Eosinophils Endotypes in Chronic Airway Inflammatory Diseases

Chronic Sinusitis Clinical Trial

— PLEIAD  

Official title:

Peripheral Eosinophils Phenotypes in Airway Inflammatory Diseases: Towards Proper Clustering and Therapeutic Targeting

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04187976
• Other study ID #: 2018_81
• Secondary ID: 2019-A01457-50
• Status: Recruiting
• Start date: March 3, 2020
• Est. completion date: March 2024

Study information

• Verified date: December 2023
• Source: University Hospital, Lille
• Contact: Cécile Chenivesse, MD,PhD
• Phone: 03 20 44 59 48
• Email: cecile.chenivesse[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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…)

Related Conditions & MeSH terms

• Chronic Sinusitis
• Eosinophilic Asthma
• Eosinophilic Rhinitis
• Pulmonary Eosinophilia
• Rhinitis
• Sinusitis

Locations

Country	Name	City	State
France	CHU Lille	Lille

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	HLADR expression is measured with flow cytometry on blood eosinophils cell surface.; The percentage of blood eosinophils positive for HLADR 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	Percentage of activated blood eosinophils in patients with uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects.	Activated status of blood eosinophils is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry. The percentage of activated blood eosinophils 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	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).	Activated status of eosinophils in blood and in induced sputum is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry.	baseline
Secondary	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).	Activated status of eosinophils in blood and in nasal polyps is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry.	baseline
Secondary	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.	Transcriptomic profiles will be compared between CRSwNP with or without uncontrolled asthma and between uncontrolled asthma with or without CRSwNP.; A two-fold differential expression will be used for comparison.	baseline