Patient Experience and Preferences for the Assessment of Olfaction: The Patient International Clinical Assessment of Smell Survey.

INTRODUCTION: Olfactory dysfunction (OD) is common and carries significant personal and societal burden of disease. Accurate assessment of olfaction is required for good clinical care and affords patients insight into their condition. However, the accuracy of assessment varies with technique used, and there is presently little standardisation of clinical practice. We therefore aimed to determine experience of and preferences for olfactory assessment in healthcare-seeking adults. METHODS: An anonymous patient co-produced survey was developed in collaboration with a UK-based OD charity. Distribution was via their social media patient forum. "Healthcare seeking" adults (i.e., who had undergone olfactory assessment by a healthcare professional [any care level/speciality] or may do so in the future) were included. RESULTS: 576 people (88.5% female, mean 46 years) responded. Hyposmia, parosmia, and retronasal OD were most frequently reported. 55.2% had been assessed by a healthcare professional - GP most commonly, followed by ENT. Importantly, only 15.6% and 16.9% of respondents had undergone systematic assessment with smell tests or symptom questionnaires, respectively. Most respondents had not undergone imaging. Mean satisfaction was higher in those seen by ENT. Interestingly, respondents prioritise orthonasal odour identification over other forms of smell test. Unfortunately, many felt that healthcare professionals (across specialities) were dismissive towards OD and lacked appropriate knowledge of both its pathophysiology and effects. We propose simple steps that can be taken to improve olfactory assessment, including education and establishment of robust referral networks. CONCLUSION: We hope these results and supporting practical recommendations will inform future service planning, funding allocation and research, as well as better aligning patient and clinician priorities.

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.

Orthonasal and retronasal odor identification in patients with parosmia.

OBJECTIVE: To compare retronasal and orthonasal perception in parosmic COVID-19 patients, in order to determine whether COVID-19 has a differential effect on these functions. METHODS: Using the Sniffin Sticks test battery orthonasal function was examined for odor threshold, discrimination and identification. Retronasal function was assessed using 20 tasteless aromatized powders. Gustatory function was measured using the Taste Strips test. RESULTS: This study included 177 patients (127 women, 50 men; mean age 45 years), of whom 127 (72%) were hyposmic and 50 (28%) normosmic. Compared to patients without parosmia, parosmic patients performed worse in odor identification for both orthonasal (F = 4.94, p = 0.03) and retronasal tests (F = 11.95, p < 0.01). However, an interaction effect between route of odor identification (orthonasal or retronasal) and parosmia status was found (F = 4.67, p = 0.03): patients with parosmia had relatively lower retronasal scores than patients without parosmia. CONCLUSION: Our results suggest that COVID-19 may affect the olfactory mucosa differently along the anterior-posterior axis, thereby possibly contributing to the pathophysiology of parosmia. Patients with parosmia also exhibit a higher degree of impairment when odors are presented through the retronasal route during eating and drinking.

Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination.

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.

Functional septorhinoplasty alters brain structure and function: Neuroanatomical correlates of olfactory dysfunction.

Introduction: We previously demonstrated functionally significant structural plasticity within the central olfactory networks, in association with improved olfaction after surgical treatment of chronic rhinosinusitis (CRS). In order to confirm and expand on these findings, the primary aim of this study was to determine whether these same regions undergo functionally significant structural plasticity following functional septorhinoplasty (fSRP), in patients with non-CRS olfactory dysfunction (OD) of mixed cause. fSRP has previously been shown to improve olfactory function, and the secondary aim of this study was to provide initial insights into the mechanism by which fSRP affects olfaction. Methods: We performed a pilot prospective, multimodal neuroimaging study in 20 participants undergoing fSRP, including patients with non-CRS OD of mixed cause, as well as normosmic surgical controls. Participants underwent psychophysical olfactory testing, assessment of nasal airway, structural and functional neuroimaging. This was performed pre- and postoperatively in patients, and preoperatively in controls. Results: There was a statistically and clinically significant improvement in mean psychophysical olfactory scores after surgery. This was associated with structural and functional plasticity within areas of the central olfactory network (anterior cingulate, orbitofrontal cortex, insula, temporal pole). Improved psychophysical scores were significantly correlated with change in bilateral measures of nasal airflow, not measures of airflow symmetry, suggesting that improved overall airflow was more important than correction of septal deviation. Conclusion: This work highlights the importance of these neuroanatomical regions as potential structural correlates of olfactory function and dysfunction. Our results also provide initial insight into the mechanistic effects of fSRP on olfaction. Further work could investigate the utility of these regions as personalised biomarkers of OD, as well as the role of fSRP in treating OD.

Prospective Audit and Review of Parathyroid Surgery in Rural Setting.

Primary hyperparathyroidism (PHPT) is a common condition associated with significant morbidity and mortality. Recently Endocrine multidisciplinary team (MDT) has greatly influenced the care of such patient and has helped in improving the outcome and reducing the complications related with surgery. We conducted a review of prospectively collected data of all consecutive parathyroidectomies carried out in our district general hospital between October 2016 and Jan 2020 by a single surgeon. The collected data include patient's characteristics, laboratory results, radiological findings and operative outcomes. There were 53 parathyroidectomies performed during this period for PHPT. Mean age of patients was 75 years. Our results demonstrated a reduction in post-operative PTH in 46 patients (92%). We have identified no cases of vocal cord palsy, significant neck haemorrhage or mortality. 6 patients had temporary hypocalcaemia and 2 patients had hungry bone syndrome. Patient selection and evaluation for parathyroidectomies under endocrine MDT has greatly influenced the outcome for our patients. We had low complication rate and surgery was done at a more convenient location for selected patients. We benefit from dedicated monthly parathyroid clinic and weekly endocrine multidisciplinary team meetings to assist with patient selection and optimisation. A team effort helps in reducing complications and improving outcomes. We feel that surgery can be provided safely and successfully in a district general hospital in rural settings.

Psychophysical Testing in Chemosensory Disorders.

Purpose of Review: To provide an overview of psychophysical testing in olfaction and gustation. Recent Findings: Subjective patient report correlates poorly with objective assessment of olfaction and gustation. It is therefore important that clinicians and researchers perform psychophysical testing during chemosensory assessment. There are several validated psychophysical tests of olfaction and gustation, with ongoing developments accelerated by the COVID-19 pandemic. These tests have been culturally and linguistically adapted globally. Screening tests have been developed with careful consideration to distinguish normosmics from those with olfactory dysfunction. Summary: Validated chemosensory tools are available for use by the clinician to support screening, diagnosis, or monitoring. There are promising advances in self-assessment and screening that provide avenues for the development of a standardised pathway for identification and formal assessment of patients with smell and taste disorders.

Advancement of PD Is Reflected by White Matter Changes in Olfactory Areas: A Pilot Study.

Loss of sense of smell is a well-known non-motor symptom of Parkinson's disease (PD). Here, we present insight into the association between PD advancement and equivalents of smell loss in olfactory-eloquent brain areas, such as the posterior cortex and orbitofrontal cortex. Twelve PD patients in different Hoehn and Yahr stages and 12 healthy normosmic individuals were examined with diffusion tensor imaging. Tract-based spatial statistics were used to analyze microstructural changes in white matter adjacent to the bilateral posterior and orbitofrontal cortex. Axial diffusivity, mean diffusivity, and radial diffusivity were significantly higher in olfactory ROIs in advanced PD patients. The results of this preliminary study indicate that PD advancement is associated with progressive neurodegeneration in olfactory-related brain areas.

Sinonasal surgery alters brain structure and function: Neuroanatomical correlates of olfactory dysfunction.

Olfactory dysfunction (OD) is more common than hearing loss, partial blindness, or blindness and can have a significant impact on the quality of life. Moreover, unexplained OD is an early biomarker in neurodegenerative diseases and increases 5-year mortality risk. Structural alterations in olfactory eloquent brain regions may represent the neuroanatomical correlates of OD. Previous studies have demonstrated reduced gray matter (GM) volume in areas of presumed olfactory relevance in patients with OD. However, being cross-sectional in nature, these studies do not provide evidence of causality, for which longitudinal work is required. At present, however, longitudinal studies addressing olfactory structural plasticity are limited, both in number and methodological approach: to our knowledge, such work has not included parallel functional imaging to confirm the relevance of structural change. We therefore performed a longitudinal multimodal neuroimaging study investigating structural and functional plasticity in 24 patients undergoing surgical treatment for chronic rhinosinusitis, compared with 17 healthy controls. We demonstrated functionally significant structural plasticity within the orbitofrontal, anterior cingulate and insular cortices, and temporal poles in patients 3 months after surgery. Of interest, GM volume decreased in these regions, in association with increased psychophysical scores and BOLD signal. To our knowledge, this is the first study to demonstrate both structural and functional plasticity of the central olfactory networks, thereby confirming these areas as neuroanatomical correlates of olfactory function/dysfunction.

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.

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.

Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines.

OBJECTIVES: The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smell during the COVID-19 pandemic. DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral, and imaging. SETTING AND PARTICIPANTS: An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists. MAIN OUTCOME MEASURES: The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic. Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean. RESULTS: Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A drops. Alpha-lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses, and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made. CONCLUSION: This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19-related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops.

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.

Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis.

BACKGROUND AND OBJECTIVE: Olfactory dysfunction has a high prevalence in chronic rhinosinusitis (CRS) patients and significantly affects quality of life. CRS is recognized as a complex disorder encompassing heterogeneous inflammatory processes in the nose and paranasal sinuses. Olfactory dysfunction in CRS patients is associated with the level of inflammatory mediators and the efficiency of inflammatory control. Learning about the association between CRS-related inflammation and olfactory function will provide clues to the pathogenesis of CRS. STRUCTURE: The first section of this review describes the assessment of olfactory function using various measures, from ratings to MR based imaging. Then, we discuss the conductive and inflammatory mechanisms related to olfactory dysfunction in CRS: olfaction is associated with certain inflammatory patterns and is potentially a marker of CRS subtype. Finally, we review anti-inflammatory therapies including conservative and surgical approaches, and their effectiveness in olfactory dysfunction in CRS. CONCLUSION: Assessment of olfactory function should be considered in the clinical evaluation of CRS patients, not only for detecting and quantifying patients' symptom, but also because it appears to be useful to objectively assess the efficacy of CRS treatment over time. In addition, olfaction can be expected to expand the library of CRS phenotypes and endotypes and, hence, pave the way for more precise, tailored treatment options.

Diagnosing nasal obstruction and its common causes using the nasal acoustic device: A pilot study.

Objectives: There is a need to develop a medical device which can accurately measure normal and abnormal nasal breathing which the patient can better understand in addition to being able to diagnose the cause for their nasal obstruction.The aim is to evaluate the accuracy of the nasal acoustic device (NAD) in diagnosing the common causes for nasal obstruction and diagnosing normal and abnormal (nasal obstruction) nasal breathing. Methods: This pilot study recruited 27 patients with allergic rhinitis (AR), chronic rhinosinusitis (CRS), and a deviated nasal septum (DNS) which represents the common causes for NO and 26 controls (with normal nasal breathing). Nasal breathing sounds were recorded by the NAD akin to two small stethoscopes placed over the left and right nasal ala. The novel outcome metrics for the NAD include inspiratory nasal acoustic score (INA) score, expiratory nasal acoustic (ENA) score and the inspiratory nasal obstruction balance index (NOBI). The change in acoustic score following decongestant is key in this diagnostic process. Results: Pre-decongestant ENA score was used to detect the presence of nasal obstruction in patients compared to controls, with a sensitivity of 0.81 (95% CI: 0.66-0.96) and a specificity of 0.77 (0.54-1.00). Post-decongestant percentage change in INA score was used to identify the presence of AR or CRS, with a sensitivity of 0.87 (0.69-1.00) and specificity of 0.72 (0.55-0.89) for AR; and a sensitivity of 0.92 (0.75-1.00) and specificity of 0.69 (0.52-0.86) for CRS. Post-decongestant inspiratory NOBI was used to identify DNS, with a sensitivity of 0.77 (0.59-0.95) and specificity of 0.94 (0.82-1.00). Conclusion: We have demonstrated that the NAD can help distinguish between normal and abnormal nasal breathing and help diagnose AR, CRS, and DNS. Such a device has not been invented and could revolutionize COVID-19 recovery telemedicine. Level of Evidence: Diagnostic accuracy study-Level III.

The best COVID-19 predictor is recent smell loss: a cross-sectional study.

BACKGROUND: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. METHODS: This preregistered, cross-sectional study used 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 singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. RESULTS: 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 single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset. CONCLUSIONS: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (10

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

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.

Short-Course Pentoxifylline Is Not Effective in Post-Traumatic Smell Loss: A Pilot Study.

It has been suggested that systemic pentoxifylline may be beneficial in the treatment of olfactory dysfunction. The postulated mechanism of action involves nonselective competitive phosphodiesterase inhibition, leading to increased intracellular cyclic adenosine monophosphate and consequent increased olfactory neuron activity. This should in theory lead to improved olfactory function. We describe a pilot case series from our tertiary referral center of patients treated with oral pentoxifylline for olfactory dysfunction. Six patients with post-traumatic impairment who were treated with systemic pentoxifylline were included. Patients were treated with 200 mg of oral prolonged release pentoxifylline, 3 times a day for 21 days. Olfactory function was tested pre and post-treatment for odor threshold (T), discrimination (D), identification (I) and composite 'TDI' score using a psychophysical test battery, the "Sniffin' Sticks." Oral pentoxifylline was well tolerated and all patients completed the treatment period. There was a small improvement in odor threshold and identification scores, but these did not reach statistical or clinical significance. There were deteriorations in discrimination and composite TDI score, which did not reach significance. While our case series was small, systemic pentoxifylline did not appear to be beneficial in the treatment of hyposmia in this patient group.