Prevalence of asthma and allergic diseases in adolescents: nine-year follow-up study (2003-2012)

JPediatr(RioJ).2015;91(1):30---35

www.jped.com.br

ORIGINAL

ARTICLE

Prevalence

of

asthma

and

allergic

diseases

in

adolescents:

nine-year

follow-up

study

(2003-2012)

夽

,

夽夽

Dirceu

Solé

,

Nelson

A.

Rosário

Filho

,

Emanuel

S.

Sarinho

,

Inês

C.

Camelo-Nunes

_,

_Bruno

_A.

_Paes

_Barreto

_,

_Mércia

_L.

_Medeiros

_,

Jackeline

Motta

Franco

_,

_Paulo

_A.

_Camargos

_,

_Javier

_Mallol

_,

_Ricardo

_Gurgel

_,

Djanira

M.

de

Andrade

_,

_Fernanda

_P.

_Furlan

_,

_Almerinda

_R.

_Silva

_,

Cristina

Cardozo

_,

_Cláudia

_Andrade

a_{DepartmentofPediatrics,EscolaPaulistadeMedicina,UniversidadeFederaldeSãoPaulo(Unifesp),SãoPaulo,SP,Brazil} b_{UniversidadeFederaldoParaná(UFPR),Curitiba,PR,Brazil}

c_{DepartmentofPediatrics,UniversidadeFederaldePernambuco(UFPE),Recife,PE,Brazil} d_{UniversidadeEstadualdoPará(UEPA),Belém,PA,Brazil}

e_{DepartmentofPediatrics,UniversidadeFederaldeAlagoas(UFAL),Maceió,AL,Brazil} f_{DepartmentofPediatrics,UniversidadeFederaldeSergipe(UFS),Aracajú,SE,Brazil}

g_{DepartmentofPediatrics,UniversidadeFederaldeMinasGerais(UFMG),BeloHorizonte,MG,Brazil} h_{UniversidadedeSantiago(USACH),Santiago,Chile}

Received27March2014;accepted30May2014 Availableonline18July2014

KEYWORDS Asthma; Adolescent;

Atopiceczema;

Epidemiology;

Allergicrhinitis;

Rhinoconjunctivitis

Abstract

Objective: Todeterminetheprevalenceofsymptomsofasthma,rhinitis,andatopiceczema

inadolescents(AD;13-14years)livinginsevenBraziliancities,byapplyingthestandardized

writtenquestionnaire(WQ)oftheInternationalStudy ofAsthmaandAllergiesinChildhood

(ISAAC),andtoevaluatethetimetrendnineyearsafterthelastassessmentofISAACphase3

(ISP3).

Methods: TheISAAC-WQwasansweredby20,099ADfromtheNorthern,Northeastern,

South-eastern, andSouthernBrazilian regions. Valuesobtained werecompared to thoseobserved

夽 _{Pleasecitethisarticleas:SoléD,RosárioFilhoNA,SarinhoES,Camelo-NunesIC,BarretoBA,MedeirosML,etal.Prevalenceofasthma}

andallergicdiseasesinadolescents:nine-yearfollow-upstudy(2003-2012).JPediatr(RioJ).2015;91:30---5.

夽夽

StudyconductedattheDisciplineofAllergy,ClinicalImmunology andRheumatology,DepartmentofPediatrics,EscolaPaulistade Medicina,UniversidadeFederaldeSãoPaulo,SãoPaulo,SP,Brazil.

∗_{Correspondingauthor.}

E-mail:alergiainmunologiareumatologia@unifesp.br,dirceu.sole@unifesp.br(D.Solé).

http://dx.doi.org/10.1016/j.jped.2014.05.002

in ISP3 using nonparametric (chi-squared or Fisher) tests, and the ratio of annual

incre-ment/decrementwasestablishedforeachofthecenters,accordingtothesymptomassessed.

Results: ConsideringthenationaldataandcomparingtovaluesofISP3,therewasadecrease

inthemeanprevalenceofactiveasthma(18.5%vs.17.5%)andanincreaseinthefrequencyof

severeasthma(4.5%vs.4.7%)andphysician-diagnosedasthma(14.3%vs.17.6%).Anincrease

inprevalenceofrhinitis,rhinoconjunctivitis,andatopiceczemawasalsoobserved.

Conclusions: The prevalenceofasthma, rhinitis,andatopiceczema inBrazil was variable;

higherprevalencevalues,especiallyofasthmaandeczema,wereobservedinregionslocated

closertotheEquator.

©2014SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Allrightsreserved.

PALAVRAS-CHAVE Asma;

Adolescente;

Eczemaatópico;

Epidemiologia;

Rinitealérgica;

Rinoconjuntivite

Prevalênciadeasmaedoenc¸asalérgicasemadolescentes:estudoevolutivodenove anos(2003a2012)

Resumo

Objetivo: Determinaraprevalênciadesintomasrelacionadosàasma,riniteeeczemaatópico

emadolescentes(13-14anos,AD)residentesemsetecidadesbrasileirasempregandoo

ques-tionárioescrito(QE)padronizadodoInternationalStudyofAsthmaandAllergiesinChildhood

(ISAAC)everificaratendênciatemporalpassadosnoveanosdaúltimaavaliac¸ãodoISAACfase

3(ISF3).

Métodos: OQEISAAC foirespondido por20.099 AD(13-14anos) moradoresem centrosdas

regiões Norte, Nordeste, Sudeste e Sul. Os índices obtidosforam comparados aos do ISF3

utilizando-se teste não paramétrico (qui-quadrado ou Fisher) e foi estabelecida a taxade

incremento/decrementoanualparacadaumdoscentrossegundoosintomaavaliado.

Resultados: Emrelac¸ãoaoISF3,considerando-seosdadosnacionais,houvequedada

prevalên-ciamédiadeasmaativa(18,5%vs.17,5%)comelevac¸ãodafrequênciadeasmagrave(4,5%vs.

4,7%)edeasmadiagnosticadapormédico(14,3%vs.17,6%).Aumentodaprevalênciaderinite

erinoconjuntiviteedeeczemaflexuraltambémocorreram.

Conclusões: Aprevalênciadeasma,riniteeeczemaatópiconoBrasilfoivariável.Valoresmais

altos,sobretudodeasmaeeczemaforamobservadosnoscentroslocalizadosmaispróximosao

Equador.

©2014SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Todososdireitos

reservados.

Introduction

The prevalence of asthma and allergic diseases in

chil-dren has shown wide variation worldwide and according

tosomeauthors,ithasincreased,especiallyindeveloping

countries.1---5_{Up toafew decadesagothisknowledgewas}

limited, for lack of a single, standardized, and validated tooltobeuseduniversally,andrestricted tostudies were performedin smallsamples,whichprecludedcomparisons betweendifferentpopulationsandatdifferenttimes.

AftertheInternationalStudyofAsthmaandAllergiesin Childhood(ISAAC),whichcreatedastandardizedprotocol, suchcomparisonsbecame possible;sincethen, havebeen widelyperformed.6_{BeforetheISAACprotocol,fewstudies,}

usingthesametool(writtenquestionnaire[WQ]),wereable toevaluatethetemporaltrendoftheprevalenceofasthma, rhinitis,andatopiceczemainchildren.Oneofthese stud-iesassessedNorwegianchildrenaged7to14yearsbetween 1985and2008,regardingtheprevalenceofasthma,rhinitis, andatopiceczema;atrendofincreasingasthmaand rhini-tisprevalenceandstabilizationforeczemawasobserved.7

Another study, with a longer follow-up, conducted from

1964to2004inEnglishschoolchildren(7-12years)observed decliningrates ofwheezing,withanincrease in rhinocon-junctivitisandatopiceczema.8

ThemeantimebetweenthecompletionofISAACPhase 1 (ISF1) and ISAAC Phase 3 (ISF3) was seven years, and the prevalence rates obtained in all centers that con-currently participated in both phases showed conflicting results,mainlyinthosecentersthatpresentedhighvalues.2

In Brazil, an increase in the prevalence of asthma symp-tomsinschoolchildrenaged6-7yearsfrom21.3%inISF1to 24.4%inISF3 andastableprevalence of rhinoconjunctivi-tis(12.5%and12.0%,respectively)andatopiceczema(6.8% and6.8%,respectively)wereobserved.Amongadolescents (ADs)therewasadecreasein prevalence ratesof asthma symptoms(22.7%to19.9%,respectively), rhinoconjunctivi-tis(16.2%to15.8%,respectively),andatopiceczema(5.3% to4.2%,respectively).2

32 SoléDetal.

Subjects

and

method

Sevenofthe21centersparticipatingintheISF3inBrazil2,9---11

accepted the invitation to participate in this study, nine years after its completion. The study was supported by FAPESP (Project PPSUS No. 2009-53303-5). The recom-mendedcriteriaweremetinallcentersandtheADswere selectedasrecommended by theISAAC6,12 _{protocol. With}

theexceptionofBelém(stateofPará,North[N]),allother centershad their ISF3 data approved by the ISAAC Inter-national DataCenter,and the following were categorized as official centers: Recife (Pernambuco, Northeast [NE]); Maceió(Alagoas,NE);Aracaju(Sergipe,NE);BeloHorizonte (MinasGerais, Southeast [SE]); SãoPaulo (São Paulo, SE); andCuritiba(Paraná,South[S])(Tables1and2).

Inall participatingcenters,ADs(13-14yearsold)were selected from public and private schools. Data on num-berof schoolsandstudentsenrolledwereprovidedbythe respectiveDepartmentsofEducationofeachcenter,anda minimumof1,000 studentswere assessed.The study was approvedbyeachResearchEthicsCommittee,andall sub-jectssignedaninformedconsent;datacollectioniniciated in2011andwascompletedin2012.Thegeneralprojectwas approvedbyUniversidadeFederaldeSãoPaulo/HospitalSão PauloResearchEthicsCommittee(n.1345/09).

After defining the sample in each of the cities, the ISAACWQ, previouslytranslated intoBrazilian Portuguese andculturallyvalidated,13---15_{wascompletedbyADsintheir}

classrooms(n=20,099),whichyieldedahighrateofproperly filledoutquestionnaires.Dataweremanuallytransferredto thedatabaseprovidedbythegeneralcoordinatorsofISAAC protocol.

FromtheISAAC-WQasthmamodule,thefollowing ques-tions wereconsidered: wheezing at some time;wheezing in the last 12 months (current asthma); wheezing severe enough to limit speech in the last 12 months (severe asthma);physician-diagnosedasthma(asthmaatsometime inlife);wheezingatexercises;andnocturnalcough.2,13

FromtheISAAC-WQrhinitismodule,thefollowing ques-tions were considered: sneezing, runny nose and nasal obstructionat sometimein thepast 12months(rhinitis), andnasalproblemsassociatedwithitchyandwateryeyesin thelast12months(rhinoconjunctivitis).2,14

From the ISAAC-WQ eczema module, the following questions were considered: skin rash that appeared and disappearedinthelast12months(eczema)andthis charac-teristicrashinplacessuchasskinfoldsandbuttocks(atopic eczema).2,15

Thevaluesobtainedwerecomparedtothosepreviously publishedin ISF39---11 _{andexpressed asan annual}

percent-ageofchange(Table2).Dataanalysiswasperformedwith non-parametrictests,chi-squaredtest,orFisher’sexacttest and5%wasestablished astherejection levelfor the null hypothesis.

Results

Table1summarizesthepercentagedataontheprevalence ofsymptomsof asthma, rhinitis,and eczemaof ADsfrom seven Brazilian centers that participated in the ISF3, as well as the current values, obtained nine years later.

Comparative analysis between the values obtained in the two studies was performed in each center; significantly highervalueswereidentified.

Consideringthegeneraldata,asignificantdecreasewas observedintheprevalenceofwheezingatsometimeinlife, wheezinginthepreviousyear(activeasthma),andwheezing associatedwithexerciseduringthisperiod(Table1). Con-versely,therewasasignificantincreaseintheprevalenceof physician-diagnosedasthma,nocturnal cough,nasal symp-toms without having a cold (rhinitis), rhinoconjunctivitis, andatopiceczema(Table1).Regardingtheannual percent-ageofchange,adecreaseof0.41%/yearwasobservedfor the prevalence of wheezing at some time in life and an increaseof0.6%/yearforthereportingofnocturnalcough (Table 2). For nasal symptoms, there was an increase of 0.68%/yearforrhinitisand0.55%/yearfor rhinoconjunctivi-tis,aswell as a0.08% annual increase for atopiceczema (Table2).

Discussion

When the prevalence rates observed in different centers

participating in this study are analyzed, nine years after

the end of ISF3, a distinct and variable behavior can

be observed. In general, a decline in the prevalence of

activeasthmaandanincreaseintheprevalenceofrhinitis,

rhinoconjunctivitis,aswellasatopiceczemawereobserved

(Tables1and2).

Regardingasthmaandrelatedsymptoms,itwasobserved thatthe decreaseinthe prevalenceof activeasthmawas partly due to the decrease observed in Belém and Ara-caju,despite thesignificant increasethatoccurred inSão Paulo. Moreover, there was a significant increase in the prevalence of physician-diagnosed asthma, which ranged between14.3%and17.6%inallcenters,exceptBelémand Aracaju.Conversely, thenumberofsevere events(speech impairment) remained unchanged,as opposedto nonspe-cific symptoms such asnocturnal cough, which increased (Tables1and2).

What happened during this time interval that would explain these changes? When analyzing the period of 18 years since the ISF1 data were obtained, it can be observedthattheHumanDevelopmentIndex(HDI)inBrazil increased, going from 0.724 in 1993/199416 _{to 0.807 in}

2012.17 _{This increasewasobserved inallcentersinvolved}

in the study;however, it wasmorepronounced inthe NE andNregions.Therewasnosignificantcorrelationbetween HDIandtheprevalenceofactiveasthma, rhinoconjunctivi-tis, and atopic eczema in both 2003 and 2012 (data not shown).

Thesedataarecorroboratedwhenconsidering thefact thattheGrossDomesticProductpresentedthesame behav-ior,goingfromUS$3,040in1994toUS$11,630in2012.18,19

Althoughthecountryeconomicstatusdidimprove,toinfer thatsuchimprovementisresponsibleforthechangesinthe prevalenceratesobservedhereinisafragileassumption.

Moreover,afterthe2000s,asthmatreatmentimproved, asthecreationoftheNationalAsthmaControlPlan(Plano NacionaldeControledaAsma-PNCA)startedprovidingdrug therapyforpatientswithsevereasthma20_{andwasextended}

Prevalence

of

asthma

and

allergic

diseases

33

Table1 Prevalenceofaffirmativeresponsestothequestionsonsymptomsofasthma,rhinitisandeczemaofthewrittenquestionnaireoftheInternationalStudyofAsthma

andAllergiesinChildhoodgivenbyadolescentfromthecentersthatparticipatedintheISAACphase3studyandinthecurrentstudy.

Question Belém Recifea _Maceióa _Aracajua

2003 2012 2003 2012 2003 2012 2003 2012

n=1,773 n=3,708 n=2,865 n=1,149 n=2,745 n=3,628 n=3,041 n=3,009

Wheezingatsometime 43.1b _{38.7 37.8}b _{32.9 29.5}b _{25.2 33.2}b _25.4

Wheezingin12months 23.1b _{20.7 19.1 19.6 14.8 13.2 18.7}2 _12.8

Speechimpairment 5.0 6.0 4.1 7.0b _5.0b _{3.5 6.8}b _3.6

Asthmadiagnosis 32.8b _{29.3 18.0 22.5}2 _{13.8 15.8}b _15.4b _12.7

Wheezingatexercises 21.7 22.5 23.0 22.5 18.9b _{14.6 19.0}b _16.4

Nocturnalcough 45.7 51.1b _{37.3 41.0}b _{42.0 40.8 41.3}b _38.3

Nasalsymptomsin12months 47.4b _{44.2 35.8}b _{26.3 26.4 38.8}b _{25.6 29.9}b

Rhinoconjunctivitis 28.5 27.9 14.5 17.3b _{13.8 19.2}b _17.4b _15.4

Skinsymptoms 11.8 12.5 10.1 8.4 7.5 8.9b _11.2b _7.1

Atopiceczema 6.2 7.9b _{5.0 3.9 4.0 5.1}b _7.9b _3.4

Question BeloHorizontea _SãoPauloa _Curitibaa _General

2003 2012 2003 2012 2003 2012 2003 2012

n=3,088 n=2,642 n=3,161 n=2,433 n=3,628 n=3,530 n=20,301 n=20,099

Wheezingatsometime 47.3 45.5 44.6 43.7 40.7 39.8 38.8 35.5b

Wheezingin12months 17.8 19.7 18.7 21.3b _{18.9 17.6 18.5 17.5}b

Speechimpairment 4.8 5.0 2.9 4.4b _{3.1 4.5}b _{4.5 4.7}

Asthmadiagnosis 9.8 17.3b _{10.4 13.6}b _{9.2 13.1}b _{14.3 17.6}b

Wheezingatexercises 18.6 21.7b _17.0b _{12.1 19.1 19.9 19.4 18.3}b

Nocturnalcough 37.4 39.3 33.3 45.4b _{34.7 42.4}b _{38.2 43.0}b

Nasalsymptomsin12months 26.1 34.1b _{27.4 49.9}b _39.2b _{31.6 31.8 37.2}b

Rhinoconjunctivitis 14.5 18.3b _{12.2 24.5}b _{17.2 18.8 16.2 20.6}b

Skinsymptoms 9.1 8.3 12.7b _{8.6 6.3 8.8}b _{9.6 9.1}

Atopiceczema 5.2 5.4 3.6 6.6b _{3.7 5.7}b _{5.0 5.6}b

Speechimpairment,wheezingsointensethatwasabletopreventtwoconsecutivewordsfrombeingsaidinthelast12months;Wheezingatexercise,wheezingduringexerciseinthe past12months;Nocturnalcough,coughingatnightwithouthavingacoldinthelast12months;Nasalsymptomsin12months,sneezing,runnynoseornasalstuffinessatsometimeinthe last12months;Rhinoconjunctivitis,nasalproblemwithitchingandwateryeyesinthelast12months;Skinsymptoms,itchyrashthatappearedanddisappearedinthelast12months; Atopiceczema,itchyrashthatappearedanddisappearedinthelast12monthsandincharacteristiclocations(skinfolds,amongothers).

34 SoléDetal.

Table2 Percentage ofvariationper yearintheprevalenceofasthma,rhinitisandeczema symptomsinadolescentswho

answeredtheInternationalStudyofAsthmaandAllergiesinChildhood(ISAAC)writtenquestionnaireincentersthatparticipated

inISAACphase3andthecurrentstudy.

Question Belém Recife Maceió Aracaju Belo

Horizonte

São Paulo

Curitiba General

Wheezingatsometime -0.63 -0.54 -0.61 -0.98 -0.20 -0.10 -0.10 -0.41

Wheezinglastyear -0.34 0.06 -0.23 -0.74 0.21 0.29 -0.14 -0.13

Speechimpairment 0.14 0.32 -0.21 -0.40 0.02 0.26 0.16 0.03

Asthmadiagnosis -0.50 0.50 0.29 -0.34 0.83 0.33 0.43 0.41

Wheezingatexercise -0.11 -0.06 -0.61 -0.33 0.34 -0.54 0.09 -0.14

Nocturnalcough 0.11 0.41 -0.17 -0.38 0.21 1.34 0.86 0.60

Nasalsymptomsin12months -0.46 -1.0 1.77 0.54 0.89 2.50 -0.84 0.68

Nasalandocularsymptoms -0.09 0.31 0.71 -0.25 0.42 1.37 0.18 0.55

Skinsymptoms 0.10 -0.19 0.20 -0.51 -0.09 -0.46 0.28 -0.06

Atopiceczema 0.24 -0.12 0.16 -0.56 0.02 0.33 0.22 0.08

Speechimpairment,wheezingsointensethatwasabletopreventtwoconsecutivewordsfrombeingsaidinthelast12months;Wheezing atexercise,wheezingduringexerciseinthepast12months;Nocturnalcough,coughingatnightwithouthavingacoldinthelast12 months;Nasalsymptomsin12months,sneezing,runnynoseornasalstuffinessatsometimeinthelast12months;Skinsymptoms, itchyrashthatappearedanddisappearedinthelast12months;Atopiceczema,itchyrashthatappearedanddisappearedinthelast12 monthsandincharacteristiclocations(skinfolds,amongothers).

InDecemberof2010,therulesforfinancingand

imple-mentationoftheBasicComponentofPharmaceuticalCare

wereapproved,providingtheasthmaandrhinitisprogram

withmedicationsfrom theNational ReferenceList of the

BasicComponentofPharmaceuticalCare.22_{Certainly,these}

facts allowed the creation of care programs for patients withasthma, whichmayexplaintheincreasedprevalence ofmedicaldiagnosis.Asthesepatientshaveaccessto treat-ment, greater control of the disease was expected, as evidencedbyareductioninthefrequencyofsevere exacer-bations,aswellasinnonspecificsymptomsobservedinpart of the Ads included in the present study. Withthe intro-ductionofmedicalguidelinesandconsensusesonasthma, therewasagreaterdisseminationofknowledgeonthe dis-ease;thus, the term‘‘asthma’’ started tobe moreoften employedbyphysiciansandpatients,replacingeuphemisms suchasbronchitisandtracheobronchitis.23 _Another

conse-quencewastheasthmatreatmentstandardization,although itisnotalwaysfullybasedonnationalorinternational23,24

guidelines.

Regarding rhinitis and rhinoconjunctivitis, an increase in the prevalence of both was observed in most centers involved in the study. After excluding the economic fac-tor, another component that could be involved in this increaseisenvironmentalpollution.Apreviousstudybythe present authors (ISF3) evaluated the association between theprevalenceofasthma, rhinitis,andeczemaandlevels of photochemicalpollutants in Brazilian centersthat had airpollutioncontrol(SaoPaulo,SantoAndré,Curitiba,and Porto Alegre). Although a characteristic pattern between the evaluated symptoms and a specific air pollutant was notdetected,anassociationwasobservedbetweengreater exposuretophotochemicalpollutantsandhighprevalence orriskofsymptomsofasthma,rhinitis,andatopiceczema.25

Ofthecentersthatparticipatedinthisstudy,onlySãoPaulo and Curitiba have had air pollutant monitoring since the ISF3wasperformed,whichallowedfortheobservation,in both centers, of an improvement of air quality in recent years.26---29

Inconclusion, the present study found thatthe preva-lenceofactiveasthmahaspossiblyreacheditshighestlevel andhasstabilized.Wouldthisfactbeduetothereduction inlevelsofairpollution?Ifso,howcantheincreased preva-lence of rhinitis, rhinoconjunctivitis, and atopic eczema beexplained?Possibleexplanations for thesefindingsstill requirefurtherstudiesthataretargetedfortheseprimary outcomes.

Funding

FAPESP-PPSUS(Processn:2009/53303-5).

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

References

1.InternationalStudyofAsthma,AllergiesinChildhoodSteering Committee.Worldwidevariationinprevalenceofsymptomsof asthma,allergicrhinoconjunctivitis,andatopiceczema:ISAAC. TheInternationalStudyofAsthmaand AllergiesinChildhood (ISAAC)SteeringCommittee.Lancet.1998;351:1225---32.

2.AsherMI,MontefortS,BjörksténB,LaiCK,StrachanDP, Wei-land SK, et al. Worldwide time trends inthe prevalence of symptomsofasthma,allergicrhinoconjunctivitis,andeczema inchildhood:ISAACPhasesOneandThreerepeatmulticountry cross-sectionalsurveys.Lancet.2006;368:733---43.

3.PearceN,Aït-KhaledN,BeasleyR,MallolJ,KeilU,MitchellE, etal.Worldwidetrendsintheprevalenceofasthmasymptoms: phaseIIIoftheInternationalStudyofAsthmaandAllergiesin Childhood(ISAAC).Thorax.2007;62:758---66.

5.OdhiamboJA, WilliamsHC, ClaytonTO,Robertson CF,Asher MI,ISAACPhaseThreeStudyGroup.Globalvariationsin preva-lenceofeczemasymptomsinchildrenfromISAACPhaseThree. JAllergyClinImmunol.2009;124:1251---8.

6.AsherMI,KeilU,AndersonHR,BeasleyR,CraneJ,MartinezF, etal.InternationalStudyofAsthmaandAllergiesinChildhood (ISAAC):rationaleandmethods.EurRespirJ.1995;8:483---91.

7.HansenTE,EvjenthB,HoltJ.Increasingprevalenceofasthma, allergicrhinoconjunctivitisandeczemaamongschoolchildren: three surveys during the period 1985-2008. Acta Paediatr. 2013;102:47---52.

8.McNeillG,TagiyevaN,AucottL,RussellG,HelmsPJ.Changesin theprevalenceofasthma,eczemaandhayfeverinpre-pubertal children: a 40-year perspective. PaediatrPerinat Epidemiol. 2009;23:506---12.

9.MallolJ,SoléD,Baeza-BacabM,Aguirre-CamposanoV, Soto-QuirosM,Baena-CagnaniC,etal.Regionalvariationinasthma symptom prevalence in Latin American children. J Asthma. 2010;47:644---50.

10.SoléD,MallolJ,Camelo-NunesIC,WandalsenGF,Latin Ameri-canISAACStudyGroup.Prevalenceofrhinitis-relatedsymptoms inLatinAmericanchildren-resultsoftheInternationalStudyof AsthmaandAllergiesinChildhood(ISAAC)phasethree.Pediatr AllergyImmunol.2010;21:e127---36.

11.SoléD,MallolJ,WandalsenGF,AguirreV,LatinAmericanISAAC Phase3 StudyGroup. Prevalence ofsymptoms ofeczema in LatinAmerica:resultsoftheInternationalStudyofAsthmaand AllergiesinChildhood(ISAAC)Phase3.JInvestigAllergolClin Immunol.2010;20:311---23.

12.EllwoodP,AsherMI,BeasleyR,ClaytonTO,StewartAW,ISAAC Steering Committee.The international study of asthmaand allergiesinchildhood(ISAAC):phasethreerationaleand meth-ods.IntJTubercLungDis.2005;9:10---6.

13.SoléD,VannaAT,YamadaE,RizzoMC,NaspitzCK.International StudyofAsthmaandAllergiesinChildhood(ISAAC)written ques-tionnaire:validationoftheasthmacomponentamongBrazilian children.JInvestigAllergolClinImmunol.1998;8:376---82.

14.VannaAT, YamadaE,ArrudaLK, NaspitzCK, SoléD. Interna-tionalStudyofAsthmaandAllergiesinChildhood:validationof therhinitissymptom questionnaireand prevalenceofrhinitis inschoolchildreninSãoPaulo,Brazil.PediatrAllergyImmunol. 2001;12:95---101.

15.YamadaE,VannaAT, NaspitzCK, SoléD.International Study ofAsthmaandAllergiesinChildhood(ISAAC):validationofthe writtenquestionnaire(eczemacomponent)andprevalenceof atopiceczemaamongBrazilianchildren.JInvestigAllergolClin Immunol.2002;12:34---41.

16.IDH --- 1991-2005. Índice de Desenvolvimento Humano (IDH) Brasil, regiões e estados, 1991-2005.[cited 10 Jan 2014].

Available from: www.sef.sc.gov.br/sites/default/files/idh 1991-05.xls

17.PNUD---ProgramadasNac¸õesUnidasparaoDesenvolvimento. Ranking IDHM Municípios 2010. [cited 10 Jan 2014]. Avail-able from: http://www.pnud.org.br/atlas/ranking/Ranking-IDHM-Municipios-2010.aspx

18.Gross national income (GNI) by country: 2000 and 2008. [cited16Jan2014].Availablefrom:http://www.census.gov/ compendia/statab/2011/tables/11s1347.pdf

19.U.S.CensusBureau,StatisticalAbstractoftheUnitedStates: 2011; GNI per capita, Atlas method (current US$). [cited 16 Jan 2014]. Available from: http://data.worldbank.org/ indicator/NY.GNP.PCAP.CD

20.Cerci Neto A, Ferreira Filho OF, Bueno T. Brazilian exam-plesofprogramsfor thecontrolofasthma.JBrasPneumol. 2008;34:103---6.

21.Rizzo JA. Disponibilidade dos medicamentos para asma e os direitos dos asmáticos. Rev Bras Alerg Imunopatol. 2006;29:142---3.

22.AmaralLM,PalmaPV,LeiteIC.Evoluc¸ãodaspolíticaspúblicase programasdecontroledaasmanoBrasilsobaperspectivados consensos.JBrasPneumol.2012;38:518---25.

23.DiretrizesdaSociedadeBrasileiradePneumologiaeTisiologia paraomanejodaasma---2012.JBrasPneumol.2012;38:S1---46. 24.GINA Report 2014. [cited May 2014]. Available from:

www.ginasthma.org

25.SoléD,Camelo-NunesIC,WandalsenGF,Pastorino AC,Jacob CM, Gonzalez C, et al. Prevalence of symptoms of asthma, rhinitis,andatopiceczemainBrazilianadolescentsrelatedto exposuretogaseousairpollutantsandsocioeconomicstatus.J InvestigAllergolClinImmunol.2007;17:6---13.

26.Comportamento sazonal da poluic¸ão do ar em São Paulo -Análise de 14 anos de dados da RMSP e Cubatão - 1981 a 1994.[cited20Dec2013].Availablefrom:http://www.cetesb. sp.gov.br/ar/qualidade-do-ar/31-publicacoes-e-relatorios 27.QualidadedoarnoestadodeSãoPaulo2012/CETESB,SãoPaulo:

CETESB, 2013. [cited 20 Dec2013]. Available from: http:// www.cetesb.sp.gov.br/ar/qualidade-do-ar/31-publicacoes-e-relatorios

28.RelatórioqualidadedoarnaregiãometropolitanadeCuritiba ---Ano de 2003 em Monitoramento da qualidade do ar ---Secretaria do meio ambiente e recursos hídricos. [cited 20 Dec2013].Availablefrom:http://www.iap.pr.gov.br/modules/ conteudo/conteudo.php?conteudo=639