Short-term association between road traffic noise and healthcare demand generated by Parkinson’s disease in Madrid, Spain

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Original article

Short-term association between road traffic noise and healthcare demand generated by Parkinson’s disease in Madrid, Spain

Julio Díaz

^a,^∗

, Pablo Martínez-Martín

^b,c

, Carmen Rodríguez-Blázquez

^b,c

, Blanca Vázquez

^d

, Maria João Forjaz

^a,e

, Cristina Ortiz

^a

, Rocío Carmona

^a

, Cristina Linares

^a

aNationalSchoolofPublicHealth,CarlosIIIInstituteofHealth,Madrid,Spain

bNationalCentreforEpidemiology,CarlosIIIInstituteofHealth,Madrid,Spain

cCIBERdeEnfermedadesNeurodegenerativas(CIBERNED),Madrid,Spain

dSUMMA112,Madrid,Spain

eReddeInvestigaciónenServiciosdeSaludenEnfermedadesCrónicas(REDISSEC),Madrid,Spain

a r t i c l e i n f o

Articlehistory:

Received16December2016 Accepted12January2017 Availableonline24March2017

Keywords:

Roadtrafficnoise Parkinson’sdisease Hospitaladmissions Timeseries

Outpatientcaredemand

a b s t r a c t

Objective:Toanalysewhetherthereisashort-termassociationbetweenroadtrafficnoiseinthecityof MadridandParkinson’sdisease(PD)-relateddemandforhealthcare.

Methods:Time-seriesanalysis(2008–2009)usingvariablesofanalysislinkedtoemergencyanddailyPD- relateddemandforhealthcare(ICD-10:G20–G21),namely,PD-hospitaladmissions(HAs),PD-outpatient visits(OVs)andPD-emergencymedicalcallsinMadrid.Thenoisepollutionmeasurementsusedwere Leqd,equivalentsoundlevelforthedaytimehours(from8a.m.to10p.m.),andLeqn,equivalentsound levelfornighttimehours(from10p.m.to8a.m.)indB(A).Wecontrolledfortemperature,pollution, trendsandseasons,andusedthePoissonregressionmodeltocalculaterelativerisk(RR).

Results: TheassociationbetweenLeqdandHAswasfoundtobelinear.LeqdandLeqnatlag0.1and temperatureatlags1and5weretheonlyenvironmentalvariablesassociatedwithincreasedPD-related healthcaredemand.TheRR(lag0)forLeqdandHAwas1.07(1.04–1.09),theRR(lag0)forLeqdandOV was1.28(1.12–1.45),andtheRR(lags0.1)forLeqnandemergencymedicalcallswas1.46(1.06–2.01).

Conclusion:TheaboveresultsindicatethatroadtrafficnoiseisariskfactorforPDexacerbation.Measures toreducenoise-exposurelevelscouldresultinalowerPD-relatedhealthcaredemand.

Asociaciónacortoplazoentreelruidodeltráficoylademandadeatención sanitariageneradaporlaenfermedaddeParkinsonenMadrid,Espa ˜na

Palabrasclave:

Ruidodetráfico EnfermedaddeParkinson Ingresoshospitalarios Seriestemporales

Demandadeatenciónmédica

re s um e n

Objetivo:AnalizarsiexisteunaasociaciónacortoplazoentreelruidodeltráficoenMadridylademanda deasistenciasanitariaporenfermedaddeParkinson(EP).

Métodos:Análisisdeseriestemporales(2008-2009)utilizandovariablesdedemandasanitariaurgente ydiariaporEP(CIE-10:G20-G21):admisioneshospitalarias(AH),visitasambulatorias(VA)yllamadas médicas(112)enMadrid.LosindicadoresderuidofueronLeqd(nivelderuidodiurnoequivalente,de8 a22h)yLeqn(nivelderuidonocturnoequivalente,de22a8h)endB(A).Secontrolóportemperatura, contaminación,tendenciasyestacionalidades,yserealizóregresióndePoissonparacalcularelriesgo relativo(RR).

Resultados:LaasociaciónentreLeqdyAHporEPeslineal.LeqdyLeqnenelretardo0,1ylatemperatura enlosretardos1y5,fueronlasvariablesambientalesasociadasconelaumentodelademandasanitaria.

SeobtuvounRR(lag0)paraLeqdyAHde1,07(1,04-1,09),yunRR(lag0)paraLeqdyVAde1,28 (1,12-1,45).ElRR(retardos0,1)paraLeqnyllamadasal112fuede1,46(1,06-2,01).

Conclusión: LosresultadosapuntanqueelruidoesunfactorderiesgoparalaexacerbacióndelaEP.

Lasmedidasparareducirlaexposiciónalruidopodríandarlugaraunamenordemandadeasistencia sanitariarelacionadaconlaEP.

∗ Correspondingauthor.

E-mailaddress:[email protected](J.Díaz).

Introduction

Roadtrafficnoiseisamajorpublichealthissue,duetoitsdocu- mentedassociationwithseveraldiseasesandthegrowingnumber of exposed persons world-wide. According to the European https://doi.org/10.1016/j.gaceta.2017.01.005

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J.Díazetal./GacSanit.2018;32(6):553–558

EnvironmentalAgency,over103millionpersonsareexposedto roadtrafficnoiselevelsabove55dB(A)ofmeandailynoise,and closeon24millionareexposedtolevelsabove65dB(A)ofLeqden (equivalentday-evening-nightlevel).¹ Ata globallevel,noise is responsiblefor1.6milliondisabilityadjusted lifeyears(DALYs) per year.² In the city of Madrid,500,000 persons are exposed to nocturnal noise levels and 132,000 are exposed to diurnal noiselevelsin excessof theWorldHealth Organisation (WHO) guidelines:80%ofthisnoiseisduetowheeledtraffic.²

Parkinson’sdisease(PD)isthesecondleadingdegenerativedis- easeinthepopulationandentailsahigheconomiccost,particularly atadvancedstagesofthedisease.³IntheUSA,theeconomicbur- den ofPD rose toover US$14.4 billionin 2010 (approximately US$22,800perpatient)andisprojectedtogrowsubstantiallyover thecomingdecades.⁴

As previously described in detail,⁵ from an environmental standpoint,someriskfactorshavebeenlinkedtodevelopmentof PD:amongthese,pesticidesarethepre-eminentagents,though noconclusiveresultshaveyetbeenobtained.⁶Certainoccupations andcircumstanceshavebeenrelatedtoanincreasedriskofsuf- feringfromPD,possiblyassociatedwithexposuretoproductsthat arepotentiallytoxictothecentralnervoussystemand,specifically, tothesubstantianigra. Theseagents presumablyactbycausing oxidativestress,inflammation,mytochondrialdysfunction,inhibi- tionofproteasome,andotherdisorders whichculminateincell death.^7,8Nevertheless,theevidencesupportingsuchproposalsis limitedorinconsistent, anduntilnow, onlyMPTP(1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine)hasbeenshowntogiveriseto aPD-likedisorderinhumanbeings.^9,10

Therehasrecentlybeenashiftinthewayinwhichthepartic- ipationofcertainenvironmentalfactorsintheaetiologyofPDis viewed.Ratherthanthisbeingseenasaquestionofexposureto environmentalfactorsaffectingaselectedpopulationsample,such asworkersandtheabovepopulationgroups,thislineofreasoning arguesthatitisfactorstowhichtheentirepopulationisexposed, suchastraffic-relatedairpollution,¹¹thatarerelatedtotheaetiol- ogyorexacerbationofneurodegenerativediseases.Anintegrative modelofbiologicalmechanismshasrecentlybeenproposedalong thesesamelines,¹²whichidentifiesroadtrafficnoiseasastressor thatactsinoneoftwoways,namely,eitherchronically,i.e.,through sustainedexposure,oracutely,i.e.,intheshortterm.Fewstud- ieshaveaddressedthequestionofwhethersuchstresscantrigger Parkinson’sdiseaseand,eventhoughthishypothesismaynotbe novel,itisnonethelesscompelling.¹³

Theanalysisproposedinthisstudywastoexplorewhethera short-termassociationcouldbeestablishedbetweenurbanroad trafficnoiseinthecityofMadridandPD-relateddemandforhealth care,i.e.,whetherdailyexposuretonoiseexacerbatedPDsufferers’

demandforhealthcare.Itsrelevanceisevident,sincethiswould notonlyleadtotheidentificationofanenvironmentalriskfactor forPDtowhichthemostoftheinhabitantsofalargecityaregener- allyexposed,butknowledgeofitwouldalsoenablethenecessary preventionmeasurestobeintroduced.

Methods Studypopulation

In Spain,many prevalencestudies focused in PDhave been carriedout.Theresultsofprevalenceobtainedvarybetween150 and1500/10⁵inhabitants.ThemeanprevalenceofEPinSpainis 682.2/10⁵withCI(127.4/10⁵-1491.7/10⁵).ThecityofMadridisa denselypopulatedmetropolitanareasituatedinthecentralregion ofSpain.Duringtheperiod2001-2009,ithadameanpopulation of3,116,897andofthistotal,284,929persons(9%)wereaged75 yearsorover.

Outcomes

We used three variables of analysis linked to PD-related demandfor health care (International ClassificationofDiseases 10^thRevision[ICD-10]codesG20-G21)inMadridacrosstheperiod 01-01-2008to31-12-2009.Thesewere:

•NumberofdailyPD-relatedemergencyhospitaladmissions(PD- hospitaladmissions)tomunicipalhospitalsin Madrid,drawn fromtheMinimumBasicDataSetcompiledbytheMinistryof Health,SocialServicesandEquality.

•NumberofdailyPD-related ambulatoryvisits(PD-ambulatory visits)to primary care centres in Madrid, obtained fromthe MadridRegionalInlandRevenueAuthority.

•NumberofdailyPD-relatedemergencymedicalservicecalls(PD- medicalcalls)madeinthecityofMadrid.Datafurnishedbythe MadridRegionalMedicalEmergencyService(SUMMA112).

Moreover,weconsidereddailyPD-mortalitydata:

•NumberofdailydeathsduetoPD(PD-mortality)(ICD-10:G20- G21)inthecityofMadridfrom01-01-2001to31-12-2009,based ondatafurnishedbytheNationalStatisticsInstitutetotheCarlos IIIInstituteofHealth(MinistryofEconomicAffairsandCompet- itiveness).

Exposure

Asdescribedindetailelsewhere,⁵themainindependentvari- ablesofanalysiswereLeqd,equivalentdiurnalnoiselevel(from 8to22h),andLeqn,equivalentnocturnalnoiselevel(from22to 8h),indB(A),usedasmeasuresofacousticpollution.Thesedata weresuppliedbytheMadridMunicipalAirQualityMonitoringGrid (http://www.mambiente.munimadrid.es/).Thisnetwork consists of27urbanbackgroundstationsacrossthecity.Toestimatedaily meannoiselevels,wefirstaveragedeachmonitor’sdailyleveland thencomputedacity-wideaverageforallthesemonitorsonany givenday.

Thereasonsofthedataperiodchosenfortheanalysisare:first, achangeinthegeographicallocationofthemonitorsofnoiseand pollutantslevelsbelongingtotheMadrid’sAirQualityMonitoring Gridsinceyear2010;second,thedifferentdatasourcesofthePD variablesconsidered:MadridRegionalInlandRevenueAuthority, MadridRegionalMedicalEmergencyServiceandMinistryofEco- nomicAffairsand Competitiveness;maketheperiod2008-2009 wastheonlyperiodoftimetoanalysethedata.

InviewofthefactthatotherstudieshavelinkedPDtourban airpollution¹¹andeventohightemperaturesduringheatwaves,⁵ wecontrolledfortheseenvironmentalvariables.Dailymeancon- centrations(␮g/m³)ofchemicalairpollutants−particulatematter lessthan2.5and10␮mindiameter(PM_2.5andPM₁₀),tropospheric ozone (O₃)and nitrogendioxide(NO₂)−werealso suppliedby theMadridMunicipalAirQualityMonitoringGrid.Maximumdaily temperature(^◦C)inMadridwereallfurnishedbytheStateMeteo- rologicalAgency.

Wecontrolledforlineartrend,seasonalityandtheautoregres- sivenatureoftheseriesitself.Dayoftheweekwasalsoaddedasa covariate.

To assess whether there might be a functional relationship betweennoiselevelsandPD,andifsoofwhattype,weplottedscat- terplotdiagrams.Thesediagramsfurnishinformationonthetype ofrelationshipthatexists(linearorotherwise)betweenadmis- sionsandmortalityduringtheperiodanalysed.Inthesediagrams, thevalueofmortalityorthevalueofPD-relatedadmissionscorre- spondstothemeanvaluetakenbythisvariableforeach0.5dB(A) intervalbetweentheminimumandmaximumvaluesofLeqd/Leqn.

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Previousstudies⁵havereportedtheexistenceofanassociation betweenPD-relatedmorbidityandmortalityduringheatwaves, withaheatwaveinMadridbeingdefinedasanydayordayson whichthemaximumdailytemperatureexceedsthethresholdof 34^◦C¹⁴.Tocontrolforthepossibleeffectoftemperatureonthe dependentvariablesconsidered,thevariableTcalwasdefinedas follows:

T_cal=0 if Tmax<Tthreshold

T_cal=Tmax−TthresholdifTmax>Tthreshold

whereTcalisthevariablethatdeterminestheexistenceoftheeffect ofaheatwaveonPD-relatedmorbidityandmortality.Giventhat theeffectofaheatwaveonPDmaynotbeimmediate,thefollow- inglaggedvariableswerecalculated:Tcal(lag1),whichtakesinto accounttheeffectofthetemperatureonday“d”onmortality,one daylater,“d+1”;Tcal(lag2),whichtakesintoaccounttheeffect ofthetemperatureonday“d”onmortality,twodayslater,“d+2”;

andsoonsuccessively.Thenumberoflagswereselectedonthe basisoftheliterature,whichestablishesthattheeffectofheaton morbidityandmortalityisshort-term(T_cal:lags1-5)¹⁴.

Insofarasnoise-relatedvariableswereconcerned,sinceearlier studiesundertakeninMadridhadreportedshort-termassociations betweennoise andmorbidity/mortalityuntillag7thevariables LeqdandLeqnwereintroducedintothemodelswithlagsofupto 7days.Asimilarapproachwastakeninthecaseofthevariablesof chemicalairpollution(PM₁₀,PM_2.5,NO₂andO₃)¹⁵.

Statisticalanalysis

Thestudydesigncorrespondstoanecologicaltimeseriesstud- iesofshort-termassociationscomparetheoutcome(PD-variables) andexposureseries(environmentalfactors).Themainmethod- ologicalissuesinthisapproachareselectionofsmoothingmethods for the decomposition of the series, the presence and estimation of delayedeffects and thepotential confounding byother time-varyingfactors.Generalisedlinearmodels(GLMs)werecon- structedwiththePoissonregressionlink.Thisenabledustoobtain theestimatorneededtocalculatetherelativerisk(RR)forincreases of1dB(A)inLeqdandLeqnlevels.BasedontheRR,wethencom- putedtheattributablerisk(AR)associatedwiththisincreaseby meansofthefollowingequation:AR=RR−1/RR.¹⁶Significantenvi- ronmentalvariablesweredeterminedusingthebackwardstepwise procedure,beginningwiththemodelthatincludedalltheexplana- toryvariables,andgraduallyeliminatingthosewhichindividually displayedleaststatisticalsignificance,withtheprocessbeingreit- erateduntilallthevariablesincludedweresignificantatp<0.05.

TheRRandARvalueswerecalculatedforincreasesof1dB(A)inthe caseofLeqdandLeqn⁵,and1^◦CinthecaseofTcal¹⁷.

AllanalyseswereperformedusingtheIBMSPSSStatistics22 andSTATAv11.2statisticalsoftwareprogrammes.

Results

Table1showsthedescriptivestatisticsforthedifferenthealth variableslinkedtoPD-relateddemandforhealthcare,alongwith thevariablesrelatingtoacousticpollution,chemicalpollutionand temperature,measureddailyinthecityofMadridacrosstheperiod 2008-2009.

Withrespecttoenvironmentalnoise levelsduringthestudy period,theWHO¹⁸diurnalthresholdnoiselevel(Leqd)of65dB(A) wasexceededon170days,i.e.,23.2%ofdays,while,theWHOnoc- turnalguidelinenoiselevel(Leqn)of55dB(A)¹⁸wasexceededon 731nights,i.e.,100%ofnights.

Table1

DescriptivestatisticsofvariablesrelatedtoParkinson’sdiseaseandindependent andcontrolvariables:Madrid,2008-2009.

Variables N Maximum Minimum Mean SD

PD-hospitaladmissions 731 25 0 9.19 3.67

PD-ambulatoryvisits 731 4 0 0.55 0.78

PD-medicalcalls 731 3 0 0.14 0.40

PD-mortality^a 3287 4 0 0.32 0.58

Tmax^b(^◦C) 731 38.4 1.0 20.5 8.9

NO2(␮g/m³) 731 121.0 17.6 54.9 17.3

PM2,5(␮g/m³) 731 41.9 3.4 13.6 5.5

PM₁₀(␮g/m³) 731 105.0 6.9 25.4 11.6

O₃(␮g/m³) 731 88.8 6.7 41.7 19.0

Leqd(dB(A)) 731 66.9 59.4 63.9 1.3

Leqn(dB(A)) 731 66.3 55.0 58.6 1.4

Leqd:equivalentdiurnalnoiselevel(from8to22h);Leqn:equivalentnocturnal noiselevel(from22to8h);NO₂:nitrogendioxide;O₃:troposphericozone;PM_2,5: particulatematterlessthan2.5␮mindiameter;PM10:particulatematterlessthan 10␮mindiameter;PD:Parkinson’sdisease;SD:standarddeviation.

aDailyPD-relatedmortalityacrosstheperiod2001-2009.

bMaximumtemperature.

Figure1showsthefunctionalrelationshipbetweenLeqdlevels anddailyPD-hospitaladmissions(scatter-plotdiagram).Aswillbe seen,therelationshipwaslinear,withoutanyspecificthreshold.

Withanr-squaredvalueof0.826andanFcoefficientof52.335, linearadjustmentwassignificantatp<0.0001.If,insteadoftotal linearadjustment,adjustmentismadeusingtheLOWESSmethod and70%ofthepoints,Figure2isobtained,fromwhichitwillbe seenthatdailydiurnalnoisehaditsgreatesteffectonemergency PD-hospitaladmissionsatvaluesrangingfrom62to65dB(A),i.e., levelslyingbelowtheWHOguidelinevalues.

Excludingthevariablesof control,trend andseasonality,the independentvariableswhichregistereda statisticallysignificant association(p<0.05)withthePDvariablesanalysedareshownin Table2.

InthecaseofthevariablesofPD-relateddemandforhealthcare, novariableofchemicalairpollutionprovedsignificantforanyofthe threehealth-carecausesanalysed.OnlythevariableTcalshowed astatisticallysignificantassociationatlags1and5,inthecaseof PD-hospitaladmissions,withanRRof1.13(1.03-1.23).Dailydiur- nalnoiselevelsweresignificantatlag0inthecaseofPD-hospital admissionsandPD-ambulatory visits;and dailynocturnalnoise levelsweresignificantatlags0and1inthecaseofPD-medical calls,withajointRRof1.46(1.06-2.01).

Leqd dB(A)

66.0 65.0 64.0 63.0 62.0 61.0 60.0 11.0

10.0

9.0

8.0

7.0

6.0

5.0

Dail y PD-related hospital admissions

Figure1. ScatterplotwithlinearfitbetweendailyPD-hospitaladmissionsanddaily diurnalnoiselevels(Leqd).O:observed;−linearfit.

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Leqd dB(A)

66.0 65.0 64.0 63.0 62.0 61.0 60.0

Daily PD-related hospital admissions

11.0

10.0

9.0

8.0

7.0

6.0

5.0

Figure2. ScatterplotbetweendailyParkinsondiseasehospitaladmissionsand dailydiurnalnoiselevels(Leqd)withlowessfit(70%).

Table2

Relativerisksforanincrementof1dB(A)indailydiurnalnoiselevelsanddaily nocturnalnoiselevelswithattributablerisks.ForTcal,relativeriskandattributable riskforeveryincrementof1^◦Cincaseswherethedailymaximumtemperature surpassedthethresholdof34^◦C.

Variables RR(95%CI) AR(95%CI)

PD-hospitaladmissions Tcal^a(lags1,5):

1.13(1.03-1.23) Leqd(lag0):1.07 (1.04-1.09)

11.4%

(3.3-18.9) 6.2%(4.1-8.3)

PD-ambulatoryvisits Leqd(lag0):1.28 (1.12-1.45)

21.6%

(10.8-31.0) PD-medicalcalls Leqn(lags0,1):

1.46(1.06-2.01)

31.4%

(5.6-50.2) PD-mortality Tcal(lag3):1.14

(1.01-1.28)

12.1%

(0.9-22.0) AR:attributablerisk;95%CI:confidenceintervalof95%;Leqd:equivalentdiurnal noiselevel(from8to22h);Leqn:equivalentnocturnalnoiselevel(from22to8h);

PD:Parkinson’sdisease;RR:relativerisk.

aVariablethatdeterminestheexistenceoftheeffectofaheatwaveonPD-related morbidityandmortality.

Asis clearfrom Table2, noise levels (Leqdand Leqn) were theonlyvariablesinthethreecauseswhich werelinkedtoPD- relateddemandforhealthcare.Furthermore,itwasnoteworthy thatonlythevariableTcal−inthiscaseatlag3−wasrelatedto dailyPD-mortality.Intermsoflagtimesbetweenanygivencause anditseffectonPD,theeffectofnoisewasseentobeimmedi- ate−invariablyatlags0and1−whereastheeffectofheatwaves extendeduntillag5inthecaseofPD-hospitaladmissions.

Fromaquantitativepointofview,theeffectofnoiseonthevari- ablesofPD-relatedhealthcareshowedthatforeverydB(A)that noiselevelsinMadridfell,dailyPD-hospitaladmissionsdecreased by6.2%,PD-ambulatoryvisitsdecreasedby21.6%,andPD-medical callsdecreasedby31.4%.

Discussion

Ourstudydesign,i.e.,ecologicaltime-seriesanalysis,hasnovel featureswithrespecttothemethodologyusedbythefewstudies thathaveanalysedtherelationshipbetweenenvironmentalfac- torsandPD^10,11.Inthelatter,exposuretotheenvironmentalfactor, traffic-relatedpollution,remainedconstantthroughoutthestudy period,somethingthatactedasabartodetectingthetemporal effectoftheincidenceofthepollutantonPD.Thismethodology isappropriateiftheaimistoshowtherelationshipbetweenthe diseaseanda possibleenvironmentalorigin. Whenitcomesto

demonstratingthattheshort-termeffectofagivenenvironmental factorcanexacerbatethesymptomsofadisease,however,time- seriesanalysis hasshown itselfto beespecially useful,since it allowsonetoestablishthetimewindowbetweencauseandeffect.

Moreover,asregardsexacerbationofspecifichealthevents,this methodologyhasdemonstrated its usefulnessin earlierstudies whichaddressedadversebirthoutcomesandroadtrafficnoise¹⁹ andPM_2.5concentrationsandheat-wavetemperatures¹⁷.

OftheenvironmentalvariablesshowninTable1,thisstudyis concernedsolelywithdailynoisegeneratedinMadrid,essentially byroadtraffic,sincetherelationshipbetweenPDandheat-wave temperatureshasalreadybeenthesubjectofpublication.⁵Despite thefact thatanalysis ofthechemical air pollutantsshowed no short-termrelationshipbetweenincreasedconcentrationsandthe PDvariablesconsidered,theexistenceofresearchlinkingPDto traffic¹¹rendereditadvisableforthesetobeintroducedascontrol variables.

TheLeqdvalues inTable1,whichexceededtheWHOguide- linevalue¹⁸ on23.2% ofdays, showroadtraffic noise tobean importantpublichealth problemin Madrid.It shouldbenoted thatfourPD-relatedvariableswereselectedforstudypurposes, threerelatingtodemandforhealthcareandonerelatingtomor- tality.AsindicatedintheMethodssection,thedataforeach of thesehealthvariablesweredrawnfromadifferentsource,sothat theresultsobtainedminimisethebiaswhichmighthaveother- wiseresultedfromusingasingledatasource,somethingthatlends robustnesstotheresults.Ofthe4variablesconsidered,dailyPD- hospitaladmissionsregisteredthehighestmeanvalue,whichis whythisvariablewaschosenforplottingthescatterplotdiagrams inFigures1and2.

Figure1indicatesthattherelationshipbetweendiurnalnoise (Leqd)andPD-hospitaladmissionsislinear,withoutanyspecific threshold,i.e., anyincreasein noise levelswould beassociated withanincreasein PD-relatedadmissions.Thisfunctionalrela- tionshipbetweennoiseandhealthindicatorshasbeenpreviously observed in the case of hospital admissions, respiratory-cause and circulatory-cause mortality, and noise and adverse birth outcomes²⁰. Furthermore,Figure2 shows that theslope ofthe associationbetweenLeqdandPD-hospitaladmissionswasmost pronounced in the 62-65 dB(A) range, i.e., values traditionally deemedbytheWHO¹⁸tobe“safe”fortheprotectionofhealth.

Fromaqualitativestandpoint,anumberofconclusionscanbe drawnfromTable2.Firstly,roadtrafficnoiseistheonlyenviron- mentalvariablethatdisplaysastatisticallysignificantassociation (p<0.05)withthethreehealth-careindicatorsanalysed,thoughnot withPD-relatedmortality,wherethesoleenvironmentalvariable toshowanassociationwasheat-wavetemperature⁵.

AfurtherqualitativeconclusiontobedrawnfromTable2isthat thevariablesofchemicalairpollutionarenotrelatedintheshort termtoPD-relatedexacerbationsormortality.Theresultsobtained byarecentDanishstudy¹¹,basedonacase-controlanalysisofsub- jectswhohadlivedinthesameplaceforover20years,reporteda relationshipbetweenexposuretotrafficandriskofPD,whichwas moremarkedinthecapitalcitythaninprovincialtowns,withno evidenceofanassociationamongruralresidents.Itwouldtherefore seemthatchemicalairpollutionproducedbyroadtrafficmaybe relatedtoprevalenceofthediseasebutnottotheshort-termeffects thatsuchurbanchemicalpollutantscanhave.Thisresultwouldalso supporttheviewthatthehealtheffectscausedbyroadtrafficnoise areindependentofthosecausedbychemicalairpollution²¹.

Withregardtothebiologicalmechanismwherebyroadtraffic noisemanagestoexacerbatePDcasestothepointoftheirrequir- inghealthcare,attentionshouldbedrawntothepaperbyRecio etal.¹²Itsauthorsproposeanintegrativemodelwhichexplains therelationshipbetweennoiseanditsensuingstressreactionsin theorganism,andhowsuchstressaffectsrespiratory,circulatory

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andendocrine diseases.Thisintegrativemodelaccountsforthe twotypesofassociationsbetweenroadtrafficnoiseandvarious adverse effects anddiseases reportedby themostrecent noise research:firstly,thoseinwhichnoiselevelsareconsideredcon- stant predictors, i.e., assumed not to vary over time and thus liabletocausechronicstress^22,23;andsecondly,thoseinvestigated inthemostrecenttime-seriesstudies,^20,22,23whoseresultsindi- catethatroadtrafficnoisecanalsohaveacuteeffectsonhealth.

Environmentalstressorscouldberelatedtothedevelopmentand worseningofneurodegenerativediseases,asdescribedbyLinares etal.²⁴fordementia-relatedhospitaladmissions,inwhich,aside frompersonalpredisposition(geneticfactors)andageing,extrin- sicfactors(e.g.,toxins,pollutants,infections)alsoplayarole.The mechanismswhereby stressorscouldaccomplish theirharmful effectwouldpresumablybevascularlesions,inflammation,com- promised immune responses,alterations in thedisease-specific protein, and others able to alter the homeostatic pathways of especiallyvulnerableneuronalsubpopulationsandglialcells.^25–27 Froma quantitativepoint ofview,noteshouldbe takenofthe highARvaluesforPD-ambulatoryvisitsandPD-medicalcalls,due to the paucity of suchservices, as shown in Table 2. Further- more,theARforPD-hospitaladmissions(6.2%)wassimilartothat foundfortheeffectofheat-wavetemperaturesonPD⁵.Compari- sonofthisvaluetothoseobtainedforemergencyadmissionsdue todiurnal noise shows it tobeslightly higherthan the values attributabletoallcauses(AR=5.1%),circulatorycauses(AR=4.2%) andrespiratorycauses(AR=3.7%)reportedbystudiesalsounder- takeninMadrid,¹⁵thoughthesedifferencesarenot statistically significant.

Withrespectto thelimitations ofthis study andany possi- ble resultingbiases,thefollowing shouldbementioned:firstly, anecologicalstudysuchasoursdoesnotpermitinferencestobe madeatanindividuallevelforfearoftheecologicalfallacyaris- ingasa result oftheuseofpooled data.Furthermore,when it comestomethodologicallimitations,mentionshouldessentially bemadeofthoseinherentinastatisticalmethodthatworkswith ahighnumberofvariablesata95%confidencelevel.Ontheother hand,anacknowledgedlimitationofallstudiesofenvironmen- taldataisthatmeasurementsfromstationaryoutdoormonitors maynotrepresentindividualexposures,thoughrelativelycrude, ambientmeasuresareoftenthemostfeasiblemeasureofexpo- sure in terms of cost and burden to the study participant. No specificvalidationwascarried outtoassesstherepresentative- ness of spatial variability in air pollutants: our study suffered fromBerkson-typemeasurementerror,including,amongothers, biasassociatedwithecologicalexposure, asis commoninmost time-seriesstudies, which leads tono or little biasbut nevertheless decreases statisticallypower. Not only do air-pollutant concentrationshavedifferentspatialdistributions,butthedegree to which outdoor levels reflect indoor levels also varies. This leads to different degrees of measurement error and, thus, of powerforeachofthese,andmayinfluencewhichassociationsare detected.

Inbrief,theresultsobtainedbythisstudygotoconfirmthat roadtrafficnoiseinalargecityisanimportantriskfactorformany diseases,includingPD,whichwouldnotappeartoberelated,in theshortterm,tochemicalpollutantsemittedbyvehicles.Thefact thattheassociationsfoundbetweenroadtrafficnoiseandPDwas especiallyevidentforvaluesbelowtheWHOguidelinethreshold fordiurnalnoise underscorestheneedfora reviewandupdate ofthesethresholds.Themainstrengthofthisanalysisisthatthe statisticallyassociationswithnoiselevelsexitswiththethreevari- ablesofPD-morbidityvariablesconsidered.Thisfactreinforcesthe non-spuriousassociations.

Fromthestandpointofprevention,theresultsofthispaperindi- catetheneedfortwodistinctandcomplementaryformsofaction:

firstly,atapublicadministrationlevel,implementingtheneces- sarymeasurestoreducenoiselevelsinMadrid,andsecondly,ata personallevel,limitingPD-sufferers’exposuretoroadtrafficnoise, whetherathomeorinplacestowhichtheyhavebeenadmitted.

Thesemeasureswouldresultina lowerPD-relateddemandfor health careand,by extension,a decreaseinthehigheconomic burdenassociatedwithPD.⁴ Amongthefuturelinesofresearch itwouldbeadvisabletocarryoutcohortstudiestoidentifytraffic noiseasanetiologicalandnon-exacerbatingfactorofthesymp- tomsofthePD.

Whatisknownaboutthetopic?

Recentresearchincohortdesignsissuggestingthattraffic noisemaybeinvolvedintheetiologyofsomeneurodegen- erativediseasessuchasParkinsondisease,Alzheimerdisease anddementia.Butnotthatatshorttermenvironmentalfactors canexacerbatethesymptomatologyofthisdisease.

Whatdoesthisstudyaddtotheliterature?

The research presented here is a novel study basedon timeseriesthatestablishattheshorttermastatisticassoci- ationbetweentrafficnoiseandParkinsondisease.Theresults obtainedgotoconfirmthattrafficnoiseinalargecityisan importantriskfactorforParkinsondisease.

Acknowledgements

Thispaperpresentsindependentresearchandresults.Theviews expressedarethoseoftheauthor(s)andnotnecessarythoseofthe InstitutodeSaludCarlosIII.

Editorincharge CarlosÁlvarez-Dardet.

Transparencydeclaration

Thecorrespondingauthoronbehalfoftheotherauthorsguar- antee the accuracy, transparency and honesty of the data and informationcontainedinthestudy,thatnorelevantinformation hasbeenomittedandthatalldiscrepanciesbetweenauthorshave beenadequatelyresolvedanddescribed.

Authorshipcontributions

C. Linares designed the study and directed its implementa- tion,includingqualityassuranceandcontrol.P.Martínez-Martín helpedconducttheliteraturereviewandpreparetheMethodsand theDiscussionsectionsofthetext.C.Rodríguez-Blázquezhelped conducttheliteraturereview andpreparetheMethodsand the Discussionsectionsofthetext.J.Forjazhelpedsupervisethefield activitiesanddesigned thestudy’s analyticstrategy.B. Vázquez Quiroga helped supervise the field activities and designed the study’s analyticstrategy. R.Carmonahelpedsupervisethefield activitiesanddesignedthestudy’sanalyticstrategy.C.Ortizhelped supervisethefieldactivitiesanddesignedthestudy’sanalyticstrategy.J.Díazdesignedthestudyanddirecteditsimplementation, includingqualityassuranceandcontrol.

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Funding

Thisstudywasfundedbya“MiguelServettype1”grant:SEPY 1037/14andaFISProjectENPY1001/13fromtheCarlosIIIInstitute ofHealth.

Conflictsofinterest None.

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