Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation
Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation
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DOI：
10.1016/j.jtcvs.2004.10.035
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发表时间：
2005-05-01
影响因子：
6
通讯作者：
Keshavjee, S
中科院分区：
文献类型：
--
作者：
D'Ovidio, F;Mura, M;Keshavjee, S
背景：吸入胃食管反流液可能导致肺移植闭塞性细支气管炎综合征（BOS）。材料和方法：对120例肺移植受者进行肺功能监测和支气管肺泡灌洗液（BALF）检测。生存6个月后诊断为BOS-（0 p-3）。如果在移植后12个月内诊断出BOS，则将其定义为“早期”。测定BALF的细胞分类计数、胆汁酸和白细胞介素8和15。如果胆汁酸高于正常血清水平（>= 8 μ mol/L），则认为胆汁酸升高。结果：120例患者中有20例（17%）BALF胆汁酸升高。107名患者中有36名（34%）被诊断为BOS，36名患者中有21名（57%）被判定为“早期”。中位BALF胆汁酸值为1.6 μ mol/L（范围，0.32 μ mol/L）在BOS患者和0.3 μ mol/L（范围，0-16 μ mol/L）（P = 0.002）;早期BOS患者为2.6 μ mol/L（范围0-32 μ mol/L），晚期BOS患者为0.8 μ mol/L（范围0-4.6 μ mol/L），（P = 0.02）。胆汁酸与BALF IL-8和肺泡嗜酸性粒细胞相关（分别为r = 0.3，P = 0.0004和r = 0.3，P = 0.004），但与IL-15无关。BALF胆汁酸升高的患者中无BOS的时间显著缩短（Cox-Mantel检验，P = .0001）。结论：肺移植后吸入胃食管反流液是普遍的，与BOS的发生有关。BALF胆汁酸升高可能通过IL-8和肺泡嗜酸性粒细胞介导的炎症过程促进早期BOS的发展。
Background: Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS.Materials and Methods: Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was defined as "early" if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels (>= 8 mu mol/L).Results: Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21 (57%) of 36. Median BALF bile acid values were 1.6 mu mol/L (range, 0.32 mu mol/L) in BOS patients and 0.3 mu mol/L (range, 0-16 mu mol/L) in non-BOS patients (P = .002); 2.6 mu mol/L (range, 0-32 mu mol/L) in early BOS patients and 0.8 mu mol/L (range, 0-4.6 mu mol/L) in late BOS patients, (P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001).Conclusions: Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.