PortoBiomed.J.2016;1(4):127–128
Porto
Biomedical
Journal
h tt p://w w w . p o r t o b i o m e d i c a l j o u r n a l . c o m /
EDITORIAL
Exercise,
Asthma
and
the
Olympics:
A
2000-year-old
tale
Stefano
Del
Giacco
∗DepartmentofMedicalSciencesandPublicHealth,UniversityofCagliari,Italy
Rio2016Olympics–theincreasinglyfamiliarscenesof asth-maticathletesdecoratingtheirneckswithgold,silverandbronze medals can be seen again. Asthmatic athletes(many of whom former“childrenwhocouldnotplaysportsduetotheirasthma”) havemadeofthisatraditionthatgoesbacktothefirstcentury A.D..Backthen,therenownedGreekphysicianAraeteusthe Cap-padocianfirstdescribedexercise-inducedrespiratorysymptoms: “iffromrunning,gymnastics,oranyotherwork,breathingbecomes difficult,itiscalledAsthma”.1Fastforward20centuries,in1962RS
Jonesetal.describedforthefirsttimetheeffectsofexerciseon ven-tilatoryfunctioninchildren, andintroducedsystematicexercise tests.2
Whilstweawaitdatafromthisyear’sOlympicgames,figures fromtheprevioussummerandwinterOlympicGamesshowthat, believeitornot,asthmaticshavewonmoremedalsthantheir non-asthmaticpeers,demonstratingbeyonddoubtthatasthmaticshave nolimitationsinsportspracticeiftheyreceiveadequatemedical treatment.3
Thegeneralpublicand healthcare professionalsare gaining interestinthepotentialhealthimplicationsofasthmaandallergy intopathletes.Whenpresent,thelattermayaffecttheir perfor-manceandachievements.However,theimpactofasthmaonsport andexercisegoesnowadaysbeyondtopathletesanditis increas-inglyexpandingtothegeneralpopulationpracticingexerciseand sportsatalllevels.
Exercise,in general,is aconcern forasthmatics. Ithasbeen claimedthatupto75-80%ofasthmapatientswithoutaninhaled anti-inflammatory therapy may face asthmatic symptoms pro-vokedbyexercise.However,subjectswithoutapreviousasthma diagnosismayalsoexperiencethesameproblems.Thisiscalled “Exercise-Induced Asthma” (EIA). The terms “Exercise-Induced Asthma” and “Exercise-Induced Bronchoconstriction” (EIB) are oftenusedinterchangeablyassynonyms.Aconsensusbetweenthe majorAmericanSocietiesofAllergy,AsthmaandImmunologyused theterm“EIBwithAsthma”toindicateEIBwithclinicalsymptoms ofAsthmaand“EIBwithoutasthma”toindicateairflow obstruc-tionwithoutclinicalasthmasymptoms.TheEuropeanAcademy of Allergy and Clinical Immunology (EAACI), together withthe EuropeanRespiratorySociety(ERS)agreedtouseEIAtoindicate symptomsofasthmaafterheavyexerciseandEIBforareduction
∗ Tel.:+39-070-6754150;fax:+39-070-6754086. E-mailaddress:stedg@medicina.unica.it
inlungfunctionoccurringafterheavyexerciseasseenina stan-dardizedexercisetest,butwithoutclinicalsymptomsofasthma.A glanceinPubMedshowsthatEIAandEIBareareasofgreatinterest toscientists,withmorethan3,500studiestryingtocompletethe jigsawofelementsthatmakeupthiscondition.
Fiftyyearsago,McNeillandcollaboratorsattemptedtoexplain thecentralmechanismsinvolvedinEIA/EIBsuggestingaroleof the“parasympatheticnervoussystem”andof“chemicalsubstances which occurin thebody, andwhich canaffectsmoothmuscles sothat the possibility existsthe exerciseeffect is either reflex orhumoralinorigin”,concludingthat“themechanismbywhich exerciseproducesitseffectisworthyofstudybecauseitmay con-tainanimportantcluetonaturallyoccurringbronchoconstrictor substance”.4Theseinitialdefinitionshaveevolvedintothecurrent
classicaltheoriesbehindEIA,theso-called“osmolar”or“vascular” (or“thermal”)hypotheses,bothbasedonthemarkedincreasein ventilationduringphysicalactivity,leadingtoincreasedwaterand heatlossthroughrespiration.Intheosmolartheory,theincreased osmolalityoftheextracellularfluidliningthebronchialmucosa leads to a release of inflammatory mediators from mast cells, eosinophils,neutrophilsandotherinflammatorycells.Inthe vas-culartheory,therespiratoryheatlossthatoccursasconsequence oftheoralbreathingpatternofathletesandoftheincreased ven-tilation,stimulatesthereflexparasympatheticnerve,whichleads tobronchoconstriction.5,6
Bothmechanismsmayworktogetherunderconditionsof sig-nificantheatlossand,asthereadercansee,confirmthebrilliant intuitionsof50yearsago.
However,inthemostrecentyears,thechangingviewonthe wholeasthmaissue,withtheimportanceof phenotypes, endo-typesandrelevantbiomarkersfora“personalized”medicine,has beenreflectedalsointhecurrentresearchtrendsinEIA/EIB.Albeit helpfulinsomeways,thisnewapproachalsorestrictsthecurrent definitionofthediseaseandopensomequestions,particularlywith regardstothemechanismsmediatingEIA/EIB.
But,comingbackto theOlympics,thequestion arises:why Olympicathleteshavesuchaprevalenceofasthma?Itisaccepted thattwoclearlyseparatedphenotypesofEIA/EIBexist:the “clas-sical”one,i.e.theasthmaticpatient,oftenallergic,experiencing symptomswhileexercising,andthe“sportsasthma”phenotype, i.e. the late-onset asthma developed by competitive, top-level athletes,linkedtoepithelialdamage,reducedrepair and subse-quent inflammation. In fact, a recent study has identified two http://dx.doi.org/10.1016/j.pbj.2016.10.001
2444-8664/©2016PBJ-Associac¸˜aoPortoBiomedical/PortoBiomedicalSociety.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
128 S.DelGiacco/PortoBiomed.J.2016;1(4):127–128
distinctasthmaphenotypesineliteathletesthroughlatent-class analysis. LCA retrieved two clusters: “atopic asthma”, defined byallergicsensitization,rhinitisandallergicco-morbidities and increasedexhalednitricoxidelevels;and“sportsasthma”defined byexercise-inducedrespiratory symptomsandairway hyperre-sponsivenesswithoutallergicfeatures.Evidencealsosuggeststhat thatwinterandwatersportsathletesareparticularlyathighrisk ofdevelopingthe“SportsAsthma”phenotype.7Thismightexplain
thehighprevalenceofasthmaamongstOlympicAthletes,forwhom isnotuncommontoshowa“SportsAsthma”phenotype,therefore raisingtheprevalenceofasthmainthisspecialcategory.However, reassuringly,themechanismleadingtothisphenotypehasbeen demonstratedtobepartiallyreversibleattheendoftheathlete’s career.6
Switchingtothedailylife,one dilemmafor thedoctors car-ingfor the asthmatic children and adolescents is what kindof recommendationshouldbegiventothosesufferingfromasthma, i.e.:whichsportscanberecommendedforasthmaticyoungsters? it is nowadays clear that endurance and winter sports are at high-riskofEIA, teamsports beara medium riskand sports in which the effortis of a short duration (less than 5-8minutes) areatlowrisk. Buta questionremains:is swimmingbeneficial ordetrimentalforasthma?Swimminghasbeenconsideredasa safeandhealthysportforchildrenwithasthma,duetothewarm andhumidairinhaledintheswimmingpools.However,recent datainchildrenshowanassociationbetweenanincreased swim-mingpool attendance in children and the risk of asthma:the “poolchlorinehypothesis”.Thissuggeststhatalinkexistsbetween chlorine-basedirritantsexposureandriskofasthmainchildren, probablyonacumulativebasis.8–10Thishypothesiswasfurther
supportedbystudiescomparingnon-chlorinatedandchlorinated swimmingpool exposures and by studiesin mouse modelson hypochlorite-inducedairwayhyperreactivity.11Thecentralroleof
chlorineexposureisinpartcontradictedbya largebirthcohort studyshowingthatBritishchildrendidnotincreasetheirasthma riskwithswimmingpoolattendance.12Ontheotherside,
competi-tiveswimmersshowanincreasedasthmaprevalence,withamixed eosinophilic-neutrophilicairway inflammation,also when mea-suredbyFeNO.13,14Inconclusion,ifthequestionisnotcompletely
clearfordevelopmentofasthmathroughoutchildhood,there is nodoubtthatcompetitiveswimmingexposestoahigherriskof asthmaincomparisontoothersports.
AnothercentraltopicinthefieldofEIA,theso-called“doping issue”hasbeenformanyyearsunderthespotlight.Initially,the commonbeliefwasthattheasthmadrugsmightimprove perfor-mance,andtheWorld-Anti-dopingAgency(WADA)issuedstrict regulationsfortheiruse.However,severalstudiesdemonstrated thatinhaledcorticosteroids,andmostoftheinhaledbeta-2 ago-nists,donotimproveperformanceattherapeuticdoses.Currently, norestrictionsexistforinhaledcorticosteroidsandforsalmeterol, formoterolandsalbutamol.Thesameappliestoleukotriene antag-onists,ipratropiumbromideandomalizumab.The“prohibitedlist” isusuallyupdatedyearlyandcanbefoundontheWADAwebsite (www.wada-ama.org).
Finally, in the recent years it has been demonstrated, both from murine models and preliminary studies on humans, that
low-to-moderateintensityaerobicexercisecandecreaseairway inflammation, remodeling,15 bronchial hyperresponsiveness,16
total and allergen specificIgE17 and Th-2 cytokines,18 showing
thataerobicexerciseprogramscanbebeneficialforasthmaticsand shouldbeincludedinasthmaactionplans.6
In summary,thelesson wecanall learnfrom the“Exercise, AsthmaandtheOlympics”taleisthatasthmaticsathletes–aslong astheyworkhardwithself-masteryanddiscipline–cancompete onparwiththeothers,andonlytheskycanbethelimit.
References
1.AdamsF.TheextantworksofAretaeus,theCappadocian.London:Sydenham Society;1856.
2.JonesRS,BustonMH,WhartonMJ.Theeffectofexerciseonventilatoryfunction inthechildwithasthma.Britishjournalofdiseasesofthechest.1962;56:78–86. 3.FitchKD.Anoverviewofasthmaandairwayhyper-responsivenessinOlympic
athletes.Britishjournalofsportsmedicine.2012;46:413–6.
4.McNeillRS,NairnJR,MillarJS,IngramCG.Exercise-inducedasthma.QJMed. 1966;35:55–67.
5.DelGiaccoSR,CarlsenKH,DuToitG.Allergyandsportsinchildren.Pediatric allergyandimmunology:officialpublicationoftheEuropeanSocietyofPediatric AllergyandImmunology.2012;23:11–20.
6.DelGiaccoSR,FirinuD,BjermerL,CarlsenKH.Exerciseandasthma:anoverview. EurClinRespirJ.2015;2:27984.
7.CoutoM,StangJ,HortaL,StensrudT,SeveroM,MowinckelP,etal.Twodistinct phenotypesofasthmaineliteathletesidentifiedbylatentclassanalysis.The Journalofasthma:officialjournaloftheAssociationfortheCareofAsthma. 2015;52:897–904.
8.BernardA,NickmilderM,VoisinC,SardellaA.Impactofchlorinated swim-mingpoolattendanceontherespiratoryhealthofadolescents.Pediatrics. 2009;124:1110–8.
9.NickmilderM,BernardA.Ecologicalassociationbetweenchildhoodasthmaand availabilityofindoorchlorinatedswimmingpoolsinEurope.Occupationaland environmentalmedicine.2007;64:37–46.
10.Bernard A,NickmilderM,DumontX.Chlorinatedpoolattendance, airway epitheliumdefectsandtherisksofallergicdiseasesinadolescents: Interrela-tionshipsrevealedbycirculatingbiomarkers.EnvironRes.2015;140:119–26. 11.Hox V, Vanoirbeek JA, Callebaut I, Bobic S, De Vooght V, Ceuppens J,
etal.Airwayexposuretohypochlorite priorto ovalbumininducesairway hyperreactivitywithoutevidenceforallergicsensitization.Toxicologyletters. 2011;204(2–3):101–7.
12.Font-RiberaL,VillanuevaCM,NieuwenhuijsenMJ,ZockJP,KogevinasM, Hen-dersonJ.Swimmingpoolattendance,asthma,allergies,andlungfunctioninthe AvonLongitudinalStudyofParentsandChildrencohort.Americanjournalof respiratoryandcriticalcaremedicine.2011;183:582–8.
13.MoreiraA,DelgadoL,PalmaresC,LopesC,JacintoT,RytilaP,etal.Competitive swimmerswithallergicasthmashowamixedtypeofairwayinflammation.The Europeanrespiratoryjournal:officialjournaloftheEuropeanSocietyforClinical RespiratoryPhysiology.2008;31:1139–41.
14.CoutoM,AndradeP,PereiraM,AraujoJ,MoreiraP,DelgadoL,etal.Effectof com-petitiveswimmingonairwayinflammation:a3-yrlongitudinalstudy.Pediatric allergyandimmunology:officialpublicationoftheEuropeanSocietyofPediatric AllergyandImmunology.2014;25:193–5.
15.VieiraRP,ToledoAC,FerreiraSC,SantosAB,MedeirosMC,HageM,etal. Air-wayepitheliummediatestheanti-inflammatoryeffectsofexerciseonasthma. Respiratoryphysiology&neurobiology.2011;175:383–9.
16.Franca-PintoA,MendesFA,deCarvalho-PintoRM,AgondiRC,CukierA,Stelmach R,etal.Aerobictrainingdecreasesbronchialhyperresponsivenessandsystemic inflammationinpatientswithmoderateorsevereasthma:arandomised con-trolledtrial.Thorax.2015;70:732–9.
17.MoreiraA,DelgadoL,HaahtelaT,FonsecaJ,MoreiraP,LopesC,etal. Physi-caltrainingdoesnotincreaseallergicinflammationinasthmaticchildren.The Europeanrespiratoryjournal:officialjournaloftheEuropeanSocietyforClinical RespiratoryPhysiology.2008;32:1570–5.
18.DelGiaccoSR,ScorcuM,ArgiolasF,FirinuD,DelGiaccoGS.ExerciseTraining, LymphocyteSubsetsandTheirCytokinesProduction:Experienceofan Ital-ianProfessionalFootballTeamandTheirImpactonAllergy.BioMedResearch International.2014;2014:6.
