Trigeminal cold receptors and airflow perception are altered in chronic rhinosinusitis.

BACKGROUND: In chronic rhinosinusitis (CRS), nasal obstruction can often be explained by anatomical deformities, polyps, or congested nasal mucosa. However, in cases with little deformity or inflammation, perceived nasal obstruction may result from reduced airflow perception caused by an alteration of the intranasal trigeminal system. The aim of this study was to assess this association. METHODOLOGY: We performed a prospective case-control study of 15 CRS patients, 18 patients with a deviated nasal septum (DNS) and 16 healthy controls. We assessed olfactory function using the Sniffin' Sticks test and Visual Analog Scales (VAS). We used the Trigeminal Lateralization Task (TLT) with eucalyptol and cinnamaldehyde to examine intranasal trigeminal function. Further, we assessed nasal patency with Peak Nasal Inspiratory Flow and VAS. Finally, we measured protein levels of trigeminal receptors (TRPM8, TRPA1 and TRPV1) and inflammatory markers (IL-13, INF-y and eosinophils) in CRS and DNS patients' mucosal biopsies using Western Blots. RESULTS: CRS patients had significantly lower olfactory function than DNS and healthy controls. They also had significantly lower TLT scores for eucalyptol than both other groups. CRS patients had significantly lower nasal patency than controls; for DNS patients this was limited to subjective measures of nasal patency. In line with this, CRS patients exhibited significantly higher levels of sTRPM8-18 than DNS patients. CONCLUSIONS: Intranasal trigeminal function is decreased in CRS patients, possibly due to the overexpression of short isoforms of TRPM8 receptors.

Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction?

BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS: The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

Predictive factors of involuntary weight loss in patients with smell and taste disorders.

BACKGROUND: Chemosensory dysfunction (olfaction, taste, and trigeminal) affects quality of life, potentially impacting eating behaviors. We investigated which factors are associated with weight loss in patients with smell and taste disorders. METHODS: Retrospective study of consecutive adult patients seen in the smell and taste clinic during a 10-year period. Patients were asked about smell, flavor and taste impairment. Psychophysically, smell was assessed with Sniffin' Sticks, flavor with a retronasal test, and taste with Taste Strips. RESULTS: A total of 554 patients (313 females) were included with a median age of 51 years (IQR 23). Seventy-six (13.7%) reported involuntary weight loss (median 6 kg, IQR 6) due to chemosensory disorders. The odds of losing weight were 2.1 times higher when patients reported subjective changes in flavor perception. Parosmia was a significant predictor of weight loss. Patients with symptoms lasting longer than two years were less likely to present with weight loss. Post-traumatic chemosensory dysfunction was a significant predictor of losing weight. On psychophysical testing, the probability of a patient losing weight increased by 8% for every 1-unit reduction in Taste Strips score. CONCLUSION: Factors associated with weight loss were self-reported changes in flavor perception, parosmia, duration of symptoms for less than two years, head injury, and psychophysically measured low Taste Strips score. These data help to identify patients at risk of weight loss from smell or taste impairment.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

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.

Trigeminal impairment in treatment-refractory chronic nasal obstruction.

BACKGROUND: Patients with anatomically unexplained, chronic nasal obstruction (CNO) that is refractory to medical treatment pose a challenge for clinicians. A surgical solution, addressing mechanical obstacles, is unsuited for these patients. CNO may result from disrupted airflow perception due to activation of the intranasal trigeminal system; therefore, aim of this study is to evaluate if intranasal trigeminal function of these CNO patients is decreased. METHODS: In this retrospective cross-sectional study, we compared 143 CNO patients and 58 healthy volunteers, between 18 to 80 years old. We assessed nasal patency by means of rhinomanometry (RM) and measured susceptibility of intranasal trigeminal system by the trigeminal lateralization task (TLT). RESULTS: TLT scores were significantly lower in CNO patients compared to controls (p less than 0.001), but RM scores were not different between groups. Accordingly, TLT allowed to identify CNO patients with an accuracy of the area under the curve (AUC) of 0.78, while the value for RM was at chance (AUC=0.47). CNO patients showed normal reaction to vasoconstrictive agents with significantly lower RM values after Xylomethazoline application. CONCLUSION: Results suggest that reported nasal obstruction in CNO patients without any obvious anatomical obstacle and resistant to medical treatment may be linked to decreased perception of nasal airflow rather than physical obstruction. In this sub-set of CNO patients, trigeminal testing more adequately reflects the reported obstruction than nasal resistance assessment does. In future studies, the relation of the trigeminal status and the subjective sensation of nasal obstruction needs to be addressed with validated patient rated outcome measures (PROMs).

Rhinology in review: from COVID-19 to biologicals.

We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

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.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Olfactory stimulation may promote oral feeding in immature newborn: a randomized controlled trial.

Premature newborns have an increased mortality and morbidity due to respiratory immaturity and inefficient oral feeding performance. Transient assistance with feeding tubes until oral performance improves is required with consequent hospital admission. Based on a controlled and randomized study, we tested whether olfactory stimulation compared to odorless stimulation could accelerate the switch from feeding tube to satisfactory oral feeding. Fifty newborns were included and randomly assigned to either odorless or olfactory stimulation with anise or cinnamon. The main outcome measurement was the duration of the hospital stay. The odor-stimulated group could be discharged from hospital on average 3.4 days earlier than the control group (p = 0.12). When including only more mature newborns into the analysis (n = 39), the difference was statistically significant (p < 0.05). This trend emphasizes that olfaction may have its place in early feeding stimulation.

mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile technology.

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Rhinophototherapy in chronic rhinosinusitis: a double blind randomized placebo-controlled trial.

BACKGROUND: This study evaluated the efficacy of rhinophototherapy in patients with chronic rhinosinusitis (CRS) without nasal polyps. METHOD: In this randomized double-blind, placebo-controlled trial, CRS patients (n=50) received either mixed visible and ultraviolet (UVA and UVB) light source application (mUV/VIS) or visible light alone that served as placebo. Both groups were treated for 3 weeks. RESULTS: Results in the rhinophototherapy and placebo group were not significantly different and failed to reduce patient-reported outcomes measures (Rhinosinusits Disability Index, Visual Analogic Scale of symptom severity) and objective scores (rhinomanometry, olfactory thresholds, nasal Nitic Oxide concentrations), immediately and one month after treatment. CONCLUSIONS: The present data suggest that rhinophototherapy is not an efficient treatment for chronic rhinosinusitis without nasal polyps.

Application of the European Test of Olfactory Capabilities in patients with olfactory impairment.

A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript 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.