The role of airway inflammation: effectiveness of mepolizumab in asthma with and without chronic rhinosinusitis and nasal polyps

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Objective: Severe eosinophilic asthma (SEA) is often associated with chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by type 2–driven eosinophilic inflammation. We sought to investigate the effect of mepolizumab on relevant clinical, functional, and inflammatory endpoints in naïve SEA patients with or without nasal polyps evaluated through induced sputum and followed for 12 months. Methods: We conducted an exploratory observational real-world cohort study including biologic-naïve SEA patients who initiated treatment with mepolizumab at an asthma referral center in Tradate, Italy. Clinical, functional, and inflammatory parameters were assessed at baseline and after 12 months. Induced sputum was used to evaluate airway inflammation. Patients were stratified by presence or absence of CRSwNP. Results: Forty patients were included, 27/40 (67.5%) had CRSwNP. After 12 months, significant reductions were observed in annual exacerbations (median, 2.0 vs. 0.0; adjusted p value [p-adj] < 0.001), maintenance oral corticosteroid use (5.0 vs. 0.0 mg; p-adj = 0.004), blood eosinophil count (543 vs. 55 cells/µL; p-adj < 0.001), and sputum eosinophil % (39.0% vs. 1.3%; p = 0.004). Asthma control and FEV1 improved significantly. In patients with CRSwNP, sinonasal symptoms markedly improved (p-adj = 0.004). No post-treatment differences in airway eosinophilia were detected between the groups. Overall, 77.5% achieved clinical remission in accordance with Severe Asthma Network Italy Delphi consensus criteria. Conclusions: Mepolizumab provided substantial clinical, functional, and anti-inflammatory benefits in SEA, regardless of CRSwNP status. Despite higher baseline eosinophilia, patients with CRSwNP showed no clear differences in outcomes when compared with those without CRSwNP, supporting the concept of united airway disease. These findings highlight the value of induced sputum as a noninvasive tool and support integrated, comorbiditydriven approaches in severe asthma management.