EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease

An intact functional mucosal barrier is considered to be crucial for the maintenance of airway homeostasis as it protects the host immune system from exposure to allergens and noxious environmental triggers. Recent data provided evidence for the contribution of barrier dysfunction to the development of inflammatory diseases in the airways, skin and gut. A defective barrier has been documented in chronic rhinosinusitis, allergic rhinitis, asthma, atopic dermatitis and inflammatory bowel diseases. However, it remains to be elucidated to what extent primary (genetic) versus secondary (inflammatory) mechanisms drive barrier dysfunction. The precise pathogenesis of barrier dysfunction in patients with chronic mucosal inflammation and its implications on tissue inflammation and systemic absorption of exogenous particles are only partly understood. Since epithelial barrier defects are linked with chronicity and severity of airway inflammation, restoring the barrier integrity may become a useful approach in the treatment of allergic diseases. We here provide a state-of-the-art review on epithelial barrier dysfunction in upper and lower airways as well as in the intestine and the skin and on how barrier dysfunction can be restored from a therapeutic perspective

Biological evaluation of structurally diverse amaryllidaceae alkaloids and their synthetic derivatives: Discovery of novel leads for anticancer drug design

Twenty-nine Amaryllidaceae alkaloids and their derivatives belonging to the five most common groups, including lycorine, lycorenine, tazettine, crinine, and narciclasine types, were evaluated for antiproliferative, apoptosis-inducing, and anti-invasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine, and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine, and haemanthamine, the apoptosis-inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent anti-invasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at nontoxic concentrations. The anti-invasive activity of buphanamine is particularly promising because this alkaloid is not toxic to cells even at much higher doses. This work has resulted in the identification of several novel leads for anticancer drug design

Histamine and T helper cytokine–driven epithelial barrier dysfunction in allergic rhinitis

Background Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and TH2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier. Objective We sought to investigate the role of histamine and TH2 cells in driving epithelial barrier dysfunction in AR. Methods Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4 kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested in vitro. In addition, the effect of activated TH1 and TH2 cells, mast cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-γ, and TNF-α on mucosal permeability was tested in vivo. Results Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated TH1 and TH2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the TH1- and TH2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ, and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation. Conclusions Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR

European symposium on the awareness of allergy: report of the promotional campaign in the European Parliament (26-28 April 2016)

From 26 to 28 of April 2016, an allergy awareness campaign was organized by the European Academy of Allergy and Clinical Immunology and the European Federation of Allergy and Airway Diseases Patients Associations in the European Parliament in Brussels, with support of the European Parliament's Interest group on Allergy and Asthma and was co-hosted by the Members of the European Parliament David Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPTs) were performed to gain attention for the increasing prevalence of allergic airway diseases in Europe. Since more than 30% of the total European population suffers from airway allergies and asthma, reaching a higher level of awareness and elaboration of an active prevention plan is mandatory. Of the 406 individuals undergoing SPT in the European Parliament, 211 participants (52%) reported to have suffered from an allergy in the past, with allergic symptoms being present in the nose and eyes (40% and 36%, respectively), the skin (27%), lower airways (14%) and the gut (8%). Of the 381 SPT with reliable results, cutaneous hypersensitivity was found in 201 (53%) participants. Of those with positive SPT (n = 201), 70 participants (35%) were monosensitized while 131 participants (65%) were polysensitized. The positive skin reactions were found mostly for grass pollen (n = 108), followed by Dermatophagoides pteronyssinus (n = 105), Dermatophagoides farina (n = 96) and birch pollen (n = 85). Of note, 54 individuals (14% of the total tested population) without reported allergy or allergic symptoms showed a positive SPT without clinical relevance. This report summarizes the main idea and goals of the symposium: chronic airway diseases are a major and growing health problem in Europe. Therefore, a joint preventive action plan needs to be developed for a better health status of European citizen

MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite allergic rhinitis

Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate (FP)) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction of nasal flow upon cold dry air exposure. The effects of AZE+/-FP on barrier integrity and airway inflammation were studied in a murine model of HDM induced NHR and on reduced activation of murine sensory neurons and human mast cells. MP29-02 but not placebo reduced NHR (p <0.0001 vs. p=0.21), levels of substance P (p=0.026 vs. p=0.941) and β-hexosaminidase (p=0.036 vs. p=0.632) in human nasal secretions. In wild type C57BL6 mice, the reduction of β-hexosaminidase levels (p <0.0001) by AZE+FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (p=0.0012) and completely reversed eosinophilic inflammation (p=0.0013). In vitro, repeated applications of AZE+FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE+FP reduced MC degranulation to the same extent as AZE alone. MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE+FP on MC degranulation, nasal epithelial barrier integrity and TRP channels provide novel insights into the pathophysiology of allergic rhinitis. This article is protected by copyright. All rights reserve