Eosinophils Endotypes in Chronic Airway Inflammatory Diseases

NCT ID: NCT04187976

Last Updated: 2023-12-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-03-03
• Study Completion Date: 2024-03-31

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

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

No interventions assigned to this group

Patients with concomitant CRSwNP and uncontrolled asthma

Patients with concomitant CRSwNP and moderate to severe uncontrolled asthma

No interventions assigned to this group

Healthy subjects

Patients without any airway inflammatory disease or atopy

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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 taking or having taken systemic corticosteroid, leukotriene receptor antagonist, theophylline or long-term macrolide therapy within 1 month prior to sample collections, anti-immunoglobulin E therapy (omalizumab) anti-IL-5/5R or anti IL-4R/anti-IL13 therapies within 6 months before inclusion
• 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…)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cécile Chenivess, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

CHU Lille

Lille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Cécile Chenivesse, MD,PhD

Role: CONTACT

Phone: 03 20 44 59 48

Email: cecile.chenivesse@chru-lille.fr

Facility Contacts

Cécile Chenivesse, MD, Ph

Role: primary

Corine Glineur, Ph

Role: backup

Other Identifiers

2019-A01457-50

Identifier Type: OTHER

Identifier Source: secondary_id

2018_81

Identifier Type: -

Identifier Source: org_study_id