结缔组织病肺间质改变的诊治进展课件

结缔组织病肺间质改变的诊治进展,北京协和医院风湿免疫科 张 烜,间质性肺病（interstitial lung disease，ILD）,CTD的常见疾病 可以是CTD的首发症状 是预后不良的原因之一 是肺动脉高压（pulmonary hypertension，PAH）的原因之一,影响肺功能,respiratory muscle dysfunction recurrent aspiration (esophageal dysmotility) thromboembolic events Inflammation of the cricoarytenoid joints or development of bronchiectasis.,ILD的发生率,15%的CTD合并ILD 70% SSc合并肺部病变，2年内可发展为ILD，组织病理77.5%SSc伴ILD 10%DM/PM合并ILD 胸片显示3.7%RA合并ILD SLE，SS，MCTD,Clin Chest Med 2004;25:549 559 Am J Respir Crit Care Med 2002;165:1581 6 Ann Rheum Dis 2003 ; 62 : 897 900,CTD中的ILD发生率、严重度及病死率的比较1）,CTD中ILD的特点,注：1）指5年之内因呼吸衰竭死亡 2）国外无对比数据 3）均为DM患者,张烜,董怡,张奉春.中华风湿病学杂志, 1999;3:247,分型的目的,自然病程、对激素反应、预后 CTD-UIP是否等同特发UIP?,ILD病理和影像学特点,Curr Opin Rheumtol 2004;16:186 191,HRCT - non-specific interstitial pneumonia,Systemic sclerosis DM/PM,HRCT - usual interstitial pneumonia,Systemic sclerosis RA DM/PM,UIP-HRCT特点,patchy pattern of peripheral “honeycombing” more prominent in the bases of the lungs, traction bronchiectasis absence of prominent ground-glass opacity.,HRCT - chronic lymphocytic interstitial pneumonia,Sjogrens syndrome RA Drug induced,HRCT obliterative bronchiolitis,RA SLE Scleroderma PM/DM,HRCT organizing pneumonia,Gold SSZ MTX Sjogrens syndrom RA,HRCT a patient with RA,33% of with RA associated parenchymal lung disease 31 IPF Radiography: 2-6% 29 HRCT: 10% - 47% 35-8 HRCT: 50% with broncioectases and bronchiolectasis,SLE - Chronic interstitial pneumonia,Radiographic - 624% HRCT 24/34 abnormal 11/34 CIP Fenlon HM, Doran M, Sant SM, et al. Am J Roentgenol 1996;166:3017. Estes D, Christian CL. Medicine (Baltimore) 1971;50:8595. Raynauds phenomenon, swollen fingers, sclerodactyly, telangiectasia, dyspnoea, nailfold capillary abnormalities May be efficacious: Corticosteroids Immunosuppressive agents,与ILD的相关因素,与病种有关 在RA中与RF的滴度有关 DM/PM与抗Jo-1抗体有关 抗RNP抗体,Clin Exp Allergy 2003;33:226 232 Arthritis Rheum 2002;47:614 622,预后,病理分型还是CTD,治疗,ILD 治疗的中心问题是GC和免疫抑制的指征 GC是最常用药，众多病人无反应 预后取决于分型 GC+CTX疗效好于单用GC,Am J Respir Crit Care Med 1996;154:400 Arthritis Rheum 1994;37:1290 Semin Arthritis Rheum 2003;32:273,治疗,ILD 治疗的中心问题是GC和免疫抑制的指征 GC是最常用药，众多病人无反应 预后取决于分型 GC+CTX疗效好于单用GC,Am J Respir Crit Care Med 1996;154:400 Arthritis Rheum 1994;37:1290 Semin Arthritis Rheum 2003;32:273,治疗RA-ILD,CTX,cyclosporine ,azathioprine, hydroxychloroquine have all been reported to be useful in the management of RA-associated ILD refractory to corticosteroids.,治疗RA-ILD TNF？,In a preliminary study, infliximab also led to stabilization or improvement in symptoms, lung function, and radiology scores in five RA-ILD . RCT trial needed 非UIP-recommend corticosteroids UIP-recommend TNF screen for secondary PH. Bosentan?,治疗SSc-ILD,prognosis better -77.5% respond to IS histopathologic subset severity of disease at presentation increased level of plasma homocysteine PH BAL eosinophil and neutrophil levels？ TGFbeta,MMP,治疗SSc-ILD-ACR2006报道,美国Denver Fischer A对27例肺活检的SSc患者（14例NSIP，8例UIP）分析表明：尽管都予同样的激素和免疫抑制剂治疗，SSc-NSIP中位生存时间为15.3年，而UIP为3年。,the first positive results of a PCT,治疗SSc-ILD-NEJM报道,DBRPCT 美国13个中心，158例患者 口服CTX或安慰剂年，随访年 PEP-FVC,治疗SSc-ILD-NEJM报道,Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC% predicted between the CTX and placebo groups was 2.53% (95%CI 0.28 to 4.79%), favoring CTX (P0.03).,治疗SSc-ILD-NEJM报道,There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the CTX group, but the difference not significant.,治疗SSc-ILD-NEJM报道,在治疗年时，HRCT纤维化严重病人在安慰剂组FVC下降明显，而在CTX组纤维化对FVC影响不明显 (P = 0.009),对SSc中已有纤维化说明存在相对早期活动性肺泡炎，如不治疗，病情容易进展。,治疗SSc-ILD-NEJM结论,One year of oral CTX in symptomatic SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 ms of the study.,治疗SSc-ILD-NEJM问题,no significant treatment-related difference was noted in the DLco,治疗ILD排除感染,mimic ILD or develop as a complication of immunosuppressive therapy. Pneumocystis carinii pneumonia. SLE, myositis,WGchronic corticosteroids, MTX, inhibitors of TNFa all patients with CTD on chronic immunosuppression (8 ws) should be considered for P. carinii prophylaxis?,治疗ILD排除感染,CMV感染,治疗ILDMTX?,acute hypersensitivity pneumonitis and pulmonary fibrosis May predispose to P. carinii independently of corticosteroid use prefer to avoid using MTX in patients with ILD recent studies suggest that low-dose MTX is associated with a very low risk of pulmonary toxicity, suggesting that patients should not be automatically discontinued from the MTX, provided that the ILD does not progress,治疗IPF启示,治疗IPF启示,The synthesis of glutathione can be accelerated by the administration of NAC, which crosses cell membranes easily and can be converted to l-cysteine. Uptake of l-cysteine is an important rate-limiting step for the synthesis of glutathione. NAC increases the pool of other antioxidant thiols that also protect cells from injury.,182 patients (92 to NAC and 90 to placebo). 155 (80 NAC and 75 placebo) had UIP, as confirmed by HRCT and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment.,57/80 taking NAC (71%) and 51/75 taking placebo (68%) completed one year of treatment. NAC slowed the deterio