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1 Quantitative systematic review of the associations between shortterm exposure to nitrogen dioxide and mortality and hospital admissions I C Mills 1 , RW Atkinson 2 , S Kang 2 , H Walton 3,4 , HR Anderson 2,3 1 ‐ Public Health England, Centre for Radiation, Chemical and Environmental Hazards, UK 2 ‐ Population Health Research Institute and MRC‐PHE Centre for Environment and Health, St George’s, University of London, London, UK 3 ‐ MRC‐PHE Centre for Environment and Health, King’s College London, UK 4 ‐ NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK and NIHR Health Protection Research Unit on Environmental Hazards at King’s College London in partnership with Public Health England Supplementary Material Contents list 1. Methods Literature search criteria Protocol for selecting estimates for meta‐analysis 2. List of countries by WHO Region and mortality strata 3. List of Tables Table S1: Random effects estimates for the percentage increase in cause specific mortality in all ages per 10 µg/m 3 increase in NO 2 Table S2: Random effects estimates for the percentage increase in respiratory hospital admissions per 10 µg/m 3 increase in NO 2 Table S3: Random effects estimates for the percentage increase in cardiovascular hospital admissions per 10 µg/m 3 increase in NO 2 4. List of Figures Figure S1: Forest plot of studies and estimates selected for meta‐analysis for all‐cause mortality, all ages, 24 hour average NO 2 . Figure S2: Forest plot of studies and estimates selected for meta‐analysis for all‐cause mortality, all ages, 1 hour average NO 2 . Figure S3: Forest plot of studies and estimates selected for meta‐analysis for all cardiovascular mortality, all ages, 24 hour average NO 2 .

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Page 1: Quantitative systematic review of the associations between ......2015/05/01  · 1 Quantitative systematic review of the associations between short‐term exposure to nitrogen dioxide

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Quantitativesystematicreviewoftheassociationsbetweenshort‐termexposure

tonitrogendioxideandmortalityandhospitaladmissions

ICMills1,RWAtkinson2,SKang2,HWalton3,4,HRAnderson2,3

1‐PublicHealthEngland,CentreforRadiation,ChemicalandEnvironmentalHazards,UK

2‐PopulationHealthResearchInstituteandMRC‐PHECentreforEnvironmentandHealth,St

George’s,UniversityofLondon,London,UK

3‐MRC‐PHECentreforEnvironmentandHealth,King’sCollegeLondon,UK

4‐NIHRBiomedicalResearchCentreatGuy’sandStThomas’NHSFoundationTrustand

King’sCollegeLondon,London,UKandNIHRHealthProtectionResearchUniton

EnvironmentalHazardsatKing’sCollegeLondoninpartnershipwithPublicHealthEngland

SupplementaryMaterial

Contentslist1. MethodsLiteraturesearchcriteriaProtocolforselectingestimatesformeta‐analysis2. ListofcountriesbyWHORegionandmortalitystrata

3. ListofTablesTableS1:Randomeffectsestimatesforthepercentageincreaseincausespecificmortalityinallagesper

10µg/m3increaseinNO2

TableS2:Randomeffectsestimatesforthepercentageincreaseinrespiratoryhospitaladmissionsper10µg/m3increaseinNO2

TableS3:Randomeffectsestimatesforthepercentageincreaseincardiovascularhospitaladmissionsper10µg/m3increaseinNO2

4. ListofFiguresFigureS1:Forestplotofstudiesandestimatesselectedformeta‐analysisforall‐causemortality,allages,

24houraverageNO2.FigureS2:Forestplotofstudiesandestimatesselectedformeta‐analysisforall‐causemortality,allages,

1houraverageNO2.FigureS3:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascular

mortality,allages,24houraverageNO2.

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FigureS4:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascular

mortality,allages,1houraverageNO2.FigureS5:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratorymortality,all

ages,24houraverageNO2.

FigureS6:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratorymortality,allages,1houraverageNO2.

FigureS7:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiacmortality,allages,24houraverageNO2.

FigureS8:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseasemortality,allages,24houraverageNO2.

FigureS9:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokemortality,allages,24houraverageNO2

FigureS10:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDincludingasthmamortality,allages,24houraverageNO2

FigureS11:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,allages,24houraverageNO2

FigureS12:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,allages,1houraverageNO2

FigureS13:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,elderly,24houraverageNO2

FigureS14:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,elderly,1houraverageNO2

FigureS15:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,children,24houraverageNO2

FigureS16:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,children,1houraverageNO2

FigureS17:Forestplotofstudiesandestimatesselectedformeta‐analysisforasthmahospitaladmissions,children,24houraverageNO2

FigureS18:Forestplotofstudiesandestimatesselectedformeta‐analysisforasthmahospitaladmissions,children,1houraverageNO2

FigureS19:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDincludingasthmahospitaladmissions,elderly,24houraverageNO2

FigureS20:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDhospitaladmissions,allages,24houraverageNO2

FigureS21:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,allages,24houraverageNO2

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FigureS22:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,allages,1houraverageNO2

FigureS23:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,elderly,24houraverageNO2

FigureS24:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,elderly,1houraverageNO2

FigureS25:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,allages,24houraverageNO2

FigureS26:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,allages,1houraverageNO2

FigureS27:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,elderly,24houraverageNO2

FigureS28:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,elderly,1houraverageNO2

FigureS29:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,allages,24houraverageNO2

FigureS30:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,elderly,24houraverageNO2

FigureS31:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,elderly,1houraverageNO2

FigureS32:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseasehospitaladmissions,allages,24houraverageNO2

FigureS33:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseaseadmissions,elderly,24houraverageNO2

FigureS34:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseaseadmissions,elderly,1houraverageNO2

FigureS35:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,allages,24houraverageNO2

FigureS36:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,elderly,24houraverageNO2

FigureS37:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,elderly,1houraverageNO2

FigureS38:Forestplotofstudiesandestimatesselectedformeta‐analysisfordysrhythmiahospitaladmissions,allages,24houraverageNO2

FigureS39:Forestplotofstudiesandestimatesselectedformeta‐analysisfordysrhythmiahospitaladmissions,elderly,24houraverageNO2

5. Listofreferencesincludedinthereview

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METHODSLiteraturesearchcriteriaBibliographicdatabasesweresearchedtoidentifypeer‐reviewedtime‐series(andcasecrossover)papersofdailyconcentrationsofNO2anddailymortalityandhospitaladmissions.Bibliographicdatabasessearched:PubMed,EMBASEorWebofScience(whichincludestheScienceCitationIndex)Thesearchstringused:

(airpollutionORpollutionORnitricoxide*ORnitrogendioxide?)AND(timeseriesORtimeseriesORtime‐seriesORdailyORcase‐crossover)AND(mortalityORdeath*ORdyingORhospitaladmission*ORadmission*ORemergencyroomORvisit*ORattendance*OR‘a&e’OR‘aande’ORaccidentandemergencyORgeneralpract*ORphysician*ORconsultation*ORemergencydepartment*)

Norestrictiononlanguagewasapplied.Thedatabasesweresearchedforpeer‐reviewedpaperspublisheduptoMay2011.Inaddition,theliteraturesearchwassupplementedwithpapersidentifiedbytheUSEPA4–thiswasthemostcomprehensivenarrativeassessmentoftheNO2evidenceavailableatthetimeofthisreview.Protocolforselectingestimatesformeta‐analysisWeappliedanaprioriprotocolfortheselectionofestimatesformeta‐analysistoavoidselectionbiasandduplicationofstudiesfromthesamepopulation.Wegaveprioritytoestimatesfrommulti‐citystudiesoverestimatesfromsingle‐citystudiesandtheresultsfromanyonecityappearedonlyonceinameta‐analysis.Ifresultsfrommorethanonemulti‐citystudywithinaWHOregionwereavailableweselected,inorderofpriority,themulti‐cityestimatefromthestudy:

(i) withthemostcities/greatestgeographicalcoverage(ii) themostrecentlypublished(iii) themostrecentstudytimeperiod.

Ifamulti‐citystudydidnotreportasummaryestimateacrossthecitiesexamined,foranalysis,wetreatedestimatesfromthesestudiesinthesamemannerasestimatesfromsingle‐citystudies.Weselectedestimatesfromsingle‐citystudiesonlyiftheydidnotappearinmulti‐citystudies.Forcitiesnotincludedinamulti‐citystudysummaryresult,weselected,inorderofpriority:

(i) themostrecentlypublished(ii) themostrecentstudytimeperiod.

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ListofcountriesbyWHORegionandmortalitystrataReproducedfromTheWorldHealthReport2002(http://www.who.int/whr/2002/en/,accessed7thFebruary2015)

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TableS1:Randomeffectsestimatesforthepercentageincreaseincausespecificmortality*inallagesassociatedwitha10µg/m3increaseinNO2WHOregion

NO224hour NO21hour

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

Cardiacmortality,allages

Overalle 12/4 4/2 1.00(0.36,1.66) 79.1 2/1 1/1 0.19(0.00,0.39) 0AMRA 3/0 3/0 0.73(0.50,0.97) ‐ ‐ EURA 4/4 2/2 1.23(‐0.66,3.15) 1/1 0/1 0.20(0.00,0.40)WPRA 1/0 1/0 ‐0.80(‐2.81,1.25) 1/0 1/0 ‐0.02(‐1.04,1.01)WPRB 4/0 3/0 1.76(1.22,2.31) ‐ ‐ Ischaemicheartdisease,allages

Overalle 5/0 3/0 1.61(0.24,2.99) 0 Noestimates EURA 2/0 2/0 2.38(‐1.39,6.30) SEARB 1/0 1/0 1.50(‐0.70,3.75) WPRB 2/0 2/0 1.49(‐0.46,3.47) Strokemortality,allages

Overalle 16/1 4/1 1.35(0.74,1.97) 50.5

Noestimates EURA 2/1 2/1 2.47(0.66,4.31) SEARB 1/0 1/0 2.80(0.70,4.94) WPRA 1/0 1/0 0.78(0.16,1.41) WPRB 12/0 6/0 1.34(0.80,1.89) COPDincludingasthmamortality,allagesf

Overalle 12/0 4/0 1.11(0.72,1.50) 0

Noestimates AMRA 3/0 3/0 1.07(0.59,1.55) EURA 3/0 2/0 4.19(‐3.44,12.42) SEARB 1/0 1/0 ‐1.40(‐5.00,2.34) WPRB 5/0 2/0 1.25(0.56,1.94)

*Insufficientestimatesformeta‐analysisofmortalitycombinationsforheartfailureanddysrhythmiaa‐Numbersofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudiesb‐Numbersofsingle‐city(SC)/multicity(MC)estimatesselectedformeta‐analysisc‐Randomeffectssummaryestimate(95%confidenceinterval)per10μg/m3increaseinNO2d‐I2statisticforheterogeneitybetweenWHOregionse‐Estimatenumbersfor‘Overall’referto:(i)thenumberofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudies;(ii)forselectedestimates,itisthenumberofpooled(fromsingle‐cityestimates)andmulti‐cityestimatesusedtocalculatetheoverallsummaryestimateacrossWHOregionsf–noestimatesforCOPDmortalityinallagesareavailableformeta‐analysisAMR,RegionoftheAmericas;EUR,EuropeanRegion;SEAR,SouthEastAsianRegion;WPR,WesternPacificRegion.

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TableS2:Randomeffectsestimatesforthepercentageincreaseinrespiratoryhospitaladmissionsper10µg/m3increaseinNO2WHOregion NO224hour NO21hour

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

Allrespiratory,allages

Overalle 19/3 5/2 0.57(0.33,0.82) 0 6/0 3/0 0.34(‐0.02,0.70) 76AMRA 1/1 1/1 0.61(0.13,1.09) ‐ ‐ ‐EURA 8/2 4/1 0.52(0.09,0.95) 3/0 3/0 0.21(0.07,0.36)SEARD 1/0 1/0 0.40(‐0.80,1.61) ‐ ‐ ‐WPRA 1/0 1/0 0.96(‐0.41,2.34) 2/0 2/0 ‐0.13(‐0.99,0.74)WPRB 8/0 6/0 0.58(0.16,1.01) 1/0 1/0 0.63(0.37,0.89)Allrespiratory,elderly

Overalle 16/1 4/1 0.69(0.17,1.21) 53.8 6/2 2/2 0.63(‐0.01,1.27) 82.7AMRA 3/0 2/0 1.43(0.45,2.42) ‐ ‐ ‐EURA 7/1 2/1 0.17(‐0.43,0.78) 4/1 1/1 0.15(‐0.25,0.56)WPRA 2/0 2/0 ‐1.12(‐8.86,7.28) 1/1 0/1 1.42(0.79,2.06)WPRB 4/0 2/0 0.93(0.61,1.24) 1/0 1/0 0.89(0.00,1.79)Allrespiratory,children

Overalle 14/4 4/2 1.20(0.35,2.05) 86.1 7/3 3/1 1.16(0.28,2.04) 94.6AMRA 1/0 1/0 4.69(1.88,7.57) ‐ ‐ ‐AMRB 5/0 1/0 0.79(0.41,1.18) 1/0 1/0 0.19(0.00,0.39)EURA 5/1 1/1 0.18(‐0.12,0.48) 2/0 2/0 0.33(0.03,0.62)WPRA 0/3 0/1 5.95(1.74,10.33) 2/3 0/1 2.70(0.93,4.51)WPRB 3/0 2/0 2.91(1.14,4.71) 2/0 1/0 2.37(1.79,2.96)Asthma,childrenf

Overalle 17/4 4/3 1.27(0.28,2.27) 86.5

8/3 1/2 0.37(‐0.08,0.82) 0AMRB 1/0 1/0 ‐0.40(‐1.00,0.20) ‐ ‐ ‐EURA 7/2 2/2 1.72(‐0.36,3.83) 5/1 2/1 0.38(‐0.18,0.94)WPRA 3/2 1/1 5.87(2.23,9.65) 3/2 0/1 1.50(‐1.28,4.37)WPRB 6/0 2/0 1.33(0.52,2.15) ‐ ‐ ‐COPDincludingasthma,elderlyg

Overalle 8/0 3/0 1.42(1.07,1.76) 30.8 1/1 1/1 0.63(0.18,1.07) 14.8AMRA 4/0 4/0 1.28(0.99,1.58) ‐ ‐ ‐EURA 3/0 2/0 3.14(0.76,5.58) 1/0 1/0 0.51(0.09,0.92)WPRA ‐ ‐ ‐ 0/1 0/1 1.05(0.16,1.95)WPRB 1/0 1/0 1.52(1.09,1.95) ‐ ‐ ‐COPD,allagesh

Overalle 6/2 2/2 1.24(‐0.01,2.50) 93.4 3/1 0/1 0.26(0.06,0.46) ‐AMRA 1/0 1/0 0.45(‐0.38,1.29) ‐ ‐ ‐EURA 4/2 0/2 0.81(0.03,1.59) 3/1 0/1 0.26(0.06,0.46)WPRB 1/0 1/0 2.60(2.20,3.00) ‐ ‐ ‐

a‐Numbersofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudiesb‐Numbersofsingle‐city(SC)/multicity(MC)estimatesselectedformeta‐analysisc‐Randomeffectssummaryestimate(95%confidenceinterval)per10μg/m3increaseinNO2d‐I2statisticforheterogeneitybetweenWHOregionse‐Estimatenumbersfor‘Overall’referto:thenumberofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudies;(ii)forselectedestimates,itisthenumberofpooled(fromsingle‐cityestimates)andmulti‐cityestimatesusedtocalculatetheoverallsummaryestimateacrossWHOregionsf–insufficientestimatesformeta‐analysisofasthmahospitalisationinadultsandelderly.g–insufficientestimatesformeta‐analysisofCOPD(includingasthma)hospitalisationinallagesfor24hourNO2andnonefor1hourNO2h‐insufficientestimatesformeta‐analysisofCOPDhospitalisationintheelderly.AMR,RegionoftheAmericas;EUR,EuropeanRegion;SEAR,SouthEastAsianRegion;WPR,WesternPacificRegion.

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TableS3:Randomeffectsestimatesforthepercentageincreaseincardiovascularhospitaladmissionsper10µg/m3increaseinNO2

WHOregion

NO224hour NO21hour

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

Allcardiovascular,allages

Overalle 6/3 3/2 0.66(0.32,1.01) 87.8 6/0 3/0 0.36(‐0.16,0.89) 43.9EURA 1/3 1/2 0.42(0.23,0.62) 3/0 3/0 0.19(0.04,0.33)WPRA 1/0 1/0 1.96(0.65,3.30) 2/0 2/0 0.01(‐1.33,1.36)WPRB 4/0 3/0 1.00(0.75,1.24) 1/0 1/0 1.00(0.16,1.84)Allcardiovascular,elderly

Overalle 5/3 2/2 1.54(0.75,2.35) 86.9 5/0 3/0 0.49(‐0.25,1.24) 0EURA 1/2 1/1 1.02(0.08,1.97) 2/0 2/0 1.19(‐0.73,3.15)WPRA 1/1 0/1 3.08(2.15,4.01) 2/0 2/0 0.17(‐1.19,1.55)WPRB 3/0 2/0 1.18(0.88,1.48) 1/0 1/0 0.47(‐0.52,1.47)Cardiac,allages

Overalle 6/5 4/3 1.10(0.76,1.43) 84.3 3/2 ½ 0.98(0.43,1.54) 79.4AMRA 1/0 1/0 0.73(0.53,0.94) 0/1 0/1 1.34(0.89,1.79)EURA 3/5 2/3 0.93(0.66,1.20) 2/0 2/0 0.36(‐0.14,0.86)WPRA 1/0 1/0 2.26(1.57,2.94) 1/1 0/1 1.21(0.84,1.58)WPRB 1/0 1/0 1.20(0.70,1.70) ‐ ‐ ‐Cardiac,elderly

Overalle 8/3 2/2 1.65(1.02,2.29) 74.3 3/1 2/1 1.44(0.71,2.18) 64.2AMRA 4/0 4/0 1.31(1.04,1.57) 1/0 1/0 0.29(‐0.89,1.49)EURA 3/2 2/1 1.54(0.97,2.10) 1/0 1/0 2.02(1.22,2.82)WPRA 1/1 0/1 3.49(1.95,5.05) 1/1 0/1 1.58(1.16,2.00)Heartfailure,allages

Overalle 4/1 3/1 1.41(‐0.01,2.86) 84.7 Noestimates AMRA 2/0 2/0 1.20(‐0.13,2.55) EURA 1/1 1/1 0.41(‐0.64,1.47) WPRB 1/0 1/0 4.40(2.50,6.34) Heartfailure,elderly

Overalle 2/2 1/2 1.99(0.54,3.46) 79.8 8/1 1/1 0.51(0.13,0.89) ‐AMRA 2/1 2/1 1.56(0.80,2.32) 8/1 7/1 0.51(0.13,0.89)WPRA 0/1 0/1 7.08(2.26,12.13) ‐ ‐ ‐Ischemicheartdisease,allages

Overalle 16/4 4/2 0.86(0.52,1.20) 0 1/1 1/1 1.06(0.58,1.54) 0AMRA 3/0 2/0 1.34(0.17,2.52) ‐ ‐ ‐EMRB 1/0 1/0 0.62(0.26,0.98) ‐ ‐ ‐EURA 7/4 2/2 0.96(0.25,1.68) 1/0 1/0 1.11(‐0.04,2.27)WPRA ‐ ‐ ‐ 0/1 0/1 1.05(0.52,1.58)WPRB 5/0 3/0 0.90(‐0.08,1.89) ‐ ‐ ‐Ischemicheartdisease,elderly

Overalle 7/4 3/2 2.42(1.71,3.13) 0 3/1 2/1 0.70(0.17,1.22) 57.8AMRA 2/0 2/0 2.18(‐0.63,5.08) ‐ ‐ ‐AMRB ‐ ‐ ‐ 1/0 1/0 0.51(‐0.69,1.71)EURA 4/2 2/1 2.28(1.34,3.22) 2/0 2/0 0.44(0.15,0.73)WPRA 0/2 0/1 2.56(1.03,4.12) 0/1 0/1 1.16(0.58,1.74)WPRB 1/0 1/0 2.79(1.06,4.55) ‐ ‐ ‐Stroke,allages

Overalle 10/3 3/2 0.30(0.02,0.57) 0 Noestimates AMRA 3/0 2/0 0.27(‐0.06,0.61) EURA 4/3 4/2 0.28(‐0.51,1.07) WPRB 3/0 2/0 0.66(‐0.32,1.65) Stroke,elderly

Overalle 2/1 2/1 0.26(‐0.48,1.01) 0 1/2 1/2 0.50(‐0.54,1.56) 58.3AMRA 1/0 1/0 ‐0.11(‐1.45,1.24) 0/2 0/2 0.91(‐0.12,1.94)EURA 1/1 1/1 0.43(‐0.46,1.33) 1/0 1/0 ‐0.16(‐1.05,0.72)

 

 

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TableS3(continued):Randomeffectsestimatesforthepercentageincreaseincardiovascularhospitaladmissionsper10µg/m3increaseinNO2

WHOregion

NO224hour NO21hour

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

AllSC/MCa

SelectedSC/MCb

RandomEffects(95%CI)c

I2(%)d

Dysrhythmia,allages

Overalle 3/1 2/1 0.50(0.15,0.86) 0 Noestimates AMRA 2/0 2/0 0.49(‐0.14,1.12) EURA 1/1 1/1 0.51(0.08,0.94) Dysrhythmia,elderly

Overalle 2/1 2/1 1.73(0.16,3.33) 26.9 Noestimates AMRA 1/0 1/0 1.82(‐0.05,3.74) EURA 1/0 1/0 3.65(0.56,6.84) WPRA 0/1 0/1 0.41(‐1.84,2.72)

a‐Numbersofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudiesb‐Numbersofsingle‐city(SC)/multicity(MC)estimatesselectedformeta‐analysisc‐Randomeffectssummaryestimate(95%confidenceinterval)per10μg/m3increaseinNO2d‐I2statisticforheterogeneitybetweenWHOregionse‐Estimatenumbersfor‘Overall’referto:(i)thenumberofsingle‐city(SC)/multi‐city(MC)estimatesavailablefromallstudies;(ii)forselectedestimates,itisthenumberofpooled(fromsingle‐cityestimates)andmulti‐cityestimatesusedtocalculatetheoverallsummaryestimateacrossWHOregionsAMR,RegionoftheAmericas;EUR,EuropeanRegion;SEAR,SouthEastAsianRegion;WPR,WesternPacificRegion.

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FigureS1:Forestplotofstudiesandestimatesselectedformeta‐analysisforall‐causemortality,allages,24houraverageNO2.1

                                                            1RMIDreferstotheReferenceIDforeachstudyinourReferenceManagerdatabase.AccessIDreferstoanIDgiventoeachestimateextractedfromastudyandenteredinourMicrosoftAccessdatabase.TheestimatefromRMID1494inFigureS1wassourcedfromTable1(page7‐33)oftheTechnicalSupportDocumentbytheCaliforniaEnvironmentalProtectionAgency(2007)becausetheestimatewasonlypresentedgraphicallyinRMID1494.

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FigureS2:Forestplotofstudiesandestimatesselectedformeta‐analysisforall‐causemortality,allages,1houraverageNO2.

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FigureS3:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularmortality,allages,24houraverageNO2.

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FigureS4:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularmortality,allages,1houraverageNO2.

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FigureS5:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratorymortality,allages,24houraverageNO2.

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FigureS6:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratorymortality,allages,1houraverageNO2.

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FigureS7:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiacmortality,allages,24houraverageNO2.

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FigureS8:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseasemortality,allages,24houraverageNO2.

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FigureS9:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokemortality,allages,24houraverageNO2

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FigureS10:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDincludingasthmamortality,allages,24houraverageNO2

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FigureS11:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,allages,24houraverageNO2

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FigureS12:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,allages,1houraverageNO2

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FigureS13:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,elderly,24houraverageNO2

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FigureS14:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,elderly,1houraverageNO2

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FigureS15:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,children,24houraverageNO2

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FigureS16:Forestplotofstudiesandestimatesselectedformeta‐analysisforallrespiratoryhospitaladmissions,children,1houraverageNO2

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FigureS17:Forestplotofstudiesandestimatesselectedformeta‐analysisforasthmahospitaladmissions,children,24houraverageNO2

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FigureS18:Forestplotofstudiesandestimatesselectedformeta‐analysisforasthmahospitaladmissions,children,1houraverageNO2

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FigureS19:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDincludingasthmahospitaladmissions,elderly,24houraverageNO2

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FigureS20:Forestplotofstudiesandestimatesselectedformeta‐analysisforCOPDhospitaladmissions,allages,24houraverageNO2

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FigureS21:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,allages,24houraverageNO2

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FigureS22:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,allages,1houraverageNO2

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FigureS23:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,elderly,24hoursaverageNO2

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FigureS24:Forestplotofstudiesandestimatesselectedformeta‐analysisforallcardiovascularhospitaladmissions,elderly,1houraverageNO2

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FigureS25:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,allages,24houraverageNO2

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FigureS26:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,allages,1houraverageNO2

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FigureS27:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,elderly,24houraverageNO2

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FigureS28:Forestplotofstudiesandestimatesselectedformeta‐analysisforcardiachospitaladmissions,elderly,1houraverageNO2

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FigureS29:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,allages,24houraverageNO2

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FigureS30:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,elderly,24houraverageNO2

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FigureS31:Forestplotofstudiesandestimatesselectedformeta‐analysisforheartfailurehospitaladmissions,elderly,1houraverageNO2

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FigureS32:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseasehospitaladmissions,allages,24houraverageNO2

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FigureS33:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseaseadmissions,elderly,24houraverageNO2

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FigureS34:Forestplotofstudiesandestimatesselectedformeta‐analysisforischaemicheartdiseaseadmissions,elderly,1houraverageNO2

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FigureS35:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,allages,24houraverageNO2

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FigureS36:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,elderly,24houraverageNO2

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FigureS37:Forestplotofstudiesandestimatesselectedformeta‐analysisforstrokeadmissions,elderly,1houraverageNO2

EstimatesfromRMID1929inFigureS37relatetotwotypesofstroke(hemorrhagicandischemic)

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FigureS38:Forestplotofstudiesandestimatesselectedformeta‐analysisfordysrhythmiahospitaladmissions,allages,24houraverageNO2

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FigureS39:Forestplotofstudiesandestimatesselectedformeta‐analysisfordysrhythmiahospitaladmissions,elderly,24houraverageNO2

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