Early-Life Wheeze Trajectories are Associated with Distinct Asthma Transcriptomes Later in Life: A Gene Expression Analysis of the ECHO-CREW Birth Cohorts
Recommended Citation
Phelan K, Roskin K, Burkle J, Chang W, Martin L, Biagini J, Satish L, Haslam D, Spagna D, Jenkins S, Parmar E, Bacharier L, Gebretsadik T, Gill M, Gold D, Jackson D, Johnson CC, Lynch S, McCauley K, McKennan C, Miller R, Ober C, Ownby D, Ryan P, Schoettler N, Singh S, Visness C, Altman M, Gern J, Hershey G. Early-Life Wheeze Trajectories are Associated with Distinct Asthma Transcriptomes Later in Life: A Gene Expression Analysis of the ECHO-CREW Birth Cohorts. J Allergy Clin Immunol 2025; 155(2):AB270.
Document Type
Conference Proceeding
Publication Date
2-1-2025
Publication Title
J Allergy Clin Immunol
Keywords
Allergy, Immunology
Abstract
Rationale: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later life asthma development. Methods: The Children’s Respiratory Environmental Workgroup (CREW) 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 utilized to associate gene expression patterns and current asthma with early-life wheeze trajectories. Results: We investigated 743 participants (mean [SD] age 17 [5.1] years, 360 [48.5%] male). Four patterns of early life wheeze were identified: infrequent, transient, late-onset, persistent. Early-life persistent wheeze was associated with gene expression modules of type 2 inflammation (FC = 1.46, 95%CI 1.24-1.73, FDR < 0.001), metabolic dysregulation (FC = 1.32, 95%CI 1.16 – 1.50, FDR < 0.001), and epithelial development (FC = 1.18, 95%CI1.08 – 1.29, FDR = 0.001), 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 (FC = 1.58, 95% CI 1.27 – 2.09, FDR = 0.005) and ciliated epithelial function (FC = 1.59, 95% CI 1.20 - 2.10, FDR = 0.005) compared to those without asthma. Conclusions: Early-life longitudinal wheeze trajectories are associated with specific asthma transcriptomes later in life. These data suggest early-life asthma prevention strategies may be most beneficial when tailored to the specific wheeze pattern.
Volume
155
Issue
2
First Page
AB270
