Frick Anna E, Verleden Stijn E, Ordies Sofie, Sacreas Annelore, Vos Robin, Verleden Geert M, Vanaudenaerde Bart M, Claes Sandra, Schols Dominique, Van Raemdonck Dirk E, Neyrinck Arne P
Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
Leuven Lung Transplant Unit, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), KU Leuven, Leuven, Belgium.
Eur J Cardiothorac Surg. 2020 Aug 1;58(2):379-388. doi: 10.1093/ejcts/ezaa043.
Primary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage.
All double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0-1 to 2-3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: 'mild' PGD (grade 0-1) and 'severe' PGD (grades 2-3).
Significant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P < 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P < 0.0001; increased intensive care unit stay; P = 0.012 and P < 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups.
Expression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.
原发性移植肺功能障碍（PGD）仍然是移植后的主要并发症，且与发病率和死亡率增加相关。引发PGD的机制尚不完全清楚，但炎症起着核心作用。我们研究了PGD与术后即刻支气管肺泡灌洗中存在的炎症蛋白之间的关联。
2002年至2018年在本机构接受双肺移植的所有受者均纳入本研究。我们回顾性选择了80例连续的肺移植受者，其PGD分级不同（PGD 0 - 1至2 - 3级各20例）。在肺移植供体主动脉阻断后24小时内进行的支气管肺泡灌洗中，通过酶联免疫吸附测定（ELISA）评估30种细胞因子、趋化因子和生长因子的浓度，并将其与供体和受体的人口统计学特征及预后相关联。为进行分析，定义了2组：“轻度”PGD（0 - 1级）和“重度”PGD（2 - 3级）。
在8种生物标志物[白细胞介素（IL）-6、IL-10、IL-13、嗜酸性粒细胞趋化因子、粒细胞集落刺激因子、干扰素γ、巨噬细胞炎性蛋白1α、表面活性蛋白D（SP-D）]中发现轻度和重度PGD之间存在显著差异（P < 0.05）。IL-10和IL-13升高，但其他蛋白均未与短期预后相关（拔管时间延长；P = 0.005和P < 0.0001；重症监护病房停留时间延长；P = 0.012和P < 0.0001；以及住院时间；P = 0.041和P = 0.002）。两组之间供体和受体特征无显著差异。
重度与轻度PGD的肺移植受者支气管肺泡灌洗液中关键炎症介质的表达谱存在显著差异，并与临床结局变量相关。进一步的研究应聚焦于导致PGD的早期机制。
