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.

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.

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.

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.

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.

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.

Response to Glucocorticosteroids Predicts Olfactory Outcome After ESS in Chronic Rhinosinusitis.

OBJECTIVES: Olfaction is frequently impaired in chronic rhinosinusitis with nasal polyps (CRSwNP) and often improves after endoscopic sinus surgery (ESS). Data about dynamics of olfactory changes after ESS are lacking, and little information is available concerning whether preoperatively administered glucocorticosteroids predict postoperative olfaction. Therefore, the aim of this study was to examine dynamics of olfaction after ESS in relation to the effect of preoperative administration of glucocorticosteroids in CRSwNP. METHODS: This prospective study included 52 CRSwNP patients (30 men, 22 women, mean age 54 ± 14 years) divided into a control group (n = 31) subjected to ESS without preoperative steroids and a treatment group (n = 21) receiving orally administered glucocorticosteroids preoperatively. Self-ratings of olfaction and olfactory testing using the extended Sniffin' Sticks test battery (threshold, discrimination and identification [TDI] score) were performed. Olfaction was measured preoperatively; after termination of glucocorticosteroid treatment (only treatment group); and 2 weeks, 1 month, and 3 months postoperatively. RESULTS: After glucocorticosteroids, TDI score significantly improved in 57% of patients, and olfactory function remained unchanged in 43%. In addition, improvement in TDI score after steroids and 3 months postoperatively were significantly correlated (r = 0.66, P = 0.01). Patients whose olfaction did not improve after glucocorticosteroids did not benefit from surgery. Regarding postoperative olfactory dynamics, TDI score reached its maximum 1 month postoperatively and decreased again approximately 3 months after surgery. CONCLUSION: Glucocorticosteroids improved olfaction in CRSwNP comparable to surgery. In addition, changes in relation to steroids predicted olfactory outcome postoperatively. Regarding the olfactory dynamics, it could be demonstrated that olfactory function increased 1 month after surgery and decreased 3 months postoperatively. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1616-1621, 2020.

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.

Clinical Diagnosis and Current Management Strategies for Olfactory Dysfunction: A Review.

IMPORTANCE: Olfactory dysfunction affects approximately 20% of the general adult population. It is associated with reduced quality of life and important health care outcomes such as neurodegeneration and death. The accurate diagnosis of olfactory dysfunction is therefore important to quantify impairment, the effect of intervention, and residual disability. This review summarizes the current evidence on the diagnosis and management of olfactory dysfunction. OBSERVATIONS: Olfactory dysfunction can be quantitative and/or qualitative. Despite numerous underlying pathophysiological causes, approximately two-thirds of cases are due to sinonasal disease or postinfectious or posttraumatic dysfunction. All patients should undergo assessment with a thorough clinical history and examination (including nasoendoscopy) followed by subjective olfactory assessment and some form of validated psychophysical test. Psychophysical tests should include assessment of odor threshold and/or odor discrimination or identification, although multicomponent testing has diagnostic advantages. Imaging of the olfactory tract and brain is indicated for a high index of suspicion for intracranial pathology. Treatment with olfactory training may benefit patients with nonsinonasal dysfunction. Treatment with medications such as phosphodiesterase inhibitors or intranasal sodium citrate require further research, as do nonchronic rhinosinusitis-related surgical procedures. CONCLUSIONS AND RELEVANCE: This multifactorial assessment and patient olfactory training may improve the accuracy and reliability with which olfactory dysfunction is diagnosed and monitored.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

Importance: Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. Objective: To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. Design, Setting, and Participants: This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Main Outcomes and Measures: Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Results: Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Conclusions and Relevance: Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Monitoring olfactory function in chronic rhinosinusitis and the effect of disease duration on outcome.

BACKGROUND: Our primary aim in this study was to determine which of the "Sniffin' Sticks" subtest components (threshold, discrimination, or identification) best reflect overall change in olfactory function during treatment for chronic rhinosinusitis (CRS). Our secondary aim was to determine whether duration of CRS affects olfactory outcomes after treatment. METHODS: A retrospective cohort study was performed. Sniffin' Sticks test scores from patients medically treated for CRS at our center from 1999 to 2016 were analyzed. Only patients with 2 test scores available were included. RESULTS: Results from 408 patients were included (mean age, 56 years; male:female ratio, 217:191). There was a statistically significant improvement in threshold (T), discrimination (D), and identification (I) scores as well as the composite "TDI" score between the two testing sessions. Controlling for age, there was a significantly greater improvement in composite TDI score in patients with CRS of ≤24 months duration. As expected, we found statistically significant correlations between change in overall composite TDI score and change in threshhold, discrimination, and identification, between sessions. Of the individual subcomponents, change in discrimination correlated best with change in composite TDI score (r = 0.82, p < 0.0001). This relationship was maintained irrespective of duration of CRS. CONCLUSIONS: In patients with CRS, odor discrimination appears to best reflect overall changes in olfactory function, as determined using the composite TDI score. Furthermore, olfactory outcomes are better when treatment is started sooner.

Olfactory brain gray matter volume reduction in patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory condition and a major cause of olfactory loss. Olfactory dysfunction has been associated with reduced olfactory bulb (OB) volume and gray matter (GM) density in the olfactory-related brain areas. The aim of this study was to investigate brain GM structural and OB volume alterations in patients with CRS. METHODS: Structural brain images were collected from 21 CRS patients and 31 healthy controls on a 3-T scanner. Voxel-based morphometry (VBM) was performed to investigate GM. Olfactory bulb volumes were measured using AMIRA software. Psychophysical olfactory testing for odor threshold (T) and identification (I) was performed using the Sniffin' Sticks battery. RESULTS: CRS patients had significantly lower scores for Sniffin' Sticks olfactory tests than controls (p < 0.001 for T, I, and combined T and I [TI] scores). Region-of-interest analyses revealed no difference in GM volume between CRS patients and healthy controls; however, in CRS patients with severe olfactory dysfunction, GM reduction was observed in the gyrus rectus, orbitofrontal cortex, thalamus, and the insula. In addition, no difference was observed for OB volume in CRS patients compared with healthy controls. CONCLUSION: In this study we identified a reduction in gray matter in olfactory brain regions in CRS patients with severe olfactory dysfunction.

Intranasal vitamin A is beneficial in post-infectious olfactory loss.

Vitamin A plays a decisive role in the regeneration of olfactory receptor neurons. In this retrospective study we investigated the effectiveness of topical vitamin A in patients with post-infectious and posttraumatic smell disorders. Retrospective cohort. A total of 170 patients (age range 18-70 years, mean age 52 years) participated. Forty-six patients were treated with smell training only. The remaining 124 patients received smell training and topical vitamin A. Olfactory function was assessed using the Sniffin' Sticks test kit, a validated technique to measure odor thresholds, discrimination and identification. The duration of olfactory training was 12 weeks. In patients receiving vitamin A, this was applied topically (head back position) at a dose of 10,000 IU/day for 8 weeks. Follow-up testing was performed approximately 10 months after the first assessment. Thirty-seven per cent of all post-infectious patients treated with vitamin A exhibited clinical improvement, whereas only 23% improved in controls. Using a Chi-square test, this was a significant result (χ 2 = 7.06, df = 2, p = 0.03). In addition, when comparing change in score after treatment, olfactory training + vitamin A produced significantly greater improvement compared with training alone, in discrimination score for all patients (1.4 points, p = 0.008), and in threshold and discrimination in the post-infectious group (1.6 points, p = 0.01 and 1.4 points, p = 0.04, respectively). Intranasal vitamin A at a dose of 10,000 IU per day for 2 months may be useful in the treatment of post-infectious olfactory loss. Further work with prospective, placebo-controlled studies is required to confirm these findings.