Dataset Information

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

ABSTRACT:

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.

SUBMITTER: Soler ZM

PROVIDER: S-EPMC8670410 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

Soler Zachary M ZM Schlosser Rodney J RJ Mulligan Jennifer K JK Smith Timothy L TL Mace Jess C JC Ramakrishan Vijay R VR Norris-Caneda Kim K Bethard Jennifer R JR Ball Lauren E LE

International forum of allergy & rhinology 20201204 8

<h4>Background</h4>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.<h4>Methods</h4>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 coul ...[more]

PMID: 33275311

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Project description:BackgroundMultiple 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.MethodsThis 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).ResultsCase 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.ConclusionThis 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.

Project description:ObjectivesPrior 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.MethodsOne 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.ResultsA 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.ConclusionCT 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 evidence2 Laryngoscope, 130:2311-2318, 2020.

Project description:BackgroundChronic 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.MethodsAdults 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.ResultsSixty-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).ConclusionSeveral 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.

Dataset Information

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

Background

Methods

Results

Conclusion

Publications

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

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