Association between nasal airway metabolome signatures and lung function at age 6 years among children with post-bronchiolitis asthma

Objective Post-bronchiolitis asthma is often associated with impaired lung function. Identifying biological mechanisms for lung function impairment in children with post-bronchiolitis asthma is important as it may provide an opportunity for early intervention. Therefore, we sought to analyze nasal airway metabolome signatures that are associated with lung function impairment in children with post-bronchiolitis asthma. Methods We performed a cross-sectional analysis of nasal airway metabolome and lung function in children with asthma diagnosis by age 6 years in a subset from the 35th Multicenter Airway Research Collaboration (MARC-35). We profiled nasal airway metabolome at age 6 years. Using a weighted gene co-expression network analysis (WGCNA) approach, we identified metabolite modules. We also examined the association of metabolite modules and their constituent individual metabolites with lung function. Results In this study, 116 children with an asthma diagnosis by age 6 years and nasal airway samples available were included. First, we identified seven distinct metabolite modules in the metabolome data. Of them, the green module was significantly correlated with BDR at age 6 years (false discovery rate [FDR]=0.040). Additionally, the green, turquoise, and yellow modules were significantly correlated with FVCpp (FDR=0.048). Second, three metabolites from the green module were significantly associated with BDR: palmitoyl-sphingomyelin (Odds ratio [OR] 1.62, 95% confidence interval [CI] 1.07–2.99, FDR=0.047); N-acetylthreonine (OR 1.63, 95% CI, 1.20–2.43, FDR=0.048); pyridoxine (OR 3.81, 95% CI 1.13–4.40, FDR=0.048). Third, 25 metabolic pathways were differentially-enriched (FDR<0.05)— e.g. , arginine biosynthesis and histidine metabolism. Conclusions The findings suggest that nasal airway metabolomic signatures may reflect pathogenetic mechanisms that underly lung function impairment in post-bronchiolitis asthma.