Studies on Clinical Features, Mechanisms, and Management of Olfactory Dysfunction Secondary to Chronic Rhinosinusitis

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.

Olfaction Recovery following Dupilumab Is Independent of Nasal Polyp Reduction in CRSwNP

“…However, the role of type 2 inflammation-mediated barrier dysfunction in the olfactory neuroepithelium remains to be determined [ 20 ]. Our speculations are in line with recent literature.…”

“…Our speculations are in line with recent literature. It is conceivable that, at the basis of the OI in CRSwNP and of the olfactory recovery following treatment with Dupilumab, there are immunological mechanisms with the direct or indirect involvement of interleukins (ILs) and in particular IL-4, IL-5, IL-13, and eosinophils [ 20 ].…”

“…Infiltrating immune cells in the olfactory neuroepithelium might account for the dysfunction of the peripheral olfactory system. So, the inflammation of the epithelium could affect olfactory neurogenesis, differentiation, and maturation of OSNs [ 20 ].…”

“…Eosinophilic infiltration may play a significant role in the OI in CRSwNP. In addition, increased levels of several cytokines in the olfactory cleft have been correlated with OI, elevated levels of IL-2, IL-5, IL-6, IL-10, and IL-13 are indeed associated with reduced test scores for smell identification and olfaction is found to be strongly correlated with levels of cytokines IL-5 and IL-13, although the role of the IL-4 and IL-13 pathways and their possible regulatory impacts on neurogenesis and homeostasis of olfactory neurons have not been determined yet [ 20 ].…”

“…However, the administration of adjuvant medical therapy post-operatively may aid the continued recovery of olfactory function [ 20 ].…”