Is the anaerobic quadriceps muscle phenotype in COPD mediated by reduced muscle concentrations of Peroxisome Proliferator-Activated Receptors a and d? (360G-Wellcome-079686_Z_06_Z)

Background Quadriceps weakness is a disabling feature of Chronic Obstructive Pulmonary Disease (COPD). It results from loss of aerobic muscle fibres. In vivo work suggests that this is mediated by reduced Peroxisome Proliferator-Activated (PPAR) a and d activity.Goals To investigate whether 1) reduced quadriceps PPARa and d concentrations correlate with an anaerobic muscle phenotype in patients with severe COPD 2) clinical interventions reverse the anaerobic phenotype and concurrently upregulate PPARa and d.Approach Study 1 75 patients with severe COPD and 30 controls undergo assessment of quadriceps function and a muscle biopsy to determine PPARa and dconcentrations and proportion of aerobic muscle fibres. Study 2 30 patients from Study 1 are randomised to cardiopulmonary training (pulmonary rehabilitation) or a control group. Study 3 30 patients from Study 1 are randomly assigned to isolated leg training with repetitive magnetic femoral nerve stimulation (rMS). Study 2 and 3 subjects are treated for 8 weeks beforebeing re-studied as in Study 1.Significance Identifying pathways underlying quadriceps abnormalities in COPD will facilitate development of treatments. RMS, if effective, could have clinical applications. This work may benefit patients with heart failure who have a similar quadriceps phenotype to those with COPD.