Berra Gregory, Huszti Ella, Levy Liran, Kawashima Mitsuaki, Fuchs Eyal, Renaud-Picard Benjamin, Riddell Peter, Dias Olivia, Rajagopala Srinivas, Ulahannan Ambilly, Ghany Rasheed, Singer Lianne Gail, Tikkanen Jussi, Martinu Tereza
Toronto Lung Transplant Program, Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
Biostatistics Research Unit, University Health Network, University of Toronto, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2022 May;41(5):599-607. doi: 10.1016/j.healun.2022.01.015. Epub 2022 Jan 23.
Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) is challenging, due to the native lung contribution to pulmonary function test (PFT). We aimed to assess the applicability and prognostic performance of International Society for Heart and Lung Transplantation (ISHLT) classification in SLTX.
In this retrospective study of adult, first, SLTX performed 2009-2017, patients with persistent drop in FEV1≥20% were assessed by 2 independent adjudicators to determine CLAD status and phenotype. Interobserver agreement (IOA) was calculated (Cohen's Kappa) for CLAD, phenotype and presence of RAS (resttrictive allograft syndrome)-like opacities (RLO). Association of CLAD phenotypes with time to death or retransplant (ReTx), adjusted for age at SLTX, sex, CMV mismatch and native lung condition, were assessed using Cox proportional hazards models.
Of 172 SLTX recipients, 92 experienced a persistent drop in FEV1>20%. Following adjudication, 67 were diagnosed with CLAD. We noted a moderate IOA for CLAD diagnosis (Kappa 0.69) and poor IOA for phenotype adjudication (Kappa 0.52). The final phenotype adjudication was 31 bronchiolitis obliterans syndrome (BOS) (46.3%), 13 RAS (19.4%), 2 mixed (3%), 2 Undefined (3%), and 19 remained Unclassified (28.3%). Using these adjudicated phenotypes, RAS was significantly associated with a higher risk of death/ReTx compared to other groups (HR 2.98, 95%CI [1.39-6.4]). The adjudication of RLO had the best IOA (Kappa 0.73). The presence of RLO was a strong predictor of death or ReTx (HR 2.37, 95%CI [1.2-4.5]), regardless of the final phenotype.
PFT interpretation is challenging in SLTX. A classification essentially relying on imaging, which harbored good IOA, obtained better prognostic performance than a classification using published physiological cut-offs.
由于单肺移植（SLTX）中自体肺对肺功能测试（PFT）有影响，对慢性肺移植功能障碍（CLAD）进行表型分析具有挑战性。我们旨在评估国际心肺移植学会（ISHLT）分类在单肺移植中的适用性和预后性能。
在这项对2009年至2017年进行的成人首次单肺移植的回顾性研究中，对第一秒用力呼气容积（FEV1）持续下降≥20%的患者由2名独立的判定者进行评估，以确定CLAD状态和表型。计算CLAD、表型以及是否存在限制性同种异体移植综合征（RAS）样混浊（RLO）的观察者间一致性（IOA）（Cohen's Kappa）。使用Cox比例风险模型评估CLAD表型与死亡或再次移植（ReTx）时间的关联，并对单肺移植时的年龄、性别、巨细胞病毒配型和自体肺状况进行校正。
在172名单肺移植受者中，92人出现FEV1持续下降>20%。判定后，67人被诊断为CLAD。我们注意到CLAD诊断的观察者间一致性中等（Kappa 0.69），表型判定的观察者间一致性较差（Kappa 0.52）。最终的表型判定为闭塞性细支气管炎综合征（BOS）31例（46.3%）、RAS 13例（19.4%）、混合性2例（3%）、未定义2例（3%），19例仍未分类（28.3%）。使用这些判定的表型，与其他组相比，RAS与更高的死亡/再次移植风险显著相关（风险比2.98，95%置信区间[1.39 - 6.4]）。RLO的判定具有最佳的观察者间一致性（Kappa 0.73）。无论最终表型如何，RLO的存在都是死亡或再次移植的强有力预测因素（风险比2.37，95%置信区间[1.2 - 4.5]）。
在单肺移植中，肺功能测试的解读具有挑战性。一种基本依赖影像学且观察者间一致性良好的分类方法，其预后性能优于使用已公布的生理学临界值的分类方法。
