JPediatr(RioJ).2017;93(3):209---210
www.jped.com.br
EDITORIAL
Bronchiolitis
and
asthma:
the
next
step
夽
,
夽夽
Bronquiolite
e
asma:
o
próximo
passo
Louis
Bont
UniversityMedicalCenterUtrecht(UMCU),WilhelminaChildren’sHospital(WKZ),DepartmentofPediatrics,Utrecht, TheNetherlands
Asthmaisoneofthemostcommonchronicconditionsduring childhood. The origin of asthma is not fully understood, butitisclearthatitisacomplexdiseaseinwhichgenetic mechanismsandenvironmentalfactorsareinvolved.Inthis issue of Jornal de Pediatria, Brandão et al. analyzed the relationship between acute viral bronchiolitis during the first year of life andasthma at school age in a cohortof 672 children in northeastern Brazil.1 Acute viral
bronchi-olitis wasdefined according to the AmericanAcademy of Pediatrics(AAP) guidelines,basicallyrequiring a combina-tionof upper andlower respiratory symptomsin the first yearoflife.Evenafteradjustingforpotentialconfounders, includingfamilyatopyor cigarettesmokeexposure, bron-chiolitis during the first year of life was independently associated with asthma at school age. Why is this study important?It hints tothepossibilitythatwe may beable to prevent asthma by preventing viral infection during early childhood. This possibility depends on the causal relationshipbetweenbronchiolitisandsubsequentasthma. Forrhinovirusbronchiolitis,thelinkisstrong,but epidemi-ologicalstudies suggest rhinovirus bronchiolitis ‘‘reveals’’ asthma ratherthan causing it.2,3 Forrespiratory syncytial
virus(RSV),thelinkislessstrong,buttheassociationmight well becausal. RSVinfectioncauses arobust neutrophilic airwayinflammation, which maycausepersistent changes totheairways,4,5resultinginchronicairwaydiseasewithout
causingallergicsensitization.Inlinewiththishypothesis,a
夽
Pleasecitethisarticleas:BontL.Bronchiolitisandasthma:the nextstep.JPediatr(RioJ).2017;93:209---10.
夽夽
SeepaperbyBrandãoetal.inpages223---9.
E-mail:l.bont@umcutrecht.nl
previousbirth cohortstudy by RenatoSteindemonstrated thatRSVdoesnotaddtotheriskofallergicsensitization.6
Causality was suggested by a complex longitudinal study byWu et al. showingthat the timegap between timeof birthand thepeakof the RSV seasondeterminesthe risk of asthma at school age.7 The most convincing evidence
is supposed to come from RSV prevention trials. For RSV infection,most trials have indicated that RSV prevention decreasestheriskofsubsequentwheeze,8---10 althoughthis
couldnot beconfirmed in a recent trial.11 The results of
these trials should be considered with caution, as all of themwhereperformed inspecialpopulations,leavingthe possibilitythat thedirection or thesize of the long-term effect of RSV on asthma is different in the normal pop-ulation. Maternal or infant vaccination against influenza is one of the potential interventions to be considered. Moreimportant,probably,arethecurrentlydevelopedRSV vaccines.12Severalcompanieshavenowenteredtheclinical
developmentstageof their RSV vaccines. A nanoparticle-basedvaccineformaternalvaccinationhasalreadyentered phaseIII.Thisvaccineisbeingdevelopedwiththesupport of theBill andMelinda Gates Foundation and is intended tobe affordable, therefore it would be available in high aswellaslow- andmiddle-income countries.The clinical RSV vaccine programs of other large companies follow rapidly,soitappears toamatter oftimebeforewe have an RSV vaccine. These upcoming RSV prevention trials in thenormalpopulationwilladdressthecausallinkbetween RSVandasthma,andshowthepotentialforprimaryasthma prevention. The clinical development of all RSV vaccines is supported by studies such as that by Brandão et al., whichshowthatpreventionofacuteviralbronchiolitisnot onlydecreasestheriskofalife-threateningacutedisease,
http://dx.doi.org/10.1016/j.jped.2016.11.001
210 BontL
butmayalsoimpactonthechild’slunghealth throughout childhoodandthereafter.
Conflicts
of
interest
UMCUhasreceivedfundingfor investigator-initiated stud-iesbyLouisBontfrom AbbVie,MedImmune, Janssen,and MeMedDiagnostics.He hasalsoreceivedfor consultations orinvitedlecturesforAbbVie,Ablynx,MabXience,Novavax, andJanssen.
References
1.Brandão HV, Vieira GO, Vieira TO, Cruz ÁA, Guimarães AC, TelesC,et al.Acuteviralbronchiolitis andriskofasthmain schoolchildren:analysisofaBraziliannewborncohort.JPediatr (RioJ).2017;93:223---9.
2.JacksonDJ,EvansMD,GangnonRE,TislerCJ,PappasTE,Lee WM,etal.Evidenceforacausalrelationshipbetweenallergic sensitizationandrhinoviruswheezinginearlylife.AmJRespir CritCareMed.2012;185:281---5.
3.JacksonDJ,GangnonRE,EvansMD,RobergKA,AndersonEL, PappasTE,etal.Wheezingrhinovirusillnessesinearlylife pre-dictasthmadevelopmentinhigh-riskchildren.AmJRespirCrit CareMed.2008;178:667---72.
4.GeerdinkRJ,PillayJ,MeyaardL,BontL.Neutrophilsin respi-ratorysyncytialvirusinfection:atargetforasthmaprevention. JAllergyClinImmunol.2015;136:838---47.
5.FunchalGA,JaegerN,CzepielewskiRS,MachadoMS,Muraro SP, Stein RT,et al. Respiratorysyncytial virus fusionprotein
promotesTLR-4-dependentneutrophilextracellulartrap forma-tionbyhumanneutrophils.PLoSOne.2015;10:e0124082.
6.SteinRT,HolbergCJ,SherrillD,WrightAL,MorganWJ,Taussig L,etal.Influenceofparentalsmokingonrespiratorysymptoms duringthefirstdecadeoflife:theTucsonChildren’sRespiratory Study.AmJEpidemiol.1999;149:1030---7.
7.WuP,DupontWD,GriffinMR,CarrollKN,MitchelEF,Gebretsadik T,etal.Evidenceofacausalroleofwintervirusinfectionduring infancyinearlychildhoodasthma.AmJRespirCritCareMed. 2008;178:1123---9.
8.SimõesEA,Carbonell-EstranyX,RiegerCH,MitchellI,Fredrick L,GroothuisJR,etal.Theeffectofrespiratorysyncytialvirus onsubsequentrecurrentwheezinginatopicandnonatopic chil-dren.JAllergyClinImmunol.2010;126:256---62.
9.Yoshihara S, Kusuda S, Mochizuki H, Okada K, Nishima S, SimõesEA, et al. Effect of palivizumab prophylaxis on sub-sequent recurrent wheezing in preterm infants. Pediatrics. 2013;132:811---8.
10.Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, et al. Respiratory syncytial virus and recurrentwheezeinhealthy preterminfants. NEngl JMed. 2013;368:1791---9.
11.O’BrienKL,ChandranA,WeatherholtzR,JafriHS,GriffinMP, BellamyT,etal.Efficacyofmotavizumabforthepreventionof respiratorysyncytialvirusdiseaseinhealthyNative American infants:aphase3randomiseddouble-blindplacebo-controlled trial.LancetInfectDis.2015;15:1398---408.
