Impact of Topical Corticosteroid Irrigations on Sinonasal Wound Healing

Abstract

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease frequently requiring surgical intervention and the long-term use of topical corticosteroids to control patient symptoms. However, corticosteroids may delay postoperative recovery following sinus surgery by disrupting tissue inflammation, a key mediator of early wound healing. This study therefore seeks to assess the impact of topical corticosteroids on sinonasal epithelial healing following local injury.MethodsPrimary human nasal epithelial cells (HNECs) were collected from two patients with CRSwNP and differentiated at air-liquid interface (ALI). A linear scratch was introduced to each monolayer of differentiated HNECs, followed by apical treatment with or without budesonide (2 μg/mL) to simulate topical use. Live-cell imaging assessed time to wound closure. Epithelial barrier function was assessed with trans-epithelial electrical resistance (TEER) before the injury as a baseline, immediately post-injury, and at 12 and 24 hours.ResultsAll wounds closed within 19 hours. The average time to wound closure was 15.1 hours for CRSwNP HNECs exposed to budesonide and 12.3 hours for those exposed to control media. This difference was statistically significant (P = .0033) despite a relatively small cohort. TEER values universally increased following an initial drop from baseline induced by scratch injury. No statistically significant difference in TEER recovery was observed between groups.ConclusionWound closure was delayed in CRSwNP HNECs exposed to budesonide versus control; however, no wounds failed to close, and no difference was identified in the return of epithelial barrier function. Topical corticosteroids may be safely initiated 24 hours following ESS.

Keywords: chronic rhinosinusitis; chronic rhinosinusitis with nasal polyps; corticosteroids; endoscopic sinus surgery; wound healing.

Figure 1.

Wound closure in CRSwNP HNECs after scratch. Time-lapsed images of control (top) and budesonide (bottom) treated CRSwNP HNECs. Images are immediately after the scratch (0H), during wound healing (5H), and right before wound closure (10H). Wound edges are highlighted in red. Scale bar represents 200 μm.

Figure 2.

Initial wound area in CRSwNP HNECs. Bar graph showing the wound area immediately after scratch in CRSwNP HNECs exposed to both steroid-free (control) and budesonide containing media. Data represented as mean ± standard error. Student’s t-test. n = 11–12 wells.

Figure 3.

Assessment of wound closure after scratch injury in CRSwNP HNECs. Bar graph showing time to wound closure in control and budesonide treated cells (A). Line graph depicting changes in wound area over time in CRSwNP HNECs exposed to budesonide or steroid-free (control) culture media (B). Student’s t-test and mixed-effects analysis. n = 11 control, 12 budesonide treated. **P ≤ .01; ****P ≤ .0001.

Figure 4.

Recovery of epithelial barrier function after scratch injury. Bar graph depicting the normalized TEER (Ω·cm²) before injury (pre-scratch), immediately after injury (0), 12 and 24 hours post-injury. Data represents mean with standard error (± SEM). Student’s t-test. n = 6 wells. *P ≤ .05; ***P ≤ .001.