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Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

ABSTRACT: BACKGROUND:Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS. METHODS:Mucosal explants from patients with and without CRS were submerged in Ringer's solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of Z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plug-in of ImageJ. RESULTS:Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53 ± 0.67 vs controls, 4.86 ± 1.68 pixels/second; p < 0.001). CONCLUSION:This study is the first to report evidence of abnormal mucus strand velocity from submucosal glands in diseased sinonasal mucosa. Future pharmacologic studies targeting this critical component of MCC are warranted.

SUBMITTER: Tipirneni KE

PROVIDER: S-EPMC6520985 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

Tipirneni Kiranya E KE Zhang Shaoyan S Cho Do-Yeon DY Grayson Jessica J Skinner Daniel F DF Mackey Calvin C Moore Lindsay L Cole Denzel D Banks Catherine G CG Woodworth Bradford A BA

International forum of allergy & rhinology 20180110 4

<h4>Background</h4>Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected ...[more]

PMID: 29319936

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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-? (TNF-?), 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

Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

Publications

Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

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