Chronic Pulmonary Disease, Pulmonary Hypertension
Conditions
Keywords
Pulmonary hypertension, chronic pulmonary disease, Phenotyping, Vascular remodeling
Brief summary
This is a monocentric, case-control, comparative study aiming at investigating the transition from physiological to pathological pulmonary circulation in patients with pulmonary hypertension (PH) and chronic lung diseases. The study will include 105 adults participants undergoing lung surgery, divided into three groups, Group A (patients with chronic lung disease and PH undergoing lung transplantation), Group B (patients with chronic lung disease without PH), and Group C (patients without chronic lung disease nor PH). The primary objective is to identify the association between vascular remodeling and PH by measuring the medial thickness of pulmonary arteries. Secondary objectives include multimodal phenotyping (clinical, radiological, tissue, and biological) to explore mechanisms of PH development. Blood, broncho-alveolar lavage, and lung tissue samples will be collected during routine care. The study aims to improve understanding of PH pathophysiology and identify potential biomarkers and therapeutic targets.
Interventions
BIOLOGICALblood sampling
22mL peripheral blood will be collected
BIOLOGICALbroncho-alveolar lavage sampling
Collected on resected tissue
BIOLOGICALlung parenchyma sampling
Collected on resected tissue
Sponsors
Assistance Publique Hopitaux De Marseille
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female over 18 years of age 2. Patient who has received information about the study and has not expressed any objection 3. Patient who is a beneficiary or entitled person under a social security scheme 4. Patient requiring thoracic surgery for an acute or chronic acquired pathology with planned resection of lung parenchyma. 5. Group A: patients on the lung transplant list with chronic lung disease and pulmonary hypertension\*. Group B: control patients with chronic lung disease without pulmonary hypertension on the lung transplant list or with an indication for lung resection surgery for diagnostic or therapeutic purposes. Group C: control patients without chronic lung disease or pulmonary hypertension with an indication for lung resection. \*Pulmonary hypertension is defined by a mean resting pulmonary arterial pressure of 20 mmHg and pulmonary vascular resistances \> 2UW and an occlusion pulmonary arterial pressure ≤ 15 mmHg.
Exclusion criteria
1. Person in exclusion period from another research protocol at the time the no-objection is collected 2. Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of pulmonary artery media thickness measured by optical microscopy | Surgical intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the radiological phenotyping of patients with pulmonary hypertension and without pulmonary hypertension, determined from patient lung scans | Baseline | — |
| Compare cardiorespiratory functional clinical phenotyping between patients with pulmonary hypertension and without pulmonary hypertension. | Baseline | Using generalized linear model for assesment of respiratory function tests, 6-minute walk test and echocardiography of patients |
| Compare the biological phenotyping of biological lung inflammation from bronchioloalveolar lavage of patients with pulmonary hypertension and without pulmonary hypertension. | Surgical intervention | Dosage of inflammatory proteins (IL1, IL10, IL6, etc.) and cytological analysis of bronchioloalveolar lavage |
| High-throughput proteomic quantification indices of circulating serum from patients with pulmonary hypertension compared with patients without pulmonary hypertension. | Baseline | — |
| Quantify endovascular (angiophagy) and perivascular (fibrosis, pro-inflammatory cells) tissue lesions. | Surgical intervention | number of stage I, II and III angiophagia lesions relative to the number of arteries analyzed on a field of anatomopathology slides and classified according to artery diameter; surface area of pulmonary fibrosis relative to the total surface area of the tissue field explored; quantification of immune system cells in interstitial tissue relative to the tissue surface area explored. |
| Compare protein tissue phenotyping of pulmonary hypertension regulatory pathways in patients with and without pulmonary hypertension evaluated with Elisa tests on lung parenchyma. | Surgical intervention | — |
| Evaluate the statistical relationships between tissue vascular remodeling and tissue, alveolar, and blood protein alterations. | Baseline and surgical intervention | — |
| Compare genetic tissue phenotyping of pulmonary hypertension regulatory pathways in patients with and without pulmonary hypertension evaluated with PCR tests on lung parenchyma. | Surgical intervention | — |
| Compare the phenotyping of pulmonary vascular microstructure by microCT in patients with pulmonary hypertension and without pulmonary hypertension. | Surgical intervention | — |
Outcome results
None listed