造血干细胞移植相关肺部并发症

造血干细胞移植相关肺部并发症Pulmonary complications after hematopoietic cell transplantation,Company Logo,overview,Infections,Phases of opportunistic infections among allogeneic hematopoietic cell transplant recipients,,Company Logo,Pre-engraftment,中性粒细胞及淋巴细胞缺乏、粘膜炎、粘膜屏障破坏、吞咽困难、误吸常见病原菌：细菌：E coli.、铜绿假单胞菌、链球菌病毒：流感病毒A/B、副流感病毒(PIV3)、RSV、h MPV真菌：念珠菌、曲菌427Allo-SCT， 1月内肺部感染，4%细菌性，9%真菌性，2%病毒性11.Aguilar-Guisado M, Jimnez-Jambrina M, Espigado I, et al. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. Clin Transplant 2011; 25:E629.,,Company Logo,曲霉菌,,Company Logo,曲霉菌,,Company Logo,,Company Logo,念珠菌肺炎,1.28Y/M,AML,移植后2.23Y/M AML3.25y/M M1a4.45y/MFranquet T, et al. Pulmonary candidiasis after hematopoietic stem cell transplantation: thin-section CT findings. Radiology 2005; 236:332.,,Company Logo,,Company Logo,肺水肿pulmonary edema,肺水肿-Butterfly,,Company Logo,植入综合征,Auto-SCT中7-10%，Allo-SCT较少发生NEU#上升,7-11天发热、皮疹、体重增加、低氧、非心源性肺水肿、腹泻,,Company Logo,A. d0正常CXR, B. d +7,皮疹, d +11CXR间质性肺水肿，T升高, 用激素治疗后好转。Chest Radiographic Features of Engraftment Syndrome.Ravenel, James; Scalzetti, Ernest; Zamkoff, Kenneth Journal of Thoracic Imaging. 15(1):56-60, January 2000,,Company Logo,植入综合征：肺小叶间隔增厚.,心源性肺水肿：中心性分布，血管扩张,植入前,,Company Logo,植入后-感染,3周至3月，细胞及体液免疫缺陷3月后，cGVHD及治疗细菌：肺炎链球菌、流感嗜血杆菌、军团菌、诺卡菌、放线菌；（第1年）分枝杆菌：TB及NTM,Allo-SCT后，1-3%,香港5.5%（10/183）.IV型超敏反应抑制PPD病毒：CMV，呼吸道病毒（流感V、副流感、RSV、腺V、人偏肺V），HHV-6;真菌：曲菌、其他侵袭性真菌、PCP；寄生虫：弓形虫Ip MS, Yuen KY, Woo PC, et al. Risk factors for pulmonary tuberculosis in bone marrow transplant recipients. Am J Respir Crit Care Med 1998; 158:1173.,,Company Logo,,Company Logo,植入后-感染,肺炎链球菌、流感嗜血杆菌军团菌、诺卡菌、放线菌,TB、NTM,弓形虫,曲菌、PCP、其他,CMV，呼吸道病毒（流感V、副流感V、RSV、腺V、人偏肺V）HHV-6,原因：3周至3月细胞及体液免疫缺陷，3月后cGVHD及治疗,D+66诺卡菌,D+55绿脓杆菌,,Company Logo,CMV,,Company Logo,E L Gasparetto.etal Cytomegalovirus pneumonia after bone marrowtransplantation: high resolution CT findings. The British Journal of Radiology, 77 (2004), 724727 ,,Company Logo,流感及副流感病毒有季节性，淋巴细胞减少常见，植入前较植入后更常见副流感病毒：潜伏期1-4天，,,Company Logo,真菌,曲霉菌，d+100，高龄、GVHD、GC、NEU#PCP,,Company Logo,TB,特发性肺炎综合征-idiopathic pneumonia syndrome,10% 4月内（中位D19始）定义：- 广泛性肺泡损伤 影像学多叶受累+肺炎症状体征+肺功能异常P(A-a)O2,PaO2.- 相隔2-14天，2次BAL或肺活检无感染证据- 无自身抗体升高病理机制尚不清楚发病率与预处理方案有关，1100患者，清髓IPS 8%，非清髓2%大剂量放疗、CTX、BUFukuda T, Hackman RC, Guthrie KA, et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102:2777.,,Company Logo,IPS,表现：呼吸困难、低氧、干咳诊断：BAL、肺活检治疗:糖皮质激素 1mg/kg (30天死亡率约75%)发现BAL中某些细胞因子IL-6、IL-8、TNF-a升高伊那西普或英夫利昔，28天生存率73-88%，1年生存率20-30%。,,Company Logo,胸膜下或气管旁GGO病理：肺泡、肺泡间隔、气管壁淋巴细胞浸润Tanaka N, Kunihiro Y, Yujiri T, et al. High-resolution computed tomography of chest complications in patients treated with hematopoietic stem cell transplantation. Jpn J Radiol 2011; 29:229.,,Company Logo,弥漫性肺泡出血-Diffuse alveolar hemorrhage,发病率80%,,Company Logo,闭塞性细支气管炎-Bronchiolitis obliterans BO,NIH共识认为BO是cGVHD唯一的肺部表现发病率210%,无GVHD者25.5%，GVHD14%死亡率13%-23%危险因素：cGVHD，ABO血型不合，高龄，PBSCT，某些病毒感染Ditschkowski M, Elmaagacli AH, etal.Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight-new perspectives?Bone Marrow Transplant. 2013 Sep;48(9):1224-9. Epub 2013 Feb 25,闭塞性细支气管炎-Bronchiolitis obliterans BO,左：H-E染色显示细支气管和支气管周围纤维化、单核炎症细胞浸润。右：弹性组织染色细支气管的弹性层和受压管腔马赛克征,机化性肺炎Organizing pneumonia,特发或与肺部放疗、GVHD、CMV感染有关边界不清的间质浸润与GGO诊断：病理治疗：激素,,Company Logo,恶性疾病,HCT后原发病复发、继发淋巴组织增殖性疾病PTLD:免疫抑制EBV特异的细胞毒性T细胞缺乏Scarsbrook AF, Warakaulle DR, Dattani M, Traill Z. Post-transplantation lymphoproliferative disorder: the spectrum of imaging appearances. Clin Radiol 2005; 60:47.,,Company Logo,肺泡蛋白沉积病-Pulmonary alveolar proteinosis PAP,“蝙蝠翼”样阴影，铺路石样改变，肺泡内充填脂蛋白样物质,,Company Logo,肺溶血性栓塞- Pulmonary cytolytic thromb PCT,病因不明，d70d400a/c GVHD? 未成年人常见发热、咳嗽、呼吸困难CXR正常，HRCT: 外周小结节病理：中小肺静脉内嗜碱性物质(细胞破裂碎片)栓塞，网罗有单个核细胞肺出血性梗死激素可能有效,,Company Logo,PCT胸膜下小结节嗜碱性栓子、网罗单个核细胞,肺静脉闭塞症-Pulmonary veno-occlusive disease PVOD,d+100呼吸困难、DLCO、限制性通气功能受损肺动脉高压、影像学肺水肿证据、PAWP正常,,Company Logo,肺静脉闭塞症-Pulmonary veno-occlusive disease PVOD,间质细线() 、片状磨玻璃影 (). 动脉增粗(), 静脉直径正常( ).,药物毒性和放射性肺炎,肺毒性的化疗药物,如 BU，CTX，BCNU，西罗莫司.放射治疗及TBI急性放射性肺炎 412周晚期放射性肺炎 612月,结缔组织病,HCT后31个月硬皮病、PM、SS、ANCA相关血管炎清髓、GVHDNIP、LIP、弥漫性肺泡损伤、OB抗Scl-70、ANCA、抗SM、RF等（+）,,Company Logo,,Company Logo,,Company Logo,,Company Logo,Auto-SCT,异无GVHD，无需免疫抑制剂病毒（CMV、VZV、RSV、HSV等）罕见机会性感染少,同粒缺4-6周细菌、真菌等感染药物及放