Eosinophils Endotypes in Chronic Airway Inflammatory Diseases

NCT04187976 | Unknown DMC

• 2 other identifiers: 2018_812019-A01457-50
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequently described as unified airway inflammatory diseases. Both heavily impacts quality of life with substantial productivity loss. They share the same pathophysiologic pattern based upon proTh2 immune response with blood eosinophils recruitment. Eosinophils are the major actor of persistent mucosal inflammation by promoting their own survival, by attracting other inflammatory cells and by producing cytotoxic proteins involved in mucosal remodeling. Promising anti-Th2 therapeutic approaches (i.e.anti-IgE, anti-interleukin 5 (IL-5), anti-IL-4, anti-IL-13) are considered as effective alternative options to long-term corticosteroid treatment. Their advantage in recalcitrant CRSwNP is under consideration. Moreover, we still need to delineate the good responders to improve theirs indications. The objective is to assess blood eosinophil immunophenotypes in asthma or CRSwNP. Flow cytometric expression of activation markers on eosinophil membrane will be compared with a group of healthy subjects. Innovative data on eosinophil involvement in airway diseases will be obtained. The major outcome will be to depict patients' endotypes for a better selection of immunotherapies.

Conditions

Eosinophilic Asthma; Chronic Sinusitis; Eosinophilic Rhinitis

Keywords

Eosinophil; asthma; chronic rhinosinusitis with nasal polyps; biotherapy; endotype

Outcome Measures

Primary Outcomes (1)

• Percentage of blood eosinophils with expression of CD69 marker in patients with uncontrolled asthma alone, recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP) alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects.

  CD69 expression is measured with flow cytometry on blood eosinophils cell surface. The percentage of blood eosinophils positive for CD69 is compared between the four groups of patients (uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects)

  Baseline

Secondary Outcomes (5)

• Percentage of blood eosinophils with expression of HLADR marker in patients with uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects.

  baseline

• Percentage of activated blood eosinophils in patients with uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects.

  baseline

• Comparison of the percentage of activated eosinophils in blood with the percentage of activated eosinophils in induced sputum in uncontrolled asthma (with or without CRSwNP).

  baseline

• Comparison of the percentage of activated eosinophils in blood with the percentage of activated eosinophils in nasal polyps in CRSwNP patients (with or without uncontrolled asthma).

  baseline

• Comparison of qualitative transcriptomic profiles of blood eosinophils in patients with uncontrolled asthma alone, recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP) alone, uncontrolled asthma and recalcitrant CRSwNP.

  baseline

Study Arms (4)

Patients with moderate to severe uncontrolled asthma

Patients with moderate to severe uncontrolled asthma defined on clinical assessment and spirometric criteria. Non controlled asthma is considered when ACQ score ≥ 1.5 or in case of acute exacerbation

Patients with recalcitrant CRSwNP requiring sinus surgery

The medical failure in CRSwNP is defined as persistent disease in spite of 3 courses of oral corticosteroid and double dose of local corticoid over 12 months

Patients with concomitant CRSwNP and uncontrolled asthma

Patients with concomitant CRSwNP and moderate to severe uncontrolled asthma

Healthy subjects

Patients without any airway inflammatory disease or atopy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients for the study will be targeted either during hospitalization in Pneumology for uncontrolled asthma patients, during ENT visit for scheduling of sinus surgery (recalcitrant CRSwNP). The healthy subjects are going to be screened in the Clinical Investigation Center of the University Hospital of Lille. Subjects will be contacted by phone after selection in the database.

You may qualify if:

• For all groups:
• Social insured patient
• Patient willing to comply with all procedures of the study and its duration
• Provision of signed and dated informed consent form prior to any study specific procedure
• For Group 1:
• \- Patients with moderate to severe uncontrolled asthma, confirmed by relevant clinical symptoms and proven variable airway obstruction, and assessed by an expert pulmonologist according to spirometry criteria (absolute and weighed Forced Expiratory Volume (FEV) and Forced Vital Capacity (FVC) before and after 2 test),(see CRF for details). Uncontrolled asthma will be defined by an ACQ score ≥ 1.5. or acute exacerbation
• For Groups 2 and 3:
• Patients with medically refractory bilateral sino-nasal polyposis requiring sinus surgery, according to an expert rhinologist. CRSwNP diagnosis is based on the presence of bilateral nasal polyps from both side of middle turbinates on nasoendoscopy and bilateral sinus opacification on CT scan. Briefly, CRSwNP is considered as refractory when symptoms are still not controlled after 3 courses of oral corticosteroid and double dose of nasal corticosteroid during the last 12 months
• Patients with both uncontrolled asthma and recalcitrant CRSwNP with or without concomitant aspirin-exacerbated respiratory disease (AERD) (group 3)
• For Group 4:
• \- Healthy subjects without any airway disease or any atopic status, as assessed by a questionnaire and a medical examination

You may not qualify if:

• For all groups:
• Patients with any other form of secondary CRSwNP (eg, cystic fibrosis, primary ciliary dyskinesia).
• Patients with any form of secondary severe asthma (eg (non)eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis)
• Patients followed up for another inflammatory or auto-immune disease
• Previous allogeneic bone marrow transplant
• Patients with ongoing sub-cutaneous or sub-lingual anti-allergenic immunotherapies
• Patients with active smoking or history of smoking \> 10 packages-year for asthma patients
• Pregnant, breastfeeding, or lactating women
• Non-coverage by the social security insurance
• Patient unable to receive informed information
• Refusal to sign the consent form
• Unwillingness or inability to follow the study procedures, in the opinion of the investigator
• Person deprived of the liberty
• Person benefiting from a system of legal protection (guardianship…)

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

CHU Lille

Lille, 59000, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Eosinophils from blood samples,nasal polyps and induced sputum

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Cécile Chenivess, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cécile Chenivesse, MD,PhD

CONTACT

03 20 44 59 48; cecile.chenivesse@chru-lille.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 5, 2019
• Study Start: March 3, 2020
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: December 8, 2023

Record last verified: 2023-12

Locations

FR (1)