IL-13-associated epithelial remodeling correlates with clinical severity in nasal polyposis.

BACKGROUND: Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. OBJECTIVE: We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. METHODS: Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. RESULTS: The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. CONCLUSIONS: These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Formal Closure of Endoscopic Endonasal Skull Base Defects With a "Bow Tie" Tri-Layer Graft.

OBJECTIVE: Risk factors for a postoperative cerebrospinal fluid leak (CSF) after surgery include an intraoperative high flow of CSF, elevated body mass index, defect size, and defect site. In our prior series, a high postoperative CSF leak rate for tumors of the central skull base (planum, sella, and clivus) appeared to be due to graft migration. We changed our closure technique from a single layer of collagen +/- fat graft to a novel graft, termed a "Bow tie" (a tri-layer fat graft with two pieces of collagen matrix), and report our results in this study. METHODS: Retrospective temporal epoch study of a single otolaryngologist's experience of closing skull base defects in our skull base center from 2005 to 2017. RESULTS: One hundred and forty-nine patients met inclusion criteria in two time periods, pre- and post-introduction of the Bow tie technique. In epoch I, from 2005 to 2013, 79 patients had reconstruction with a single layer of dural graft (25 had additional free fat graft). In epoch II, from 2014 to 2017, 70 patients had reconstruction with the Bow tie. RESULTS: CSF leak rates were 8.7% overall: 15.2% in epoch I and 1.4% in epoch II (p = 0.01). After controlling the procedure, defects with a size greater than 2 cm had a 5.7 greater likelihood of failure. Epoch II had a lower incidence of major complications. CONCLUSION: Using a single surgeon's experience, the multilayer Bow tie has a significant reduction in postoperative CSF leak and associated major complications for defects of the central skull base. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1568-1575, 2023.

IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function.

Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single-cell RNA sequencing of airway epithelium and mouse modeling, we found that IL-13 expanded and programmed airway tuft cells toward eicosanoid metabolism and that tuft cell deficiency led to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bore a signature of PGE2 activation, and PGE2 activation led to cystic fibrosis transmembrane receptor-dependent ion and fluid secretion and accelerated mucociliary transport. These data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.

Septum submucosal glands exhibit aberrant morphology and reduced mucin production in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by significant accumulation and thickening of mucus in the sinonasal cavities. One contributor of aberrant mucus production and impaired mucociliary clearance (MCC) is altered function of the sinonasal submucosal glands (SMGs), yet contributions of SMGs to upper airway disease initiation and progression remain unknown. The objective of this study was to characterize the morphology and secretory cell identities of the nasal septum SMGs in both healthy and CRS adults. METHODS: Biopsies from adult participants with CRS without nasal polyps (CRSsNP, n = 4), CRS with nasal polyps (CRSwNP, n = 8), and non-CRS controls (n = 14) were collected from the posterior septum. Glandular morphology and mucus markers were investigated using histological techniques and high-resolution confocal microscopy. RESULTS: Analysis revealed a significant decrease in gland density in the posterior septum of CRSsNP (28% ± 6.15%) and CRSwNP (23% ± 3.09%) compared to control participants (53% ± 1.59%, p < 0.0001). Further analysis of the CRS SMG secretory function revealed an overall decrease in Mucin 5B+ gland mucus being produced. Dilated and cystic ductal structures filled with inspissated mucus were also common to CRS glands. CONCLUSION: Here, we describe a significant alteration in SMG structure and function in the adult CRS posterior septum suggesting reduced gland contribution to MCC. The SMGs of both the nose and sinuses may represent targets for future therapeutic approaches.

Endoscopic skull base and transoral surgery during COVID-19 pandemic: Minimizing droplet spread with negative-pressure otolaryngology viral isolation drape.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has raised concern of transmission of infectious organisms through aerosols formation in endonasal and transoral surgery. METHODS: Retrospective review. We introduce the negative-pressure otolaryngology viral isolation drape (NOVID) system to reduce the risk of aerosol. NOVID consists of a plastic drape suspended above the patient's head and surgical field with a smoke evacuator suction placed inside the chamber. RESULTS: Four patients underwent endonasal (4) and endo-oral surgery (1). Fluorescein was applied to the surgical field. Black light examination of fluorescein-treated operative fields revealed minimal contamination distant to the surgical field. In two prolonged cases with high-speed drilling, droplets were identified under the barrier and on the tip of the smoke evacuator. Instruments and cottonoids appeared to be a greater contributor to field contamination. CONCLUSIONS: Negative-pressure aspiration of air under a chamber barrier, which appears to successfully keep aerosol and droplet contamination to a minimum.

The impact of frailty on perioperative outcomes and resource utilization in sinonasal cancer surgery.

OBJECTIVES/HYPOTHESIS: Frailty is a measure of decreased physiologic reserve that has been associated with adverse outcomes in older surgical patients. We aimed to measure the association of preoperative frailty with outcomes in patients undergoing sinonasal cancer surgery. STUDY DESIGN: Retrospective cohort study. METHODS: We identified 5,346 patients in the Nationwide Readmissions Database undergoing sinonasal cancer surgery from 2010 to 2014. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Multivariate regression was used to analyze the association of frailty with postoperative outcomes. RESULTS: Frailty was present in 7.4% of patients. Frailty was a significant independent predictor of intensive care unit-level complications (odds ratio [OR]: 4.83; 95% confidence interval [CI]: 2.95-7.93; P < .001) and nonhome discharge (OR: 3.07; 95% CI: 1.68-5.60; P < .001). Compared to nonfrail patients, frail patients had threefold longer median length of stay (12 days vs. 4 days; P < .001) and more than twofold higher median hospital costs ($44,408 vs. $18,660; P < .001). Frailty outperformed advanced comorbidity (defined as Charlson-Deyo score ≥3), age ≥80 years, and markers of surgical complexity (e.g., skull base/orbit involvement, flap reconstruction, neck dissection) in predicting serious complications, nonhome discharge, length of stay, and hospital costs. CONCLUSIONS: Frailty appears to have a stronger and more consistent association with adverse outcomes and increased resource utilization after sinonasal cancer surgery than age or comorbidity index. This information may be used in surgical risk stratification and can guide strategies to prevent or mitigate adverse events in this high-risk group. LEVEL OF EVIDENCE: NA Laryngoscope, 130:290-296, 2020.