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[Preprint]. 2025 Jan 29:2025.01.28.25321301.
doi: 10.1101/2025.01.28.25321301.

SEVERITY OF LUNG OBSTRUCTION AND OLDER AGE, BUT NOT PHYSICAL ACTIVITY, PREDICT LOCOMOTOR MUSCLE OXIDATIVE IMPAIRMENT IN COPD

Alessandra Adami  1 , Fenghai Duan  2 , Robert A Calmelat  3 , Zeyu Chen  2 , Richard Casaburi  3 , Harry B Rossiter  3
Affiliations

SEVERITY OF LUNG OBSTRUCTION AND OLDER AGE, BUT NOT PHYSICAL ACTIVITY, PREDICT LOCOMOTOR MUSCLE OXIDATIVE IMPAIRMENT IN COPD

Alessandra Adami et al. medRxiv. .

Abstract

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. Gastrocnemius 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 (FEV1%predicted), diffusing capacity (DLCO), 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. FEV1%predicted, DLCO, 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 FEV1%predicted, age and race were significantly associated with k (R2=0.26). Model coefficients equate a 10% lower FEV1%predicted to a 4.4% lower k, or 10-years of aging to a 9.7% lower k. In 118 cases with CT available, FEV1%predicted and age remained associated with k (R2=0.24). Physical activity was not retained in any model.

Conclusions: Locomotor muscle oxidative capacity was positively associated with FEV1%predicted and negatively associated with age. Physical activity or radiographic COPD manifestations were not significantly associated with muscle oxidative impairment.

Keywords: Computed tomography; Near-infrared spectroscopy; PRISm; Physical activity; Smokers; Triaxial accelerometry.

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Conflict of interest statement

Alessandra Adami is supported by National Health Institute grant R01HL151452. Fenghai Duan reports consulting fee from EarlyDiagnostics Inc. Richard Casaburi reports consulting fees from Inogen, Harry Rossiter is supported by grants from National Health Institute (R01HL151452, R01HL166850, R01HL153460, P50HD098593, R01DK122767) and the Tobacco Related Disease Research Program (T31IP1666). He reports consulting fees from the National Health Institute RECOVER-ENERGIZE working group (1OT2HL156812), and is involved in contracted clinical research with United Therapeutics, Genentech, Regeneron, Respira, Mezzion and Intervene Immune. He is a visiting Professor at the University of Leeds, UK. All other authors have nothing to disclose.

Figures

Figure 1.
Figure 1.. Study flow diagram.
Study enrollment and allocation of participants to final analysis based on completion of the muscle test to determine skeletal muscle oxidative capacity (study primary outcome) and physical activity monitoring.
Figure 2.
Figure 2.
Comparison of (a) the rate constant of muscle oxygen consumption recovery (k; proportional to muscle oxidative capacity; n=214), (b) physical activity (mean vector magnitude units per minute; n=222), and (c) number of steps per day (n=222), among smokers with normal spirometry (reference group; Controls), never smokers, and individuals with PRISm and COPD. k, rate constant of muscle oxygen consumption recovery; VMU, vector magnitude units; PRISm, preserved ratio impaired spirometry; COPD, chronic obstructive pulmonary disease; FEV1 %pred, forced expiratory volume in 1 second as a percentage of the predicted value. *p<0.05; ** p<0.01; *** p<0.001.
Figure 3.
Figure 3.
Chronic (a) and acute (b) effects of smoking on the rate constant of muscle oxygen consumption recovery (k; proportional to muscle oxidative capacity) in participants with normal spirometry.
See this image and copyright information in PMC

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