Nasal Cytology as a Local Read-Out of Type 2 Inflammation and Epithelial Barrier Dysfunction in Chronic Rhinosinusitis with Nasal Polyps

Background: Chronic rhinosinusitis with nasal polyps, CRSwNP, represents one of the most clinically relevant models of type 2 inflammation in the upper airways. Its pathogenesis is not sustained by a single mechanism but by the continuous interaction between epithelial barrier damage, immune activation and tissue remodeling. Although several systemic biomarkers are currently used in clinical practice, they do not always reflect the inflammatory processes occurring directly within the sinonasal mucosa. Objective: This review discusses nasal cytology as a local and clinically accessible read-out of type 2 inflammation and epithelial barrier dysfunction in CRSwNP. Particular attention is given to the relationship between cytological patterns, underlying immune mechanisms and the use of biologic therapies. Methods: A narrative review of the literature was conducted, focusing on epithelial barrier abnormalities, type 2 inflammatory pathways, cytological phenotypes and available monoclonal antibodies. The clinical relevance of these elements was considered, with particular regard to patient stratification and therapeutic decision-making. Results: Epithelial barrier disruption promotes the release of alarmins such as TSLP, IL-25 and IL-33. These mediators activate both innate and adaptive type 2 immune responses and contribute to the persistence of mucosal inflammation. Nasal cytology allows direct assessment of the local inflammatory infiltrate and makes it possible to identify eosinophilic, mast cell-predominant and mixed eosinophil–mast cell patterns. These profiles appear to mirror different inflammatory settings. In particular, the coexistence of eosinophils and mast cells may identify patients with more severe, persistent or recurrent disease. When integrated into clinical tools such as clinical–cytological grading (CCG), nasal cytology may improve disease stratification, support follow-up and help orient biologic therapy according to the level of the inflammatory cascade predominantly involved. These cytological profiles may also support biologic treatment selection, therapeutic monitoring, and future tapering strategies by reflecting the predominant inflammatory pathway active at the mucosal level. Conclusions: Nasal cytology is a direct, reproducible and clinically useful approach for evaluating local inflammation in CRSwNP. By providing information from the mucosal site of disease, it complements systemic biomarkers and may support personalized therapeutic strategies and biologic treatment selection in CRSwNP.