COPD Patients, Healthy
Conditions
Keywords
Flow-mediated dilatation, COPD, Pulmonary Rehabilitation, Comorbidities, endothelial cell, oxidative stress
Brief summary
Vascular comorbidities constitute a major burden in COPD patients. The atherosclerosis process is preceded by the onset of an endothelial dysfunction (assessed by the flow-mediated dilatation (FMD)), which is a risk factor for later ischemic vascular complications and death. In COPD, this endothelial dysfunction could be explained by intrinsic endothelial cell properties, or the effect of a pathogenic endothelial cell microenvironment (inflammation and/or oxidative stress). Exercise training constitue a powerful stimulus for the endothelial function, and could be mediated by the mobiliaztion and function of endothelial progenitors. While exercise training is an efficient intervention in COPD patients, its vascular effect appear blunted. The endothelial function response to training has appeared heterogeneous in COPD patients, and possibly linked to the endothelial cel lesion. Thus, endothelial function (assessed by the FMD) response to exercise training would be lower in COPD patients with a baseline impairment of the their FMD. In addition, of biological and functional factors could explained the magnitude of the FMD response in COPD patients.The aim of the study are thus : To compare the FMD change in COPD patients with FMD above (FMD+) and under the median FMD (FMD-) after 4 weeks of exercise training in the whole study population. To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects, the endothelial inflammation and senescence at baseline and the endothelial progenitor mobilization and function change induced by exercise (maximal exercise test and training). To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects the effect of the endothelial microenvironment on the cellular pathways regulating the endothelial function in vitro at baseline and changes after exercise training. To test in COPD patients the association between the magnitude of the FMD changes after training and biological, functional and clinical factors (inflammation oxidative stress markers, endothelial biomarkers, pulmonary impairment and phenotype, cardiovascular risks factors, vascular function, metabolic markers, physical activity level, …)
Interventions
OTHERFMD analysis
Blood sample and vascular exploration.
Sponsors
University Hospital, Montpellier
University Hospital, Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
COPD patient group (n=50) and Healthy control Group (n=24)
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
A/ COPD patients * age between 35 and 85 years old * spirometry showing an FEV1/VC \< lower limit of normal * with an indication for a pulmonary rehabilitation program * written and informed consent for this study signed by the patient B/ Healthy subjects * age between 35 and 85 years old * no cardiovascular or respiratory disease * normal spirometry
Exclusion criteria
* Unstabilized comorbidity * Subject in a period of exclusion relative to another protocol * Major protected by law * Subject participating in another research protocol * Subject not affiliated to a social security scheme * Pregnant or lactating woman * Patient deprived of freedom by court or administrative order
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Flow-Mediated Dilatation (FMD) | post exercise and after 4 +/- 2 weeks of training | Measure of FMD by EndoPAT2000© |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of biological vascular markers | after 4 +/- 2 weeks of training | E-selectin soluble (sE-sel), endotheline 1 (ET1), facteur von Willebrand (vWF), vascular endothelial growth factor A (VEGF-A), Fms-like tyrosine kinase receptor 1 soluble (sFlt-1), Angiopoietine 1 et 2 (Ang-1 Ang-2) |
| Number of colonies and function of Endothelial-Colony Formaing cells (ECFC) in vitro | post exercise and after 4 +/- 2 weeks of training | — |
| Number endothelial progenitors | post exercise and after 4 +/- 2 weeks of training | CD34+, CD45+ and KDR + subpopulations by flow cytometry |
| Vascular function parameters | after 4 +/- 2 weeks of training | Systolic pressure index (in AU) |
| Pulse-wave velocity (in ms-1) | after 4 +/- 2 weeks of training | — |
| Markers of systemic inflammation | after 4 +/- 2 weeks of training | C-Reactive protein (in ng/ml) |
| Markers of oxidative stress | after 4 +/- 2 weeks of training | Lipid peroxidation (in micromol/L) |
| Muscle function parameters | after 4 +/- 2 weeks of training | Maximum isometric voluntary contraction (in N.m) |
| Exercise capacity and vascular adaptation parameters | after 4 +/- 2 weeks of training | Maximal oxygen uptake (VO2max, in mL/kg/min) |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORFares Gouzi, MD, PhD
UH Montpellier
Outcome results
None listed