Ciliation and Mucus Rheology Parameters Determined Via Air-liquid-interface Cell Cultures in Non-smoking, Smoking, COPD and Asthmatic Patients (RhéMuc)

Demonstration of the Diagnostic Character of the Rheology of Mucus

This is a prospective study comparing 4 groups: (1) non-smoking controls, (2) smokers without chronic obstructive pulmonary disease (COPD), (3) smokers with COPD, (4) severe asthma.

Bronchial biopsy specimens from each subject will be obtained to produce air-liquid-interface cell cultures. These will then be used to make observations concerning cilia and mucus rheology.

This is a first pilot study. The working hypothesis is that the largest group differences will be found for cilia densities; the latter metric was thus chosen as a primary criterion.

Study Overview

• Status: Terminated
• Conditions: Smoking; Pulmonary Disease, Chronic Obstructive; Asthma
• Intervention / Treatment: Procedure: Bronchial Biopsy; Other: ALI culture

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • CHU Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria for non smoking controls:

• The subject has given free and informed consent and signed the consent form
• The subject is affiliated with or beneficiary of a medical insurance program
• The subject has never smoked
• No obstructive breathing disorder (forced expiratory volume at one second (FEV1) >70% of predicted value; the ratio of FEV1 to forced vital capacity (FEV1/FVC) is > 0.7)
• No known respiratory disease

Inclusion criteria for smokers without COPD:

• The subject has given free and informed consent and signed the consent form
• The subject is affiliated with or beneficiary of a medical insurance program
• Smoker or former smoker (>= 30 pack years)
• No obstructive breathing disorder (forced expiratory volume at one second (FEV1) >70% of predicted value; the ratio of FEV1 to forced vital capacity (FEV1/FVC) is > 0.7)

Inclusion criteria for smokers with COPD:

• The subject has given free and informed consent and signed the consent form
• The subject is affiliated with or beneficiary of a medical insurance program
• Smoker or former smoker (>= 30 pack years)
• Subject presenting with COPD: FEV1/FVC < 0.7 (based on spirometry values in the medical file and performed in the 3 months prior to inclusion)
• The subject requires bronchial fibroscopy (decision made by pneumologist)
• COPD of grade "2" or "3" according to GOLD criteria (Global Initiative for Chronic Obstructive Lung Disease)

Inclusion criteria for subjects with severe asthma:

• The subject has given free and informed consent and signed the consent form
• The subject is affiliated with or beneficiary of a medical insurance program
• Non-smoker or former smoker (<10 pack years)
• Subject presenting with severe asthma: FEV1/FVC >= 0.7 and FEV1 < 80%
• The subjects requires bronchial fibroscopy (decision made by pneumologist)

Exclusion criteria:

• The subject has an extensive neoplastic disease
• The subject has another active lung disease (tuberculosis, pulmonary interstitium disease, active or recent pulmonary infection)
• The subject has had a recent psychiatric disorder (within one year prior to inclusion and documented by a specialist consultation)
• Emergency situations (object extractions...)
• Subject consuming illicit drugs or alcohol
• The subject is in an exclusion period determined by a previous study
• The subject is under judicial protection, or is an adult under any kind of guardianship
• It is impossible to correctly inform the patient
• The subject cannot fluently read French

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-smoking controls; Subjects in this group have never smoked and have no known lung disorders. Intervention: Bronchial Biopsy + ALI culture (Air Liquid Interface)	Procedure: Bronchial Biopsy; Bronchial biopsies will be performed on all subjects.; Other: ALI culture; Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.
Experimental: Smokers without COPD; Subjects in this group are smokers or former smokers who do not have signs of obstructive disease (no chronic obstructive pulmonary disease (COPD)) Intervention: Bronchial Biopsy + ALI culture	Procedure: Bronchial Biopsy; Bronchial biopsies will be performed on all subjects.; Other: ALI culture; Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.
Experimental: Smokers with COPD; Subjects in this group are smokers or former smokers who have COPD Intervention: Bronchial Biopsy + ALI culture	Procedure: Bronchial Biopsy; Bronchial biopsies will be performed on all subjects.; Other: ALI culture; Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.
Experimental: Severe asthma; Subjects in this group are non-smokers or former (light) smokers who have severe asthma. Intervention: Bronchial Biopsy + ALI culture	Procedure: Bronchial Biopsy; Bronchial biopsies will be performed on all subjects.; Other: ALI culture; Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surface density of active cilia	Surface density of active cilia	Day 0 + approximately 2 months of cell culture time

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cilia beating frequency	The frequency at which cilia beat.	Day 0 + approximately 2 months of cell culture time
Mucus viscosity	The viscosity of mucus produced by cell cultures.	Day 0 + approximately 2 months of cell culture time
Mucus elasticity	The elasticity of mucus produced by cell cultures.	Day 0 + approximately 2 months of cell culture time
Cilia beat orientation	The direction in which cilia beat	Day 0 + approximately 2 months of cell culture time

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Study Director: Anne Sophie Gamez, MD, Montpellier University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Actual): April 26, 2022
• Study Completion (Actual): December 26, 2022

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: mucus; Bronchial epithelial cell; Air Liquid Interface
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Lung Diseases, Obstructive; Chronic Disease; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: RECHMPL18_0222

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No