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Browsing by Author "Schlosser, Rodney J."
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Item All Chronic Rhinosinusitis Endotype Clusters Demonstrate Improvement in Patient Reported and Clinical Outcome Measures after Endoscopic Sinus Surgery(Wiley, 2024) Chapurin, Nikita; Schlosser, Rodney J.; Gutierrez, Jorge; Mace, Jess C.; Smith, Timothy L.; Bodner, Todd E.; Khan, Sofia; Mulligan, Jennifer K.; Mattos, Jose L.; Alt, Jeremiah A.; Ramakrishnan, Vijay R.; Soler, Zachary M.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: 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.Item Disease control after surgery for chronic rhinosinusitis: Prospective, multi-institutional validation of the Sinus Control Test (SCT)(Wiley, 2021) Little, Ryan E.; Schlosser, Rodney J.; Smith, Timothy L.; Storck, Kristina A.; Alt, Jeremiah A.; Beswick, Daniel M.; Mace, Jess C.; Mattos, Jose L.; Ramakrishnan, Vijay R.; Soler, Zachary M.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: The Sinus Control Test (SCT) is a 4-question, patient-reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS. Methods: Adults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively. Results: A total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT-22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT. Conclusion: Improvement in disease control following ESS as measured by the SCT correlated with improvements in SNOT-22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient-reported and objective measures of disease severity.Item Endotyping Chronic Rhinosinusitis Based on Olfactory Cleft Mucus Biomarkers(Elsevier, 2021) Soler, Zachary M.; Schlosser, Rodney J.; Bodner, Todd E.; Alt, Jeremiah A.; Ramakrishnan, Vijay R.; Mattos, Jose L.; Mulligan, Jennifer K.; Mace, Jess C.; Smith, Timothy L.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: 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.Item Ethmoid-to-Maxillary Opacification Ratio: A Predictor of Postoperative Olfaction and Outcomes in Nasal Polyposis?(Wiley, 2021) Beswick, Daniel M.; Smith, Timothy L.; Mace, Jess C.; Alt, Jeremiah A.; Farrell, Nyssa F.; Ramakrishnan, Vijay R.; Schlosser, Rodney J.; Soler, Zachary; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Inflammatory profiles for patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) vary between North American and Asian populations. An elevated ethmoid-to-maxillary (E/M) opacification ratio on preoperative imaging is associated with certain postoperative outcomes in Asian populations and populations that are non-type 2 dominant. In this study we explore this factor in North American/type 2-based populations. Methods: Adult patients (n = 165) from a North American population with CRSwNP who underwent endoscopic sinus surgery (ESS) were prospectively enrolled into an observational, multi-institutional study. The 22-item Sino-Nasal Outcome Test (SNOT-22), Brief Smell Identification Test (BSIT), and Lund-Kennedy (LK) endoscopic scores were obtained pre- and postoperatively. Patients were stratified according to increasing E/M ratios based on Lund-Mackay (LM) scores. Results: On average, significant within-subject postoperative improvement was found in all patients for SNOT-22 total and domain scores, and also BSIT results (p ≤ 0.019). Preoperatively, elevated E/M ratio correlated with worse BSIT scores (r = -0.343, p < 0.001). Postoperatively, elevated E/M ratio correlated with BSIT improvement (r = 0.284, p = 0.002), but did not correlate with SNOT-22 improvement or polyp recurrence. An elevated E/M ratio was associated with greater likelihood of reporting a minimal clinically important difference in BSIT scores (χ2 = 9.96, p = 0.041). Conclusion: Elevated E/M ratios were found to associated with worse baseline olfaction and an increased likelihood of achieving a clinically meaningful postoperative improvement in olfaction in this North American population with CRSwNP. Elevated E/M ratios did not predict postoperative changes in SNOT-22 measures or polyp recurrence. This suggests that prognostic factors may vary according to geography and generalized inflammatory profiles (type 2 vs non-type 2) in patients with CRS.Item Olfactory cleft mucus inflammatory proteins in CRS: A case control study(Wiley, 2021) Smith, Timothy L.; Schlosser, Rodney J.; Soler, Zachary M.; Mace, Jess C.; Mattos, Jose L.; Ramakrishnan, Vijay R.; Beswick, Daniel M.; Alt, Jeremiah A.; Mulligan, Jennifer K.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Multiple hypotheses are evolving that suggest several, potentially overlapping etiologies for olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). Understanding inflammatory cytokine profiles of the olfactory cleft (OC) and their association with olfactory function is foundational for future clinical care and research. Methods: This cross-sectional, case-control study evaluates associations among OC mucus inflammatory proteins, psychophysical olfactory testing, and computed tomography (CT) analysis of the OC and sinuses. Normative reference intervals were determined for each protein and odds ratios (ORs) were used to compare proportions of altered expression between CRS without nasal polyposis (CRSsNP) and CRS without nasal polyposis (CRSwNP). Results: Case subjects with CRS (n = 151) and controls (n = 74) were evaluated. A majority of OC proteins tested were found within detectable ranges for cases and controls. The CRS cohort had significantly higher concentrations for 23 of 26 proteins. CRS cases with abnormal levels of C-C motif chemokine ligand 2 (CCL2), CCL3, interleukin 5 (IL5), IL10, and IL13 associated with greater olfactory deficits. The prevalence of elevated IL5 and IL13 in anosmic patients was 64.6% and 62.5%, respectively (p < 0.004). CRS cases with the highest odds of elevated expression in CRSwNP were IL5 (OR = 10.83) and IL13 (OR = 8.36). However, both IL5 and IL13 were still elevated in approximately 14% of CRSsNP patients. The highest magnitude of correlation between the total percent of OC opacification was found to be with IL5 (r = 0.543; p < 0.001), whereas other moderate correlations were noted with immunoglobulin E (IgE), IL10, and IL13. Conclusion: This study confirmed that OC inflammatory proteins vary both by disease phenotype and in their association with OD. Type 2 inflammatory mediators are increased in CRS, especially within the CRSwNP group. However, a substantial proportion of CRSsNP also express type 2 inflammatory mediators. Further research is necessary to understand the complex roles OC mucous inflammatory proteins might play in defining endotype and in impacting CRS-related OD.Item Olfactory Function After Surgical Treatment of CRS: A Comparison of CRS Patients to Healthy Controls(Sage, 2021) Mattos, Jose L.; Soler, Zachary M.; Schlosser, Rodney J.; Mace, Jess C.; Alt, Jeremiah A.; Ramakrishnan, Vijay R.; Payne, Spencer C.; Smith, Timothy L.; Beswick, Daniel M.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Many patients with chronic rhinosinusitis (CRS) have persistent olfactory dysfunction (OD) following endoscopic sinus surgery (ESS). Few studies compare outcomes to control subjects so it is unknown if residual OD is due to persistent CRS. Objective: Compare postoperative measures of OD in case patients with CRS to healthy controls without sinonasal disease. Methods: Prospective, observational, multicenter cohort study between October, 2016 and May, 2019. Case participants were selected from referred adult patients diagnosed with CRS, with or without nasal polyposis (NP), electing ESS as subsequent treatment modality. Controls voluntarily enrolled from a community-based sample without a history of CRS. Primary outcomes included measures of preoperative and postoperative OD using "Sniffin' Stick" pens which summarize odorant threshold (T), discrimination (D), and identification (I) scores. Secondary outcomes included the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) survey and olfactory cleft endoscopy scores (OCES). Results: Outcomes were compared between 113 cases and 164 controls of similar average age and gender. Cases reported significantly worse baseline Sniffin' Sticks TDI total scores (-6.8[SE ± 1.0]; 95% CI: -4.9 to -8.7), QOD-NS (8.9[SE ± 1.1]; 95% CI: 6.8-10.9), and OCES (3.5[SE ± 0.4]; 95% CI: 2.9-4.2) on average. Cases reported significant postoperative improvement in TDI total score (3.7[SD ± 8.2]; 95% CI: 2.2-5.2), QOD-NS (-5.9[SD ± 8.7]; 95% CI: -7.6 to -4.3), and OCES (-1.7[SD ± 3.8]; 95% CI: -2.7 to -0.8) on average, while 63% of anosmics reported improved postoperative olfaction. Multivariate regression identified that NP (OR = 0.4; 95% CI: 0.2-1.0) and previous ESS (OR = 0.3; 95% CI: 0.1-0.8) decreased the odds of postoperative improvement equal to mean TDI scores of controls, while septoplasty increased those odds (OR = 4.5; 95% CI: 1.5-13.7). Conclusion: ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.Item Psychometric Properties of the Brief Version of the Questionnaire of Olfactory Disorders in Patients with Chronic Rhinosinusitis(Wiley, 2021) Mattos, Jose L.; Bodner, Todd E.; Mace, Jess C.; Schlosser, Rodney J.; Beswick, Daniel M.; Ramakrishnan, Vijay; Alt, Jeremiah; Payne, Spencer C.; Smith, Timothy L.; Soler, Zachary; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: 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.