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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
23
Collect sputum, blood and nasopharyngeal swab during the exacerbation and at steady state 8 to 16 weeks later.
Measure lung function and follow it during 4 years
University hospital of Lille
Lille, France
Roubaix hospital
Roubaix, France
Seclin hospital
Seclin, France
Tourcoing hospital
Tourcoing, France
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.
Time frame: 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 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Between 8 to 16 weeks (steady-state)
Compare sputum microbiota between exacerbation and steady-state
Metagenomic analysis on sputum
Time frame: 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).
Time frame: 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.
Time frame: At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Describe exacerbation phenotype
Collect respiratory symptoms, received treatments and hospitalization duration.
Time frame: At inclusion (exacerbation)
Describe environmental exposure
Collect informations on the patient's occupation, occupational exposures and smoking.
Time frame: 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
Time frame: 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.
Time frame: Between 8 to 16 weeks (steady-state)
Quantify Quality of Life
Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.
Time frame: 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.
Time frame: 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.
Time frame: Between 8 to 16 weeks (steady-state) and annually for 4 years
Measure airway resistances
Measure resistances with the forced oscillation technique.
Time frame: Between 8 to 16 weeks (steady-state) and at 2 and 4 years
Measure exercise tolerance
Perform a 6-minute walk-test.
Time frame: 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.
Time frame: Between 8 to 16 weeks (steady-state) and at 2 and 4 years
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