Analysis of risk factors for the development of bronchiolitis obliterans syndrome
Analysis of risk factors for the development of bronchiolitis obliterans syndrome
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DOI：
10.1164/ajrccm.159.3.9607099
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发表时间：
1999-03-01
影响因子：
24.7
通讯作者：
Garrity, ER
中科院分区：
文献类型：
--
作者：
Husain, AN;Siddiqui, MT;Garrity, ER
肺移植后的慢性排斥反应表现为闭塞性细支气管炎综合征(BOS)，已成为患者和移植物长期存活的主要挑战。为了阐明发生BOS的危险因素，我们利用1995年修订的同种异体肺移植排斥反应分类工作公式[1]，设计了一种定量方法来回顾研究所有存活至少90d的患者的肺移植活检组织，所有经支气管镜活检的急性血管周围排斥反应和淋巴细胞性支气管炎/毛细支气管炎(LBB)被重新分级为0到4级，并在一段时间内对每个患者进行累加，分别给出两个分数。同时还检查了急性排斥反应和LBB发作的时间以及免疫抑制的减少，定义为两个或两个以上的环孢素A水平&200 ng/ml。66名BOS患者和68名无BOS(NBOS)的患者符合我们纳入研究的标准。包括年龄、性别和主要诊断在内的人口统计学数据相似。平均随访822d(113~2,146)，BOS的血管周围评分平均为6.2，而NBOS的平均血管周围评分超过550 d(97~1,734)，平均为3.2。在相同的随访期内，气道评分分别为5.3和1.7。尽管两组的平均随访期有显著差异，但随访期长短与排斥反应或LBB评分之间没有相关性。晚期急性排斥反应和LBB与BOS显著相关，免疫抑制的减少也是如此。除血管周围排斥反应外，LBB、晚期急性排斥反应和免疫抑制降低也是BOS发生的重要危险因素。对目前数据的分析使我们相信，在没有感染的情况下，LBB实际上是急性排斥的一种表现，对移植肾功能的影响类似于急性血管周围排斥。
Chronic rejection after lung transplantation, manifesting as bronchiolitis obliterans syndrome (BOS), has become the dominant challenge to long-term patient and graft survival. In order to elucidate risk factors for development of BOS we utilized the 1995 revision of the working formulation for the classification of lung allograft rejection (1), and devised a quantitative method to retrospectively study lung transplant biopsies from all patients who survived at least 90 d. All transbronchial biopsies were regraded 0 to 4 for acute perivascular rejection and lymphocytic bronchitis/bronchiolitis (LBB), and the grades were totaled over a period of time to give two scores, respectively, for each patient. Also examined were timing of acute rejection and LBB episodes and decreased immunosuppression defined as two or more cyclosporine A levels < 200 ng/ml. Sixty-six patients with BOS and 68 with no BOS (NBOS) satisfied our criteria for inclusion in the study. Demographics including age, sex, and primary diagnoses were similar. The mean perivascular score for BOS was 6.2 over a mean follow-up of 822 d (range, 113 to 2,146) compared with 3.2 for NBOS over 550 d (range, 97 to 1,734) mean follow-up. Airway scores were 5.3 and 1.7, respectively, for the same follow-up periods. There was no correlation between length of follow-up and rejection or LBB scores, although mean length of followup for the two groups was significantly different. Late acute rejection and LBB were significantly associated with BOS as was decreased immunosuppression. In addition to perivascular rejection, LBB, late acute rejection, and decreased immunosuppression are significant risk factors for the development of BOS. Analysis of the current data leads us to believe that LBB, in the absence of infection, is in fact a manifestation of acute rejection, with similar implications for graft function as acute perivascular rejection.