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Am J Respir Crit Care Med. 2011 Apr 15;183(8):1062-70. doi: 10.1164/rccm.201005-0742OC. Epub 2010 Dec 17.
Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotent mesenchymal stromal cell population. However, the clinical relevance of this novel cellular component of BAL and its association with bronchiolitis obliterans syndrome (BOS), a disease marked by progressive airflow limitation secondary to fibrotic obliteration of the small airways, remains to be determined.
In this study we investigate the association of number of mesenchymal stromal cells in BAL with development of BOS in human lung transplant recipients.
Mesenchymal colony-forming units (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung transplant recipients. Poisson generalized estimating equations were used to determine the predictors of BAL mesenchymal CFU count.
Higher CFU counts were noted early post-transplantation; time from transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P = 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated with a 2.11-fold higher CFU count (P = 0.02). There were 2.62- and 2.70-fold higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis obliterans (P = 0.05) and organizing pneumonia (0.0003), respectively. In BAL samples obtained from BOS-free patients greater than 6 months post-transplantation (n = 173), higher mesenchymal CFU counts (≥10) significantly predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P < 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P < 0.0001) Cox regression analysis.
Measurement of mesenchymal CFUs in the BAL provides predictive information regarding future BOS onset.
从人类肺移植物的支气管肺泡灌洗液（BAL）中可以证明存在多能间充质基质细胞群。然而，BAL 中这种新型细胞成分的临床意义及其与闭塞性细支气管炎综合征（BOS）的关系（BOS 是一种以小气道纤维化闭塞导致进行性气流受限为特征的疾病）仍有待确定。
在这项研究中，我们调查了 BAL 中间充质基质细胞数量与肺移植受者 BOS 发展的关系。
对 162 例肺移植受者的 405 例 BAL 样本进行了间充质集落形成单位（CFU）的定量分析。泊松广义估计方程用于确定 BAL 间充质 CFU 计数的预测因子。
在移植后早期观察到更高的 CFU 计数；BAL 距移植时间大于 3 个月预测 CFU 计数降低 0.4 倍（P=0.0001）。BAL 前 BOS 诊断等于或小于 365 天与 CFU 计数增加 2.11 倍相关（P=0.02）。在组织学诊断为闭塞性细支气管炎（P=0.05）和机化性肺炎（0.0003）的情况下，CFU 计数分别增加 2.62 倍和 2.70 倍。在移植后大于 6 个月 BOS 无发生的 BAL 样本（n=173）中，更高的间充质 CFU 计数（≥10）在单变量（危险比，5.61；95%置信区间，3.03-10.38；P<0.0001）和多变量（危险比，5.02；95%置信区间，2.40-10.51；P<0.0001）Cox 回归分析中显著预测了 BOS 的发生。
BAL 中间充质 CFU 的测量提供了关于未来 BOS 发病的预测信息。
