Olfaction Now and in the Future in CRSwNP

Abstract

Background Chronic rhinosinusitis (CRS) is the leading cause of olfactory dysfunction in the general population. Olfactory dysfunction is more common in patients with CRS with nasal polyposis (CRSwNP) compared to those without polyps. Purpose The present review aims to summarize the current literature on the mechanism behind olfactory dysfunction in CRSwNP and the impact of therapy on olfactory outcomes in this patient population. Methods A comprehensive review of the available literature on olfaction in CRSwNP was performed. We evaluated the most recent evidence from studies on the mechanisms behind smell loss in CRSwNP and the impact of medical and surgical therapy for CRS on olfactory outcomes. Results The mechanism behind olfactory dysfunction in CRSwNP is not completely understood, but evidence from clinical research and animal models suggests both an obstructive component causing conductive olfactory loss and an inflammatory response in the olfactory cleft leading to sensorineural olfactory loss. Oral steroids and endoscopic sinus surgery have both shown efficacy in improving olfactory outcomes in CRSwNP in the short term; however, the long-term response of these treatments remains uncertain. Newer targeted biologic therapies, such as dupilumab, have also shown remarkable and durable improvement in smell loss for CRSwNP patients. Conclusion Olfactory dysfunction is highly prevalent in the CRSwNP population. Although significant advances have been made in our understanding of olfactory dysfunction in the setting of CRS, additional studies are needed to elucidate cellular and molecular changes mediated by type 2-mediated inflammation in the olfactory epithelium with potential downstream effects on the central olfactory system. Further identification of these underlying basic mechanisms will be vital for developing future therapies targeted to improve olfactory dysfunction in patients with CRSwNP.

Factors influencing olfactory function in an adult general population sample: the CHRIS study

“…It is interesting to note that we did not observe a reduction of olfactory function in several other conditions that are typically thought to be associated with a reduction of olfactory function. This includes a history of surgery for nasal polyposis ( Qureshi and Lane 2023 ), kidney disease including kidney failure ( Frasnelli et al 2002 ), diabetes ( Faour et al 2022 ), epilepsy ( Khurshid et al 2019 ), and migraine ( Kandemir et al 2022 ). Similarly, self-reported exposure to a variety of relatively common potential toxins such as detergents, exhausts, wood dust, pesticides, and others was also not associated with a reduction of odor identification abilities.…”

Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications

“…The pathophysiology of OD in patients with CRS is not completely understood. While it has been hypothesized that OD results from airflow obstruction often secondary to polyps [ 21 , 22 ], studies have shown residual OD in some individuals even with medical and surgical treatments to reduce or remove polyps [ 22 , 23 ]. It has also been hypothesized that OC inflammation may impair signaling between olfactory receptors and the olfactory cortex [ 21 , 22 ].…”

“…While it has been hypothesized that OD results from airflow obstruction often secondary to polyps [ 21 , 22 ], studies have shown residual OD in some individuals even with medical and surgical treatments to reduce or remove polyps [ 22 , 23 ]. It has also been hypothesized that OC inflammation may impair signaling between olfactory receptors and the olfactory cortex [ 21 , 22 ]. As future studies investigate and provide a better understanding of the pathophysiology of OD in CRS, novel treatments that need to be delivered to the OC to improve olfactory function will likely be developed.…”