Angiotensin-converting Enzyme (ACE)-Inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease (COPD)

ACE-inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease

A double blind randomised placebo controlled parallel trial of the effect of fosinopril, an angiotensin converting enzyme inhibitor, on the quadriceps muscle in 80 COPD patients who have quadriceps weakness. Patients will have a baseline assessment including measures of quadriceps strength and endurance and a quadriceps biopsy. Patients with weakness will be randomised to ACE inhibitor or placebo and re-assessed after three months of treatment.

The investigators aim to show that ACE-inhibition will alter the IGF-1/AKT/FoXO/atrogene pathways involved in muscle wasting in COPD.

Inclusion Criteria:

• Adult patient with COPD diagnosed according to GOLD criteria.

Exclusion Criteria:

• Clinically unstable patients (within one month of exacerbation), those with a permanent pacemaker (which is a contraindication to magnetic stimulation), or significant co-morbidity, patients with an accepted indication for ACE inhibition (left ventricular dysfunction, diabetes) or a contraindication such as renovascular disease; creatinine clearance (estimated) <50); hypotension; use of anticoagulants (contra-indication to biopsy) or ACE-I or ATII receptor antagonists.
• Allergy to ACE-inhibitors.
• Pregnancy.

Patients will not be enrolled within three months of participation in a pulmonary rehabilitation program.