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z(I-IV)z(2003,WHO,)zzzzPAH(ACCP2007)70%-1“”D'AlonzoGE,etal.AnnInternMed1991;115(5):343-9MHumbert,etal.AmJRespirCritCareMed.2006z26%IPAHz50%-70%FPAHzSimonneauGetal.JAmCollCardiol2004;43:5S-12SLaneKBetal.NatGenet2000;26(1):81–4BMPR2TATACCAAT;Egr-1,Myf5Smad3,Smad4.•••••IntimalproliferationAdventitialproliferationMedialhypertrophyNormalPAHPAHPlexiformlesionz:SSCPAH1IPAH2.8168%348%534%III6IV6Mayo521%z6300WHO,••••••COPD••••••()•••JACC2004;43:S5-S12,Chest2004;126:14S-34S•XX•zz20%z20%z13%z10%z10%zzzz•–•••–•••40mmHg3.0m/s––•“”––––•••–••••••••••TimePre-symptomatic/CompensatedSymptomatic/DecompensatingSymptomThresholdRVFailureRVFailureDeclining/DecompensatedCOPAPPVRCXREchoECGCOCTEPHPHSPAP40mmHg,HIV-CT,MRICTEPH,--CTEPH?6minPHPHCTEPHPHAE/BE/AAE/ACBCBBE/BBBBE/Azz-PaP255mmHg15h/z90/100/zzzcalciumchannelblockersCCB,CCBzepoprostenolFlolan®IVPAH(Iloprost,Ventavis®)III(A)IV(B)treprostinil2002IIIIIsodiumberaprostIIIIIzBosentan:ETAETBIIIIV625mgbid,4125mgbid250mgbid16Sitaxsentan:ETAambrisentanETAz(SildenafilRevatio)20mgtidIIIIIIV2005FDA••595CCB•40z1216PAHIII•CCB:3060mg/d60120mg/d2.5-10mg,1/d3040506070809010006121824303642485460MonthsProbabilityofSurvivaNIHRichetal:NEJM1992;327,76-81N=17N=17N=47N=47N=187N=187zmPAP10mmHg40mmHgSitbonO,SitbonO,HumbertHumbertM,M,JaisJaisX,etal.Circ2005;111:3105X,etal.Circ2005;111:3105--1111..zCCBz1030zCCBzCCB6.8%zNO1015min•••((FlolanFlolan®®))((RemodulinRemodulin®®))((RemodulinRemodulin®®))((VentavisVentavis®®))®z1234CTEPH)zzzzz–203IIIIV–1137–12+4–NYHAOlschewskiH,etal.NEnglJMed2002;347(5):322-9••:–6–NYHA–Mahler–––••–NYHA–12610%––OlschewskiH,etal.NEnglJMed2002;347(5):322-938%25%17%26%13%5%0%20%40%610%NYHAendpointiloprostp=0.032p=0.007:PercentageofpatientswhoimprovedexcludingdeathordeteriorationatanytimeOlschewskiH,etcal.NEnglJMed2002;347(5):322-9•126-40-2002040baseline4weeks8weeks12weeksIloprostPlaceboOlschewskietal,NEnglJMed.2002;5:322-347cT-Test,p0.004forweek12LOCF,imputation:death=0-300-200-1000100200PlaceboIloprostpreIloprostpost12p0.001vsp0.05vsp0.05vsPVR[dyn×s×cm-5]Olschewskietal,NEnglJMed.2002;5:322-347c•6-9Iloprost2.55µg5-10z®zzzz“”AC-052-351“Lancet”AC-052-352BREATHE-1“NEJM”Channicketal.Lancet2001;3581119-1123ChangeinWalkDistancemn=11125mgbidn=21-100204060BL4812±SEM62.5mg125mg*=76p0.02Channicketal.Lancet2001;3581119-1123**1127213RubinetalNEJM2002346896-903–-40-20020406080n=144n=6916*16p=0.000262.5mgbid∆SEM***44.2125mg250mgRubinetalNEJM2002346896-903n=144n=69%02550751000481216202428p=0.0015p=0.03889%63%n=35n=13FlolanFlolanRubinetalNEJM2002346896-903zzzzzzRevatio®(sildenafilcitrate)packageinsert.PfizerInc.NewYork,NY.Brown,D.G.etal.Crystalstructuresofhumanphosphodiesterase5.z640z(Revatio[Viagra])z-3.5-3-2.5-2-1.5-1-0.500.5mPAP(mmHg)CI(l/min/m2)PVR(U)RAP(mmHg)GalieN,etal.Sildenafilcitratetherapyforpulmonaryarterialhypertension.NEnglJMed2005;353(20):2148-57zIloprostsildenafilzN=7214(,zIloprost6GhofraniHA,RoseF,etal.JAmCollCardiol2003;42(1):158-164zzNOzzAABBCCDDIIE/AE/AE/BE/BE/CE/CE/DE/D-Chest.2007;131:1917-1928Figure1.TreatmentalgorithmforIPAH,orPAHassociatedwithconnectivetissuediseaseoranorexigenuse.CCB+—+CCBs—(a)(a)(a)(a)(a)(a)PAH(ACCP2007)/FunctionalClassIIzSildenafil:firstchoice–A(First-linetherapy)zSubcutaneous-BzIVtreprostinil-CChest.2007;131:1917-1928FunctionalClassIIIzBosentan:-A(First-linetherapy)zSildenafil:-A(First-linetherapy)zIVepoprostenol-A(First-linetherapy)zInhalediloprost-A(First-linetherapy)zSCtreprostinil-BzIVtreprostinil-CzCombinationtherapy?(RCTsstudying)zAtrioscptostomyorLungtransplantationChest.2007;131:1917-1928FunctionalClassIVzIVEpoprostenol:-AFirst-linetherapyzBosentan:-BzInhalediloprost:-BzSildenafil:-CzSCtreprostinil:-CzIVtreprostinil-CzCombinationtherapy?(RCTsstudying)zAtrioscptostomyorLungtransplantation-Chest.2007;131:1917-1928TreatingshouldbeconsideredzCardiopulmonaryhemodynamics(NYHA),z6MWdistance,zSignsandsymptomsofright-heartfailure,zSideeffectprofile,zDrug-druginteractions,zCost.Chest.2007;131:1917-1928z(I-IV)z(2003,WHO,)zzzzPAH(ACCP2007)!