Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Nasal chemosensory tests: biomarker between dementia with Lewy bodies and Parkinson disease dementia.

BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are progressive and disabling neurodegenerative disorders, which are often misdiagnosed due to theirs overlapping clinical and paraclinical features. Nevertheless, their adequate management requires an accurate differential diagnosis. The main aim of this study was to investigate the usefulness of olfactory and trigeminal nasal testing for the differential diagnosis between DLB and PDD. METHODS: Odor thresholds to three odorants differentially activating the olfactory and trigeminal systems were assessed in patients with DLB, PDD and healthy controls (n = 20 per group). RESULTS: Odor thresholds were significantly different between the three groups of subjects. More precisely, we found that DLB patients had significantly lower detection threshold performances compared to PDD patients. Moreover, using a standard canonical discriminant analysis, we confirmed a plain differentiation between the three groups. CONCLUSIONS: The current study highlights that DLB patients have very poor olfactory and trigeminal detection threshold performances, which are significantly lower, compared to PDD patients. These results suggest that olfactory testing, using odorants that stimulate both the olfactory and trigeminal systems, could constitute an interesting biomarker and contribute to the differential diagnosis of PDD and DLB patients. Further researches, notably on olfacto-trigeminal interactions, are warranted in these populations to support our findings.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

Neural plasticity in developing and adult olfactory pathways - focus on the human olfactory bulb.

The topic of human adult neural plasticity and neurogenesis is of great interest for medical and scientific community, but it is also largely debated. In the last years, an increasing interest has been paid to the olfactory system, and particularly to the plasticity of the olfactory bulb (OB). While the molecular/cellular mechanisms underlying OB plasticity remain a matter of debate, measurements of the OB using magnetic resonance imaging clearly indicate that it is a highly plastic structure. In this review, we present results regarding the plasticity of the human adult olfactory system.

Development of a new psychophysical method to assess intranasal trigeminal chemosensory function.

BACKGROUND: The aim of this study was to develop a new psychophysical test to assess intranasal trigeminal chemosensory function. METHODOLOGY: The test is similar to the Sniffin’ Sticks test, but using pens impregnated with substances preferentially activating trigeminal afferents. Our test comprises detection threshold, discrimination, identification and lateralization tasks. In a first study, we evaluated healthy controls. In a second study, we evaluated the potential usefulness of this test in patients with rhinological conditions. RESULTS: Study 1: 86 controls were included. Threshold, identification and lateralization performance decreased with age. Test-retest reliability was similar to that of olfactory tests. Study 2: results of the controls group were compared to those of 59 patients (14 allergic rhinitis, 11 chronic rhinosinusitis with nasal polyps (CRSwNP), 9 without nasal polyps (CRSsNP), and 25 with an olfactory disorder (OD)). Controls had 1) lower detection thresholds compared to CRSwNP, CRSsNP and OD, 2) better discrimination and identification scores compared to OD, and 3) better lateralization scores compared to CRSwNP and CRSsNP. CONCLUSIONS: Our test allows to identify age-related changes in trigeminal chemosensory function. Trigeminal function seems to be differently affected in different pathologies. Further studies are necessary to validate our results and evaluate the impact of olfactory co-activation on the observed results.

Parkinson disease in eldery patients: lessons from odour detection thresholds on olfacto-trigeminal interaction.

BACKGROUND: Human nasal chemosensation is mediated by two separate, though interacting sensory pathways: the trigeminal and olfactory systems. Trigeminal sensitivity and olfacto-trigeminal interactions have not yet been well studied in idiopathic Parkinsons disease (IPD). OBJECTIVES: The aim of this study was to assess odour detection thresholds in elderly IPD patients, and compare them to the odour detection thresholds of healthy controls. Finally, we investigated potential interactions between trigeminal and olfactory sensitivity. METHODS: 89 IPD patients aged over 65 and 89 matched healthy participants were enrolled in the study. Odour detection thresholds to 3 stimuli differentially activating olfactory and trigeminal afferents (Phenyl-ethyl alcohol, n-Butanol and Pyridine) were assessed, using an ascending staircase, binary forced-choice procedure. RESULTS AND CONCLUSION: Detection threshold scores were able to discriminate between elderly IPD and controls. Pyridine was less effective than the two other odorants, suggesting that trigeminal pathway is less impaired than the olfactory system. We found that the detection thresholds were significantly different between IPD patients with good autonomy, and patients with impaired autonomy.

Olfaction in Chronic Rhinosinusitis.

Olfactory dysfunction is a frequent complaint in chronic rhinosinusitis patients and has a significant impact on quality of life. Therefore, it is essential that clinicians are aware of the importance of olfactory dysfunction in chronic rhinosinusitis (CRS) patients and know how to deal with it. Notably, the evaluation of olfactory function (i.e., using psychophysical testing) and imagery of olfactory bulb play an important role in the evaluation of patients and give essential information about the "baseline" olfactory function. Because the high impact of olfactory function on quality of life and medical and/or surgical treatment should be proposed to patients. However, it remains difficult to predict the outcome of treatment as well as long-term efficacy. The first section of this review is dedicated to the assessment of olfactory function. Secondly, we will discuss the etiopathology of olfactory dysfunction in CRS with and without nasal polyps. Finally, we will review literature findings about the efficacy of different treatments on olfactory function.

Post-injury smell disorders.

Post-injury smell disorders. PROBLEMS/OBJECTIVES: Head trauma is the third most common aetioiogy of post-traumatic olfactory loss (PTOL). This literature review aims to report the existing knowledge surrounding this issue, exploring the current understanding of the inducing pathogenesis and the assessment and management standards from the early phases to longer-term considerations. METHODOLOGY: Literature search and appraisal in PubMed on the following themes directly associated with PTOL: olfactory disorders, trauma, pathogenesis, examination, recovery and treatment. RESULTS: Scientific evidence was mainly available for epidemiology and exploration tools in cases suffering from PTOL. The current research into obj6ctive batteries of olfactory tests is promising. CONCLUSIONS: This paper highlights the importance of an adequate assessment of PTOL for an early start in olfactory training.

[ENT localisation of amyloidosis: 20 patients report].

Background: Amyloidosis is a rare pathology, due to a toxic accumulation of amyloid proteins infiltrating tissues. Published studies have low statistical power. However it seems that ENT localization have favorable prognosis. Management and check up are not well codified. Methods: Bicentric retros­pec­tive study conducted between 1987 and 2015, from patient diagnosed with ENT amyloidosis. The study was performed to the database of the pathology department. People concerned, history, symptoms and diagnostic features were analysed. The immunologic and clinical status, locations, extension check, treatment and prognosis have been evaluated. Results: Twenty patients were evaluated, ten men and ten women, average age was 55.5 year of age. Three patients were afflicted with familial amyloidosis. Main localisation was larynx (80%), main type was immunoglobulinic (AL) (80%). Amyloidosis was mostly localised (90%) and primary form (80%). Dysphonia was the most frequently encountered symptom. Most performed exami­na­tion were local biopsy and creatinine clearance (100%), serum protein electrophoresis (SEP) (89%), myelogram and/or bone marrow aspiration (75%), and trans thoracic echography (TTE) (75%). Surgical removal was performed for 75% of the patients. Global rate of recurrence was 70%, about 4.6 years after diagnosis. In familial forms, overall survival was 66% at ten years. In non-familial forms, overall survival was 100%. Conclusion: ENT amyloidosis are mostly AL, laryngeal, prima­ry and localised. Distant extension check should be managed by internal medicine specialist and associate creati­ni­ne clea­ran­ce, local biopsy, TTE, SEP and myelogram. Head and neck forms treatment is based on surgical removal, familial forms are of poor prognosis.

Clinical usefulness and feasibility of time-frequency analysis of chemosensory event-related potentials.

BACKGROUND: The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. METHODOLOGY: We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. RESULTS: The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. CONCLUSION: Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.

Chemosensory function assessed with psychophysical testing and event-related potentials in patients with atrophic rhinitis.

Atrophic rhinitis (AR) is a chronic inflammation of the nose characterized by an atrophy of the nasal mucosa. This is typically associated with an impaired sense of smell and a subjective sensation of poor nasal breathing. The aim of this study is to assess chemosensory function in patients suffering from AR using psychophysical testings and event-related potentials (ERP) responses. A cohort of nine patients was extensively studied. Eight out of nine had secondary AR sequela of a bilateral total inferior turbinectomy whereas one patient had a primary AR. All the patients had a clinical evaluation using Sniffin' Sticks test and a retro-olfaction test and an electrophysiological evaluation based upon ERPs obtained after both olfactory and trigeminal stimuli. All the patients complained of a poor nasal breathing and presented a distortion of the chemosensory function. Actually, the orthonasal psychophysical testing showed that four patients out of nine had anosmia, three out of nine had hyposmia and two out of nine were normosmic. All the patients demonstrated retro-olfaction scores inferior to the normal values. The chemosensory ERP showed that seven patients had no olfactory response whereas six had no trigeminal response. Four patients had neither olfactory nor trigeminal ERP response. In conclusion, this study demonstrates that most patients with AR secondary to a total bilateral inferior turbinectomy have a reduction of the chemosensory function measured objectively by psychophysical testings and ERP [corrected].

Assessment of chemosensory function using electroencephalographic techniques.

Electroencephalographic techniques are widely used to provide an objective evaluation of the chemosensory function and to explore neural mechanisms related to the processing of chemosensory events. The most popular technique to evaluate brain responses to chemosensory stimuli is across trial time-domain averaging to reveal chemosensory event-related potentials (CSERP) embedded within the ongoing EEG. Nevertheless, this technique has a poor signal-to-noise ratio and cancels out stimulus-induced changes in the EEG signal that are not strictly phased-locked to stimulus onset. The fact that consistent CSERP are not systematically identifiable in healthy subjects currently constitutes a major limitation to the use of this technique for the diagnosis of chemosensory dysfunction. In this review, we will review the different techniques related to the recording and identification of CSERP, discuss some of their limitations, and propose some novel signal processing methods which could be used to enhance the signal-to-noise ratio of chemosensory event-related brain responses.

Consequences of chronic inflammation in children on facial growth, growth, behavioural disorders and smell.

Adenotonsillar hypertrophy is a common paediatric/otolaryngological disorder that may be associated with secondary growth or facial growth impairment, sleep disturbances, neurocognitive deficits, or smell loss. Surgical removal of the hypertrophic tissue eliminates the mechanical obstacle of the airways and is therefore curative in most cases. The purpose of the present review is to outline the impact of adenotonsillar hypertrophy and adenotonsillectomy on growth, facial growth, sleep, behaviour and smell.

Physiology of the mouth and pharynx, Waldeyer's ring, taste and smell.

This paper reviews the contribution of the different parts of the oral cavity and the pharynx to the basic physiology of breathing, phonation, speech, swallowing, and of Waldeyer's ring to the functioning of the immune system. We discuss the development of taste and smell, as well as possibilities for chemosensory testing in children.

Functional Imaging in Olfactory Disorders.

Purpose of Review: The aim was to synthesize key findings regarding the use of functional MRI (fMRI) to assess olfactory dysfunction (OD), and thus, to evaluate whether fMRI could be a reliable clinical diagnostic tool. Recent Findings: In response to olfactory stimulation, patients with quantitative OD display reduced activation in olfactory-related brain regions but also stronger activation in non-olfactory brain areas. Parosmic patients also seem to show both weaker and higher brain signals. As to trigeminal chemosensory system, fMRI suggests that central processing may be declined in patients with OD. Functional connectivity studies report a possible correlation between altered neuronal connections within brain networks and olfactory performances. Summary: fMRI emerges as a valuable and promising objective method in OD evaluation. Yet, its high inter-individual variability still precludes its routine clinical use for diagnostic purpose. Future research should focus on optimizing stimulation paradigms and analysis methods.

Olfactory Dysfunction Predicts Frailty and Poor Postoperative Outcome in Older Patients Scheduled for Elective Non-Cardiac Surgery.

OBJECTIVES: Frailty has been suggested to take part in the recently demonstrated link between olfactory dysfunction and overall mortality risk. Preoperative assessment of frailty is essential to detect the most vulnerable patients scheduled for surgery. The aim of this study was to evaluate whether olfactory dysfunction is a reliable predictor of preoperative frailty and postoperative outcome. DESIGN: This was a single-center prospective observational study conducted between July and October 2020 in Brussels, Belgium. SETTING AND PARTICIPANTS: 155 preoperative patients aged from 65 years old and scheduled for elective non-cardiac surgery. MEASUREMENTS: Olfactory function was examined using the Sniffin' Sticks 12-item identification test. Frailty was assessed using the Edmonton Frail Scale (EFS) and handgrip strength. The clock drawing test (CDT) from the EFS was also analyzed separately to evaluate cognitive function. Patients were followed for postoperative complications and mortality over one year. RESULTS: Olfactory dysfunction was significantly associated with the EFS score, anosmic patients having a higher median EFS score than normosmic patients (6[4-7] vs 4[2-5], p = .025). Anosmic patients had an increased odds of being frail after adjusting for possible confounding factors (OR: 6.19, 95% CI: 1.65-23.20, p = .007) and were more at risk of poor postoperative outcome (including complications and death) (OR: 4.33, 95% CI: 1.28-14.67, p = .018). CONCLUSIONS: Olfactory dysfunction is associated with preoperative frailty determined by the EFS and with poor post-surgical outcome at one-year.

Adaptation of the Sniffin' Sticks Test in South-Kivu.

AIM: The "Sniffin' Sticks" test is widely used in Europe as a standard test to assess olfaction. Several culturally-adapted versions have been developed. However, no version adapted to Sub-Saharan African populations exists. The aims of the present study were (1) to assess the applicability of the Sniffin' Sticks test in the population of South Kivu (DR Congo), and (2) to develop a culturally adapted version with normative values. MATERIALS AND METHODS: In a first study, 157 volunteers were tested with the original Sniffin' Sticks test. Based on these results, we selected odors that were poorly recognized in the identification test and replaced them by culturally adapted odors. In a second study, we assessed the modified version of the Sniffin' Sticks test in 150 volunteers and defined normative values. RESULTS: In the first study, we found that olfactory function (threshold-discrimination-identification: TDI score) significantly decreased with age and was better in females. Five odors were poorly recognized and were replaced by culturally adapted odors. In the second study, we found that this adapted version led to a higher rate of correctly identified odors. We defined normative values for the South-Kivu population (TDI score: 18-35 years: 30.4±6.0; 36-55 years: 26.2±5.3; >55 years: 25.6±5.0). CONCLUSION: This culturally adapted version of the Sniffin' Sticks test is culturally adapted to the South Kivu population. The normative values will provide the basis for clinical evaluation of pathologic subjects.

Chemosensory pathways: from periphery to cortex.

The aim of this article is to summarise the anatomy of the chemosensory pathways. The vomeronasal organ, the olfactory system, the trigeminal system and the gustatory system will be reviewed in succession. For each of these systems, we will provide a description of the anatomy of the pathways sending the sensory message from the peripheral receptor to the cortical areas, passing through different relays in the nervous system. Particular emphasis will be paid to the anatomical features of the structures involved in chemosensory perception. This will help us to understand better how these systems interact and influence our social lives, our memories and our behaviour, and to evaluate patients with chemosensory dysfunction better.

Post-infectious olfactory loss: a cohort study and update.

Post-infectious olfactory loss is defined as an olfactory dysfunction in the course of an upper respiratory tract infection. Quantitative olfactory dysfunction is usually moderate to severe, with many patients experiencing a qualitative disorder such as parosmia. Diagnosis is made on the basis of patient history, normal clinical examination (no inflammatory disease in the olfactory cleft) and decreased olfactory function. This paper provides an update of pathophysiology, clinical management and prognosis, and also looks at the clinical characteristic of a cohort of 122 patients from our department. Results from orthonasal and retronasal testing, chemosensory event-related potentials and olfactory bulb volume confirmed previous findings: our post-infectious olfactory patients were middle-aged women (sex ratio 2.4; mean age 53.9), with 47.5% and 18% of them complaining of parosmia and phantosmia respectively. More of them were hyposmic than anosmic (64.7% and 35.3% respectively) and 18 suffered repeat episodes. Olfactory bulb volume was correlated to psychophysical olfactory testing and orthonasal to retronasal scores. Olfactory-event-related potentials were found in about one-third of the patients and the vast majority of them had reproducible intranasal trigeminal event-related potentials. As there is no proven medical therapy for this disease, complete clinical evaluation of the patients may help to counsel patients about the recovery prognosis that applies to one-third of them.