AsthmapreventionandmanagementstrategyinJapanAsthmadeathinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapan(Asthma-COPDoverlapsyndrome)Asthmapreventionandmanagementstrategy

inJapanAsthmadeathsinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapanAsthmaasavariablediseaseAnnualchangesinasthmadeathsCompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline20152,0008,00016,00018,0004,000Numberofasthmadeaths06,00012,00014,00010,00019501955196019651970197519801985199019952000200520101,550deathsin2014Asthmadeathsbyagegroup

in2013Numberofasthmadeaths(Deaths)(agegroups)FemaleMale5002505003501504503004002001000-45-915-1930-3420-2425-2935-3940-4445-4950-5455-5960-6465-6970-7475-7980-8485-8990-9495-99≥10010-14CompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015Annualchangesinasthmamortalitybyage1100100.1(per0.1millionpopulation)0～45～910～1415～1920～2425～2930～3435～3940～4445～4950～5455～5960～6465～6970～7475～7980～8485～8990～9495～99100(age)200320082013～CompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015Globalchangesinasthmamortality

(populationaged5to34yearsold)19606570758085909520000510(year)4.500.004.003.503.002.502.001.501.000.50Mortalityfromasthma(per0.1millionpopulation)JapanHongKongTheU.S.CanadaSwedenTheU.K.FranceNewZealandAustraliaCompiledunderthesupervisionofSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline20151)Copyright2013IMSJapancoSource:IMSJPM(MAT2012Dec)Allrightsreserved.2)MinistryofHealth,LabourandWelfare,VitalStatistics2012KenOhta:Mebio.27:27-33,20103)MHLWVitalStatistics

JapaneseGuidelinesforAsthma(millionyen)（year）1,0002,0003,0008,00004,0006,0007,0005,000SalesofinhaledcorticosteroidsNumberofasthmadeathsInhaledcorticosteroids+long-actingβ2-agonistcombinations1)

Inhaledcorticosteroids1)Numberofasthmadeaths2,3)

JGL?12Asthmadeaths

andsalesofinhaledcorticosteroidsJGL?93JGL?95JGL?98JPGL?00JPGL?02JGL?03JPGL?05JGL?06JPGL?08JGL?09JPGL?1210,00020,00030,000120,000050,00040,00060,00080,00070,00090,000100,000110,000?14?13?11?85?93?95?97?01?03?05?09?87?89?91?99?071,550AsthmadeathinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapan(Asthma-COPDoverlapsyndrome)Asthmapreventionandmanagementstrategy

inJapanAsthmadeathsinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapanAsthmaasavariablediseaseWell-controlled(meetsallcriteria)Partlycontrolled(meets1or2criteria)UncontrolledAsthmasymptoms(inthedaytimeornight-time)NoneOnceormoreaweekMeets3ormoreofthepartlycontrolledcriteriaUseofrelieverNoneOnceormoreaweekLimitationofactivities,includingexerciseNonelimitedLungfunction(FEV1andPEF)≥80%ofpredictedorpersonalbestvalue<80%ofpredictedorpersonalbestvalueDiurnal(weekly)variationinPEF<20%*≥20%ExacerbationNoneOnceormoreayearOnceormoreamonth?* Normallimitis<8%whenmeasuredtwiceaday.? Oneormoreexacerbationsamonthisassessedasuncontrolled,evenifothercriteriaarenotmet.AssessmentofasthmacontrolCompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015GINAassessmentofasthmacontrolGINA2014,Box2-2ATreatmentstep1Treatmentstep2Treatmentstep3Treatmentstep4Symptoms（Mildintermittent）LessthanonceaweekMildandbriefOccuratnightlessthantwiceamonth（Mildpersistent）Onceormoreaweek,noteverydayDisturbeverydaylifeorsleeponceormoreamonthOccuratnighttwiceormoreamonth（Moderatepersistent）EverydayRequireshort-actinginhaledβ2agonistalmosteverydayDisturbeverydaylifeorsleeponceormoreaweekOccuratnightonceormoreaweek（Severepersistent）FrequentlyexacerbatedevenundertreatmentEverydayEverydaylifelimitationFrequentlyoccuratnightSymptomsandtreatmentstepsforuntreatedpatientsCompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015AgentProductNameDevicePictureDrypowderFluticasone

propionateFlutideRotadiskDiskhalerFluticasone

propionateFlutideDiskusDiskusBudesonidePulmicortTurbuhalerMometasone

furoate

AsmanexTwisthalerpMDIBeclometasone

propionateQvarpMDICiclesonideAlvescopMDIFluticasone

propionateFlutideAirpMDISuspen-sionBudesonidePulmicort

RespulesNebulizerICSavailableinJapanPharmaceuticalcompaniesofficialsites,Packageinserts.AgentProductNameDevicePicturepMDIFluticasone

propionate/FormoterolFumarateHydrateFlutiformpMDIFluticasone

propionate/SalmeterolxinafoateAdoairAIRpMDIDrypowderFluticasone

propionate/SalmeterolxinafoateAdoairDiskusDiskusBudesonide/

FormoterolFumarateHydrateSymbicortTurbuhalerFluticasoneFuroate/VilanterolTrifenatateRelvarElliptaICS/LABAcombinationsavailableinJapanPharmaceuticalcompaniesofficialsites,Packageinserts.

Treatmentstep1Treatmentstep2Treatmentstep3Treatmentstep4Long-termmanagementagentsBasictreatmentICS(lowdose)ICS(lowtomediumdose)ICS(mediumtohighdose)ICS(highdose)Ifabovecannotbeused,useoneofthefollowingagents.?LTRA?Sustained-releasetheophylline(unnecessaryforraresymptoms)Ifaboveisineffective,concomitantlyuseoneofthefollowingagents.?LABA (acombinationagentcanbeused)?LTRA?Sustained-releasetheophyllineConcomitantlyuseoneormoreofthefollowingagents.?LABA (acombinationagentcanbeused)?LTRA?Sustained-releasetheophylline?LAMA#Concomitantlyusemultipleagentsfromthefollowing.?LABA (acombinationagentcanbeused)?LTRA?Sustained-releasetheophylline?LAMA#

Ifuncontrolled,addeitherorbothofthebelow.?Anti-IgEantibody??Oralcorticosteroids§AdditionaltreatmentAntiallergicsotherthanLTRA?AntiallergicsotherthanLTRA?AntiallergicsotherthanLTRA?AntiallergicsotherthanLTRA?Exacerbationtreatment?InhaledSABAInhaledSABAInhaledSABAInhaledSABATreatmentstepsforasthmaLTRA,leukotrienereceptorantagonists;LABA,long-actingβ2agonist;SABA,short-actingβ2

agonist;LAMA,long-actingmuscarinicantagonists?Antiallergicsrefertomediatorantireleasers,histamineH1antagonists,thromboxaneA2inhibitors,andTh2cytokineinhibitors.?Anti-IgEantibodyisindicatedforpatientswhoarepositiveforperennialinhaledallergenwithserumtotalIgEvalueof30-1,500IU/mL.§Oralcorticosteroidsareintermittentadministrationforashortperiod.Keeptheminimummaintenancedoseifapatientcannotbecontrolledbyenhancedtreatmentwithotheragentsandshortintermittentadministration.# Tiotropiumrespimatonly?Managementagainstmildexacerbationsisshown.CompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015GINA2015–changestoSteps4and5?GlobalInitiativeforAsthmaGINA2015,Box3-5,Steps4and5*Forchildren6-11years,theophyllineisnotrecommended,andthepreferredStep3ismediumdoseICS**ForpatientsprescribedBDP/formoterolorBUD/formoterolmaintenanceandrelievertherapy#Tiotropiumbysoft-mistinhalerisindicatedasadd-ontreatmentforpatientswithahistoryofexacerbations;itisnotindicatedinchildren<18years.Other

controller

optionsRELIEVERSTEP1STEP2STEP3STEP4STEP5LowdoseICSConsiderlowdoseICSLeukotrienereceptorantagonists(LTRA)Lowdosetheophylline*Med/highdoseICSLowdoseICS+LTRA(or+theoph*)As-neededshort-actingbeta2-agonist(SABA)Lowdose

ICS/LABA*Med/high

ICS/LABAReferforadd-ontreatmente.g.anti-IgEPREFERRED

CONTROLLER

CHOICEAddtiotropium#HighdoseICS

+LTRA

(or+theoph*)Addtiotropium#Addlow

doseOCSAs-neededSABAor

lowdoseICS/formoterol**AsthmadeathinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapan(Asthma-COPDoverlapsyndrome)Asthmapreventionandmanagementstrategy

inJapanAsthmadeathsinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapanAsthmaasavariablediseaseDaytimeNighttimeDuringphysical

activityAny0Percentageofpatients45%29%27%62%70(%)605040301020Asthmaticsymptomsinthepreviousmonth:62%MitsuruAdachi,etal.,Allergology&Immunology2012;19(10),1562-1570Surveyperiod:November18toDecember26,2011Subjects:Total400patientsconsistingofthosepreviouslydiagnosedwithasthmaandwhoexperiencedasthmaticsymptomsinthepreviousyearaswellasadultpatients(aged16yearsorolder)whouseddrugsforthetreatmentofasthmainthepreviousyearMethodofsurvey:ArandomtelephoneinterviewsurveywithComputerAssistedTelephoneInterview(CATI)usingthelargestpanelforofflineinvestigationinJapanDailyactivitylimitations:60%MitsuruAdachi,etal.,Allergology&Immunology2012;19(10),1562-1570Isometimesforgetinhalationtherapy.Ihaveonceinterrupted/discontinuedinhalationtherapywhenIfeltwell.IhaveonceforgottentobringtheinhalantwithmewhenIwassupposedtoinhaleit.Ihaveonceinterrupted/discontinuedinhalationtherapybecauseoftheexpense.Inhalationtherapyissometimesinterruptedbecauseofthedelayinvisitingclinic/hospital.Ihaveonceinterrupted/discontinuedinhalationtherapybecauseIthoughtthedrugwasineffective.Ihaveexperiencednoneoftheabove.Patientswithhighadherence22.7%(n=127)Patientswithlowadherence77.3%(n=432)01020304070(%)22.7%50604.8%10.2%12.5%14.0%35.1%60.6%(n=559)*Patientswhoindicated“haveexperiencednoneoftheabove”wereassumedtobepatientswithhighadherenceintheanalysis.Forgetorinterrupt/discontinueinhalation:77.3%Haveyoueverforgottenorinterrupted/discontinuedtheuseofinhalants?

(Multipleanswersallowed)QuestiontoPatientsNagaseHetal.,AllergolImmunol2013;20(9),1332-1347Changedthefrequency?(n=559)YesNoIncreasedthefrequency255(45.6%)304

(54.4%)Decreasedthefrequency301

(53.8%)258

(46.2%)(n=301)33.6%19.9%9.3%4.7%4.0%3.3%BecauseItakemedicineonlywhenIhavesymptoms.BecauseIamworriedaboutprescriptioncharge.BecauseIamworriedaboutadversedrugreactions.Becausethefrequencyofinhalationperdayseemstobetoooften.Becausethenumberofinhalationsperdoseseemstobetoomany.BecauseIamsatisfiedwiththeoraltreatment.0510152040(%)30352545Takemedicineonlywhenhavingsymptoms:33.6%Haveyoueverincreasedordecreasedthefrequencyoftheinhalationtherapyatyourdiscretion?QuestiontoPatientsWhydidyouincreaseordecreasethefrequencyoftheinhalationtherapyatyourdiscretion?(Multipleanswersallowed)QuestiontoPatientsNagaseHetal.,AllergolImmunol2013;20(9),1332-1347Questionnaires

AsthmaControlTest

(ACT) AsthmaControlQuestionnaire(ACQ),etc.Pulmonaryfunction

Spirometry,peakexpiratoryflow(PEF)

Forcedoscillationtechnique(FOT)SputumeosinophilcountFractionalexhalednitricoxide(FeNO)AirwayhyperresponsivenesstestMeasuresofasthmacontrolNOisfoundinhighconcentrationsintheexhaledbreathofasthmapatients.NOisproducedbyrespiratoryepithelialcells,eosinophils,neutrophils,andmacrophages.ActivityofinducibleNOsynthase(iNOS)isincreasedduetoinflammatorycytokines,etc.inasthmapatients.FeNOisanoninvasiveandmeasurablebiomarkerofeosinophilicairwayinflammation.SummaryofFeNOCHESTMI,Inc.NIOXMINOFeNOasanindicatorofadherenceBeck-RippJ,etal.;EurRespirJ2002;19:1015-9.25CompliancewithBUD%ofprescribed■■■■■■■■■■■■■■■■■100050-505075100ReductionineNO%Flowoflong-termasthmamanagementCompiledundersupervisionoftheSpecialCommitteeonAsthmaGuidelines,GeneralIncorporatedAssociationofJapaneseSocietyofAllergology;AsthmaPreventionandManagementGuideline2015*IfthediseaseisstillpoorlycontrolleddespitethetreatmentatStep3orabove,itisrecommendedthatthepatientbereferredtoaspecialist.TreatmentofotherdiseasesAdditionalguidanceSmokingcessation,change/discontinuationofthedrugwhichmayaggravateasthma,andthoroughmanagementofcomplicationsReferraltoaspecialist(TreatmentStep4)CannotattainfavorablecontrolwithtreatmentIfcontrolhasbeenachievedandmaintained,stepdown

treatmentafter3

months.Isthediagnosisofasthmacorrect?Doesthepatientshow

goodadherencetothemedication?Istheinhalation

techniquecorrect?Areaggravatingfactorsand

comorbidityproperlycontrolled?Improvementwithastep-upoftreatmentYesYesYesYesYesNoNoNoNoImpactofinhalertechniqueguidanceonPEFKuboYandTohdaY.Asthma18;64-68,2005(%)(month)123456789101112131415161718-10Firstinhalationguidance20515100-5Guidanceshouldbeprovidedrepeatedlytoeachpatient.Subjects:OutpatientswithasthmaMethod:InvestigatedtheimplementationofinhalationguidanceforretrainingandimprovementinpeakflowrateResults:Improvementsinpeakflowratewereoftenobservedoneortwomonthsafterguidanceeveninpatientswhohadusedinhalantsproperlyatthetimeofretraining.Ontheotherhand,thepeakflowratedecreasedafter

anaverageofapproximatelyninemonthsinpatientswhohadnotbeenretrained.(Theabovegraphshowsatypicalcaseofimprovementinpeakflowrateafterretraining.)ImprovementrateinPEFAdditionalguidanceSecondinhalationguidanceAsthmadeathinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapan(Asthma-COPDoverlapsyndrome)Asthmapreventionandmanagementstrategy

inJapanAsthmadeathsinJapanJapaneseguidelinesforadultasthmaAsthmadilemmainJapanAsthmaasavariablediseaseSurveyofPatients(TheACQUIREstudy)

AsthmaControl,QUalityofLIfeandEmotionalFeelingsinaREalLifeSetting

-APostalMailSurveyofAdultAsthmaPatientsinJapanMitsuruAdachietal.,Allergology&Immunology22:1446-1460,20151,248patientsaged20yearsorolderwithasthmatreatedinJapanwho:1)werepreviouslygivenadiagnosisofbronchialasthmabyaphysician,2)areoncontinuousoutpatienttreatment,and3)havebeenprescribedatleastonelong-termasthmacontroldrug*forfourweeksormore.SentAsthmaDiaryandAsthmaTreatmentSurveyQuestionnairetopatientsbypostalmailandrequestedthemtoanswer.Evaluatedasthmacontrol(JGL2012Standard)from1-weekAsthmaDiaryrecords,andexacerbationhistoryinthepastoneyear.PsychologicalstateofpatientsfromtheAsthmaTreatmentSurveyQuestionnaireControlofasthmainthemonthaftertheAsthmaTreatmentSurveyQuestionnaireHowasthmawascontrolledbyACQ-5QOLevaluationbyMiniAQLQNationwideMay,2014AstraZenecaK.K.SubjectsPrimaryendpointMethodDistrictswherethesurveywasconductedSurveyperiodSecondaryendpointCOI*ICS,LABA,ICS/LABAcombinationdrug,leukotrienereceptorantagonist(LTRA),theophylｌinesustained-releasepreparation,andotherasthmatherapeuticagents(suchasoralsteroid,mediatorreleaseinhibitor,HistamineH1antagonist,thromboxameA2

inhibitor,andTh2cytokineinhibitor.)PrescribedtherapeuticagenttotreatasthmaTherapeuticagentn%ICS31425.2ICS/LABAcombinations83867.1LABA29423.6

(Inhaler)362.9

(Plaster)21016.8

(Internal)927.4Leukotrienereceptorantagonist(LTRA)55144.2Theophylｌinesustained-releasepreparation36629.3Oralcorticosteroid14911.9InhalerCOPDtherapeuticagent(LAMA,LABA/LAMA)262.1Anti-IgEantibody80.6Asthmaattackinhalertherapeuticagent*90172.2Unknown50.4*Includingas-neededuseofinhaleradditionformaintenancetherapysuchasbudesonide/formoterol.Subjects:1,248patientsaged20yearsorolderwithasthmatreatedinJapanwho:1)werepreviouslygivenadiagnosisofbronchialasthmabyaphysician,2)areoncontinuousoutpatienttreatment,and3)havebeenprescribedatleastonelong-termasthmacontroldrug*forfourweeksormore.Method:Surveyedprescribedasthmatherapeuticagentbypostalmailquestionnaire.Districtswherethesurveywasconducted:Nationwide

Surveyperiod:May2014COI:AstraZenecaK.K.MitsuruAdachietal.,Allergology&Immunology22:1446-1460,2015n=1,248Eventhoughtheadultasthmapatientsweretreatedwithanti-asthmaagents(ICS,ICS/LABA,etc.)regularlyandwithgoodadherence*,themajorityhadasthmaticsymptomsAsthmacontrolstatusMitsuruAdachietal.,Allergology&Immunology22:1446-1460,2015*Longtermcontroldrugwastakenfor6.0（SD2.2）daysonaverageoutof7daysasinstructedbyadoctor.Subjects:1,248patientsaged20yearsorolderwithasthmatreatedinJapanwho:1)werepreviouslygivenadiagnosisofbronchialasthmabyaphysician,2)areoncontinuousoutpatienttreatment,and3)havebeenprescribedatleastonelong-termasthmacontroldrugforfourweeksormore.Method: SurveyedasthmacontrolconditionevaluatedbasedonJGL2012standard#

fromexacerbationhistoryinpastoneyearaswellasfromtherecordinAsthmaDiaryforoneweekbypostalmailquestionnaire.Districtswherethesurveywasconducted:NationwideSurveyperiod:May2014COI:AstraZenecaK.K.#Asthmaconditions(daytimeandnighttime),useofasthmaattacktherapeuticagents,restrictioninactivitiesincludingphysicalexercise,exacerbation(receiveunplannedmedicalconsultation,

emergencyconsultation,hospitaladmission)wereusedasevaluationcriteria,andcalculationsweredonebasedonJGL2012.ICS:Inhaledcorticosteroid;ICS/LABA:Inhaledcorticosteroid/long-actingβ2-agonist;SABA:Short-actingβ2-agonist

Partly73.6%(919)Poor17.3%(216)Well9.1%(113)PercentageofpatientswhoexperiencedsymptomsintheirAsthmaDiaryoveroneweekn=1,248020406080100(%)87.567.064.644.147.062.346.538.520.833.342.919.63.1Subjects:1,248patientsaged20yearsorolderwithasthmatreatedinJapanwho:1)werepreviouslygivenadiagnosisofbronchialasthmabyaphysician,2)areoncontinuousoutpatienttreatment,and3)havebeenprescribedatleastonelong-termasthmacontroldrug*forfourweeksormore.Method:Surveyedrecordinasthmadiaryforoneweekbypostalmailedquestionnaire.Districtswherethesurveywasconducted:Nationwide

Surveyperiod:May2014COI:AstraZenecaK.K.*Ifapatientwasunabletoconductdailywork,schoolactivities,exerciseordohousekeepingworkbecauseofasthmasymptomsMitsuruAdachietal.,Allergology&Immunology22:1446-1460,2015DaytimeconditionsCoughSputumShortbreathStridorNighttimeconditionsCoughSputumShortbreathStridorActivitylimitations*UseofasthmaattacktherapeuticagentsReceiveunplannedmedicalconsultation

?Emergency

consultation

?HospitaladmissionDetaileddaytimeconditionsDetailednight-timeconditionsPathophysiologyofasthmaSinceasthmaisaheterogeneousdisease,symptomsmayoccurduetovariousfactorsevenwhenpatientsareundertreatmentwithlong-termcontroldrugs(suchasICSandcombinationproductsofICS/LABA).Ifuntreated,thediseasemaycauseseizures/aggravations.CompiledunderthesupervisionofDr.MitsuruAdachi,ProfessorofClinicalResearchCenterforMedicineofInternationalUniversityofHealthandWelfare,andClinicalAllergy/Asthma,InternalMedicine,SannoHospitalICS;inhaledcorticosteroid:ICS/LABA;inhaledcorticosteroid/long-actingbeta-2agonistLevelofsymptomsAllergenViralinfectioncommoncoldWeatherSymptomsWorsening/exacerbationMitesSymptomsImmediatestrengtheningofanti-inflammatory