Girgis R E, Tu I, Berry G J, Reichenspurner H, Valentine V G, Conte J V, Ting A, Johnstone I, Miller J, Robbins R C, Reitz B A, Theodore J
Division of Pulmonary and Critical Care Medicine of the School of Medicine, Stanford University, Calif, USA.
J Heart Lung Transplant. 1996 Dec;15(12):1200-8.
Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables.
Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome.
Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation.
Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.
急性排斥反应已成为肺移植后闭塞性细支气管炎的一个重要危险因素。我们进行了多变量分析以评估其他变量的影响。
本研究纳入了74例存活超过90天且在数据分析前15个月以上接受移植的受者（48例心肺联合移植、18例单肺移植和8例双侧肺移植受者）。将多个变量纳入Cox回归分析以确定它们与闭塞性细支气管炎综合征发生的关联。
74例患者中有48例（65%）发生了闭塞性细支气管炎综合征。检测到急性排斥反应评分（定义为每个单独急性排斥反应发作的病理分级之和）与闭塞性细支气管炎综合征显著相关（p = 0.0004，似然比检验值 = 12.4），淋巴细胞性细支气管炎也与之显著相关（p = 0.03）。在二元模型中，机化性肺炎发作以及细菌或真菌性肺炎显著增加了急性排斥反应评分的似然比检验值。将反映感染频率和严重程度的巨细胞病毒感染评分加入急性排斥反应评分与细菌或真菌性肺炎发作的组合中，导致似然比检验值进一步显著增加。气流受限中重度阶段的显著危险因素为至少一次≥2级急性排斥反应发作、受者年龄较小以及移植后180天或更长时间发生的任何急性排斥反应发作。
急性排斥反应发作频率和严重程度的增加与闭塞性细支气管炎综合征的发生密切相关。淋巴细胞性细支气管炎在单变量分析中似乎具有显著性，但在双危险因素模型中，它并未增强急性排斥反应的影响。机化性肺炎、细菌或真菌性肺炎以及巨细胞病毒感染严重程度和频率的增加会增强急性排斥反应的作用。急性排斥反应的晚期发作以及受者年龄较小会增加发生晚期疾病的风险。
