Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life
Recommended Citation
Phelan KJ, Roskin KM, Burkle JW, Chang WC, Martin LJ, Biagini JM, Satish L, Haslam DB, Spagna D, Jenkins S, Parmar E, Bacharier LB, Gebretsadik T, Gill M, Gold DR, Jackson DJ, Johnson CC, Lynch SV, McCauley KE, McKennan CG, Miller R, Ober C, Ownby DR, Ryan PH, Schoettler N, Singh S, Visness CM, Altman MC, Gern JE, and Khurana Hershey GK. Early-Life Wheeze Trajectories Are Associated with Distinct Asthma Transcriptomes Later in Life. J Allergy Clin Immunol 2025.
Document Type
Article
Publication Date
4-4-2025
Publication Title
The Journal of allergy and clinical immunology
Abstract
BACKGROUND: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.
OBJECTIVE: We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.
METHODS: The Children's Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing. Early-life wheeze trajectories were defined using latent class analysis of longitudinal early-life wheezing data. Weighted gene correlation network analysis was used to associate gene expression patterns and current asthma with early-life wheeze trajectories.
RESULTS: We investigated 743 children (mean age, 17 ± 5.1 years; 360 [48.5%] male). Four patterns of early-life wheeze were identified: infrequent, transient, late-onset, and persistent. Early-life transient wheeze was associated with gene expression patterns related to increased antiviral response, and late-onset wheeze was associated with decreased insulin signaling and glucose metabolism. Early-life persistent wheeze was associated with gene expression modules of type 2 inflammation and epithelial development, but these modules did not distinguish those with current asthma. Children who had persistent wheeze in early life and current asthma displayed a unique increase in expression of genes enriched for neuronal processes and ciliated epithelial function compared with those without asthma.
CONCLUSIONS: Early-life longitudinal wheeze trajectories are associated with specific asthma transcriptomes later in life. These data suggest that early-life asthma prevention strategies may be most beneficial when tailored to the specific wheeze pattern.
Medical Subject Headings
Humans; Asthma/genetics/immunology; Respiratory Sounds/genetics/immunology; Male; Female; Transcriptome; Adolescent; Child; Child; Preschool; Longitudinal Studies; Wheeze; asthma; pediatrics; transcriptomics
PubMed ID
40189159
ePublication
ePub ahead of print
Volume
156
Issue
3
First Page
640
Last Page
650
