Micro-environment Involvement in Muscle Alteration Induced

Study Overview
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Brief Summary
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Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airway obstruction and inflammatory response of the lungs and bronchi. Episodes of exacerbations contribute to increase the severity and prognosis of the disease. Muscle dysfunction (loss of strengh and muscle mass) is one of comorbidities affecting 30% to 60% of patients and playing a key role in their prognosis. During exacerbation, some studies have suggested an association between muscle dysfunction and modifications of inflammatory circulating factors such as CRP, TNF-alpha, IL- 6, IL8, but no exhaustive study has identified precisely one (or more) biomarker(s) that can induce this muscle wasting during the exacerbation of COPD. Our hypothesis is that the serum of exacerbated COPD patients represents a deleterious microenvironment for the muscle cells which would amplify the mechanisms of atrophy linked to hospitalization. Our team has already developed a cell culture model to study the effects of the plasma microenvironment on atrophy of cultured myotubes. The investigators have shown that the serum of COPD patients can induce muscle atrophy. The objectives of this study are : 1/ to evaluate the effects of circulating pro-inflammatory factors on atrophy and the myogenic capacities of muscle cells; and 2/ to identify one (or more) circulating biomarker (s) that may be responsible for the muscle damage induced by the microenvironment of hospitalized patients for exacerbation of COPD. First, myotubes and myoblasts of healthy subjects will be cultivated with 9 exacerbation copd patient serum or 9 copd patient serum or 9 healthy subject serum. Myotube diameters, atrophy, inflammatory and oxidative stress markers and alteration of the myogenic capacity of satellite cells will be compared between three groups. Second, the differential expression of circulating proinflammatory molecules will be compared in the serum of the three groups. Identifying circulating factors associated with muscle weakness is a necessary step to better understand the mechanisms and consider a personalized therapeutic approach that can improve the functional and clinical prognosis of disease. .

Official Title
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Micro-environment Involvement in Muscle Alteration Induced by Copd Exacerbation

Conditions
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Chronic Obstructive Pulmonary Disease, Exacerbations, Skeletal Muscle Atrophy

Participation Criteria
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Eligibility Criteria
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Inclusion criteria 1/ for COPD patients hospitalized for exacerbation: Hospitalization for COPD exacerbation 2/ for COPD patients COPD patients GOLD II à IV Not having followed respiratory réhabilitation stay for at least one year 3/ for Healthy subjects healthy and sedentary (Voorips score <9) Exclusion criteria: for COPD patients hospitalized for exacerbation: concomitant acute cardiac évent trachéal intubation with mechanical ventilation chronic respiratory disease other than COPD locomotor, neurologic or psychiatric comorbidities for COPD patients Exacerbation with récent hospitalization (<4 weeks) Neurologic comorbidity for Healthy subjects - long term drug treatment with proven central effects

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy subject<br>Healthy subject | |
| Stable COPD patients<br>Stable COPD patients | |
| Exacerbation COPD patients<br>Exacerbation COPD patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects evaluation of circulating pro-inflammatory factors on atrophy | Atrophy marker evaluation in cultured muscle cells (myotubes) cultured myotube diameter exposed to the three serum groups (immunofluorescence) atrophy (ubiquitin proteasome system, proteolytic autophagy pathway), inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot) | 6 months | 
| Effects evaluation of circulating pro-inflammatory factors on the myogenic capacities of muscle cells | Myogenic capacities of cultured muscle cells (myoblastes) inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot) regeneration markers (Notch and myogenesis signaling pathways) expressed by cells exposed to the three serum groups (PCR et WesternBlot) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of one (or more) circulating biomarker (s) | Identification of one (or more) circulating biomarker (s) that may be responsible for the muscle alteration induced by the microenvironment of patient in exacerbation of COPD | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD Exacerbation, Muscle atrophy, Inflammation, Oxidative stress, Biomarkers