Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life.
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Phelan Kieran J, Roskin Krishna M, Burkle Jeffrey W, Chang Wan-Chi, Martin Lisa J, Biagini Jocelyn M, Satish Latha, Haslam David B, Spagna Daniel, Jenkins Seth, Parmar Elsie, Bacharier Leonard B, Gebretsadik Tebeb, Gill Michelle, Gold Diane R, Jackson Daniel J, Johnson Christine C, Lynch Susan V, McCauley Kathryn E, McKennan Chris G, Miller Rachel, Ober Carole, Ownby Dennis R, Ryan Patrick H, Schoettler Nathan, Singh Sweta, Visness Cynthia M, Altman Matthew C, Gern James E, Khurana Hershey Gurjit K, Environmental Influences on Child Health Outcomes–Children’s Respiratory and Environmental Workgroup
Аннотация
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.