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微生物性哮喘:一项针对重度学龄前喘息幼儿呼吸道微生物群的前瞻性研究,以更好地了解他们未来的呼吸道状况。

Microbiosthma: a prospective study following respiratory microbiota in young children with severe preschool wheezing to better understand their respiratory future.

作者信息

Petat Hortense, Hassel Chervin, Michel Alice, Charbonnier Camille, Plantier Jean-Christophe, Marguet Christophe

机构信息

Department of Paediatrics and Adolescent Medecine, Univ Rouen Normandie, Dynamicure INSERM UMR 1311, CHU Rouen, Rouen, F-76000, France.

Department of Virology, Univ Rouen Normandie, Dynamicure INSERM UMR 1311, CHU Rouen, Rouen, F-76000, France.

出版信息

BMC Pulm Med. 2025 Jul 16;25(1):342. doi: 10.1186/s12890-025-03812-9.

DOI:10.1186/s12890-025-03812-9
PMID:40670979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12269099/
Abstract

Preschool wheeze is a frequent infant disease, which can be severe. A continuous infection/inflammation loop at the heart of the pathophysiology is described, which could lead to a dysbiosis. In this context, the main objective of the "Microbiosthma" project is to assess whether dysbiosis of the upper and lower respiratory microbiomes could constitute a physiopathological biomarker of severe preschool wheeze in young children. This project will be divided into three parts: (i) determine the basal composition of the respiratory microbiomes (ii) monitor these microbiomes longitudinally over the course of the severe preschool wheeze, with a one-year follow-up, and (iii) assess the role of immune cell activation and inflammation in the pathogenesis of severe preschool wheeze. The "Microbiosthma" project is a bicentric, prospective study. Bronchial fibroscopy is performed on children aged < 24 months with severe preschool wheeze. One hundred infant nasopharyngeal, bronchoalveolar lavage and sputum samples will be collected over 2 years, and patients will be followed for 12 months. This collection started in September 2023. Microbiome analyses will use a metatranscriptomic approach and immunological analyses for all samples collected. For immunological analysis, key inflammatory cytokines in bronchoalveolar lavage samples will be measured. Host sequencing data obtained by NGS sequencing will be analysed for transcriptomic signatures of inflammatory profiles. The aim of the "Microbiosthma" project is to understand the respiratory microbiome of the physiopathological process involved in the development of severe preschool wheeze. This original project will therefore identify the nature of potential dysbiosis, the relationship between different respiratory microbiomes and the potential role of the immune system in this pathogenesis. The registration number is NCT06044051 (CCP Nord-Ouest, 07/11/2023).

摘要

学龄前喘息是一种常见的婴幼儿疾病,可能较为严重。文中描述了其病理生理学核心存在的持续感染/炎症循环,这可能导致生态失调。在此背景下,“微生物哮喘”项目的主要目标是评估上下呼吸道微生物群的生态失调是否可能构成幼儿严重学龄前喘息的生理病理生物标志物。该项目将分为三个部分:(i)确定呼吸道微生物群的基础组成;(ii)在严重学龄前喘息病程中对这些微生物群进行纵向监测,随访一年;(iii)评估免疫细胞激活和炎症在严重学龄前喘息发病机制中的作用。“微生物哮喘”项目是一项双中心前瞻性研究。对年龄小于24个月的严重学龄前喘息儿童进行支气管纤维镜检查。将在2年内收集100份婴幼儿鼻咽、支气管肺泡灌洗和痰液样本,并对患者进行12个月的随访。该样本收集于2023年9月开始。微生物组分析将采用宏转录组学方法,并对所有收集的样本进行免疫学分析。对于免疫学分析,将测量支气管肺泡灌洗样本中的关键炎症细胞因子。将分析通过NGS测序获得的宿主测序数据,以获取炎症谱的转录组特征。“微生物哮喘”项目的目的是了解严重学龄前喘息发展过程中涉及的生理病理过程的呼吸道微生物群。因此,这个原创项目将确定潜在生态失调的性质、不同呼吸道微生物群之间的关系以及免疫系统在这一发病机制中的潜在作用。注册号为NCT06044051(法国西北部临床试验中心,2023年11月7日)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ca/12269099/00995398e320/12890_2025_3812_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ca/12269099/a6bdcea5b352/12890_2025_3812_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ca/12269099/00995398e320/12890_2025_3812_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ca/12269099/a6bdcea5b352/12890_2025_3812_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ca/12269099/00995398e320/12890_2025_3812_Fig2_HTML.jpg

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本文引用的文献

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The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial.气道微生物群调节阿奇霉素治疗学龄前儿童反复哮喘样症状发作的效果:一项随机临床试验。
Am J Respir Crit Care Med. 2021 Jul 15;204(2):149-158. doi: 10.1164/rccm.202008-3226OC.
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The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury.在儿科造血干细胞移植前的肺部宏转录组可识别移植后肺部损伤。
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Burden of preschool wheeze and progression to asthma in the UK: Population-based cohort 2007 to 2017.
英国学龄前喘息负担及向哮喘进展:2007 年至 2017 年基于人群的队列研究。
J Allergy Clin Immunol. 2021 May;147(5):1949-1958. doi: 10.1016/j.jaci.2020.12.643. Epub 2021 Jan 13.
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Early Life Microbiota and Respiratory Tract Infections.早期生活微生物群与呼吸道感染。
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Optimizing a Metatranscriptomic Next-Generation Sequencing Protocol for Bronchoalveolar Lavage Diagnostics.
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Clinical phenotypes in asthma during childhood.儿童哮喘的临床表型。
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[Increase in asthma prevalence among young children in France].[法国幼儿哮喘患病率上升]
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The Microbiome and the Respiratory Tract.微生物群与呼吸道
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