哮喘治疗策略

Whatisoptimalasthmamanagementstrategy?哮喘治疗最佳策略WhatwelearnfromGOALandCONCEPTstudies?我们从GOAL和CONCEPT研究中能学到什么？TheDebateStabledosingadjustedwithphysiciantoachieveandmaintainasthmacontrol:e.g.GOAL“Symptom-Free”VersusSelf-adjustmentindoseinresponsetosymptoms“Symptom-Driven”P-SelectinE-SelectiniNOSCOX-2VCAM-1ICAM-1Mac-1LFA-1TGFIL-5IL-3IL-4IL-5GM-CSFTNFIL-1IL-1MCP-1ElastaseTryptaseEotaxinMIP1TNFIL-2IL-8IL-8IL-8RantesIFNTCELLENDOTHELIUMMACROPHAGEEOSINOPHILIL-6CollagenaseStromelysinIL-12TNFMASTCELLFIBROBLASTSIL-5IL-4IL-10MultipleinflammatoryGenesExpressedAsthmaNEUTROPHILP-SelectinE-SelectiniNOSCOX-2VCAM-1ICAM-1Mac-1LFA-1TGFIL-5IL-3IL-4IL-5GM-CSFTNFIL-1IL-1MCP-1ElastaseTryptaseEotaxinMIP1TNFIL-2IL-8IL-8IL-8RantesIFNTCELLENDOTHELIUMMACROPHAGEEOSINOPHILIL-6CollagenaseStromelysinIL-12TNFMASTCELLFIBROBLASTSIL-5IL-4IL-10StopGeneExpressiontoStopInflammationNEUTROPHILSTOPSTOPSTOPSTOPSTOPSTOPControllingeosinophilicinflammationinasthmaleadstoareductioninasthmaexacerbationsBTSmanagementgroupSputummanagementgroup3%SevereExacerbationsTime(months)0123456789101112120100806040200Green.Lancet.2002;360:1715-1721.AHRContinuestoimproveevenafterlungfunctionhasplateaued95100105110-2-101Baseline36121MonthaftertreatmentTime(months)FEV1(%baseline)Log10PD20(mg)AHRFEV1Derivedfrom:Wardetal.2000TimecoursefortheImprovementofVariousParameters-%improvement100Woolcock,ERS2000YearsMonthsDaysWeeksNonightsymptomsPEFamFEV1AHRNoSABAuseDataderivedfromReddelHetal.2000?TOTALCONTROLachievedwithsustainedtreatment(PhaseII)%ofpatientsSeretidePhaseIISeretidePhaseIFPPhaseIIFPPhaseI44%29%50%16%28%40%208060400Steroidnaïve(S1)LowdoseICS(S2)ModeratedoseICS(S3)Batemanetal,AmJRespirCritCareMed,July2004TreatmentaimedatcontrollingairwayinflammationprovidesbetterasthmacontrolAndittakestimeUSAEuropeAsiaPacificJapanPatientsarepooratassessingasthmacontrol304060050%ofpatients1020PatientswithseverepersistentsymptomsRabeetal.EurRespirJ2000;:CompletecontrolC&EEuropePhysiciansarealsopooratassessingasthmacontrol30405060708090100EntirepopulationResidentsPrimarycareFellowsAsthmaspecialists%Correctp0.05comparedwithallothersQuestionstotestknowledgeonNHLBIasthmaguidelinesKevinCetal.AJRCCM1999;159:1735–41.AccuracyofPatientPerceptionofSymptomsGaugingsymptomsaccuratelyisfundamentaltoasymptom-basedapproachtoasthmamanagementHowever,asignificantproportionofasthmaticscannotreliablydetectchangesinlungfunction(1),therebyeitheroverorunder-estimatingsymptomseverityUnder-estimationisbelievedtobeamajorreasonfordelaysintreatmentwhichmayresultinincreasedmorbidity&mortality(2)Toomuchfocusonsymptomsmayresultinunwarrantedillnessbehavioursandrestrictions,excessivemedicationuse,overutilisationofmedicalservicesandnegativeemotions(3.)1-3ReferencesavailableinbibliographyStabledoseregimenwithsalmeterol/fluticasone(Seretide™Diskus™)50/250μgbidvsSymptom-based,AMDwithformoterol/budesonide(SymbicortTurbuhaler™)6/200μg52-weekrandomisedcontrolledtrialDouble-blind,double-dummyFitzGeraldetalClinTher2005CONtrolCEntredPatientTreatmentstudyCONCEPT:StudyschematicFitzGeraldetalClinTher2005200-500µgICS+LABAor500-1000µgICS/dayRWeeks1-4Weeks5-52SALM/FP50/250bid+placeboTurbuhaleradjustablemaintenancedosingBUD/FORM6/200adjustablemaintenancedosing+placeboDiskusbidAdjustablemaintenancedosing:1inhalationbidstepped-downto1od,ifcontrolled,stepped-upto4bidfor7-14daysifsymptomatic.Run-in(2wks)SALM/FP50/250bid+placeboTurbuhaler2bidBUD/FORM6/2002bid+placeboDiskusbidSymbicortAdjustableMaintenanceDosing2x21x24ax21x21x1AsthmasignsNumberofinhalationsxdosefrequency/dayaapprovedDec2003‘Whencontrolhasbeenachieved,thedoseshouldbetitratedtothelowesteffectivedose,whichcouldincludeSymbicortTurbuhalergivenoncedaily’IllustrationadaptedafromSymbicortProductMonograph20011-2puffstwicedailyincreasedifnecessarytomax.4puffstwicedaily,reducedto1puffoncedailyifcontrolmaintained–BNF2004CONCEPT:StudyendpointsPrimaryendpoint:Symptom-freedaysKeySecondaryendpoints:Exacerbations(requiringoralsteroidsand/orERvisitsand/orhospitalisation)ExposuretooralsteroidsFitzGeraldetalClinTher2005p=0.034SALM/FPn=344BUD/FORMn=34458.852.1010203040506070Median%symptom-freedaysWeeks1-52FitzGeraldetalClinTher2005Primaryendpoint:Symptom-freedaysSymptom-freedaysbystudyphaseWeeks1-4(stabledosing)Weeks5-52(SALM/FPstabledosingvsBUD/FORMAMDdosing)Weeks5-52:p=0.0300102030405060708025%25%SALM/FP1bidBUD/FORM2bidMedian%symptom-freedays74%65%SALM/FP1bidBUD/FORMAMDFitzGeraldetalClinTher2005Timetofirstexacerbation05101520250369121518212427303336394245485154Timetofirstexacerbation(week)Patientswhoexacerbated(%)SALM/FPBUD/FORMTreatmentgroupFitzGeraldetalPresentedatWAC2005SignificantlylowerexacerbationratewithSALM/FPstabledosep=0.008SALM/FPn=344BUD/FORMn=3440.180.3300.10.20.30.4Adjustedannualmeanrateofmoderate/severeexacerbationsModerate/severeexacerbations:deteriorationinasthmarequiringERvisit,hospitalisationand/oruseoforalcortico