Substudy : Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Its prevalence is in progression and COPD is expected to become the fourth leading cause of death by 2030. COPD is characterized by periods of stability interspersed with acute infectious/inflammatory flare-ups, also called acute exacerbations, during which patients deteriorate, sometimes to the point of requiring immediate medical assistance. Although most patients eventually recover, repeated episodes of exacerbations may accelerate COPD progression. Exacerbations may further compromise the integrity of limb muscles by promoting further loss in muscle mass and strength. The overall objective of this substudy is to elucidate how an acute COPD exacerbation may affect limb muscles.

Detailed Description
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Focusing our attention during exacerbations, a period of aggravated systemic inflammation, should be more rewarding in terms of understanding the link between inflammation burst and muscle disease in COPD. We have recently acquired experimental data supporting a role for the ubiquitin proteasome pathway in the worsening of limb muscle structure and function during an acute exacerbation, providing a solid framework for this investigation. The overall objective of this proposal is to substantiate these preliminary findings and elucidate how systemic inflammation during acute COPD exacerbation may affect limb muscles. Ultimately, our research could open new therapeutic avenues to minimize the systemic consequences of an acute exacerbation.

Official Title
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Muscle Atrophy in Patients With Chronic Obstructive Pulmonary DIsease : Substudy With Patients Who Experienced an Acute Exacerbation

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Other: No specific intervention for this study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and female COPD with an FEV1 of under 60% of predicted non-smoker between 50 and 75 years old experiencing an acute exacerbation of COPD (24-48 hours, before treatment) Exclusion Criteria: all inflammatory disease (HIV, cancer, renal and cardiac deficiency) hormonal dysregulation inferior limb pathology neuromuscular pathology history of tobacco or alcool abuse oxygen dependent

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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 |
| --- | --- |
| COPD exacerbation<br>No specific intervention for this study | Other: No specific intervention for this study<br>* No specific intervention for this study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased levels of ubiquitin proteasome pathway proteins in patients experiencing an acute exacerbation of COPD | Our view is that targeting exacerbation is likely to unravel important mechanisms linking systemic inflammatory processes to downstream consequences on remote organs such as limb muscles. Inflammatory burst observed during exacerbation may be associated with upregulation of ubiquitin proteasome pathway (Atrogin-1, MuRF-1, Nedd4, ubiquitin C, poly-Ub), the main proteolytic pathway in this tissue, and thus with the occurrence of atrophying process. | during an acute exacerbation of COPD (first 24-48 hours, before treatment) |