C97-01 5-year Follow-up Reveals Faster Decline in Muscle Oxidative Capacity Than Pulmonary Function in COPD

Abstract Rationale Muscle oxidative capacity is associated with exercise performance, quality-of-life and mortality. We previously reported that severe COPD patients have a 34-37% lower muscle oxidative capacity compared to peers with normal spirometry and similar smoking history; age and FEV1 were significantly associated with this difference. The longitudinal rate of decline in muscle oxidative capacity in COPD is unknown. In this study, we aimed to determine the rate of decline in muscle oxidative capacity in people with COPD. We hypothesized that longitudinal decline in muscle oxidative capacity is related to decline in FEV1. Methods The Muscle Health Study is an ancillary of COPDGene conducted between 2014-2016 (Phase 2 COPDGene). Of 215 Muscle Health Study baseline participants who had spirometry and muscle oxidative capacity measurements (i.e., primary outcome cohort), 107 had COPD. These participants were invited for follow-up after 5-years (Phase 3 COPDGene). Assessments at baseline and follow-up included: gastrocnemius muscle oxidative capacity from the O2 consumption recovery rate constant (k, index of muscle oxidative capacity) using near-infrared spectroscopy, spirometry, smoking status, smoking history (pack-years), among other variables. Annualized rate of decline was calculated from the change of each variable between baseline and follow-up. Results Mean follow-up was 5.3±0.9 years. Muscle k was available at follow-up for 41(38%) people (GOLD 1/2/3-4 n = 9/20/12; 18(44%) women; age 73±9 yrs; BMI 26±5 kg/m2). Missing k was due to failed NIRS test (n = 1), participants declining to continue, moved out of local area, or lost to follow up (n = 33), or death (n = 32). There was no significant difference in ATS pack-years (p = 0.438) across GOLD stages. GOLD 1 were older than other groups (p = 0.016) (Table). Annualized rates of decline in FEV1 was -49±65 mL.year-1, and in k was -0.06±0.07 min-1.year-1, and neither differed among GOLD group (p 0.259). There was no association between 5-year decline in FEV1 and k (r = 0.06; p = 0.365). 5-year decline in k (-23±23%) tended to be greater than that of FEV1 (-15±19%) (p = 0.094). Conclusions Although we previously found a cross-sectional association between muscle oxidative capacity and FEV1 at baseline, the decline in these two variables over 5-years was not associated. Analysis of 5-year follow-up in COPD revealed a rapid decline in muscle oxidative capacity, that was not different among GOLD groups and tended to be greater than the decline in pulmonary function. Further study is warranted to identify variables associated with the decline in muscle oxidative capacity in COPD. Support NHLBI R01HL151452, U01HL089856, U01HL089897. NIH contract 75N92023D00011. This abstract is funded by: NHLBI R01HL151452. U01HL089856. U01HL089897. NIH contract 75N92023D00011.