医学交流课件：Post-ATS FLAME MSL

ILLUMALTESTUDY1Weenrolledmenandwomen40yearsofageorolder,currentorformersmokerswithasmokinghistoryofatleast10pack-years,post-bronchodilatorFEV1between40%and80%ofpredictedvalue,andpost-bronchodilatorFEV1toforcedvitalcapacity(FVC)ratiolessthan0・70.PatientswithahistoryofaCOPDexacerbationneedingtreatmentwithantibiotics,systemiccorticosteroids,orhospitalisationintheyearleadinguptoandincludingrandomisationwereexcluded.入组了40岁以上的男性和女性患者，当前或者以前吸烟并伴有至少每年10包的吸烟史。支扩剂之后FEV1在40%-80%预计值，FEV1/FVC＜0.7.同时排除前一年因COPD急性加重需要抗生素、全身激素或者住院治疗的患者。全文摘要2背景：QVA149是一种联合吸入治疗方法用于治疗COPD。它联合了印达特罗和格隆溴安成为一种复合支气管扩张剂。研究的目的是比较QVA149和SFC对于中重度COPD患者在26周内的有效性、安全性和耐受性。方法：多中心双盲，双模拟，平行研究。523名患者40岁以上的COPD患者符合GOLD2-3级，在入组前一年没有急性加重史随机分为两组，分别接受一天一次的QVA或者一天两次的SFC。评估两组的有效性及安全性。首要研究终点是证明在26周时QVA149与SFC相比在支扩及后FEV1AUC0-12H的差异，259名患者随机接受了QVA149的治疗，还有264名患者接受了SFC的治疗。结果：在第26周，FEV1AUC0-12H在QVA149组显著升高；总的不良事件包括AECOPD在内是55.4%VS60.2%分别对应QVA149和SFC，严重不良事件发生率两组间相似。COPD的恶化是最频繁的严重不良事件。结论：每天一次的QVA149给药可以显著持续提高有临床意义上的肺功能与每天两次给药SFC相比，同时症状控制方面也获益也明显；这些结果暗示双重支扩剂可以作为没有急性加重的COPD患者的选择。主要研究结果3Adverseevents,includingCOPDexacerbations,andvitalsignswererecordedateachvisit,andelectrocardiogram(ECG)andlaboratoryanalyses(haematology,clinicalchemistry,andurinalysis)weredoneonday1andweek26.Patientswhohadamoderate-to-severeCOPDexacerbation(definedbymodifiedAnthonisencriteria,10commonlyusedinCOPDclinicaltrials)不良事件包括AECOPD，生命特征在每次随访时被记录，心电图和实验室检查会在第一天和26周进行。中重度COPD的急性发作通过Anthonisencriteria定义。在第26周，FEV1AUC0-12H在QVA149组显著升高，差异为0.138L。总的不良事件包括AECOPD在内是55.4%VS60.2%分别对应QVA149和SFC。严重不良事件发生率两组间相似.ILLUMINATE小结StudydetailInformationPIClausVogelmeierPrimaryendpointSuperiorityofUltibrooverSeretideforFEV1AUC0-12hat26weeksUltibro在26周FEV1

AUC0-12优于舒利迭SecondaryendpointsLungfunctionmeasuresSGRQTDIRescuemedicationuseExpectedstudycompletiondateStudycompletedandpublishedin2013TodemonstratethatUltibroissuperiortoSeretideintermsofimprovementsinlungfunction证明ULTIBRO在提高肺功能方面优于舒利迭。ToinvestigatethesafetyandtolerabilityofUltibrocomparedwithSeretide评估与舒利迭相比，ULTIBRO安全性和依从性。Objective92sitesglobally(1:1)N=523QDInd/Gly(110/50)Breezhaler筛选中重度

COPDGOLDStageII-IIINomod/severeexacinprevious12mBiDSalm/Flu(50/500)AccuhalerAtweek26,FEV1AUC0–12hwassignificantlyhigherwithQVA149thanwithSFC(treatmentdifference0·138L;95%CI0·100–0·176;p<0·0001)在第26周，QVA149FEV1曲线下面积显著高于舒利迭（治疗差异0.138L)。Overallincidenceofadverseevents(inclCOPDexacerbations)was55.4%(143of258)fortheUltibrogroupand60.2%(159of264)fortheSeretidegroup总的不良事件发生率（包括COPD的急性加重），在Ultibro组是55.4%，在舒利迭组是60.2%。NofurtherdetailsuppliedinpublicationVogelmeieretal.LancetRespirMed.2013Mar;1(1):51-60ILLUMINATEZhongetal.IntJChronObstructPulmonDis.2015Jun5;10:1015-26LANTERN一项事后分析ILLUMINATE研究显示在19.8%的重度COPD患者中，与舒利迭相比，QVA149延长了到首次急性加重的时间。Zhongetal2015-LANTERNstudyfulltext5LANTERNSTUDY

NanshanZhong1ChangzhengWang2XiangdongZhou3NuofuZhang1MichaelHumphries4LindaWang4ChauThach5FrancescoPatalano6DonaldBanerji5OnbehalfoftheLANTERNInvestigators2015.6.5

4BeijingNovartisPharmaCo.Ltd.,Shanghai,People’sRepublicofChina;5NovartisPharmaceuticalsCorporation,EastHanover,NJ,USA;6NovartisPharmaAG,Basel,Switzerland6LANTERNSTUDY

Background:ThecurrentGlobalinitiativeforchronicObstructiveLungDisease(GOLD)treatmentstrategyrecommendstheuseofoneormorebronchodilatorsaccordingtothepatient’sairflowlimitation,theirhistoryofexacerbations,andsymptoms.TheLANTERNstudyevaluatedtheeffectofthelong-actingβ2-agonist(LABA)/long-actingmuscarinicantagonist(LAMA)dualbronchodilator,QVA149(indacaterol/glycopyrronium),ascomparedwiththeLABA/inhaledcorticosteroid,salmeterol/fluticasone(SFC),inpatientswithmoderate-to-severeCOPDwithahistoryof1exacerbationinthepreviousyear.当前的GOLD指南治疗策略根据病人气流受限的情况和他们的急性加重史及症状严重度推荐使用一种或者多种的支扩剂进行治疗。LANTERN研究评估了LABA和LAMA双重支扩剂QVA149（印达特罗/格隆溴安）与SFC相比，在中重度的COPD且前一年有小于等于1次急性加重史的患者中的有效性。Methods:Inthisdouble-blind,double-dummy,parallel-groupstudy,744patientswithmoderate-to-severeCOPDwithahistoryof1exacerbationsinthepreviousyearwererandomized(1:1)toQVA149110/50μgoncedailyorSFC50/500μgtwicedailyfor26weeks.TheprimaryendpointwasnoninferiorityofQVA149versusSFCfortroughforcedexpiratoryvolumein1second(FEV1)atweek26.方法：双盲双模拟平行研究，744例中重度的COPD患者，前一年有小于等于1次急性加重史，随机1：1分为QVA149QD和舒利迭50/500BID治疗26周。首要研究终点是在26周时QVA149在FEV1谷值上不劣效于舒利迭。Results:Overall,676patientscompletedthestudy.TheprimaryobjectiveofnoninferioritybetweenQVA149andSFCintroughFEV1atweek26wasmet.QVA149demonstratedstatisticallysignificantsuperioritytoSFCfortroughFEV1(treatmentdifference[Δ]=75mL;P0.001).QVA149demonstratedastatisticallysignificantimprovementinstandardizedareaunderthecurve(AUC)from0hoursto4hoursforFEV1(FEV1AUC0–4h)atweek26versusSFC(Δ=122mL;P0.001).QVA149andSFChadsimilarimprovementsintransitiondyspneaindexfocalscore,StGeorgeRespiratoryQuestionnairetotalscore,andrescuemedicationuse.However,QVA149significantlyreducedtherateofmoderateorsevereexacerbationsby31%(P=0.048)overSFC.Overall,theincidenceofadverseeventswascomparablebetweenQVA149(40.1%)andSFC(47.4%).TheincidenceofpneumoniawasthreefoldlowerwithQVA149(0.8%)versusSFC(2.7%)结果：总的来说，676名患者完成了研究。首要终点达到了在26周时的FEV1谷值方面QVA149不劣效于舒利迭。同时与SFC相比，在FEV1的谷值方面QVA149表现出显著的优势，平均差异75ML。研究还证明QVA149与舒利迭相比在26周时显著提高FEV1AUC0-4H；除此之外，QVA149和SFC在呼吸困难指数评分、圣乔治评分和缓解药物使用方面相似。然而，与舒利迭相比，QVA149显著减少了中重度急性加重的比率达到31%；肺炎的发生率舒利迭组比QVA149组高三倍。Conclusion:ThesefindingssupporttheuseoftheLABA/LAMA,QVA149asanalternativetreatment,overLABA/inhaledcorticosteroid,inthemanagementofmoderate-to-severeCOPDpatients(GOLDBandGOLDD)withahistoryof1exacerbationinthepreviousyear.结论：这些结果支持LABA/LAMA的使用，证明QVA149作为一种可选择的治疗方法，成为管理中重度只有≤1次急性加重史的COPD患者优于ICS/LABA的选择。LANTERN概述StudydetailInformationPINanshanZhong首要研究中的Non-inferiorityofUltibrocomparedtoSeretidefortroughFEV1at26weeks在26周时Uitibr比FEV1不劣效于舒利迭次要研究终点LungfunctionmeasuresSGRQTDIRescuemedicationuse急性加重被包括作为一个探索性的研究终点预计研究完成时间Studycompletedandpublishedin2015TodemonstratethatUltibroisnon-inferiortoSeretideintermsoftroughFEV1at26weeks证明ULTIBRO不劣效于舒利迭在26周的FEV1方面。ToinvestigatethesafetyandtolerabilityofUltibrocomparedwithSeretide评估ULTIBRO与舒利迭相比的安全性和耐受性目标56sites全球(AllLATAM+APAC)(1:1)N=774QDInd/Gly(110/50)Breezhaler筛选中/重度

COPDGOLDStageII-III≤1次中重度急性加重

在之前一年50%GOLDB50%GOLDDBiDSalm/Flu(50/500)AccuhalerZhongetal.IntJChronObstructPulmonDis.2015Jun5;10:1015-26LANTERNSupplementarymaterialsavailableat:/pmc/articles/PMC4461092/pdf/copd-10-1015.pdf8主要研究结果-FEV1FEV1谷值Post-dosetroughFEV1wasdefinedasthemeanofFEV1valuesobtained23hours15minutesand23hours45minutespost-dose亚组分析FEV1谷值森林图在FEV1的谷值方面，与SFC相比QVA149表现出显著的优势，在26周时平均差异75ML。QVA149还证明与舒利迭相比在26周时从0到4小时的FEV1AUC0-4H曲线下标准面积显著提高。9文中最有争议的结论：文中结论：与舒利迭相比，Ultibro显著减少31%的重度和极重度的急性加重比率。延长到首次中度和极重度的急性加重时间（减少35%的风险）？补充材料：Exacerbationsdefinedasworseningofsymptoms急性加重定义为症状恶化

(获取viatheeDiary)Moderateandsevereexacerbationswerealsocapturedinthecasereportform中重度急性加重同样也是从事件报告中获取(CRF)Anthonisencriteriawereusedtodefinethesymptomsofanexacerbation。Anthonisen标准用于定义急性加重的症状。Exacerbationswereconsideredmoderateifpatientsweretreatedwithsystemiccorticosteroidsorantibioticsorboth.中度急性加重定义为使用全身激素或者是抗生素或者两者都用。ExacerbationswereconsideredsevereifpatientswerehospitalizedorexperiencedanERvisitlongerthan24hours.重度急性加重被定义为病人需要住院或者需要急诊访视超过24小时。10患者基线值Importantly,therewasahigherproportionofpatientsrandomizedtoSFCwhohadapriorhistoryofmoderateorsevereexacerbationsatbaseline,butthatwasarandomphenomenon.更重要的是，在基线值时SFC组随机后的患者有更高的中重度急性加重史比率。随机后发现两组在急性加重史（≤1次）患者比率有差异为（QVA149组16.4%VSSFC组25.2%）有≤1次急性加重的患者的比率不超过20%。11所有患者的中重度急性加重QVA149同时也显著延长到了首次中重度急性加重的时间和减少了风险发生这类急性加重35%。所有患者人群中，与SFC相比，年中重度急性加重的比率在QVA149组是显著降低，减少了31%的风险。中重度急性加重的患者比率中重度急性加重的年率12所有急性加重Allpatients所有入组患者(QVAVSSFC)数量年率RRP值减少风险是否有统计学意义中重度急性加重（全文）急性加重次数：53VS810.3VS0.460.69P＜0.0531%有到首次中重度急性加重时间（全文）急性加重百分比12%VS18.9%0.65P＝0.02835%

有所有急性加重（轻重中）补充材料急性加重次数105vs1310.59VS0.750.7931%无统计学差异重度急性加重（补充材料）重度急性加重次数6VS170.03vs0.090.31P＜0.0569%有到首次重度急性加重时间（补充材料）0.32P＝0.02768%有补充材料：Thetotalnumberofallexacerbations(mild,moderateandsevere)waslowerintheQVA149treatmentarm(105)comparedwiththeSFCtreatmentarm(131).therateofallCOPDexacerbationsperyearwaslowerintheQVA149(0.59)treatmentgroupwhencomparedwithSFC(0.75)treatmentarmalthoughthisdifferencedidnotreachstatisticalsignificance所有急性加重的数量在QVA149组更低与SFC相比，105VS131；总的COPD年急性加重的比率也在QVA149组与SFC相比更低，分别为0.59VS0.75;但是这些差异没有显著统计学差异。13急性加重分层分析有中重度急性加重史的患者（QVA140vsSFC))年比率率RR值P值有无统计学差异中度或者重度急性加重（全文）0.49vs0.810.600.086无全文和补充材料中关于有中重度急性加重史的患者发生中重度急性加重的比率不一致所有急性加重（轻中重）补充材料0.78VS1.810.430.003有中度或者重度急性加重（补充材料）0.430.003有Duetotheobserveddifferentpercentagesofpatientswithahistoryofexacerbationatbaselineinthetreatmentgroups(16.4%ofQVA149and25.2%ofSFC),posthocanalyseswereperformedonsubgroupsofpaientswithorwithoutabaselinehistoryofexacerbation.因为发现入组的患者在两组急性加重史比率的基线值上有差异（QVA149组16.4%VSSFC组25.2%），所以对患者按有急性加重史和没有急性加重史进行分层的事后分析。Furthermore,theannualizedrateofCOPDexacerbationswassignificantlylowerinpatientswithahistoryofmoderateorsevereCOPDexacerbationsatbaselinetreatedwithQVA149comparedwithSFCgroupforallexacerbations(rateratio:0.43;P=0.003;TableS6),andmoderateorsevereexacerbations(rateratioof0.43;P=0.003;TableS6).补充材料无中重度急性加重史的患者（QVA140vsSFC)年率RR值P值有无统计学差异中重度急性加重（全文）0.23vs0.300.760.266无所有急性加重（轻中重）补充材料0.66VS0.670.980.916无14PercentageofpatientsWithorwithouthistoryofexacerbationsatbaseline有急性加重史的患者没有急性加重史的患者有急性加重史的这部分患者中，QVA149组的所有急性加重、中重度急性加重和重度急性加重的患者比率都要显著低于SFC组；没有急性加重史的患者中，所有的急性加重患者比率都没有差异。15总结Boththetotalnumberandrateofall(mild,moderateandsevere)COPDexacerbationswerenumericallylowerintheUltibrogroupvsSeretide(non-significant)所有的COPD急性加重（轻中重）的数量和比率在数量上ULTIBRO组低于舒利迭组，没有显著差异。Ultibrosignificantlyreducedtherateofmoderateandsevereexacerbationsby31%(P=0.048)overSeretide,andprolongedtimetofirstmoderateandsevereexacerbation(reducedhazardriskby35%,P=0.028)Ultibro显著减少31%的重度和极重度的急性加重比率与舒利迭相比。延长到首次中度和极重度的急性加重时间（减少35%的风险）。TheLANTERNauthorssuggestalinkbetweentheimprovementsinFEV1andreductioninexacerbationriskLANTERN的作者认为提高FEV1和减少急性加重风险之间存在联系。Annualizedrateofsevereexacerbationsshoweda69%reductionintheUltibrogroupvsSeretide(Significant)年重度急性加重率显示在ULTIBRO组有显著降低69%与舒利迭组相比。32.9%ICSusersasbaselineinUltibrovs37.1%inSeretidegroup32.9%的在基线值使用ICS患者VS37.1%在舒利迭组。TheincidenceofpneumoniawasthreefoldlowerwithUltibro(0.8%)versusSeretide(2.7%)肺炎的发生率在ULTIBRO是舒利迭组的1/3(0.8%VS2.7%)Duetounequalnumbersofpatientswithhistoryofexacerbationsatbaseline(16.4%ofUltibroand25.2%ofSeretidepatients),apost-hocanalysiswasdoneinpatientswithandwithouthistoryofexacerbations(Howeverinsupplementarymaterials,thereseemstobeconflictingdatawithfulltextreport,seenextslide)由于病人在基线值的急性加重史数量方面不对等（16.4%VS25.2%），事后分析研究进行了有和无急性加重史的病人来进行分层。但是在补充材料中，显示了和全文相矛盾的数据。LANTERN:有急性加重史的患者的事后因果分析

Zhongetal.IntJChronObstructPulmonDis.2015Jun5;10:1015-26LANTERNSupplementarymaterialsavailableat:/pmc/articles/PMC4461092/pdf/copd-10-1015.pdf“在基线值时有中重度急性加重史的患者中，所有年COPD的发病率(rateratio:0.43;P=0.003),和中重度COPD发病率(rateratio0.43;P=0.003)”QVA149组显著降低与舒利迭组相比在有急性加重史的患者中，后来发生所有急性加重（轻中重）的患者比率一如既往的减少在QVA149组与SFC相比。(mild,moderateandsevere)(QVA149:24.6%;SFC:46.2%,P=0.007),中度和重度急性加重

(QVA149:19.7%;SFC:34.4%,P=0.048)andsevere(QVA149:0%;SFC:7.5%,P=0.043)exacerbations”在基线值时有中重度急性加重史的患者中，中重度COPD急性加重年发生率为40%在QVA149组，低于SFC组，比值0.6.“(rateratio:0.60;P=0.086)”全文

publication补充材料从

LANTERN补充材料中：Exacerbationsdefinedasworseningofsymptoms急性加重定义为症状恶化

(获取

viatheeDiary)Moderateandsevereexacerbationswerealsocapturedinthecasereportform中重度急性加重同样也是从时间报告中获取

(CRF)Anthonisencriteriawereusedtodefinethesymptomsofanexacerbation。

Anthonisen标准用于定义急性加重的症状Exacerbationswereconsideredmoderateifpatientsweretreatedwithsystemiccorticosteroidsorantibioticsorboth中度急性加重定义为使用全身激素或者是抗生素或者两者都用。ExacerbationswereconsideredsevereifpatientswerehospitalizedorexperiencedanERvisitlongerthan24hours重度急性加重被定义为病人需要住院或者需要急诊访视超过24小时。Exacerbationdefinitions17前期相关研究Zhongetal.IntJChronObstructPulmonDis.2015Jun5;10:1015-26LANTERNSupplementarymaterialsavailableat:/pmc/articles/PMC4461092/pdf/copd-10-1015.pdfLANTERNThepost-hocanalysisofannualizedrateofmoderateandsevereexacerbationsinpatientswithahistoryofexacerbationsatbaselineisreporteddifferentlyinthefulltextandsupplementarymaterials,andsodoesnoofferaclearinsightintothelikelyFLAMEoutcome事后分析研究显示在基线值时有急性加重史的患者年中重度急性加重的比率在全文和补充材料中报道的有差异，同时在FLAME研究结果报道中也没有能给予一个清晰的观点。Fulltext:(0.49vs.0.81exacerbationsperyear,RR=0.60,p=0.086)NON-SIG.

全文0.49VS0.81急性加重/年无显著Suppl.materials:(0.78vs.1.81exacerbationsperyear,RR=0.43,p=0.003)SIG.补充材料0.78VS1.81急性加重显著Thepercentageofpatientswhoexperiencedamoderate/severeexacerbationinthispost-hocanalysiswassignificantlylowerintheUltibrogroup(19.7%vs.34.4%,p=0.048)SIG.在有急性加重史的患者中，两组中重度急性加重的患者比率在此次事后分析研究中在ULTIBRO组显著降低（19.7VS34.4)有显著差异。Overallpatientsnumbersinthisanalysiswerelow,howevertherewasacleartrendtowardsanexacerbationimprovementwithUltibrovs.Seretide在此次分析中的病人总数较低，但是仍然有很明确的倾向认为ULTIBRO可以减少急性加重与组舒利迭组相比。RoleofICSinCOPD19规律使用ICS治疗可以提高肺功能改善症状和生活质量及减少COPD患者的急性加重的频次1GOLDguidelines(2016)Globalinitiativeforchronicobstructivelungdisease.GlobalStrategyforDiagnosis,Management,andPreventionofCOPD.Availableat:/GINAGOLDACOS(2015)Diagnosisofdiseasesofchronicairflowlimitation:Asthma,COPDandAsthma-COPDoverlapSyndrome(ACOS)availableatandHansel&Barnes(2009)Newdrugsforexacerbationsofchronicobstructivepulmonarydisease.Lancet.2009Aug29;374(9691):744-55Cellietal(2008)EffectofPharmacotherapyonRateofDeclineofLungFunctioninChronicObstructivePulmonaryDisease.AmJRespirCritCareMedVol178.pp332–338,2008Jenkinsetal(2009)Efficacyofsalmeterol/fluticasonepropionatebyGOLDstageofchronicobstructivepulmonarydisease:analysisfromtherandomised,placebo-controlledTORCHstudy.RespiratoryResearch2009,10:59ManypatientswithCOPDalsohaveunderlyinginflammationandthishasbeenlinkedtoanincreasedriskofexacerbation许多COPD的患者都存在潜在的炎症，这也会导致急性加重风险的增加3Goaloftherapytomaximisebronchodilationandatthesametimecontrolinflammation,toreduceexacerbations治疗的目的是最大化的进行支气管扩张同时控制炎症，减少急性加重1重度或极重度COPD同时伴有急性加重高风险1COPD伴有哮喘特征2GOLDC

&

DICS/LABA可以减少COPD患者FEV1下降的比率和死亡率，不过还需要更充分的证明1

Time(weeks)-39mL/yr*-42mL/yr*-42mL/yr*-55mL/yr*PlaceboSALFPSFCFEV1(mL)24487209612015620CombininganICSwithaLABAreducestheriskofexacerbations,andimproveslungfunctionandhealthstatusinCOPDpatientswithahistoryofexacerbations

在有急性加重史的COPD患者中，联合ICS和LABA可以减少急性加重的风险，提高肺功能和改善健康状况Calverleyetal(2003)Maintenancetherapywithbudesonideandformoterolinchronicobstructivepulmonarydisease.EurRespirJ2003;22:912–919Rennardetal(2009)EfficacyandTolerabilityofBudesonide/FormoterolinOneHydrofluoroalkanePressurizedMetered-DoseInhalerinPatientswithChronicObstructivePulmonaryDisease.Drugs2009;69(5):549-565Combiningbudesonidewithformoterol:联合BUD和褔莫特罗：Reducestherateofexacerbations减少急性加重比率vs.formoterol(26%)andplacebo(24%)

1Providessignificantlygreaterimprovementsinpre-doseFEV1显著提高给药前FEV1vs.formoterol(p=0.008)orplacebo(p=0.001)ImprovesHRQoL

提高健康相关生命质量量表vs.placebo(differenceof7.5units,p<0.001)1n=1,02221WithdrawingICSabruptlyorinappropriatelyisassociatedwithasignificantdecreaseinlungfunction,qualityoflife,andmayprecipitateanincreaseinexacerbationsandacceleratelungfunctiondecline突然或者不适当的撤掉ICS或者与显著的肺功能减少、生命质量降低、促进急性加重的增加和加速肺功能的下降相关Magnussenetal(2014)WithdrawingICSinCOPD:WISDOM.NEnglJMed2014;371:1285-94Kimetal(2016)OutcomeofInhalerWithdrawalinPatientsReceivingTripleTherapyforCOPD.TubercRespirDis2016;79:22-30Watzetal(2014)ERSInternationalCongress2014-WISDOMPosterWithdrawingICSfrompatientsontriple三联药物中撤掉ICS:SignificantdeclineintroughFEV1

of43ml显著的减少FEV1低谷值(p<0.01)1Significantdeclineinhealthstatus显著减少健康状况

(p

=0.047)1Numericalincreaseinexacerbations增加急性加重的数量1MayalsoaccelerateFEV1decline加速FEV1降低

(54.7vs.10.7ml/yr,p=0.007)206121852AdjustedmeanchangefrombaselineinFEV1Fluticasonepropionatedose:Reducedto250μgBIDReducedto100μgBIDReducedto0μg(placebo)ChangefrombaselineintotalSGRQscore圣乔治评分至基线值的改变1Week27Week52ICSICSwithdrawalICSwithdrawalICS22FreetripleiscurrentlyrecommendedasachoiceforGOLDGroupDpatientswhohavemanysymptomsandahighriskofexacerbations

三联疗法当前被推荐作为一种选择用于治疗GOLDD级症状多且急性加重风险高的患者1GOLDguidelines(2016)Globalinitiativeforchronicobstructivelungdisease.GlobalStrategyforDiagnosis,Management,andPreventionofCOPD.Availableat:/GINAGOLDACOS(2015)Diagnosisofdiseasesofchronicairflowlimitation:Asthma,COPDandAsthma-COPDoverlapSyndrome(ACOS)availableatandTripletherapyisrecommended三联疗法被推荐:ForsevereorverysevereCOPDairflowlimitation,withfreq