A practical test for retronasal odor identification based on aromatized tablets.

BACKGROUND: Olfactory perceptions elicited by odors originating from within the body (retronasal olfaction) play a crucial role in well-being and are often disrupted in various medical conditions. However, the assessment of retronasal olfaction in research and the clinical practice is impeded by the lack of commercially available tests and limited standardization of existing testing materials. NEW METHOD: The novel ThreeT retronasal odor identification test employs 20 flavored tablets that deliver a standardized amount of odorous stimuli. The items represent common food- and non-food-related odors. RESULTS: The ThreeT test effectively distinguishes patients with olfactory dysfunction from healthy controls, achieving a specificity of 86% and sensitivity of 73%. Its scores remain stable for up to 3 months (r=.79). COMPARISON WITH EXISTING METHOD: ThreeT test exhibits a strong correlation with "Tasteless powders" measure of retronasal olfaction (r=.78) and classifies people into healthy and patient groups with similar accuracy. Test-retest stability of ThreeT is slightly higher than the stability of "Tasteless powders" (r=.79 vs r=.74). CONCLUSIONS: ThreeT is suitable for integration into scientific research and clinical practice to monitor retronasal odor identification abilities.

Differential connectivity of the posterior piriform cortex in Parkinson's disease and postviral olfactory dysfunction: an fMRI study.

Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson's disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.

Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning.

Loss of olfactory function is a typical acute coronavirus disease 2019 (COVID-19) symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows for assessing the long-term prognosis of its olfactory impact. Participants (n = 722) of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days were approached in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on an 11-point numerical scale [0,…10]. Neither the frequency of olfactory diagnostic categories nor olfactory test scores showed any COVID-19-related effects. Olfactory diagnostic categories (anosmia, hyposmia, or normosmia) were similarly distributed among former patients and controls (0.86%, 18.97%, and 80.17% for former patients and 1.17%, 17.51%, and 81.32% for controls). Former COVID-19 patients, however, showed differences in their subjective perception of their own olfactory function. The impact of this effect was substantial enough that supervised machine learning algorithms detected past COVID-19 infections in new subjects, based on reduced self-awareness of olfactory performance and parosmia, while the diagnosed olfactory function did not contribute any relevant information in this context. Based on diagnosed olfactory function, results suggest a positive prognosis for COVID-19-related olfactory loss in the long term. Traces of former infection are found in self-perceptions of olfaction, highlighting the importance of investigating the long-term effects of COVID-19 using reliable and validated diagnostic measures in olfactory testing.

Impact of a 12-week olfactory training programme in women with migraine with aura: protocol for a double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Migraine is a leading cause of disability and suffering worldwide. However, conventional pharmacological migraine preventive therapies are often challenging and accompanied by adverse effects. Recently, structured odour exposure has shown to successfully increase pain thresholds in patients with chronic back pain. Despite the importance of the olfactory system in migraine, there are no studies investigating the impact of structured odour exposure in patients with migraine. METHODS AND ANALYSIS: This double-blind randomised placebo-controlled trial will be conducted at the Headache Clinic of the University Pain Center at TU Dresden, Germany and aims at investigating the impact of a 12-week structured exposure to odours in women with migraine. Fifty-four women between 18 and 55 years with migraine with aura will be recruited and randomised to training with odours and odourless training. The primary outcomes are mechanical and electrical pain thresholds. Secondary outcomes comprise olfactory threshold and the number of headache days. Other exploratory measurements are headache associated pain intensity, acute analgesic intake, symptoms of anxiety and depression, and quality of life. Additionally, this protocol assesses neuroanatomical and neurofunctional changes associated with the 12-week olfactory training. Data analysis will be executed on the basis of the general linear model considering repeated measurements. ETHICS AND DISSEMINATION: Ethical approvals were obtained from the Ethics Board of the TU Dresden (Protocol No. BO-EK-353082020). Participation will only be possible after written informed consent is provided. Findings will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00027399.

Correlations between gustatory, trigeminal, and olfactory functions and nasal airflow.

PURPOSE: To determine the relationship of chemosensory screening and nasal airflow tests among the same set of participants, and to determine other factors that are related to the outcomes of these tests. METHODS: Participants had no chemosensory complaints. Structured medical history was taken. Participants underwent 5 screening tests: q-sticks (orthonasal olfaction), q-powders (retronasal olfaction), trigeminal lateralization test, taste sprays, and peak nasal inspiratory flow (PNIF). Ratings of smell/taste ability and nasal airflow were obtained using visual analogue scales (VAS). Composite sinusitis symptoms and significance of olfaction questionnaire scores were also determined. RESULTS: Four hundred participants were included in the study, 156 men, 244 women; aged 18-82 years (mean: 46). The q-powders and taste spray scores were weakly positively correlated with all the other chemosensory tests and PNIF. However, chemosensory test scores were not correlated with VAS, composite sinusitis symptoms, and significance of olfaction questionnaire scores. Various tests showed significant decrease starting at specific ages (in years, PNIF and trigeminal lateralization: 40, q-powders: 60, and q-sticks: 70). CONCLUSION: Chemosensory screening tests and self-rated chemosensory function showed no correlation in participants without chemosensory complaints. In addition, gustatory function appeared to be correlated with olfactory and trigeminal function but also with nasal airflow, and nasal airflow was related not only to olfactory but also to trigeminal and taste function. Over all, the results suggest that chemosensory functions (orthonasal olfactory, trigeminal, retronasal olfactory, gustatory) and nasal airflow are correlated with each other, which we propose may be possibly mediated, at least in part, through central nervous system interactions.

Migraine with aura: less control over pain and fragrances?

BACKGROUND: Accumulating data emphasizes the importance of olfaction in migraine pathophysiology. However, there are only a few studies evaluating how the migraine brain processes olfactory stimulation, and virtually no studies comparing patients with and without aura in this context. METHODS: This cross-sectional study recorded event-related potentials from 64 electrodes during a pure olfactory or pure trigeminal stimulus in females with episodic migraine with aura (n = 13) and without aura (n = 15), to characterize the central nervous processing of these intranasal stimuli. Patients were tested in interictal state only. Data were analyzed in the time domain and in the time-frequency domain. Source reconstruction analysis was also performed. RESULTS: Patients with aura had higher event-related potentials amplitudes for left-sided trigeminal and left-sided olfactory stimulations, and higher neural activity for right-sided trigeminal stimulation in brain areas related to trigeminal and visual processing. Following olfactory stimulations patients with aura displayed decreased neural activity in secondary olfactory structures compared to patients without aura. Oscillations in the low frequency bands (< 8 Hz) differed between patient groups. CONCLUSIONS: Altogether this may reflect hypersensitivity to nociceptive stimuli in patients with aura relative to patients without aura. Patients with aura have a bigger deficit in engaging secondary olfactory-related structures, possibly leading to distorted attention and judgements towards odors. The cerebral overlap between trigeminal nociception and olfaction might explain these deficits.

Depression Severity Is Different in Dysosmic Patients Who Have Experienced Traumatic Brain Injury Compared with Those Who Have Not.

Traumatic brain injury (TBI) in humans can result in olfactory, cognitive, and affective changes. Surprisingly, research on the consequences of TBI often did not control for olfactory function in the investigated groups. Consequently, the affective or cognitive differences might be misleading as related rather to different olfactory performance than to a TBI experience. Hence, our study aimed to investigate whether TBI occurrence would lead to altered affective and cognitive functioning in two groups of dysosmic patients, one with TBI experience and one without. In total, 51 patients with TBI experience and 50 controls with varied causes of olfactory loss were thoroughly examined in terms of olfactory, cognitive, and affective performance. Student t-tests demonstrated that the only significant difference between the groups appeared in the depression severity, with TBI patients being more depressed (t = 2.3, p = 0.011, Cohen's d = -0.47). Regression analyses further showed that TBI experience was significantly associated with depression severity (R2 = 0.05, F [1, 96] = 5.5, p = 0.021, beta = 1.4). In conclusion, the present study showed that TBI experience is linked to depression, which is more pronounced compared to individuals with olfactory loss without TBI.

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches.

Objective: Headache prevalence among children and adolescents has increased over the last few years. Evidence-based treatment options for pediatric headaches remain limited. Research suggests a positive influence of odors on pain and mood. We investigated the effect of repeated exposure to odors on pain perception, headache-related disability, and olfactory function in children and adolescents with primary headaches. Methods: Eighty patients with migraine or tension-type headache (mean 13.1 ± 3.29 years) participated, of whom 40 underwent daily olfactory training with individually selected pleasant odors for 3 months and 40 received state-of-the-art outpatient therapy as a control group. At baseline and after a 3-month follow-up, olfactory function [odor threshold; odor discrimination; odor identification; comprehensive Threshold, Discrimination, Identification (TDI) score], mechanical detection and pain threshold (quantitative sensory testing), electrical pain threshold, patient-reported outcomes on headache-related disability [Pediatric Migraine Disability Assessment (PedMIDAS)], pain disability [Pediatric Pain Disability Index (P-PDI)], and headache frequency were assessed. Results: Training with odors significantly increased the electrical pain threshold compared to the control group (U = 470.000; z = -3.177; p = 0.001). Additionally, olfactory training significantly increased the olfactory function (TDI score [t(39) = -2.851; p = 0.007], in particular, olfactory threshold, compared to controls (U = 530.500; z = -2.647; p = 0.008). Headache frequency, PedMIDAS, and P-PDI decreased significantly in both groups without a group difference. Conclusions: Exposure to odors has a positive effect on olfactory function and pain threshold in children and adolescents with primary headaches. Increased electrical pain thresholds might reduce sensitization for pain in patients with frequent headaches. The additional favorable effect on headache disability without relevant side effects underlines the potential of olfactory training as valuable nonpharmacological therapy in pediatric headaches.

Self-assessment of olfactory function using the "Sniffin' Sticks".

BACKGROUND: A precise and reliable test of the olfactory function is indispensable for the diagnosis of the olfactory disorder (OD). Despite of this, in a clinical context, often there is no place in daily routine for time-consuming procedures. This study aimed to examine if the assessment of olfactory function using the "Sniffin' Sticks" is suitable for self-assessment. METHODS: Participants comprised 84 healthy control subjects (HC) and 37 OD patients. The "Sniffin' Sticks" test battery consisting of odor threshold (T), discrimination (D) and identification (I) tests was used for self- and assisted assessments. To save time, we applied the 8-item wide step version of the T test and the 8-item D test, whereas the I task remained the same as the original version. The whole test included two sessions, with each session comprising a self-assessment part performed by the participants themselves, and an assisted-assessment part performed by the examiner. RESULTS: Sniffin' Sticks self-assessment was efficient in distinguishing between self-reported HC subjects and OD patients (p's < 0.01), and the scores did not differ significantly from the assisted-assessment (p's > 0.05). In the self-administered I and TDI tests, there was a moderate to excellent test-retest reliability (ICC = 0.51-0.93, p's < 0.01), and a strong to excellent correlation with the assisted assessment (r = 0.71-0.92, p's < 0.01). However, the self-administered T and D tests only exhibited low to moderate test-retest reliability (ICC = 0.30-0.72, p's < 0.05) and correlations with the assisted test (r = 0.31-0.62, p's < 0.05). CONCLUSIONS: The Identification self-test is appropriate to be solely applied, and is therefore an easy-to-use alternative for olfactory screening in a larger segment of patients. The whole "Sniffin' Sticks" self-test also shows good measurement properties and is therefore a suitable backup in clinical practice, but improvement is needed due to the simplified D and T self-test.

Impact of COVID-19-Mediated Olfactory Loss on Quality of Life.

INTRODUCTION: COVID-19 can be associated with a variety of longer-lasting impairments that can have a significant impact on patients' quality of life (QoL). While this is well described in the literature for limitations in lung capacity or permanent headaches, there is little research on the impact of olfactory dysfunction in the context of COVID-19 on patients' QoL. METHODS: In 65 patients with a history of COVID-19, the present olfactory ability was assessed using the Sniffin' Sticks test. In addition, olfactory QoL was assessed by the Questionnaire of Olfactory Disorders. Self-assessment was performed with visual analogue scales. The data were compared with the results obtained in healthy individuals and in patients with hyposmia due to other viral infections. RESULTS: The QoL of COVID-19 patients was significantly lower compared to the healthy control group. Even recovered subjects whose olfaction had already returned to the normal range still had a reduced QoL. The severity of the olfactory impairment correlated with the reduction in QoL. However, the olfactory QoL of COVID-19 patients was not worse than that of patients' olfactory loss due to other viral infections. Patients with parosmia had reduced QoL and rated their situation worse than patients without parosmia. CONCLUSION: QoL appears to be impaired in patients with long-lasting COVID-19 olfactory disorders several months after overcoming acute symptoms, even if olfaction has normalized. However, the impairment is not more pronounced than in patients with other postviral olfactory disorders of the same duration.

Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections.

PURPOSE: This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. METHODS: In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and "Sniffin' Sticks" extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. RESULTS: C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. CONCLUSIONS: Patients with C19 and non-C19 URTI exhibit a similar improvement over 3-4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

Migraine Type-Dependent Patterns of Brain Activation After Facial and Intranasal Trigeminal Stimulation.

In migraine, the trigeminal nerve is intimately involved in the pathophysiology of the disease. We hypothesized that alterations in the sensory trigeminal activation in migraine would be reflected by EEG-derived event-related potentials (ERP). We aimed to investigate differences in the temporal and spatial processing of trigeminal stimuli between interictal migraine patients and healthy subjects. ERP to trigeminal stimuli were recorded at 128-channels to allow localization of their cortical sources with high temporal resolution. Seventeen patients with episodic migraine without aura, 17 subjects with episodic migraine with aura, and 17 healthy subjects participated in the study. The first branch of the trigeminal nerve was stimulated using intranasal chemical (CO2), cutaneous electrical, and cutaneous mechanical (air puff) stimuli. Analyses were performed with regard to micro-state segmentation, ERP source localization, and correlation with the patients' clinical characteristics. Topographical assessments of EEG configurations were associated with the pathological condition. The source analysis revealed altered trigeminal-sensory response patterns in the precuneus, temporal pole, and cerebellum for both migraine groups during the interictal phase. The estimated current source density was positively correlated with migraine disease duration, indicating brain functional and structural changes as a consequence of the disease. Hyperactivity of the cerebellar posterior lobe was observed as a specific trigeminal response of migraine patients with aura. In conclusion, our results suggest the presence of brain changes accompanying the advancement of migraine as an expression of dysfunctional central pain processing. Hence, we identified EEG patterns in response to mechano-/chemosensory stimuli that can serve as biomarkers of migraine.

Topical Administration of Mometasone Is Not Helpful in Post-COVID-19 Olfactory Dysfunction.

Persistent olfactory dysfunction is a major concern post-COVID-19, affecting up to 5% of all patients. Different therapeutic options, including mometasone nasal spray, have been recommended, only some of which have been validated for post-COVID-19 olfactory dysfunction. In this study we psychophysically assessed the effect of intranasally applied mometasone furoate on the recovery of olfaction. The spray was applied with a long applicator so that the olfactory cleft could be reached effectively. After olfactory dysfunction had been confirmed psychophysically using Sniffin' Sticks, patients were randomly assigned to two different treatment arms: the study group (n = 40) underwent olfactory training and intranasal administration of mometasone furoate twice daily, whereas the control group (n = 46) performed olfactory training only. After a study duration of three months, psychophysical testing of olfaction was repeated using Sniffin' Sticks. We found no benefit of an additional topical administration of mometasone furoate compared to olfactory training alone. These results psychophysically confirm two previous studies which were based on patients' subjective self-ratings. Our findings are in contrast to current recommendations for the management of olfactory dysfunction post-COVID-19, which might have to be adapted accordingly.

Interictal osmophobia is associated with longer migraine disease duration.

BACKGROUND: Sensitization to sensory stimuli is an essential feature of migraine attacks. The relationship between the clinical course of migraine and increased sensitivity to olfactory stimuli has been little studied so far. METHODS: We analyzed the frequency and quality of osmophobia depending on the phase of migraine in patients with episodic and chronic migraine treated in an tertiary headache center with regard to gender, age, medical history and migraine disability assessment score (MIDAS). Standardized diagnostic questions were used for the assessment of osmophobia. RESULTS: In our cross-sectional investigation (n = 113), 38.1% of the patients showed an increased preictal hypersensitivity to odors, whereas 61.9% described ictal and 31.9% interictal hypersensitivity to odors, odor-triggered migraine was described in 30.1%. Median migraine disease duration has been statistically significantly longer in patients who suffered from interictal hypersensitivity to odors (28.5 years vs. 20 years; p = 0.012). There was a significant correlation between interictal hypersensitivity and higher age (54.50 vs. 45; p = 0.015). Patients with higher migraine disability in MIDAS experienced more frequently preictal and interictal olfactory sensitization and odor triggered migraine attacks. CONCLUSIONS: In patients with longer migraine disease duration and higher migraine-related impairment, osmophobia was more frequently observed. These results might support the hypothesis of increasing sensitization with increasing burden of migraine.

Well-being in patients with olfactory dysfunction.

This cross-sectional, retrospective study aimed to investigate the differences in well-being among patients with olfactory disorder (OD) with quantitative and/or qualitative olfactory dysfunctions, and to identify factors associated with well-being (WB). We included 470 OD patients. WB (WHO-5 questionnaire), quantitative olfactory function (Sniffin' Sticks) and qualitative dysfunction were assessed. Overall, 35% of the OD patients reported a poor WB, higher than 22% of the normative data in general population. For quantitative function, anosmia patients showed lower WB scores than hyposmia and normosmia patients (all p's < 0.03). For qualitative dysfunction, patients with severe parosmia showed lower WB scores than patients without and with less severe parosmia (p's < 0.01). Regarding OD causes in hyposmic patients, post-infectious patients showed poorer WB than idiopathic patients (p = 0.01); sinonasal patients had lower WB than post-traumatic and idiopathic patients (all p's < 0.04). There was a weak but significant positive correlation between WB score and Threshold test score (r = 0.11, p = 0.02). Hierarchical regression analyses showed that women gender, Threshold and overall Sniffin' Sticks scores (TDI) significantly predicted WB score in OD patients. Our results implied that quantitative and qualitative dysfunction is associated with WB. However, only patients with severe dysfunction showed significantly lower WB. While this needs to be better understood, in order to improve well-being, in these patients it appears to be highly important to improve olfactory function, and here especially olfactory sensitivity.

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.

Training with Odors Impacts Hippocampal Thickness in Patients with Mild Cognitive Impairment.

BACKGROUND: The olfactory system is affected early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI). Olfactory training is effective for improving olfactory and cognitive function by stimulating the olfactory pathway, but its effect on patients with MCI remains unclear. OBJECTIVE: The aim of this randomized, prospective, controlled, blinded study was to assess whether a 4-month period of olfactory training (frequent short-term sniffing various odors) may have an effect on olfactory function, cognitive function, and morphology of medial temporal lobe (MTL) subregions and olfactory bulb in MCI patients. METHODS: A total of thirty-seven MCI patients were randomly assigned to the training group or a placebo group, which were performed twice a day for 4 months. Olfactory assessments, cognitive tests and magnetic resonance imaging were performed at the baseline and follow-up period. RESULTS: After the training, there was an increase in odor discrimination, and increased cortical thickness of bilateral hippocampus (CA23DG and CA1) and mean MTL. Additionally, the change of olfactory score was positively associated with change of volume of olfactory bulb and hippocampus; the change of global cognition was positively associated with change of cortical thickness of hippocampus, entorhinal cortex and mean MTL; the change of cortical thickness of entorhinal cortex was positively associated with change of executive function. CONCLUSION: Olfactory training was associated with an increase in cortical thickness of the hippocampus but not olfactory bulb volume in patients with MCI. Olfactory training may serve as an early intervention of preventing hippocampal atrophy.

International consensus statement on allergy and rhinology: Olfaction.

BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

Symptoms of depression change with olfactory function.

Olfactory loss is associated with symptoms of depression. The present study, conducted on a large cohort of mostly dysosmic patients, aimed to investigate whether improvement in olfactory performance would correspond with a decrease in depression severity. In 171 participants (157 dysosmic), we assessed olfactory function and severity of depression before and after an average interval of 11 months, with many patients showing improvement in olfactory function. Separate analyses were conducted for (a) the whole group of patients and (b) the group of dysosmic patients using both classic and Bayesian approaches. For odor identification, Student t test demonstrated that the whole sample improved consistently, especially within the group of dysosmic patients. The dysosmic group also improved in odor threshold and overall olfactory function. Pearson correlation showed that an increase in olfactory function was associated with a decrease in depression severity, particularly in dysosmic patients. To conclude, the present results indicate that symptoms of depression change with olfactory function in general and odor identification in particular.

SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses.

The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss.