Prognosis and Risks for Probable Chronic Lung Allograft Dysfunction: A Prospective Multicenter Study.

IF 19.3 1区 医学 Q1 CRITICAL CARE MEDICINE American journal of respiratory and critical care medicine Pub Date : 2024-10-29 DOI:10.1164/rccm.202403-0568OC
Jamie L Todd, S Sam Weigt, Megan L Neely, Maria V Grau-Sepulveda, Kristen Mason, Michelle L Sever, Karen Kesler, Jerry Kirchner, Courtney W Frankel, Tereza Martinu, Michael Y Shino, Annette M Jackson, Elizabeth N Pavlisko, Nikki Williams, Mark A Robien, Lianne G Singer, Marie Budev, Wayne Tsuang, Pali D Shah, John M Reynolds, Laurie D Snyder, John A Belperio, Scott M Palmer
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Abstract

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: 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 5 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 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 HR 4.38, p<0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and specifically late presence (>90 days 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.

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可能的慢性肺移植功能障碍的预后和风险:一项前瞻性多中心研究
理由慢性肺移植功能障碍(CLAD)阻碍了肺移植的成功。2019 年的一项共识完善了 CLAD 诊断,根据肺功能的持续下降引入了可能或明确的 CLAD。可能的 CLAD 的预后和风险仍不确定:在前瞻性多中心队列中确定可能的 CLAD 的预后和临床风险:器官移植临床试验-20》纳入了5个中心的745名符合CLAD条件的成年肺部受者,并采用严格的方法对可能的CLAD进行前瞻性判定。使用将 CLAD 视为时间依赖协变量的 Cox 模型确定了可能的 CLAD 对移植物损失的影响。使用带 LASSO 惩罚的正则化 Cox 模型来评估供体或受体特征以及移植后事件的发生和发生时间作为可能的 CLAD 风险。对明确的CLAD也进行了类似的分析:29.7%的患者在移植后3年发生了可能的CLAD,并显著增加了移植物丢失的风险(未经调整的HR为4.38,p为移植后90天),供体特异性抗体、急性排斥反应、急性肺损伤或组织性肺炎对可能的CLAD风险的独立信息贡献最大。明确的CLAD风险相似:结论:可能的CLAD可识别移植物丢失的高风险患者,支持前瞻性地识别这种情况,以尽早启动CLAD定向干预。需要采取更有效的策略来预防移植后巨细胞病毒、抑制异种特异性免疫和减少组织损伤,以减少可能的 CLAD 并提高肺部受体的存活率。
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来源期刊
CiteScore
27.30
自引率
4.50%
发文量
1313
审稿时长
3-6 weeks
期刊介绍: The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences. A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.
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