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Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Objectives: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice., Design: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup., Participants: ENT surgeons who assess olfaction., Results: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents., Conclusions: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems., (© 2023 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Background: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping., Summary: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text., Key Messages: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects., (© 2021 ARS-AAOA, LLC.)

Objective/hypothesis: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease., Study Design: Prospective cohort study., Methods: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities., Results: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction., Conclusions: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function., Level of Evidence: 3 Laryngoscope, 131:1095-1100, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD)., Objective: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists., Methods: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD., Results: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction., Conclusions: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time.

Background: Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in chronic rhinosinusitis (CRS)., Objective: To assess and to compare the effectiveness of three modalities of corticosteroids administration in patients with CRS., Study Design: A prospective randomized controlled study, Methods: Thirty patients with CRS were randomized in three groups depending on the route of corticosteroids administration: 16 days by oral route (Medrol (Pfizer, Belgique), 32 mg/8 days -16 mg/4 days-8 mg/4 days); nasal spray (Rhinocort (AstraZeneca, Belgique), 2 × 2 × 64 µg/nostril); or sonic nebulization (Pulmicort (AstraZeneca, Belgique), 2 × 1 mg/4 mL) (Sonic nebulizer, AOHBOX-NL11SN, DTF, France). Olfactory function was assessed using orthonasal threshold discrimination identification and retronasal psychophysical olfactory tests (RNT) before and after the treatment. Same intranasal modalities were previously tested for in vitro airways scintigraphic deposition., Results: In vitro differences in drug deposition pattern between both intranasal modalities were demonstrated. Threshold discrimination identification and RNT were similar between three groups at baseline. Threshold discrimination identification improved by 5.5, 5.8, and -1.1 for sonic nebulization, oral, and nasal spray groups, respectively (P = 0.010). This improvement was clinically relevant for oral and nebulized administration. It was similar between oral and nebulized administration but significantly higher than nasal spray administration. Retronasal psychophysical olfactory tests improved similarly for the three groups (P = 0.231) CONCLUSION: Effectiveness of sonic nebulized and oral administration is demonstrated on orthonasal olfactory. The clinical benefit is better than with nasal spray., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

The aim of this study was to investigate the olfactory bulb (OB) and sulcus (OS) in a large group of patients who have been well-characterized in terms of olfactory function, with a specific focus on the comparison between patients with olfactory loss due to chronic rhinosinusitis, head trauma, or acute infections. A retrospective study of 378 patients with olfactory loss was performed. Orthonasal olfactory function was assessed with the"Sniffin' Sticks" test kit, including tests for odor threshold, odor discrimination, and odor identification. Magnetic resonance imaging analyses were focused on OB volume and OS depth. Major results of the present study included the (1) demonstration of a correlation between olfactory function and OB volume across the various pathologies in a very large group of subjects; (2) the three functional tests exhibited a similar degree of correlation with OB volume. (3) The right, but not the left OS correlated with olfactory function; in addition, (4) OS was negatively correlated with age. In contrast to OS, (5) no side differences were found for the OB. Finally, (6) the three different causes of olfactory loss exhibited different patterns of results for the three olfactory tests. The present data suggest that the morphological assessment of the OB volume and OS depth produces useful clinical indicators of olfactory dysfunction.

Background: Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage., Objectives: Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI)., Methods: Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls., Results: As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups., Conclusion: MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

Objectives: Several prognostic factors influencing the recovery from olfactory dysfunction have been described. The aim of this study was to investigate whether olfactory bulb volume could be used as a new predictor of olfactory recovery in postinfectious and posttraumatic olfactory loss., Study Design: Cohort study; Level of evidence, 4. Setting Tertiary university clinic, department of otolaryngology., Subjects and Methods: A cohort of 60 patients with postinfectious (n = 28) and posttraumatic olfactory loss (n = 32) was investigated. Assessment of olfactory function was performed using orthonasal (Sniffin' Sticks test) and retronasal psychophysical olfactory tests, at the time of the diagnosis (t1) and 15 months later (t2). All patients were examined on 3 tesla magnetic resonance imaging, and the olfactory bulbs volume was assessed using planimetric contouring at the time of the diagnosis (t1)., Results: Recovery rate was 25% in patients with posttraumatic olfactory loss and 36% in patients with postinfectious olfactory loss. There was a correlation between both orthonasal and retronasal olfactory testing and the initial measurement of the total olfactory bulb volume. In addition, we observed a significant correlation between changes in olfactory functions and initial measurement of the total olfactory bulb volume, with larger volumes relating to higher improvement of olfactory function. Finally, we found that none of the patients with a total olfactory bulb volume of 40 mm(3) or less exhibited recovery of olfactory function., Conclusion: Olfactory bulb volume seems to be a predictor of olfactory recovery in patients with postinfectious and posttraumatic olfactory loss.

Objectives/hypothesis: The aim of the present study was to evaluate the course of olfactory dysfunction in patients with olfactory loss following infections of the upper respiratory tract., Study Design: Prospective cohort., Methods: A total of 27 patients were included; each patient was evaluated twice. Psychophysical testing of olfactory function was performed with the Sniffin' Sticks test and chemosensory functions with event-related potential (ERP)., Results: At T1, 15 patients were considered hyposmic, 12 as anosmic. Accordingly, nine and 27 patients demonstrated olfactory ERP. At T2, 16 and 11 patients were considered as hyposmic and anosmic, and 11 demonstrated olfactory ERP. Analysis of variance did not show significant differences for any parameters between T1 and T2: threshold, discrimination, identification (TDI) scores at the Sniffin' Sticks and amplitudes and latencies of N1 and P2 in the ERP. However, seven patients demonstrated an increase of more or equal to six points at the TDI score, indicating significant improvement. Four of the seven patients had olfactory ERP at T1 (57%); of those patients who did not show improvement, five of 20 (25%) exhibited olfactory ERP. Thus, the presence of olfactory ERP predicts a positive evolution of olfactory function with a relatively high specificity of 83%., Conclusions: The current findings clearly confirm earlier results on recovery rate of postinfectious olfactory loss. The new finding is that the presence of olfactory ERP at the first consultation is also a positive predictive factor of a favorable outcome in this disease.