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HDAC2 is reduced by oxidative stress through the activation of phosphoinisitide-3-kinase-�� (PI3K-��). Low concentrations of theophylline restore the low levels of HDAC2 levels in COPD macrophages to normal and reverse steroid resistance in vitro and in vivo by blocking PI3K-��. These studies may lead to new therapeutic approaches with the use of low dose theophylline and in the future PI3K-�� selective inhibitors to reverse corticosteroid resistance. ""COPD patients have reduced exercise capacity and skeletal muscle function. The aim of this study was to investigate the effects of one leg exercise training on mitochondrial respiration in COPD patients. We hypothesised that by exercising a small muscle group (quadriceps muscle), a significant improvement of the quadriceps oxidative capacity could be expected. Seven patients with COPD (65?��?7?years,) with FEV1 52.8?��?11 (% pred), FEV1 % FVC 44?��?11 (% pred) and a smoking history of 34?��?9 packyears performed a six week (3?d/week) high intensity interval aerobic knee extensor exercise program. Five age- and sex-matched healthy individuals served as reference group. Spirometry, peak oxygen uptake (VO2peak) of the quadriceps muscle and mitochondrial respiration were measured before and after the 6?week training program. Peak work and maximal mitochondrial respiration were significantly reduced in the COPD group (p? peak work from 15.4?��?1.6?W to 20.0?��?2.0?W (p?