoolchildren

2

Yungling

Leo

Lee

a,b

_,

_Wen-Hua

_Wang

a

_,

_Chia-Wen

_Lu

c

_,

_Ya-Hui

_Lin

a

_,

_Bing-Fang

_Hwang

d,∗

3

a_{InstituteofEpidemiologyandPreventiveMedicine,CollegeofPublicHealth,NationalTaiwanUniversity,Taipei,Taiwan}

4

b_{ResearchCenterforGenes,EnvironmentandHumanHealth,CollegeofPublicHealth,NationalTaiwanUniversity,Taipei,Taiwan}

5

c_{DepartmentofFamilyMedicine,NationalTaiwanUniversityHospital,Taipei,Taiwan}

6

d_{DepartmentofOccupationalSafetyandHealth,CollegeofPublicHealth,ChinaMedicalUniversity,Taichung,Taiwan}

7 8

a

r

t

i

c

l

e

i

n

f

o

9 10 Articlehistory: 11 Received10January2011 12

Receivedinrevisedform1May2011 13 Accepted17May2011 14 15 Keywords: 16 Children 17 Airpollution 18 Nitrogenoxides 19 Carbonoxide 20 Ozone 21 Sulfurdioxide 22 PM2.5 23 PM10 24 Pulmonaryfunction 25 Epidemiology 26

a

b

s

t

r

a

c

t

Literaturehasshownadverseeffectsofambientairpollutionexposureonvariousasthmarelated out-comesinchildhood.However,theassociatedevidenceonpulmonaryfunctioneffectsisstillinconsistent. Weconductedapopulation-basedstudycomprisedofseventh-gradechildrenin14Taiwanese com-munities.Pulmonaryfunctiontestsandquestionnaireswerecompletedon3957subjects.Weevaluated theeffectsofambientairpollutionexposuresbasedonthedatacollectedin2005–2007byexistingair monitoringstations.Multiplelinearmixedeffectmodelswerefittedtoestimatetherelationshipbetween communitypollutantlevelsandpulmonaryfunctionindices.Afteradjustmentforindividual-level con-founders,pulmonaryfunctiondifferedonlyslightlybetweencommunitieswithdifferentlevelsofair pollution.Wefoundgreatereffectsofambientairpollutantsonpulmonaryfunctionforboysthanfor girls.Amongboys,traffic-relatedpollutantsCO,NOx,NO2,andNOweregenerallyassociatedwithchronic adverseeffectsonFVCandFEV1,andsubchronicadverseeffectsmainlyonmaximalmid-expiratoryflow (MMEF)andpeakexpiratoryflowrate.Amonggirls,onlyNOxandNO2 showedsubchronicadverse effectsonMMEF.AlthougheffectestimatesofSO2,PM10,andPM2.5weregenerallynegativeforboys, noneachievedstatisticalsignificance.

Ourdatasuggeststhatambienttraffic-relatedpollutionhadchronicadverseeffectsonpulmonary functioninschoolchildren,especiallyforboys.

© 2011 Published by Elsevier GmbH.

Introduction

27

Manystudieshavereportedadverseeffectsofambientair

pollu-28

tiononvariousaspectsofrespiratoryhealthinchildren,including

29

asthmaexacerbations(Schildcroutetal.,2006),doctor-diagnosed

30

asthma (Brauer et al., 2002; Hwang et al., 2005; Shima et al.,

31

2003),and asthmatic symptoms(Braun-Fahrlanderet al.,1997;

32

Morgensternetal.,2007).Pulmonaryfunctionasasensitivemarker

33

ofrespiratoryhealtheffectsofthelowerairwayhasbeen

docu-34

mentedinpreviousstudies(Anon.,1996a,b).Mostmajorpollutants

35

canalterpulmonaryfunctioninadditiontootherhealth effects

36

whentheexposureconcentrationsarehigh.However,some

stud-37

ieshaveindicatednoassociationbetweenambientairpollution

38

andpulmonaryfunction,especiallyinambientlow-doseexposure

39

(Brunekreefetal.,1995;Dockeryetal.,1989).

40

Abbreviations: CO, carbon monoxide;NOx, nitrogenoxides; NO,nitrogen monoxide;NO2,nitrogendioxides;O3,ozone;SO2,sulfurdioxide;PM2.5,particulate

matterwith50%cut-offaerodynamicdiameterof2.5␮m;PM10,particulatematter

with50%cut-offaerodynamicdiameterof10␮m;SD,standarddeviation;IQR, inter-quartilerange;FVC,functionalvitalcapacity;FEV1,forcedexpiratoryvolumein1s;

MMEF,maximalmid-expiratoryflow;PEFR,peakexpiratoryflowrate. ∗ Correspondingauthor.Tel.:+886422071861;fax:+886422071861.

E-mailaddress:[email protected](B.-F.Hwang).

AlthoughtheproblemsofairpollutioninTaiwanarerelatively 41

severe,it wasnot untilrecent yearsthat therespiratory health 42

effects associatedwithair pollutionwerereported(Chenetal., 43

1999;Hoetal.,2007;Hwangetal.,2005;Yangetal.,2007;Yu 44

etal.,2005).FromourpreviousTaiwaneseISAACstudy,chronic 45

exposuretotraffic-relatedairpollutantswasfoundtobeassoci- 46

atedwiththeriskofasthmainschoolchildren(Hwangetal.,2005). 47

Wedidnotcollectpulmonaryfunctiondataatthattimeandsome 48

importantindoorexposureswerenot includedin thequestion- 49

naire.In presentstudy,we usedthedatafromTaiwanChildren 50

HealthStudy(TCHS)toinvestigatethechronicadverseeffectsof 51

ambientairpollutiononpulmonaryfunction.Inpresentstudy,air 52

monitoringdatawasappliedtoelaboratetherelationshipofdiffer- 53

entsourcesofpollutantswithfourkindsofpulmonaryindicesin 54

Taiwanesechildren. 55

Methods 56

Studydesign 57

TaiwanChildrenHealthStudy(TCHS)wasbasedonamulti- 58

purpose nationwide design that focused on CO, NOx, O3, SO2, 59

and particulatematters as outdoorpollutants ofprimary inter- 60

est(HwangandLee,2010).CommunitiesofTaiwanwereselected 61 1438-4639/$–seefrontmatter © 2011 Published by Elsevier GmbH.

2 Y.L.Leeetal./InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx

withtheaimofmaximizing thevariabilityand minimizingthe

62

correlationsincriteriaoutdoorpollutantsbasedonhistoric

rou-63

tineairmonitoringdata.Incommunitieswithpollutionpatternsof

64

interest,neighborhoodswithstable,largelymiddle-income

pop-65

ulations, ethnically representative of Taiwan as a whole, were

66

identified from 2004 censusdata. To address community-level

67

sourcesofvariability,wesoughttomaximizethenumberof

partic-68

ipatingcommunitieswithinexistingfinancialconstraints.School

69

districtrepresentativesin participatingcommunities were

con-70

sultedtoidentifysuitableschools,basedondemographicstability,

71

likelyparentalcooperation,andabsenceoflocalpollutionsources.

72

Presentationsweremadetoschooladministrators,teachers,and

73

studentstoexplainthestudyaims.Finally,ourstudypopulation

74

comprisedsubjectsfrom14 communitiescovering diverseparts

75

ofTaiwan,whichwasrepresentativeofTaiwanesemiddle-school

76

children.

77

Atotal of 4765seventh-grade children were recruited from

78

publicschoolsin14communitiesin2007.Thequestionnairewas

79

distributedtoallschoolsinSeptember,andsubjectswerearranged

80

tocompletepulmonaryfunctiontestsinthefollowingtwoweeks.

81

Questionnaireresponsesbyparentsorguardianswereusedto

cate-82

gorizechildren’sbasicinformation,medicalhistory,familyhistory,

83

personalhabits,housingcharacteristics,andenvironmental

con-84

ditions.Inanyclassroomtargetedforparticipation,everystudent

85

wasinvitedtovolunteer.Ineachschool,science,health,or

physi-86

caleducationclassesweretargeted,excludinganyspecialclasses

87

forgifted orlearning-disabled subjects.Thestudyprotocolwas

88

approvedbytheInstitutionalReviewBoardatouruniversity

hos-89

pital,anditcompliedwiththeprinciplesoutlinedintheHelsinki

90

Declaration(Helsinki,1990).

91

Airmonitoringdata

92

Complete monitoring data for outdoor pollutants carbon

93

monoxide(CO),nitrogenoxides(NOx),nitrogenmonoxide(NO),

94

nitrogendioxides(NO2),ozone(O3),sulfurdioxide(SO2),

partic-95

ulatematterwith 50%cut-off aerodynamicdiameter of 2.5␮m

96

(PM2.5),and10␮m(PM10)werecollectedfromTaiwan

Environ-97

mental Protection Agency (EPA) air monitoring stations in 14

98

communities. Concentrations of each pollutantwere measured

99

continuouslyandreportedhourly–CObynon-dispersiveinfrared

100

absorption,NOxbychemiluminescence,O3byultraviolet

absorp-101

tion,SO2 byultravioletfluorescence,and particulatemattersby

102

beta-gauge.Chronicvaluesofpollutantsweredefinedasannual

103

averageconcentrationscalculatedfromthemonthlyaveragesof

104

theyear2005–2007.Subchronicvaluesweredefinedasmonthly

105

averagesofJulytoSeptember2007.

106

Pulmonaryfunctiontest(PFT)

107

Pulmonaryfunctiontestswereperformedduringthemorning

108

hoursinindoorbuildingstoavoiddailyandannualpeakair

pol-109

lutionlevels,whichoccurmostoftenduringsummerandautumn

110

afternoon.Thechildrenwhoreturnedparentalquestionnairewere

111

included.Afterexcludingsubjectswithincompletequestionnaire,

112

recentsymptomaticupperrespiratory infections,orotheracute

113

pulmonaryorcardiacdiseases,theremaining4355childrenwere

114

eligibleforpulmonaryfunctiontests.

115

Eachsubject wasaskedtoperform threesatisfactory blows,

116

definedasbothofthetwolargestfunctionalvitalcapacity(FVC)

117

andforcedexpiratoryvolumein1s(FEV1)agreeingwithin200ml,

118

extrapolationvolumelessthan150mlor5%ofFVC,andforced

expi-119

ratorytimeexceeding6s,notlessthan5s.Thesecriteriaarebased

120

onAmericanThoracicSocietyrecommendations,updatedin2005,

121

modifiedforchildren.Nomorethan5blowswereattempted per

122

time,nomorethantwotimeswereaskedperchild.Restingformore

123

than10minwasrequiredforeverysubjecttopreventexercisebias. 124

Topredictsubjects’pulmonaryfunction,height,andweightwere 125

measuredatthetimeoftesting,usingthesamedevice,withshoes 126

andcoatsremoved,whileage,sex,andotherpotentialconfounders 127

weredeterminedfromparents’questionnaireresponses.Twofully 128

trainedtechniciansperformedPFT,usingtwoidenticalspirometers 129

(ChestgraphHI-101,CHESTM.I.,Inc.).Eachschoolwasvisitedfor 130

onetime.Spirometers’calibrationswerecheckedbefore,during, 131

andaftereverymorning’stestingusing1Lflow-volumesyringes. 132

Statisticalanalysis 133

ToinvestigatetherelationshipbetweenPFTandairpollutants, 134

weusedmultiplelinearmixedeffectmodels(PROCMIXED)forana- 135

lyzingtwo-stagehierarchicaldata.Themodelsassumetwosources 136

ofvariation:thevariationamongsubjectsinthefirststage,partof 137

whichcouldbeexplainedbytheindividualcharacteristics,andthe 138

variationamongcommunitiesinthesecondstage,partofwhich 139

couldbeexplainedbyvariablesmeasuredatcommunitylevel.In 140

theanalyseswe assumed that (i)theoutcome variablefollows 141

normaldistribution;(ii)intercepttermsarerandomatthecom- 142

munitylevel;and(iii)alltheexplanatoryvariablesarefixedeffects. 143

Wefittedlinearregressionmodelstoadjustforpersonalvariables 144

suchassex,age,height,andweightaswellasthosepotentialcon- 145

foundersdescribedinTable3foreachPFTindex,includingFVC, 146

FEV1,maximalmid-expiratory flow(MMEF),orpeakexpiratory 147

flowrate(PEFR).Multiplelinearregressionmodelswereutilized 148

todeterminewhichpotentialconfounderwassignificantlycorre- 149

latedwithPFTindices.Thepotentialconfounderswiththep<0.15 150

foragivenPFTindexwereincludedinallsubsequentmodelsof 151

pollutanteffects. 152

Sincethenumericalscaleofeffectestimatesisdifferentamong 153

thevariouspollutants,we standardizeeach toitsinter-quartile 154

range,alongwiththeir95%CIs,acrosscommunities.Subjectswith 155

missingcovariateinformationwereincludedinthemodelusing 156

missing indicators (Huberman and Langholz, 1999). The above 157

modelswereappliedtoallsubjectsinthedatasetandtosubsets 158

stratifiedbysex.Sincethepollutantmeasuresrepresentoutdoor 159

ambientlevels,wealsotriedtodeterminewhetherthehabitof 160

outdooractivitymodifiedthePFT–pollutantrelationship.Atstudy 161

entry,subjects’parentswereaskedinquestionnaireiftheirchil- 162

drenhave thehabit todo outdoors activity. Responses to this 163

questionwereutilized tostratifysubjectsintoeitherthe“more 164

outdooractivity”groupor“lessoutdooractivity”group.Regres- 165

sionanalysesofpollutanteffectswerethenperformedseparately 166

foreachofthetwogroups.Using similarmethodology,wealso 167

stratifiedour populationbased onhabitof air cleaner useand 168

doctor-diagnosedasthma.AllanalyseswereperformedbySASsoft- 169

wareversion9.1(SASInstitute,Gary,NC,USA)andassumeda0.05 170

significantlevelbasedonatwo-sidedestimate. 171

Results 172

TheoverallresponserateinTCHSwas86.5%.Afterdropping 173

outsubjectsabsentinthetestingday,withactivesmokinghabits, 174

poorcomplianceor unsatisfactoryblow,ourstudyfinally com- 175

prised3957(90.9%)childrenwithcompletepulmonaryfunction 176

data.Allsubjectswere12–13yearsofageandofthesameHan 177

Chineseethnicorigin. 178

Table1summarizesthedistributionofairpollutantsfrommon- 179

itoringstationsin14communities.Meansandstandarddeviations 180

ofpulmonaryfunctionindicesamongseven-gradeschoolchildren 181

ofourstudyshownormaldistribution(Table2).Wecouldfindthat 182

boyshadhigherFVC,FEV1,MMEF, andPEFRthangirls.Table3 183

Y.L.Leeetal./InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx 3

Table1

Distributionofairpollutantsdatafrom14monitoringstationsinTaiwan.

Mean SD Maximum Minimum Range 25percentile 75percentile IQR CO(ppm) Chronic 0.53 0.12 0.78 0.30 0.47 0.46 0.58 0.12 Subchronic 0.40 0.11 0.68 0.23 0.44 0.35 0.46 0.12 NOx(ppb) Chronic 23.99 7.25 36.99 13.34 23.65 17.88 29.32 11.45 Subchronic 17.39 6.04 28.84 9.03 19.81 11.74 21.95 10.22 NO(ppb) Chronic 5.85 2.37 10.34 2.52 7.82 4.18 6.83 2.66 Subchronic 4.19 1.89 8.06 1.74 7.25 2.73 5.12 2.39 NO2(ppb) Chronic 18.13 5.02 26.84 10.80 16.04 13.63 22.49 8.86 Subchronic 13.21 4.40 20.78 7.01 13.77 9.32 17.22 7.91 O3(ppb) Chronic 27.21 3.90 37.01 20.95 16.06 24.93 28.74 3.80 Subchronic 25.93 3.90 31.90 18.87 13.03 23.07 28.60 5.53 SO2(ppb) Chronic 4.68 2.20 10.09 2.16 7.92 3.24 5.54 2.30 Subchronic 3.90 1.48 7.87 1.87 6.00 2.97 4.65 1.68 PM10(␮g/m3) Chronic 60.84 17.07 88.97 36.72 52.25 47.70 76.63 28.93 Subchronic 43.24 6.89 54.67 30.33 24.33 37.67 47.50 9.83 PM2.5(␮g/m3) Chronic 34.50 10.67 51.94 19.97 31.97 26.13 44.67 18.54 Subchronic 24.88 4.70 31.00 17.00 14.00 20.75 29.58 8.83

Definitionofabbreviations:SD=standarddeviation;IQR=inter-quartilerange;PM10=particulatematterwith50%cut-offaerodynamicdiameterof10␮m.

Chronicvaluesaredefinedasaverageconcentrationscalculatedfromthemonthlyaveragesfromyear2005to2007.Subchronicvaluesaredefinedasmonthlyaveragesfrom July2007toSeptember2007.

Table2

Meansandstandarddeviationsofpulmonaryfunctionindicesamongseven-grade schoolchildreninourstudy.

Allsubjects(n=3957)Boys(n=1989) Girls(n=1968) Mean SD Mean SD Mean SD FVC(ml) 2758.5 511.0 2945.4 563.4 2569.0 364.3 FEV1(ml) 2500.0 446.0 2630.4 506.8 2367.7 324.9

MMEF(ml) 3109.8 728.6 3163.0 803.4 3055.8 639.7 PEFR(ml) 4841.2 1225.9 5229.4 1289.0 4447.4 1017.1 Definitionofabbreviations:SD=standarddeviation;FVC=functionalvital capac-ity;FEV1=forcedexpiratoryvolumein1s;MMEF=maximalmid-expiratoryflow;

PEFR=peakexpiratoryflowrate.

monaryfunctionresults.Olderage,higherheightandhigherweight

185

wereuniformlyassociatedwithpulmonaryfunctionincrements.

186

ChildrenwithhigherparentaleducationlevelhadincreasedFVC

187

andPEFR.Intheanalysesofpollutanteffects,itemswiththep<0.15

188

ineachpulmonaryfunctionindexwereincludedinthefirststage

189

model.Aconsiderableamountofvariationwasaccountedforby

190

thesefactorswithR2_{of0.90forFVCand0.88forFEV}

1.Theadjusted

191

valuesofpulmonaryfunctionindicesforthe14communitieswere

192

computedbasedontheregressionmodelsshowninTable3.Forall

193

subjects,therewasastatisticallysignificantdifferenceofall

pul-194

monaryfunctionindicesacrossthecommunities.Whenallsubjects

195

weredividedbysex,theboysshowedgreatercommunityvariation 196

thangirls. 197

The relationships between pulmonary function indices and 198

ambientairpollutants arepresentedin Table4for allsubjects, 199

boysandgirls.Ingeneral,wefoundgreatereffectsofoutdoorair 200

pollutantsonpulmonaryfunctionindicesforboysthanforgirls. 201

Amongboys,COwassignificantlyassociatedwithchronicandsub- 202

chronicadverseeffectsonFVC,FEV1,MMEF,andPEFR;NOx,NO, 203

andNO2wereassociatedwithchronicadverseeffectsonFVCand 204

FEV1;NO2showedsimilarchronicandsubchronicadverseeffects 205

onMMEF.AlthougheffectestimatesofSO2,PM10,andPM2.5were 206

generallynegativeforboys,noneachievedstatisticalsignificance. 207

Amonggirls,onlyNOxandNO2showedsubchronicadverseeffects 208

onMMEF(Table4). 209

Wefurtherstratifiedthedatabyoutdooractivityaccordingto 210

thequestionnairestodeterminewhethertheeffectsof outdoor 211

CO,NOx,NO,andNO2aregreaterinthesubjectswhospendmore 212

timeoutdoors(TableS1).Wefoundeffectestimatesweregener- 213

allylargerforthosespendingmoretimeoutdoorsinbothsexes.For 214

boyswithmoreoutdooractivity,NOx,NO,andNO2hadstatistically 215

significantchroniceffectsonFVCandFEV1.Forgirlswithmoreout- 216

dooractivity,NOxandNOwereassociatedwithsubchronicadverse 217

effectsonFEV1andMMEF;NO2wassignificantlyassociatedwith 218

subchronicadverseeffectsonMMEF.For thestratificationanal- 219 Table3

Regressioncoefficientsofcovariatesonpulmonaryfunctionindicesinourpopulation.

FVC FEV1 MMEF PEFR

ˇ 95%CI ˇ 95%CI ˇ 95%CI ˇ 95%CI

Age(year) 181.4$ _{(155.8,207.0) 173.4}$ _{(150.3,196.5) 221.1}$ _{(181.1,261.0) 356.8}$ _{(292.3,421.3)}

Girls 387.0$ _{(358.6,415.4) 274.2}$ _{(248.5,299.8) 129.9}$ _{(85.4,174.4) 819.3}$ _{(747.9,890.7)}

Height(cm) 2.4$ _{(0.9,3.9) 2.1}$ _{(0.7,3.4) 1.9}* _{(−0.5,4.3) 5.1}$ _(1.2,8.9)

Weight(kg) 2.6$ _{(1.8,3.4) 1.7}$ _{(1.0,2.4) 0.8 (−0.4,2.0) 2.1}# _(0.1,4.0)

Parentseducationlevel(>9years) 38.4# _{(0.2,76.6) 31.0 (−3.4,65.4) 19.8 (−39.9,79.5) 99.2}# _(3.2,195.3)

Mothersmokingduringpregnancy 35.2 (−36.5,107.0) 32.5 (−32.2,97.2) 70.4 (−42.2,182.9) 7.3 (−173.0,187.6)

Passivesmokingathome 11.1 (−17.7,39.9) 10.6 (−15.4,36.6) 6.2 (−39.4,51.8) 9.2 (−63.2,81.6)

Dogathome 11.2 (−20.2,42.7) 15.9 (−12.5,44.2) 37.8 (−12.3,88.0) 15.1 (−64.0,94.1)

Catathome −13.8 (−76.4,48.8) 14.4 (−42.1,70.8) 65.7 (−110.8,242.2) 77.1 (−80.2,234.3)

Visiblemouldathome −4.3 (−34.2,25.7) 1.2 (−25.8,28.2) 6.8 (−40.1,53.8) 25.9 (−49.4,101.2)

Waterdamageathome −7.3 (−53.5,38.9) −13.6 (−55.3,28.1) −22.3 (−94.8,50.3) −42.8 (−159.0,73.4)

Fordefinitionofabbreviations,seeTable2.

Allmodelsareadjustedforcommunities.

Factorswithp<0.15areadjustedforeachotherineachpulmonaryfunctionindex;remainingvariablesareadjustedonlyforthevariableswithp<0.15.

Factorswithp<0.15areincludedinthefinaladjustmentmodelsforeachpulmonaryfunctionindex.

*_p<0.15.

#_p<0.05.

4 Y.L.Leeetal./InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx Table4

Changesinpulmonaryfunctionindices(ml)perinter-quartilerangeelevationofeachairpollutant.

Allsubjects(n=3957) Boys(n=1989) Girls(n=1968) Estimate 95%CI Estimate 95%CI Estimate 95%CI

FVC CO Chronic −40.0# _{(−64.9,−15.0) −56.8}# _{(−87.1,−26.4) −20.8 (−47.1,5.5)} Subchronic −44.1# _{(−76.0,−12.3) −60.3}# _{(−101.0,−19.5) −24.4 (−56.1,7.3)} NOx Chronic −79.1* _{(−140.3,−17.9) −99.8}* _{(−181.9,−17.7) −50.4 (−108.5,7.8)} Subchronic −73.2 (−148.2,1.8) −81.4 (−183.6,20.8) −54.0 (−120.2,12.3) NO Chronic −44.9* _{(−84.5,−5.4) −54.8}* _{(−108.3,−1.3) −30.3 (−66.6,6.0)} Subchronic −43.4 (−93.7,7.0) −45.7 (−114.5,23.1) −35.4 (−78.5,7.7) NO2 Chronic −94.5* (−166.6,−22.3) −120.7* (−216.8,−24.7) −58.7 (−127.8,10.5) Subchronic −75.1 (−153.5,3.3) −85.1 (−191.2,21.1) −53.0 (−122.9,16.9) O3 Chronic 22.9 (−18.6,64.5) 46.7 (−3.0,96.4) 0.4 (−36.7,37.5) Subchronic −6.2 (−74.9, 62.5) 10.4 (−79.0, 99.7) −16.1 (−73.9,41.8) SO2 Chronic −14.6 (−60.8,31.7) −3.6 (−65.5,58.3) −21.8 (−60.2,16.6) Subchronic −7.1 (−64.5,50.2) 18.3 (−56.5,93.0) −25.6 (−72.5,21.2) PM10 Chronic 5.1 (−75.3,85.6) 7.3 (−97.7,112.4) 6.1 (−62.3,74.6) Subchronic −6.2 (−75.9,63.5) −6.8 (−97.7,84.1) −4.0 (−63.5,55.5) PM2.5 Chronic −3.3 (−82.2,75.6) −5.1 (−108.2,98.0) 2.5 (−64.6,69.7) Subchronic −7.1 (−94.4,80.2) −13.3 (−127.0,100.5) 5.2 (−69.0,79.4) FEV1 CO Chronic −33.3# (−55.5,−11.2) −46.8# (−72.0,−21.6) −17.4 (−42.6,7.7) Subchronic −37.8# _{(−65.3,−10.2) −49.6}# _{(−83.4,−15.8) −22.4 (−52.2,7.4)} NOx Chronic −69.4# _{(−121.7,−17.1) −83.9}* _{(−151.4,−16.5) −46.3 (−101.0,8.3)} Subchronic −70.3* _{(−132.4,−8.2) −71.9 (−155.1,11.3) −57.5 (−117.6,2.5)} NO Chronic −39.2* _{(−73.2,−5.2) −45.4}* _{(−89.6,−1.1) −27.7 (−61.9,6.5)} Subchronic −38.9 (−81.8,4.0) −35.5 (−92.8,21.7) −36.5 (−75.9,2.9) NO2 Chronic −83.2# (−144.7,−21.6) −102.3* (−180.8,−23.8) −54.1 (−119.1,10.9) Subchronic −73.8* _{(−138.2,−9.5) −78.4 (−163.8,7.1) −57.4 (−120.7,5.9)} O3 Chronic 21.4 (−14.0,56.9) 43.1* (4.0,82.2) 1.0 (−33.8,35.8) Subchronic 1.6 (−57.7,61.0) 18.7 (−54.3,91.7) −8.7 (−63.4,46.0) SO2 Chronic −13.3 (−53.2,26.7) −2.2 (−53.6,49.2) −19.9 (−56,16.1) Subchronic −11.3 (−60.4,37.9) 14.2 (−47.8,76.2) −29.1 (−71.9,13.8) PM10 Chronic 7.6 (−61.6,76.8) 8.1 (−78.8,95.0) 11.6 (−52.4,75.5) Subchronic −6.6 (−66.7,53.5) −10.1 (−85.2,65.0) −0.8 (−56.5,55.0) PM2.5 Chronic 1.2 (−66.8, 69.2) −1.2 (−86.6,84.1) 9.1 (−53.6,71.7) Subchronic −7.2 (−82.4,68.0) −14.7 (−108.7,79.2) 8.1 (−61.4,77.5) MMEF CO Chronic −40.2 (−80.4,0.0) −52.7* _{(−97.1,−8.4) −25.4 (−71.5,20.8)} Subchronic −50.5* _{(−97.9,−3.1) −59.4}* _{(−113.6,−5.1) −38.8 (−92.5,14.8)} NOx Chronic −92.1* _{(−181.8,−2.4) −101.2 (−206.7,4.4) −74.2 (−174.5,26.1)} Subchronic −117.1* _{(−213.2,−21) −108.5 (−227.5,10.5) −116.0}* _{(−219.3,−12.7)} NO Chronic −52.5 (−109.6,4.5) −54.4 (−122.2,13.4) −45.2 (−107.5,17.2) Subchronic −59.5 (−127.9,8.9) −47.5 (−131.0,36.0) −66.5 (−136.7,3.8) NO2 Chronic −110.1* (−216,−4.3) −123.9* (−247.5,−0.2) −86.1 (−205.2,33.0) Subchronic −126.6* _{(−224.7,−28.5) −122.4}* _{(−243.2,−1.5) −120.4}* _{(−228.2,−12.6)} O3 Chronic 36.5 (−18.8,91.8) 67.0* (11.7,122.4) 10.1 (−51.7,71.8) Subchronic 30.7 (−60.8,122.3) 61.4 (−38.8,161.7) 11.9 (−85.5,109.3) SO2 Chronic −11.7 (−75.7,52.2) 1.3 (−73.6,76.2) −18.5 (−85.1,48.2) Subchronic −24.1 (−101.2,53.1) 8.8 (−82.1,99.7) −48 (−125.5,29.5) PM10 Chronic 36.2 (−71.2,143.5) 31.7 (−92.8,156.3) 49.9 (−61.3,161.2) Subchronic 2.9 (−91.9,97.8) −6.7 (−115.6,102.2) 17.6 (−81.6,116.8) PM2.5 Chronic 28.9 (−77.0,134.7) 23.6 (−99.1,146.3) 44.6 (−64.8,154.0) Subchronic 0.9 (−117.8,119.6) −8.4 (−144.8,127.9) 22.5 (−101.3,146.2) PEFR CO Chronic −76.1 (−161.3,9.2) −107.2* _{(−202.6,−11.8) −40.8 (−128.7,47.1)} Subchronic −99.0 (−198.6,0.6) −126.0* _{(−240.8,−11.2) −66.2 (−168.4,36.0)} NOx Chronic −167.2 (−359.3,24.9) −200.0 (−427.5,27.4) −119.5 (−311.7,72.6) Subchronic −224.7* _{(−429.4,−20) −229.5 (−483.3,24.3) −201.5}* _{(−400.9,−2.0)} NO Chronic −96.1 (−217.2,25) −112.3 (−256.4,31.7) −71.8 (−191.2,47.6) Subchronic −136.8 (−274.5,0.9) −145.2 (−312.9,22.6) −120.0 (−253.6,13.7) NO2 Chronic −199.0 (−426.3,28.2) −240.1 (−508.4,28.3) −139.9 (−367.8,88.0) Subchronic −227.7* _{(−443.3,−12) −228.6 (−495.2,37.9) −206.1 (−415.1,2.9)} O3 Chronic 59.8 (−58.5,178.0) 116.1 (−11.8,244) 8.4 (−108.5,125.4) Subchronic 58.9 (−132.5,250.4) 118.0 (−100.2,336.1) 16.6 (−167.8,200.9) SO2 Chronic −19.9 (−152.0,112.2) −12.9 (−170.7,144.9) −19.4 (−145.1,106.4) Subchronic −42.8 (−202.7,117.1) −6.3 (−198.6,186.0) −67.7 (−216.7,81.4) PM10 Chronic 121.2 (−94.3,336.7) 124.7 (−133.1,382.5) 128.4 (−74.8,331.6) Subchronic 52.3 (−141.9,246.5) 54.0 (−175.5,283.5) 55.5 (−128.8,239.8) PM2.5 Chronic 104.0 (−110.0,318.1) 102.7 (−153.1,358.5) 117.6 (−83.0,318.2) Subchronic 77.2 (−165.1,319.5) 86.8 (−199.4,373) 82.6 (−146.8,312)

Fordefinitionofabbreviations,seeTable2.

SinglepollutantmodelsareadjustedforpotentialconfoundersdescribedinTable3.

Modelsforgirlsandboysareadjustedforthesamefactorsexceptsex.

* _p<0.05.

Y.L.Leeetal./InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx 5

ysesbyhouseholdaircleaneruse(TableS2), outdoorpollutants

220

showedgreatereffectsonthosewithoutaircleaneruseathome.

221

Forboyswithoutaircleaneruse,CO,NOx,andNO2showed

signif-222

icantlyadverseeffectsonFVC,FEV1,andPEFR.Forgirlswithoutair

223

cleaneruse,NOwasassociatedwithsubchronicadverseeffectson

224

FEV1andMMEF;NO2wassignificantlyassociatedwithsubchronic

225

adverseeffectsonMMEFandPEFR.

226

Discussion

227

Our population-based epidemiologic study in 14 Taiwanese

228

communitieswasdesignedtohaveadequatepowerforidentifying

229

respiratoryeffectofspecificambientairpollutant.Itshowedthat

230

traffic-relatedpollutantsCO,NOx,NO2,andNOhadchronicadverse

231

effectsonpulmonaryfunctioninchildren.Deficitsinpulmonary

232

functionindiceswerenotsignificantlyrelatedtotheambientlevels

233

ofO3,SO2,PM2.5,andPM10.Afteradjustmentforindividual-level

234

confounders,pulmonaryfunctiondifferedonlyslightly between

235

communitieswithdifferentlevelsofairpollution. Theseresults

236

supportrecentcohortdatainSouthernCaliforniademonstrating

237

thatexposuretopollutionfromtraffichasadverseeffectson

chil-238

dren’spulmonaryfunctiondevelopment(Gaudermanetal.,2004,

239

2007).

240

Age,sex,height,weight,andactivesmokinghabitswere

con-241

stitutionallyassociatedwithpulmonaryfunction.Wefoundthat

242

childrenwithhighparentaleducationlevelwereassociatedwith

243

betterpulmonaryfunction(Table3),whichwasconsistentwitha

244

previousstudyfromUnitedStates(Harik-Khanetal.,2004).We

245

minimizedinterferencefromtheseconfoundersbystratifying

fur-246

theranalysesbysex, and adjustingfactorswiththe p<0.15 by

247

regressionmodels.Becausetheprevalenceofactivesmoking(0.7%)

248

wastoolowforstratificationanalysesinourdata,weexcluded

249

subjectswithactivesmokinghabitsforfurtheranalyses.Thestudy

250

communitieswerelocatedindifferentregionsofTaiwanand

there-251

fore exhibited differences in indoor residentialfactors. Dog/cat

252

ownership,visiblemouldathome,andwaterdamagedidnotshow

253

significantinfluenceonchildren’spulmonaryfunctionandwere

254

nottreatedasconfoundersinourfurtherregressionmodels.

255

OurstudyindicatedthatchronicexposuretoambientNOxand

256

COsignificantlydecreasespulmonaryfunctioninchildren.These

257

findingsareinconcordancewithseveralpreviousepidemiologic

258

studiesconcerningchroniceffectsofambientairpollutionfrom

259

Italy(Rosenlundetal.,2009),Finland(Timonenetal.,2002),and

260

California(Petersetal.,1999).Inpresentdata,wefound

consis-261

tenteffectsofNOxandCOonFVCandFEV1thatrepresentcentral

262

airways,whereastheeffectsonMMEFandPEFRthatprovide

infor-263

mationprimarilyondamageoftheperipheralairwayswasmore

264

limited(Table4).OutdoorNO2isstronglyinfluencedbylocal

traf-265

ficdensity(Jerrettetal.,2005).FromourpriorstudyinTaiwan,

266

ambientNOxandCOwerefoundtobehighlycorrelatedandmight

267

serveasindicatorsoftraffic-relatedairpollution(Leeetal.,2008).

268

Similarly,anotherrecentcohortstudyfromCaliforniarevealedan

269

adverseeffectofprenatalexposuretoNO2andCOonpulmonary

270

functioninasthmaticchildren(Mortimeretal.,2008).

271

Airpollutioncaninduceoxidativestressintherespiratorytract

272

resultinginairwayinflammation(Cesaronietal.,2008;Lietal.,

273

2003).Chronicairwayinflammationcouldproducethedecreases

274

inpulmonaryfunctionindicesandthecentralairwaysseemtobe

275

mainlyaffectedgiventhestrongersignalthatwedetectedforFVCin

276

thepresentstudy.PlausiblemechanismsofNO2pulmonarytoxicity

277

havebeenwelldescribed (Persingeretal., 2002)and may

con-278

tributetopartofourfindings.However,inhumanexposurestudies,

279

adverse pulmonaryeffects of NO2 have generally been

demon-280

stratedatlevelsofexposureamagnitudehigherthanreportedhere

281

(Kraftetal.,2005).ThelowambientNO2levelswefoundaremore

282

likelytohaveservedasasurrogatefortraffic-relatedairpollutants. 283

Althoughit isdifficulttodiscuss etiologicalmechanismsin our 284

cross-sectionaldesign,webelievethesepollutantsmaybecausally 285

relatedtopulmonaryfunctionthroughoxidativestressresponses 286

inducedbypollutantshighlycorrelatedwithNO2(Lietal.,2003; 287

SeatonandDennekamp,2003). 288

Exposuretoparticulateairpollutionhasbeenfoundtobeassoci- 289

atedwithsmallairwayremodeling(Churgetal.,2003),pulmonary 290

function deterioration (Lewis et al., 2005; Trenga et al., 2006), 291

andimpairedpulmonaryfunctiongrowthinchildren(Gauderman 292

et al., 2004).Effects of ambientO3 were alsoreported onFVC 293

andFEV1decrements(Chenetal.,1999;Sternetal.,1994).How- 294

ever,thepresentdatashowednosignificantrelationshipbetween 295

pulmonary functionindices and ambientlevelsof O3,SO2,and 296

particulate matters (Table 4). Similar with our findings, some 297

epidemiologicstudiesfailedtoshowsignificanteffectsofambi- 298

entO3 andparticulatemattersinchildren(Dockeryetal.,1989; 299

Rabinovitchetal.,2004;Wareetal.,1986).Thelackofassociation 300

forthesepollutantsmaybeduetotheirlowambientlevels(Hoek 301

andBrunekreef,1994). 302

Wehaveminimizedthepossibilityofacuteeffectsbyscheduling 303

PFT to avoid daily variation of ambient air pollutants. A pre- 304

vious study of Californian children has showed that the acute 305

effectofambientNO2 wasabout−0.4ml/ppbincontrasttothe 306

chroniceffectof−1.7ml/ppbonmorningFVCmeasurements(Linn 307

et al., 1996).Our data alsoindicated that the chronic effectof 308

NO2 (−10.7ml/ppb) was slightly larger than subchronic effect 309

(−9.5ml/ppb)onFVC.Althoughthechronicandsubchroniccon- 310

centrationofNO2 washighlycorrelatedinourdata(correlation 311

coefficient=0.88), subchronic effects of NO2 were significantly 312

greaterthanchroniceffectsonMMEFandPEFR(Table4).Because 313

ofvariationsinemissionsourcesandmeasurementtechniques,it 314

isdifficulttocomparepollutantsconcentrationsbetweenstudies 315

fromdifferentcountries. 316

Whenthesubjectswere dividedbysex, ourresultsshowed 317

statistically significant relationships between certain pollutant 318

exposuresandpulmonaryfunctiondeficits,primarilyamongboys, 319

whichmayhavepublichealthsignificance.Availableliteratureon 320

differencesbetweensexesinresponsetoairpollutiondidnotpro- 321

videaclearpicture.AstudyofGermanchildrenindicatedmore 322

pronouncedeffectsforboys(Ulmeretal.,1997)whileastudyin 323

theNetherlandsoftraffic-relatedpollutionshowedstrongerasso- 324

ciationsforgirls(Brunekreefetal.,1997).Wefoundasignificantly 325

greatereffectofNO2onpulmonaryfunctionamongboysthangirls. 326

Themechanismofsuchmale-ledsusceptibilityisnotwellunder- 327

stood.Onepossibleexplanationconsideredisthatboysmighthave 328

moreextensiveexposuresbecausetheyarerelativelyactiveand 329

spendmoretimeoutdoorsand,therefore,aremoreinfluencedby 330

airpollutants.Sex-differencesinthepathogenesisofpulmonary 331

functioneffectsmightbepartlyduetodifferenceinlifestyle,hor- 332

monalfactors,ordifferencesinpulmonarygrowthphysiology. 333

OurresultsshowedthateffectsofCO,NOx,NO,andNO2were 334

greateramongchildrenwhospentmoretimeoutdoors(TableS1). 335

Thisfindingisconsistentwitha previousreportindicatingthat 336

chronicexposuretoambientairpollutionwassignificantlyasso- 337

ciatedwithlowerFVCandFEV1onlyamongchildrenwithmore 338

outdoor activities (Peters et al., 1999).Numerous studies have 339

demonstratedthatambientairpollutionwasassociatedwithpul- 340

monaryfunctiondeteriorationinchildren,especiallyinasthmatics 341

(Delfinoetal.,2004;Mortimeretal.,2002).Althoughtheassocia- 342

tionbetweentraffic-relatedairpollutionandchildhoodasthmahas 343

beenconfirmedinourpreviousISAACstudy(Hwangetal.,2005), 344

inpresentdata,wecouldnotfindgreatereffectsofairpollution 345

amongasthmaticchildren(TableS3).Thephenomenonindicated 346

theindependentpathognomonic pathwayofambientair pollu- 347

6 Y.L.Leeetal./InternationalJournalofHygieneandEnvironmentalHealthxxx (2011) xxx–xxx

ratherthanthroughasthma.Theexactreasonisstillunknownand

349

warrantsfurtherinvestigations.

350

Largestudiesofprospectivecohortdesign arebetterableto

351

addresshealtheffectsofchronicenvironmentalexposures.TCHS

352

wasdesigned tobea longitudinallyprospective study.We

tar-353

getedallschoolchildreninthepredefinedclassrooms/schoolsand

354

thehigh response rate (90.9%) makes selection bias less likely

355

happen.Wedonotthinkwehavemissedanyimportant

poten-356

tialconfoundersinouranalyses.Migratingfromonecommunity

357

toanothercouldleadtomisclassificationofexposure.However,

358

errorsinexposureassessmentwerelikelytoberandom,which

359

wouldreducethemagnitudeofassociation,butwouldnot

intro-360

duceapositivebiasintheassociations.Measurementsofambient

361

airpollutantsweremadebycommunity-levelmonitoringstations.

362

Biascouldbeintroducedifdifferentialchangesofcertainpollutants

363

werefoundbetweencommunities,butannualmeanpollutant

con-364

centrationsseemratherstableinTCHScommunitiesduringrecent

365

years.Therearevariationsofambientconcentrationswithin

com-366

munitiesoverwhichwehavenocontrol.However,mostpollutants

367

donotshowseasonalvariationgreatlywithincommunities,and

368

airmonitoringstationsarelikelytobeagoodrepresentationof

369

outdoorexposuresinourstudy.

370

Conclusion

371

Traffic-relatedairpollutants(CO,NOx,NO,andNO2)showed

372

chronicandsubchronicadverseeffectsonpulmonaryfunctionin

373

children,especiallyforboys.Theeffectswerelargerinthose

spend-374

ing more time outdoors and/or not using air cleanerat home.

375

Children’sindividualexposuretoairpollutantsaswellas

measure-376

mentsoftimeactivityshouldbeassessedinmoredetailtoestimate

377

thedose–responserelationshipprecisely.Publichealthpolicyfor

378

reducingrespiratoryhealthburdenmayrequireastrongerfocuson

379

traffic-relatedairpollutantswherechildrencouldgainsignificant

380

benefitsinTaiwan.

381

Ethicalapproval

382

ThestudywasapprovedbytheInstitutionalReviewBoardat

383

ouruniversityhospital,andallproceduresweredoneaccordingto

384

theresearchethicsoftheDeclarationofHelsinki.

385 Conflictofinterest 386 None. 387 Acknowledgements 388

Thisstudywassupportedbygrant#95-2314-B-006-103and

389

#96-2314-B-006-053fromTaiwanNationalScienceCouncil.We

390

thank allthe field workers who supported data collection,the

391

schooladministratorsandteachers,andespeciallytheparentsand

392

childrenwhoparticipatedinthisstudy.

393

AppendixA. Supplementarydata

394

Supplementarydataassociatedwiththisarticlecanbefound,in

395

theonlineversion,atdoi:10.1016/j.ijheh.2011.05.004.

396

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