Evaluation of Mepolizumab Effectiveness in Patients With Chronic Rhinosinusitis With Nasal Polyps and Comorbid Severe Eosinophilic Asthma: an Integrative Multi-omics Approach to Assess Biomarker Signatures of Responsive Disease Endotypes
The goal of this observational study is to learn about clinical and functional outcomes in patients with Chronic rhinosinusitis with nasal polyps and comorbid Severe Eosinophilic Asthma and patients with Chronic rhinosinusitis with nasal polyps only treated with mepolizumab compared to healthy controls. Participants will be asked to give nasal, blood and sputum samples before mepolizumab administration (T0) and at 3 (T3), 6 (T6) and 12 (T12) months after mepolizumab initiation The main aims are to identify airways microbiota modifications and differential gene expression after mepolizumab initiation. Researchers will compare: * Patients with Chronic rhinosinusitis with nasal polyps and comorbid Severe Eosinophilic Asthma * Patients with Chronic rhinosinusitis with nasal polyps only * Healthy subjects The research will address the following questions: 1. What are the prospective clinical and functional outcomes of mepolizumab treatment 2. What is the impact of mepolizumab therapy on the airways microbiota and how this may relate to a potentially reduced need for steroids 3. What are the host differential gene expression patterns and the immune/inflammatory (cytokines/chemokines) profile alterations in airways microenvironment and in systemic circulation in response to therapy 4. What are the associations between host and microbiome variables for building up diagnostic and predictive biomarker classifiers of responsive disease endotypes
• Eligible for inclusion will be patients diagnosed with CRSwNP according to the European Position Paper on Rhinosinusitis and Nasal Polyps that fulfill the criteria for initiating treatment with biologics as standard of care \[49\], suffering or not from comorbid severe asthma (CRSwNP + AS, CRSwNP - AS, respectively) who will consent to participate in the study. The study will not influence prescribing of mepolizumab to patients.
⁃ Eligible to treatment women in childbearing potential will be informed before consent that they must take care of contraception and potential pregnancy during therapy as there is not enough data regarding the use of mepolizumab during pregnancy. All patients with severe asthma will be qualified for treatment with mepolizumab in accordance with GINA guidelines.