Liu Qi-Fa, Luo Xiao-Dan, Fan Zhi-Ping, Ning Juan, Xu Dan, Sun Jing, Zhang Yu, Xu Bing, Wei Yong-Qiang
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. liuqifa@fimmu. com
Zhonghua Yi Xue Za Zhi. 2009 Mar 3;89(8):538-42.
To investigate the characteristics of chest high-resolution computed tomography (HRCT) and pathogenesis of acute graft versus host disease (aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation (allo-HSCT).
Chest HRCT was performed in 47 patients with aGVHD of grade II - IV after allo-HSCT. Twenty-four of the patients underwent different treatment regimens against aGVHD. Before the treatment peripheral blood samples were collected to detect the serum interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment. Pulmonary function was examined in the patients who survived more than 6 months in every 3 months.
Twenty of the 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be with aGVHD-induced lung injury. The HRCT images were characterized by diffused interstitial infiltrate in 5 cases, diffused interstitial and alveolar infiltrate in 7 cases, and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases. Nine cases had bilateral pleural effusion and hydropericardium, including 4 cases accompanied by myocardial hypertrophy. The levels of serum IFN-gamma and TNF-alpha of the patients with lung injury were (6.9 +/- 1.8) microg/L and (400 +/- 102) microg/L respectively, both not significantly different from those of the patients without lung injury [(6.3 +/- 1.2) microg/L and (428 +/- 83) microg/L respectively, P = 0.202, 0.306]. The histopathology of the lung tissue was characterized by disorganization, epithelial cell damage, interstitial fibroplasia, and interstitial T lymphocyte or macrophage infiltrate. The effective rate of treatment for aGVHD-induced lung injury was positively correlated with that for aGVHD (r = 0.771, P = 0.01). Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function, including 7 out of the 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without aGVHD-induced lung injury. There was no significant difference in the incidence of abnormal pulmonary function between the patients with and without lung injury (P = 0.033).
Lung is one of the target organs of aGVHD. IFN-gamma and TNF-alpha may play a role in the pathogenesis of aGVHD-induced lung injury. Acute GVHD-induced lung injury may progress to late-onset non-infectious lung injury.
探讨异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)所致肺损伤的胸部高分辨率计算机断层扫描(HRCT)特征及发病机制。
对47例allo-HSCT后发生II-IV级aGVHD的患者进行胸部HRCT检查。其中24例患者接受了不同的aGVHD治疗方案。治疗前采集外周血样本检测血清干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)。对4例治疗后未完全恢复的患者进行了经支气管活检。对存活超过6个月的患者每3个月进行一次肺功能检查。
47例患者中20例胸部HRCT图像异常,其中17例怀疑为aGVHD所致肺损伤。HRCT图像表现为:5例为弥漫性间质浸润,7例为弥漫性间质和肺泡浸润,5例为弥漫性间质和节段性大叶肺泡浸润。9例有双侧胸腔积液和心包积液,其中4例伴有心肌肥厚。肺损伤患者血清IFN-γ和TNF-α水平分别为(6.9±1.8)μg/L和(400±102)μg/L,与无肺损伤患者[分别为(`6.3±1.2)μg/L和(428±83)μg/L,P=0.202,0.306]相比,差异均无统计学意义。肺组织病理表现为结构紊乱、上皮细胞损伤、间质纤维化以及间质T淋巴细胞或巨噬细胞浸润。aGVHD所致肺损伤的治疗有效率与aGVHD的治疗有效率呈正相关(r=0.771,P=0.01)。24例存活超过6个月的患者中11例肺功能异常,其中9例aGVHD所致肺损伤患者中有7例,15例无aGVHD所致肺损伤患者中有4例。有肺损伤和无肺损伤患者肺功能异常发生率差异无统计学意义(P=0.033)。
肺是aGVHD的靶器官之一。IFN-γ和TNF-α可能在aGVHD所致肺损伤的发病机制中起作用。急性GVHD所致肺损伤可能进展为迟发性非感染性肺损伤。