Development of a novel self-assessment tool following endoscopic sinus surgery in the management of chronic rhinosinusitis.

OBJECTIVE: To propose a novel quality metric tool for retrospectively examining ESS performed on chronic rhinosinusitis (CRS) patients, ultimately to facilitate clinician self-assessment and optimize care provision within this population. DESIGN: Quality improvement study. SETTING: Multi-center. PARTICIPANTS: Observational, prospective research database of adult patients with medically recalcitrant CRS, presenting to seven North-American academic rhinology centers, who underwent ESS between 2011 and 2021. Participant characteristics, comorbidities, and preoperative study measures were collected. MAIN OUTCOMES AND MEASURES: A simple ratio of preoperative Lund-Mackay (LM) score to the number of sinus regions operated on during the course of ESS was determined for each participant and dichotomized into ratios of >1.0 or <1.0. RESULTS: 828 study participants with medically recalcitrant CRS met final study inclusion, of which 47.8 % were male with an average age of 49.0 years. Approximately 50.9 % of participants had a history of previous ESS. Overall mean ratio between preoperative LM scores and numbers of surgically addressed sinuses for all patients with CRS (n = 828) was 1.61 (range: 0.00-6.00), with a minority of subjects (n = 108; 13.0 %) found to have ratios below 1.00. Mean ratios between patients who underwent primary ESS versus revision ESS were not statistically different (2.00 [±0.83] vs 1.98 [±0.88]; 0.02 %, 95 % CI -0.10, 0.14; P = 0.76), whereas differences in mean ratios between CRSsNP patients (without nasal polyposis) and CRSwNP patients (with nasal polyposis) were statistically significant (1.78 [±0.93] vs 2.26 [±0.67]; 0.48 %, 95 % CI 0.37, 0.59; P ≤ 0.001). CONCLUSIONS AND RELEVANCE: This quality metric ratio represents a simple operational means for clinicians to integrate qualitative methodology into self-reflection when evaluating the extent of ESS performed on CRS patients. Its use as a clinical tool for retrospective self-reflection enables the surgeon to identify areas for improvement, assess situational specifics, and hone their craft.

Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers.

BACKGROUND: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss. OBJECTIVES: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach. METHODS: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters. RESULTS: A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/Th17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ182=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all). CONCLUSIONS: Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.

Predicting olfactory loss in chronic rhinosinusitis using machine learning.

OBJECTIVE: Compare machine learning (ML)-based predictive analytics methods to traditional logistic regression in classification of olfactory dysfunction in chronic rhinosinusitis (CRS-OD) and identify predictors within a large multi-institutional cohort of refractory CRS patients. METHODS: Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study were assessed for baseline CRS-OD using a smell identification test (SIT) or brief SIT (bSIT). Four different ML methods were compared to traditional logistic regression for classification of CRS normosmics versus CRS-OD. RESULTS: Data were collected for 611 study participants who met inclusion criteria between 2011 April and 2015 July. Thirty-four percent of enrolled patients demonstrated olfactory loss on psychophysical testing. Differences between CRS normosmics and those with smell loss included objective disease measures (CT and endoscopy scores), age, sex, prior surgeries, socioeconomic status, steroid use, polyp presence, asthma, and aspirin sensitivity. Most ML methods performed favorably in terms of predictive ability. Top predictors include factors previously reported in the literature, as well as several socioeconomic factors. CONCLUSION: Olfactory dysfunction is a variable phenomenon in CRS patients. ML methods perform well compared to traditional logistic regression in classification of normosmia versus smell loss in CRS, and are able to include numerous risk factors into prediction models. Several actionable features were identified as risk factors for CRS-OD. These results suggest that ML methods may be useful for current understanding and future study of hyposmia secondary to sinonasal disease, the most common cause of persistent olfactory loss in the general population.

Contemporary treatment patterns and outcomes of salivary gland carcinoma: a National Cancer Database review.

PURPOSE: Salivary gland carcinomas (SGC) are rare malignancies and data regarding treatment outcomes stratified by histologic subtype are currently limited. This study aims to examine current, national treatment patterns and overall survival (OS) of patients with the major histologic subtypes of salivary gland carcinoma. SUBJECTS AND METHODS: A review was performed of the National Cancer Database (NCDB) of patients with confirmed diagnoses of mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, or carcinoma ex pleomorphic receiving curative treatment between 2004 and 2014. Univariate and multivariate regression modeling were performed to identify risk factors significantly associated with overall survival (OS). Adjusted survival analyses stratified by treatment and staging were performed with the primary outcome of overall survival (OS) and were further stratified based on histologic subtype. RESULTS: The final analysis included 7342 patients [3547 men (48.3%) and 3795 women (51.7%); mean age 58.3 years (range 18-90 years)]. Mucoepidermoid carcinoma was the most common histology encountered [n = 2669 (36.4%)]. Unadjusted and adjusted analysis demonstrated improved survival with surgery and radiation therapy (RT) for adenoid cystic (HR = 0.69; p = 0.029), adenocarcinoma (HR = 0.61; p < 0.001), high-grade mucoepidermoid carcinoma (HR = 0.70; p = 0.026), and carcinoma ex pleomorphic (HR = 0.64; p = 0.028), while surgery with chemoradiation therapy (CRT) was associated with worse OS regardless of histologic subtype. The impact of advanced stage on survival varied amongst the histologic subtypes but portended the worst prognosis for patients with adenocarcinoma and carcinoma ex pleomorphic. CONCLUSIONS: The results of this NCDB review demonstrate unique treatment patterns and survival outcomes for SGC based on major histologic subtype.

Can sinus anatomy predict quality of life outcomes and operative times of endoscopic frontal sinus surgery?

PURPOSE: Endoscopic sinus surgery (ESS) can manipulate sinus anatomy, but with limitations due to skull base and orbit anatomy. These anatomical structures dictate the maximal extent of ESS in the frontal recess and may limit surgical extent or operative duration. This study investigates the impact of these anatomical constraints on operative time and quality-of-life (QOL) outcomes. MATERIALS AND METHODS: Patients with medically refractory chronic rhinosinusitis undergoing Draf IIa frontal sinus surgery were prospectively enrolled. Anatomic measurements of the frontal sinus anatomy were collected during computed tomography review and included: widest distance between the frontal beak and posterior table, narrowest point in the ethmoid bed, Keros height, presence of an anterior ethmoid artery on a mesentery, and presence of inter-sinus septal cells. Primary outcomes included mean operative time and improvement in SinoNasal Outcome Test (SNOT-22) survey scores. RESULTS: 63 adult participants were enrolled and followed 13.8 (5.2) months on average. The ethmoid bed mean width was 7.2 (1.4) mm, the mean distance from frontal beak to the posterior table at widest was 9.0 (2.7) mm, and mean Keros height was 5.1 (1.8) mm. 49/63 (83.1%) of participants had inter-sinus septal cells and 30/63(50.8%) had anterior ethmoid arteries on a mesentery. Mean operative time was 121.5 (44.0) min while SNOT-22 scores significantly (p<0.001) improved 26.1 (21.6) on average. Anatomic measurements were not predictive of operative time or mean QOL change (p>0.050). CONCLUSIONS: Frontal sinus surgery is an effective treatment for a range of frontal and ethmoid sinus anatomy. Further study with larger sample size and measures of more restricted anatomy might elucidate treatment limitations of ESS.

Investigation of Expectations and Satisfaction After Sinus Surgery for Chronic Rhinosinusitis.

OBJECTIVE: To perform the first mixed-methods analysis of patient expectations and satisfaction after endoscopic sinus surgery (ESS). METHODS: Semi-structured interviews of subjects undergoing ESS were performed to understand pre-operative expectations and 6-month post-operative satisfaction. Descriptive statistics, logistic regression, and mediation analyses were performed. Quantitative questions were followed by qualitative probes for subjects to expand on quantitative answers. Study sample size was determined by thematic saturation based on qualitative responses. Data visualization was used to triangulate quantitative and qualitative data wherein themes emerged. RESULTS: A total of 52 participants were included in the mixed-method analysis, and 110 were included in the mediation analysis. 56% of participants were male, with an average age of 55.7 (SD ± 2.18). Mean change in SNOT-22 was 20.8 (SD ± 3.74), and 25% of participants did not achieve a minimal clinically important difference (MCID). Of the participants who did not achieve MCID, 79% would still choose to have sinus surgery again. Qualitative interviews revealed multiple preliminary categories describing the patient experience with ESS. Regression analysis showed that the most important predictor of satisfaction was whether pre-operative expectations were met (OR = 3.8, p < 0.001). In mediation analysis, the effect of the clinical outcome on patient satisfaction was completely mediated by pre-operative expectations (indirect effect p = 0.009, direct effect p = 0.17). CONCLUSION: Patient expectations and satisfaction are important yet understudied measures in CRS and ESS. In ESS, satisfaction with outcome is driven by the fulfillment of pre-operative expectations. Aligning such expectations is the most important intervention a sinus surgeon can perform to maximize success. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Multi-institutional validation of an AI-based sinus CT analytic platform with olfactory assessments.

KEY POINTS: AI-based CT sinus analysis may have advantages over visual based systems, for example, Lund-Mackay score. Here, we show multi-institutional validation of an AI algorithm using novel OMC classification. Significant, robust correlations are seen between algorithm outputs and clinical outcomes.

Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy.

BACKGROUND: The indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy. METHODS: Retrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease-specific outcomes were measured using the sinonasal outcomes test (SNOT-22). RESULTS: Within 87 patients with CRSwNP, 24.1% had aspirin-exacerbated respiratory disease (AERD). Significant improvement in SNOT-22 score was found in CRSwNP with AERD (p < 0.001) and without AERD (p = 0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p = 0.02), prior aspirin desensitization (p = 0.02), and worse preoperative Lund-MacKay scores (p < 0.001). No association between biologic rescue and frontal recess antero-posterior diameter was found (p = 0.20). CONCLUSIONS: Draf 3 surgery in CRSwNP was associated with significant improvement in SNOT-22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period.

Single-Sided Peak Nasal Inspiratory Flow as an Adjunct Objective Measure in Functional Septorhinoplasty.

OBJECTIVE: Nasal obstruction can negatively impact patient quality of life, which can be alleviated by functional nasal surgery. Quantification of improvement is most commonly evaluated with the use of validated survey instruments but lacks widely utilized objective measures. Herein, we evaluate the utility of single-sided peak nasal inspiratory flow (PNIF) as an objective outcome measure in the evaluation and management of nasal obstruction. METHODS: Adults presenting with nasal obstruction who were recommended septorhinoplasty were included in the study. Single-sided and bilateral PNIF measures, nasal obstruction symptom evaluation (NOSE) scores, surgeon-rated percent nasal obstruction, and nasal obstruction visual analog scale (VAS) scores were recorded preoperatively with Spearman's correlation coefficients (ρ) calculated. Correlation coefficients were also calculated between the change in the above variables from the pre- to postoperative state. RESULTS: One Hundred Fifteen patients were enrolled in the study and underwent septorhinoplasty. Significant correlations between single-sided PNIF and the associated VAS scores of the same laterality were found for the worse (ρ = -0.366; p < 0.001) and better (ρ = -0.313; p < 0.001) breathing sides. Correlations between postoperative improvement in single-sided PNIF and improvement in VAS scores were also found (ρ = -0.330; p = 0.007, ρ = -0.354; p = 0.004). No correlation between NOSE scores and single-sided PNIF was found except in the subgroup of patients presenting with bilateral asymmetric nasal obstruction, in who NOSE scores correlated with worse side PNIF (ρ = -0.369; p = 0.038). CONCLUSIONS: Single-sided PNIF has a better correlation to patients' symptoms as rated by VAS score than bilateral PNIF and may be a useful adjunct objective measure in the evaluation and quantification of improvement in patients undergoing septorhinoplasty. LEVEL OF EVIDENCE: Level III Laryngoscope, 2024.

All chronic rhinosinusitis endotype clusters demonstrate improvement in patient-reported and clinical outcome measures after endoscopic sinus surgery.

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.

Does air pollutant exposure impact disease severity or outcomes in chronic rhinosinusitis?

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/m3) 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.

The Impact of Acute Peri-operative Particulate Matter Exposure on Endoscopic Sinus Surgery Outcomes: A Preliminary Multi-site Investigation.

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 (ß) 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.

Health care disparities and chronic rhinosinusitis: Does neighborhood disadvantage impact outcomes in sinonasal disease?

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 (φc) 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 (φc = 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.

Impact of sinus surgery in people with cystic fibrosis and chronic rhinosinusitis in the era of highly effective modulator therapy: Protocol for a prospective observational study.

INTRODUCTION: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. METHODS AND ANALYSIS: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. ETHICS AND DISSEMINATION: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04469439).

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

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.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

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.

Recurrence morbidity of olfactory neuroblastoma.

BACKGROUND: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence. METHODS: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses. RESULTS: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence. CONCLUSIONS: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

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.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

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 (ß = â€’4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (ß = â€’2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (ß = â€’0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (ß = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (ß = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (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.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

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.