Publications by authors named "Vijay R Ramakrishnan"

122 Publications

Specialized pro-resolving mediator lipidome and 16S rRNA bacterial microbiome data associated with human chronic rhinosinusitis.

Data Brief 2021 Jun 1;36:107023. Epub 2021 Apr 1.

Department of Medicine, Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Chronic rhinosinusitis (CRS) is a clinical syndrome defined by symptoms including nasal congestion, facial pain and pressure, anosmia, and rhinorrhea lasting more than 12 weeks. Several mechanistically distinct processes lead to the development of clinical symptoms in CRS including innate immune dysfunction, dysregulated eicosanoid metabolism and perturbations in host-microbiome interactions [1]. We developed a database comprised of patient demographic information, lipid mediator metabolomic profiles, and 16S bacterial rRNA gene sequence data from 66 patients undergoing endoscopic sinus surgery. Briefly, ethmoid sinus tissue and middle meatal swabs were collected from patients, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways from arachidonic acid (AA) and docosahexanoic acid (DHA) were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. This database provides a useful compendium of AA/DHA metabolomic profiles and associated bacterial microbiota in patients with varying disease subtypes, demographics, and risk factors/comorbidities.
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http://dx.doi.org/10.1016/j.dib.2021.107023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076692PMC
June 2021

Psychometric properties of the brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis.

Int Forum Allergy Rhinol 2021 Apr 17. Epub 2021 Apr 17.

Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.

Background: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample.

Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey.

Results: EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD.

Conclusion: The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS.
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http://dx.doi.org/10.1002/alr.22800DOI Listing
April 2021

CFTR-related disorder in an adult with refractory chronic rhinosinusitis: A missed diagnosis and novel mutation.

Int Forum Allergy Rhinol 2021 Apr 6. Epub 2021 Apr 6.

Department of Otolaryngology, University of Colorado, Aurora, Colorado, USA.

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http://dx.doi.org/10.1002/alr.22792DOI Listing
April 2021

Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium.

BMC Genomics 2021 Mar 30;22(1):224. Epub 2021 Mar 30.

Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Background: Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection.

Results: Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons.

Conclusion: Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.
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http://dx.doi.org/10.1186/s12864-021-07528-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007386PMC
March 2021

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

Int Forum Allergy Rhinol 2021 Mar 16. Epub 2021 Mar 16.

Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany.

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.
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http://dx.doi.org/10.1002/alr.22788DOI Listing
March 2021

Olfactory cleft mucus inflammatory proteins in CRS: a case-control study.

Int Forum Allergy Rhinol 2021 Feb 24. Epub 2021 Feb 24.

Division of Pulmonary, Critical Care & Sleep Medicine, University of Florida, Gainesville, FL.

Background: 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. ©2021 ARSAAOA, LLC.
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http://dx.doi.org/10.1002/alr.22770DOI Listing
February 2021

Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers.

J Allergy Clin Immunol 2021 May 4;147(5):1732-1741.e1. Epub 2021 Feb 4.

Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Ore. Electronic address:

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/T17-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=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.
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http://dx.doi.org/10.1016/j.jaci.2021.01.021DOI Listing
May 2021

Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.

J Allergy Clin Immunol 2021 05 13;147(5):1704-1719. Epub 2021 Jan 13.

Fifth Sense, Barrow-in-Furness, United Kingdom; Norfolk Smell and Taste Clinic, James Paget University Hospital NHS Foundation Trust, Gorleston, United Kingdom; Norwich Medical School, University of East Anglia, Norwich, United Kingdom. Electronic address:

Background: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD).

Objective: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists.

Methods: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD.

Results: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction.

Conclusions: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.
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http://dx.doi.org/10.1016/j.jaci.2020.12.641DOI Listing
May 2021

Altered tissue specialized pro-resolving mediators in chronic rhinosinusitis.

Prostaglandins Leukot Essent Fatty Acids 2021 01 26;164:102218. Epub 2020 Nov 26.

Department of Medicine, Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:

Current literature implicates arachidonic acid-derived leukotrienes and prostaglandins in the pathogenesis of chronic rhinosinusitis. However, other omega-3 and omega-6 derived lipid mediators, such as specialized pro-resolving mediators (SPMs), may also be important in chronic inflammatory disorders of the upper airway. We hypothesize that SPMs differ among CRS subtypes compared to controls and in relation to sinonasal microbiota. Ethmoid sinus tissue and middle meatal swabs were collected from a convenience sample of 66 subjects, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. Resolvin D2 was elevated in both CRSwNP (p = 0.00076) and CRSsNP (p = 0.030) compared with non-CRS controls. Lipoxin A was significantly increased in CRSwNP compared with CRSsNP (p = 0.000033) and controls (p = 0.044). Cigarette smoking was associated with significantly lower concentrations of several 15-lipoxygenase metabolites including resolvin D1 (p = 0.0091) and resolvin D2 (p = 0.0097), compared with never-smokers. Several of the lipid compounds also correlated with components of the sinonasal mucosal microbiota, including bacterial pathogens such as Pseudomonas aeruginosa. These data suggest that dysfunctional lipid mediator pathways in CRS extend beyond the traditional descriptions of leukotrienes and prostaglandins and include SPMs. Furthermore, dysregulated SPM signaling may contribute to persistent inflammation and bacterial colonization in CRS.
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http://dx.doi.org/10.1016/j.plefa.2020.102218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855833PMC
January 2021

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

Int Forum Allergy Rhinol 2021 Mar;11(3):213-739

Rutgers New Jersey Medical School, Newark, NJ.

I.

Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.

Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.

Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.

Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
March 2021

Objective sleep measures after endoscopic sinus surgery in patients with chronic rhinosinusitis.

Int Forum Allergy Rhinol 2020 Nov 23. Epub 2020 Nov 23.

Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.

Background: Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient-reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient-reported outcome measures (PROMs).

Methods: Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient-reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22-item Sino-Nasal Outcome Test (SNOT-22).

Results: Thirty-six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow-up 9.6 ± 7.7 months. Mean PSQI and SNOT-22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT-22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1).

Conclusion: In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient-reported sleep quality and CRS-specific QOL.
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http://dx.doi.org/10.1002/alr.22738DOI Listing
November 2020

Olfactory Function After Surgical Treatment of CRS: A Comparison of CRS Patients to Healthy Controls.

Am J Rhinol Allergy 2021 May 20;35(3):391-398. Epub 2020 Sep 20.

Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, Colorado.

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.
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http://dx.doi.org/10.1177/1945892420960671DOI Listing
May 2021

Disease control after surgery for chronic rhinosinusitis: prospective, multi-institutional validation of the Sinus Control Test.

Int Forum Allergy Rhinol 2021 Feb 26;11(2):106-114. Epub 2020 Jul 26.

Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.

Background: 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.
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http://dx.doi.org/10.1002/alr.22659DOI Listing
February 2021

Ethmoid-to-maxillary opacification ratio: a predictor of postoperative olfaction and outcomes in nasal polyposis?

Int Forum Allergy Rhinol 2021 Jan 18;11(1):48-57. Epub 2020 Jun 18.

Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC.

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 (χ = 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.
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http://dx.doi.org/10.1002/alr.22625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746627PMC
January 2021

Transcriptional profiling reveals TRPM5-expressing cells involved in viral infection in the olfactory epithelium.

bioRxiv 2020 May 15. Epub 2020 May 15.

Understanding viral infection of the olfactory epithelium is essential because smell loss can occur with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), and because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of fluorescent protein markers for olfactory sensory neurons and TRPM5. We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells and olfactory sensory neurons. These cells express the transcript that encodes for a serine protease that primes the SARS-CoV-2 spike protein before entry into host cells. Our study provides new insights into a potential role for TRPM5-expressing cells in viral infection of the olfactory epithelium.
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http://dx.doi.org/10.1101/2020.05.14.096016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263547PMC
May 2020

The Combined Endoscopic Endonasal Far Medial and Open Postauricular Transtemporal Approaches As a Lesser Invasive Approach to the Jugular Foramen: Anatomic Morphometric Study With Case Illustration.

Oper Neurosurg (Hagerstown) 2020 09;19(4):471-479

Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona.

Background: Access to the jugular foramen (JF) requires extensive approaches. An endoscopic endonasal far medial (EEFM) approach combined with a postauricular transtemporal (PTT) approach may provide adequate exposure with limited morbidities.

Objective: To provide a quantitative anatomic comparison of the EEFM, the PTT, and the combined EEFM/PTT approaches. A clinical case of the combined approach is presented.

Methods: Five cadaveric heads were dissected. Each specimen received PTT and EEFM approaches on opposite sides followed by an EEFM approach on the side of the PTT approach. Morphometric and quadrant analyses were conducted. Three groups were obtained and compared: PTT (group A), EEFM (group B), and combined (group C).

Results: Group B had a significantly higher area of exposure of the JF as compared to group A (112.3 and 225 mm2, respectively, P = .004). The average degree of freedom (DOF) in the cranio-caudal plane for groups A and B was 63.6 and 12.6 degrees, respectively (P < .00001). Group A had a higher DOF in the medial-lateral plane than group B (49 vs 13.4 degrees, respectively, P < .00001. The average volume of exposure in groups A and B was 1469.2 and 1897.4 mm3, respectively (P = .02). By adding an EEFM approach to the PTT approach, an additional 56.1% of the anterior quadrant was exposed, representing a 584.4% increase in the anterior exposure.

Conclusion: The PTT and EEFM approaches provide optimal exposures to different aspects of the JF and in combination may constitute a less invasive alternative to the more extensive approaches.
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http://dx.doi.org/10.1093/ons/opaa080DOI Listing
September 2020

Volumetric assessment of paranasal sinus opacification on computed tomography can be automated using a convolutional neural network.

Int Forum Allergy Rhinol 2020 Nov 15;10(11):1218-1225. Epub 2020 Jun 15.

Department of Radiology, National Jewish Health, Denver, CO.

Background: Computed tomography (CT) plays a key role in evaluation of paranasal sinus inflammation, but improved, and standardized, objective assessment is needed. Computerized volumetric analysis has benefits over visual scoring, but typically relies on manual image segmentation, which is difficult and time-consuming, limiting practical applicability. We hypothesized that a convolutional neural network (CNN) algorithm could perform automatic, volumetric segmentation of the paranasal sinuses on CT, enabling efficient, objective measurement of sinus opacification. In this study we performed initial clinical testing of a CNN for fully automatic quantitation of paranasal sinus opacification in the diagnostic workup of patients with chronic upper and lower airway disease.

Methods: Sinus CT scans were collected on 690 patients who underwent imaging as part of multidisciplinary clinical workup at a tertiary care respiratory hospital between April 2016 and November 2017. A CNN was trained to perform automatic segmentation using a subset of CTs (n = 180) that were segmented manually. A nonoverlapping set (n = 510) was used for testing. CNN opacification scores were compared with Lund-MacKay (LM) visual scores, pulmonary function test results, and other clinical variables using Spearman correlation and linear regression.

Results: CNN scores were correlated with LM scores (rho = 0.82, p < 0.001) and with forced expiratory volume in 1 second (FEV ) percent predicted (rho = -0.21, p < 0.001), FEV /forced vital capacity ratio (rho = -0.27, p < 0.001), immunoglobulin E (rho = 0.20, p < 0.001), eosinophil count (rho = 0.28, p < 0.001), and exhaled nitric oxide (rho = 0.40, p < 0.001).

Conclusion: Segmentation of the paranasal sinuses on CT can be automated using a CNN, providing truly objective, volumetric quantitation of sinonasal inflammation.
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http://dx.doi.org/10.1002/alr.22588DOI Listing
November 2020

The Microbiome and Chronic Rhinosinusitis.

Immunol Allergy Clin North Am 2020 05 16;40(2):251-263. Epub 2020 Jan 16.

Department of Otolaryngology-Head and Neck Surgery, University of Colorado, 12631 East 17th Avenue, B205, Aurora, CO 80045, USA. Electronic address:

Chronic rhinosinusitis (CRS) is persistent inflammation and/or infection of the nasal cavity and paranasal sinuses. Recent advancements in culture-independent molecular techniques have enhanced understanding of interactions between sinus microbiota and upper airway microenvironment. The dysbiosis hypothesis-alteration of microbiota associated with perturbation of the local ecological landscape-is suggested as a mechanism involved in CRS pathogenesis. This review discusses the complex role of the microbiota in health and in CRS and considerations in sinus microbiome investigation, dysbiosis of sinus microbiota in CRS, microbial interactions in CRS, and development of preclinical models. The authors conclude with future directions for CRS-associated microbiome research.
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http://dx.doi.org/10.1016/j.iac.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154041PMC
May 2020

Quality-of-life and olfaction changes observed with short-term medical management of chronic rhinosinusitis.

Int Forum Allergy Rhinol 2020 05 3;10(5):656-664. Epub 2020 Feb 3.

Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health Center, Oregon Health & Science University, Portland, OR.

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.
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http://dx.doi.org/10.1002/alr.22532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220819PMC
May 2020

Identification of Novel Genes and Biological Pathways That Overlap in Infectious and Nonallergic Diseases of the Upper and Lower Airways Using Network Analyses.

Front Genet 2019 17;10:1352. Epub 2020 Jan 17.

Department of Otolaryngology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Previous genetic studies on susceptibility to otitis media and airway infections have focused on immune pathways acting within the local mucosal epithelium, and outside of allergic rhinitis and asthma, limited studies exist on the overlaps at the gene, pathway or network level between the upper and lower airways. In this report, we compared [1] pathways identified from network analysis using genes derived from published genome-wide family-based and association studies for otitis media, sinusitis, and lung phenotypes, to [2] pathways identified using differentially expressed genes from RNA-sequence data from lower airway, sinus, and middle ear tissues, in particular cholesteatoma tissue compared to middle ear mucosa. For otitis media, a large number of genes ( = 1,806) were identified as differentially expressed between cholesteatoma and middle ear mucosa, which in turn led to the identification of 68 pathways that are enriched in cholesteatoma. Two differentially expressed genes and overlap in middle ear, sinus, and lower airway samples and are potentially novel genes for otitis media susceptibility. In addition, 56 genes were differentially expressed in both tissues from the middle ear and either sinus or lower airways. Pathways that are common in upper and lower airway diseases, whether from published DNA studies or from our RNA-sequencing analyses, include chromatin organization/remodeling, endocytosis, immune system process, protein folding, and viral process. Taken together, our findings from genetic susceptibility and differential tissue expression studies support the hypothesis that the unified airway theory wherein the upper and lower respiratory tracts act as an integrated unit also applies to infectious and nonallergic airway epithelial disease. Our results may be used as reference for identification of genes or pathways that are relevant to upper and lower airways, whether common across sites, or unique to each disease.
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http://dx.doi.org/10.3389/fgene.2019.01352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979043PMC
January 2020

The Utility of Image Guidance in Endoscopic Sinus Surgery: A Narrative Review.

JAMA Otolaryngol Head Neck Surg 2020 03;146(3):286-290

Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora.

Importance: More than a quarter-million cases of endoscopic sinus surgery (ESS) are performed annually in the United States. Most surgeons use image-guided systems as an adjunct during surgery in certain situations. Understanding the association of image-guided surgery (IGS) with surgical outcomes, complications, and surgeon factors is paramount.

Observations: Three systematic or evidenced-based review articles demonstrated no clear evidence that IGS improves surgical outcomes for chronic rhinosinusitis, including completeness of surgical dissection, patient-reported outcomes, or rates of revision surgery. Results from 2 systematic reviews suggest that major and total surgical complications may be decreased with use of IGS in certain cases, although bias may confound these findings. When complications were analyzed individually, there was no definitive evidence that IGS is associated with decreased rates of orbital, intracranial, or hemorrhagic complications. The rarity of complications in ESS, developing surgical experience, evolving training strategies, and selective use of IGS in more complex cases make future study on the association of IGS with complications challenging. Limited data on the influence of IGS on surgeon satisfaction and stress level suggests that more experienced surgeons might glean benefits in these realms, whereas junior surgeons may feel additional stress when using the technology.

Conclusions And Relevance: Level 2A evidence from systematic reviews suggests that in certain cases IGS may be associated with decreased major and total surgical complications, though the potential for bias and confounding exists in these conclusions. It is possible that, among more experienced surgeons, the use of IGS is associated with improvements in stress and satisfaction, although evidence in this realm is limited and there may be additional stresses associated with IGS for surgeons early in their career. The choice to use IGS in any endoscopic procedure remains best determined by the operating surgeon based on factors including case complexity and surgeon comfort.
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http://dx.doi.org/10.1001/jamaoto.2019.4161DOI Listing
March 2020

Factors driving olfactory loss in patients with chronic rhinosinusitis: a case control study.

Int Forum Allergy Rhinol 2020 01;10(1):7-14

Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.

Background: Olfactory dysfunction (OD) in chronic rhinosinusitis (CRS) is common. It is likely that numerous factors such as sex, race, age, allergies, asthma, smoking, and other comorbidities play a role in CRS-related OD. In order to determine which aspects of OD are due solely to CRS and which are associated with other confounders, control populations are needed to allow appropriate risk assessments.

Methods: Prospective, multi-institutional enrollment of patients with CRS and control subjects without CRS was performed. Demographic information, comorbidities, and olfactory testing (Sniffin' Sticks) of threshold (T), discrimination (D), and identification (I) scores (TDI) was collected.

Results: A total of 224 patients with CRS and 164 control subjects were enrolled. Olfaction was worse in CRS patients compared to controls (mean ± standard deviation (SD) TDI = 22.4 ± 9.5 vs 28.8 ± 7.0, respectively, p < 0.001). Only 27% of CRS patients were normosmic compared to 49% of controls (p < 0.001). When stratifying by nasal polyp (NP) status, CRSwNP patients had significant impairments in TDI, T, D, and I compared to controls with mean differences of 11.2, 3.3, 3.5, and 4.4 points, respectively (all p < 0.001). In contrast, CRSsNP patients only had impaired T when compared to controls with a mean difference of 2.2 points (p < 0.001). Multivariate modeling of TDI scoring showed that OD was driven by polyps, asthma, diabetes, and age. CRSsNP was not independently associated with worse TDI scores.

Conclusion: OD in CRS patients is multifactorial. Independent drivers appear to be polyp status, asthma, diabetes, and age. OD in patients with CRSsNP is similar to controls with the exception of impaired thresholds.
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http://dx.doi.org/10.1002/alr.22445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948021PMC
January 2020

Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis.

Int Forum Allergy Rhinol 2020 03 19;10(3):343-355. Epub 2019 Dec 19.

Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health Sciences University, Portland, OR.

Background: Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort.

Methods: Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin' Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification.

Results: Sixty-two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C-C motif ligand 2 (CCL2), interleukin-5 (IL-5), IL-6, IL-13, IL-10, IL-9, tumor necrosis factor-α (TNF-α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C-X-C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL-6, IL-10, vascular endothelial growth factor-A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund-Mackay score correlated only in the CRSsNP group (CXCL5, IL-5, IL-13, IgE).

Conclusion: Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.
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http://dx.doi.org/10.1002/alr.22499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145735PMC
March 2020

Sample collection for laboratory-based study of the nasal airway and sinuses: a research compendium.

Int Forum Allergy Rhinol 2020 03 17;10(3):303-313. Epub 2019 Dec 17.

Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO.

Background: Collection of biologic samples from the nasal cavity and paranasal sinuses is of critical importance to the study of infectious or inflammatory conditions that affect both upper and lower airways. Numerous techniques for the study of ex-vivo samples exist, with specific applications, strengths, and weaknesses associated with each of them. In this compendium we summarize the available methods for collection of primary human samples and incorporate expert discussion of the pros, cons, and applications associated with each technique.

Methods: An expert panel containing members of the American Rhinologic Society's Research and Grants Committee compiled this educational reference. Rationale for use and the potential advantages and disadvantages are discussed. Research protocols and key references are enumerated.

Results: Sampling of the nasal cavity and paranasal sinuses can be achieved through a number of methods. Nonspecific sinonasal secretions may be collected via forced exhalation, nasal lavage, and nasal spray aspiration. Targeted collection of sinonasal secretions may be achieved via endoscopic placement of absorbent matrices. Nasal cytology or collection of superficial epithelium may be completed via brushing or scraping of endonasal structures. Collection of mucosal biopsies may be completed via sinonasal explant or full-thickness biopsy.

Conclusion: Multiple sampling techniques are available to collect biologic samples from the sinonasal cavity. These techniques differ in their ease of application, reproducibility, sample yield, and utility for different sinonasal pathologies or research goals. An appreciation of the benefits and drawbacks of each approach will allow investigators to select the techniques most appropriate for achieving research objectives.
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http://dx.doi.org/10.1002/alr.22510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184785PMC
March 2020

Olfactory cleft and sinus opacification differentially impact olfaction in chronic rhinosinusitis.

Laryngoscope 2020 10 11;130(10):2311-2318. Epub 2019 Oct 11.

Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina.

Objectives: Prior studies have indicated that olfactory cleft (OC) opacification correlates with olfaction in patients with chronic rhinosinusitis (CRS). However, the results have been unclear in patients without polyps. The purpose of this study was to further explore the relationship between OC opacification, sinus opacification, and olfactory function in patients with CRS.

Methods: One hundred and forty-eight patients with CRS were prospectively enrolled across five institutions. Olfactory function was evaluated using the Sniffin' Sticks tests (Burghardt, Wedel, Germany) and the 17-item Questionnaire of Olfactory Disorders (QOD-NS). Computed tomography (CT) scans for each patient were acquired and Lund-Mackay scores recorded. Opacification of the OC was determined using OsiriX MD (Pixmeo, Bernex, Switzerland) and correlated with olfaction scores.

Results: A total of 148 CRS patients, 73 CRS without nasal polyps (CRSsNP) and 75 CRS with nasal polyps (CRSwNP), as well as 30 control subjects were enrolled. Overall OC opacification averaged 63.7% in CRS patients and 47.1% in control subjects (P < 0.001). In the overall cohort, OC opacification significantly correlated with threshold, discrimination, and identification (TDI) (r = -0.520; P < 0.001) and QOD-NS scores (r = 0.374; P < 0.001). CRSwNP patients demonstrated a significant correlation between OC opacification and TDI scores (r = -0.464; P < 0.001) but not the CRSsNP group (r = -0.143; P = 0.229). Lund-Mackay score correlated with TDI in both the CRSsNP (r = -0.300; P = 0.010) and CRSwNP (r = -0.271; P = 0.019) groups.

Conclusion: CT opacification is associated with olfactory dysfunction differentially based on nasal polyp status. Smell loss in CRSwNP correlated with both OC opacification and Lund-Mackay score, whereas CRSsNP correlated only with Lund-Mackay score, indicating different relationships between olfactory function and local inflammatory processes in these disorders.

Level Of Evidence: 2 Laryngoscope, 130:2311-2318, 2020.
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http://dx.doi.org/10.1002/lary.28332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484975PMC
October 2020

A Subset of Olfactory Sensory Neurons Express Forkhead Box J1-Driven eGFP.

Chem Senses 2019 10;44(9):663-671

Department of Otolaryngology, University of Colorado School of Medicine, MS, Aurora, CO, USA.

Forkhead box protein J1 (FOXJ1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. In a transgenic mouse where an enhanced green fluorescent protein (eGFP) transgene is driven by the human FOXJ1 promoter, robust eGFP expression is observed not only in the multiciliated cells of the respiratory epithelium but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons expresses eGFP and is distributed throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP-labeled axons terminate in many glomeruli in both anterior and posterior portions of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons, although neither receptor cell population possess motile cilia.
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http://dx.doi.org/10.1093/chemse/bjz060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821233PMC
October 2019

Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium.

Chem Senses 2019 09;44(7):511-521

Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, USA.

Mucins are a key component of the surface mucus overlying airway epithelium. Given the different functions of the olfactory and respiratory epithelia, we hypothesized that mucins would be differentially expressed between these 2 areas. Secondarily, we evaluated for potential changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed to evaluate expression of mucins 1, 2, 5AC, and 5B in nasal respiratory and olfactory epithelia of control mice and 1 week after exposure to 8 Gy of radiation. Mucins 1, 5AC, and 5B exhibited differential expression patterns between olfactory and respiratory epithelium (RE) while mucin 2 showed no difference. In the olfactory epithelium (OE), mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in RE it was intermittently expressed by surface goblet cells. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the OE. Mucin 5B was expressed by submucosal glands in OE and by surface epithelial cells in RE. At 1-week after exposure to single-dose 8 Gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine OE and RE express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 Gy) does not appear to affect mucin expression at 1 week.

Level Of Evidence: N/A (Basic Science Research).IACUC-approved study [Protocol 200065].
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http://dx.doi.org/10.1093/chemse/bjz046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357245PMC
September 2019

Socioeconomic status impacts postoperative productivity loss and health utility changes in refractory chronic rhinosinusitis.

Int Forum Allergy Rhinol 2019 09 27;9(9):1000-1009. Epub 2019 Jun 27.

Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, OR.

Background: Social determinants of health can have a substantial impact on treatment outcomes. Prior study has shown that socioeconomic status influences the likelihood of improvement in quality-of-life (QOL) following endoscopic sinus surgery (ESS). However, the impact of socioeconomic factors on changes in productivity loss and health utility after ESS remains unknown.

Methods: Adult patients (≥18 years of age) with chronic rhinosinusitis (CRS) who underwent ESS were prospectively enrolled into a multi-institutional cohort study. Productivity losses were calculated using the human capital approach and monetized using U.S. government-estimated wage rates. Health utility values (HUVs) were derived from the Medical Outcomes Study Short-Form-12 survey using University of Sheffield algorithms. Independent socioeconomic factors of interest included: age, gender, ethnicity, insurance status, educational attainment, and household income categorized via the Thompson-Hickey model.

Results: A total of 229 patients met inclusion criteria, and 163 (71%) provided postoperative follow-up. All subjects reported significant, within-subject improvement in both mean monetized productivity loss (p < 0.001) and HUV postoperatively (p < 0.001). Using paired sample statistics, patients with lowest income (≤$25,000/year) and with Medicare insurance did not report significant improvement in productivity loss (p ≥ 0.112) or HUV (p ≥ 0.081), although sample size limitations may have contributed to this finding. Patients in higher income tiers ($25,001 to $100,000/year and $100,001+/year) and those with employer-provided/private health insurance reported significant postoperative improvements in productivity loss and HUV (all p ≤ 0.003).

Conclusion: Socioeconomic factors, including income and insurance provision, may impact improvements in productivity loss and HUV following ESS. Further research to validate these findings, ascertain mechanisms behind these results, and improve these outcomes is warranted.
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http://dx.doi.org/10.1002/alr.22374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718304PMC
September 2019

Expression of Bitter Taste Receptors and Solitary Chemosensory Cell Markers in the Human Sinonasal Cavity.

Chem Senses 2019 09;44(7):483-495

Department of Otolaryngology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Some bitter taste receptors (TAS2R gene products) are expressed in the human sinonasal cavity and may function to detect airborne irritants. The expression of all 25 human bitter taste receptors and their location within the upper airway is not yet clear. The aim of this study is to characterize the presence and distribution of TAS2R transcripts and solitary chemosensory cells (SCCs) in different locations of the human sinonasal cavity. Biopsies were obtained from human subjects at up to 4 different sinonasal anatomic sites. PCR, microarray, and qRT-PCR were used to examine gene transcript expression. The 25 human bitter taste receptors as well as the sweet/umami receptor subunit, TAS1R3, and canonical taste signaling effectors are expressed in sinonasal tissue. All 25 human bitter taste receptors are expressed in the human upper airway, and expression of these gene products was higher in the ethmoid sinus than nasal cavity locations. Fluorescent in situ hybridization demonstrates that epithelial TRPM5 and TAS2R38 are expressed in a rare cell population compared with multiciliated cells, and at times, consistent with SCC morphology. Secondary analysis of published human sinus single-cell RNAseq data did not uncover TAS2R or canonical taste transduction transcripts in multiciliated cells. These findings indicate that the sinus has higher expression of SCC markers than the nasal cavity in chronic rhinosinusitis patients, comprising a rare cell type. Biopsies obtained from the ethmoid sinus may serve as the best location for study of human upper airway taste receptors and SCCs.
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http://dx.doi.org/10.1093/chemse/bjz042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357247PMC
September 2019