The influence of corticosteroids and Azelastine on epithelial cell integrity in chronic rhinosinusitis with polyps

Abstract

Background:The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still not completely understood. Regarding the pathogenesis an impaired barrier function of the sino-nasal epithelium has been shown in CRS. Intranasal corticosteroids are widely used for treatment and part of current guidelines. This study aims to analyse the influence of corticosteroids on the epithelial integrity in air-liquid-interface (ALI) epithelial cell cultures of patients with CRSwNP.Methodology: Polyp tissue from 11 patients with CRSwNP undergoing a sphenoethmoidectomy was collected. The epithelial cells were cultured in ALI. After differentiation of the cells, the permeability of the cell layer was defined by measuring the transepithelial resistance (TER). Commonly used corticosteroids, (Fluticasone & Mometasone) and Azelastine were added and their impact on the TER was documented and compared to the TER of ALI cultures without additives (controls). Results:After 48 hours, Fluticasone showed a significant increase of the TER. Mometasone and Azelastine had no significant impact on the TER. The paracellular passage of Dextran molecules in ALI cultures showed a negative correlation to the TER. Preoperative in vivo corticosteroid treatment had no effect on the baseline TER. Further analysis of the impact of preoperative corticosteroid treatment showed no effect on polyp size, sense of smell, histopathologic eosinophilic count and allergic sensitization. Conclusion:Fluticasone shows a direct effect in restoring sino-nasal epithelial barrier in-vitro, even in the absence of inflammatory cells.

Outside-in hypothesis revisited

“…36 An increase in transepithelial resistance and a decrease in paracellular flux were observed when fluticasone propionate, a steroid used routinely to treat nasal symptoms, was added to cell cultures of patients with CRS and nasal polyp, whereas azelastine, an antihistamine, had no effects in the absence of histamine. 118,119 A similar effect was observed in AR. The disruption of TJ by pollen was reported in vitro, in which pollen peptidases lead to a loosening of the mechanical barrier.…”

Rhinology in review: from COVID-19 to biologicals

“…In the treatment of CR, azelastine has an increasingly prominent role. This drug that originally was classified as an antihistamine has been shown to be effective in some forms of NAR and in a combination preparation with local corticosteroids it has been shown to be very effective in control of disease in AR (103,104) .…”