婴幼儿毛细支气管炎的鼻咽真菌亚型与疾病严重程度风险。

Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity risk.

机构信息

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

EBioMedicine. 2023 Sep;95:104742. doi: 10.1016/j.ebiom.2023.104742. Epub 2023 Aug 1.

DOI:10.1016/j.ebiom.2023.104742

PMID:37536062

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10415709/

Abstract

BACKGROUND

Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics.

METHODS

In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data.

RESULTS

In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungivirus, B) fungivirus, C) fungivirus, D) fungivirus mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05).

INTERPRETATION

In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics.

FUNDING

This study was supported by the National Institutes of Health.

摘要

背景

细支气管炎是婴儿住院的主要原因。最近的研究表明，细支气管炎存在异质性，以及气道病毒和细菌与细支气管炎严重程度的关系。然而，对于真菌的病理生物学作用知之甚少。我们旨在通过整合真菌和病毒数据来确定细支气管炎的真菌型，并确定它们与细支气管炎严重程度和生物学特征的关系。

方法

在一项针对 398 名（年龄<1 岁，男性占 59%）因细支气管炎住院的婴儿的多中心前瞻性队列研究中，我们通过整合住院时鼻咽真菌（在 RNA 测序数据中检测到）和病毒数据（呼吸道合胞病毒[RSV]、鼻病毒[RV]）应用聚类方法来确定真菌型。我们通过鼻咽宏转录组和转录组数据检查它们与细支气管炎严重程度（由正压通气[PPV]使用定义）和生物学特征的关系。

结果

在因细支气管炎住院的婴儿中，我们确定了四种真菌型：A）病毒-真菌，B）病毒-真菌，C）病毒-真菌，D）病毒-真菌真菌型。与真菌型 A 婴儿（最大的亚型，n=211）相比，真菌型 C 婴儿（n=85）使用 PPV 的风险显著降低（7%对 1%，调整后的优势比，0.21；95%置信区间，0.02-0.90；p=0.033），而真菌型 B 或 D 使用 PPV 的风险无显著差异。在宏转录组和转录组数据中，真菌型 C 具有相似的细菌组成和微生物功能，但失调的途径（例如，Fcγ受体介导的吞噬途径和趋化因子信号通路；FDR<0.05）。