Fibre Specific Signalling in the Locomotor Myopathy of Chronic Obstructive Pulmonary Disease

Fibre Specific Signalling in the Locomotor Myopathy of COPD

Skeletal muscle is composed of two fibre types which are intertwined. Skeletal muscle weakness, particularly of the walking muscles, is an important complication of Chronic Obstructive Pulmonary Disease (COPD) but so far the investigators do not know what mechanisms drive the process.

All existing studies have investigated signalling pathways in the whole muscle so they have been forced to consider type I and type II fibres together. It is possible that disease selectively affects one fibre type, most likely type I fibres which are in fact lost in COPD patients. For this reason mechanisms of disease may have been overlooked by current studies.

The applicants have acquired the technology which allows type I and type II fibres in a muscle specimen to be split (by laser capture microdissection) and so signalling pathways can be assessed separately in type II and type I fibres which is what this proposal sets out to do.

The proposal therefore aims to capture well characterised clinical data from 60 COPD patients and 20 age matched controls, from whom a biopsy of the main walking muscle, the quadriceps, will be taken. In the samples the investigators will assess at a fibre specific level inflammatory signalling. Surplus material will be retained for subsequent fibre specific analysis.

Inclusion Criteria:

• Male or female aged 40 - 90 years inclusive.
• A clinical diagnosis of COPD based on spirometry (FEV1/FVC ratio < 70% on entry to the study with FEV1 < 80% predicted)

Exclusion Criteria:

• History or current diagnosis of alpha 1-anti-trypsin deficiency, asthma, lung cancer, bronchiectasis or other significant respiratory disease (including treated TB in the past 10 years)
• Contraindication to biopsy for research purpose (e.g. use of anticoagulant in the 1 week prior to biopsy)
• Joint or neurological disease which on its own would preclude exercise