Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Department of Biomathematics, University of California at Los Angeles, Los Angeles, CA.
Am J Transplant. 2018 Jan;18(1):136-144. doi: 10.1111/ajt.14397. Epub 2017 Aug 2.
The clinical significance and treatment strategies for minimal acute rejection (grade A1), the most common form of acute rejection (AR), remain controversial. In this retrospective single-center cohort study of 441 lung transplant recipients, we formally evaluate the association between minimal AR and chronic lung allograft dysfunction (CLAD) and test a novel hypothesis using bronchoalveolar lavage (BAL) CXCL9 concentration during minimal AR as a biomarker of subsequent CLAD development. In univariable and multivariable models adjusted for all histopathologic injury patterns, minimal AR was not associated with CLAD development. However, minimal AR with elevated BAL CXCL9 concentrations markedly increased CLAD risk in a dose-response manner. Minimal AR with CXCL9 concentrations greater than the 25th, 50th, and 75th percentile had adjusted hazard ratios (HRs) for CLAD of 1.1 (95% confidence interval [CI] 0.8-1.6), 1.6 (95% CI 1.1-2.3), and 2.2 (95% CI 1.4-3.4), respectively. Thus we demonstrate the utility of BAL CXCL9 measurement as a prognostic biomarker that allows discrimination of recipients at increased risk of CLAD development after minimal AR. BAL CXCL9 measurement during transbronchial biopsies may provide clinically useful prognostic data and guide treatment decisions for this common form of AR, as a possible strategy to minimize CLAD development.
微小急性排斥反应（A1 级）是最常见的急性排斥反应（AR）形式，其临床意义和治疗策略仍存在争议。在这项对 441 例肺移植受者进行的回顾性单中心队列研究中，我们正式评估了微小 AR 与慢性肺移植物功能障碍（CLAD）之间的关联，并使用微小 AR 期间支气管肺泡灌洗（BAL）中 CXCL9 浓度这一新型假说作为随后 CLAD 发展的生物标志物进行了测试。在调整了所有组织病理学损伤模式的单变量和多变量模型中，微小 AR 与 CLAD 发展无关。然而，伴有 BAL CXCL9 浓度升高的微小 AR 则以剂量反应的方式显著增加了 CLAD 风险。微小 AR 伴有 CXCL9 浓度大于第 25、50 和 75 百分位数时，CLAD 的校正风险比（HR）分别为 1.1（95%置信区间 [CI] 0.8-1.6）、1.6（95% CI 1.1-2.3）和 2.2（95% CI 1.4-3.4）。因此，我们证明了 BAL CXCL9 测量作为预后生物标志物的效用，它可以区分微小 AR 后 CLAD 发展风险增加的受者。经支气管镜活检时测量 BAL CXCL9 可能为这种常见形式的 AR 提供有临床意义的预后数据，并指导治疗决策，作为一种最小化 CLAD 发展的可能策略。
