Kneidinger Nikolaus, Ghiani Alessandro, Milger Katrin, Monforte Víctor, Knoop Christiane, Jaksch Peter, Parmar Jasvir, Ussetti Piedad, Solé Amparo, Müller-Quernheim Joachim, Voelp Andreas, Behr Juergen, Neurohr Claus
Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
Department of Pulmonology and Respiratory Medicine, Robert-Bosch-Hospital, Stuttgart, Germany.
Front Med (Lausanne). 2022 Jun 2;9:897581. doi: 10.3389/fmed.2022.897581. eCollection 2022.
Chronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx).
10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis.
A total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality ( < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk.
Based on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions.
慢性肺移植功能障碍（CLAD）的定义是第一秒用力呼气容积（FEV1）逐渐下降，且与过早死亡相关。本研究的目的是调查肺移植（LTx）后患者FEV1下降与死亡风险之间的直接关联。
使用参与随机安慰剂对照临床试验的肺移植受者的10年随访数据，该试验研究吸入脂质体环孢素A（L-CsA-i）在预防闭塞性细支气管炎综合征中的作用（NCT01334892）。使用联合建模和Cox回归分析评估FEV1随时间变化的过程与死亡风险之间的关联。
共纳入130例患者。FEV1下降的预测因素是基线时较高的绝对FEV1和男性性别。联合模型分析表明FEV1变化与死亡风险之间存在显著关联（<0.001），FEV1每下降1%，预测死亡风险增加3.4%。进展性表型的显著预测因素是单肺移植和接受安慰剂治疗（与L-CsA-i相反）。随访结束时，82例患者（63.1%）仍存活。Cox回归分析确定只有单肺移植是高风险的预测因素。
基于我们对10年间FEV1与死亡率密切关联的观察，我们建议FEV1作为死亡率的有效预测指标和早期干预研究中合适的替代终点。
