Search

Chengetai R Mahomva,1,&ast; Kristine A Smith,1,&ast; Prince AB Minkah,2 Benjamin L Witt,3 Gretchen M Oakley,1 Richard R Orlandi,1 Jeremiah A Alt,1,2,4 Abigail Pulsipher1,2,4 1Department of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA; 2Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, UT, USA; 3Cytopathology Section, University of Utah School of Medicine, Salt Lake City, UT, USA; 4Utah Center for Nanomedicine, University of Utah College of Pharmacy, Salt Lake City, UT, USA&ast;These authors contributed equally to this workCorrespondence: Abigail Pulsipher, University of Utah School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 36 South Wasatch Drive, Salt Lake City, UT, 84112, USA, Tel +1 4342493268, Fax +1 8015855744, Email abigail.pulsipher@utah.eduBackground: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown. This study sought to determine the transcriptional changes in CCL19, its receptors, and associated cytokines and their association with disease severity in CRS.Methods: A clinical database of control subjects and patients with CRS was examined. Lund-Kennedy, Lund-Mackay, Sinonasal Outcomes Test 22 (SNOT-22), and rhinosinusitis disability index (RSDI) scores were collected at enrollment. mRNA was extracted from sinonasal tissues and subjected to multiplex gene expression analysis. Gene transcript differences between patients with CRS and controls were compared and correlated with disease severity metrics. Immunohistochemical analyses of CCL19, CCR7, and CCRL1 were conducted to compare differences in protein expression between cohorts. A subgroup analysis was performed to compare transcriptional and protein expression difference between patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls.Results: Thirty-eight subjects (control group, n=7; CRS group, n=31) were included in this study. CCRL1 (p=0.0093) and CCR7 (p=0.017) levels were significantly elevated in CRS compared to those in controls. CCL19 (p=0.038) and CCR7 (p=0.0097) levels were elevated in CRSwNP and CCRL1 was elevated in CRSsNP (p=0.0004). CCR7 expression was significantly elevated in sinonasal epithelial cells in CRSwNP (p=0.04). CCL19 expression was positively correlated with TNFA expression (p< 0.0002). CCL19 and CCR7 expression was positively correlated with SNOT-22 and RSDI scores (p< 0.05).Conclusion: CCL19 and CCR7 may modulate TNF-α-driven pro-inflammatory signaling and contribute to increased disease severity in CRS. Mechanistic studies are required to further elucidate the role of CCRL1 in CRS.Keywords: chronic rhinosinusitis with nasal polyps, chemokines, cytokines, gene expression, protein expression

Brennan J Blight, Amarbir S Gill, Jorgen S Sumsion, Chelsea E Pollard, Shaelene Ashby, Gretchen M Oakley, Jeremiah A Alt, Abigail Pulsipher Division of Otolaryngology-Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USACorrespondence: Abigail PulsipherDivision of Otolaryngology-Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, 50 North Medical Drive, Room 3C120, Salt Lake City, UT, 84132, USAEmail abigail.pulsipher@utah.eduPurpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology.Materials and Methods: A prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns.Results: Integrin and ICAM genes were significantly elevated in the blood (p< 0.001 to p< 0.05) and sinuses (p< 0.0003 to p< 0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (p< 0.01 to p< 0.05) and sinuses (p< 0.01) were observed between ITGAM, ITGAX, ITGB2, and ICAM3. ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (p< 0.0001 to p< 0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (p< 0.02).Conclusion: The systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.Keywords: integrins, intercellular adhesion molecule 3, macrophage-1 antigen, Th2 pathophysiology, transcriptional analysis, allergy, asthma

Amarbir S Gill,1 Abigail Pulsipher,1 Jorgen S Sumsion,2 Gretchen M Oakley,1 Laurie W Leclair,3 Heather Howe,3 Richard R Orlandi,1 Jeremiah A Alt1 1Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, UT, USA; 2School of Medicine, University of Utah, Salt Lake, USA; 3Department of Pulmonology/Critical Care Medicine, University of Utah, Salt Lake City, UT, USACorrespondence: Jeremiah A AltDivision of Otolaryngology – Head & Neck Surgery, Department of Surgery, University of Utah School of Medicine, 50 North Medical Drive, Room 3C120, Salt Lake City, UT, 84132, USATel +1 801 585-7143Fax +1 801 585-5744Email jeremiah.alt@hsc.utah.eduBackground: Data regarding the inflammatory profile of patients with asthma and chronic rhinosinusitis (CRS-A) with (CRSwNP-A) and without (CRSsNP-A) nasal polyposis remain limited.Objective: Define and compare systemic transcriptional changes in patients with CRS-A to those with non-asthma-related CRS with (CRSwNP) and without nasal polyposis (CRSsNP).Methods: Thirty-four patients with CRS-A (n=19) and CRS (n=15) were prospectively enrolled into an observational study. Demographic information and subjective and objective disease severity measures were recorded. Multiplex gene expression analysis of mRNA extracted from peripheral blood was performed. A total of 594 genes associated with innate/adaptive immunity were analyzed using NanoString technology. Gene expression ratios were reported for genes that were differentially expressed among these cohorts. Linear regression analysis was used to compare the mRNA transcript copy numbers for each gene with disease severity.Results: There was no significant difference in age, gender, nasal polyposis, or health-related quality of life measures between the two groups (p> 0.05). HLA class II histocompatibility antigen, DRB3-1 beta chain (HLA-DRB3) was significantly upregulated in the peripheral blood of patients with CRSsNP-A compared to CRSsNP, whereas chemokine (C-C motif) ligands 4 (CCL4) and zinc finger protein helios (IKZF2) were significantly upregulated in CRSwNP-A compared to CRSwNP (p< 0.05).Conclusion: Patients with CRSsNP-A demonstrate a molecular endotype associated with a Th2-dominant inflammatory profile compared to CRSsNP. Patients with CRSwNP-A similarly demonstrate an overrepresentation of genes associated with Th2-driven inflammation compared to patients with CRSwNP.Keywords: chronic rhinosinusitis, asthma, gene transcription, inflammatory markers, nasal polyposis, endotype

Objectives: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF)., Methods: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22., Results: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5., Conclusion: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF., Level of Evidence: 3 Laryngoscope, 134:3965-3973, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Key Points: EPX activity has been correlated with eCRS diagnosis and baseline disease severity. Herein, EPX activity is shown to correlate with post-operative antibiotic and steroid use in CRS. EPX activity has potential to act as a prognostic biomarker of CRS disease severity and control., (© 2024 ARS‐AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied., Methods: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI., Results: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p = 0.14). Non-ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055)., Conclusions: Nasal congestion and post-nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes., Methods: A total of 642 study participants with CRS were prospectively enrolled and self-selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded pre- and post-treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φ c ) with 95% confidence interval (CI) were calculated., Results: A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φ c  = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT-22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF-6D values (Rs = -0.20; 95% CI: -0.27, -0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within-subject improvement, or achievement of >1 minimal clinically important difference, in SNOT-22 or SF-6D scores after treatment were found., Conclusions: Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease-specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied., Methods: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression., Results: Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (β = ‒4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (β = ‒2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (β = ‒0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (β = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (β = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV 1 ). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV 1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores., Conclusions: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF., Clinical Trials: NCT04469439., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown., Objective: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS)., Methods: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 μm and <10 μm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (β) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed., Results: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P   =  .01) and after covariate adjustment with multivariate analysis ( B   =  1.06, 95% CI: 0.001, 2.14, P   =  .05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively., Conclusion: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.M.B: Grant support from CF Foundation and from the International Society of Inflammation and Allergy of the Nose, unrelated to this work. Garner Health, consultant, equity. Honoraria from Rockpointe and Trinity Sciences. J.A.A: GlycoMira consultant, equity. GSK speaker panel. OptiNose consultant, Medtronic consultant. Z.M.S: Lyra, Optinose, Regeneron consultant. Medical director Healthy Humming.

Introduction: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF., Methods: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement., Results: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04)., Conclusion: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner., (© 2023 ARS‐AAOA, LLC.)

Background: There is a limited understanding of site-specific, quality of life (QOL) outcomes in anterior skull base surgery (ASBS). The objective of the present investigation was to characterize postoperative change in QOL outcomes for anterior skull base lesions following open and endoscopic surgery., Methods: A comprehensive review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PubMed, Scopus, Embase, and Cochrane databases for studies reporting pre- and postoperative, site-specific, QOL outcome measures in ASBS using validated questionnaires. Studies utilizing the anterior skull base quality of life (ASBQ) questionnaire or the skull base inventory were included. Investigations focusing on skull base surgery for pituitary lesions, as well as survey validation and non-English studies, were excluded., Results: A total of 112 studies were screened; 4 studies, comprising a total of 195 patients and focusing exclusively on the ASBQ, were included in the systematic review. Using a fixed effect model for the meta-analysis, the mean ASBQ score was similar at six (3.45, P = 0.312; -0.19, 95% confidence interval: -0.57, 0.18) and 12 months postoperatively (3.6, P = 0.147; 0.3, 95% confidence interval: -0.11, 0.72) compared to baseline (3.53)., Conclusions: Across a variety of anterior skull base pathologies, skull base-specific QOL demonstrated no improvement at 6 months and 12 months postsurgery. Few studies to date have published pre- and postoperative QOL data for patients undergoing ASBS, highlighting a current shortcoming in the available literature. Long-term follow-up in patients undergoing open and endoscopic approaches will be necessary to better understand and optimize outcomes for patients having ASBS., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Budesonide high-volume saline irrigations (HVSIs) are routinely used to treat chronic rhinosinusitis (CRS) due to improved sinonasal delivery and efficacy compared to intranasal corticosteroid sprays. The off-label use of budesonide is assumed to be safe, with several studies suggesting the systemically absorbed dose of budesonide HVSI is low. However, the actual budesonide dose retained in the sinonasal cavity following HVSI is unknown. The objective of this study was to quantify the retained dose of budesonide after HVSI., Methods: Adult patients diagnosed with CRS who had undergone endoscopic sinus surgery (ESS) and were prescribed budesonide HVSI were enrolled into a prospective, observational cohort study. Patients performed budesonide HVSI (0.5 mg dose) under supervision in an outpatient clinic, and irrigation effluent was collected. High-performance liquid chromatography was employed to determine the dose of budesonide retained after HVSI., Results: Twenty-four patients met inclusion criteria. The average corrected retained dose of budesonide across the cohort was 0.171 ± 0.087 mg (37.9% of administered budesonide). Increased time from ESS significantly impacted the measured retained dose, with those 3 months post-ESS retaining 27.4% of administered budesonide ( P  = .0004)., Conclusion: The retained dose of budesonide in patients with CRS after HVSI was found to be significantly higher than previously estimated and decreased with time post-ESS. Given that budesonide HVSI is a cornerstone of care in CRS, defining the retained dose and the potential systemic implications is critical to understanding the safety of budesonide HVSI., Competing Interests: Declaration of Conflicting InterestsThe authors would like to declare the following conflict of interest with respect to the research, authorship, and/or publication of this article: P.S: None; B.Y.: None; A.P.: GlycoMira Therapeutics, Inc.; A.S.G: None; C.P: None; V.Y.: JSK Therapeutics, Consultant; H.G.: Theratarget; J.A.A: GSK, GlycoMira, Medtronic, OptiNose; K.S: SanofiGenzyme; Consultant.

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures., Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES)., Results: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures., Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes., (© 2023 ARS‐AAOA, LLC.)

Background: Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS-specific disease severity. We assessed the impact of air pollutants on sinonasal-specific and general quality-of-life (QOL) measures in a multi-institutional cohort of patients with CRS., Methods: Participants with CRS were prospectively enrolled in a cross-sectional study and self-selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association., Results: A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD] ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT-22 or SF-6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, [95% confidence interval {CI}: 0.003, 0.234]; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m 3 ) did not correlate with change in total SNOT-22 or SF-6D scores after treatment. Nevertheless, sulfur dioxide (SNOT-22: ρ = -0.121 [95% CI: -0.210, -0.030]; p = 0.007; SF-6D: ρ = 0.095 [95% CI: 0.002, 0.186]; p = 0.04) and carbon monoxide (SNOT-22: ρ = -0.141 [95% CI: -0.230, 0.050]; p = 0.002) exposure did correlate with these outcome measures., Conclusion: Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied., Methods: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS., Results: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p = 0.004) was associated with pursing medical therapy., Conclusions: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden., (© 2023 ARS‐AAOA, LLC.)

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field., Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication., Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention., Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Chronic rhinosinusitis (CRS) is a chronic health condition affecting the sinonasal cavity. CRS-associated mucosal inflammation leads to sinonasal epithelial cell death and epithelial cell barrier disruption, which may result in recurrent bacterial infections and biofilm formation. For patients who fail medical management and elect endoscopic sinus surgery for disease control, bacterial biofilm formation is particularly detrimental, as it reduces the efficacy of surgical intervention. Effective treatments that prevent biofilm formation in post-operative patients in CRS are currently limited. To address this unmet need, we report the controlled release of silver nanoparticles (AgNps) with silk-elastinlike protein-based polymers (SELPs) to prevent bacterial biofilm formation in CRS. This polymeric network is liquid at room temperature and forms a hydrogel at body temperature, and is hence, capable of conforming to the sinonasal cavity upon administration. SELP hydrogels demonstrated sustained AgNp and silver ion release for the studied period of three days, potent in vitro antibacterial activity against Pseudomonas aeruginosa (**** p < 0.0001) and Staphylococcus aureus (**** p < 0.0001), two of the most commonly virulent bacterial strains observed in patients with post-operative CRS, and high cytocompatibility with human nasal epithelial cells. Antibacterial controlled release platform shows promise for treating patients suffering from prolonged sinonasal cavity infections due to biofilms.

Background: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence-based management strategies for CRS in this population., Methods: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit-harm assessments, as well as value judgment and recommendations, were provided RESULTS: Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes., Conclusion: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status., (© 2023 ARS-AAOA, LLC.)

Background: Despite significant morbidity, there remains a critical need for prospective analyses to investigate the impact of comorbid chronic rhinosinusitis (CRS) with asthma (CRSwA) on patient centered outcomes. The objective of this study was to ascertain critical stakeholder feedback from patients that could inform future study design based on patient preferences, in an effort to optimize patient enrollment., Methods: A prospective, descriptive study was performed in order to determine the importance of various factors on CRSwA treatment among critical stakeholders. A Likert-scale survey highlighting various aspects of treatment of CRSwA and elucidating patient enthusiasm for clinical enrollment was constructed and prospectively administered to patients with CRSwA. A univariate analysis was instituted to understand the significance of the different trial design preferences., Results: Survey responses were collected from a total of 17 patients with CRSwA. With Likert scores >4/5, responses indicated significant stakeholder interest in research focused on understanding symptom triggers, including the impact of air quality and allergens. Importantly, the highest mean scores noted were for studies focused on improving (1) overall quality of life (4.8/5) and (2) lung function (4.8/5). Patients appeared least interested in participation in a randomized trial, whereas the greatest support was communicated for a purely observational trial ( P  = .08)., Conclusion: Patients with CRSwA demonstrate enthusiasm for participation in research that focuses on improving patient centered outcomes-specifically quality of life and lung function. Stakeholder feedback also indicates a preference for observational study design over randomized control trials.

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the nasal and paranasal sinuses of approximately 11.5% of the United States adult population. Oral corticosteroids are effective in controlling sinonasal inflammation in CRS, but the associated adverse effects limit their clinical use. Topical budesonide has demonstrated clinical efficacy in patients with CRS. Herein, we investigated the systemic delivery of liposomes tethered with poly(ethylene glycol) (PEG) and loaded with budesonide in a murine model of CRS. PEGylated liposomes encapsulated with budesonide phosphate (L-BudP) were administered via tail vein injection, and the feasibility of L-BudP to reduce sinonasal inflammation was compared to that of free budesonide phosphate (F-BudP) and topical budesonide phosphate (T-BudP) treatment over a 14-day study period. Compared to a single injection of F-BudP and repeat T-BudP administration, a single injection of L-BudP demonstrated increased and prolonged efficacy, resulting in the significant improvement of sinonasal tissue histopathological scores (p < 0.05) with decreased immune cell infiltration (p < 0.05). Toxicities associated with L-BudP and T-BudP treatment, assessed via body and organ weight, as well as peripheral blood liver enzyme and differential white blood cell analyses, were transient and comparable. These data suggest that systemic liposomal budesonide treatment results in improved efficacy over topical treatment., (Copyright © 2023. Published by Elsevier B.V.)

Background: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients., Objective: We sought to evaluate a new clinical tool that uses a nasal swab and colorimetric EPX activity assay to predict a diagnosis of eCRS., Methods: A prospective, observational cohort study was conducted using nasal swabs and sinonasal tissue biopsies obtained from patients with CRS electing endoscopic sinus surgery. Patients were classified as non-eCRS (n = 19) and eCRS (n = 35) on the basis of pathologically determined eosinophil counts of less than 10 or greater than or equal to 10 eosinophils/HPF, respectively. Swab-deposited EPX activity was measured and compared with tissue eosinophil counts, EPX levels, and CRS-specific disease metrics., Results: EPX activity was significantly increased in patients with eCRS than in patients without eCRS (P < .0001). With a relative absorbance unit cutoff value of greater than or equal to 0.80, the assay demonstrated high sensitivity (85.7%) and moderate specificity (79.0%) for confirming eCRS. Spearman correlations between EPX activity and tissue eosinophil counts (r s  = 0.424), EPX levels (r s  = 0.503), and Lund-Kennedy endoscopy scores (r s  = 0.440) in eCRS were significant (P < .05)., Conclusions: This investigation evaluates a nasal swab sampling method and EPX activity assay that accurately confirms eCRS. This method could potentially address the unmet need to identify sinonasal tissue eosinophilia at the point-of-care, as well as to longitudinally monitor eosinophil activity and treatment response., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Indocyanine green (ICG) fluorescent image (FI)-guided surgery has demonstrated success in improving intraoperative visualization and tumor resections. The objectives were to evaluate the use of IGC in FI-guided transoral robotic surgery (TORS) and the underlying molecular mechanism., Methods: HPV+ oropharyngeal squamous cell carcinoma (OPSCCa) patient (n = 10) undergoing TORS were enrolled in this prospective study. Participants received intravenous ICG. Excised tissues were evaluated for ICG accumulation, tumor demarcation, and pathological characteristics using In-vivo imaging system (IVIS), histology, and RNA sequencing., Results: ICG accumulation was significantly increased in primary tumor and pathological lymph nodes compared with normal tissues (p < 0.001). IVIS was 91.3% accurate in identifying OPSCCa in excised tissues; the correlation between IVIS- and histologically determined tumor tissues was significant (R 2  = 0.8301; p = 0.001). Genes associated with vascular and angiogenic signaling pathways were significantly upregulated in OPSCCa tissues., Conclusion: ICG effectively demarcates tumor margins in OPSCCa, due to the increased upregulation of genes associated with vascular permeability., (© 2023 Wiley Periodicals LLC.)

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA)., Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus., Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated., Conclusion: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy., (© 2022 ARS-AAOA, LLC.)

Objective: Inflammatory pathologies of the sella and orbit are rare but require prompt diagnosis to initiate effective treatment. Because uniform recommendations for treatment are currently lacking, we performed an evidence-based review to identify recommendations., Methods: We performed a literature search of the PubMed, Embase, and Web of Science databases to identify papers evaluating treatment of inflammatory pathologies of the sella and orbit. We used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to define recommendations, specifically examining aggregated sample sizes, disease-specific patient follow-up, and clinical trials focused on inflammatory diseases of the sella and orbit., Results: A total of 169 studies were included and organized by disease pathology. Treatments for various pathologies were recorded. Treatment options included surgery, radiation, steroids, targeted treatments, immunomodulators, intravenous immune globulin, and plasmapheresis. Steroids were the most often employed treatment, second-line management options and timing varied. Pathological diagnosis was highly associated with treatment used. Most evidence were level 3 without available control groups, except for 13 trials in neuromyelitis optica with level 1 or 2 evidence., Conclusions: This is the first evidence-based review to provide recommendations on specific treatments for pathologies of the orbit and sella. The reported data may be useful to help guide randomized clinical trials and provide resource for clinical management decisions based on the available evidence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although it has been postulated that tobacco use, as well as other environmental exposures, may contribute to chronic rhinosinusitis (CRS), the data remain limited. Here, we utilised a large state population database to assess the association between tobacco use and CRS prevalence among patients undergoing endoscopic sinus surgery (ESS)., Methods: Employing a case-control study design, the Utah Population Database was queried for patients age >18 with a diagnosis of CRS and tobacco use who underwent ESS between 1996 and 2018. Smoking status was compared between patients with CRS (n = 34 350) and random population controls matched 5:1 on sex, birth year, birthplace, time residing in Utah, and pedigree (i.e., familial) information (n = 166 020). Conditional logistic regression models were used for comparisons between CRS patients and their matched controls. All analyses were repeated, additionally adjusting for race, ethnicity, tobacco use, asthma history, and interaction between tobacco use and asthma history., Results: A total of 200 370 patients were included in the final analysis. Patients with CRS were significantly more likely to demonstrate a history of tobacco use than controls (19.6% vs. 15.0%; p < .001), with an adjusted odds ratio (aOR) of 1.42, 95% confidence interval 1.37-1.47; p < .001. More patients with CRS and comorbid asthma used tobacco (19.5%) than controls with asthma (15.0%; p < .001)., Conclusion: History of tobacco use may portend increased risk for the development of CRS among patients undergoing ESS compared to healthy controls., (© 2022 John Wiley & Sons Ltd.)

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document., Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work., Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost., Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to assess productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS., Methods: This investigation was a prospective, multi-institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) questionnaire before surgery and approximately 6 months after the procedure. Factors associated with minimal clinical important differences (MCIDs) for productivity and activity impairment were identified., Results: A total of 279 study participants were screened for inclusion, of whom 176 (63.1%) with postoperative follow-up were included in the final cohort. Preoperative productivity and activity impairment were observed in 63.2% and 69.8% of the patients, respectively. Among these patients, postoperative improvement equaling at least 1 MCID was reported in both productivity (76.1%) and activity (76.4%) impairments. Multivariate regression identified sphenoidotomy (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.03-17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR, 8.45; 95% CI, 2.33-30.68) and migraine (OR, 0.35; 95% CI, 0.12-0.96) were associated with differential odds of activity improvement., Conclusion: CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared decision-making regarding surgical management for CRS., (© 2022 ARS-AAOA, LLC.)

Objective: Discrepancies in medical coding can negatively impact institutional revenue and result in accusations of medical fraud. The objective of the present study was to prospectively assess the utility of a dynamic feedback system for otolaryngology providers in improving the coding/billing accuracy of outpatient clinic encounters., Methods: A billing audit of outpatient clinic visits was performed. Dynamic billing/coding feedback, consisting of a virtual lecture and targeted e-mails, was provided at distinct intervals by the institutional billing and coding department. χ 2 was used for categorical data, and the Wilcoxon test was used to compare changes in accuracy over time., Results: A total of 176 clinic encounters were reviewed. Prior to feedback, 60% of encounters were inaccurately billed by otolaryngology providers, requiring upcoding and representing a potential 35% work relative value unit (wRVU) loss of E/M generated productivity. After 1 year of feedback, providers significantly increased the accuracy of their billing from 40% to 70% (odds ratio [OR]: 3.55, p  < .001, 95% confidence interval [CI]: 1.69, 7.29), with a corresponding decrease in potential wRVU loss from 35% to 10% (OR: 4.87, p  < .001, 95% CI: 0.81, 10.51)., Discussion: Dynamic billing feedback significantly improved outpatient E/M coding among otolaryngology healthcare providers in this study., Implications for Practice: This study demonstrates that educating providers on appropriate medical coding and billing policies, while providing dynamic, intermittent feedback, may improve billing accuracy, translating into appropriate charges and reimbursements for services provided., Competing Interests: J.A.A: Consultant for Medtronic, Optinose, GSK, and GlycoMira. A.S.G., D.M., P.S., J.S., and M.E.: None., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: Esthesioneuroblastoma (ENB) is a rare sinonasal malignant neoplasm with 40% 5-year survival. Because of the rarity of the tumor, the optimal treatment and subsequent prediction of prognosis are unclear. We studied a modern series of patients with ENB to evaluate the association of immunohistochemical (IHC) markers and clinical stages/grades with outcomes., Methods: A single-center retrospective review of patients with ENB treated during a 25-year period was performed. A systematic literature review evaluating the prognostic benefits of current staging systems in evaluating survival outcomes in ENB was undertaken., Results: Among 29 included patients, 25 (85%) were treated surgically at our institution, with 76% of those endoscopically resected; 7 (24.1%) received chemotherapy, and 18 (62.1%) received radiation therapy. The 5-year overall survival (OS) was 91.3%, and 10-year OS was 78.3%. Progression-free survival at 5 and 10 years was 85.6% and 68.2%, respectively. A total of 36 distinct IHC markers were used to diagnose ENB but were inconsistent in predicting survival. A systematic literature review revealed predictive accuracy for OS using the Kadish, TNM, and Hyams staging/grading systems was 68%, 42%, and 50%, respectively., Conclusions: This study reports the 5- and 10-year OS and progression-free survival in a modern series of patients with ENB. No traditional IHC marker consistently predicted outcome. Some novel reviewed markers show promise but have yet to enter clinical mainstream use. Our systematic review of accepted staging/grading systems also demonstrated a need for further investigation due to limited prognostic accuracy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Olfactory dysfunction (OD) can occur from a variety of etiologies. However, there are few reports examining whether varying etiologies have unique profiles of psychophysical testing that may provide insight into the pathophysiology of OD., Methods: Adults with chronic rhinosinusitis with and without nasal polyps (CRSwNP/CRSsNP) and healthy control adults with no sinus complaints underwent olfactory assessment with Sniffin' Sticks. Profiles of identification and discrimination were compared between CRS and non-CRS subjects across the spectrum of OD., Results: Normosmics with or without CRS identified apple, pineapple, and turpentine less frequently than expected (range 52%-68% correct). Hyposmics with CRS correctly identified orange more frequently than control hyposmics (83%-93% vs 68% for controls) with similar findings for rose. Hyposmics of all cohorts were unable to identify apple (26%). Discrimination profiles were similar across the spectrum of OD and between diagnostic groups., Conclusions: Identification and discrimination rates of specific odorants may provide unique information regarding the etiology of OD, however psychophysical testing is a complex interplay of olfactory and trigeminal function, the strength of target odorant, distractor choices, and familiarity with odorants.

Background: Large epidemiologic studies have suggested that a history of tobacco use may be associated with an increased risk of developing chronic rhinosinusitis (CRS). The impact of tobacco use on revision rates of endoscopic sinus surgery (ESS), however, remains limited., Objective: This study seeks to define the independent risk of tobacco use (active or prior) on revision rates of ESS among a large cohort of patients with CRS., Methods: A state population database was queried for patients age ≥18 years with CRS who underwent at least one ESS between 1996 and 2018. Demographic characteristics, history of ESS, and tobacco use status were compared across patients with CRS, using t tests for continuous variables and χ 2 tests for categorical variables. Unadjusted and adjusted logistic regression models were used to understand the impact of tobacco status on revision surgery., Results: The final analysis included 34 350 patients (29 916 CRS with no revision surgery and 4434 CRS with revision surgery). Unadjusted regression analysis demonstrated an increased odds of undergoing revision ESS (OR 1.12, 95% CI: 1.00-1.25, P  = .05) among males with a history of tobacco use and CRS. Adjusted regression analysis demonstrated that the risk of revision ESS among CRS patients with a history of asthma and tobacco use was 1.72-fold, while the risk among CRS patients who were tobacco users without asthma was 1.11-fold., Conclusion: History of tobacco use is an independent risk factor for revision ESS among patients with CRS.

Importance: The distance traveled by patients for medical care is associated with patient outcomes (ie, distance bias) and is a limitation in outcomes research. However, to date, distance bias has not been examined in rhinologic studies., Objective: To evaluate the association of distance traveled by a cohort of patients with chronic rhinosinusitis with baseline disease severity and treatment outcomes., Design, Setting, and Participants: A total of 505 patients with chronic rhinosinusitis were prospectively enrolled in a multi-institutional, cross-sectional study in academic tertiary care centers between April 2011 and January 2020. Participants self-selected continued appropriate medical therapy or endoscopic sinus surgery. The 22-item Sinonasal Outcome Test (SNOT-22) and Medical Outcomes Study Short Form 6-D (SF-6D) health utility value scores were recorded at enrollment and follow-up. Data on the distances traveled by patients to the medical centers, based on residence zip codes, and medical comorbid conditions were collected., Exposures: Distance traveled by patient to obtain rhinologic care., Main Outcomes and Measures: SNOT-22 and SF-6D scores. Scores for SNOT-22 range from 0 to 110; and for SF-6D, from 0.0 to 1.0. Higher SNOT-22 total scores indicate worse overall symptom severity. Higher SF-6D scores indicate better overall health utility; 1.0 represents perfect health and 0.0 represents death., Results: The median age for the 505 participants was 56.0 years (IQR, 41.0-64.0 years), 261 were men (51.7%), 457 were White (90.5%), and 13 were Hispanic or Latino (2.6%). These categories were collected according to criteria described and required by the National Institutes of Health and therefore do not equal the entire cohort. Patients traveled a median distance of 31.6 miles (50.6 km) (IQR, 12.2-114.5 miles [19.5-183.2 km]). Baseline (r = 0.00; 95% CI, 0.00-0.18) and posttreatment (r = 0.01; 95% CI, -0.07 to 0.10) SNOT-22 scores, as well as baseline (r = -0.12; 95% CI, -0.21 to -0.04) and posttreatment (r = 0.07; 95% CI, -0.02 to 0.16) SF-6D scores, were not associated with distance. There was no clinically meaningful correlation between distance traveled and mean comorbidity burden. Nevertheless, patients with a history of endoscopic sinus surgery were more likely to travel longer distances to obtain care (Cliff delta = 0.28; 95% CI, 0.19-0.38)., Conclusions and Relevance: Although this cross-sectional study found that some patients appear more willing to travel longer distances for chronic rhinosinusitis care, results suggest that distance traveled to academic tertiary care centers was not associated with disease severity, outcomes, or comorbidity burden. These findings argue for greater generalizability of study results across various cohorts independent of distance traveled to obtain rhinologic care., Trial Registration: ClinicalTrials.gov Identifier: NCT02720653.

Objective  Although the role of intraoperative alcoholization of the pituitary gland has been examined for the management of malignant tumor metastases and Rathke's cleft cysts, no such studies have been conducted relating to growth hormone (GH) secreting pituitary tumors, despite the high rate of recurrence in this cohort of patients. Here, we sought to understand the impact of adjunctive intraoperative alcoholization of the pituitary gland on recurrence rates and perioperative complications associated with resection of GH-secreting tumors. Methods  This is a single-institution retrospective cohort study analyzing recurrence rates and complications among patients with GH-secreting tumors who received intraoperative alcoholization of the pituitary gland postresection versus those that did not. Welch's t -tests and analysis of variance (ANOVA) analyses were employed to compare continuous variables between groups, whereas chi-squared tests for independence or Fisher's exact tests were used for comparing categorical variables. Results  A total of 42 patients ( n  = 22 no alcohol and n  = 20 alcohol) were included in the final analysis. The overall recurrence rates did not significantly differ between the alcohol and no alcohol groups (35 and 22.7%, respectively; p  = 0.59). The average time to recurrence in the alcohol and no alcohol groups was 22.9 and 39 months, respectively ( p  = 0.63), with a mean follow-up of 41.2 and 53.5 months ( p  = 0.34). Complications, including diabetes insipidus, were not significantly different between the alcohol and no alcohol groups (30.0 vs. 27.2%, p  = 0.99). Conclusion  Intraoperative alcoholization of the pituitary gland after resection of GH-secreting pituitary adenomas does not reduce recurrence rates or increase perioperative complications., Competing Interests: Conflict of Interest J.A.A. is a consultant for OptiNose, Glycomira, Medtronic, and GSK. M.K. receives royalties from Thieme Medical Publishing., (Thieme. All rights reserved.)

Background: Comorbid chronic rhinosinusitis (CRS) of adulthood is increasing among patients with cystic fibrosis (CF) due to improved median survival. However, little is known about the natural history of endoscopic sinus surgery (ESS) in this cohort. The objective of this study was to evaluate the revision rate of ESS and associated risk factors among adults with CRS and CF (CRSwCF). Methods: The Utah Population Database was queried for patients age >18 with CRS who underwent at least one ESS between 1996 and 2018. Demographic information and ESS history were collected and compared for CRSwCF versus CRS without CF (CRSsCF) using chi-square and t-tests. Risk factors for revision were analyzed using Cox proportional hazard models and logistic regression analysis. Results: A total of 34 050 patients (33 639 CRSsCF and 411 CRSwCF) were included in the final analysis. The mean duration of follow-up was 9.3 and 9.3 years, respectively ( P  = .98). Adult patients with CF were significantly more likely to undergo revision ESS (18.7%) than those without CF (13.4%; P  < .01). Logistic regression analysis indicated that a diagnosis of CF independently elevated the risk for revision ESS in the absence of nasal polyps (odds ratio [OR] 2.18, confidence interval [CI] 1.34-3.54), asthma (OR 1.36, CI 0.94-1.98), and allergies (OR 1.29, CI 0.90-1.73). Conclusion: In the era before highly effective modulator therapies, the mean revision rate of ESS among adults with CRSwCF was 18.7%, significantly greater than that of adults with CRSsCF. CF was an independent risk factor for revision ESS in the absence of nasal polyps, asthma, and allergies.

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger , and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease., Competing Interests: DC and JK hold intellectual property in PM-43I. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with the author YZ at the time of review., (Copyright © 2022 Sun, Damania, Mair, Otukoya, Li, Polsky, Zeng, Alt, Citardi, Corry, Luong and Knight.)

Background: Patient satisfaction has a significant bearing on medical therapy compliance and patient outcomes. The purpose of this study was to (1) describe patient satisfaction, as characterized by the Patient Satisfaction Questionnaire-18 (PSQ-18), in the care of patients with chronic rhinosinusitis (CRS) and (2) analyze the impact of comorbidities on satisfaction using the functional comorbidity index (FCI)., Methods: Patient demographics, disease severity measures, and PSQ-18 scores for patients with CRS presenting to a tertiary rhinology clinic between November 2019 and April 2020 were collected and analyzed. FCI was calculated retrospectively using the electronic medical record; individual comorbidities were tabulated. Spearman's correlations followed by multivariate regression was used to assess the relationship between medical comorbidities and PSQ-18., Results: Sixty-nine patients met criteria for analysis. There were no significant differences in age, gender, and Sinonasal Outcomes Test-22 scores between CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps. There was no significant difference in the mean FCI for patients with CRSwNP versus CRSsNP (5.1 and 4.3, respectively) ( P  = .843). Similarly, there was no significant difference in the mean sum PSQ-18 score (78/100 in both) between these cohorts ( P  = .148). The mean sum PSQ-18 score was not significantly associated with anxiety ( P  = .728), depression ( P  = .624), or FCI ( P  = .282), but was significantly associated with hearing impairment ( P  < .001)., Conclusion: Patient satisfaction in the care of CRS is generally high with a diagnosis of comorbid hearing impairment demonstrating a negative association with satisfaction in this cohort., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TOS is a consultant for Stryker and Intersect ENT. JAA is a consultant for OptiNose, AstraZeneca, Medtronic, and GlycoMira.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted safety concerns surrounding possible aerosol-generating procedures, but comparative data on the smallest particles capable of transmitting this virus remain limited. We evaluated the effect of nasal endoscopy on aerosol concentration and the role of a high-efficiency particulate air (HEPA) filter in reducing aerosol concentration., Methods: Otolaryngology patients were prospectively enrolled in an outpatient, cross-sectional study. Demographic information and clinic room characteristics were recorded. A scanning mobility particle sizer and GRIMM aerosol monitor measured aerosols 14.3 nm to 34 μm in diameter (i.e., particles smaller than those currently examined in the literature) during (1) nasal endoscopy (± debridement) and (2) no nasal endoscopy encounters. One-way analysis of variance (ANOVA) and Student's t test were performed to compare aerosol concentrations and impact of HEPA filtration., Results: Sixty-two patients met inclusion criteria (25 nasal endoscopy without debridement; 18 nasal endoscopy with debridement; 19 no nasal endoscopy). There was no significant difference in age or gender across cohorts. Aerosol concentration in the nasal endoscopy cohort (± debridement) was not greater than the no nasal endoscopy cohort (p = 0.36; confidence interval [95% CI], -1.76 to 0.17 μg/m 3 ; and p = 0.12; 95% CI, -0.11 to 2.14 μg/m 3 , respectively). Aerosol concentrations returned to baseline after 8.76 min without a HEPA filter versus 4.75 min with a HEPA filter (p = 0.001; 95% CI, 1.73-6.3 min)., Conclusion: Using advanced instrumentation and a comparative study design, aerosol concentration was shown to be no greater during nasal endoscopy versus no endoscopy encounters. HEPA filter utilization reduced aerosol concentrations significantly faster than no HEPA filter., (© 2021 ARS-AAOA, LLC.)

Background: Medical comorbidities are commonly encountered in chronic rhinosinusitis (CRS) and may impact both physical function and patient reported health-related quality-of-life (HRQOL). The functional comorbidity index (FCI) is designed to elucidate the role of comorbidities on functional prognosis. The objective of this study was to understand the impact of comorbidities known to impact physical function on baseline HRQOL using the FCI.Methodology: Patients meeting diagnostic criteria for CRS were prospectively enrolled in a cross-sectional study. Responses from the Sinonasal Outcomes Test-22 (SNOT-22), a measure of patient HRQOL, as well as the Lund-Kennedy and Lund-Mackay scores were recorded at enrollment. FCI was calculated retrospectively using the electronic medical record. Information was collected and compared for patients without (CRSsNP) and with nasal polyps (CRSwNP) using chi-square and t-tests. Spearman's correlations, followed by multivariate regression analysis, were used to assess the association between FCI and SNOT-22 scores., Results: One hundred and three patients met inclusion criteria for analysis. There were no significant differences in age, gender, and SNOT-22 scores between patients with CRSsNP and those with CRSwNP. FCI was significantly and independently associated with worse SNOT-22 scores ( P  = .012). FCI did not correlate with endoscopy and computed tomography scores. The mean FCI for patients with CRSsNP and CRSwNP was 2.02 and 2.24, respectively, and did not differ significantly between the two cohorts ( P  = .565)., Conclusions: Major medical comorbidities known to affect physical function are associated with worse SNOT-22 scores in patients with CRS as measured by the FCI.

Background: The impact of multiple coexisting medical comorbidities on treatment outcomes in chronic rhinosinusitis (CRS) is unknown. In this study we sought to evaluate the effect of comorbidities on sinonasal quality of life (QOL) and general health utility values by utilizing the Functional Comorbidity Index (FCI) in CRS patients., Methods: Patients with CRS were prospectively enrolled in a cross-sectional study of medical and surgical therapies. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Medical Outcomes Study Short-Form 6D (SF-6D) scores were recorded at enrollment and 6-month follow-up; Lund-Kennedy endoscopy and Lund-Mackay computed tomography scores were recorded at enrollment. The FCI was calculated using the electronic medical record. The impact of cumulative comorbidity burden on baseline and posttreatment outcomes was assessed using univariate and bivariate correlations., Results: A total of 428 participants with CRS were included. The average (mean standard ± deviation) FCI score was 3.03 ± 2.28 (range, 0-12). Significant linear correlations were identified between increasing FCI score and baseline SNOT-22 and SF-6D scores (R = 0.166, p = 0.001 and R = -0.245, p < 0.001, respectively). There was no correlation between FCI and change in SNOT-22 or SF-6D scores after CRS treatment (R = 0.066, p = 0.17 and R = -0.087, p = 0.074, respectively). Achievement of a minimally clinically important difference was also independent of FCI., Conclusion: Although cumulative comorbidity burden, as measured by FCI, is associated with worse baseline SNOT-22 and SF-6D scores, it does not appear to limit posttreatment improvement in either outcome measure. On average, patients with high comorbidity burden report substantial improvement in both QOL and health utility after CRS treatment, similar to those with fewer comorbidities., (© 2021 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is known to have a significant impact on economic productivity. Sleep dysfunction is associated with staggering productivity losses and is highly prevalent in patients with CRS. The effect of sleep dysfunction on productivity in CRS has not been elucidated. The objective of this study was to determine the relationship between sleep dysfunction and lost productivity in patients with CRS., Methods: Eighty-two adult patients with CRS were prospectively enrolled into a cross-sectional cohort study. Patients with obstructive sleep apnea were excluded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Presenteeism (reduced work efficiency), absenteeism (missed work days), and lost work, household, and overall productivity were analyzed. The primary aim was assessing the correlation between PSQI and productivity. Regression analyses were performed to account for disease severity, pain, and depression., Results: Sleep dysfunction is significantly correlated with overall lost productivity (R 2  = 0.397, P  < .05). Presenteeism is the most strongly affected by sleep dysfunction (R 2  = -0.441, P  < .001). Higher PSQI scores were significantly associated with productivity losses, whereas lower scores were not. Sleep remained an independent predictor of productivity when regression analysis accounted for disease severity, depression, and pain., Conclusion: Sleep dysfunction has a significant association with lost productivity in patients with CRS, particularly with worsening PSQI scores. More clearly defining those components of CRS that most impact a patient's daily function will allow clinicians to more optimally manage and counsel patients with CRS.

Background: The SNOT-22 is a validated and widely used outcomes tool in chronic rhinosinusitis (CRS). We hypothesized that SNOT-22 scores and response patterns could be used as a diagnostic tool to differentiate between patients with CRS and those who present with CRS-like symptoms but prove not to have CRS., Methodology/principal: SNOT-22 measurements were collected from 311 patients who presented with a chief complaint of sinusitis to a tertiary rhinology practice. Following a full diagnostic evaluation, patients were diagnosed with CRS or determined to have non-CRS diagnoses. A response pattern "heatmap" of the SNOT-22 scores for each group was compared. An optimal cutoff point for total SNOT-22 score in predicting CRS was sought using a receiver operating characteristic (ROC) curve., Results: A total of 109 patients were diagnosed with CRS and 202 patients were assigned to non-CRS. The non-CRS SNOT-22 total score histogram had lower overall scores compared to the CRS group, although there was substantial overlap. The CRS SNOT-22 heatmaps had a distinctive pattern compared to the non-CRS group. As individual measures, 3 of the 4 cardinal symptoms of CRS (nasal congestion, loss of smell, and rhinorrhea) were found to be significantly different between the 2 groups ( P  < .002). However, the ROC analysis showed the total SNOT-22 score to be a poor instrument to differentiate CRS from non-CRS patients., Conclusions: Our results cause us to reject our hypothesis and conclude that, while an effective outcomes tool, the SNOT-22 (using total score and response pattern) is a poor differentiator between CRS and non-CRS patients.

Chronic rhinosinusitis (CRS) is a debilitating inflammatory disorder of the sinonasal mucosa that substantially diminishes patient quality of life. Progress surrounding management of this disease has been crippled by a lack of therapeutic innovation. It has been posited that increased vascularity within the diseased sinuses of patients with CRS may allow for improved systemic drug delivery via nanoscale liposomal carriers. Such a system could enhance drug distribution, accumulation, and retention within the sinuses, ultimately leading to improved patient outcomes. PEGylated liposomes loaded with indocyanine green (ICG) were synthesized, characterized and systemically administered in a mouse model of CRS. Accumulation and retention of ICG in sinonasal tissue were evaluated. Compared to healthy controls, CRS mice showed significant sinonasal tissue accumulation and retention of PEGylated liposomal ICG for up to 21 days (P < 0.001). Conversely, free ICG was eliminated from the body after 24 h in both groups., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample., Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey., Results: EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD., Conclusion: The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS., (© 2021 ARS-AAOA, LLC.)