Muscle atrophy is common systemic feature of advanced COPD. Although primarily a lung disease, muscle atrophy is an important prognostic factor in the mortality caused by COPD but the mechanisms leading to muscle dysfunction remain unknown. FHL proteins are actin binding proteins that can shuttle between the cytoplasm and the nucleus and have been shown to be important in cell differentiation and protein turnover. Recent data has shown that mutations in FHL1 lead to muscle wasting and that over expression of FHL1 causes hypertrophy and increases the proportion of type IIa fibres in some muscles (Cowling et al) suggesting that it may be involved in COPD associated muscle atrophy. FHL1, type I MHC, type IIa MHC and RPLPO mRNA levels were measured in 41 patients and 18 healthy age matched controls by quantitative RT-PCR. Strength was measured as maximal voluntary contraction of the quadriceps and activity measured by triaxial accelerometry. Statistical analysis was performed using the Mann-Whitney U test and Spearman’s rank correlation. COPD patients had a reduced FEV1 (COPD 35% vs control 108% of predicted), were less active (COPD 56.03± 7.03 mins/day vs cont 100±10.88 mins/day) and were weaker (maximal voluntary contraction COPD 29.6± 1.5kg vs cont 36.2± 2.5kg) than the controls. The expression MHC type I was reduced 3 fold and the expression of MHC type IIa was increased 1.5 fold in the patients compared to the controls. FHL1 expression was not different between patients and controls. Correlation of FHL1 expression with activity and strength showed an inverse correlation of both FHL1 mRNA and protein with strength (R²=-0.408, p<0.01) and activity (R²=-0.552 p<0.005) in the patients but not in the controls. FHL1 mRNA was also strongly correlated with the expression of type IIa mRNA in both patients (R²=0.495 p<0.001) and controls (R²=0.491 p<0.01) but was not correlated with type I MHC in either group. The inverse correlation between FHL1 mRNA and activity and strength observed in patients is surprising given previous data in human and animal studies showing increased FHL1 expression following exercise. However, FHL1 has been shown to be associated with hypertrophy and we and others have found that Akt phosphorylation is increased in patients with reduced activity or muscle wasting compared to controls (Doucet et al). Our data correlating FHL1 with type IIa MHC suggests that FHL1 may also modify the expression of MHC type IIa in humans as well as rodents.