Asthma is known to display different phenotypes across the life-course, suggesting that age related changes are particularly relevant to understanding asthma pathogenesis and remission. We have previously demonstrated that a lung function phenotype associated with asthma, bronchodilator response, is reduced with age, at rate of 0.24 percent per year. In this study, we interrogated the serum metabolome, to determine whether circulating metabolites mediate age-related changes in bronchodilator response (BDR) for individuals with asthma. We used data on 295 participants from the follow-up phase of the CAMP clinical trial (age 12.2-25.9 years; mean BDR of 8%, standard deviation 7%). Using a counterfactual framework, we analyzed over 500 pareto-scaled metabolites using mediation analysis to identify indirect effects of age through potential metabolite mediators. There was a significant indirect effect of age on BDR through 4 plasmalogens (C36:1 PC and related metabolites) (Indirect Effect Beta = -0.001, = 0.006). Our findings suggest that plasmalogens may contribute to age-related asthma phenotypes, and may also serve as potential pharmacologic targets for enhancement of lung function in individuals with asthma. This work uses data from the previous clinical trial of asthma, the Childhood Asthma Management Program (CAMP), registered at ClinicalTrials.gov, # NCT00000575.
Front Med (Lausanne)
Plasmalogens Mediate the Effect of Age on Bronchodilator Response in Individuals With Asthma.