Influence of Chronic Hypoxia on Oxidative Phenotype in Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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.

Official Title
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Influence of Chronic Hypoxia on Oxidative Phenotype in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Procedure: Muscle biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COPD patients with chronic hypoxemia<br>COPD patients with chronic and severe arterial hypoxemia at rest (paO2<55mmHg). | Procedure: Muscle biopsy<br>* The biopsy is performed on the vastus lateralis muscle at rest and 2 hours after an acute exercise, with a local anesthesia.<br>|
| COPD patients with normoxia<br>COPD patients with normoxia at rest (paO2>67mmHg), matched for age, sex, bronchial obstruction and lean mass. | Procedure: Muscle biopsy<br>* The biopsy is performed on the vastus lateralis muscle at rest and 2 hours after an acute exercise, with a local anesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of expression of muscle messenger ribonucleic acid (mRNA) of HIF-1α and PGC-1α | 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 | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type I muscle fibers | 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. | Day 1 | 
| Oxidative enzyme capacity | 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. | Day 1 | 
| Level of expression of muscle mRNA of HIF-1α after acute exercise | Comparison of response to acute exercise for expression level of HIF-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups. | Day 1 | 
| Level of expression of muscle mRNA of PGC-1α after acute exercise | Comparison of response to acute exercise for expression level of PGC-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Muscle biopsy, Chronic hypoxia, OXYPHEN, Oxydative phenotype, Exercise