Abstract
Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.