The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

"Sniffin' Sticks" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as "TDI score", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.

Normative data for the "Sniffin' Sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects.

Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non-motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose - hence the term 'dual-hit'.

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Parkinson's disease: a dual-hit hypothesis.

“Sniffin’ Sticks” is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score – i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject’s age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using “Sniffin’ Sticks.”

Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds.

Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

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Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study

'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.

‘Sniffin’ Sticks': Olfactory Performance Assessed by the Combined Testing of Odor Identification, Odor Discrimination and Olfactory Threshold

"Sniffin' Sticks" is a new test of nasal chemosensory performance based on pen-like odour-dispensing devices. This portable test is suited for repetitive, inexpensive screening of odour identification. The test includes a forced odour-identification task for seven odours performed by means of a list of four items (multiple-choice). In 146 subjects the basic screening test was compared to a down-scaled version of the UPSIT (CC-SIT). Sniffin' Sticks exhibited a relatively higher coefficient of correlation with the subjects' age; they also demonstrated the women's superior olfactory sensitivity more pronounced when compared to men. In addition, the coefficient of correlation between age and olfactory performance was slightly higher when the sticks were used. Preliminary investigations in nine patients with impaired olfactory function (i.e., anosmic or hyposmic patients) revealed significantly lower scores in patients compared to healthy controls matched for age and sex (p < 0.001). It is concluded that Sniffin' Sticks may be useful in the routine clinical assessment of olfactory performance where both time and costs matter.

B. Sekinger

Papers

‘Sniffin’ Sticks': Olfactory Performance Assessed by the Combined Testing of Odor Identification, Odor Discrimination and Olfactory Threshold

"Sniffin' sticks": screening of olfactory performance.