Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD
- Conditions
- Bacterial InfectionsPulmonary Disease, Chronic Obstructive
- Interventions
- Other: Sample collectingOther: Lung function measure
- Registration Number
- NCT02655302
- Lead Sponsor
- University Hospital, Lille
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Diagnosed COPD according GOLD guidelines
- Current or ex-smoker (at least 10 pack-years)
- Hospitalized for COPD exacerbation
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-bacterial exacerbations Sample collecting Patients without detected bacteria or below 10\^7 UFC/ml in sputum during their first COPD exacerbation. Bacterial exacerbations Sample collecting Patients with at least 10\^7 UFC/ml bacteria in their sputum during their first COPD exacerbation. Non-bacterial exacerbations Lung function measure Patients without detected bacteria or below 10\^7 UFC/ml in sputum during their first COPD exacerbation. Bacterial exacerbations Lung function measure Patients with at least 10\^7 UFC/ml bacteria in their sputum during their first COPD exacerbation.
- Primary Outcome Measures
Name Time Method Measure cytokines by ELISA At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the sputum,between the two groups of patients.
- Secondary Outcome Measures
Name Time Method Quantification of immune cell types in the blood At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Quantify by flow cytometry different immune cells in the blood: monocytes, macrophages, B and T cells, innate lymphocytes.
Describe exacerbation phenotype At inclusion (exacerbation) Collect respiratory symptoms, received treatments and hospitalization duration.
Describe environmental exposure At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years Collect informations on the patient's occupation, occupational exposures and smoking.
Analysis exercise tolerance Between 8 to 16 weeks (steady-state) and at 2 and 4 years Perform a cardiopulmonary exercise test on a bicycle.
Identify IL-17 and IL-22 producing cells in the blood At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the blood.
Quantification of immune cell types in the sputum At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Quantify by flow cytometry different immune cells in the sputum: monocytes, macrophages, B and T cells, innate lymphocytes.
Quantification of pro-inflammatory cytokines in blood At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) 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.
Quantification of pro-inflammatory cytokines in sputum At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) 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.
Compare sputum microbiota between exacerbation and steady-state At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Metagenomic analysis on sputum
Quantification of oxidative stress in exhaled condensates At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Quantification by ELISA of nitrite species in exhaled condensates.
Identify IL-17 and IL-22 producing cells in the sputum At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the sputum.
Describe COPD treatments At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years Collect informations on treatments related to COPD including inhaled treatments, influenza and pneumococcal vaccinations, oxygen therapy and respiratory rehabilitation.
Measure static lung function Between 8 to 16 weeks (steady-state) and annually for 4 years Test the lung function with spirometry and plethysmography repeated annually to measure the decline of respiratory function.
Measure airway resistances Between 8 to 16 weeks (steady-state) and at 2 and 4 years Measure resistances with the forced oscillation technique.
Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the blood. At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) 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.
Identify pathogens linked to the exacerbation At inclusion (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.
Identify persistent pathogens at steady-state Between 8 to 16 weeks (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.
Compare oxidative stress in the blood between exacerbation and steady-state At inclusion (exacerbation) and between 8 to 16 weeks (steady-state) Quantification by ELISA in the blood of oxidative stress markers (isoprostane, superoxyde dismutase, 3-nitrotyrosine, peroxyde, catalase).
Describe COPD radiological phenotype Between 8 to 16 weeks (steady-state) Realization of a chest CT scan if not performed during the 2 previous years.
Describe COPD clinical phenotype At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years Collect morphological informations, history of exacerbations
Quantify Quality of Life At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.
Measure exercise tolerance At inclusion (end of the hospitalization for exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years Perform a 6-minute walk-test.
Trial Locations
- Locations (4)
Tourcoing hospital
🇫🇷Tourcoing, France
Roubaix hospital
🇫🇷Roubaix, France
University hospital of Lille
🇫🇷Lille, France
Seclin hospital
🇫🇷Seclin, France