Division of Pulmonary, Allergy, and Critical Care, Department of Medicine.
Department of Epidemiology, Biostatistics, and Informatics.
Am J Respir Crit Care Med. 2022 Dec 15;206(12):1508-1521. doi: 10.1164/rccm.202112-2786OC.
Primary graft dysfunction (PGD) is the principal cause of early morbidity and mortality after lung transplantation. The lung microbiome has been implicated in later transplantation outcomes but has not been investigated in PGD. To define the peritransplant bacterial lung microbiome and relationship to host response and PGD. This was a single-center prospective cohort study. Airway lavage samples from donor lungs before organ procurement and recipient allografts immediately after implantation underwent bacterial 16S ribosomal ribonucleic acid gene sequencing. Recipient allograft samples were analyzed for cytokines by multiplex array and pepsin by ELISA. We enrolled 139 transplant subjects and obtained donor lung ( = 109) and recipient allograft ( = 136) samples. Severe PGD (persistent grade 3) developed in 15 subjects over the first 72 hours, and 40 remained without PGD (persistent grade 0). The microbiome of donor lungs differed from healthy lungs, and recipient allograft microbiomes differed from donor lungs. Development of severe PGD was associated with enrichment in the immediate postimplantation lung of oropharyngeal anaerobic taxa, particularly . Elevated pepsin, a gastric biomarker, and a hyperinflammatory cytokine profile were present in recipient allografts in severe PGD and strongly correlated with microbiome composition. Together, immediate postimplantation allograft / ratio, pepsin, and indicator cytokines were associated with development of severe PGD during the 72-hour post-transplantation period (area under the curve = 0.81). Lung allografts that develop PGD have a microbiome enriched in anaerobic oropharyngeal taxa, elevated gastric pepsin, and hyperinflammatory phenotype. These findings suggest a possible role for peritransplant aspiration in PGD, a potentially actionable mechanism that warrants further investigation.
原发性移植物功能障碍（PGD）是肺移植后早期发病率和死亡率的主要原因。肺部微生物组与后期移植结果有关，但尚未在 PGD 中进行研究。本研究旨在确定移植前肺部细菌微生物组及其与宿主反应和 PGD 的关系。这是一项单中心前瞻性队列研究。供体肺在器官获取前和受体同种异体肺在植入后立即进行气道灌洗样本，进行细菌 16S 核糖体核糖核酸基因测序。通过多重分析和 ELISA 分析受体同种异体移植物中的细胞因子和胃蛋白酶。我们共纳入 139 例移植患者，并获得了供体肺（n=109）和受体同种异体肺（n=136）样本。15 例患者在最初 72 小时内发生严重 PGD（持续 3 级），40 例患者无 PGD（持续 0 级）。供体肺的微生物组与健康肺不同，受体同种异体肺的微生物组与供体肺不同。严重 PGD 的发生与植入后即刻肺部口咽厌氧菌的富集有关，特别是 。在严重 PGD 中，胃生物标志物胃蛋白酶和促炎细胞因子谱升高，并且与微生物组组成强烈相关。在严重 PGD 中，植入后即刻同种异体移植物/比值、胃蛋白酶和指示细胞因子与移植后 72 小时内严重 PGD 的发生相关（曲线下面积=0.81）。发生 PGD 的肺同种异体移植物中富含口咽厌氧菌、胃蛋白酶升高和促炎表型。这些发现表明移植前吸入可能在 PGD 中起作用，这是一种潜在的可操作机制，值得进一步研究。
