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Introduction: Reduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation., Methods: Thirty-seven patients with COPD (grade II-IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n=25) or absence (COPD functional, n=12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates., Results: Presence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p=0.04), reduced resting O 2 saturation (p=0.003) and physical inactivity (p=0.01), and specific amino acid metabolic disturbances (enhanced leucine (p=0.02) and arginine (p=0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia)., Conclusion: COPD patients with muscle dysfunction show characteristics of a cognitive - metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)