Flow Cytometry Analysis of Eosinophils in Severe Asthma Patients.

NCT05001529 | Unknown Phase 4

• 1 other identifier: EoAG
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is a heterogeneous disease, characterized by reversible airflow obstruction, airway hyperresponsiveness, and airway inflammation, in which 40% of patients exhibit eosinophil-driven pathobiology.The main treatment of asthma is the use of corticosteroid, whose use induces a reduction in eosinophils that is considered a strong predictor of response to treatment. Corticosteroids have remained the mainstay treatment of asthma and reduction in eosinophils has remained the unequivocal predictor of steroid response. The prevalence of asthma, which is expected to increase, it is about 300 million people worldwide. About 5-10% of asthma patients have severe disease, which is defined as asthma that requires high-dose inhaled corticosteroids (ICSs) plus a second controller to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy. Patients with severe disease have worse quality of life, and disproportionately high morbidity, mortality, and use of health care resources when compared with their peers with well-controlled disease.The pathophysiology of asthma is complex and heterogeneous between patients, as the disease itself; however, on the basis of immune system involvement, it is possible to define 2 subtypes - or endotypes- of asthma. These endotypes are named T2 (for type 2 cells) high or low, and are defined by the levels of expression of the T2 cytokines, IL-4, IL-5, and IL-13 produced by T helper 2 lymphocytes, and innate lymphoid cell-2.T2 high endotype patients display an increase in the number of blood and sputum eosinophils, and have a better response to the current available biological therapies , such as the administration of mepolizumab (anti IL-5 antibody). Eosinophilic asthma is associated to a more severe clinical phenotype,but patients with a T2 endotype respond better to biological therapies. The hypothesis of the present proposal is that the activation status of these cells, analyzed by the expression of activation markers, can be used to define a new, different, endotype, in which eosinophils, although quantitatively low or normal, are qualitatively more active and aggressive, and could therefore act as an indicator of the progression toward a T2 high endotype.Moreover, the investigators will verify whether a different expression of these molecules on eosinophil's surface might be associated with different clinical response to biologic medications.

Conditions

Severe Asthma

Keywords

severe asthma; eosinophils phenotype; anti-IL5R antibody

Outcome Measures

Primary Outcomes (2)

• Measurement by flow cytometry of differences in the percentages of eosinophils expressing activation-related molecules

  The presence of activated eosinophils will be evaluated by flow cytometry analysis of the expression of CD193, CD63, CD294, CD125, and HLA-DR on eosinophils membrane. Results will be expressed in term of percentage (%) of eosinophils expressing the molecules;

  12 months

• Measurement by flow cytometry of the expression levels of activation markers on eosinophils membrane

  Activation-associated membrane markers (CD193, CD63, CD294, CD125, and HLA-DR) on eosinophils membrane will be evaluated by flow cytometry and results will be expressed in term of Mean Fluorescence intensity (MFI) of the molecules. MFI is a measure of the amount of the molecule expressed on eosinophils membrane: the higher the MFI, the higher the density of molecules on cellular membrane. The values will be expressed as arbitrary units (AU), defined by the instrument, comparing the samples with a negative (unstained) control.

  12 months

Secondary Outcomes (2)

• Correlation between activated eosinophils phenotype and disease progression

  12 months

• Change in the percentage of activated eosinophils in the group of patients receiving the biological treatment.

  12 months

Study Arms (2)

Group A

EXPERIMENTAL

Subject with severe asthma, treated with anti IL5R antibodies

Biological: anti IL5 receptor antibodies

Group B

NO INTERVENTION

Subject with severe asthma, treated with conventional therapy

Interventions

anti IL5 receptor antibodies BIOLOGICAL

Subjects with severe uncontrolled asthma will be assigned to treatment with Omalizumab (anti Ig E antibodies) or Mepolizumab (anti IL-5 antibodies) according to medical advice and standardized protocols for asthma treatment.

Group A

Eligibility Criteria

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

You may qualify if:

• proved diagnosis of severe, refractory eosinophilic asthma, according to GINA recommendations and International ERS/ATS guidelines;
• agreeing to participate this study and signing an informed consent.

You may not qualify if:

• current smoking habit (both tobacco and e-cigarettes),
• concomitant diseases requiring chronic administration of immunosuppressors, biologic medications or systemic corticosteroids for any disease other than asthma
• History of previous or concomitant acute or chronic disease known to directly or indirectly affect eosinophil count, both in a quantitative and qualitative manner (eosinophilic lung and gastrointestinal diseases, systemic vasculitis, allergic bronchopulmonary aspergillosis, parasitic infections, etc)
• COPD/Asthma overlap.
• Inability or denial to sign the informed consent.

Sponsors & Collaborators

• Scarlata, Simone, M.D.: lead
• IRCCS San Raffaele: collaborator

Study Sites (1)

Campus Bio Medico University and Teaching Hospital

Roma, 00136, Italy

RECRUITING

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Simone Scarlata, M.D.

CONTACT

+393939259912; s.scarlata@unicampus.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: August 12, 2021
• Study Start: March 18, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2023
• Last Updated: August 12, 2021

Record last verified: 2021-08

Locations

IT (1)