Modeling Bronchial Epithelium in Severe Asthma With Human Induced Pluripotent Stem Cells (iPSC)

NCT05616338 | Completed

• 2 other identifiers: RECHMPL22_03842022-A02059-34
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus. The development of a model of bronchial epithelium generated from patients with chronic lung disease will allow the modeling of bronchial tissue to understand the formation of these mucus plugs. This study aims to validate this model The investigators propose to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments: Differentiation of an Induced Pluripotent Stem cell (iPSC) clone derived from blood sample (Peripheral Blood Mononuclear Cells) of Type 2 inflammation (T2) severe asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in order to obtain differentiated bronchial epithelia in vitro.

Conditions

Severe Asthma; Allergic Bronchopulmonary Aspergillosis (ABPA)

Keywords

Severe asthma; ABPA; Pluripotent stem cells; Airway epithelium; Eosinophils; Crystal

Outcome Measures

Primary Outcomes (1)

• Obtention of functional bronchial epithelium from iPSC: yes/no

  Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood? (yes/no) The achievement of functional bronchial epithelium (iALI) from iPSCs of a T2 severe asthma patient and an ABPA patient will be assessed by quantification of differentiation markers by immunofluorescence, integrity of the bronchial epithelium by measurement of trans-epithelial resistance (TEER), secretory function by measurement of mucin concentrations (CCSP, MUC5AC and MUC5B) and analysis of ciliary beat

  Day 0 + culture (cross-sectional study)

Secondary Outcomes (5)

• Comparison of the transcriptomic profile between iALI and airway epithelial cells

  Day 0 + culture (cross-sectional study)

• Comparison of the transcriptomic profile between bronchial epithelia generated from severe asthma patients and from healthy subjects

  Day 0 + culture (cross-sectional study)

• Differentiation of iPSC into mature eosinophils : yes/no

  Day 0 + culture (cross-sectional study)

• Evaluation of immune cell/bronchial epithelium dialogue

  Day 0 + culture (cross-sectional study)

• Obtention of iPSC from peripheral blood sampling : yes/no

  Day 0 + culture (cross-sectional study)

Study Arms (1)

Eligible patients

EXPERIMENTAL

Other: Blood sample

Interventions

Blood sample OTHER

A blood sample and a nasal brush for each participant. The nasal brushing will allow the isolation of epithelial cells that will serve as a comparison for the bronchial tissue produced from blood-derived iPS. A blood sample of approximately 14 ml will be taken for isolation and freezing of the blood mononuclear cells allowing the generation of iPS.

Also known as: nasal brush

Eligible patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Smoking \< 10 BP and weaned \> 1 year.
• Diagnostic criteria for Severe asthma group T2 :
• History of severe asthma diagnosed by a physician (according to GINA criteria)
• Blood eosinophilia in history (previous years) \> 300/mm3
• Diagnostic criteria for Allergic bronchopulmonary aspergillosis (ABPA) group
• \- Diagnosis of ABPA defined by the following 3 mandatory criteria:
• Diagnosis of asthma by the physician for at least 12 months based on the 2019 recommendations of the Global Initiative for Asthma (GINA) group
• Evidence of hypersensitivity to Aspergillus Fumigatus by skin test (on screening or previous documented positive skin test within the last 12 months), or serum Immunoglobulin E (IgE) specific antibodies to A. Fumigatus (≥ 0.35 kUnit/l) at screening.
• Elevated total serum IgE (\> 1000 IU/ml). If the 3 ancillary criteria for the diagnosis of of ABPA (below) are met, an IgE level ≤ 1,000 IU/ml is acceptable. If the patient is receiving oral corticosteroids (OCs) at screening, a previous documented IgE level \>1000 IU/ml within the last 12 months is acceptable.
• And at least 2 of the following ancillary criteria:
• Blood eosinophil count \>500 cells/μl at screening for patients not receiving OCs at screening. For patients receiving OCs at screening, blood eosinophil count \> 500 cells/μl at screening or documented previous eosinophil count \> 500 cells/μl in the last 12 months.
• Presence of precipitating antibodies or serum immunoglobulin G (IgG) to A. Fumigatus at screening.
• Documented radiological abnormalities consistent with ABPA (such as transient mucoid impaction, hyperdense mucus \[high attenuation of mucous plugs\], opacities of centro-lobular nodules attenuation of mucous plugs\], opacities of centro-lobular nodules, telectasis, bronchiectasis, etc.) by chest X-ray or high-resolution computed tomography (HR-CT) within the last 18 months or at screening.

You may not qualify if:

• Other associated respiratory diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis)
• Protected populations according to the French public health code: Parturient, nursing or pregnant women; subjects deprived of liberty by judicial or administrative decision; Major protected by law (under any form of guardianship).
• Lack of informed consent
• Non-beneficiary of the national health insurance system

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

university Hospital of Montpellier

Montpellier, 34295, France

Location

MeSH Terms

Conditions

Asthma; Aspergillosis, Allergic Bronchopulmonary

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Respiratory Tract Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Anne Sophie GAMEZ, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: November 29, 2022
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: September 30, 2025

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Datasets that underlie the results reported in the article (text, tables, figures, and appendices) can be requested after the publication process has been completed.
• Access Criteria: The conditions under which members of the public will be granted access to datasets are: * The data will be used/examined in a not-for-profit manner; * The data will not be used in an attempt to identify a participant or group of participants; * The user does not work for a private insurance company; * The data will not be used in support of any kind of private insurance policy or health penalties; * The data will be used/examined for the advancement of science/ teaching while respecting participant/patient privacy and rights; * The user will state why they wish to access the data.

Locations

FR (1)