Deep multiomic profiling reveals molecular signatures that underpin preschool wheeze and asthma.

Background: 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.
Objectives: This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling.
Methods: 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.
Results: 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.
Conclusions: 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.
Competing Interests: Disclosure statement The study is supported by a Wellcome Trust grant (108818), a L.E.W. Carty Charitable Fund awarded to C.P., funding from The Hospital Research Foundation Group (2022-SF-EOI-001) awarded to B.J.M. and C.P., and a National Health and Medical Research Council Senior Research Fellowship (1154344) awarded to B.J.M. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)