Chronic Obstructive Pulmonary Disease Clinical Trial
Official title:
Micro-environment Involvement in Muscle Alteration Induced by Copd Exacerbation
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.
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