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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02999-4

摘要内容如下：

造血细胞移植（HCT）使用细胞毒性化疗和/或放疗，然后静脉输注干细胞来治疗恶性肿瘤、骨髓衰竭和先天性免疫、血红蛋白和代谢缺陷。肺损伤是该过程的已知并发症，部分是由于损伤（如感染、同种异体反应性炎症和细胞毒性）对肺微环境的破坏。微生物、免疫和呼吸道上皮如何相互作用导致肺损伤尚不确定，限制了预防和治疗策略的发展。在这里，我们使用278支气管肺泡灌洗液（BAL）样本来研究2014年至2022年期间在32家儿童医院接受HCT治疗的229名儿童患者的肺部微环境。通过利用配对微生物组和人类基因表达数据，我们确定了与住院死亡率相关的高风险BAL组成（P=0.007）。不利特征包括细菌过度生长伴中性粒细胞炎症，微生物组收缩伴上皮纤维增生，严重共生耗竭伴病毒和葡萄球菌富集，淋巴细胞活化和细胞损伤，并在荷兰的独立队列中重复（p=0.02 2）。此外，还发现了一系列以前隐匿的病原体，以及抗生素暴露、共生细菌耗竭与病毒和真菌富集之间的密切联系。总之，这些肺-免疫系统-微生物相互作用阐明了接受HCT的儿科患者致死性肺损伤的重要驱动因素。需要进一步研究，以确定如何对异质性肺部微环境进行个性化解释，以改善儿科HCT结果。

英文原文如下：

Abstracts

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

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