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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Demonstration of the Diagnostic Character of the Rheology of Mucus

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive, Asthma, Smoking

Intervention / Treatment
-----------------
* Procedure: Bronchial Biopsy
* Other: ALI culture


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-smoking controls<br>Subjects in this group have never smoked and have no known lung disorders. Intervention: Bronchial Biopsy + ALI culture (Air Liquid Interface) | Procedure: Bronchial Biopsy<br>* Bronchial biopsies will be performed on all subjects.<br>Other: ALI culture<br>* Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.<br>|
| Experimental: Smokers without COPD<br>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<br>* Bronchial biopsies will be performed on all subjects.<br>Other: ALI culture<br>* Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.<br>|
| Experimental: Smokers with COPD<br>Subjects in this group are smokers or former smokers who have COPD Intervention: Bronchial Biopsy + ALI culture | Procedure: Bronchial Biopsy<br>* Bronchial biopsies will be performed on all subjects.<br>Other: ALI culture<br>* Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.<br>|
| Experimental: Severe asthma<br>Subjects in this group are non-smokers or former (light) smokers who have severe asthma. Intervention: Bronchial Biopsy + ALI culture | Procedure: Bronchial Biopsy<br>* Bronchial biopsies will be performed on all subjects.<br>Other: ALI culture<br>* Air-liquid-interface cell cultures will be derived from bronchial biopsy specimens. We are expecting several replicate cell lines from each biopsy specimen.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bronchial epithelial cell, mucus, Air Liquid Interface