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Background: There is no known predictor for olfactory function recovery with dupilumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP). This study assessed whether patient-reported recovery of olfactory function on oral corticosteroids (OCS) is a prognostic factor., Methods: Retrospective analysis of pre-biological OCS-responsiveness on olfactory functioning (OCS-responsive or OCS-unresponsive; OCS-r and OCR-u, respectively) as predictor for olfactory functioning after 6 months of dupilumab therapy for severe CRSwNP., Results: 212 CRSwNP patients treated with dupilumab were divided between OCS-r (reported improvement of olfactory function with OCS before dupilumab treatment, n = 152), and OCS-u (OCS-unresponsive; no such improvement, n = 60). Olfactory function was tested with Sniffin's Sticks Identification Test (12 pens; SSIT-12). At baseline, both groups had a median SSIT-12 score of 3 / 12 indicating anosmia. Hyposmia and normosmia rates were also comparable (5.9% and 3.3% in OCS-r, respectively; 5.0% and 1.7% in OCS-u, respectively). After 6 months of dupilumab treatment, OCS-r showed higher olfactory scores (median SSIT-12: 8/12; 52.6% hyposmia and 17.8% normosmia) than OCS-u (median SSIT-12: 5/12; 31.7% hyposmia and 3.3% normosmia). The positive predictive value of OCS-responsiveness on scoring <7 (normosmia/hyposmia) on the SSIT-12 after 6 months of dupilumab treatment was 70.4%. Conversely, the negative predictive value of OCS-unresponsiveness on scoring <7 (anosmia) on the SSIT-12 after 6 months of dupilumab treatment was 65.0%., Conclusion: Patients who report olfactory function improvement on OCS have a higher chance of recovery of olfactory function during the first six months of treatment with dupilumab than patients who do not.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently leads to olfactory dysfunction. This study aimed to assess the impact of dupilumab on CRSwNP patients, focusing on olfactory outcomes and potential correlations with other clinical factors., Methods: CRSwNP patients eligible for dupilumab therapy received subcutaneous Dupixent® injections every two weeks (300mg/2ml dupilumab). The 12-item Sniffin' Sticks Test (SST-12), fractional exhaled nitric oxide (FeNO) and Nasal Polyp Score (NPS) were assessed at baseline and after one, three, and six months. Patients also completed the Sino-Nasal Outcome Test (SNOT-22) weekly., Results: 26 CRSwNP patients were included. After one month, dupilumab led to substantial reductions in FeNO, SNOT scores, andNPS, whereas SST-12 scores improved significantly only after three months. A shift toward normosmia occurred, with 81% achieving normosmia after six months, and a drop in anosmia prevalence to 9.5%. Significant negative correlations between olfaction (SST-12) and polyp severity (NPS) at baseline and after six months were found, while no significant correlations were observed between SST-12 and FeNO or SNOT scores. Age did not correlate with olfaction., Conclusions: Dupilumab demonstrated efficacy in restoring olfaction in CRSwNP patients. Reaching normosmia in over 80% ofpatients after six months of treatment underscores the drug's effectiveness in managing this challenging symptom.

Background: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP)., Methodology: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed., Results: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo., Conclusions: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Background: Olfactory dysfunction is a typical post-COVID-19 presentation, affecting patients' quality of life. There are currently multiple treatment options in this group of patients such as oral and intranasal corticosteroids, olfactory training, oral vitamin-mineral supplementation, amongst others. This meta-analysis aims to consolidate existing evidence for current therapies in patients with persistent olfactory dysfunction related to COVID-19 infection and evaluate the possible role of corticosteroid add-on therapy in olfactory training., Methodology: A systematic review and meta-analysis to study current treatments/interventions for olfactory dysfunction in post-COVID-19 infection were conducted. Data were pooled for the meta-analysis. The outcomes include subjective or objective olfactory assessment major and minor adverse reactions., Results: Eleven studies (1414 participants) were included in this review, with six studies (916 participants) then assessed for the meta-analysis. Combined treatment of intranasal corticosteroid (INCS) with olfactory training (OT) has no benefit over OT monotherapy from both a VAS score improvement and identification component of Sniffin' Sticks test standpoint. In addition, there were no differences in improvement of TDI score between combined oral corticosteroid (OCS) with OT therapy compared to OT alone. Olfactory function was, however, significantly improved after OT., Conclusion: There were no significant differences in the improvement of olfactory scores in combination INCS+OT or OCS+OT therapies compared to OT monotherapy. However, there is improvement in olfactory function after OT.

Background: The growing number of COVID-19 patients with long-lasting olfactory disorders makes it necessary to identify ef- fective treatments that enhance the spontaneous recovery of olfactory function., Methods: Multicentre randomised case-control study that involved 18 patients with COVID-19 related anosmia or severe hyposmia for more than 30 days. Nine patients were prescribed systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days. The other 9, untreated, patients were used as controls. The olfactory function was evaluated with CCCRC test at 20 and 40 days from the first evaluation., Results: In the control group, a median olfactory score of 20 (IQR 30) was detected at baseline. At the 20-day control there was no significant improvement in olfactory function. The improvement in olfactory performance became significant at the 40-day follow-up compared to baseline scores [60 (IQR 60) versus 20 (IQR 30)]. In the treatment group, patients had a mean olfactory score of 10 (IQR 15) at initial control. At the 20-day control, a significant im-provement in the olfactory scores, compared to the baseline, was detected [70 (IQR 40) versus 10 (IQR 15)]. Olfactory function further improved at 40 days [median score 90 (IQR 50)]. Patients in the treatment group reported significantly higher improvements of the olfactory scores than the controls at both the 20-day [40 (IQR 45) versus 10 (IQR 15)] and 40-day [60 (IQR 40) versus 30 (IQR 25)] evaluations., Conclusions: Based on the results of this study, the mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity.

Background: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blind trial., Methodology: Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using Sniffin Sticks, before and after treatment. Treatment consisted of one-off sodium citrate solution application to the olfactory cleft. Sodium chloride solution was applied to the contralateral olfactory cleft, which therefore acted as placebo control. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients., Results: 57 patients participated, aged 22-79. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup., Conclusions: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia.

Background: The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients., Methodology: Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration., Results: When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index., Conclusion: Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

Background and Aim: Olfactory dysfunction is a common complaint in a large number of people. As the aetiologies of olfactory dysfunction vary greatly so do the treatment approaches. The aim of this retrospective study was to evaluate treatment with systemic corticosteroids, particularly focusing on its effectiveness on the different olfactory dysfunction aetiologies. Although a prospective randomized control trail is preferred for such an investigation, using the current approach, we were able to test a very large patient population., Material and Methods: A total of 425 patients with olfactory dysfunction were treated with systemic corticosteroids for 14 days. Olfactory performance was measured using the `Sniffin` Sticks` battery before and after the treatment., Results: The treatment with systemic corticosteroids significantly increased the performance on the TDI score and on each of the three subtests; threshold, discrimination and identification. In 26.6% of the patients improvement of more than six points of the TDI score was observed. The treatment proved to be more effective in patients with sinunasal olfactory dysfunction, where this percentage increased to 36.7, compared to other aetiologies. In addition, the increase in olfactory function was negatively correlated with the TDI score before the treatment., Conclusion: This study confirms the effectiveness of systemic corticosteroids on olfactory dysfunction in a large patient population. Specifically, the results show that treatment is: (a) more effective in patients with sinunasal than in patients with idiopathic olfactory dysfunction, (b) most effective in patients with sinunasal disease with nasal polyps, and (c), at best, effective in half of the patients. The current study may provide help in counselling patients.

Olfactory dysfunction is a common symptom in patients with inflammation of the nasal mucosa. Among numerous drugs, so far only the use of steroids has been shown to have a positive effect on olfactory function. Therefore the aim of the present study was to investigate whether patients with sinonasal disease would benefit in terms of olfactory function from oral treatment with a herbal drug (combination of primrose, gentian root, vervain, elder flowers, and sorrel: Sinupret(r)) which is commonly used in sinusitis. Olfactory function was tested using a standardised olfactory test kit (`sniffin` sticks`). The drug was applied in a double-blind fashion: after an initial therapy of 7 days of oral prednisolone for all participants with a sinonasal olfactory disease, participants were divided into a placebo- and a verum-group; tests were performed before and after treatment over a 2 months period. Statistical analysis did not reveal any major differences in olfactory function in relation to treatment. Considering that its benefit for the inflammatory component of sinusitis has been shown, the herbal drug may exhibit positive effects on olfactory function in a different setting, e.g., when applied without preceding administration of prednisolone, or when used in patients with certain degrees of rhinosinusitis.

Systemic administration of corticosteroids was attempted in the treatment of olfactory loss resistant to topical corticosteroid treatment in patients with nasal and paranasal disease and post-upper respiratory infection. Significant efficacy was achieved with a short course of high-dose oral corticosteroids in patients with non-allergic sinus disease. On the other hand, anosmia induced by upper respiratory infection failed to respond to systemic corticosteroid treatment, suggesting permanent damage to the olfactory receptor cell. The underlying mechanism of effectiveness observed in patients with sinus disease may be explained by improvement of the mucosal thickening of the olfactory fissure, leading to the access of an odorant to the olfactory neuroepithelium.