Abstract

Chronic rhinosinusitis (CRS) is one of the most common causes of inflammation of the olfactory system, warranting investigation of the link between chronic inflammation and the loss of olfactory function. Type 2 inflammation is closely related to the clinical features and disease mechanisms of olfactory dysfunction secondary to CRS. Patients with eosinophilic CRS, aspirin-exacerbated respiratory disease, and central compartment atopic disease report increased olfactory dysfunction. Increased levels of interleukin-(IL-)2, IL-5, IL-6, IL-10, and IL-13 in the mucus from the olfactory slit have been reported to be associated with reduced olfactory test scores. The influence of several cytokines and signaling transduction pathways, including tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinases, on olfactory signal processing and neurogenesis has been demonstrated. Corticosteroids are the mainstay treatment for olfactory dysfunction secondary to CRS. Successful olfaction recovery was recently demonstrated in clinical trials of biotherapeutics, including omalizumab and dupilumab, although the treatment effect may diminish gradually after stopping the use of the medications. Future studies are required to relate the complex mechanisms underlying chronic inflammation in CRS to dysfunction of the olfactory system.

Highlights

  • Olfactory dysfunction is one of the cardinal symptoms of chronic rhinosinusitis (CRS) [1–3]

  • Olfactory dysfunction has been regarded as the consequence of obstructed air flow to the olfactory slit but increasing evidence has shown that inflammation in the olfactory neuroepithelium leads to dysfunction of the transduction of olfactory signals

  • We present the clinical features related to olfactory dysfunction, investigate the influence of inflammation on neurogenesis and olfactory processing, and analyze the medical management of olfactory dysfunction secondary to chronic rhinosinusitis

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Summary

INTRODUCTION

Olfactory dysfunction is one of the cardinal symptoms of chronic rhinosinusitis (CRS) [1–3]. This spatial location makes the olfactory neuroepithelium susceptible to various inhaled substances, including viruses, molds, allergens, pollutants, and toxic materials These epithelial stimulants may lead to recruitment of inflammatory cells, increased proinflammatory factors, and changes in ciliary function and secretion from goblet cells. The risk factors for olfactory dysfunction differed between CRS endotypes, and CRS patients with type 2 inflammation endotype reported loss or reduction of olfaction more frequently than those with non-type 2 CRS [19]. In non-eosinophilic CRS, only ethmoid opacification and olfactory cleft polyps were identified as independent risk factors for olfactory dysfunction. Inflammation of the epithelium can affect olfactory neurogenesis, differentiation, and maturation of OSNs. Researchers have worked on identifying types of cytokines or biomarkers in the olfactory neuroepithelium, and increased levels of several cytokines in the olfactory cleft have been correlated with olfactory dysfunction in CRS patients. The same research group applied a hierarchal cluster analysis and machine learning algorithms to data from

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