1、特发性间质性肺炎新分类及治疗进展,中国医学科学院 北京协和医院呼吸科 徐作军,内 容,特发性间质性肺炎的新分类实用临床分类分子生物学标记物检测IPF治疗进展,内 容,特发性间质性肺炎的新分类实用临床分类分子生物学标记物检测IPF治疗进展,Diffuse Parenchymal Lung Diseases / Interstitial Lung Disease(DPLD / ILD),已知原因：药物、CTD、粉尘、放射 等,肉芽肿性疾病：结节病、外源性过敏性肺炎 等,其他：LAM、PLCH、EP等,特发性间质性肺炎 (IIP),ATS/ERS statement: AJRCCM 2002;165
2、:277,特发性肺纤维化（IPF/UIP）,非特异性间质性肺炎（NSIP）,隐原性机化性肺炎（COP）,淋巴细胞间质性肺炎（LIP）,脱屑型间质性肺炎（DIP）,急性间质性肺炎（AIP）,呼吸性细支气管炎伴间质性肺病（RBILD）,Schedule of IIP classification project,May, 2010 ATS/New Orleans September, 2010 ERS/Barcelona January, 2011 Writing committee, NYC April, 2011 Modena, Italy May, 2011 ATS/Denver Septe
3、mber, 2011 ERS/Amsterdam January, 2012 Writing committee, NYC April, 2012 Final draft submitted September, 2012 Submission of revision,Members of the ATS/ERS Committee on IIP,William Travis, MD. (Chair)Talmadge E. King, Jr., MD, (Co-Chair)Ulrich Costabel, (Co-Chair)Athol Wells, (Co-Chair),PULMONARY
4、(17+4),Jay H. Ryu, USA (Subcommittee Chair)Jurgen Behr, GermanyDemosthenes Bouros, GreeceKevin Brown, USAHarold Collard, USACarlos Robalo Cordeiro, PortugalVincent Cottin, FranceMarjolein Drent, The Netherlands,Jim Egan, IrelandKevin Flaherty, USATravis, WDYoshikazu Inoue, JapanDong Soon Kim, KoreaF
5、ernando Martinez, USAGanesh Raghu, USALuca Richeldi, ItalyDominique Valeyre, France,RADIOLOGY,David Hansell, United Kingdom (Subcommittee co-chair)David Lynch, USA (Subcommittee co-chair)Takeshi Johkoh, JapanNicola Sverzellati, Italy,PATHOLOGY,Andrew Nicholson, United Kingdom (Subcommittee Chair)Tho
6、mas V. Colby, USAMasanori Kitaichi, JapanJeffrey Myers, USA,MOLECULAR BIOLOGY,Moises Selman, Mexico (Subcommittee chair)Bruno Crestani, FranceCory Hogaboam, USAJames Loyd, USA,EVIDENCE BASED ANALYSIS,Christopher Ryerson, Canada (Subcommittee chair)Jeffrey Swigris, USA,REFERENCE LIBRARIANS,Rosalind F
7、. Dudden, M.L.S.Shandra Protzko, M.L.S.,Final face-to-face meeting, Modena, June 2008,Word Count: 3489Abstract word count: 248Tables: 4Figures: 8Supplemental materials: 2 Tables and 1 AppendixReference: 159,新分类方案与2002年IIP专家共识的区别,（1）明确了特发性NSIP（iNSIP）是一种独立的临床病理的类型，其临床过程呈高度异质性；（2）收集了更多的吸烟相关性间质性肺病的信息，特别
8、是肺气肿合并肺纤维化（CEPF）；（3）认为IPF的自然病程多样性，可以长期稳定，可以快速进行性进展，可以在病程中出现急性加重；,AJRCCM 2011; 183: 788-824 (modified),DISEASE PROGRESSION,TIME,NATURAL HISTORY OF IPF,RAPID PROGRESSION,SLOW PROGRESSION,STABLE,（4）对慢性致纤维化性间质性肺炎的“急性加重（AE）”有了明确的定义和描述；（5）首次明确提出部分IIP患者病理难以归入现有的IIP类型中（不能分类的IIP）.,新分类方案与2002年IIP专家共识的区别,（6）提出
9、需要推出IIP的临床诊疗途径，尤其是对于没有病理学诊断和HRCT不符合某一典型的IIP影像学表现时；（7）提出了一种新的IIP类型PPFE；（8）提出了某些分子生物学标记物和基因学研究结果可能对IIP的分类和诊断有一定帮助。,新分类方案与2002年IIP专家共识的区别,Major Idiopathic Interstitial PneumoniasIdiopathic pulmonary fibrosisIdiopathic nonspecific interstitial pneumoniaRespiratory bronchiolitis interstitial lung disease
10、Desquamative interstitial pneumoniaCryptogenic organizing pneumoniaAcute interstitial pneumoniaRare Idiopathic Interstitial PneumoniasIdiopathic lymphoid interstitial pneumoniaIdiopathic pleuropulmonary fibroelastosisUnclassifiable idiopathic interstitial pneumonias,特发性间质性肺炎分类 (2012),特发性间质性肺炎（IIP）,急
11、性/亚急性IP COP AIP,吸烟相关性IP DIP RBILD,特发性间质性肺炎的分类(2012年),主要的IIP,慢性致纤维化性IP IPF NSIP,家族性 2-20%, 非家族性 80%,少见的IIP,特发性淋巴细胞间质性肺炎特发性胸膜肺纤维弹性组织增生症,特发性间质性肺炎（IIP）,急性/亚急性IP COP AIP,吸烟相关性IP DIP RBILD,特发性间质性肺炎的分类(2012年),主要的IIP,少见的IIP,慢性致纤维化性IP IPF NSIP,特发性淋巴细胞间质性肺炎特发性胸膜肺纤维弹性组织增生症,由于证据不够下列二个病理类型未被列入疾病分类:急性纤维素性机化性肺炎气道中
12、心性间质性肺炎,家族性 2-20%, 非家族性 80%,特发性间质性肺炎（IIP）,急性/亚急性IP COP AIP,吸烟相关性IP DIP RBILD,特发性间质性肺炎的分类(2012年),主要的IIP,少见的IIP,不能分类的IIP,慢性致纤维化性IP IPF NSIP,特发性淋巴细胞间质性肺炎特发性胸膜肺纤维弹性组织增生症,由于证据不够下列二个病理类型未被列入疾病分类:急性纤维素性机化性肺炎气道中心性间质性肺炎,家族性 2-20%, 非家族性 80%,不能分类IIP的原因,1. 临床、放射或病理学资料不充分；2. 临床、放射或病理学发现存在显著不一致：先前的治疗导致放射或病理学表现出现重
13、要改变 , (如，病理证实的 DIP 随着激素治疗后表现为残留NSIP表现)出现不认识的表现或已认识的表现出现了不寻常的变异，而不能放在目前ATS/ERS分类中 , (如. OP表现同时伴有显著的纤维化)同一个患者出现多种 HRCT和 / 或病理学类型.,“Unclassifiable disease” 10% of IIPs,内 容,特发性间质性肺炎的新分类实用临床分类分子生物学标记物检测IPF治疗进展,根据疾病行为提出了实用的临床分类,Historically, the primary question has been “what is the diagnosis”?Pragmatica
14、lly, the primary question is “what are you going to do about it”?,We need a different question,（A pragmatic clinical classification）,临床分类的综合考量因素-1,疾病预后：虽然ILD病因不同，临床表现各异，但疾病预后大致可归纳如下：自限性炎症稳定性纤维化炎症为主伴有不同程度纤维化进行性纤维化可逐渐达到稳定状态不可终止的纤维化,临床分类的综合考量因素-2,疾病和患者的特征： 诊断病因主要的形态学异常疾病严重程度疾病的动态改变患者个人情况,临床分类的综合考量因素-3,
15、处理方法： 对于不同预后的 疾病采取不同的临床策略：观察：自限性炎症/稳定性纤维化积极治疗，达到目标后，维持治疗结果：炎症为主(大部分可逆）伴有不同程度纤维化治疗防止其进展：进行性进展有逐渐达到稳定状态可能的纤维化治疗让其缓慢进展：不可终止的纤维化,疾病临床行为综合判定,Patient-specific modifiersAgeSuspected etiologyDisease severityReversibility of disease,MD Diagnosis-Clinical-Radiologic-Pathologic(when available),Longitudinal beh
16、aviour:“Prior history”-Impact of therapy-Rate of progression (symptoms, PFTs, radiology),Group 1,Reversible,Irreversible,+,+,Group 2,Group 3,Group 4,Group 5,内 容,特发性间质性肺炎的新分类实用临床分类分子生物学标记物检测IPF治疗进展,Serum/BALF biomarkers in ILDs,Biomarkers for outcome in blood and BAL,内 容,特发性间质性肺炎的新分类实用临床分类分子生物学标记物检测I
17、PF治疗进展,N Engl J Med 2012, May 21, (10.1056/NEJMoa1113354),PANTHER 研究,362 Patients were assessed for eligibility,112 Were excluded24 Had DLCO 12 wk45 Had other reasons14 Were undergoing screening at time of discontinuation of study group,236 Underwent randomization,81 receive NAC alone,77 receive pre
18、d, aza, and NAC,78 receive placebo,data from this ongoingstudy not included,77 Were included in the primary analysis,78 Were included in the primary analysis,N Engl J Med 2012, May 21,Panther 研究结论,中期结果表明，与安慰剂组相比，三联治疗组:死亡率高 (11% VS 1%);住院率高 (29% VS 8%);严重不良事件更多 (31% VS 9%);肺功能无显著性差异;患者依从性低 (78% VS 98
19、%).,The Anticoagulant Effectiveness in Idiopathic Pulmonary Fibrosis (ACE-IPF) trial,探讨华法令抗凝治疗对IPF死亡率、住院率和FVC下降的影响。,目 的,方 法,随机、双盲、安慰剂对照研究；按照1:1比例将IPF患者分为二组，一组给予华法令，另一组给予安慰剂，观察48周；治疗组维持INR 2.0 - 3.0之间；,ACE-IPF研究,72 Were assigned to receive warfarin,73 Were assigned to receive placebo,72 Were included in primary analysis,73 Were included in primary analysis,由于华法令组患者的死亡明显升高 (14 warfarin vs. 3 placebo deaths; p=0.005);并且获益可能性低；独立的数据和安全监测委员会（IDSMB）建议终止这个研究【计划入组256，实际入组145(72 warfarin, 73 placebo)】；平均随访时间28周。,结 论,Thank you,
