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

TITLE=Plasmalogens Mediate the Effect of Age on Bronchodilator Response in Individuals With Asthma

JOURNAL=Frontiers in Medicine

VOLUME=Volume 7 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.00038

DOI=10.3389/fmed.2020.00038

ISSN=2296-858X

ABSTRACT=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 approximately 0.3 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 to 29.5 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.