Macowan Matthew, Pattaroni Céline, Bonner Katie, Chatzis Roxanne, Daunt Carmel, Gore Mindy, Custovic Adnan, Shields Michael D, Power Ultan F, Grigg Jonathan, Roberts Graham, Ghazal Peter, Schwarze Jürgen, Turner Steve, Bush Andrew, Saglani Sejal, Lloyd Clare M, Marsland Benjamin J
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia.
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia.
J Allergy Clin Immunol. 2025 Jan;155(1):94-106. doi: 10.1016/j.jaci.2024.08.017. Epub 2024 Aug 28.
Wheezing in childhood is prevalent, with over one-half of all children experiencing at least 1 episode by age 6. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear.
This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling.
Unsupervised, group-agnostic integrative multiomic factor analysis was performed using host/bacterial (meta)transcriptomic and bacterial shotgun metagenomic datasets from bronchial brush samples paired with metabolomic/lipidomic data from bronchoalveolar lavage samples acquired from children 1-17 years old.
Two multiomic factors were identified: one characterizing preschool-aged recurrent wheeze and another capturing an inferred trajectory from health to wheeze and school-aged asthma. Recurrent wheeze was driven by type 1-immune signatures, coupled with upregulation of immune-related and neutrophil-associated lipids and metabolites. Comparatively, progression toward asthma from ages 1 to 18 was dominated by changes related to airway epithelial cell gene expression, type 2-immune responses, and constituents of the airway microbiome, such as increased Haemophilus influenzae.
These factors highlighted distinctions between an inflammation-related phenotype in preschool wheeze, and the predominance of airway epithelial-related changes linked with the inferred trajectory toward asthma. These findings provide insights into the differential mechanisms driving the progression from wheeze to asthma and may inform targeted therapeutic strategies.
儿童喘息很常见，超过一半的儿童在6岁前至少经历过1次喘息发作。喘息的病理生理学，尤其是为什么有些儿童会发展为哮喘而有些儿童不会，仍不清楚。
本研究通过使用多组学分析来研究从学龄前喘息到哮喘的转变，以填补这一知识空白。
使用来自1至17岁儿童支气管刷样本的宿主/细菌（元）转录组学和细菌鸟枪法宏基因组学数据集，以及来自支气管肺泡灌洗样本的代谢组学/脂质组学数据，进行无监督、与组无关的综合多组学因素分析。
确定了两个多组学因素：一个表征学龄前复发性喘息，另一个捕捉从健康到喘息和学龄期哮喘的推断轨迹。复发性喘息由1型免疫特征驱动，同时免疫相关和中性粒细胞相关的脂质和代谢物上调。相比之下，1至18岁向哮喘的进展主要由与气道上皮细胞基因表达、2型免疫反应以及气道微生物群成分相关的变化主导，如流感嗜血杆菌增加。
这些因素突出了学龄前喘息中与炎症相关的表型，以及与推断的哮喘轨迹相关的气道上皮相关变化的优势之间的区别。这些发现为驱动从喘息到哮喘进展的不同机制提供了见解，并可能为靶向治疗策略提供依据。
