Treatment With Mepolizumab on Patients With Severe Refractory Eosinophilic Asthma With or Without CRSwNP.

Study Overview
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Brief Summary
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Patients with severe or difficult-to-treat asthma represent a small amount of total asthmatic patients, but weight on the national health system for the costs of disease management. Chronic rhinosinusitis with nasal polyposis, which the Italian severe/uncontrolled asthma registry reported with a prevalence of 30%, represents a comorbidity that significantly impact lung function and asthma control in severe asthma. Recent evidence indicates that there is a consistent heterogeneity regarding mucosal alterations present in subjects with nasal polyposis involving different pathways: inflammatory cells, remodeling, T cell activation, local IgE production, alteration induced by interactions between microorganisms and epithelial cells.

Detailed Description
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Nasal, bronchial and systemic inflammation can differ among patients with severe refractory eosinophilic asthma with or without CRSwNP. Treatment with Mepolizumab could modify nasal, bronchial and systemic inflammation of patients with severe refractory eosinophilic asthma and nasal polyposis acting on disease control.

Official Title
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Biomarkers Evaluation and Effect of Mepolizumab on Lower and Upper Airways Inflammation in Severe Refractory Eosinophilic Asthma and Nasal Polyposis

Conditions
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Asthma, Nasal Polyps, Sinusitis Chronic

Intervention / Treatment
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* Drug: Mepolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:age >18 years diagnosis of severe refractory asthma according to the ERS/ATS criteria ATS Blood eosinophils >150 cells/mcL at the screening visit and at least one value of 300 or more eosinophils/mcL during the previous year; at least two exacerbations despite maximal therapy with long-acting bronchodilators and high dose inhaled corticosteroids in the previous year or the need for continued therapy with oral corticosteroids in addition to maximal inhaled therapy for at least 6 months in the previous year written informed consent. For CRSwNP diagnosis, the EPOS 2020 guidelines will be considered as reference. All the above-mentioned inclusion criteria must be met. Exclusion Criteria:Pregnancy Eosinophilic Granulomatosis with Polyangiitis (EGPA); Serious life threatening cardiopulmonary disorders; Systemic immunologic disorder in the last 12 months; Positive history for malignant tumors ever in patient's life; Immunodeficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRSwNP<br>10 patients with severe refractory eosinophilic asthma plus CRSwNP | Drug: Mepolizumab<br>* Treatment with Mepolizumab could modify nasal, bronchial and systemic inflammation of patients with severe refractory eosinophilic asthma and nasal polyposis acting on disease control<br>* Other names: Nucala;|
| No CRSwNP<br>10 patients with severe refractory eosinophilic asthma and no CRSwNP | Drug: Mepolizumab<br>* Treatment with Mepolizumab could modify nasal, bronchial and systemic inflammation of patients with severe refractory eosinophilic asthma and nasal polyposis acting on disease control<br>* Other names: Nucala;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function tests | by the helium dilution method | 2 years | 
| Nasal cytology | mediator evaluations | 2 years | 
| Induced sputum | high sensitive tests ELISA | 2 years | 
| Exhaled NO | measurement of FeNO | 2 years | 
| Inflammatory markers | ELISA test | 2 years | 
| EBC sampling | α-amylase activity | 2 years | 
| NMR-based metabolomics | NMR spectroscopy | 2 years |