The Significance of Circulating Microvesicles in Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease

Study Overview
=================
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.

Official Title
-----------------
Characterization and Significance of Circulating Microvesicles in Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease

Conditions
-----------------
Pulmonary Hypertension Due to Chronic, Obstructive Pulmonary Disease, Circulating Microvesicles, Circulating Markers of Endothelium Damage

Intervention / Treatment
-----------------
* Procedure: Catheterization


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Catheterization|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|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study the rate of circulating endothelial microparticles (EPPs) according to the severity of pulmonary hypertension associated with COPD. | 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. | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if hemodynamic control is required (RHC) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease | Circulating markers of endothelium damage with circulating microvesicles will be dosed. | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC) | 
| Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease | Proinflammatory markers with circulating microvesicles will be dosed. | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC) | 
| Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease | Cell stimulation estimated with circulating microvesicles will be dosed. | - During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC) |