Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Muscle biopsy, Chronic hypoxia, OXYPHEN, Oxydative phenotype, Exercise
Brief summary
In addition to chronic airflow obstruction, patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from skeletal muscle dysfunction which is a prominent and disabling feature and also an independent determinant of survival. Muscular impairment involves loss of muscle oxidative phenotype (OXPHEN: a slow-to-fast shift in fibre types and reduced oxidative capacity). Since hypoxia obviously is a key feature of COPD, the aim of this study is to elucidate the role of hypoxia in loss of muscle OXPHEN. Thus, OXPHEN and expression levels of its key regulators will be determined in the baseline biopsies for association with the degree of hypoxemia. In addition, expression levels of the key OXPHEN regulators will be measured in pre/post exercise biopsies.
Interventions
The biopsy is performed on the vastus lateralis muscle at rest and 2 hours after an acute exercise, with a local anesthesia.
Sponsors
Study design
Eligibility
Inclusion criteria
* Diagnosis of COPD confirmed according to GOLD score. * Hypoxemia group: resting arterial paO2 \<55 mmHg. * Normoxemia group : resting arterial paO2 \> 67 mmHg
Exclusion criteria
* Unstable cardiorespiratory status (acute respiratory failure) * Oxygen treatment started * Inclusion in a pulmonary rehabilitation program in the last 6 months * Anticoagulant treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of expression of muscle messenger ribonucleic acid (mRNA) of HIF-1α and PGC-1α | Day 1 | Comparison of expression levels of Hypoxia-inducible Factors (HIF-1α) and Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α), two OXYPHEN regulators, in muscle biopsy, between COPD patients with chronic hypoxemia and those with normoxemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Type I muscle fibers | Day 1 | It is an indicator of the muscle phenotype (with a muscle biopsy). It used to compared the muscle phenotype in the 2 groups of patients. It is a percentage. |
| Oxidative enzyme capacity | Day 1 | It is an other indicator of the muscle phenotype (with a muscle biopsy). It used to compared the muscle phenotype in the 2 groups of patients. |
| Level of expression of muscle mRNA of HIF-1α after acute exercise | Day 1 | Comparison of response to acute exercise for expression level of HIF-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups. |
| Level of expression of muscle mRNA of PGC-1α after acute exercise | Day 1 | Comparison of response to acute exercise for expression level of PGC-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups. |
Countries
France