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The purpose of the project is to investigate changes in the quadriceps muscle and cardiovascular regulation during exercise in relation to improved lung function after lung transplantation in patients with COPD.
Dysfunctional skeletal musculature of the lower limbs is related to low quality of life, exercise intolerance and higher mortality in patients with COPD. Limb muscle dysfunction in COPD consists of muscle atrophy and reduced muscle strength but also intra-muscular alterations in oxidative capacity and mitochondrial function are often present. Moreover, reduced blood flow to exercising muscle may also contribute to the muscle dysfunction in COPD. The mechanisms responsible for muscle dysfunction in COPD patients remain unclear but could be a consequence of reduced lung function, inflammation, medications or low physical activity. Loss of lung function with COPD is normally irreversible so the transition to near-normal lung function after lung transplantation is a unique model to investigate the adaptation of the limb muscle to improved lung function. Thus, the purpose of this project is to investigate the effect of lung transplantation on limb muscle function (mitochondrial function, oxidative enzyme capacity, fiber type distribution, oxygen delivery/uptake) and daily physical activity level in patients with COPD. The project has a translational focus on muscle dysfunction in COPD and uses methodologies from clinical medicine, integrative physiology and molecular biochemistry in order to gain knowledge of mechanisms behind limb muscle dysfunction and exercise intolerance in COPD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| COPD patients | COPD patients on the waiting list for a lung transplantation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lung transplantation | Other | Single or double lung transplantation in patients with COPD |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in leg blood flow (mL/min) | Endothelium function will be evaluated during acute exercise (one legged kicking) by Flow doppler | Change from baseline at 6 months |
| Change in 6 min walking test | Exercise capacity | Change from baseline at 6 months |
| Change in health-related quality of life | Health-related quality of life will be assessed by total mean score of St. George's Respiratory Questionnaire (SGRQ) (2 parts,3 components questionnaire). Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units are considered clinically relevant. | Change from baseline at 6 months |
| Change in health-related quality of life | Health-related quality of life will be assessed by mean score of a validated Danish version of the COPD Assessment Test (CAT). The CAT is a short 8-item questionnaire with scoring range of 0-40, where higher scores indicating more limitations. A change of 2 units suggests a meaningful difference. | Change from baseline at 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in skeletal muscle function | Muscle biopsy | Change from baseline at 6 months |
| Change in blood volume | CO re-breathing method | Change from baseline at 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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COPD patients on the waiting list for a lung transplantation
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ulrik Winning Iepsen, MD, PhD | Contact | +4540732842 | ulrik_winning@hotmail.com | |
| Camilla Koch Ryrsø, MSc | Contact | ryrsoe@yahoo.dk |
| Name | Affiliation | Role |
|---|---|---|
| Ulrik Winning Iepsen, MD, PhD | Centre for Physical Activity Research, Copenhagen University Hospital, Copenhagen, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the Centre for Physical Activity Research, Copenhagen University Hospital | Recruiting | Copenhagen | Denmark |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D016040 | Lung Transplantation |
| ID | Term |
|---|---|
| D013510 | Pulmonary Surgical Procedures |
| D019616 | Thoracic Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D016377 | Organ Transplantation |
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Blood samples (plasma), muscle biopsies (m. quadriceps femoris), transbronchial biopsy.
| Change in capillarization of lung tissue | Transbronchial biopsy (only COPD patients) | Change from baseline at 6 months |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014180 | Transplantation |