31P MRS Ischaemic Exercise Optimisation and COPD

In part A subjects will be recruited until numbers are sufficient to meet the objectives of Part A, up to a maximum of 25 subjects. Up to 15 subjects will be studied in part B. Up to 25 subjects with COPD and 25 control subjects will be enrolled to allow at least 12 patients and 12 age- and sex- matched controls to be studied in part C.

Inclusion Criteria:

1. Fit to safely tolerate procedures
2. Male or female between 18 and 80 years of age
3. If pre-menopausal female, non-pregnant on dipstick urinalysis
4. Subject and responsible physician agree that the subject will be able to comfortably lie in scanning position in the scanner for up to 90 minutes
5. Capable of giving written informed consent
6. All four limbs are intact and free of disease

The following criteria apply to patients with COPD myopathy only:

1. Established diagnosis of COPD with a disease classification of GOLD Stage II and above with suspected or established diagnosis of myopathy and/or COPD with low BMI (under 20 for men and under 19 for women) and/or MVC under 120% of the BMI.
2. At least a 20 pack year history of smoking
3. Resting oxygen saturation above 85% on room air
4. Ambulant and not oxygen-dependent at rest or during mild exertion

Exclusion Criteria:

1. Ineligible for MRI/MRS scanning in accordance to local MR safety regulations
2. Any medical condition, acute or chronic, that will lead to potential discomfort when lying supine in the magnet for periods up to 90 min
3. Any medical condition that will lead to potential discomfort with repetitive movement of the limb being tested in the scanner
4. Subjects undergoing ischaemic/anaerobic 31P MRS must have no history of clinically significant peripheral vascular disease, abnormal blood clotting, deep vein thrombosis or pulmonary embolism or suspected clinically significant signs of limb vascular disease on screening examination.
5. Subjects undergoing ischaemic/anaerobic 31P MRS must not have taken the oral contraceptive pill, hormone replacement therapy, or undergone anaesthesia within past 1 month, or have a history of recent prolonged immobility greater than 4 hours (e.g. air travel), or considered unfit in the opinion of the study physician
6. Concurrent medical conditions known or suspected that in the opinion of the responsible physician could confound interpretation of results.
7. A medical or psychiatric history that in the opinion of the responsible physician would risk safety of the subject or well-being of the subject.

The following criteria apply to control subjects and COPD patients participating in Part C of the study:

1. Oxygen saturations below 85% on room air at rest, or significant desaturation on mild exertion.
2. Current or recent (<4 weeks) infectious exacerbation of COPD requiring corticosteroid therapy at the time of screening or scanning visit day.
3. Any significant medical illness other than COPD which, in the opinion of the study physician, may preclude participation or which by virtue of being associated with muscle weakness may cause distortion of the results (e.g. neuromuscular disease, severe heart failure &c).
4. Control subjects with any history of regular smoking