Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes.

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 O2 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.

Determination of ß-hydroxy-ß-methylbutyrate concentration and enrichment in human plasma using chemical ionization gas chromatography tandem mass spectrometry.

Our objective was to develop a quick and simplified method for the determination of ß-Hydroxy-ß-methylbutyrate (HMB) and ɑ-ketoisocaproic acid (KIC) concentrations and enrichments by GC/MS/MS to determine the turnover rate of HMB in humans. In experiment 1, we provided a pulse of L-[5,5,5-2H3]leucine to younger adults in the postabsorptive state then collected blood samples over a 4h time period. In experiment 2, we provided a pulse of [3,4,methyl-13C3]HMB to older adults in the postabsorptive state then collected blood samples over a 3h time period. Plasma concentrations of KIC and HMB and MPE of KIC and HMB were determined by GC/MS/MS. Plasma enrichment of leucine was determined by LC/MS/MS. To determine plasma enrichment of [5,5,5-2H3]HMB and [3,4,methyl-13C3]HMB, samples were derivatized using pentafluorobenzyl bromide and analyzed using chemical ionization mode. The final methods used included multiple reaction monitoring of transitions 117.3>59.3 for M+0 and 120.3>59.3 for M+3. In experiment 1, peak MPE of Leu peaked at 9.76% generating a peak MPE of KIC at 2.67% and a peak HMB MPE of 0.3%. In experiment 2, the rate of appearance for HMB was 0.66µmol/kg ffm/h. We calculated that production of HMB in humans accounts for 0.66% of total leucine turnover.

Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes / La presencia o ausencia de disfunción muscular esquelética en la enfermedad pulmonar obstructiva crónica está asociada a fenotipos distintos

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 O2 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). (AU)

Introducción: El funcionamiento reducido del músculo esquelético y del rendimiento cognitivo son signos extrapulmonares comunes en la Enfermedad Pulmonar Obstructiva Crónica (EPOC), pero su conexión sigue sin estar clara. Es necesario investigar más si la presencia o ausencia de disfunción muscular esquelética en pacientes con EPOC está relacionada con un fenotipo específico que consiste en un rendimiento cognitivo reducido, comorbilidades y trastornos nutricionales y metabólicos.Métodos: Se separaron treinta y siete pacientes con EPOC (grado II-IV) en dos cohortes fenotípicas en función de la presencia (EPOC disfuncional, n=25) o ausencia (EPOC funcional, n=12) de disfunción muscular. Estas cohortes se compararon con 28 controles sanos, emparejados por edad. Se midieron la fuerza muscular (dinamometría), el rendimiento cognitivo (test de senderos y test de Stroop), la composición corporal (absorciometría de rayos X de doble energía), la actividad física habitual, las comorbilidades y el estado de ánimo (cuestionarios). Se administraron aminoácidos trazadores estables en pulsos para medir las tasas de producción de todo el cuerpo.Resultados: La presencia de disfunción muscular en la EPOC resultó ser independiente de la masa muscular o la gravedad de la obstrucción al flujo de aire, pero se asoció con afectación del rendimiento en el test de Stroop (p=0,04), una saturación en reposo de O2 disminuida (p=0,003) e inactividad física (p=0,01), y trastornos metabólicos de aminoácidos específicos [producción aumentada de leucina (p=0,02) y arginina (p=0,06)]. Por el contrario, los pacientes con EPOC con función muscular normal presentaron ansiedad, aumento de la masa grasa, de la concentración de glucosa en plasma y de las comorbilidades relacionadas con el síndrome metabólico (hipertensión y dislipidemia). (AU)