特发性肺纤维化IPF

2017/12/22,1,弥漫性实质性肺疾病,西京医院呼吸科 李志奎,2017/12/22,2,肺实质是指各级支气管及肺泡结构肺泡主要指肺泡腔及肺泡上皮细胞。,肺间质是指肺泡上皮基底膜与毛细血管内皮基底膜之间的潜在间隙 其中充填着弹力纤维、胶原纤维、网状纤维、无定形细胞外基质及少量细胞, 是肺的重要支撑组织。,2017/12/22,3,特发性间质性肺炎,原因不明异质性弥漫性间质性肺病病变不仅侵犯肺间质, 肺实质也明显受累, 故美国胸科协会(ATS)/欧洲呼吸协会(ERS)于02年颁布的国际多学科共识将其称为弥漫性实质性肺疾病累及肺泡腔、肺泡上皮、外周气道、小血管及其内皮细胞。,2017/12/22,4,弥漫性实质性肺疾病,2. 特发性肺纤维化（IPF） a. 概述及病因 b.发病机制 c.病理； d.诊断; e.治疗3.其它非IPF特发性间质性肺炎4.病因确定的弥漫性实质性肺疾病5.肉芽肿性弥漫性实质性肺疾病6.其它少见的弥漫性实质肺疾病,1.弥漫性实质性肺疾病概述,2017/12/22,5,一组主要侵犯周边肺组织即肺泡、肺泡间隔、邻近的小气道和小血管的弥漫性炎症性疾病两肺野或大部分肺野满布大小不等的结节状、小片状、线条或网格状、蜂窝状阴影主要为间质性肺疾病,弥漫性间质性肺疾病(interstitial lung disease，ILD)概 念,2017/12/22,6,1 临床：活动后呼吸困难2 X线：双肺弥漫性阴影3 肺功能:限制性通气功能障碍、弥散功能降低、肺泡-动脉血氧分压差增大4 组织学：显示不同程度的纤维化和炎性变伴或不伴有肺实质肉芽肿或继发性血管病变,本组疾病有以下特点:,2017/12/22,7,(1)原因确定的DPLD: 药物或与某种病变相关,如结缔组织病(2)特发性间质性肺炎(IIP)(3)肉芽肿性DPLD: 如结节病(4)其他类型的DPLD: 如肺淋巴管肌瘤病组织细胞增生症X (ATS)美国胸科协会 (ERS)欧洲呼吸协会,2002年ATS/ERS分类将弥漫性肺实质病变(DPLP)的分下列四类:,2017/12/22,8,DPLD-Classification,2017/12/22,9,原因确定的DPLD: 已明确的病因,1.放射性肺炎:2.无机粉尘:矽肺3.有机粉尘:过敏性肺炎4.药物:博莱霉素,2017/12/22,10,肉芽肿性DPLD : 病因未明，病理特殊,1.感染性及异物性肉芽肿：如结核性、霉菌性肉芽肿，铍肺2.肺血管炎和肉芽肿病：如支气管中心性肉芽肿病（BCG）、Wegener肉芽肿（WG）、坏死性结节病样肉芽肿（NSG）、类风湿性关节炎肺内类风湿结节。坏死性肉芽肿伴血管炎3.不明原因的肉芽肿：如结节病。非干酪样类上皮肉芽肿。多器管受累,2017/12/22,11,其他类型的DPLD 病因未明,但病理特殊,1.肺泡蛋白沉积症:2.肺泡微石症:.肺出血肾炎综合症(Good-Pastare综合症)4.淋巴管平滑肌瘤(lam)5弥漫性肺淀粉样变性（PAM）,2017/12/22,12,(1)特发性肺纤维化(IPF)或隐源性纤维化肺泡炎 (2)非特异性间质性肺炎(NSIP)(3)隐源性机化性肺炎(COP)(4)急性间质性肺炎(AIP),IIP分为7个临床放射学病理学实体疾病:按发病率多少依次是,(5)呼吸性细支气管炎一间质性肺病(RB-ILD)(6)脱屑性间质性肺炎(DIP)(7)淋巴细胞间质性肺炎(LIP),2017/12/22,13,弥漫性实质性肺疾病,1.弥漫性实质性肺疾病概述 a. 概述及病因 b.发病机制 c.病理 d.诊断 e.治疗3.其它非IPF特发性间质性肺炎4.病因确定的弥漫性实质性肺疾病5.肉芽肿性弥漫性实质性肺疾病6.其它少见的弥漫性实质肺疾病,2. 特发性肺纤维化（IPF）,2017/12/22,14,较为多见临床上独特进行性呼吸困难，双肺Velcro罗音，20-50%有杵状指并肺心病时可出现右心衰竭X线：弥漫性网状斑片状或结节状影肺功能为限制性其预后与肺癌相同。,特发性肺纤维化概况(idiopathic pulmonary fibrosis，IPF)：,2017/12/22,15,50%,Years,RespiratoryFunction/Symptoms,1,2,3,4,FVC,Traditional View of UIP/IPF Progression,Progression of IPF:Acute Exacerbation vs Slow Decline,FVC = forced vital capacity,2017/12/22,16,50%,Years,RespiratoryFunction/Symptoms,1,2,3,Acute exacerbation,Step Theory of UIP/IPF Progression,Progression of IPF:Acute Exacerbation vs Slow Decline,FVC,0,4,2017/12/22,17,准确发病率和流行情况尚不清楚以前估计总发病率为3610万。近来IPF的患病率为男性20.210万，女性13.210万，每年的新发病率为男性10.710万，女性7.410万。,IPF发病情况,2017/12/22,18,男性多于女性中年居多，通常在4070岁。60岁以上者占23，平均年龄为66岁，患病率随年龄增加而增高儿童发病情况不清楚，即使有也属罕见,年龄和性别,2017/12/22,19,Epidemiology of IPF,Estimated 83,000 CurrentPatients in the United States,Estimated 31,000 New Patients per Year in the United States,0,50,100,150,200,250,300,45-54,55-64,65-74,75+,Male,Female,0,20,40,60,80,100,120,45-54,55-64,65-74,75+,Male,Female,Weycker D, et al. Prevalence, Incidence, and Economic Costs of Idiopathic Pulmonary Fibrosis. Paper presented at: CHEST 2002, November 2-7, 2002; San Diego, California.,Prevalence,Incidence,2017/12/22,20,年龄增加而增加日本IPF的死亡率为3.010万，其中男性为3.310万，女性为2.510万。存活期为确诊后的3.25年。IPF的中位存活时间为出现呼吸系统症状后的28.2月,病程和死亡率：,2017/12/22,21,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,0 1 2 3 4 5 6 7 8 9,Cumulative Proportion Surviving,Survival Curve for IIP Patients Grouped by Histologic Classification,P 5%，最高可达 50%； EC% ， 40%-60% 5%；只有 10%-20%患者LC% 。（二）胶原酶,2017/12/22,77,病理诊断（金标准） 1、开胸肺活检或通过电视胸腔镜肺活检（TBLB不能作为IPF活检手段） 2、病理组织学符合UIP图像 、经皮肺活检,2017/12/22,78,为肺叶外周片状分布的腺泡结构毁损、纤维化、蜂窝形成以及散在的成纤维细胞灶病变不均一，间质有炎症、纤维化、蜂窝样改变与正常肺组织，纤维母细胞灶交互出现。病变轻重不一，新老并存是诊断UIP的重要依据，也是与其他IPF相区别的关键鉴别点,病理特征：普通型间质性肺炎(UIP):,2017/12/22,79,Pathology of IPF:Peripheral Accentuation of Disease,Slide courtesy of Kevin Leslie, MD,2017/12/22,80,Pathology of IPF:Transition to Uninvolved Lung Present in the Biopsy,Slide courtesy of Kevin Leslie, MD,2017/12/22,81,Pathology of UIP/IPF,Slide courtesy of Kevin Leslie, MD,2017/12/22,82,Fibroblastic Focus in UIP,Slide courtesy of Kevin Leslie, MD,2017/12/22,83,弥漫性实质性肺疾病,1.弥漫性实质性肺疾病概述2. 特发性肺纤维化（IPF） a. 病因; b.发病机制 c.病理； d.诊断; e.治疗4.病因确定的弥漫性实质性肺疾病5.肉芽肿性弥漫性实质性肺疾病6.其它少见的弥漫性实质性肺疾病,3.其它非IPF特发性间质性肺炎,2017/12/22,84,Differential Diagnosis,Other idiopathic interstitial pneumoniasNSIP AIPDIP COPRB-ILD,ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664.,2017/12/22,85,（一）AIP（急性间质性肺炎）,过去归为IPF的急性型，特称之为Hamman-Rich综合征。 本病的病理分为急性炎症渗出期和慢性增生纤维化期，相似于ARDS。透明膜是AIP的组织学标志, 可与UIP、DIP、NSIP等鉴别。,2017/12/22,86,AIP（急性间质性肺炎）临床表现,平均发病年龄为50岁。往往先有上呼吸道病毒感染史, 主诉肌痛、关节痛、畏寒、发热及乏力数日后出现进行性劳力性呼吸困难。有肺实变征及广泛湿哆音。患者迅速出现低氧血症和呼吸衰竭, 需机械通气维持.,2017/12/22,87,AIP（急性间质性肺炎）临床表现,临床过程极似ARDS，故又称之为无原因可寻的ARDS。持久的Velcro罗音严重的低O2血症半数病人发热，WBC明显增高X线除蜂窝肺少见外，余均可见到，肺容量不减少。,2017/12/22,88,AIP（急性间质性肺炎）CT片:,早期:渗出阶段表现为多发性片状磨玻璃影, 与正常肺组织相间,形成地图样也可见下肺和低垂部位的实变影, 提示因重力和静水压所致肺泡闭陷图晚期:机化阶段可见支气管血管束的扭曲变形, 牵拉性支气管扩张,2017/12/22,89,AIP患者HRCT示磨玻璃影及实变影呈地图样分布,2017/12/22,90,AIP in a 48-year-old woman. Thin-section CT scan of the right lung obtained 2 cm below the level of the tracheal carina,demonstrates diffuse ground-glass attenuation and intralobular reticular opacities (arrows).,2017/12/22,91,Acute interstitial pneumonia in a 43-year-old woman. Thin-section CT scan obtained in the right lung 20 days after onset of symptoms.,extensive areas of ground-glass attenuation and intralobular reticular opacities.,Traction bronchiectasis extends to the level of the segmental bronchi (solid arrows,Also note a small pleural effusion (open arrows) in the major fissure.,2017/12/22,92,Acute interstitial pneumonia in a 64-year-old woman. Thin-section CT scan obtained in the right lung at the level of the tracheal carina 7 days after the onset of symptoms,patchy airspace consolidation and traction bronchiectasis (small arrows). Subsegmental bronchi (large arrows) and arteries are distorted, indicating architectural distortion.,2017/12/22,93,AIP（急性间质性肺炎）治疗,无特殊有效治疗激素治疗无效抗感染、支持和对症治疗多在1个月内死亡，80%-90%半年内死亡，存活仅占10%-20%,2017/12/22,94,（二）NSIP（非特异性间质性肺炎）,NSIP是1994年由Katzenstein及Fiorelli提出指那些不符合任一特定病理类型的IIP与IPF不同,预后较好Katzenstein等NSIP分为三型:型病理改变以间质性炎症为主型兼有炎症及纤维化型以纤维化为主患者的预后与病理类型相关, 型最佳, 型最差。,2017/12/22,95,NSIP临床表现,年龄较IPF约早10年, 中位发病年龄40一50岁与吸烟关系不密切起病缓慢或呈亚急性主要症状:气短、咳嗽、乏力, 半数有体重减轻平均6Kg女多于男病程较长，就诊时一般已达到数月或数年蜂窝肺约占5%-25%,2017/12/22,96,NSIP,半数以上患者BALF中淋巴细胞数显著增高。BALF中性粒细胞和或嗜酸性粒细胞也可增多细胞亚型对激素反应较好:治疗后女性100%、男性90%可存活510年；纤维化亚型5年病死率为10%-20%；混合亚型介于其间。,2017/12/22,97,NSIP胸部影像,CT片多呈磨玻璃样影约1/3患者磨玻璃影为仅有的异常征象, 可合并牵拉性支气管扩张, 蜂窝肺或肺实变较少见约1/3患者的片难以与IPF鉴别,2017/12/22,98,病理,病理可见不同程度间质性炎症或纤维化病理不具备UIP、DIP、COP或LIP特征镜下纤维化程度比较均一, 无成纤维细胞灶细胞浸润以淋巴细胞为主, 少量肥大细胞, 但肺泡隔淋巴细胞不如LIP那样密集显著。,2017/12/22,99,Non-specific Interstitial PneumoniaFibroticNon-specific Interstitial PneumoniaCellular,Common Diseases Mistaken for IPF,Images courtesy of Kevin O. Leslie, MD,2017/12/22,100,NSIP in a 69-year-old woman. Thin-section CT scan,demonstrates areas of air-space consolidation (straight arrows) with a predominantly peribronchovascular distribution. Focal areas of ground-glass attenuation (curved arrows) also are present.,2017/12/22,101,shows bilateral areas of ground-glass attenuation (arrows) with a predominantly central distribution. The reviewers believed that these findings were more compatible with alveolar proteinosis(蛋白沉积)than with NSIP.,Transverse high-resolution CT image obtained at the level of the lingular bronchus in a 33-year-old woman with NSIP,2017/12/22,102,NSIP 影像学,2017/12/22,103,（三）隐源性机化性肺炎(COP),COP由Davison等 1983年提出。1985年，Epler等称本病为阻塞性细支气管炎伴机化性肺炎(BOOP)。后这一称谓曾获得普遍接受。但多数学者认为COP更符合本病的特点,2017/12/22,104,病理改变,病理特征为肺泡道和肺泡的机化, 可伴有细支气管的机化息肉样阻塞性细支气管炎小气道和肺泡内肉芽肿，肺泡周围的淋巴细胞浸润呼吸性细支气管闭塞,2017/12/22,105,COP病理表现,2017/12/22,106,临床表现,本病无性别差异平均发病年龄55岁主要症状为不同程度的咳嗽和气短, 可有白色清痰体重减轻、多汗、畏寒、间歇性发热及乏力十分常见, 往往疑诊为感染而反复用抗生素肺部听诊可闻局限或广泛湿哆音, 无杵状指,2017/12/22,107,临床表现,血沉增快C一反应蛋白增高外周血中性粒细胞计数常升高肺功能显示限制性通气障碍和弥散障碍BALF中淋巴细胞数及百分比升高, 可达细胞总数的40%,2017/12/22,108,临床表现,BOOP过程较轻，病程较短，一般210周，3/4病人2周，只有24%病人症状持续1年以上。影象学图形以 “蝴蝶形”阴影为特征。激素治后多可完全恢复, 但泼尼松减量（15mg/d以下)或停用时, 部分患者在3个月内复发。故推荐激素至少应用6个月。少部分患者可自愈, 极少发展为呼吸衰竭,2017/12/22,109,胸部影像,CT片显示有实变, 位于胸膜下和支气管周围, 下肺野最常见实变区常见空支气管征及轻度柱状支气管扩张图患者支气管血管束周围可见的小结节影, 须与肺泡癌、淋巴瘤、结节病、嗜酸性粒细胞性肺炎等鉴别如呈支气管周围及胸膜下片状实变, 经数周抗生素治疗阴影反增多者, 应高度疑COP,2017/12/22,110,shows poorly defined arcadelike(拱廊样) and polygonal(多角形的) opacities (perilobular pattern) in the left lower lobe in both subpleural and central regions of the lung. The opacities resemble thickened interlobular septa.,Transverse thin-section CT scan at the level of dome of the right hemidiaphragm in a 50-year-old woman with cryptogenic organizing pneumonia,2017/12/22,111,Few abnormally thickened interlobular septa (arrowheads) are seen anteriorly in both upper lobes. These linear opacities are thinner and more sharply demarcated,Transverse thin-section CT scan through upper lobes in a 49-year-old woman with cryptogenic organizing pneumonia,2017/12/22,112,There is extensive airspace consolidation posteriorly(后面的) in the right lower lobe.,Transverse thin-section CT scan at the level of lung base in a 51-year-old woman with cryptogenic organizing pneumonia,Perilobular opacities (arrows) are seen abutting(邻接的) the pleural surface in the left lower lobe,2017/12/22,113,The perilobular opacities (arrows) in right lower lobe are centrally located and surrounded by aerated lung parenchyma.,Transverse thin-section CT scan through lower lobes in a 44-year-old man with cryptogenic organizing pneumonia,2017/12/22,114,Perilobular opacity (arrow) not immediately obvious is located adjacent to a focus of airspace consolidation in the left lower lobe. There are few bandlike opacities (arrowheads) in th