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

BACKGROUND: 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 because it may provide an opportunity for early intervention. Therefore, we sought to analyse 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 an asthma diagnosis by age 6 years in a subset from the 35th Multicenter Airway Research Collaboration. We profiled nasal airway metabolome at age 6 years. Using a weighted gene co-expression network analysis approach, we identified metabolite modules. We also examined how metabolite modules and their constituent individual metabolites associate with lung function. RESULTS: This study included 116 children with an asthma diagnosis by age 6 years and available nasal airway samples. We identified seven distinct metabolite modules in the metabolome data. The peptide and amino acid derivatives module was significantly correlated with bronchodilator response at age 6 years (false discovery rate (FDR)=0.040). Three modules (peptide and amino acid derivatives; urea cycle, aromatic and branched-chain; and N-acetylated amino acid modules) were significantly correlated with forced vital capacity (FDR=0.048). Three metabolites from the peptide and amino acid derivatives module were significantly associated with bronchodilator response: 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) and pyridoxate (OR 3.81, 95% CI 1.13-4.40, FDR=0.048). We found that 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.