Shitrit David, Amital Anat, Fox Ben, Kramer Mordechai R
Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel.
Respir Med. 2008 Feb;102(2):205-9. doi: 10.1016/j.rmed.2007.09.010. Epub 2007 Oct 31.
Bronchiolitis obliterans syndrome (BOS) following lung transplantation is common and potentially devastating. Its exact cause is undefined, but multiple immune and nonimmune processes contribute to its pathogenesis. The diagnosis of BOS syndrome is based on clinical presentation of progressive decline in the lung functions together with appropriate pathological findings. Severe acute rejection and recurrent acute rejection have been shown to confer the greatest risk for obliterative bronchiolitis, signifying the central importance of alloimmunity in the disease process. BOS is associated with activation of the coagulation system, and is a major cause of lung allograft loss. The aim of the study was to determine if there is an association between D-dimer levels and functional exercise capacity in lung transplant recipients with BOS. This prospective group comparison study was conducted at a tertiary-care, university-affiliated medical center. The sample included 46 patients (29%) who underwent lung transplantation between January 1997 and May 2006 and had positive findings on screening for BOS. Blood samples were collected for measurement of plasma D-dimer levels by the rapid MiniQuant assay. Correlational analysis was used to determine the association of D-dimer levels with demographic clinical data, pulmonary function, and functional exercise capacity parameters, including the 6-min walk test and cardiopulmonary exercise testing. D-dimer levels were associated with FEV1 (r=-0.43, p=0.001), 6-min walk test (r=-0.53, p=0.04), and VO2/kg/min (r=-0.36, p=0.04). No correlations were noted between D-dimer levels and total lung capacity, diffusion capacity, and oxygen saturation. On multivariate logistic regression, only FEV1 was a significant predictor of BOS (OR 0.885, CI: 0.812-0.965). We conclude that in lung transplant recipients with BOS, D-dimer levels are highly associated with functional exercise capacity and may serve as a useful marker for noninvasive monitoring. Further coagulation assays are needed to complete our observations.
肺移植后闭塞性细支气管炎综合征（BOS）很常见，且可能具有毁灭性。其确切病因尚不清楚，但多种免疫和非免疫过程参与了其发病机制。BOS综合征的诊断基于肺功能进行性下降的临床表现以及适当的病理发现。严重急性排斥反应和反复急性排斥反应已被证明是闭塞性细支气管炎的最大风险因素，这表明同种免疫在疾病过程中至关重要。BOS与凝血系统激活有关，是肺移植失败的主要原因。本研究的目的是确定BOS肺移植受者的D-二聚体水平与功能锻炼能力之间是否存在关联。这项前瞻性组间比较研究在一家三级医疗、大学附属的医学中心进行。样本包括46例患者（29%），他们在1997年1月至2006年5月期间接受了肺移植，且BOS筛查结果呈阳性。采集血样，通过快速MiniQuant检测法测量血浆D-二聚体水平。采用相关性分析来确定D-二聚体水平与人口统计学临床数据、肺功能以及功能锻炼能力参数之间的关联，这些参数包括6分钟步行试验和心肺运动试验。D-二聚体水平与第一秒用力呼气量（FEV1）（r = -0.43，p = 0.001）、6分钟步行试验（r = -0.53，p = 0.04）以及每公斤体重每分钟摄氧量（VO2/kg/min）（r = -0.3, p = 0.04）相关。未发现D-二聚体水平与肺总量、弥散功能和血氧饱和度之间存在相关性。在多因素逻辑回归分析中，只有FEV1是BOS的显著预测指标（比值比0.885，可信区间：0.812 - 0.965）。我们得出结论，在患有BOS的肺移植受者中，D-二聚体水平与功能锻炼能力高度相关，可作为无创监测的有用标志物。需要进一步的凝血检测来完善我们的观察结果。
