Scaravilli Vittorio, Turconi Gloria, Colombo Sebastiano Maria, Guzzardella Amedeo, Bosone Marco, Zanella Alberto, Bos Lieuwe, Grasselli Giacomo
Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
ERJ Open Res. 2024 Aug 5;10(4). doi: 10.1183/23120541.00121-2024. eCollection 2024 Jul.
Lung transplantation (LUTX) is often complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping.
Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following International Society for Heart and Lung Transplantation (ISHLT) guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases.
Among the 1050 papers screened, 25 prospective observational studies were included, with only nine conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44-119)). Most (n=21) compared PGD grade 3 to less severe PGD, but only four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve analysis, yielding a median value of 0.58 (0.51-0.78) in 406 patients (276 double LUTX).
Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms and advanced statistical approaches are essential.
肺移植（LUTX）常并发原发性移植肺功能障碍（PGD）。血浆生物标志物在PGD表型分析和靶向治疗方面具有潜力。本范围综述旨在收集现有文献以寻找用于PGD表型分析的血清生物标志物。
按照JBI和PRISMA指南，我们进行了一项系统综述，在MEDLINE、Web of Science、EMBASE和Cochrane图书馆中检索报告再灌注72小时内测量的血清生物标志物与PGD之间关联的论文，遵循国际心肺移植学会（ISHLT）指南。我们提取了研究细节、患者人口统计学信息、PGD定义和时间、生物标志物浓度及其在识别PGD病例中的表现。
在筛选的1050篇论文中，纳入了25项前瞻性观察性研究，其中近十年仅进行了9项。这些论文包括1793例独特的成年患者（1195例双肺移植，研究规模中位数为100（四分位间距44 - 119））。大多数（n = 21）将3级PGD与较轻的PGD进行比较，但只有4项符合2016年PGD定义。酶联免疫吸附测定法和多重微珠阵列技术分别在23篇和2篇论文中使用。总共鉴定出26种候选生物标志物，包括13种炎症标志物、3种内皮激活标志物、3种上皮损伤标志物、3种细胞损伤标志物和2种凝血调节异常标志物。仅5种生物标志物（sRAGE、ICAM - 1、PAI - 1、SP - D、FSTL - 1）进行了受试者操作特征曲线下面积分析，在406例患者（276例双肺移植）中得出的中位数为0.58（0.51 - 0.78）。
几种生物标志物在未来旨在进行肺移植后PGD表型分析的研究中显示出前景。为了揭示现有的重大知识差距，纳入更新诊断标准、现代平台和先进统计方法的进一步国际前瞻性研究至关重要。
