Background

Aspiration is a known risk-factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration – however they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs while others, like pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant.

Methods

Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to pre-existing markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after anti-reflux surgery was assessed in a third cohort of LTRs.

Results

PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Anti-reflux surgery was associated with reduced airway PGA4.

Conclusions

Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

中文翻译：

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气道胃蛋白酶原 A4 通过微抽吸识别肺移植受者并预测慢性肺同种异体移植功能障碍

背景

误吸是肺移植后不良后果的已知危险因素。气道胆汁酸是误吸的金标准生物标志物，但它们会释放到十二指肠中，可能反映并发的胃肠动力障碍。先前调查气道胃蛋白酶总量的研究发现其与肺移植后不良后果的关系存在矛盾。这些研究测量了气道中的总胃蛋白酶和胃蛋白酶原。某些胃蛋白酶原在肺部组成型表达，而另一些胃蛋白酶原，如胃蛋白酶原 A4 (PGA4)，则不然。我们试图评估测量气道 PGA4 作为肺移植受者 (LTR) 移植后早期不良结果的误吸生物标志物和预测因子的效用。

方法

将PGA4的表达与肺组织中其他胃蛋白酶原的表达进行比较。在大气道支气管冲洗液中测量总胃蛋白酶和 PGA4，并与预先存在的误吸标记物进行比较。两个独立的 LTR 队列用于评估气道 PGA4 与慢性肺同种异体移植功能障碍 (CLAD) 之间的关系。在第三组 LTR 中评估了抗反流手术后气道 PGA4 的变化。

结果

PGA4在健康人的胃中表达，但在肺中不表达。气道 PGA4（而非总胃蛋白酶）与误吸相关。在两个独立的 LTR 队列中，气道 PGA4 与 CLAD 风险增加相关。抗反流手术与气道 PGA4 减少相关。

结论

气道 PGA4 是预测 LTR 中 CLAD 的吸入标志物。在监测支气管镜检查中测量 PGA4 有助于对高风险 LTR 进行分类，以进行抗反流手术。