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.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Study protocol: the ear-nose-throat (ENT) prospective international cohort of patients with primary ciliary dyskinesia (EPIC-PCD).

INTRODUCTION Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10 000. It affects mainly the upper and lower airways due to impaired mucociliary clearance. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems, although the ENT clinical phenotype may present great variability. Despite that, data on PCD ENT manifestations are scarce and based on small single-centre studies. To date, we know little about the spectrum and severity of PCD ENT disease, its association with lung disease, its course over life and its determinants of prognosis.This study protocol describes the aims and methods of the first prospective, observational, multinational cohort study focusing on ENT disease in patients with PCD. METHODS AND ANALYSIS The ENT prospective international cohort of patients with PCD (EPIC-PCD) is a prospective standardised observational clinical cohort set up as a multinational multicentre study, embedded into routine patient care. It aims to longitudinally characterise ENT disease in patients with PCD and its association with lung disease, and to identify determinants of its prognosis. Patients of all ages, diagnosed with PCD who undergo an ENT clinical assessment at least once a year at one of the participating centres will be invited to participate. Collected data include diagnostic test results, results of ENT examinations, lung function measurements, information on management of ENT disease and patient-reported data on clinical symptoms and health-related quality of life (QoL). Data are collected using the standardised PCD-specific FOLLOW-PCD form and the validated QoL-PCD questionnaire. ETHICS AND DISSEMINATION The study has been reviewed and approved by the Human Research Ethics Committees at all participating centres, based on local legislation. The results of the study will be published in scientific journals, presented at scientific conferences and disseminated to participants and national patient organisations. TRIAL REGISTRATION NCT04611516

Mepolizumab reduces the need for surgery in patients with chronic rhinosinusitis with nasal polyps

Background: For patients with chronic rhinosinusitis with nasal polyps (CRSwNP), endoscopic sinus surgery (ESS) can be associated with high recurrence rates despite intranasal corticosteroids (as part of standard of care [SoC]). We assessed the impact of mepolizumab, a humanized anti-interleukin-5 antibody, on the need for repeat ESS in patients with CRSwNP. Methods: SYNAPSE, a randomized, double-blind, placebo-controlled, multicenter study, enrolled patients with CRSwNP uncontrolled with SoC. All patients had ≥1 ESS in the past 10 years and were eligible for repeat ESS. Patients received 4-weekly subcutaneous (SC) mepolizumab 100 mg or placebo, plus SoC, for 52 Weeks. We assessed the proportion of patients with a need for ESS (visual analog scale overall symptom score >7; endoscopic bilateral NP score ≥5), time to inclusion on a waiting list for ESS (Kaplan–Meier [KM] estimate), and the proportion of patients included on a waiting list, by Week 52. Results: Data from 407 patients (placebo n=201; mepolizumab n=206) were analyzed. Mean (SD) duration of CRSwNP was 11.4 (8.4) years; 218 (54%) patients had ≥2 ESS in the past 10 years. After 52 weeks, more patients using mepolizumab vs placebo were identified as not needing ESS (72% vs 51%, respectively; odds ratio [95% confidence interval] 2.46 [1.59, 3.79]; P<0.001). KM estimates indicated a ~50% lower risk of inclusion on a waiting list for ESS with mepolizumab than placebo. Up to Week 52, 16% vs 30% of patients using mepolizumab vs placebo were due for ESS on a waiting list. Conclusions: Mepolizumab 100 mg SC reduces the need for repeat surgery compared with placebo for patients with recurrent CRSwNP despite SoC therapy

Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers

International audienceChronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed. All patients also undergo a sampling of purulent secretions sampled from the middle meatus under endoscopic view for bacteriological analysis. In our series, CT opacities were consistent in all the patients, as well as mainly partial and located in ethmoid cells (100% of patients) and in maxillary sinuses (85.4% of patients), and stayed stable over time. In the 31 patients who had purulent secretions, bacteriological culture showed at least one bacterium in 83.9% (n = 26). There was no significant difference in positive cultures for Pseudomonas aeruginosa in patients >40 years old versus those <40 (p = 0.17; Fisher). Surgical management was performed in only 19% of patients in order to improve sinonasal mechanical drainage. Our data support the hypothesis that the sinuses can be considered as a bacterial reservoir. From this retrospective study, we have introduced several changes into our routine clinical practice in our reference centers. Based on our analyses, medical and surgical treatments benefit from incorporating bacteriological information and sinonasal symptoms much more than CT scan evaluation alone. All patients now undergo systematically an annual simultaneous bacteriological sampling of the middle meatus and sputum to follow the relationship between ENT and lung disease and to help to antibiotic therapy strategy