结缔组织相关性肺病 PPT课件.ppt

,结缔组织相关性肺病,1,.,讨论内容,结缔组织病肺病的概念CTD的肺部受累情况常见CTD肺病的累积部位CTD对ILD的影响ILD病理类型对疾病的影响AE-CTD-ILDCTD-ILD的治疗,2,相关概念,肺部优势性肺病Lung-dominantCTD（LD-CTD）自体免疫优势性肺病Autoimmune-FeaturedILD（AIF-ILD）结缔组织病相关肺病CTD-associatedlungdisease(LunginvolvementinCTD)胶原血管病相关性肺病CVD-associatedILD（CTD-ILD）未分化结缔组织病相关性肺病（UCTD-ILD）,3,4,肺部优势性肺病,“肺部优势性肺病LD-CTD”系血清学抗体阳性或病理学提示CTD特征，但不符合明确CTD标准，即缺乏诊断CTD的肺外症状。LD-CTD意味血清学抗体阳性或病理学提示CTD特征单独可以明确CTD-IP.,AryehFischer，ConnectiveTissueDisease-AssociatedInterstitialLungDisease.CHEST/138/2/AUGUST,2010,5,诊断标准,AryehFischer，ConnectiveTissueDisease-AssociatedInterstitialLungDisease.CHEST/138/2/AUGUST,2010,6,自身免疫特征性间质性肺病,WeproposeanewtermtodescribeasubsetofpulmonaryILDpatientswithfeaturesofaconnectivetissuediseasethatdonotmeetACRcriteria:autoimmune-featuredILD(AIF-ILD).间质性肺病伴有结缔组织病特征尚未满足美国风湿病学会诊断标准的一类疾病称为自身免疫特征性间质性肺病-RekhaVij，etal.Autoimmune-FeaturedInterstitialLungDisease:ADistinctEntity.CHEST2011;140(5):12921299,7,自身免疫特征性间质性肺病的诊断标准,RekhaVij，etal.Autoimmune-FeaturedInterstitialLungDisease:ADistinctEntity.CHEST2011;140(5):12921299,8,RF的关节外症状发生,TuressonC.Extra-articularrheumatoidarthritis.CurOpinRheumatol2013;25(5):3606,9,CTD-ILD肺部受累及情况,10,CTD中ILD的发生情况,RF-ILD15-60%SSC53%PM/DM20-80%SjS25%SLE9%MCTD30-50%,ExpertRev.Clin.Pharmacol.5(2),219227(2012),11,各种类风湿病肺病发病率,CastelinoandVargaInterstitiallungdiseaseinconnectivetissuediseases:evolvingconceptsofpathogenesisandmanagementArthritisResTher.2010;12(4):213,12,CTD相关性肺病的类别,胸膜病胸膜炎积液/增厚气道病变上气道(a)环杓关节炎(b)气管病变下气道(a)支气管扩张(b)细支气管炎血管病变,肺实质病变间质性肺病NSIP,UIP,OP,LIP,DAD,DIP弥漫性肺泡出血急性肺炎类风湿结节感染药物毒性反应,13,CTD-LD疾病谱,系统硬化最易累及肺间质和血管、皮肌炎最易累及肺间质,AryehFischer,RolandduBois.InterstitiallungdiseaseinconnectivetissuedisordersLancet2012;380:68998,14,CTD-ILD与病理分型,deLauretisA.Reviewseries:Aspectsofinterstitiallungdisease:connectivetissuedisease-associatedinterstitiallungdisease:howdoesitdifferfromIPF?Howshouldtheclinicalapproachdiffer?ChronicRespiratoryDisease20118(1)5382,15,CTD-ILD病理类型分布,EuniceJ.Kim,RheumatoidArthritis-AssociatedInterstitialLungDisease-TheRelevanceofHistopathologicandRadiographicPattern.CHEST/136/5/NOVEMBER,20091397,16,CTD与ILD关联和影响,17,.,IIP与UCTD-ILD病理类型比较,BrentW.Kinder。IdiopathicNonspecificInterstitialPneumoniaLungManifestationofUndifferentiatedConnectiveTissueDisease?AmJRespirCritCareMedVol176.pp691697,2007,结论：特发性非特异性间质性肺炎很多符合UCTD的诊断标准，iNSIP是否与自身免疫相关,18,UCTD对ILD的影响,232例IIP（活检病理学诊断）IPF138例NSIP94例14例(31%)NSIP伴UCTD7例(13%)IPF伴UCTD,T.J.Corte.Significanceofconnectivetissuediseasefeaturesinidiopathicinterstitialpneumonia.EurRespirJ2012;39:661668,19,UCTD对NSIP的影响,1990-2009期间62例肺活检诊断iNSIPUCTD诊断标准为Kinder提出6例出现PM被剔除56例中有47例出现至少4项反应UCTD全身炎症指标这47例中有22例（47%）符合UCTD诊断标准,TakafumiSuda.Distinctprognosisofidiopathicnonspecificinterstitialpneumonia(NSIP)fulfillingcriteriaforundifferentiatedconnectivetissuedisease(UCTD).RespiratoryMedicine(2010)104,1527-1534,20,NSIP与CVD有关联,2000-2006约翰霍普金斯医院ILD诊断：临床+影像+肺功能+病理160例，121例做过自身抗体检测，7例药物反应，余114例结节病与SSc单独34符合明确CVD17(50%)已有CVD诊断17新近诊断CVDCVD疾病谱：5例特发炎性肌病，5例RA,3例SLE,2例重叠综合征,1例干燥，1例SSc.ANA+29例1:320,其中18(62%)有CVD(p=0.01).RF+与CVD关联小(p=1.0).,ShikhaMittooAscertainmentofcollagenvasculardiseaseinpatientspresentingwithinterstitiallungdiseaseRespiratoryMedicine(2009)103,1152-1158,21,NSIP与CVD有关联,76例(66%)至少1中血清抗体阳性26例(23%)至少2项以上自身抗体阳性最常见为ANA，其次RF，后anti-Roanti-Jo-1anti-Scl70anti-La外科活检最常见病理类型UIP(n=20)27%其次NSIP(n=18)25%NSIP是与CVD-ILD唯一相关的病理类型NSIP的诊断与新诊断CVD有关联趋势,ShikhaMittooAscertainmentofcollagenvasculardiseaseinpatientspresentingwithinterstitiallungdiseaseRespiratoryMedicine(2009)103,1152-1158,22,系统性疾病对ILD的影响,23,.,CTD对纤维化的影响,998例IPF，其中108例合并CTD，对照组5988例随访898例单纯LCFA（IPF），107例FA-CTD（RF86例80%，SSc15例14%）随访期间386例（44%）LCFA死亡54例（50%）死亡（45例RF，3例PM，5例SSc，1例MCTD）对照组601例（10%）死亡,Rheumatology200241：676,24,死亡率,LCFA270/1000.年FA-CTD280/1000.年普通人群41/1000.年平均生存期LCFA2.6yFA-CTD2.4y结论：CTD不伴有FA生存提高,Rheumatology200241：676,25,UCTD对ILD的影响,232例IIP（活检病理学诊断）IPF138例NSIP94例14例(31%)NSIP伴UCTD7例(13%)IPF伴UCTD,T.J.Corte.Significanceofconnectivetissuediseasefeaturesinidiopathicinterstitialpneumonia.EurRespirJ2012;39:661668,26,UCTD与生存无相关,T.J.Corte.Significanceofconnectivetissuediseasefeaturesinidiopathicinterstitialpneumonia.EurRespirJ2012;39:661668,UIP病理死亡率高UCTD不增加死亡率,27,UCTD对NSIP的影响,1990-2009期间62例肺活检诊断iNSIPUCTD诊断标准为Kinder提出6例出现PM被剔除56例中有47例出现至少4项反应UCTD全身炎症指标这47例中有22例（47%）符合UCTD诊断标准,TakafumiSuda.Distinctprognosisofidiopathicnonspecificinterstitialpneumonia(NSIP)fulfillingcriteriaforundifferentiatedconnectivetissuedisease(UCTD).RespiratoryMedicine(2010)104,1527-1534,28,UCTD对NSIP生存影响,UCTD-NSIP5年生存率100%非UCTD-NSIP5年生存率58%;p=0.0092).,TakafumiSuda.Distinctprognosisofidiopathicnonspecificinterstitialpneumonia(NSIP)fulfillingcriteriaforundifferentiatedconnectivetissuedisease(UCTD).RespiratoryMedicine(2010)104,1527-1534,29,三种UIP病理特征疾病的转归,UIP118例LD-CTD-28CTD-ILD-29（RF12，mCTD6，SLE5，SSc4，PM2IPF61三组CTD年龄轻，女性多，少吸烟，ANA+RF+多，激素+免疫抑制剂多，其它三组无显著差异,EsamH.Alhamad.Comparisonofthreegroupsofpatientswithusualinterstitialpneumonia.RespiratoryMedicine(2012)106,1575-1585,30,UIP生存情况,23例死亡，6例LD-CTD，2例CTD-ILD，15例IPF。LD-ILD83%死于呼吸因素CTD-ILD100%呼吸因素UIP-IPF66%死于呼吸因素,p=0.028CTD-UIPvsIPF,p0.05LD-UIPvsIPFLD-UIPvsCTD-UIP,EsamH.Alhamad.Comparisonofthreegroupsofpatientswithusualinterstitialpneumonia.RespiratoryMedicine(2012)106,1575-1585,31,UIP病理类型预后差RF,54例类风湿性肺病，肺部病理活检UlP15NSIP16OP4无法分类肺炎2DIP1细支气管病16,YutaroNakamura.Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169.,32,RLD生存曲线,5年生存率93.8%10年生存率平均76.6%,UIP10年生存率52.5%肺UIP10年生存率84.3%(p=0.0452)UIPvsNSIP无显著差异,YutaroNakamura.Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169.,p=0.0452,33,SSc-ILD死亡率与肺病理,80例SSc患者，外科手术病理诊断其中NSIP(n=62,77.5%),细胞型NSIP(n=15)，纤维化型NSIP(n=47)UIP(n=6)终末期肺病(ESL,n=6)其它类型(n=6)25例死亡，NSIP16/62,26%;UIP/ESL6/12,50%)5年生存：NSIP(91%)；UIP/ESL(82%)死亡率与DL(CO)和FVC相关(p=0.004andp=0.007),BourosD,HistopathologicSubsetsofFibrosingAlveolitisinPatientswithSystemicSclerosisandTheirRelationshiptoOutcome.AmJRespirCritCareMedVol165.pp15811586,2002,34,SSC-ILD不同病理类型的生存情况,BourosD,HistopathologicSubsetsofFibrosingAlveolitisinPatientswithSystemicSclerosisandTheirRelationshiptoOutcome.AmJRespirCritCareMedVol165.pp15811586,2002,p0.05,5年生存率NSIP90%UIP82%10年生存率NSIP69%UIP29%,35,SSC-NSIP生存与BAL中E,BourosD,HistopathologicSubsetsofFibrosingAlveolitisinPatientswithSystemicSclerosisandTheirRelationshiptoOutcome.AmJRespirCritCareMedVol165.pp15811586,2002,P=0.03,36,SSC-NSIP的生存与DLCO,BourosD,HistopathologicSubsetsofFibrosingAlveolitisinPatientswithSystemicSclerosisandTheirRelationshiptoOutcome.AmJRespirCritCareMedVol165.pp15811586,2002,37,SSc-ILD1、肺病理类型与生存无显著关联2、BAL嗜酸性粒细胞增加、DLCO降低生存率低,BourosD,HistopathologicSubsetsofFibrosingAlveolitisinPatientswithSystemicSclerosisandTheirRelationshiptoOutcome.AmJRespirCritCareMedVol165.pp15811586,2002,38,.,IIPvsCVD-ILDsurvival,1990-2006年间韩国亚洲医疗中心362例外科病理诊断UIP类型(269例IIP，93例CVD-IP)UIP类型(203例IPF，36例CVD-UIP)纤维化型NSIP(66例i-NSIP，57例CVD-NSIP),DemosthenesBourosPrognosisoffibroticinterstitialpneumonia:idiopathicversuscollagenvasculardisease-relatedsubtypes.AmJRespirCritCareMed.2007Apr1;175(7):705-11,39,CVD-IPvsIIP生存,CVD-IP生存期平均131.0+9.1mo)IIPgroup平均80.5+6.3月P0.001年龄,FVC,DlCO及CVD为预后的独立因素,DemosthenesBourosPrognosisoffibroticinterstitialpneumonia:idiopathicversuscollagenvasculardisease-relatedsubtypes.AmJRespirCritCareMed.2007Apr1;175(7):705-11,40,CVD-UIP与IPF-UIP比较,年轻、女性、非吸烟者CVD-UIP生存(平均125.5+16.0月)高于IPF-UIP(66.9+6.5月)3-year生存率分别为(81.6vs.57.4%)5-year生存率分别为(81.6vs.44.8%)CVD-UIP生存高于IPF-UIP(p0.001).,DemosthenesBourosPrognosisoffibroticinterstitialpneumonia:idiopathicversuscollagenvasculardisease-relatedsubtypes.AmJRespirCritCareMed.2007Apr1;175(7):705-11,41,UIP生存分析,平均生存期CVD-UIP125.5+16.0月IPF-UIP66.9+6.5月p0.0013年生存率CVD-UIP81.6IPF-UIP57.4%5年生存率CVD-IPF81.6IPF-UIP44.8%(p0.001),DemosthenesBourosPrognosisoffibroticinterstitialpneumonia:idiopathicversuscollagenvasculardisease-relatedsubtypes.AmJRespirCritCareMed.2007Apr1;175(7):705-11,CTD-NSIP与iNSIP生存无显著差异CTD-UIP与CVD-NSIP生存无显著差异,3年生存率CVD-NSIP88.9%iNSIPP77.6%5年生存率CVD-NSIP81.5iNSIP67.4%多因素分析显示年龄、FVC为NSIP的生存相关，CVD无关,42,CTD与ILD生存,2533例肺纤维化患者,324例(13%)并存结缔组织病CTD，如下,RF(8.4%)，SSc(1.6%)最常见2.3随访IPF-CS（特发肺纤维化临床综合征）有1073例(48.6%)死亡CTD-PF有113(34.9%)死亡IPF-CS死亡率229.8/1000人/年CTD-PF死亡率123.6/1000人/年years(95%ConfidenceInterval:102.8e148.7)平均生存年限IPF-CS3.1年CTD-PF6.5年(p=0.043),NavaratnamV,Doesthepresenceofconnectivetissuediseasemodifysurvivalinpatientswithpulmonaryfibrosis?RespirMed.2011Dec;105(12):1925-30,43,NavaratnamV,Doesthepresenceofconnectivetissuediseasemodifysurvivalinpatientswithpulmonaryfibrosis?RespirMed.2011Dec;105(12):1925-30,44,IIP与CVD-IP的差异,UIP320例，其中IPF/UIP272例;CVD-UIP,48例CVD-UIP生存时间143.8月IPF/UIP生存时间40.1月P0.001)1年死亡率CVD-UIP7.9%vsIPF/UIP17.3%,3年死亡率CVD-UIP13.9%vsIPF/UIP43.2%P0.001,JinWooSong,PathologicandRadiologicDifferencesBetweenIdiopathicandCollagenVascularDisease-RelatedUsualInterstitialPneumoniaCHEST2009;136:2330),45,JinWooSong,PathologicandRadiologicDifferencesBetweenIdiopathicandCollagenVascularDisease-RelatedUsualInterstitialPneumoniaCHEST2009;136:2330),46,ComparisonofthesurvivalcurvesforIPF/UIP(Ab)andIPF/UIP(Ab)patients.,JinWooSong,PathologicandRadiologicDifferencesBetweenIdiopathicandCollagenVascularDisease-RelatedUsualInterstitialPneumoniaCHEST2009;136:2330),47,RF中，UIP类型有重要意义,48,.,49,2001.1.-2008.11.1加州大学与MayoClinic,KimEJ,Usualinterstitialpneumoniainrheumatoidarthritis-associatedinterstitiallungdisease.EurRespirJ.2010Jun;35(6):1322-8.doi:10.1183/09031936.00092309.Epub2009Dec8.,50,RA-UIP与RA-非UIP,KimEJ,Usualinterstitialpneumoniainrheumatoidarthritis-associatedinterstitiallungdisease.EurRespirJ.2010Jun;35(6):1322-8.doi:10.1183/09031936.00092309.Epub2009Dec8.,51,生存分析,RA-ILD5.0年RA-UIP3.2年RA-非UIP6.6年,RF-非UIP,RF-UIP,IPF-UIP,KimEJ,Usualinterstitialpneumoniainrheumatoidarthritis-associatedinterstitiallungdisease.EurRespirJ.2010Jun;35(6):1322-8.doi:10.1183/09031936.00092309.Epub2009Dec8.,52,生存分析-根据HRCT分型,P=0.02UIPvsNSIP;中间类型与其它无差异,NSIP可能,UIP/NSIP,UIP明确,KimEJ,Usualinterstitialpneumoniainrheumatoidarthritis-associatedinterstitiallungdisease.EurRespirJ.2010Jun;35(6):1322-8.doi:10.1183/09031936.00092309.Epub2009Dec8.,53,病理证实类风湿性关节炎肺病预后分析,1989.122009.12期间日本浜松大学医学院30M、24W，平均年龄60.3y组织病理学NSIP16，UIP15，OP4，无法分类2，DIP1，细支气管病变16,YutaroNakamura,Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169,54,RF-ILD病10年生存比较,10年生存率比较RF-非UIP84.3%,RF-UIP52.5%(p=0.0452)RF-UIP与NSIP比较无显著差异(p=0.2648),RF-UIP较其它类型显著差异更大(p=0.0147),YutaroNakamura,Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169,55,RF-ILD病生存分析,10年生存率为76.6%,YutaroNakamura,Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169,56,RF-UIP与RF-非UIP-生存曲线,p=0.0452,YutaroNakamura,Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169,57,YutaroNakamura,Rheumatoidlungdisease:Prognosticanalysisof54biopsy-provencases.RespiratoryMedicine(2012)106,1164-1169,58,结缔组织相关间质性肺病与急性加重,59,.,60,RyoTachikawa，Respiration2012;83:2027,61,RyoTachikawa，Respiration2012;83:2027,62,RyoTachikawa，Respiration2012;83:2027,63,RyoTachikawa，Respiration2012;83:202