Cytokine Profile in Quadriceps Muscles of Patients with Severe Chronic Obstructive Pulmonary Disease

BACKGROUND: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. Objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function, and exercise capacity. METHODS: We conducted a cross-sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and 7 healthy controls. Subsequently, selected cytokines [tumor necrosis factor (TNF)-alpha, TNF-alpha receptors I and II, interleukin (IL)-6, interferon-gamma, transforming growth factor (TGF)-beta, and vascular endothelial growth factor (VEGF)], as well as protein carbonylation (oxidative stress index) were determined using enzyme-linked immunosorbent assay (ELISA) in all muscles. RESULTS: As compared to controls, vastus lateralis of COPD patients showed significantly lower protein ELISA levels of TNF-alpha, which positively correlated with their quadriceps function, TNF-alpha receptor II, and VEGF. Protein ELISA levels of IL-6, interferon-gamma, and TGF-beta did not differ between patients and controls. Quadriceps protein carbonylation was greater in the patients and inversely correlated with quadriceps strength amongst them. CONCLUSIONS: These findings do not support the presence of a pro-inflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness

Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre

Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre