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, 2024.

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.

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Objectives: Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods: Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results: Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. Conclusions: RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Taste dysfunction after endoscopic endonasal resection of olfactory groove meningioma: Case series and review of the literature.

PURPOSE: The incidence of ageusia and dysgeusia after endoscopic endonasal (EEA) resection of olfactory groove meningioma (OGM) is not well established despite recognized impairment in olfactory function. METHODS: We retrospectively administered a validated taste and smell survey to patients undergoing EEA for resection of OGM at two institutions. Demographics and clinical characteristics were collected and survey responses were analyzed. RESULTS: Twelve patients completed the survey. The median time from surgery was 24 months. The average total complaint score was 5.5 out of 16 [0-13]. All patients reported a change in sense of smell while only 42 % reported a change in sense of taste. Taste changes did not consistently associate with laterality or size of the neoplasm. Significant heterogeneity existed when rating severity of symptoms. CONCLUSIONS: To our knowledge this is the first case series examining taste changes after EEA resection of OGM. Despite universal olfactory dysfunction, only a minority of patients reported a change in their sense of taste. Our findings may improve patient counseling and expectations after surgery.

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.

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.

SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM. METHODS: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains. RESULTS: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes. CONCLUSIONS: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains.

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.

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.

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.

Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.

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

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 patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.

Long-term quality of life after treatment in sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame. METHODS: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL. RESULTS: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01). CONCLUSION: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment.

Impact of Medicaid Expansion on Rhinologic Cancer Presentation, Treatment, and Outcomes.

OBJECTIVE: The United States Patient Protection and Affordable Care Act allocated funds for states to expand Medicaid coverage. However, several states declined expansion. We aim to determine whether Medicaid expansion is associated with healthcare coverage, cancer stage at diagnosis, treatment, and survival among patients with rhinologic cancer. Rhinologic cancer was defined to include cancer of the nasal cavity, paranasal sinus, nasopharynx, or olfactory nerve. STUDY DESIGN: Cohort study. METHODS: Patients diagnosed with primary rhinologic malignancies between 2007 to 2016 were extracted from the National Cancer Institute Surveillance, Epidemiology, End Results (SEER) registry. Patients were grouped by diagnosis before and after 2014 (when Medicaid expansion became effective) and whether their state had expanded Medicaid. Multivariable logistic regression controlling for age, sex, race, ethnicity, and income/education was utilized to examine associations between Medicaid expansion/insurance status and stage at diagnosis, treatment, and survival. Overall and disease-specific survival were examined using Kaplan-Meier analysis. RESULTS: Analysis included 10,164 patients. The proportion of uninsured patients decreased after 2014 (2.4%) compared to before 2014 (4.8%, P < .001). After 2014, patients in nonexpanded states were more likely to be diagnosed with advanced stage disease compared to patients in expanded states (N = 2,364; OR = 1.27, 95% CI 1.01-1.60). Being uninsured in any state was associated with advanced stage disease at diagnosis (OR = 1.75, 95% CI 1.41-2.22) and increased risk of disease-specific death (HR = 1.54, 95% CI 1.32-1.82). Survival measures were not associated with diagnosis before versus after 2014 or Medicaid expansion. CONCLUSIONS: Patients lacking insurance or residing in nonexpanded states may be more likely to present with advanced stage rhinologic cancer. Longitudinal studies should validate these findings. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:43-50, 2023.

Sex Differences in Presentation and Surgical Outcomes From a Prospective Multicenter Chronic Rhinosinusitis Study.

OBJECTIVE: Despite extensive research into chronic rhinosinusitis (CRS) epidemiology, presentation, and outcomes, there is scant knowledge on sex-specific differences. The objective of this study was to identify differences between male and female patients with CRS in baseline disease severity at presentation, choice for surgery vs continued medical treatment, and postoperative response. STUDY DESIGN: We evaluated data on demographic and health characteristics, clinical objective disease measures, and sinus-specific and general health patient-reported outcome measures. SETTING: Secondary analysis of prospective multicenter outcome study. METHODS: Comparison of cohort characteristics and baseline and postoperative measures was performed with a t test, chi-square test of independence, or Fisher exact test. Within-subject improvement was compared between sexes with a linear mixed model. RESULTS: Females reported worse quality of life on presentation and postsurgery, despite experiencing less severe disease by standard clinical measures. Overall, females and males showed similar within-subject improvement after surgery. However, certain quality of life domains and disease measures showed sex-specific improvement. Females demonstrated greater within-subject improvement in SF6D-derived health utility and the SNOT-22 ear and facial, psychological, and sleep subdomains, although this did not reach statistical significance for the overall cohort. CONCLUSION: Incorporating data on sex-specific differences may be important to personalize CRS treatment decision making. The discordance between patient-reported and clinical measures in CRS has been demonstrated in other pathologies and appears to be exaggerated by sex. Biological and psychological bases for sex-specific differences in CRS manifestations are an intriguing topic for further research.

Work productivity and activity impairment in patients with chronic rhinosinusitis undergoing endoscopic sinus surgery-A prospective, multi-institutional study.

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.

A comparative analysis of endoscopic sinus surgery versus biologics for treatment of chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available. METHODS: A prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase-3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund-Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab-LIBERTY-NP-24&52, omalizumab-POLYP-1&2, and Mepolizumab-SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible. RESULTS: A total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin-exacerbated respiratory disease status, smell identification, LK-polyp score, and Lund-Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT-22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001). CONCLUSION: At 24 weeks and 52 weeks, ESS offers comparable SNOT-22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT-22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies.