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Clinical, Radiological, Tissue and Biological Phenotyping for the Analysis of the Transition From Physiology to Pathology in Pulmonary Diseases With Pulmonary Hypertension

Not yet recruiting
Conditions
Pulmonary Hypertension
Chronic Pulmonary Disease
Interventions
Biological: blood sampling
Biological: broncho-alveolar lavage sampling
Biological: lung parenchyma sampling
Registration Number
NCT07184671
Lead Sponsor
Assistance Publique Hopitaux De Marseille
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
105
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).

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Patients with chronic pulmonary disease and pulmonary hypertensionblood samplingPatients on the lung transplant list with chronic pulmonary disease and pulmonary hypertension
Patients with chronic pulmonary disease and pulmonary hypertensionbroncho-alveolar lavage samplingPatients on the lung transplant list with chronic pulmonary disease and pulmonary hypertension
Patients with chronic pulmonary disease and pulmonary hypertensionlung parenchyma samplingPatients on the lung transplant list with chronic pulmonary disease and pulmonary hypertension
Control patients with chronic pulmonary disease without pulmonary hypertensionblood samplingControl 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 with chronic pulmonary disease without pulmonary hypertensionbroncho-alveolar lavage samplingControl 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 with chronic pulmonary disease without pulmonary hypertensionlung parenchyma samplingControl 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 hypertensionblood samplingControl patients without chronic pulmonary disease or pulmonary hypertension with an indication for lung resection.
Control patients without chronic pulmonary disease or pulmonary hypertensionbroncho-alveolar lavage samplingControl patients without chronic pulmonary disease or pulmonary hypertension with an indication for lung resection.
Control patients without chronic pulmonary disease or pulmonary hypertensionlung parenchyma samplingControl patients without chronic pulmonary disease or pulmonary hypertension with an indication for lung resection.
Primary Outcome Measures
NameTimeMethod
Percentage of pulmonary artery media thickness measured by optical microscopySurgical intervention
Secondary Outcome Measures
NameTimeMethod
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 the radiological phenotyping of patients with pulmonary hypertension and without pulmonary hypertension, determined from patient lung scansBaseline
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
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

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