Extracellular Vesicle-mediated Inflammatory Response in COPD is Negatively Enriched by High-intensity Exercise

<bold>Introduction</bold> Pulmonary rehabilitation is the most effective therapy in COPD. A putative mediator of these benefits is inter-cellular communication via extracellular vesicles (EVs). <bold>Aim</bold> To investigate whether EV protein cargos are enriched by exercise, and whether this enrichment is moderated by COPD or age. <bold>Methods:</bold> Eight COPD patients (FEV1 65±16%predicted), 10 age-matched (O) and 10 young (Y) controls performed high-intensity interval cycling (10x [1-min 120% peak ramp-incremental work rate, 2-min recovery]). Body composition was measured by DXA. Serum EVs were isolated at baseline (BL), end-exercise (EE), after 30min and 2hrs of rest. Differential protein abundance (using LC-LC/MS) and biological pathway enrichment were measured in EVs (adj.p<0.05). <bold>Results:</bold> Principal components of EV protein cargo revealed associations (p<0.05) with lean mass (r=0.28), % fat mass (r=0.33) and sex (r=-0.34), which were used as covariates. Acute exercise differentially enriched EV cargo at EE compared to BL (24 proteins in Y; 4 in O; 3 in COPD), which increased across 2hr recovery (32 in Y; 11 in O; 22 in COPD). Sixty-five biological processes were positively enriched in O vs. Y, including “innate immune response” and “B cell mediated immunity” at BL, but switched negative during recovery. Before exercise, these processes were among 75 that were positively enriched in COPD vs. O, and 16 of these, including complement system and “inflammatory response”, became negatively enriched during recovery. <bold>Conclusion</bold> Acute exercise differentially enriched EV protein cargo in all groups. Enrichment of complement and inflammatory response in EVs at baseline in COPD was negatively moderated by exercise.