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Background: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores., Methods: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up., Results: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively., Conclusions: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up., Level of Evidence: 4 Laryngoscope, 135:59-65, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Viral infections have long been implicated in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Given widespread exposure to the common cold coronavirus 229E (HCoV229E), we sought to investigate how HCoV-229E is cleared and stimulates interferon pathways in air-liquid interface (ALI) cultures from patients with CRSwNP., Objective: The objective of this study was to identify whether viral clearance and ISG expression is different in ALI cultures from donors with CRSwNP compared with controls., Methods: Plaque assays were used to quantify infectious virus released by infected air-liquid interface (ALI) cultures derived from patients with CRSwNP compared to patients without CRS (controls). Additionally, mock and induced levels of Interferon Stimulated Genes (ISGs) mRNA following HCoV-229E infection were quantified by RT-qPCR., Results: Quantification of infectious virus by plaque assay reveals that CRSwNP ALI cultures were equally susceptible to HCoV-229E infection, and surprisingly viral titers dropped significantly faster than in the control ALI cultures. We further demonstrate that this accelerated viral clearance correlates with increased mRNA expression of at least 4 ISGs following viral infection in the CRSwNP ALIs compared to the control ALIs., Conclusion: This study paradoxically demonstrates that ALI cultures from patients with CRSwNP are more efficient at clearing the common cold HCoV-229E virus compared to controls. We also demonstrate significantly increased ISG mRNA expression following HCoV-229E infection in CRSwNP. These findings call for further investigation into the effect of unimpaired interferon signaling on the type 2 inflammatory environment in patients with CRSwNP., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments., Methods: A Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre- and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality-of-life improvements., Results: The CoSI assesses surgical extent on a scale of 0-100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT-22 scores improved at 6 months postoperatively, with durable and consistent improvement at 24 months (p < 0.001). Preoperative CoSI scores in revision surgery patients were 49.4 ± 26.0, improving to 91.0 ± 8.1 postoperatively. SNOT-22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p = 0.029)., Conclusions: It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention., (© 2024 ARS‐AAOA, LLC.)

Background: The inability of topical medications to reach sinus cavities is a potential reason for lack of efficacy in chronic rhinosinusitis (CRS). One purpose of endoscopic sinus surgery (ESS) is to enable delivery of medications into the sinus cavities. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE) creates unique biomechanics that enable deposition of intranasal corticosteroid into sinuses and sinus drainage pathways but may have differing efficacy in operated versus unoperated sinuses. Two 24-week randomized trials (ReOpen1/2) evaluated EDS-FLU versus EDS-placebo in patients with CRS, stratified by surgical status., Methods: Surgery-naive (n = 332) and prior-surgery (n = 215) patient groups were analyzed as pooled data from ReOpen1/2. Outcome measures (least-squares mean change from baseline) included combined symptom score (CSS) and congestion score at weeks 4, 8, and 12 and average of percentages of opacified volume (APOV) of ethmoid/maxillary sinuses on CT and Sinonasal Outcome Test 22 (SNOT-22) total score at week 24., Results: Baseline scores suggested moderate-severe disease: mean CSS = 5.8; APOV = 67.2%. EDS-FLU produced significant improvement versus placebo (p < 0.05): CSS (surgery-naive, -0.68 vs. -1.42; prior ESS, -0.70 vs. -1.87); congestion (surgery-naive, -0.24 vs. -0.59; prior ESS, -0.24 vs. -0.69); and SNOT-22 (surgery-naive, -7.56 vs. -18.30; prior ESS, -10.72 vs. -18.74). Similar results were observed for APOV (p < 0.05). No statistically significant difference was observed between surgery subgroups with either EDS-FLU dose., Conclusion: EDS-FLU improved symptoms, sinus opacification, and quality of life in patients with CRS with or without prior ESS, suggesting a role for EDS-FLU in both populations., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Key Points: We created a LangChain/OpenAI API-powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR-RS). The ICAR-RS chatbot is able to provide direct and actionable recommendations. Utilization of consensus statements provides an opportunity for AI applications in healthcare., (© 2023 ARS‐AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays., Objective: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps)., Methods: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24., Results: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids., Conclusions: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling., Methods: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL., Results: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005)., Conclusions: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL., (© 2023 ARS‐AAOA, LLC.)

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear., Methods: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020., Results: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051)., Conclusions: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors., (© 2024 S. Karger AG, Basel.)

Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma., Methods: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air-liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium., Results: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium-mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta-defensin 2, an antimicrobial peptide, compared to treatment with a control solution., Conclusion: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS., (© 2022 ARS-AAOA, LLC.)

Purpose: Assess if a rigid, image-guided balloon could be used effectively and safely in revision sinus surgery., Materials and Methods: A prospective, non-randomized, single-arm, multicenter study to assess the safety and device performance of the NuVent™ EM Balloon Sinus Dilation System. Adults with CRS in need of revision sinus surgery were enrolled for balloon sinus dilation of a frontal, sphenoid, or maxillary sinus. The primary device performance endpoint was the ability of the device to (1) navigate to; and (2) dilate tissue in subjects with scarred, granulated, or previously surgically-altered tissue (revision). Safety outcomes included the assessment of any operative adverse events (AEs) directly attributable to the device or for which direct cause could not be determined. A follow-up endoscopy was conducted at 14 days post-treatment for assessment of any AEs. Performance outcomes included the surgeon's ability to reach the target sinus (es) and dilate the ostia. Endoscopic photos were captured for each treated sinus pre- and post-dilation., Results: At 6 US clinical sites, 51 subjects were enrolled; 1 subject withdrew before treatment due to a cardiac complication from anesthesia. 121 sinuses were treated in 50 subjects. The device performed as expected in 100 % of the 121 treated sinuses, with investigators able to navigate to the treatment area and dilate the sinus ostium without difficulty. Ten AEs were seen in 9 subjects, with 0 related to the device., Conclusion: The targeted frontal, maxillary or sphenoid sinus ostium were safely dilated in every revision subject treated, with no AEs directly attributed to the device., Competing Interests: Declaration of competing interest Author disclosures/conflicts of interest are: 1) Joseph K. Han works as a consultant for Medtronic Xomed, Inc.; 2) James Nathan Palmer is a consultant for OptiNose, Acclarent, and Medtronic Xomed, Inc.; 3) Nithin Adappa is a consultant for Acclarent and on the Clinical Trial Steering Committee for OptiNose; 4) Rakesh K. Chandra is a consultant for Regeneron, Astra Zeneca and GSK, and on the Clinical Trial Steering Committee for OptiNose; 5) Joseph B. Jacobs has no disclosures to report; 6) Peter Manes received Research and Grant Support from OptiNose; and 7) Karen McKenzie is an employee of Medtronic Xomed, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD)., Materials and Methods: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis., Results: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304)., Conclusion: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls., Methods: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry., Results: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10 -9 M, 1.00 × 10 -8 M, 1.78 × 10 -8 M, 3.16 × 10 -8 M, 5.62 × 10 -8 M, and 1.00 × 10 -7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10 -8 M and 3.16 × 10 -8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012)., Conclusion: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10 -8 M for future study of clinical utility., (© 2020 ARS-AAOA, LLC.)

I., Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document., Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary., Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided., Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS., (© 2021 ARS-AAOA, LLC.)

Background: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull-base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement., Methods: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty-three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund-Mackay (LM) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Results: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre-SBS and post-SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre-SBS and post-SBS SNOT-22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013)., Conclusion: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS., (© 2020 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process., Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients., Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot-Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high-power field (44.4% vs 73.6%, p < 0.017)., Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide-based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management., (© 2019 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Methods: Data from 1252 adult CRS patients electing to undergo ESS (2007-2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT-22 scores at 0, 3, and 6 months after surgery. Changes in SNOT-22 scores were analyzed using a mixed models analysis., Results: After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre-ESS SNOT-22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT-22 scores declined by 20.7 points at 3 months post-ESS and 16.1 points at 6 months post-ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post-ESS (p = 0.7952 and p = 0.1057, respectively)., Conclusion: Both age groups showed significant and durable improvement in SNOT-22 scores after ESS. Patients younger than 50 years of age have higher pre-ESS SNOT-22 scores, but converge to the same SNOT-22 scores by 3 months post-ESS. The rate of change of SNOT-22 scores is not different between those younger than 50 years and those of at least 50 years., (© 2019 ARS-AAOA, LLC.)

Objective: Chronic rhinosinusitis (CRS) is a proposed risk factor for meningitis and other intracranial complications following the endoscopic endonasal transsphenoidal approach (TSA). Some have recommended staging TSA following surgery for CRS; however, delaying TSA has important ramifications. The objective of this study is to determine whether asymptomatic sinonasal inflammation (RSNI) on preoperative computed tomography scans, without clinical CRS, is associated with postoperative complications following TSA., Methods: All consecutive TSA cases performed at a single tertiary care institution from January 1, 2009, to December 31, 2017, were reviewed for patient demographics, prior surgery, presence of RSNI on preoperative computed tomography scan based on Lund-Mackay (LM) score, intraoperative cerebrospinal fluid (CSF) leak, and postoperative complications (postoperative CSF leak, bleeding, infection). The association between preoperative RSNI and postoperative complications was analyzed via multivariate logistic regression., Results: One hundred seventy-one cases of TSA were included with mean patient age of 52.6 years, 42.7% males, 18.1% revision cases, and mean LM score of 1.9 ± 2.7. Complications were identified in 9.9% of patients at the following rates: 5.3% postoperative CSF leak, 2.9% bleeding, and 1.8% infection (all sinusitis, no episodes of meningitis). Neither total LM score nor LM score > 5 (representative of clinically significant radiographic CRS) were predictors of any postoperative complication (both P > 0.05). Age, sex, revision status, intraoperative CSF leak, and total LM score were not independent predictors of any postoperative complication on multivariate analysis (all P > 0.05)., Conclusion: In asymptomatic patients, radiographic evidence of sinonasal inflammation is not associated with increased risk of complications following TSA., Level of Evidence: 4 Laryngoscope, 129:1545-1548, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Solitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin-25 (IL-25), an innate cytokine eliciting T-helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation., Methods: Multicolor flow cytometry, immunofluorescence, and enzyme-linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL-25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry., Results: SCCs producing IL-25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL-25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki-67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls., Conclusion: Although fungal antigens are known to potentiate immune response through innate cytokines, including IL-25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention., (© 2019 ARS-AAOA, LLC.)

Large cohort studies of chronic rhinosinusitis (CRS) prevalence often include patients who have been inappropriately diagnosed with the disease. In this investigation, new patients presenting to a tertiary rhinology practice completed a screening questionnaire that included questions about self-reported CRS status, demographic information, and symptomatology. Treating rhinologists evaluated patients according to clinical practice guideline criteria for CRS; 91 patients were ultimately diagnosed with CRS. The sensitivity of self-report for CRS was 84%; the specificity was 82%; and the estimated negative predictive value ranged from 97% to 99%. Prior sinus surgery or oral steroid use correlated with CRS self-report, and a concurrent self-report of nasal polyps or nasal steroid use improved the positive predictive value of CRS self-report. Self-report of CRS status may represent an effective and relatively inexpensive screening mechanism for CRS in large cohort studies, particularly when combined with other associated diagnostic features that improve performance parameters of self-report.

Background: Chronic rhinosinusitis (CRS) is believed to create a substantial population-level disease burden in the United States due to its high prevalence and significant disease morbidity, but many studies of CRS epidemiology are based on administrative or historical record sources rather than primary population sources. Objective: To characterize CRS symptoms, burden, and patient characteristics by using a primary U.S. population-based representative sample. Methods: A demographically and geographically representative sample of 10,336 U.S. adults recruited from a general panel of 4.3 million were obtained by using three-stage randomization. Data collected included a range of respondent-reported CRS symptoms, symptom impact and severity, symptom duration, and treatment. Results: Approximately 11.5% of the respondents (n = 1189) reported defining symptom and duration criteria for CRS. A previous diagnosis of nasal polyps was reported by ∼10% of this population. The remaining respondents reported severe (7.3%) or moderate (3.1%) symptom severity. The most frequently reported defining symptoms were nasal congestion and/or obstruction (94-97%) and drainage (89-92%). CRS participants reported a high average degree of symptom burden ( e.g., on a 0-10 scale, 8.2 for CRS with nasal polyps, 8.4 for CRS without nasal polyps with severe symptoms, and 6.4 for CRS without nasal polyps with moderate symptoms). The participants with CRS reported high health-care use for CRS, adverse effects of CRS symptoms on multiple areas of daily life, and high dissatisfaction with currently available treatments. Conclusion: More than 10% of the general U.S. adult population have CRS symptoms. Most report severe symptoms, lack of satisfaction with current treatment options, and a substantial adverse impact on daily functioning.

Background: IL-25 can function as an early signal for the respiratory type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive., Objective: In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium., Method: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with CRSwNP. Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or chronic rhinosinusitis without nasal polyps and IL-25 levels determined by using ELISA. Lastly, sinonasal epithelial cultures derived from polyp and turbinate tissue were stimulated with IL-13 and analyzed for SCC proliferation and IL-25 production., Results: This study demonstrates that a discrete cell type, likely an SCC, characterized by expression of the taste-associated G protein gustducin and the intestinal tuft cell marker doublecortin-like kinase 1, is the predominant source of IL-25 in the human upper airway. Additionally, we show that patients with CRSwNP have increased numbers of SCCs in nasal polyp tissue and that in vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucosal layer., Conclusions: Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25., (Published by Elsevier Inc.)

Background: Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients., Methods: Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre- and postoperative self-reported QoL outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) were collected and evaluated over 12 months. Five hundred sixty-eight patients met the inclusion criteria. Longitudinal linear mixed-effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS)., Results: Preoperative LMCTS were significantly associated with preoperative SNOT-22 scores (p < 0.01) and postoperative SNOT-22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT-22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2-21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7-25.4) and 23.1 points (95% CI, 18.3-27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT-22 scores after FESS (29.9 points; 95% CI, 24.9-34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0-20.2; p < 0.001)., Conclusion: Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting., (© 2018 ARS-AAOA, LLC.)

Background: Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS., Methods: Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air-liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed in vitro ., Results: Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation ( p  < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects., Conclusion: Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses.

Background: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes., Methods: Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations., Results: There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) (p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.012)., Conclusion: Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity., (© 2017 ARS-AAOA, LLC.)

Background: Upper airway epithelial cells produce bactericidal nitric oxide (NO) in response to both gram-positive and gram-negative bacteria. Our previous work demonstrated that T2R38, a bitter taste receptor (T2R) expressed in airway epithelium, produces NO in response to quorum-sensing molecules secreted by Pseudomonas aeruginosa. We also demonstrated that Staphylococci products elicit an NO response when using a T2R-independent pathway. When screening additional human pathogens for epithelial T2R activation, we found that the gram-positive aerobe Bacillus cereus secretes a T2R agonist that yields NO production., Objective: The objective of this study was to characterize the activating B. cereus product(s) and to describe the epithelial cell signaling pathway involved., Methods: Sinonasal air-liquid interface cultures were treated with B. cereus conditioned medium (CM), and NO production was measured by using 4-amino-5-methylamino-2',7'-difluorofluorescein fluorescence imaging. Ciliary beat frequency (CBF) was assessed in response to B. cereus CM. Pharmacologic studies that use inhibitors of the T2R-signaling pathway were used to determine if the production of NO was mediated by a T2R. Purification studies were performed to analyze the physical properties of the activating product(s) contained in the CM., Results: A product(s) secreted by B. cereus induced NO production and increased CBF. The response varied markedly between individual patients and involved two important components of bitter taste signaling, phospholipase C isoform β-2 and the transient receptor potential melastatin isoform 5 ion channel., Conclusions: This study demonstrated that a B. cereus product(s) elicited an NO-mediated innate defense response in upper airway epithelium that seemed to be partially mediated by a T2R signaling pathway. The active product that elicited the NO response was likely a small nonpeptide compound, but further purification is required for identification. Patient variation in the NO response to B. cereus products could potentially be due to genetic differences in T2Rs.

Background: Bitter taste receptors (T2R) have recently been demonstrated to contribute to sinonasal innate immunity. One T2R, T2R38, regulates mucosal defense against gram-negative organisms through nitric oxide (NO) production, which enhances mucociliary clearance and directly kills bacteria. To determine whether additional T2Rs contribute to this innate defense, we evaluated two other sinonasal T2Rs (T2R4 and T2R16) for regulation of NO production and expression within the human sinonasal cavity., Methods: Primary human sinonasal cultures were stimulated with ligands specific to T2R4 and T2R16, colchicine and D-salicin, respectively. Cellular NO production was measured by intracellular 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence. For T2R expression mapping, sinonasal tissue was obtained from patients who underwent sinus surgery of the middle turbinate, maxillary sinus, ethmoid sinus, or sphenoid sinus. The expression of T2R4, T2R16, and T2R38 was evaluated by using immunofluorescence with validated antibodies., Results: Similar to T2R38, T2R4 and T2R16 trigger NO production in a dose-dependent manner by using the canonical taste signaling pathway in response to stimulation with their respective ligands. All three receptors were expressed in the cilia of human epithelial cells of all regions in the sinonasal cavity., Conclusion: These three T2Rs signaled through the same NO-mediated antimicrobial pathway and were ubiquitously expressed in the sinonasal epithelium. Additional T2Rs besides T2R38 may play a role in sinonasal immune defense. Mapping of T2R expression demonstrated the potential widespread role of T2Rs in sinonasal defense, whereas the genetics of these T2Rs may contribute to our understanding of specific endotypes of chronic rhinosinusitis and develop into novel therapeutic targets.

Background: Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed., Methods: Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients., Results: Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings (p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients (p = 0.0026)., Conclusion: In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients., (© 2016 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients., Methods: ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment., Results: A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05)., Conclusion: Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients., (© 2015 ARS-AAOA, LLC.)

Chronic sinusitis is a burdensome disease that has substantial individual and societal impact. Although great advances in medical and surgical therapies have been made, some patients continue to have recalcitrant infections. Microbial biofilms have been implicated as a cause of recalcitrant chronic sinusitis, and recent studies have tried to better understand the pathogenesis of chronic sinusitis as it relates to microbial biofilms. Here, we provide an overview of biofilms in chronic sinusitis with emphasis on pathogenesis, treatment, and future directions. In addition, recent evidence is presented, elucidating the role of bitter taste receptors as a possible key factor leading to biofilm formation.

Background: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS)., Methods: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus., Results: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS., Conclusion: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed., (© 2016 ARS-AAOA, LLC.)

Background: Over 550,000 sinus surgeries are performed annually in the United States on patients with chronic rhinosinusitis (CRS). Although the results of sinus surgery vary widely, no known genetic factor has been identified to predict surgical outcomes. The bitter taste receptor T2R38 has recently been demonstrated to regulate upper airway innate defense and may affect patient responses to therapy. Our goal was to determine whether TAS2R38 genetics predicts outcomes in CRS patients following sinus surgery., Methods: A prospective study of patients undergoing sinus surgery evaluating postoperative outcomes through the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were genotyped for TAS2R38., Results: A total of 123 patients with CRS were initially analyzed; 82 patients showed nasal polyps (CRSwNP) and 41 patients were without nasal polyps (CRSsNP). Six months after surgery, the overall SNOT-22 improvement was 25 ± 23 points. The TAS2R38 genotype was found to significantly correlate with surgical outcomes in patients without polyps; homozygotes for the functional receptor had a mean improvement of 38 ± 21, whereas heterozygotes or homozygotes for the nonfunctional receptor had a mean improvement of 12 ± 22 (p = 0.006). This result was confirmed with a multivariate regression that incorporated further patients with 1-month and 3-month scores (n = 207)., Conclusion: In patients undergoing sinus surgery for CRS, we have identified a genetic polymorphism that predicts variability in quality of life improvement following surgery at 6 months in nonpolypoid CRS. This is the first genetic polymorphism identified that has demonstrated to predict surgical outcome for a select group of CRS patients., (© 2015 ARS-AAOA, LLC.)

Background: Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS., Methods: Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed., Results: A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions., Conclusion: S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes., (© 2015 ARS-AAOA, LLC.)

Background: It remains unclear how much chronic rhinosinusitis (CRS) patients with bacterial biofilms can benefit from functional endoscopic sinus surgery (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with quality of life (QOL) improvement after FESS., Methods: This retrospective cohort study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus samples were taken to evaluate for biofilm-formation in vitro using a modified Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3-month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Patients' characteristics and medications were collected. Clinical significant QOL change was defined as a difference of at least 0.5 standard deviation (SD) of baseline SNOT-22 score in the reference group., Results: A total of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24). Patients with biofilm-forming bacteria had significantly worse preoperative SNOT-22 scores compared to patients without biofilm-forming bacteria (48 ± 20 vs 38 ± 23, p = 0.048). Both groups had clinically significant QOL improvement after FESS, and the differences in their 1-month (23 ± 19 vs 17 ± 20) and 3-month (27 ± 18 vs 18 ± 19) post-FESS SNOT-22 scores were not significant. However, patients with biofilm-forming bacteria demonstrated significantly less QOL improvement than patients without biofilm-forming bacteria from pre-FESS to 6-month post-FESS visits after adjusting for clinical factors (35 ± 25 vs 14 ± 15; β-coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p = 0.016)., Conclusion: CRS patients with biofilm-forming bacteria demonstrated clinically significant QOL improvement following FESS, but the degree of improvement was decreased overtime and became significantly worse than patients without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was independent of other risk factors for CRS., (© 2015 ARS-AAOA, LLC.)

Objectives: To evaluate nasal mucus glucose concentrations in patients with and without chronic rhinosinusitis and determine if corticosteroid therapy alters mucus glucose., Study Design: Prospective observational study., Setting: Single tertiary care center., Subjects: Ninety-five patients presenting to an otolaryngology clinic., Methods: Participants completed questionnaires that included a history of medical and surgical therapies as well as sinusitis-specific quality-of-life measurements. Nasal mucus was collected in an outpatient clinic using an open cell foam technique. The nasal mucus glucose concentrations of patients with and without chronic rhinosinusitis were compared to the use of systemic and topical glucocorticoid treatment., Results: A statistically significant difference was measured between mean nasal glucose secretions of control patients, 10.2 mg/dL, compared with patients diagnosed with chronic rhinosinusitis, 18.4 mg/dL (P < .0001). Use of corticosteroids, both topical and systemic, did not correlate with nasal glucose concentrations., Conclusion: Patients diagnosed with chronic rhinosinusitis have elevated nasal glucose concentrations compared with control patients, and this elevated nasal glucose level was independent of corticosteroid use. Nasal glucose may independently contribute to the pathophysiology of chronic rhinosinusitis., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

The American Academy of Otolaryngology-Head and Neck Surgery Foundation has published a supplement to this issue featuring the updated "Clinical Practice Guideline: Adult Sinusitis" as a supplement to Otolaryngology-Head and Neck Surgery. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background: Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity., Methods: Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture., Results: A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034)., Conclusion: Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates., (© 2014 ARS-AAOA, LLC.)

Background: The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population., Methods: A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive., Results: Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were "supertasters," experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables., Conclusion: This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals., (© 2014 ARS-AAOA, LLC.)

Background: It is unclear whether chronic rhinosinusitis (CRS) patients with both nasal polyps and asthma have different quality of life (QOL) improvement after functional endoscopic sinus surgery (FESS). We aimed to determine whether CRS patients with asthma and nasal polyps had a greater QOL improvement after FESS compared to patients without asthma or polyps., Methods: This retrospective analysis included adult CRS patients who underwent FESS between 2007 and 2011. QOL was measured using the 22-item Sino-Nasal Outcome Test (SNOT-22). Variables collected included baseline demographics, clinical factors, SNOT-22 scores before FESS, and 1 month, 3 months, and 6 months post-FESS. Groups tested were asthma alone, polyps alone, asthma and polyps, and no asthma or polyps. Linear mixed-effects regression model was performed to calculate β-coefficients, which represent the adjusted mean QOL differences., Results: Among the 376 patients included, 40.16% had both asthma and polyps (n = 151), 14.36% had asthma alone (n = 54), 19.45% had polyps alone (n = 75), and 25.53% had no asthma or polyps (n = 96). After adjusting for all factors, there were significantly more QOL improvements in patients with both asthma and nasal polyps from baseline to 1-month (β-coefficient = -10.05; 95% CI, -15.86 to -4.23; p = 0.001) and 3-month follow-up (β-coefficient = -8.27; 95% CI, -14.98 to -1.56; p = 0.016), and patients with asthma alone from baseline to 6-month follow-up (β-coefficient = -8.78; 95% CI, -17.45 to -0.11; p = 0.047), when compared to patients without asthma or nasal polyps., Conclusion: CRS patients with both asthma and nasal polyps or asthma alone experience a larger QOL benefit from FESS immediately after FESS compared to CRS patients without asthma or polyps., (© 2014 ARS-AAOA, LLC.)

Background: Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS)., Methods: This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed., Results: Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences., Conclusion: Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome., (© 2014 ARS-AAOA, LLC.)

Background: Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS)., Methods: We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis., Results: Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p = 0.004) and Gram-negative rods (26.32% vs 8.96%; p = 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS., Conclusion: DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM., (© 2014 ARS-AAOA, LLC.)

Background: The bitter taste receptor T2R38 was recently described to play a role in upper airway innate mucosal defense. When activated by bacterial quorum-sensing molecules, T2R38 stimulates the ciliated epithelial cells to produce nitric oxide (NO), resulting in bactericidal activity and an increase in mucociliary clearance (MCC). Polymorphisms within the T2R38 gene (TAS2R38) confer variability in activation of the receptor yielding dramatic differences in upper airway defensive responses (NO production and accelerated MCC) to microbial stimulation based on genotype. Our objective was to determine whether the nonprotective TAS2R38 polymorphisms, which render the receptor inactive, correlate with medically recalcitrant chronic rhinosinusitis (CRS) necessitating surgical intervention in the context of known risk factors, and thus identify whether the TAS2R38 genotype is an independent risk factor for patients undergoing functional endoscopic sinus surgery (FESS)., Methods: CRS patients undergoing primary FESS were prospectively genotyped for TAS2R38. Chi-square analysis was performed on the genotype distribution with respect to other risk factors, including allergies, asthma, nasal polyposis, aspirin sensitivity, diabetes, and smoking exposure., Results: Seventy primary FESS patients were genotyped demonstrating a statistically significant skewing from the expected distribution of the general population (p < 0.0383). CRS patients with a particular polymorphism seemed less likely to have allergies, asthma, nasal polyposis, aspirin sensitivity, and diabetes, but this did not demonstrate statistical significance., Conclusion: Our investigation suggests that TAS2R38 genotype is an independent risk factor for patients failing medical therapy, necessitating surgical intervention., (© 2013 ARS-AAOA, LLC.)

Background: Surfactants are a class of amphiphilic surface active compounds that show several unique physical properties at liquid-liquid or liquid-solid surface interfaces including the ability to increase the solubility of substances, lower the surface tension of a liquid, and decrease friction between two mediums. Because of these unique physical properties several in vitro, ex vivo, and human trials have examined the role of surfactants as stand-alone or adjunct therapy in recalcitrant chronic rhinosinusitis (CRS)., Methods: A review of the literature was performed., Results: The data from three different surfactants have been examined in this review: citric acid zwitterionic surfactant (CAZS; Medtronic ENT, Jacksonville FL), Johnson's Baby Shampoo (Johnson & Johnson, New Brunswick NJ), and SinuSurf (NeilMed Pharmaceuticals, Santa Rosa, CA). Dilute surfactant therapy shows in vitro antimicrobial effects with modest inhibition of bacterial biofilm formation. In patients with CRS, surfactants may improve symptoms, most likely through its mucolytic effects. In addition, surfactants have several distinct potential benefits including their ability to improve an irrigant's penetration of the nonoperated sinus and their synergistic effects with antibiotics. However, surfactants potential for nasal irritation and possible transient ciliotoxicity may limit their use., Conclusion: Recent data suggest a possible therapeutic role of surfactants in treating rhinopathologies associated with mucostasis. Further investigation, including a standardization of surfactant formulations, is warranted to further elucidate the potential benefits and drawbacks of this therapy.

Background: We recently demonstrated the bitter taste receptor T2R38 upregulates sinonasal mucosal innate defense in response to gram-negative quorum-sensing molecules through increased nitric oxide production and mucociliary clearance. T2R38 was initially identified in the quest to understand the variability in bitter taste perception to the compound phenylthiocarbamide (PTC) and demonstrated to have polymorphisms generating diplotypes dividing people into PTC supertasters, heterozygotes (with variable PTC detection), and nontasters. We have further demonstrated that sinonasal epithelial cultures derived from supertasters significantly increase innate defenses in response to gram-negative quorum-sensing molecules compared with sinonasal cultures derived from heterozygotes and nontaster individuals. Based on this data, we hypothesize that supertasters are less likely to require sinus surgery compared with heterozygous or nontasters and that supertasters have improved surgical outcomes., Methods: Banked sinonasal tissue samples from patients who had undergone primary functional endoscopic sinus surgery at the University of Pennsylvania or the Philadelphia Veterans Affairs Medical Center were genotyped for T2R38 and compared to the expected population distribution. Necessity for additional antibiotic therapy following the postoperative healing time frame was evaluated., Results: A total of 28 patients were included in the study. Only 1 supertaster was identified (expected 5.6, p < 0.043). Additionally, 14 heterozygous and 13 nontaster patients were identified., Conclusion: This pilot study investigating the genetics of the bitter taste receptor T2R38 in the context of primary sinonasal surgery demonstrates supertaster patients are less likely to need surgical intervention for chronic rhinosinusitis. Additional study is necessary to ascertain postsurgical outcomes., (© 2013 ARS-AAOA, LLC.)