Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD (COPD1722)

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory disease of the airways linked to environmental exposure. The chronic course of COPD is often interrupted by acute exacerbations which have a major impact on the morbidity and mortality of COPD patients. A bacterial etiology for these exacerbations is common (almost 50%). Moreover, airway bacterial colonization linked to an increased susceptibility is observed in COPD patients. Effective Th17 immune response is needed to develop a good response against bacteria. Thus, this study aims to demonstrate that there is a defective IL-17/ IL-22 response to bacteria in COPD leading to airway bacterial colonization and infection.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Disease, Chronic Obstructive; Bacterial Infections
• Intervention / Treatment: Other: Sample collecting; Other: Lung function measure

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie Bautin, MD; Phone Number: +33 320444318; Email: nathalie.bautin@chru-lille.fr
• Study Contact Backup: Name: Olivier Le Rouzic, MD; Phone Number: +33 320444318; Email: olivier.lerouzic@chru-lille.fr

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • University Hospital of Lille
    • Contact: Nathalie Bautin, MD; Email: nathalie.bautin@chru-lille.fr
    • Contact: Olivier Le Rouzic, MD; Email: olivier.lerouzic@chru-lille.fr
    • Principal Investigator: Nathalie Bautin, MD
    • Sub-Investigator: Olivier Le Rouzic, MD
    • Sub-Investigator: Thierry Perez, MD
    • Sub-Investigator: Jean-François Bervar, MD
  • Roubaix, France, 59100
    • Recruiting
    • Roubaix hospital
    • Contact: Olivier Le Rouzic, MD; Email: olivier.lerouzic@chru-lille.fr
    • Principal Investigator: Nicolas Just, MD
  • Seclin, France, 59113
    • Not yet recruiting
    • Seclin hospital
    • Contact: Olivier Le Rouzic, MD; Email: olivier.lerouzic@chru-lille.fr
    • Principal Investigator: Julie Delourme, MD
    • Sub-Investigator: Cyrielle Jardin, MD
  • Tourcoing, France, 59200
    • Recruiting
    • Tourcoing Hospital
    • Contact: Olivier Le Rouzic, MD; Email: olivier.lerouzic@chru-lille.fr
    • Principal Investigator: Laurence Thirard, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed COPD according GOLD guidelines
• Current or ex-smoker (at least 10 pack-years)
• Hospitalized for COPD exacerbation

Exclusion Criteria:

• Asthma or Cystic fibrosis
• No other chronic lung disease
• Solid Tumor unhealed or not considered in remission
• Inhaled drug consumption
• Women of childbearing potential without effective contraception
• Pregnant or breastfeeding women
• Incapable of consent
• Lack of social security coverage

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bacterial exacerbations; Patients with at least 10^7 UFC/ml bacteria in their sputum during their first COPD exacerbation.	Other: Sample collecting; Collect sputum, blood and nasopharyngeal swab during the exacerbation and at steady state 8 to 16 weeks later.; Other: Lung function measure; Measure lung function and follow it during 4 years
Other: Non-bacterial exacerbations; Patients without detected bacteria or below 10^7 UFC/ml in sputum during their first COPD exacerbation.	Other: Sample collecting; Collect sputum, blood and nasopharyngeal swab during the exacerbation and at steady state 8 to 16 weeks later.; Other: Lung function measure; Measure lung function and follow it during 4 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure cytokines by ELISA	Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the sputum,between the two groups of patients.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the blood.	Measure cytokines by ELISA in the blood at exacerbation and at steady-state. Compare the delta of these cytokines between the two groups of patients.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Identify IL-17 and IL-22 producing cells in the blood	Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the blood.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Identify IL-17 and IL-22 producing cells in the sputum	Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the sputum.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Quantification of immune cell types in the blood	Quantify by flow cytometry different immune cells in the blood: monocytes, macrophages, B and T cells, innate lymphocytes.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Quantification of immune cell types in the sputum	Quantify by flow cytometry different immune cells in the sputum: monocytes, macrophages, B and T cells, innate lymphocytes.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Quantification of pro-inflammatory cytokines in blood	Quantify by ELISA Th1 (IL-12, IFN gamma), Th2 (IL-4, IL-5), Th17 (IL-1 beta, IL-6, IL-23, TGF beta), regulatory (IL-10) and pro-inflammatory cytokines (IL-8) in the blood.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Quantification of pro-inflammatory cytokines in sputum	Quantify by ELISA Th1 (IL-12, IFN gamma), Th2 (IL-4, IL-5), Th17 (IL-1 beta, IL-6, IL-23, TGF beta), regulatory (IL-10) and pro-inflammatory cytokines (IL-8) in the sputum.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Identify pathogens linked to the exacerbation	Research of classical bacteria and fungi by usual microbial cultures from sputum and of respiratory virus and non conventional bacteria (Mycoplasma, Legionella, Bordetella pertussis and parapertussis and Chlamydophila pneumoniae) by PCR on nasopharyngeal swab.	At inclusion (exacerbation)
Identify persistent pathogens at steady-state	Research of classical bacteria and fungi by usual microbial cultures from sputum and of respiratory virus and non conventional bacteria (Mycoplasma, Legionella, Bordetella pertussis and parapertussis and Chlamydophila pneumoniae) by PCR on nasopharyngeal swab.	Between 8 to 16 weeks (steady-state)
Compare sputum microbiota between exacerbation and steady-state	Metagenomic analysis on sputum	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Compare oxidative stress in the blood between exacerbation and steady-state	Quantification by ELISA in the blood of oxidative stress markers (isoprostane, superoxyde dismutase, 3-nitrotyrosine, peroxyde, catalase).	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Quantification of oxidative stress in exhaled condensates	Quantification by ELISA of nitrite species in exhaled condensates.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Describe exacerbation phenotype	Collect respiratory symptoms, received treatments and hospitalization duration.	At inclusion (exacerbation)
Describe environmental exposure	Collect informations on the patient's occupation, occupational exposures and smoking.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Describe COPD clinical phenotype	Collect morphological informations, history of exacerbations	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Describe COPD radiological phenotype	Realization of a chest CT scan if not performed during the 2 previous years.	Between 8 to 16 weeks (steady-state)
Quantify Quality of Life	Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Describe COPD treatments	Collect informations on treatments related to COPD including inhaled treatments, influenza and pneumococcal vaccinations, oxygen therapy and respiratory rehabilitation.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Measure static lung function	Test the lung function with spirometry and plethysmography repeated annually to measure the decline of respiratory function.	Between 8 to 16 weeks (steady-state) and annually for 4 years
Measure airway resistances	Measure resistances with the forced oscillation technique.	Between 8 to 16 weeks (steady-state) and at 2 and 4 years
Measure exercise tolerance	Perform a 6-minute walk-test.	At inclusion (end of the hospitalization for exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Analysis exercise tolerance	Perform a cardiopulmonary exercise test on a bicycle.	Between 8 to 16 weeks (steady-state) and at 2 and 4 years

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Nathalie Bautin, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2018
• Primary Completion (Anticipated): July 1, 2028
• Study Completion (Anticipated): July 1, 2028

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota; Immunity; Exacerbations; Interleukin-17; Mucosal; Interleukin-22
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections and Mycoses; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Bacterial Infections
• Other Study ID Numbers: 2013_76; 2015-A00190-49 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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