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

Frontiers in Medicine

article

Joanne E. Sordillo¹  Sharon M. Lutz¹  Rachel S. Kelly²  Michael J. McGeachie²  Amber Dahlin²  Kelan Tantisira²  Clary Clish³  Jessica Lasky-Su²  Ann Chen Wu¹ 

[1] PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, United States;Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, United States;The Broad Institute, United States

关键词: bronchodilator response (BDR);    metabolites;    age;    interaction;    plasmalogen;   

DOI  :  10.3389/fmed.2020.00038

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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 , # {"type":"clinical-trial","attrs":{"text":"NCT00000575","term_id":"NCT00000575"}} NCT00000575 .

【 授权许可】

CC BY