Data_Sheet_1_Plasmalogens Mediate the Effect of Age on Bronchodilator Response in Individuals With Asthma.docx (16.01 kB)

Data_Sheet_1_Plasmalogens Mediate the Effect of Age on Bronchodilator Response in Individuals With Asthma.docx

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posted on 14.02.2020 by Joanne E. Sordillo, Sharon M. Lutz, Rachel S. Kelly, Michael J. McGeachie, Amber Dahlin, Kelan Tantisira, Clary Clish, Jessica Lasky-Su, Ann Chen Wu

Background: 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.

Methods: 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.

Results: There was a significant indirect effect of age on BDR through 4 plasmalogens (C36:1 PC and related metabolites) (Indirect Effect Beta = −0.001, p = 0.006).

Conclusions: 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.

Trial Registration: This work uses data from the previous clinical trial of asthma, the Childhood Asthma Management Program (CAMP), registered at ClinicalTrials.gov, # NCT00000575.

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