COPD
Conditions
Keywords
Muscle dysfunction, Cardiovascular regulation, Lung transplantation (LTx)
Brief summary
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.
Detailed description
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.
Interventions
OTHERLung transplantation
Single or double lung transplantation in patients with COPD
Sponsors
Rigshospitalet, Denmark
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* COPD with or without alpha 1-antitrypsin deficiency on the waiting list for a lung transplantation * Single or double lung transplantation * ≥ 18 years * Ability to give informed consent
Exclusion criteria
* Retransplantation * Multiple-organ transplantation (heart-lung transplantation) * Musculoskeletal disorders which substantially inhibits physical activity * Need for crossmatching in connection with lung transplantation * Anticoagulant therapy before lung transplantation (except acetylsalicylic acid)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in leg blood flow (mL/min) | Change from baseline at 6 months | Endothelium function will be evaluated during acute exercise (one legged kicking) by Flow doppler |
| Change in 6 min walking test | Change from baseline at 6 months | Exercise capacity |
| Change in health-related quality of life | Change from baseline at 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in skeletal muscle function | Change from baseline at 6 months | Muscle biopsy |
| Change in blood volume | Change from baseline at 6 months | CO re-breathing method |
| Change in capillarization of lung tissue | Change from baseline at 6 months | Transbronchial biopsy (only COPD patients) |
Countries
Denmark
Contacts
Primary ContactUlrik Winning Iepsen, MD, PhD
Backup ContactCamilla Koch Ryrsø, MSc
Outcome results
None listed