Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; German Centre for Lung Research (DZL/BREATH), Hannover, Germany.
German Centre for Lung Research (DZL/BREATH), Hannover, Germany.
J Heart Lung Transplant. 2023 Feb;42(2):209-217. doi: 10.1016/j.healun.2022.09.022. Epub 2022 Oct 5.
Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treatment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course.
Retrospective analysis of patients completing ≥3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were compared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation.
Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photopheresis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation.
Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treatment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible.
慢性肺移植物功能障碍（CLAD）是肺移植中移植物丧失的主要原因。尽管如此，目前缺乏令人信服的治疗数据，而且不同中心的方案差异很大。CLAD 存在表型，但表型转变增加了设计临床相关研究的挑战。体外光化学疗法（ECP）长期以来一直是一种被提议的挽救治疗方法，但疗效似乎难以预测。本研究描述了我们使用新型时间表型对光化学疗法的经验，以说明临床过程。
对 2007 年至 2022 年间接受 ECP 治疗 CLAD 且治疗时间≥3 个月的患者进行回顾性分析。采用混合效应模型的潜在类别分析，根据光化学疗法前 12 个月的肺功能轨迹以及光化学疗法开始后 4 年内移植物丧失，对患者进行分组。比较治疗反应和生存结局的时间表型。线性判别分析仅依赖于光化学疗法开始时可用的数据，用于评估表型的可预测性。
利用 373 例患者的 5169 次门诊就诊数据构建模型。确定了 5 个轨迹，光化学疗法 6 个月后，肺功能的变化是一致的。Fulminant 型患者（N=25，7%）预后最差，中位生存时间为 1 年。在其余患者中，光化学疗法开始时的肺功能较差导致预后较差。该分析揭示了重要的混杂因素，这些因素影响了决策和结果解释。
时间表型为 CLAD 中的 ECP 治疗反应提供了新的见解，特别是及时干预的重要性。指导治疗决策的%基线值的局限性需要进一步分析。光化学疗法的效果可能比以前认为的更均匀。在光化学疗法开始时预测生存似乎是可行的。
