Carlo Cavaliere, Elena Cantone, Carlotta Pipolo, Giancarlo Ottaviano, Frank Rikki Mauritz Canevari, Ignazio La Mantia, Giandomenico Maggiore, Gabriele Brembilla, Maria Rosaria Mollo, Omar Shalby, Ernesto Pasquini, Giancarlo Pecorari, Veronica Seccia, Eugenio De Corso
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly debilitating airway disease primarily characterized by type 2 inflammation and eosinophilic infiltration. Among the key cytokines involved, Interleukin-5 (IL-5) plays a relevant role in eosinophil biology and contributes, together with other mediators of type 2 inflammation, to epithelial barrier dysfunction, immune dysregulation, mucus hypersecretion, and tissue remodeling. Therapies targeting this cytokine have demonstrated both efficacy and safety in patients with CRSwNP. This narrative commentary summarizes current evidence in understanding IL-5's role in CRSwNP, integrating insights from an Italian otolaryngology expert panel, with a particular focus on the patient journey in Italy. Available evidence suggests that IL-5 is associated with disease severity and may contribute to multiple aspects of CRSwNP pathophysiology beyond eosinophilia. Targeting the IL-5 pathway has been shown to improve clinical outcomes, including nasal polyp burden, symptom control, olfactory function, and quality of life, in selected patients. From a clinical perspective, the expert panel highlighted several critical unmet needs in the Italian setting, including diagnostic delay, heterogeneous implementation of care pathways, suboptimal patient selection, and limited adherence to long-term management strategies. The importance of structured diagnostic work-up, endotyping, multidisciplinary management, and patient awareness was emphasized. The implementation of shared Diagnostic and Therapeutic Care Pathways (PDTA) and network-based models may support more standardized and timely management, although further evidence is needed to define their impact on clinical outcomes. Overall, improving the understanding of IL-5-driven mechanisms and addressing organizational gaps may contribute to optimizing the management of CRSwNP in clinical practice.