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肺移植术后微量误吸与胃肠功能障碍的管理:一篇叙述性综述

Management of microaspiration and gastrointestinal dysfunction after lung transplantation: A narrative review.

作者信息

Hage René, Steinack Carolin, Schuurmans Macé M

机构信息

Division of Pulmonology, University Hospital Zurich, 8091 Zurich, Switzerland.

Faculty of Medicine, University of Zurich, 8032 Zurich, Switzerland.

出版信息

JHLT Open. 2025 Aug 8;10:100363. doi: 10.1016/j.jhlto.2025.100363. eCollection 2025 Nov.

Abstract

BACKGROUND

Chronic Lung Allograft Dysfunction (CLAD) is the leading cause of late morbidity and mortality following lung transplantation. Increasing evidence implicates microaspiration, often secondary to gastroesophageal reflux disease (GERD) and gastrointestinal (GI) dysfunction, as a critical non-alloimmune driver of CLAD. However, its often silent presentation, diagnostic complexity, and heterogeneous management contribute to persistent knowledge and treatment gaps.

METHODS

This narrative review synthesizes recent literature on the pathophysiology, diagnosis, and clinical impact of microaspiration and GI dysfunction in lung transplant recipients. We focus on emerging biomarkers (e.g., conjugated bile acids and pepsinogen A4), diagnostic modalities, and both medical and surgical treatment strategies aimed at mitigating aspiration-induced graft injury.

KEY CONTENT AND FINDINGS

Microaspiration leads to epithelial damage, surfactant disruption, immune activation, and microbial dysbiosis, collectively promoting allograft dysfunction. Conjugated bile acids in large airway bronchial wash fluid and pepsinogen A4 have shown superior specificity as aspiration biomarkers compared to pepsin alone. Gastrointestinal disorders, such as GERD, gastroparesis, and esophageal dysmotility, frequently co-exist post-transplant and contribute to aspiration risk. Pharmacologic interventions provide limited benefit, while anti-reflux surgery significantly improves graft outcomes, particularly when performed early. Conservative measures such as head-of-bed elevation also reduce reflux burden and may complement therapeutic strategies.

CONCLUSIONS

Microaspiration is a modifiable and underrecognized contributor to allograft injury. Integration of aspiration biomarkers, early reflux evaluation, and personalized stepwise management, including surgical intervention when indicated, may improve long-term transplant outcomes. This review provides clinicians with a structured framework for diagnosis and management of microaspiration-related injury in lung transplantation.

摘要

背景

慢性肺移植功能障碍(CLAD)是肺移植术后晚期发病和死亡的主要原因。越来越多的证据表明,微误吸(通常继发于胃食管反流病(GERD)和胃肠(GI)功能障碍)是CLAD的关键非同种免疫驱动因素。然而,其通常隐匿的表现、诊断复杂性和多样化的管理导致了知识和治疗方面的持续差距。

方法

本叙述性综述综合了关于肺移植受者微误吸和胃肠功能障碍的病理生理学、诊断及临床影响的最新文献。我们重点关注新兴生物标志物(如结合胆汁酸和胃蛋白酶原A4)、诊断方法以及旨在减轻误吸所致移植损伤的药物和手术治疗策略。

关键内容与发现

微误吸会导致上皮损伤、表面活性剂破坏、免疫激活和微生物群落失调,共同促进移植功能障碍。与单独的胃蛋白酶相比,大气道支气管灌洗液中的结合胆汁酸和胃蛋白酶原A4作为误吸生物标志物具有更高的特异性。GERD、胃轻瘫和食管动力障碍等胃肠疾病在移植后经常并存,并增加误吸风险。药物干预的益处有限,而抗反流手术可显著改善移植结局,尤其是早期进行手术时。床头抬高之类的保守措施也可减轻反流负担,并可作为治疗策略的补充。

结论

微误吸是移植损伤中一个可改变但未得到充分认识的因素。整合误吸生物标志物、早期反流评估和个性化的逐步管理(包括在必要时进行手术干预)可能会改善长期移植结局。本综述为临床医生提供了一个用于诊断和管理肺移植中与微误吸相关损伤的结构化框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efae/12398909/3e1bdc6cf8c7/gr1.jpg

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