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Published on: August 7, 2017
Deep multiomic profiling reveals molecular signatures that underpin preschool wheeze and asthma
Matthew Macowan1, Céline Pattaroni1, Katie Bonner2
1Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia.
Insights
Childhood wheeze transitions to asthma through distinct multiomic pathways. Preschool wheeze involves inflammation, while asthma progression shows airway epithelial and microbiome changes, guiding targeted therapies.
Area of Science:
- Pediatric respiratory medicine
- Multiomics research
- Immunology
Background:
- Childhood wheeze affects over 50% of children by age 6.
- The progression from wheeze to asthma is not fully understood.
Purpose of the Study:
- Investigate the transition from preschool wheeze to asthma.
- Utilize multiomic profiling to uncover underlying mechanisms.
Main Methods:
- Integrative multiomic factor analysis of host/bacterial (meta)transcriptomics, metagenomics, metabolomics, and lipidomics.
- Data from bronchial brush and bronchoalveolar lavage samples of children aged 1-17 years.
- Unsupervised, group-agnostic approach.
Main Results:
- Identified two key multiomic factors: one for preschool wheeze and one for the wheeze-to-asthma trajectory.
- Preschool wheeze linked to type 1-immune signatures and specific lipids/metabolites.
- Asthma progression associated with airway epithelial gene expression, type 2-immune responses, and increased Haemophilus influenzae.
Conclusions:
- Preschool wheeze exhibits an inflammation-related phenotype.
- Asthma progression is characterized by airway epithelial changes and microbiome alterations.
- Findings offer insights into differential mechanisms and potential therapeutic targets for 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.
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