Rationale: Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain. Objectives: We sought to determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort. Methods: Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at five centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with least absolute shrinkage and selection operator (LASSO) penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD. Measurements and Main Results: Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted hazard ratio = 4.38, P < 0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and, specifically, late presence (>90 d posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar. Conclusions: Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival. Clinical trial registered with www.clinicaltrials.gov (NCT02631720).

中文翻译：

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可能的慢性肺同种异体移植物功能障碍的预后和风险：一项前瞻性多中心研究。


理由： 慢性肺同种异体移植物功能障碍 （CLAD） 阻碍肺移植成功。2019 年共识改进了 CLAD 诊断，根据肺功能持续下降引入了可能或明确的 CLAD。可能的 CLAD 的结局和风险仍不确定。目的： 我们试图确定前瞻性多中心队列中可能 CLAD 的预后和临床风险。方法： 器官移植 20 临床试验包括 5 个中心的 745 名符合 CLAD 条件的成年肺受者，并应用严格的方法来前瞻性地判断可能的 CLAD。使用 Cox 模型确定可能的 CLAD 对移植物损失的影响，该模型将 CLAD 视为时间依赖性协变量。具有最小绝对收缩和选择运算符 （LASSO） 惩罚的正则化 Cox 模型用于评估供体或受体特征以及移植后事件的发生和时间作为可能的 CLAD 风险。对明确的 CLAD 进行了类似的分析。测量和主要结果： 移植后 3 年，29.7% 的患者可能发生 CLAD，并导致移植物丢失的风险显着增加 （未校正风险比 = 4.38，P < 0.001）。大多数疑似 CLAD 患者 （80%） 进展为明确的 CLAD。巨细胞病毒感染，特别是晚期存在 （移植后 >90 d） 供体特异性同种抗体、急性排斥反应、急性肺损伤或机化性肺炎，是关于可能的 CLAD 风险的最大独立信息。明确的 CLAD 风险相似。结论： 可能的 CLAD 识别出移植物丢失风险高的患者，支持前瞻性识别这种情况以早期开始 CLAD 定向干预。 需要更有效的策略来预防移植后巨细胞病毒、抑制同种异体免疫和减少组织损伤，以减少可能的 CLAD 并提高肺受者的存活率。在 www.clinicaltrials.gov 注册的临床试验 （NCT02631720）。