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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with chronic pulmonary disease and pulmonary hypertension | Patients on the lung transplant list with chronic pulmonary disease and pulmonary hypertension |
| |
| Control patients with chronic pulmonary disease without pulmonary hypertension | Control patients with chronic pulmonary disease without pulmonary hypertension on the lung transplant list or with an indication for lung resection surgery for diagnostic or therapeutic purposes. |
| |
| Control patients without chronic pulmonary disease or pulmonary hypertension | Control patients without chronic pulmonary disease or pulmonary hypertension with an indication for lung resection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sampling | Biological | 22mL peripheral blood will be collected |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of pulmonary artery media thickness measured by optical microscopy | Surgical intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Quantify endovascular (angiophagy) and perivascular (fibrosis, pro-inflammatory cells) tissue lesions. | 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. |
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Inclusion Criteria:
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:
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Recruitment will be carried out on a continuous, daily basis in the thoracic surgery department of the Hôpital Nord in Marseille.
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| broncho-alveolar lavage sampling | Biological | Collected on resected tissue |
|
| lung parenchyma sampling | Biological | Collected on resected tissue |
|
| Surgical intervention |
| 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. | Using generalized linear model for assesment of respiratory function tests, 6-minute walk test and echocardiography of patients | Baseline |
| Compare the biological phenotyping of biological lung inflammation from bronchioloalveolar lavage of patients with pulmonary hypertension and without pulmonary hypertension. | Dosage of inflammatory proteins (IL1, IL10, IL6, etc.) and cytological analysis of bronchioloalveolar lavage | Surgical intervention |
| High-throughput proteomic quantification indices of circulating serum from patients with pulmonary hypertension compared with patients without pulmonary hypertension. | Baseline |
| Compare the phenotyping of pulmonary vascular microstructure by microCT in patients with pulmonary hypertension and without pulmonary hypertension. | Surgical intervention |
| 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 |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D066253 | Vascular Remodeling |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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