EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

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.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

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.

The intranasal trigeminal system: roles in rhinitis (allergic and non-allergic).

The aim of this paper is to review intranasal trigeminal system and associated reflexes. The literature survey was performed on PubMed, ProQuest Central database of Kirikkale University and Google Scholar. The intranasal trigeminal system and associated reflexes play an important role in humans in both health and disease, including in rhinitis of non-allergic and mixed type. The intranasal trigeminal nerve provides sensory perception to the lining of the nose, supplying information on how patent the nasal airway is and responding to various chemical signals. The reflexes known to exist within the intranasal trigeminal system are nasobronchial reflex, trigemino-cardiac reflex, nasogastric reflex, and nasal cycle. The intranasal trigeminal system and its reflexes play a vital role in normal human physiology. Alterations in how this system operates may underlie multiple forms of rhinitis and more research is needed to fully understand the mechanisms involved.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

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.

[Immunodeficiency in chronic rhinosinusitis : An important and often underestimated cause]. / Immundefekte bei chronischer Rhinosinusitis : Eine bedeutende und oft unterschätzte Ursache.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. METHODS: A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. RESULTS: The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. CONCLUSION: Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies.

ARIA masterclass 2018: From guidelines to real-life implementation.

Over the past 20 years, ARIA (Allergic Rhinitis and its Impact on Asthma) has developed various guidelines for the treatment of allergic rhinitis (AR) and asthma multimorbidity. Over time, the ARIA initiative has evolved to ensure the highest level of bestpractices adoption in real life settings. It has evolved towards Integrated Care Pathways (ICPs) using mobile technology, and has now entered a new phase in which change management is key to provide an active and healthy life to all AR patients. With that in mind, the first ARIA masterclass was held on 12th September 2018 in Brussels, Belgium. The masterclass aimed at informing clinicians about the principles of change management, providing unbiased education on diagnosis and treatments, sharing the most recent research data on AR and multimorbidities, and creating a snowball effect to increase the adoption of best practices around the globe. This report provides an overview of the ARIA masterclass concept, summarizes the key lectures and discussions, and gives an outline of the future key development.

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.

Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: a BelSACI-Abeforcal-EUFOREA statement.

Allergic rhinitis (AR) affects 23-30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient- and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.

FcεRI expression and IgE binding by dendritic cells and basophils in allergic rhinitis and upon allergen immunotherapy.

BACKGROUND: In humans, both basophils and dendritic cells (DCs) express the high-affinity IgE receptor (FcεRI). OBJECTIVE: To gain more insight into the relation between serum IgE levels and FcεRI expression and IgE binding by DCs and basophils in house dust mite (HDM) allergy and during subcutaneous immunotherapy (SCIT). METHODS: We measured FcεRI, IgE and HDM allergen on DCs (conventional type 2 DCs, cDC2s; plasmacytoid dendritic cells, pDCs) and basophils by flow cytometry in 22 non-allergic vs 52 allergic subjects and upon HDM SCIT in 28 allergic subjects. IgE levels were measured in serum. RESULTS: Serum IgE correlated differentially with FcεRI expression and IgE binding depending on cell type and allergic status. In non-allergic subjects, FcεRI/IgE surface densities increased with serum IgE to a significantly stronger degree on basophils compared to cDC2s. By contrast, in allergic subjects FcεRI/IgE surface densities increased with serum IgE to a slightly stronger degree on cDC2s compared to basophils. In addition, the data set suggests sequential loading of IgE onto FcεRI expressed by these cells (basophils>cDC2s>pDCs). Finally, HDM SCIT induced a temporary increase in serum IgE, which was paralleled by a peak in FcεRI and IgE on DCs, but not on basophils. CONCLUSIONS & CLINICAL RELEVANCE: This study provides a comprehensive insight into the relation between serum IgE and FcεRI/IgE on basophils and DC subsets. The novel finding that HDM SCIT induces a temporary increase in FcεRI expression on DCs, but not on basophils, can be an incentive for future research on the potential tolerogenic role of IgE/FcεRI signalling in DCs in the setting of allergen immunotherapy.

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.

Prospective study on the outcome of the sphenoid drill out procedure.

BACKGROUND: Chronic sphenoid sinusitis refractory to both medical therapy and sphenoidotomy requires a more extended intervention based on the principles of salvage surgery. Our aim is to describe the sphenoid drill out technique as a sphenoid salvage intervention and to outline its implications on clinical outcome and quality of life. METHODOLOGY: 12 patients with chronic sphenoiditis undergoing a sphenoid drill out procedure were examined by nasal endoscopy preoperatively and postoperatively for one year. Preoperative and postoperative quality of life questionnaires (RSOM-31 and SF-36) were obtained. RESULTS: All but one patient had a completely patent neostium without scar formation. No major complications occurred after this procedure. All patients reported at least an improvement of their symptoms, 50% of patients were even symptom free at one year after surgery. The median postoperative RSOM-31 score was significantly lower than the preoperative score. Both the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 score improved significantly. None of the patients needed a revision procedure. CONCLUSION: Sphenoid drill out is a safe and effective technique with a high success rate. In patients with chronic sphenoid sinusitis refractory to medical therapy and surgery it could be a valid alternative to revision sphenoidotomy.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels-A pilot study.

BACKGROUND: Administration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. OBJECTIVE: To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy. METHODS: Based on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE, we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro. RESULTS: Intranasal challenge with Bet v 1 induced increases in Bet v 1-specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen-specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab. CONCLUSION: Intranasal administration of allergen induced rises of allergen-specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels.

Multi-morbidities of allergic rhinitis in adults: European Academy of Allergy and Clinical Immunology Task Force Report.

This report has been prepared by the European Academy of Allergy and Clinical Immunology Task Force on Allergic Rhinitis (AR) comorbidities. The aim of this multidisciplinary European consensus document is to highlight the role of multimorbidities in the definition, classification, mechanisms, recommendations for diagnosis and treatment of AR, and to define the needs in this neglected area by a literature review. AR is a systemic allergic disease and is generally associated with numerous multi-morbid disorders, including asthma, eczema, food allergies, eosinophilic oesophagitis (EoE), conjunctivitis, chronic middle ear effusions, rhinosinusitis, adenoid hypertrophy, olfaction disorders, obstructive sleep apnea, disordered sleep and consequent behavioural and educational effects. This report provides up-to-date usable information to: (1) improve the knowledge and skills of allergists, so as to ultimately improve the overall quality of patient care; (2) to increase interest in this area; and (3) to present a unique contribution to the field of upper inflammatory disease.