Micro-environment Involvement in Muscle Alteration Induced (MicAMI-BPCO)

University Hospital Center (CHU)

Status

Completed

Conditions

Chronic Obstructive Pulmonary Disease

Exacerbations

Skeletal Muscle Atrophy

Study type

Observational

Funder types

Other

Identifiers

NCT04448626

RECHMPL20_0137

Details and patient eligibility

About

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.

Enrollment

27 patients

Sex

All

Ages

40 to 85 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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