J. Pediatr. (Rio J.) vol.90 número2

JPediatr(RioJ).2014;90(2):209---212

www.jped.com.br

LETTERS

TO

THE

EDITOR

International

collaborative

research

for

pediatric

and

neonatal

lung

injury:

the

example

of

an

ESPNIC

initiative

to

validate

definitions

and

formulate

future

research

questions

Pesquisa

colaborativa

internacional

sobre

lesão

pulmonar

pediátrica

e

neonatal:

exemplo

de

uma

iniciativa

da

ESPNIC

para

validar

definic

¸ões

e

formular

questões

de

pesquisas

futuras

DearSir,

An interesting review of acuterespiratory distress(ARDS) definitionshasbeenrecentlypublishedintheJornalde Pedi-atria, focusingon actual needs in terms of research and clinicalcareofpediatricARDS.1

Unfortunately,timingpreventedtheconsiderationofan importantstepforwardinthisfield.TheEuropeanSociety forPediatricandNeonatalIntensiveCare(ESPNIC),together withsomemembersoftheoriginalARDSTaskForce,haveset upaninternationalcollaborativeprojecttovalidatethenew Berlindefinitionforinfantsandtoddlers.2_{Thisprojectisthe}

firstinitiativelinkingdifferentpediatricintensivecareunits (PICU)inordertoreachenoughstatisticalpowertoaddressa specificresearchneed.Figure1showstheESPNICnetforthis project.Indeed,asFiorettoetal.summarized,1_nospecific

pediatricvalidationhadeverbeenconducted,eventhough somechildrenwereincludedintheoriginalARDSdefinition proposedbyAshbaughetal.in1967.3

Fiorettoetal.described severalpossible limitationsof theBerlindefinition:however,someofthepointsraisedby theseauthorsshouldnotbeconsideredasalimitation,since the newBerlin definitionis not supposed to be a predic-tivetool,butratheraframeworktodefineasyndromefor epidemiology,clinicalcare,andresearch.

夽 _{Pleasecitethisarticleas:DeLucaD,KneyberM,Rimensberger}

PC.Internationalcollaborativeresearchforpediatricandneonatal lunginjury:theexampleofanESPNICinitiativetovalidate defi-nitionsandformulatefutureresearchquestions.JPediatr(RioJ). 2014;90:209---11.

Inaddition,concernswereexpressedregardingthe appli-cationofthenewBerlincriteriatothepediatricpopulation, as there were no children in their original development population.4,5 _{This isthe reasonwhythe Respiratory}

Fail-ureSectionofESPNICstartedtheabove-mentionedproject to evaluate the reliability of the new Berlin definition in a homogeneous and adequately large pediatric popu-lation. The project focused on the early pediatric age (range: 30 days to 18 months), since especially at this age, the syndrome is distinctly different from ARDS in adults.2,6_{Infact,infantsandtoddlerspresentpeculiarities}

regardinglungdevelopment,respiratorysystemmechanics, andco-morbidities, whichareresponsible forthepeculiar epidemiologyandprognosisofARDSinthesepatients.6

ThemainresultsdemonstratedthatthenewBerlin def-initionhasthe samereliabilityboth for the pediatricand adultpatientsintermsofmortalityandneedfor extracor-poreallife support.2 _{To aid the clinical applicationof the}

definition,asetofchestX-rayswithaninterpretationguide andalistofARDSriskfactors,asestimatedbyresearchers participatinginthiscollaborativeeffort,wereestablished. Botharepractical tools thathave proventobehelpful in clinicalpracticeandresearch.2,4,7,8

However,the ESPNIC collaborative work validating the newBerlincriteriaforpediatricARDSpatientshassome lim-itationsthathavealreadybeen pointedout.2,9_Besidesthe

retrospective character of this pediatric validation study, only one of the several secondary variables that have beentestedinadults(i.e.standardizedminuteventilation [(Vecorr) =minute ventilation xworst PaCO2/40])couldbe

tested.2_{However,othervariables(suchaslungvolume}

esti-mation,surfactantamountandactivity,biomarkers)could havebeentested,andthenewBerlindefinitioncouldhave beenmoretailoredtopediatricpatientswithanadequate prospectivestudypopulation.Infact,theMurraylunginjury scorereviewedbyFiorettoelal.hasalreadybeenmodified forpediatricARDS,10_{butitwasneversubjectedtofurther}

validationstudies.Finally,otherpediatricageshadnotbeen considered:whileARDSinadolescentscouldbeconsidered asverysimilartothesyndromeinadults,neonatesdeserve aspecificprojecttodefinethesyndromeanddistinguishit fromotherformsofneonatallunginjury.

Thus,the ESPNICcollaborativework wasan initialand substantialstepforward,anddisseminatedavalidatedARDS definitionforaparticularpediatricpopulation,answeringa specificneedof pediatricintensivists.Clearly,many other questionsremainopen,andtheycanbeaddressedonlywith

210 LETTERSTOTHEEDITOR

Figure1 CentersparticipatingintheESPNICRespiratorySectionprojecttovalidatetheBerlindefinitionofARDSfortheearly

pediatricage.221patientswereenrolled.

similarinternationalcollaborativeprojects.Suchstudiesare needed,giventhecomplexrealityofasyndromewith mul-tiplecausesandco-morbiditiessuchasARDS.Furthermore, itisnecessarytostudylargerpediatricpopulationsinorder toreachanadequatestatisticalpower,sinceARDSis signif-icantlylessfrequentinchildrenandneonatesthaninadult patients.

We are looking forward to proceed with other similar projects in order to answer some of the open questions described above. To do this, and toachieve more repre-sentativeresults,aworldwidecollaborativeworkbetween the Respiratory Failure Section of ESPNIC and other non-Europeanresearchersandclinicalcenterswillbeneeded.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

References

1.Fioretto JR, de Carvalho WB. Temporal evolution of acute respiratory distress syndrome definitions. J Pediatr (Rio J). 2013;89:523---30.

2.DeLucaD,PiastraM,ChidiniG,TissieresP,CalderiniE,Essouri S, et al. on behalf of the Respiratory Section of the Euro-pean Society for PediatricNeonatal Intensive Care (ESPNIC)

TheuseoftheBerlin definitionforacuterespiratorydistress syndromeduringinfancyandearlychildhood:multicenter eval-uation and expert consensus. Intensive Care Med. 2013;39: 2083---91.

3.AshbaughDG,BigelowDB,PettyTL,LevineBE.Acute respira-torydistressinadults.Lancet.1967;290:319---23.

4.ARDSdefinitiontaskforce.Acuterespiratorydistresssyndrome: theBerlindefinition.JAMA.2012;307:2526---33.

5.FergusonND,FanE,CamporotaL,AntonelliM,AnzuetoA,Beale R,etal.TheBerlindefinitionofARDS:anexpandedrationale, justification,andsupplementarymaterial.IntensiveCareMed. 2012;38:1573---82.

6.Randolph AG. Management of acute lung injury and acute respiratory distress syndrome in children. Crit Care Med. 2009;37:2448---54.

7.AngoulvantF,LlorJ,AlbertiC,KhenicheA,ZaccaruaI,Garel C,etal.Inter-observervariabilityinchestradiographreading fordiagnosingacutelunginjuryinchildren.PediatrPulmonol. 2008;43:987---91.

8.MeadeMO,CookRJ,GuyattGH,GrollR,KachuraJR,BedardM, etal.Interobservervariationininterpretingchestradiographs forthediagnosisofacuterespiratorydistresssyndrome.AmJ RespirCritCareMed.2000;161:85---90.

9.KhemaniRG, Wilson DF,Esteban A, FergusonND. Evaluating the Berlin definition in pediatric ARDS. Intensive Care Med. 2013;39:2213---6.

LETTERSTOTHEEDITOR 211

DanieleDeLucaa,b,∗_{,MartinKneyber}c,d_,

PeterC.Rimensbergere

a_{DivisionofPediatricsandNeonatalCriticalCare,}

DepartmentofFAME,SouthParisUniversityHospitals, MedicalCenter‘‘A.Béclére’’---APHP,Paris,France

b_{InstituteofAnesthesiologyandCriticalCare,Catholic}

UniversityoftheSacredHeart,Rome,Italy

c_{DepartmentofPediatrics,DivisionofPediatricIntensive}

Care,BeatrixChildren’sHospital,UniversityMedical CenterGroningen,Groningen,TheNetherlands

d_{Peri-operativeMedicineandEmergencyMedicine(CAPE),}

UniversityofGroningen,Groningen,TheNetherlands

e_{ServiceofNeonatologyandPediatricCriticalCare,}

DepartmentofPediatrics,UniversityHospitalofGeneva, Geneva,Switzerland

∗_{Correspondingauthor.}

E-mail:[email protected](D.DeLuca).

http://dx.doi.org/10.1016/j.jped.2013.12.003

ARDS

definitions

in

children:

one

step

forward

Definic

¸ões

da

SDRA

em

crianc

¸as:

um

passo

adiante

DearSir,

It waswith greatinterest and pleasure that we read the Letter tothe Editor entitled ‘‘International collaborative researchforpediatricandneonatallunginjury:theexample of an ESPNIC initiative to validate definitions and formu-latefutureresearchquestions’’byDanieleDeLucaetal.1

The authors commented that the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) published the first validation of the acute respiratory distress syn-drome (ARDS) Berlin Definition (BD) in early childhood.2

MembersoftheESPNICRespiratorySectionperformeda ret-rospective international(Italy,Spain, France,Austria, and theNetherlands)multicenterstudyincludingchildrenaged between30daysand18monthswithARDSaccordingtothe American-EuropeanConsensusConference(AECC)criteria.3

Itelegantlyaddressesourconcerns onthe applicabilityof BDinpediatricswhenwedescribed theevolutionofARDS definitions.4

A time lapse between the two publications prevented exact connections between them; nowis the opportunity todoso.TheBD5_{foradultsandchildrenisanadvance,in}

thesensethatARDSstratificationisimportantfordiagnosis andtreatment.However,itwasobvious thatpediatricians workinginclinicalorbasicresearchneededtovalidatethe new datain children. The work performed by The Respi-ratory Section of ESPNIC2 _{enrolled 221 children, median}

age6months(range2-13months),whichwerecategorized according to the two definitions. The authors found very interesting andimportantresults. Applying AECC,36 chil-drenwereclassifiedasALIand185asARDS,withmortality ratesof13.9%and17.8%,respectively.Conversely,36were classifiedasmild,97 asmoderate, and88assevereARDS

DOIofreferstoarticle:http://dx.doi.org/10.1016/j.jped.2013. 12.003

夽

Please cite this article as: Fioretto JR, de Carvalho WB. ARDSdefinitionsinchildren:onestepforward.JPediatr(RioJ). 2014;90:211---2.

when applyingthe BD. The BD described the clinical sit-uationbetterthan AECC, withsimilarresults publishedin adults.Also,themainoutcomesweresignificantlydifferent onlyfor severe ARDS; mortalitywas13.9% for mild ARDS, 11.3%formoderateARDS,and25%forsevereARDS.Theydid notfindsignificantdifferencesbetweenmildandmoderate classes.However,theinclusionofaseverecategoryinthe BDhelpedtoincreaseitsvalidity.Despitenotaimedat iden-tifyingrisk factors andtheir association withARDS, some werepresented (sepsis, near-drowning, congenital immu-nodeficiencies,thoracic trauma, etc.). As expected, they aredifferent than those in the adult population. A prop-erlydesigned study is therefore necessary toaddress this issue.TheauthorsconcludedthatthenewARDS definition correctlyadjustsandisabletodefinethesyndromein its population, subdividing it into mild/moderate and severe ARDS.

Some limitations were addressed. Firstly, the number of patients included was not large. This is a difficulty in all pediatric studies, as populations of children in inten-sivecare aremuchsmallerthanthoseofadults.Secondly, clinicaldatawasnotcorrelatedwithlungmorphology. How-ever,lungbiopsyisnotcommonlyperformedincriticallyill children.

The Brazilian Pediatric ARDS Study Group6 _performed

a prospective, multicentre cohort study from March to Septemberof2013,whichaimed:(1)toevaluatethe preva-lenceofARDS;(2)todetermineriskfactorsforARDS;and (3)toevaluatewhethertheuseofBDincriticallyillchildren canbetterdiscriminatetheseverityofthediseasecompared withtheAECCdefinition.Thedistributionandoutcomesof the patients according to the AECC and BD areshown in Table1.

TheBDbetterdiscriminatestheseverityofARDSin chil-drenwhen comparedtothe AECCdefinition, asshown by the incremental increase in mortality rates and reduced number of ventilation-free days in patients with severe ARDS.

In summary, we congratulateDe Luca etal.2 _{for their}