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Background: Mechanisms of smell loss in chronic rhinosinusitis (CRS) are still unclear and likely multifactorial. Little attention has been given to olfactory cleft (OC) mucus proteins involved in odorant binding and metabolizing enzymes and their potential role in smell loss. Methods: Mucus from the OC was sampled from patients with CRS (n = 20) and controls (n = 10). Liquid chromatography and mass spectrometry were performed, followed by data processing so that protein groups could be identified, quantified, and compared. Hierarchical clustering and bioinformatic analysis were performed on significantly different proteins to explore for enrichment in known biologic pathways. Results: A total of 2514 proteins were found in OC mucus from all 30 subjects. Significant differences in protein abundance were found between CRS and controls, including both CRSsNP (n = 351 proteins; log2 fold change range: –3.88 to 6.71) and CRSwNP (n = 298 proteins; log2 fold change range: –4.00 to –6.13). Significant differences were found between patients with normosmia and those with dysosmia (n = 183; log2 fold change range: –3.62 to –2.16) and across groups of interest for a number of odorant binding proteins and metabolizing enzymes. Conclusion: OC mucous in CRS displays a rich and abundant array of proteins, many of which have been implicated in odorant transport and metabolization in animal studies. Significant differences in the olfactory mucus proteome were seen between CRS subtypes and controls, as well as between those with normal and abnormal olfaction. Further study should confirm these findings and explore the role individual proteins play in odorant transport and metabolization. ©2020 ARSAAOA, LLC. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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/T h 17-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, χ 18 2 = 178.64 ; P <.001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P <.001 for all). 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. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic rhinosinusitis (CRS) commonly experience both reduced quality of life (QOL) and olfactory dysfunction (OD). Literature on the impacts of appropriate medical therapy (AMT) for CRS on QOL and OD is limited, and the focused design of these studies may limit their applicability to usual clinical practice. Methods: Adults with symptomatic CRS were prospectively enrolled (November 2016 to October 2018) into an observational, multi‐institutional study. Individualized AMT was initiated using standard practice according to evidence‐based guidelines. Endoscopy examination (Lund‐Kennedy), olfactory function (Sniffin' Sticks) testing, and QOL survey responses (22‐item Sino‐Nasal Outcome Test [SNOT‐22], Questionnaire of Olfactory Disorders―Negative Statements [QOD‐NS]) were obtained at enrollment and follow‐up. Results: Baseline measures demonstrated heterogeneity of QOL and OD. After an average of 7.8 weeks, within‐subject median SNOT‐22 total improved by 39.5% (n = 39, p < 0.001) relative to baseline, including 50% (p = 0.014) improvement for item #21, "Sense of smell/taste." QOD‐NS improvement was also statistically significant (p = 0.044). Sniffin' Sticks score relative improvement of 10.9% (n = 33, p = 0.109) was not statistically significant and lacked correlation with SNOT‐22 total scores (R = −0.247, p = 0.165) or QOD‐NS total scores (R = −0.016, p = 0.930), but correlated moderately with endoscopy score (R = −0.436, p = 0.018). Conclusions: Participants with varied impacts of CRS, treated with individualized short‐term AMT, demonstrated significant improvements in CRS‐ and olfactory‐specific QOL measures, without corresponding improvement in clinically measured olfactory function. Olfactory function changes moderately correlated with endoscopy score changes, but lacked an association with QOL measurements. [ABSTRACT FROM AUTHOR]