Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease

Not Applicable

Recruiting

• Conditions: Chronic Obstructive Lung Disease; Chronic Obstructive Pulmonary Disease
• Interventions: Other: Thoracic resection surgery

• Registration Number: NCT05227547
• Lead Sponsor: Centre Hospitalier Intercommunal Creteil

Brief Summary

To evaluate the regenerative capacities of mesenchymal cells composing the microenvironment of alveolar type 2 cells in a population of patients, undergoing thoracic surgery for suspected cancer, who are smokers with and without COPD compared to non-smokers patients

Detailed Description

Chronic obstructive pulmonary diseases (COPD) have a major public health impact, as evidenced by the 250 million patients affected by these diseases and the 50% 5-year mortality for severe stages of chronic obstructive pulmonary disease (COPD). One pathophysiological mechanism of COPD and emphysema is a depletion of alveolar progenitor cells inducing a loss of alveolar-reparation capacities after an aggression. The genesis of these alterations and the mechanisms involved remain unknown. Alveolar type 2 cells (AT2) are the alveolar epithelial progenitor cells. AT2 proliferate and differentiate into alveolar type 1 cells (AT1) which form the alveolar-capillary barrier, along with endothelial cells, through which respiratory gas exchanges take place. The proliferation and differentiation of AT2 into AT1 are under the control of mesenchymal cells and endothelial cells located in close proximity. Together these cells form the alveolar stem cell niche. The characteristics and interactions of the different cell populations have been well described during lung growth, in the normal adult lung or during pulmonary fibrosis; however, participants are poorly described during smoking exposure and chronic obstructive diseases.

Study Timeline

• Study First Submitted: 2021-11-04
• Study First Submitted QC: 2022-01-26
• Study First Posted: 2022-02-07
• Study Start: 2022-10-05
• Status Verified: 2022-11
• Last Update Submitted: 2023-03-06
• Last Update Posted: 2023-03-08
• Primary Completion: 2025-10-31
• Study Completion: 2030-10-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1. Age ≥ 18
2. Patient undergoing lung resection surgery (lobectomy, pneumonectomy, segmentectomy) for cancer or suspected cancer
3. Acceptance to participate in the protocol
4. Affiliated to a social security plan

Exclusion Criteria

1. Chronic autoimmune disease
2. Patient under guardianship or curators
3. Neo-adjuvant chemotherapy
4. History of thoracic radiotherapy
5. Pregnant woman
6. Minor patient
7. Person not able to consent
8. Person deprived of liberty

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Thoracic resection surgery	Thoracic resection surgery	Smokers (active or ex-smokers) and non-smokers with COPD and without COPD undergoing thoracic resection surgery

Primary Outcome Measures

Name	Time	Method
Number of alveolar organoids	through study completion, an average of 3 years	Comparison of the number of alveolar organoids formed 21 days after culture of fibroblasts with alveolar type II cells between smokers with and without COPD and non-smoking patients

Secondary Outcome Measures

Name	Time	Method
Fibroblast proliferation capacity	through study completion, an average of 3 years	Evaluated by their doubling time, number of cells collected compared to the number of cells seeded
Differentiation into myofibroblasts	through study completion, an average of 3 years	By immunofluorescence marking: number of alpha-smooth muscle actin (alpha-SMA) + cells compared to total cells
Measurement of pulmonary diffusion capacity of CO (DLCO)	through study completion, an average of 3 years	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of pulmonary diffusion capacity of CO (DLCO)
Identification of different cell types on total lung	through study completion, an average of 3 years	Cell types composing the lung stem cell microenvironment measured by single cell analysis
Measurement of CO transfer coefficient (KCO)	through study completion, an average of 3 years	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of CO transfer coefficient (KCO)
Fibroblast migration capacity	through study completion, an average of 3 years	Evaluated in Boyden chamber
Modulated signaling pathways in isolated fibroblasts between groups	through study completion, an average of 3 years	Evaluated by Ribonucleic acid (RNA) sequencing of fibroblasts
Modulated signaling pathways in endothelial cells between groups	through study completion, an average of 3 years	Evaluated byRibonucleic acid (RNA) sequencing of endothelial cells
Evaluation of cytokines in fibroblasts supernatant	through study completion, an average of 3 years	Evaluated by Luminex Assay
Tumor progression	through study completion, an average of 3 years	By studying the migration and invasion of tumor cells
Measurement of Forced Vital Capacity (FVC )	through study completion, an average of 3 years	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced Vital Capacity (FVC )
Severity of pulmonary emphysema,	At inclusion, every year, up to 5 years after surgery	Change of lung density assessed by computed tomography scan
Type of pulmonary emphysema	At inclusion, every year, up to 5 years after surgery	Assessed by computed tomography scan : \[centro-lobular or pan-lobular, para-septal\]
Research of pulmonary biomarkers	through study completion, an average of 3 years	Searched according to the results obtained during cell cultures (immunohistochemistry, immunofluorescence)
Identification of biomarkers in the pre and postoperative circulating blood	through study completion, an average of 3 years	Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers
Identification of biomarkers in the intestinal microbiota	through study completion, an average of 3 years	Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers
Measurement of Forced expiratory volume at one second (FEV1)	through study completion, an average of 3 years	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced expiratory volume at one second (FEV1)

Trial Locations

Locations (4)

Rousseau-Bussac; 🇫🇷 Créteil, France

Hopital Tenon; 🇫🇷 Paris, France

Hopital Cochin; 🇫🇷 Paris, France

HEGP; 🇫🇷 Paris, France