New Concepts in Barrier Dysfunction in CRSwNP and Emerging Roles of Tezepelumab and Dupilumab

Abstract

Background Epithelial barrier disturbances in CRSwNP patients play an important role in both the innate and adaptive immune responses, contributing to chronic inflammation, olfactory dysfunction, and impairments in quality of life. Objective To evaluate the role of the sinonasal epithelium in disease and health, review the pathophysiology of epithelial barrier dysfunction in CRSwNP, and the immunologic targets for treatment. Methods Literature review. Results Blockade of cytokines such as thymic stromal lymphopoietin (TSLP), IL-4, and IL-13 have shown promise in barrier restoration and IL-13, specifically may be central to olfactory dysfunction. Conclusion The sinonasal epithelium plays a crucial role in the health and function of the mucosa and immune response. Increased understanding of the local immunologic dysfunction has led to several therapeutics that can potentially restore epithelial barrier function and olfaction. Real world and comparative effectiveness studies are needed.

The last step to achieve barrier damage control

“…Comorbidities involving both upper and lower airway diseases typically stem from a shared underlying immunologic response initiated by epithelial barrier damage, leading to “unified airway disease” definition, particularly in the context of the T2 immunologic endotype. Regarding CRSwNP, a 52-weeks clinical trial to investigate the effectiveness of tezepelumab is currently ongoing ( 52 ). Promising data in severe asthma patients with comorbid CRSwNP are already available: tezepelumab demonstrated clinically meaningful effect on sinonasal symptoms with the greatest improvements seen for the sleep, function and nasal domains of Sino-Nasal Outcome Test (SNOT)-22 questionnaire.…”

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update

“… 126 , 127 Other authors also mention that current immunobiologicals (especially dupilumab and tezepelumab) act not only on the T2 response, but also on epithelial barrier dysfunction. 128 , 129…”