Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

Abstract

BackgroundChronic rhinosinusitis (CRS) is a clinical syndrome primarily characterized by long-term mucosal inflammation of the nasal cavity and sinuses. The pathogenesis of CRS is still unclear due to its high heterogeneity. A number of studies have recently focused on the sinonasal epithelium. Thus, there has been a quantum leap in awareness of the role of the sinonasal epithelium, which is now understood as an active functional organ rather than simply an inert mechanical barrier. Undoubtedly, epithelial dysfunction plays a vital role in the onset and development of CRS.ObjectiveIn this article, we discuss the potential contribution of sinonasal epithelium dysfunction to CRS pathogenesis and explore a few current and developing therapeutic options targeting the sinonasal epithelium.ResultsImpaired mucociliary clearance (MCC) and an abnormal sinonasal epithelial barrier are usually considered to be the main causative factors in CRS. Epithelial-derived bioactive substances, such as cytokines, exosomes, and complements, play a vital role in the regulation of innate and adaptive immunity and contribute to the pathophysiological alterations of CRS. The phenomena of epithelial–mesenchymal transition (EMT), mucosal remodeling, and autophagy observed in CRS offer some novel insights into the pathogenesis of this disease. In addition, existing treatment options targeting disorder of sinonasal epithelium can help to relieve the main symptoms associated with CRS to some extent.ConclusionThe presence of a normal epithelium is fundamental for maintaining homeostasis in the nasal and paranasal sinuses. Here, we describe various aspects of the sinonasal epithelium and highlight the contributions of epithelial dysfunction to CRS pathogenesis. Our review provides sound evidence of the need for in-depth study of the pathophysiological alterations of this disease and for the development of novel epithelium-targeting alternative treatments.

The destruction of mucosal barriers, epithelial remodeling, and impaired mucociliary clearance: possible pathogenic mechanisms of Pseudomonas aeruginosa and Staphylococcus aureus in chronic rhinosinusitis

“…This dysfunction compromises the protective capabilities of the nasal mucosa, making it more susceptible to bacterial attachment and biofilm formation. These findings highlight the significance of mucociliary dysfunction in the pathogenesis of CRS [ 3 ].…”

“…Due to CRS’s great degree of heterogeneity, its pathophysiology is still unclear. Different factors, such as racial and geographical factors, the dysfunction of mucociliary clearance (MCC), destruction of epithelial barriers, disrupted immune response, biofilm community of microorganisms, and dysbiosis of sinus microbiota, be related to the onset and development of CRS [ 3 , 4 ].…”

“…The nasal mucosa is protected by the epithelium, which serves as the initial barrier against potential threats. The fundamental mechanical barrier is formed by cell-cell contact and the MCC system [ 3 ].…”

“…In this regard, the sinonasal epithelium is known to have a significant impact on both innate and adaptive immunity. Hence, the atypical functionality of the epithelium can exert a substantial influence on the initiation and progression of CRS [ 3 ].…”

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“…Trapped into the mucosal layer, the inhaled agents are transported towards the pharynx and swallowed via the process of mucociliary clearance which is characterized by the rhythmic beating of cilia in cells lining the surface epithelium of the airways [1]. However, lack of appropriate clearance due to barrier dysfunction and proinflammatory responses induced by inhaled agents can disrupt normal functioning of the nose, resulting in bothersome nasal symptoms [2].…”