Severity of Lung Obstruction and Older Age, but Not Physical Activity, Predict Locomotor Muscle Oxidative Impairment in Copd

Background Low muscle oxidative capacity is an extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) with unclear etiology. We sought to determine clinical and behavioral features associated with muscle oxidative capacity in smokers with and without COPD and never smoker individuals. Methods 243 adults enrolled in the Muscle Health Study , an observational study ancillary to COPDGene. G astrocnemius oxidative capacity was measured by near-infrared spectroscopy from muscle oxygen uptake recovery rate constant ( k ). Physical activity by accelerometry (vector magnitude units, VMU/min). Pulmonary assessments included spirometry (FEV 1 %predicted), diffusing capacity (DL CO ), and quantitative chest computed tomography (CT). Eighty-seven variables related to COPD features were considered. Variables selected by univariate analysis of log-transformed k with p≤0.20, and filtered by machine learning, were entered into multivariable linear regression to determine association with k . Results 241(99%) participants were allocated to analysis. FEV 1 %predicted, DL CO , CT, pack-years, age and VMU/min were among 24 variables selected by univariate analysis. After machine learning filtering on 161(66%) cases with complete data, 11 variables were included in multivariable analysis. Only FEV 1 %predicted, age and race were significantly associated with k (R 2 =0.26). Model coefficients equate a 10% lower FEV 1 %predicted to a 4.4% lower k , or 10-years of aging to a 9.7% lower k . In 118 cases with CT available, FEV 1 %predicted and age remained associated with k (R 2 =0.24). Physical activity was not retained in any model. Conclusions Locomotor muscle oxidative capacity was positively associated with FEV 1 %predicted and negatively associated with age. Physical activity or radiographic COPD manifestations were not significantly associated with muscle oxidative impairment.