Background: The obese-asthma phenotype can be difficult-to-treat and severe in children; however, underlying mechanisms are unknown.

Objective: Explore if gene expression patterns in children with mild/moderate vs severe (MMA vs SA) asthma differ by age and sex-adjusted BMI z-scores (BMIz), and if these differentially expressed patterns have functional significance.

Methods: We performed a cross-sectional analysis of baseline clinical and blood transcriptome data from the U-BIOPRED cohort, including children aged 5-17 years with MMA (N=37) or SA (N=74). We ran gene-specific regression models for the outcome, asthma status (MMA vs SA), including age, sex, gene expression, BMIz, and a gene expression*BMIz interaction term. We then identified a list of top candidate genes (raw p<0.05) with differential expression by BMIz and assessed their functional significance using a pathway-centric approach.

Results: We identified 157 down- and 258 up-regulated differentially expressed genes by BMIz. Pathway enrichment in severe asthma showed down-regulation of purinergic receptor pathways in children with lower BMIz, while DNA damage pathways were up-regulated in the higher BMIz group (Fig. 1).

Conclusion: We found differential gene expression and implicated pathways for children with lower vs higher BMIz by asthma severity group, which could provide possible mechanisms underlying the obese-asthma phenotype. Larger studies are needed to validate this.