International clinical assessment of smell: An international, cross-sectional survey of current practice in the assessment of olfaction.

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.

Axonal Regrowth of Olfactory Sensory Neurons In Vitro.

One of the most prevalent causes of olfactory loss includes traumatic brain injury with subsequent shearing of olfactory axons at the level of the cribriform plate (anterior skull base). Scar tissue at this level may prevent axonal regrowth toward the olfactory bulb. Currently, there is no cure for this debilitating and often permanent condition. One promising therapeutic concept is to implant a synthetic scaffold with growth factors through the cribriform plate/scar tissue to induce neuroregeneration. The first step toward this goal is to investigate the optimum conditions (growth factors, extracellular matrix proteins) to boost this regeneration. However, the lack of a specifically tailored in vitro model and an automated procedure for quantifying axonal length limits our ability to address this issue. The aim of this study is to create an automated quantification tool to measure axonal length and to determine the ideal growth factors and extracellular proteins to enhance axonal regrowth of olfactory sensory neurons in a mouse organotypic 2D model. We harvested olfactory epithelium (OE) of C57BL/6 mice and cultured them during 15 days on coverslips coated with various extracellular matrix proteins (Fibronectin, Collagen IV, Laminin, none) and different growth factors: fibroblast growth factor 2 (FGF2), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), retinoic acid (RA), transforming growth factor ß (TGFß), and none. We measured the attachment rate on coverslips, the presence of cellular and axonal outgrowth, and finally, the total axonal length with a newly developed automated high-throughput quantification tool. Whereas the coatings did not influence attachment and neuronal outgrowth rates, the total axonal length was enhanced on fibronectin and collagen IV (p = 0.001). The optimum growth factor supplementation media to culture OE compared to the control condition were as follows: FGF2 alone and FGF2 from day 0 to 7 followed by FGF2 in combination with NGF from day 7 to 15 (p < 0.0001). The automated quantification tool to measure axonal length outperformed the standard Neuron J application by reducing the average analysis time from 22 to 3 min per specimen. In conclusion, robust regeneration of murine olfactory neurons in vitro can be induced, controlled, and efficiently measured using an automated quantification tool. These results will help advance the therapeutic concept closer toward preclinical studies.

Assessment of olfactory fluctuations in a clinical context.

PURPOSE: The aim of the study was to investigate whether olfactory fluctuations (OF) are pronounced in patients with sinonasal olfactory dysfunction (OD). METHODS: The retrospective investigation included patients aged 18 years or older, who consulted a tertiary referral center for olfactory loss. Patients with normal smell function were excluded. Patients answered a structured questionnaire about their olfactory symptoms, with specific questions related to the presence of OF and its average frequency, amplitude, duration, time since most recent OF, and associated symptoms of self-reported OF. Patients also underwent clinical evaluation including a structured medical history and physical examination including nasal endoscopy. In addition, we assessed orthonasal olfactory function using Sniffin' Sticks, and gustatory function using "taste sprays". RESULTS: Participants included 131 men and 205 women (n = 336), aged 18 to 86 years (mean 50, SD 16). Patient-reported fluctuations occurred most frequently in sinonasal (38%), idiopathic (29%), and postviral (29%) OD. Amplitude of OF was highest in postviral OD (p = 0.009). Average frequency, duration, and the time since the most recent fluctuation were not significantly different between groups (all p's > 0.42). Odor discrimination (p = 0.002) and identification (p = 0.017) scores were higher among those individuals with OF. CONCLUSION: Amplitude of OF may help distinguish postviral from other causes of OD, especially in patients presenting with equivocal symptoms of sinonasal disease.

Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.

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.

[Parosmia and phantosmia: clinical update]. / Parosmie et fantosmie: mise à jour.

Olfactory disorders became known by large parts of the population since the Covid-19 pandemic. The causes of olfactory dysfunctions are manifold. Similar to other sensory impairments the disruption can be qualitative or quantitative. Quantitative olfactory disorders such as anosmia or hyposmia are well explored, whereas the knowledge on qualitative disorders such as parosmia or phantosmia is still limited. This article gives an update on the current clinical knowledge and workup of parosmia and phantosmia.

Depuis la pandémie de Covid-19, la population est davantage informée sur les troubles de l'odorat. Ils peuvent être d'origines multiples. Comme pour toute modalité sensorielle, il existe des atteintes quantitatives et qualitatives. Les troubles quantitatifs sont mieux connus et pris en charge mais les troubles qualitatifs restent méconnus. Cet article traite des troubles de l'odorat qualitatifs, notamment de la parosmie et de la fantosmie, ainsi que de leur prise en charge.

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

SMELL-S and SMELL-R: Olfactory tests not influenced by odor-specific insensitivity or prior olfactory experience.

Smell dysfunction is a common and underdiagnosed medical condition that can have serious consequences. It is also an early biomarker of neurodegenerative diseases, including Alzheimer's disease, where olfactory deficits precede detectable memory loss. Clinical tests that evaluate the sense of smell face two major challenges. First, human sensitivity to individual odorants varies significantly, so test results may be unreliable in people with low sensitivity to a test odorant but an otherwise normal sense of smell. Second, prior familiarity with odor stimuli can bias smell test performance. We have developed nonsemantic tests for olfactory sensitivity (SMELL-S) and olfactory resolution (SMELL-R) that use mixtures of odorants that have unfamiliar smells. The tests can be self-administered by healthy individuals with minimal training and show high test-retest reliability. Because SMELL-S uses odor mixtures rather than a single molecule, odor-specific insensitivity is averaged out, and the test accurately distinguished people with normal and dysfunctional smell. SMELL-R is a discrimination test in which the difference between two stimulus mixtures can be altered stepwise. This is an advance over current discrimination tests, which ask subjects to discriminate monomolecular odorants whose difference in odor cannot be quantified. SMELL-R showed significantly less bias in scores between North American and Taiwanese subjects than conventional semantically based smell tests that need to be adapted to different languages and cultures. Based on these proof-of-principle results in healthy individuals, we predict that SMELL-S and SMELL-R will be broadly effective in diagnosing smell dysfunction.

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

[Psychophysical olfactory testing : what's new ?] / Tests psychophysiques de l'olfaction : quoi de neuf ?

Olfactory disorders are common and may lead to severe consequences on quality of life. Medical management including treatment options can be proposed to the patients. For this reason, a correct diagnosis is important. Olfactory testing is one of the cornerstones for the diagnosis of smell impairment which helps to quantify the deficit. Despite good and widespread psychophysical olfactory tests, there are still many challenges in testing olfaction. Most of the current available test may not fully account for some cultural and genetic biases. Therefore it is difficult to develop olfactory tests and standardize them across different populations. In this paper we discuss an alternative method based on « white smells ¼ which may help to overcome these issues.

Les troubles olfactifs sont fréquents et peuvent parfois entraîner des conséquences importantes pour la qualité de vie des personnes concernées. Une prise en charge médicale et des traitements peuvent être proposés pour certains patients. Les tests olfactifs sont une des pierres angulaires dans le processus diagnostique qui permettent la quantification de la perte de l'odorat. Pour améliorer ces tests, des défis sont encore à relever. Leurs résultats peuvent parfois être biaisés par des facteurs culturels ou génétiques. L'une des possibles méthodes pour contourner ces problèmes est l'utilisation d'« odeurs blanches ¼, discutée dans cet article.

Gustatory Function in Patients With Cerebellopontine Angle Masses.

OBJECTIVE: To investigate the impact of cerebellopontine angle (CPA) masses on subjective and measured taste function. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral center. PATIENTS: Consecutive adult patients with untreated CPA masses. INTERVENTIONS: Gustatory function was psychophysically measured with Taste Strips (range, 0-16) on both sides of the tongue. Subjective taste complaints were assessed using a questionnaire. MAIN OUTCOME MEASURES: Half-sided taste impairment (hemi-ageusia) was defined as side-to-side asymmetry ≥4 points with <9 points on the side of the CPA mass. We used the Koos classification for vestibular schwannomas (VS) and, in the case of facial nerve palsy, the House-Brackmann grading system. RESULTS: We included 135 patients (mean [standard deviation (SD)] age, 55.3 ± 14.1 yr; 62 males). The most common CPA mass was VS (77%). Overall, the measured taste function was lower on the affected compared with the healthy side of the tongue (mean score, 9.8 ± 3.3 versus 11 ± 2.9; p < 0.0001). Looking for clinically relevant one-sided taste impairment revealed 18 (13.3%) patients with hemi-ageusia, but only 4 (30.8%) of those subjectively complained of taste dysfunction. Regarding VS, Koos IV masses presented the lowest score on the affected side (mean score, 7.5 ± 3.7). Six patients presented with facial palsy. Having facial palsy did not result in a lower Taste Strips score (p = 0.23). CONCLUSION: Before any CPA mass treatment, a measurable ipsilateral decrease in gustatory function is present in many patients. Most patients do not notice this preexisting taste impairment. From a medicolegal standpoint, this warrants consideration. To avoid postoperative claims regarding taste function, a preoperative assessment may be considered.

Mechanically evoked tinnitus after cochlear implantation with preservation of residual hearing.

In the recent past, inclusion criteria for cochlear implant surgery expanded to patients with ever more residual acoustic hearing in the low frequencies. By applying the meticulous hearing preservation surgical strategy and specifically designed atraumatic electrode arrays, residual hearing can be preserved to a meaningful extent in a large majority of patients. In this paper, we describe two female patients suffering from mechanically evoked tinnitus after hearing preservation cochlear implantation surgery with MEDEL flex electrodes. The occurrence of audible perceptions through mechanical stimulation in the region of the external ear is believed to be due to the direct transmission of movements via the electrode array to the basilar membrane of the inner ear. In both cases, the mechanically evoked tinnitus led to revision surgery with immobilization of the array in the mastoid cavity. Despite eliminating the tinnitus, the revision surgery led to a loss of residual hearing in one patient, whereas the relatively poor residual hearing in the other revision case remained unchanged. The presence of mechanically evoked tinnitus seems to be associated with increased fragility of inner ear structures and hearing function, possibly due to direct mechanical contact of the electrode array with the basilar membrane. Consequently, the electrode array needs to be carefully immobilized in the mastoid cavity at a distance from soft tissue to prevent mechanical damage of inner ear structures, particularly in female patients with fine muscular tissue.

Mediastinal abscess revealed by computed tomography after pharyngeal fish-bone impaction.

Fishbone impactions in the upper aerodigestive tract are frequent but rarely cause serious complications when recognized and treated early. In this report, we describe the case of a patient that sought medical attention as late as 2 weeks after the fishbone impaction. A 52-year-old male was presented with fever, odynophagia and a toxic appearance. CT scan revealed a large cervicomediastinal abscess. The patient was immediately started on large-spectrum antibiotics, treated by surgical drainage, and recovered uneventfully. This case report highlights the occurrence of severe complications of upper digestive tract fishbone impaction and the usefulness of a preoperative CT scanner in this context.

How to Manage Taste Disorders.

Purpose of the Review: This study aims to summarize the current state of the art of how taste disorders are clinically best managed. Recent Findings: Taste disorders are distressing for the concerned patients since eating and drinking become bothersome or impossible. Apart from nutritional problems, quality of life is impaired. Still, diagnosis and treatment of taste disorders are elusive, and general knowledge about taste and its affection is little within the population and the medical community. This review stresses the importance of accurate workup and diagnosis of taste disorders in order to offer an effective treatment. Yet unclear aspects of taste disorders are discussed, and interesting findings regarding the treatment of taste disorders are reviewed. A special focus is given to current pharmacological options on how to treat taste disorders. Summary: Despite impressive insights into the gustatory function and molecular logic of taste receptor cells, there is currently poor clinical knowledge on the pathophysiology of taste disorders in humans. Diagnosing, measuring, and treating gustatory disorders remain restricted to a handful of specialized smell and taste centers worldwide. Despite interesting work on potential drugs treating taste disorders, many of the reported medications lack controlled and randomized trials confirming their efficacy in taste dysfunction. Future efforts need to be focused on the treatment of taste disorders.

Features of Mild-to-Moderate COVID-19 Patients With Dysphonia.

INTRODUCTION: To explore the prevalence of dysphonia in European patients with mild-to-moderate COVID-19 and the clinical features of dysphonic patients. METHODS: The clinical and epidemiological data of 702 patients with mild-to-moderate COVID-19 were collected from 19 European Hospitals. The following data were extracted: age, sex, ethnicity, tobacco consumption, comorbidities, general, and otolaryngological symptoms. Dysphonia and otolaryngological symptoms were self-assessed through a 4-point scale. The prevalence of dysphonia, as part of the COVID-19 symptoms, was assessed. The outcomes were compared between dysphonic and nondysphonic patients. The association between dysphonia severity and outcomes was studied through Bayesian analysis. RESULTS: A total of 188 patients were dysphonic, accounting for 26.8% of cases. Females developed more frequently dysphonia than males (P = 0.022). The proportion of smokers was significantly higher in the dysphonic group (P = 0.042). The prevalence of the following symptoms was higher in dysphonic patients compared with nondysphonic patients: cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea, and vomiting. The severity of dyspnea, dysphagia, ear pain, face pain, throat pain, and nasal obstruction was higher in dysphonic group compared with nondysphonic group. There were significant associations between the severity of dysphonia, dysphagia, and cough. CONCLUSION: Dysphonia may be encountered in a quarter of patients with mild-to-moderate COVID-19 and should be considered as a symptom list of the infection. Dysphonic COVID-19 patients are more symptomatic than nondysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation.

Specific roles for the Ccr4-Not complex subunits in expression of the genome.

In this work we used micro-array experiments to determine the role of each nonessential subunit of the conserved Ccr4-Not complex in the control of gene expression in the yeast Saccharomyces cerevisiae. The study was performed with cells growing exponentially in high glucose and with cells grown to glucose depletion. Specific patterns of gene deregulation were observed upon deletion of any given subunit, revealing the specificity of each subunit's function. Consistently, the purification of the Ccr4-Not complex through Caf40p by tandem affinity purification from wild-type cells or cells lacking individual subunits of the Ccr4-Not complex revealed that each subunit had a particular impact on complex integrity. Furthermore, the micro-arrays revealed that the role of each subunit was specific to the growth conditions. From the study of only two different growth conditions, revealing an impact of the Ccr4-Not complex on more than 85% of all studied genes, we can infer that the Ccr4-Not complex is important for expression of most of the yeast genome.

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review.

To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. The following outcomes were considered: sample origin (animal versus human); detection method; anatomical location and cell types. PRISMA checklist and modified population, intervention, comparison, outcome, timing and setting (PICOTS) framework were used to perform the review. Of the 24 identified studies, 17 met our inclusion criteria. Thirteen studies were conducted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. TMPRSS2 was found in goblet and apical respiratory cells. ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. Animal studies suggested that ACE2 expression may vary regarding age. There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

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.