Effects of Corticosteroid Treatment on Olfactory Dysfunction in LATY136F Knock-In Mice.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients. METHODS: LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons. RESULTS: Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group. CONCLUSION: Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.

Subjective and objective effects of radioiodine therapy on the sense of smell.

PURPOSE: Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests. METHOD: In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT. RESULTS: Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up. CONCLUSION: A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction.

Incidence and influencing factors of olfactory dysfunction in patients 1 week after endoscopic transsphenoidal resection of pituitary tumor: a cross-sectional study of 158 patients.

Objective: To investigate the current situation of olfactory dysfunction in patients after endoscopic transsphenoidal resection of pituitary tumors, and analyze its influencing factors, to provide references for clinical nursing and rehabilitation. Methods: A cross-sectional study design and convenience sampling method were used to investigate 158 patients with pituitary tumors treated by endoscopic transsphenoidal pituitary tumor resection in the Department of Neurosurgery of three Grade-A general hospitals in Sichuan Province from January 2022 and June 2023. The olfactory function of patients was evaluated 1 week after surgery, and the general clinical data and olfactory related data of patients were collected, and the influencing factors of olfactory disorder were analyzed by logistic regression. Results: The incidence of olfactory dysfunction was 73.42%. analysis revealed that the formation of blood scabs, nasal cavity adhesion, cerebrospinal fluid leakage and operation time were independent risk factors for olfactory dysfunction in patients after transsphenoidal pituitary tumor resection (p < 0.05). Conclusion: The incidence of olfactory dysfunction is high in patients after endoscopic transsphenoidal resection of pituitary tumors, suggesting that medical staff should pay close attention to and identify patients with olfactory dysfunction based on the guidance of disease knowledge and skills, develop targeted nursing interventions, and promote the improvement of patients' olfactory function and quality of life.

Olfactory perceptual fingerprints of people with olfactory dysfunction and healthy controls.

Objectives: An olfactory perceptual fingerprint (OPF) defines one's olfactory perception using perceptual descriptor ratings (such as odor pleasantness, intensity) for a set of odors. OPFs have been shown to distinguish patients with COVID-related olfactory dysfunction (OD) and healthy controls with 86% accuracy. However, all participants rated the same odorants. With the aim to evaluate whether the OPFs are indeed odorant independent, previously published dataset by Lötsch et al. was reanalyzed. Furthermore, this independent dataset was used to check whether the OPFs separate patients with OD due to various causes from controls. Methods: The study included 104 controls and 42 patients, who were randomized into four odor sets with 10 odorants each. Odorants were presented using a computer-controlled olfactometer and evaluated on scales from 1 (not at all) to 5 (very) using perceptual descriptors pleasant, intensive, familiar, edible, irritating, cold/warm, and painful. Results: Permutational multivariate analysis of variance showed that the odor set did not have a significant effect on the OPFs, confirming that the OPFs are indeed odorant independent. On the other hand, both diagnosis and age affected the OPFs (p < .001) and explained around 11% and 5% of the variance of the OPFs, respectively. Furthermore, a supervised machine learning method, random forest classifier, showed that OPF can distinguish patients and controls with 80% accuracy. Conclusion: OPFs are odorant independent. Patients perceived odors as less familiar, less intense, and less edible than controls. Other perceptual descriptors were much less important for the separation of patients and controls. Level of evidence: 3.

The Association of Odor Identification with Nutritional Status and Systemic Inflammation in Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Anorexia is common in patients with chronic kidney disease (CKD) and could lead to protein energy wasting (PEW). An altered sense of smell, a reflection of olfactory dysfunction, is a potential mechanism that exacerbates the impact of anorexia on PEW. In this study, we examined the extent of the altered sense of smell and its association with PEW in patients with moderate to advanced CKD. METHODS: We studied 139 individuals (34 healthy subjects - controls, 50 patients with stage 3-4 CKD, 55 patients on maintenance hemodialysis - MHD) using the odor identification test (Sniffin' Sticks odor screening test containing 12 different smells). The odor identification test was scored as either correct or incorrect, and each participant's total odor score was calculated. Malnutrition Inflammation Score (MIS) was used to assess PEW. RESULTS: Patients with CKD had higher C-reactive protein (CRP) and lower serum albumin concentrations compared to healthy individuals. Total odor scores were different between groups, with controls having the highest scores and MHD patients having the lowest scores. A similar difference was observed in MIS, MHD patients displaying the worst nutritional score (p ≤ 0.001). The number of participants with severe olfactory dysfunction (≤ 6 correct answers) was significantly higher in the CKD and MHD groups compared to the controls (p ≤ 0.01). There was an inverse trend between the total odor score and the MIS score for the study population. However, this relationship was not statistically significant (r = -0.124, p = 0.21). CONCLUSION: This cross-sectional study suggests that olfactory dysfunction, as assessed by the odor identification test, is altered in patients with advanced CKD, most notably in ones on MHD. Although the diminished sense of smell was observed alongside development of PEW, we explicitly noted that there is no statistically significant correlation.

Impaired olfactory system in metabolic imbalance-related neuropathology.

Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb's connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.

Neurological soft signs and olfactory dysfunction in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a serious disorder with a lifetime prevalence of 2.7-5.9% and is thought to correlate with altered neuroplasticity. The aim of the present study is to investigate possible associations of BPD (-severity) and alterations in neurological soft signs (NSS) and olfactory function. METHODS: For the monocentric observational study, 39 female subjects with a BPD diagnosis and 19 female healthy control subjects were recruited. The groups were matched by age. Olfactory functions were examined using Sniffin' Sticks. NSS were assessed by a standardized test with 50 items. RESULTS: BPD subjects have higher NSS scores in group comparison. By contrast, there are no alterations in the total score of olfactory function, while the BPD subjects scored higher in smell identification. Within the BPD group, the total NSS score was discovered to have a negative correlation with olfactory function. BPD subjects taking antipsychotics show more NSS than those without. We found no significant influence of posttraumatic stress disorder on the NSS or olfactory function. The BPD-severity correlates with NSS. LIMITATIONS: Due to the cross-sectional design, we did not have a follow up examination. The sample size was small, and all patients had psychiatric comorbidities. Additionally, we did not perform MRI to connect our findings with possible structural abnormalities. CONCLUSIONS: Our study confirmed altered NSS in BPD patients, whereas no impairment in the olfactory function was found. Further research is required to establish NSS and smell tests as clinical screening tools in BPD patients and to uncover the disorder's impact on neuroplasticity.

Neurological Complications of COVID-19 Infection: A Comprehensive Review.

The COVID-19 pandemic is well on its way to reaching endemic status across the globe. While the medical community's understanding of the respiratory complications induced by COVID-19 is improving, there is still much to be learned about the neurological manifestations associated with COVID-19 infection. This review aimed to compile relevant, available evidence of COVID-19-induced neurological complications and to provide information for each complication regarding symptomology, progression patterns, demographic risk factors, treatment, and causative mechanism of action when available. Data for this review was collected using a confined search on PubMed using the keywords ["COVID-19" OR "SARS-CoV-2"] AND ["neurological complications" OR "olfactory symptoms" OR "gustatory symptoms" OR "myalgia" OR "headache" OR "dizziness" OR "stroke" OR "seizures" OR "meningoencephalitis" OR "cerebellar ataxia" OR "acute myelitis" OR "Guillain Barré Syndrome" OR "Miller Fisher Syndrome" OR "Posterior Reversible Encephalopathy Syndrome"] between 2019 and 2023. A wide range of neurological manifestations impact a significant percentage of COVID-19 patients, and a deeper understanding of these manifestations is necessary to ensure adequate management. The most common neurological complications identified consist of olfactory and gustatory dysfunctions, myalgia, headache, and dizziness, while the most severe complications include stroke, seizures, meningoencephalitis, Guillain-Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome. While this review effectively provides a roadmap of the neurological risks posed to COVID-19 patients, further research is needed to clarify the precise incidence of these complications and to elucidate the mechanisms responsible for their manifestation.

Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19.

PURPOSE: Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. METHODS: The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the "Sniffin' Sticks" test, measuring threshold, discrimination and identification scores before and after treatment. RESULTS: Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. CONCLUSION: This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. TRIAL REGISTRATION: DFM-IRB00012367-23-10-001.

A novel olfactory sorting task.

BACKGROUND: This study aimed to develop a simple self-administered screening tool for odor memory, which allowed users to self-test their olfactory function repeatedly even at home. METHODS: One hundred and ten participants were recruited (30 men, age = 50.1 ± 9.9 years; 80 women, age = 47.1 ± 11.5 years); half of them were heathy volunteers, the other half were patients with olfactory dysfunction. Fifty-one healthy participants volunteered for a retest within an interval of a maximum of 14 days. Olfactory function was assessed using the extended Sniffin' Sticks test (SST) comprising tests for odor threshold, identification, and discrimination. All participants received the Novel Olfactory Sorting Task (NOST) which is based on the sorting of 12 matching pairs of odors involving olfactory and cognitive functions. After that, all participants rated questions related to their test performance and the practicability of the test. RESULTS: Consistent with the previous literature, significant effects of age were found. Results showed an acceptable test-retest reliability and a satisfactory validity of the NOST. The NOST score not only had positive correlations with SST, but also was capable of differentiating severe hyposmia/anosmia from normosmia by the score of 5.5 (sensitivity of 76.2%, specificity of 77.6%). CONCLUSION: The present study showed the good reliability, validity, and possible clinical usefulness of the NOST. As a self-performed screening test, it can be comprehended and conducted easily, which may provide a quick and simple approach to obtaining a global estimation of olfactory and cognitive functions.

Effect of Olfactory Rehabilitation on the Recovery of Post-Coronavirus Disease Olfactory Dysfunction: A Randomized Controlled Trial.

Introduction Persistent olfactory dysfunction was seen in many patients upon coronavirus disease 2019 (COVID-19) infection recovery. However, research on its management was very limited, especially among the Southeast Asian population. Objectives We aim to investigate the role of olfactory rehabilitation and topical corticosteroids among post-COVID-19 olfactory dysfunction patients in Malaysia, and at the same time to determine factors leading to olfactory recovery post-COVID-19 infection. Methods Adult Malaysians with persistent olfactory dysfunction one month post-COVID-19 recovery were recruited. Thirty-one patients were randomly assigned into three groups with 10 patients being given olfactory training (Group 1), another 10 being given mometasone furoate nasal spray/olfactory training (Group 2), and 11 patients being assigned to the control group (Group 3). All groups were followed up for an average duration of six months. Olfactory function was evaluated by Top International Biotech Smell Identification Test (TIBSIT) scores and Olfactory Disorder Questionnaire (eODQ) prior to randomization, at three and six months after recruitment. Results The baseline characteristics of patients were similar in all groups. Generally, patients of all three groups showed a statistically significant improvement in the TIBSIT scores after six months. The TIBSIT scores for Group 2 were statistically significantly higher than the control at three months but not at six months. As for Group 1, no statistically significant differences in TIBSIT scores at both three and six months were noted when compared to control. Statistically significant improvements were seen in the eODQ scores in all three groups. Conclusion No superiority of intervention for post-COVID-19 olfactory dysfunction was seen compared to control.

A new surgical technique to increase airflow in the olfactory cleft: superior turbinate lateralization procedure.

BACKGROUND: The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established. METHODS: We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function. RESULTS: ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3 months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group. CONCLUSION: The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.

Comparative imaging study of patients with persistent olfactory dysfunction due to mild COVID-19 using structural and functional MRI.

INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging. MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function. RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively. CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.

Maximizing Participation in Olfactory Training in a Sample with Post-COVID-19 Olfactory Loss.

PURPOSE: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients. METHODS: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals' perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11). RESULTS: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations. CONCLUSIONS: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies.

Association of prior military service with olfactory function among older adults.

Objective: Olfactory dysfunction (OD) is a condition primarily affecting older adults. Several factors have been implicated in OD, such as age, socioeconomic status, and neurodegenerative disease; however, the effect of military service still requires additional investigation. Here, we aim to determine if there is an association between prior military service and OD among older adults. Methods: This cross-sectional study included 2268 adults from Round 1 of the National Social Life, Health, and Aging Project. OD was defined as 0-3 odors correctly identified on the 5-item Sniffin' Sticks test. Bivariate analysis was conducted to calculate crude odds ratios (cOR) for the association of prior military service with OD and identify covariates for regression. Associations between prior military service and OD were assessed using logistic regression, and adjusted odds ratios (aOR) were calculated controlling for age, gender, race/ethnicity, education, stroke history, dementia, diabetes, and mental health. All analyses were weighted using survey weights to account for sampling design. Results: OD was present in 489 adults (21.6%). Among those with OD, the average age was 71.0 ± 7.9 years, whereas the average age in those without OD was 67.0 ± 7.2 years. Among adults with OD, 34.4% reported prior military service, compared to 27.7% of adults without OD (cOR = 1.37; 95% CI: 1.05-1.79). However, after adjusting for covariates, prior military service was not associated with OD (aOR: 1.09; 95% CI: 0.79-1.50). Older age (aOR: 1.07; 95% CI: 1.05-1.09) and worse mental health (aOR: 1.68; 95% CI: 1.14-2.49) were associated with OD. Conclusion: Prior military service was not associated with OD among older adults after controlling for covariates. More nuanced research is needed to examine correlations between OD and specific elements of military service such as duration, toxin exposure, and head trauma.Level of Evidence: Level 4.

Paper based analytical devices for ions determination in nasal secretions demonstrating association with olfactory function.

Nasal ions environment plays a crucial role in maintaining nasal physiology and supports olfactory transmission. Addressing the limited research on nasal ion levels and their association with olfactory function, paper-based sensors were developed for determination of sodium, potassium, calcium and chloride in the nasal mucus of healthy volunteers and patients with olfactory dysfunction. Multi-walled carbon nanotubes and carbon quantum dots from beetroot were incorporated into paper substrate where sensors were designed with ion association complexes for sodium, potassium, calcium and chloride enhancing the recognition sensing capabilities. The sensors composition was optimized, including ion-exchange materials and plasticizers, to enhance sensitivity and selectivity. The performance of the sensors is evaluated based on Nernstian slope, dynamic range, detection limit and response time. Selectivity of the sensors was tested and the results demonstrated high selectivity for the target ions. The sensors were successfully determined sodium, potassium, calcium and chloride levels in nasal mucus of healthy volunteers and patients with olfactory dysfunction. The results revealed elevated calcium levels in patients with olfactory dysfunction, highlighting associated diagnostic implications. This suggests that the proposed sensors could serve as a diagnostic tool for olfactory evaluation, particularly in resource-constrained settings where access to advanced diagnostic tools is limited.

Clinical studies in COVID-related olfactory disorders: Review of an institutional experience.

Objective: To share a single institutional experience with clinical research on COVID-related olfactory dysfunction (OD). Data Source/Method: Narrative review of published original data and ongoing clinical trials on COVID-related OD at Washington University from 2020 to 2023. Results: There were three new diagnostic-/patient-reported outcome measures developed and tested. We report five clinical trials of interventions for COVID-related olfactory disorders: combined Visual-Olfactory Training (VOLT) with patient-preferred scents versus standard olfactory training (VOLT trial), oral gabapentin versus placebo (Gabapentin for the Relief of Acquired Chemosensory Experience trial), nasal theophylline irrigations versus placebo (Smell Changes and Efficacy of Nasal Theophylline trial), stellate ganglion block (single-arm), and mindfulness-based stress reduction (MBSR) versus lifestyle intervention (MBSR trial). Conclusions: Initial intervention trials for COVID-related OD have shown potential for improving subjective and objective olfactory outcomes. However, there remains no gold standard treatment that definitively outperforms placebo in controlled trials. Therefore, continued investigation of novel therapeutic strategies for COVID-related OD is necessary to maximize olfactory outcomes for affected patients.

The current possibilities of diagnosing and therapies for olfactory disorders.

INTRODUCTION: Olfactory disorders significantly affect individuals, diminishing their capacity to detect dangers, appreciate flavors, and engage socially. Despite their considerable impact on quality of life, these disorders often receive less attention compared to other sensory impairments. This review emphasizes the importance of olfactory function and explores both traditional and innovative diagnostic and therapeutic approaches. AREAS COVERED: This review comprehensively covers the pathophysiology, diagnostic challenges, and treatment options for olfactory disorders. It delves into the nuances of different disorders, such as anosmia and parosmia, and discusses the array of diagnostic tools from traditional sniff tests to advanced imaging techniques. The review also evaluates therapeutic strategies, from pharmacological treatments to emerging therapies like electrical stimulation and regenerative medicine, highlighting recent advances in the field. EXPERT OPINION: Current insights suggest a growing recognition of the significance of olfactory disorders, driven by recent pandemics and advances in diagnostic and therapeutic technologies. Future perspectives indicate a promising direction toward more personalized medicine approaches and enhanced regenerative therapies. Continuous research and improved clinical awareness are critical for evolving the management strategies of olfactory impairments, potentially leading to better patient outcomes and quality of life enhancements.

Structures and functions of the normal and injured human olfactory epithelium.

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection.