Circulating Markers of Endothelium Damage, Circulating Microvesicles, Obstructive Pulmonary Disease, Pulmonary Hypertension Due to Chronic
Conditions
Brief summary
Mild to moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. A small proportion of COPD patients may present with severe pulmonary hypertension, defined by a mean pulmonary artery pressure more than 35 mmHg (or more than 20 mmHg with a low cardiac index \< 2 l/min/m2) with pulmonary vascular resistance more than 3 Wood units, measured by right heart catheterization (RHC). In these patients, pulmonary microvessels remodeling is the main cause of increase in pulmonary arterial pressure and is thought to result from the combined effects of hypoxia, inflammation, and loss of capillaries but the mechanisms are complex. For these patients, no drugs have been approved for treatment and lung transplantation must be considered for the more severe patients who are eligible. A better characterization of these patients is needed. We hypothesize that microvesicles generation and endothelial damage could be related to the severity of pulmonary hypertension due to COPD, assessed by pulmonary hemodynamic parameters. Circulating biomarkers of vascular damage and cell activation will be measured in blood samples from 80 COPD patients who have hemodynamic assessment by RHC. To go further, the origin of the particles will be characterized.
Interventions
Right heart catheterization, using the Swan-Ganz standard technique, to measure mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output and pulmonary vascular resistance
Sponsors
Study design
Eligibility
Inclusion criteria
* Age ≥ 18 * COPD: obstructive ventilatory insufficient on spirometry and history of smoking * patients who will perform right heart catheterization * Signature of written informed consent
Exclusion criteria
* LVEF \< 45% (echocardiography) * Post-capillary pulmonary hypertension (pulmonary capillary wedge pressure \> 15 mmHg) * Chronic Thromboembolic hypertension * Pulmonary embolism \< 6 months * Acute coronary syndrome \< 3 months * Significant cardiac valvulopathy (echocardiography) * Portal hypertension * Connective tissue disease * chronic renal insufficient (clearance \< 40 ml/min) * Glycated hemoglobin \> 7% (if diabetes) * Non controlled arterial hypertension * Positive beta-HCG * Respiratory exacerbation during the inclusive period * Patients under guardianship or curatorship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study the rate of circulating endothelial microparticles (EPPs) according to the severity of pulmonary hypertension associated with COPD. | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if hemodynamic control is required (RHC) | Circulating biomarkers of vascular damage and cell activation will be measured in blood samples from COPD patients who have hemodynamic assessment by RHC. Samples will be withdrawn from occluded pulmonary artery and jugular vein during the exam. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC) | Circulating markers of endothelium damage with circulating microvesicles will be dosed. |
Countries
France