Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study

Abstract Objectives Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbina...

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Main Authors: Jorge A. Gutierrez III, Jeremy L. Barth, Rodney J. Schlosser, Thomas S. Edwards, Timothy L. Smith, Zachary M. Soler
Format: Article
Language:English
Published: Wiley 2024-03-01
Series:World Journal of Otorhinolaryngology-Head and Neck Surgery
Subjects:
Online Access:https://doi.org/10.1002/wjo2.123
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author Jorge A. Gutierrez III
Jeremy L. Barth
Rodney J. Schlosser
Thomas S. Edwards
Timothy L. Smith
Zachary M. Soler
author_facet Jorge A. Gutierrez III
Jeremy L. Barth
Rodney J. Schlosser
Thomas S. Edwards
Timothy L. Smith
Zachary M. Soler
author_sort Jorge A. Gutierrez III
collection DOAJ
description Abstract Objectives Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL‐4 and IL‐13 signaling, IL‐10 signaling, and rhodopsin‐like receptors. Conclusions RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL‐10, rhodopsin‐like receptors, and IER3 in the pathogenesis of olfactory dysfunction.
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spelling doaj.art-b6d499f080314ba4b21890bc78cb78fe2024-03-29T05:19:24ZengWileyWorld Journal of Otorhinolaryngology-Head and Neck Surgery2095-88112589-10812024-03-01101293610.1002/wjo2.123Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot studyJorge A. Gutierrez III0Jeremy L. Barth1Rodney J. Schlosser2Thomas S. Edwards3Timothy L. Smith4Zachary M. Soler5Department of Otolaryngology–Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USADepartment of Regenerative Medicine & Cell Biology Medical University of South Carolina Charleston South Carolina USADepartment of Otolaryngology–Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USADepartment of Otolaryngology–Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USADepartment of Otolaryngology–Head and Neck Surgery Oregon Health & Science University Portland Oregon USADepartment of Otolaryngology–Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USAAbstract Objectives Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL‐4 and IL‐13 signaling, IL‐10 signaling, and rhodopsin‐like receptors. Conclusions RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL‐10, rhodopsin‐like receptors, and IER3 in the pathogenesis of olfactory dysfunction.https://doi.org/10.1002/wjo2.123chronic rhinosinusitis without nasal polypsolfactory dysfunctionRNA sequencing
spellingShingle Jorge A. Gutierrez III
Jeremy L. Barth
Rodney J. Schlosser
Thomas S. Edwards
Timothy L. Smith
Zachary M. Soler
Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
World Journal of Otorhinolaryngology-Head and Neck Surgery
chronic rhinosinusitis without nasal polyps
olfactory dysfunction
RNA sequencing
title Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
title_full Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
title_fullStr Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
title_full_unstemmed Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
title_short Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study
title_sort utilization of rna sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps a pilot study
topic chronic rhinosinusitis without nasal polyps
olfactory dysfunction
RNA sequencing
url https://doi.org/10.1002/wjo2.123
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