European Academy Of Allergy And Clinical Immunology Research Articles

Definition von Pollenexpositionszeiten für klinische Studien zur Allergen-Immuntherapie bei polleninduzierter Rhinokonjunktivitis – ein EAACI-Positionspapier

Background: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. Methods: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. Results: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for “pollen season”, “high pollen season” (or “peak pollen period”) and “high pollen days”. Conclusion: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

Raising the Clinical Bar Beyond Current Biologics in Uncontrolled Persistent Asthma: Translating Emerging Data in Future Clinical Decisions

Asthma is a heterogeneous disease with multiple phenotypes, caused by a complex interplay of inflammatory pathways. Up to 70% of patients with asthma have Type 2 inflammation, characterised by the presence of interleukin (IL)-4, IL-5, and IL-13. Uncontrolled persistent asthma represents a considerable disease burden associated with a higher rate of exacerbations, more frequent hospitalisations, greater oral corticosteroid (OCS) use, more impaired lung function, reduced health-related quality of life (QoL), and Type 2 inflammatory comorbidities versus controlled asthma. There remains an unmet need for new therapies for patients with uncontrolled persistent asthma. Several agents targeting mediators of Type 2 inflammation are in clinical development for severe asthma, including prostaglandin D2 receptor 2 (DP2)/chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) antagonists and monoclonal antibodies (mAb) that specifically bind IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and IL-4 receptor (IL-4Rα). Dupilumab blocks signalling of IL-4 and IL-13 and is under investigation in various diseases driven by Type 2 inflammation. In Phase III clinical trials in patients with uncontrolled, persistent asthma, dupilumab was well tolerated and demonstrated significant efficacy versus placebo in reducing the rate of asthma exacerbations, and improving lung function, asthma symptoms, and QoL. This article summarises the proceedings of a symposium held at the European Academy of Allergy and Clinical Immunology (EAACI) 2018 Congress, which brought together an international faculty of experts to explore current understandings of asthma pathophysiology, with particular focus on Type 2 inflammatory pathways, and to provide an overview of current therapies, unmet medical needs, and the potential role of emerging biologics in the treatment of uncontrolled persistent asthma.

Towards Optimised Management of Cow’s Milk Protein Allergy

This symposium took place during the 2018 meeting of the European Academy of Allergy and Clinical Immunology (EAACI). Focussing on the fundamental issues of suboptimal management of patients with cow’s milk protein allergy (CMPA), the speakers discussed key themes for optimising management. Prof Madrazo-de la Garza evaluated the challenges of diagnosis and management of CMPA in infants. Nonspecific symptoms, indicative of other conditions, mean that CPMA is often misdiagnosed as lactose intolerance, a rare condition in infants. Increased awareness of CMPA symptoms and a clear distinction from lactose intolerance may facilitate earlier, accurate diagnosis and implementation of appropriate dietary interventions. Dr Nutten followed by exploring variability in the composition of commercialised extensively hydrolysed formulas (eHF) intended for the management of CMPA and the associated potential clinical impact. Large variations in peptide profiles and residual allergenicity reflect a lack of definition for eHF composition. Although the clinical trials required to confirm the efficacy of eHF by demonstrating tolerance in >90% of infants with CMPA are performed, composition analyses for characterisation, quality control, and reproducibility are crucial for ensuring safe and suitable products throughout the product lifecycle. Prof O’Mahony concluded the meeting by focussing on the importance of the gut microbiome in food allergy. The establishment of a stable gut microbial community closely tracks host growth and immune development. Delayed or altered establishment leads to microbiome immaturity, which has been associated with an increased risk of food allergies. Nutritional strategies, such as the use of eHF containing lactose, to support microbiome development complement existing CMPA treatment.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.

Effects of nursing intervention on bronchial asthma in children: a 10-year follow-up study

Objective To explore the importance of nursing intervention in long-term follow-up and prognosis in children with asthma. Methods A retrospective study was conducted to in 100 asthmatic children who were treated in the outpatient department of Children's Hospital of Nanjing Medical University and cooperated with nursing interventions actively. The observation period was 10 years. During the study period, patients' status at the beginning of treatment, the end of medication therapy, the 6th year of follow-up and the 10th year of follow-up were recorded. The content of the follow-up evaluation included an asthma symptom evaluation referring to the symptom score standard of the Children's Bronchial Asthma Guideline for Diagnosis and Prevention (2016 version), a rhinitis score referring to the World Allergy Organization (WAO) Guidelines and the European Academy of Allergy and Clinical Immunology (EAACI) Guidelines, a medication score referring to the scoring program of the WAO Guidelines and clinical evaluation and the number of asthma attack in the past year. SPSS 20.0 was used for data processing and analysis. Chi-square test was used to compare the enumeration data. When the data were not normal distribution or the variance was uneven, the nonparametric test of multiple correlation samples (Friedman test) was adopted for inter-group comparison. Results At the end of treatment, the 6th year of follow-up and at 10th year follow-up, the scores of asthma symptom scores were (1.70±0.68) , (0.78±0.39) and (0.70±0.58) respectively, which were all lower than that before treatment (1.80±0.70) , and the differences were statistically significant (F=79.63, P<0.01) . The differences of asthma symptom scores among the 6th year of follow-up, the 10th year of follow-up and the end of treatment were statistically significant (F=23.40, P<0.01) . The rhinitis scores at the end of treatment, the 6th year and 10th year of follow-up were all lower than that before treatment, with statistical significance (F=36.21, P<0.01) . However, there was no statistical difference in rhinitis score at the 3 time points (F=5.30, P=0.07) . The medication scores at the end of treatment, the 6th and 10th year of follow-up were all lower than that before treatment, with statistical significant (F=143.60, P<0.01) , and the differences of the 3 time points were statistically significant as well (F=96.00, P<0.01) . The acute episodes in the past year at the end of treatment, the 6th and 10th year of follow-up were all lower than that before treatment, with statistical significance (F=116.40, P<0.01) , but there was no significant difference in the 6th and 10th year of follow-up compared with the end of treatment (F=3.20, P=0.20) . Conclusions Nursing interventions significantly increases the degree of attention paid to the disease in children and their family, contributes to the long-term mitigation of bronchial asthma in children, and promotes the outcome of the disease. Key words: Child; Asthma; Nursing intervention; Long-term influence

Current state and future of pediatric allergology in Europe: A road map.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Emerging concepts and challenges in implementing the exposome paradigm in allergic diseases and asthma.

Exposome research can improve the understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the life span. The exposomic approach provides a risk profile instead of single predictors and thus is particularly applicable to allergic diseases and asthma. Under the PRACTALL collaboration between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma, and Immunology (AAAAI), we evaluated the current concepts and the unmet needs on the role of the exposome in allergic diseases and asthma.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availabilityof guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy

ABSTRACTBackground: Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. Materials and methods: In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Results: Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. Conclusion: We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

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.

EAACI guidelines on allergen immunotherapy: Prevention of allergy.

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2years post-AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials.

Editorial introductions

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Isabella Annesi-MaesanoIsabella Annesi-MaesanoIsabella Annesi-Maesano is Research Director at the French NIH (INSERM) and Professor of Environmental Epidemiology at Université Pierre and Marie Curie (UPMC) and Université Denis Diderot in Paris. Since 2006, she has headed the Department of Epidemiology of Allergic and Respiratory diseases (EPAR) at the Institute Pierre Louis of Epidemiology and Public Health of INSERM and Université Pierre and Marie Curie (UPMC) in Paris. Her research includes the explanation of the development of allergic and respiratory diseases and their comorbidities (metabolic diseases, cardiovascular diseases, neurodevelopmental troubles...) through an exposomic approach. She is presently Principal Investigator and Coordinator of the FP7-ENV Health and Environment-wide Associations based on Large Population Surveys (www.health-eu.eu). Dr Annesi-Maesano acted and still acts as a member of executive committees and programme and congresses committees of several medical societies (ERS, EAACI, IUATLD, ATS…). She held position of head and secretary of ad hoc assemblies, section and interest groups of these societies. She also contributes to international and national steering committee in the field of allergic and respiratory health. She is a respiratory epidemiologist by training through a PhD, a DSc and a post-doc (Department of Public Health Sciences at St George's Hospital, London) in Epidemiology and Public Health. She graduated in Physics (Rome) and Medicine (Paris). She is the authors of over 350 papers, reviews and chapters in peer-reviewed publications. She contributed to position papers in the frame of adverse effects of the environment on health of several medical societies (ERS, EAACI, IUATLD, ATS…). Presently, she is Associate Editor of 8 international journals and 1 national journal. Antonella CianferoniAntonella CianferoniDr Cianferoni is an ABAI certified practicing pediatric allergist with a special clinical and research interest in food allergy and eosinophilic esophagitis. She did her medical school and pediatric training at the University of Florence, Italy and completed her US training in general pediatrics at the Children's Hospital of Philadelphia and her allergy and Immunology Training at Boston Children's Hospital, having previously completed a research fellowship at the Hopkins allergy and Asthma's center. Since 2007 she has been an assistant professor of pediatrics at the University of Pennsylvania, Perelman School of Medicine, and she is an attending physician in the Allergy and Immunology division at Children's Hospital of Philadelphia (CHOP). She is the co-director of the FARE Food Allergy Center at CHOP and a member of the Center for Pediatric Eosinophilic Disorders (CPED) at CHOP. She is the secretary of the Basic And Clinical immunology Interest section for The American Academy of Allergy Asthma and Immunology (AAAAI) and a member of EoE interest group for European Academy of Allergy and Clinical Immunology (EAACI). Her research has been focused on understanding the role of invariant Natural Killer T cell, basophils and T cells in food allergy pathogenesis, genetics of Eosinophilic esophagitis and transcription of cytokine in T cells. She has also clinically characterized many classic allergic diseases such as anaphylaxis and drug and venom allergy. Gianenrico SennaGianenrico SennaDr Gianenrico Senna is Director of the Allergy Unit, Verona University and General Hospital, Italy, Referral Centre for prevention, diagnosis and treatment of allergic diseases and GA2LEN collaboration Centre. Dr Senna first specialized in Internal Medicine at Padua University, Italy and then in Allergy and Clinical Immunology at Pavia University, Italy. Since 2006 he has been Observer Consultant at Allergy & Asthma Dept, Brompton Hospital, London UK. He conducted allergy research mainly in the field of immunotherapy, clinical and therapeutics of allergic and non-allergic rhinitis, clinical and therapeutics of asthma in adults and children, safety and tolerability of antihistamines, drug allergy, hymenoptera venom allergy and molecular allergy. He has extensively published in international journals and he also acts as a referee of many allergy journals. He is Past-President of AAITO, Italian Association of Allergists and Clinical Immunologists, and a member of the Executive Committee of Italian Federation of Allergy and Immunology Societies. Currently he serves as Vice President of SIAAIC, Italian Society of Allergy and Clinical Immunology, he is a member of the board of the Immunotherapy Interest Group of European Academy of Allergy and Clinical Immunology (EAACI). He is adjunct Professor of allergy and clinical immunology at the Rheumatology School of Specialization, University of Verona, Italy. Mariana CastellsMariana CastellsDr Castells is a clinician, researcher and teacher at Brigham and Women's Hospital and Dana Farber Cancer Institute. She is the Director of the Drug Hypersensitivity and Drug Desensitization Center, as well as the Director of the Mastocytosis Center and has served as the Allergy and Immunology Training Program Director for 15 years. She serves on the Board of Directors of the AAAAI and of the International College of Allergy (CIA) and has directed the International Drug Desensitization Meeting (DDIM) in Barcelona, Spain for the last 5 years. She has spearheaded the evaluation and understanding of drug anaphylaxis and hypersensitivity and provided new desensitization protocols which are used as standards around the world, treating thousands of patients with cancer and chronic inflammatory diseases, maintaining these patients on their first line therapy. Her research has uncovered mast cell inhibitory mechanisms which are pertinent to desensitization. She has been involved in the new diagnostic criteria for mast cell activation disease and mastocytosis and, with Dr Cem Akin, created the Mastocytosis Center. Leonard BieloryLeonard BieloryDr Bielory attended Lehigh University in Bethlehem, Pennsylvania, USA, where he completed his BS in Engineering (Fundamental Science) and a Masters in Molecular Biology (1976). He went on to acquire an MD degree from Rutgers University (previously UMDNJ) - New Jersey Medical School, USA, (1976–1980), before undertaking his internal medicine training at the University of Maryland Hospital, USA; and then his subspecialty training in allergy and immunology and diagnostic laboratory immunology at the National Institutes of Health (NIH), USA, as a medical staff fellow in the – National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) where his research focus has been on the classic immune complex disorder – serum sickness. He was recruited back to his alma mater to direct the Division of Allergy and Immunology at the Rutgers University (previously UMDNJ) - New Jersey Medical School where he has been for 25 years as Professor of Medicine, Pediatrics and Ophthalmology and directed the only training program in Allergy and Immunology in the State of New Jersey for 20 years. He is presently appointed as a research professor to the Rutgers University Center of Environmental Prediction. He has consistently been selected as one of the New Jersey and New York “Top Docs” in the New Jersey and New York metropolitan area surveys over the past 20 years. He has published several hundred publications in peer-reviewed journals, presently serves as an associate editor of the Annals of Allergy, Asthma and Immunology, serves on several other editorial boards and as a reviewer for multiple journals. He continues to serve in various capacities in a variety of national organizations including as a member of the Board of Directors for the American College of Allergy, Asthma and Immunology (ACAAI), multiple committee chairs for various committees in the American Academy of Allergy, Asthma and Immunology (AAAAI) and ACAAI, World Allergy Organization, past Chairman of the NIH – National Heart, Lung and Blood Institute Raynaud's Treatment Trial; the program Chairman for the ACAAI International Symposium on Complementary Interventions in Treatment of Asthma and Allergy and reviewer for the NIH National Center for Complementary and Alternative Medicine Centers (NCCAM) of Excellence for Research on Complementary and Alternative Medicine (CERC). He has been appointed by the Governor of New Jersey to sit on the Clean Air Council advisory to the New Jersey Department of Environmental Protection and is presently its Chair of the recent annual public hearing on Climate Change. Dr Bielory has participated on two United States Pharmacopoeia (USP) Council of Experts Committees (Immunology as well as Respiratory and Allergy). He was an original member of the USP Medicare Model Formulary Committee mandated by the United Stated Congress. He is an international expert in inflammatory disorders of the anterior portion of the eye – especially various forms of ocular allergy and is a regional expert on pollen and climate change. He has successfully completed over 50 clinical research studies in asthma and allergic disorders. Active research focuses on new immune treatments for asthma and a rare disorder known as hereditary angioedema. He has recently been awarded an US Environmental Protection Agency grant as the Principal Investigator focusing on Climate and Allergic Airway Disease that has supported the March 2011 publication in Proceedings of the National Academy of Sciences on Climate Change and Ragweed Pollination with several other publications on climate change under review. Abraham SolomonAbraham SolomonAbraham (Avi) Solomon is an associate professor of Ophthalmology at the Department of Ophthalmology at Hadassah-Hebrew University Medical Center, Jerusalem, Israel. He was born in Tel-Aviv, Israel, and completed his MD degree at the University of Tel-Aviv School of Medicine. He performed his residency in Ophthalmology at the Department of Ophthalmology at Hadassah-Hebrew University Medical Center (1992–1997), followed by a fellowship in Cornea and External Eye Disease at Bascom Palmer Eye Institute, in Miami Florida (1998–2001). Prof. Solomon has published 90 articles and reviews in peer-reviewed journals. Prof. Solomon is currently the Head of the Cornea Service at the Department of Ophthalmology at Hadassah-Hebrew University Medical Center, Jerusalem, Israel. He served as the Chairman of the Department of Optometry, Hadassah College Jerusalem (2003–2007); the head of the Teaching Program in Ophthalmology, the Hadassah-Hebrew University Faculty of Medicine (2007–2010); the chairman of the Israeli Cornea Society (2010–2012); and until recently as the Chairman of the Israeli Society for Vision and Eye Research (ISVER), which is an ARVO chapter affiliate (2012–2015). Prof. Solomon's main clinical expertise is in the area of cornea and external eye diseases and refractive surgery. His main clinical and basic research interests are in the areas of ocular surface diseases and ocular surface reconstructive surgery, limbal stem cell deficiency, ocular surface inflammation and anti-inflammatory drug research, ocular allergic eye diseases and topical anti-allergic drug research.

Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high-risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy. Overall, the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high-risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy.

Future of the Allergists and Allergen Specific Immunotherapy (FASIT) Meets EACCI

The symposium provided a flavour of key presentations and issues discussed at the 2017 Future of the Allergists and Allergen Specific Immunotherapy (FASIT) workshop held in Hamburg, Germany. Prof Wahn explained that the FASIT meeting brought together basic scientists, clinicians, and practitioners to brainstorm issues around allergy. Prof Jutel considered FASIT presentations exploring how precision medicine can be used to select optimal patients for allergen immunotherapy (AIT). He outlined the role of phenotypes and endotypes, reviewed some biomarkers that are currently under validation, and considered the role of adjuvants. Prof Kleine-Tebbe considered a number of promising Phase II studies that have failed to be translated into successful Phase III studies. Factors influencing results, he said, include high placebo effects, natural variability of the environment, patient heterogeneity, and the use of different endpoints for Phase II and III trials. Prof Pfaar considered whether allergen exposure chambers (AEC) are at a stage to be used for Phase III (pivotal) trials in AIT. He provided an overview of the history and advantages behind these facilities and reported the regulatory view. Prof Pfaar reported a recently published Position Paper from the European Academy of Allergy and Clinical Immunology (EAACI) addressing the current status of allergen chambers and setting the ‘frame’ for further developments, such as clinical validation. The position paper included the views of all relevant stakeholders, including clinicians, chamber operators, and regulators. In the second part of his talk, Prof Pfaar reviewed the introduction of paediatric investigation plans (PIP), which are required for allergen products prior to receiving marketing authorisation and considered the methodological problems for fulfilling these regulatory demands. Finally, Prof Pfaar called for further consultation and collaboration between all parties involved in AIT regarding possible improvement of PIP. Prof Kuna highlighted the European Union (EU) Directive 2001/83EC, which threatens both allergy diagnostics and the entire discipline of allergology. The directive states that allergens should be considered as drugs, and makes no distinction between allergens used for therapeutic procedures and those used for diagnostic purposes. The cost of obtaining and keeping marketing authorisations for test allergens is expensive. Already there are signs that allergen testing has been reduced in Europe. Prof Kuna concluded that it is essential for all stakeholders (authorities, allergists’ societies like the EAACI, the European Medicines Agency (EMA), European legislators, and allergen manufacturers) to come together to ensure the continued availability of in vivo allergen diagnostic tests in the EU.

Education Is Key! Call for Action!

I have been asked to share my opinion about the diagnostics of anaphylaxis and how to treat it. As you probably know, anaphylaxis is the extreme outing of an allergic reaction and is likely if any one of three criteria is fulfilled (Figure 1).1 Assessing anaphylaxis is hard to do because you must first assess or establish the eliciting condition. The European Academy of Allergy and Clinical Immunology (EAACI) has produced guidelines for allergic conditions to help clinicians establish the correct diagnosis and treatment for that condition.2 Although anaphylaxis may occur with different allergic conditions, one of the major eliciting factors for anaphylaxis is food, and food has been the main immunoglobulin (Ig)E-mediated cause for anaphylaxis hospitalisation in recent years.1,3 These guidelines are instrumental in the education of anyone dealing with patients at risk of anaphylaxis.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis.

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR)=0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR=0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future – an EAACI Position Paper

Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Modulation of allergy risk by breast feeding.

Breastfeeding has been suggested as a candidate for primary prevention of allergies. However, recent comprehensive and thoughtfully written systematic reviews reported mixed results and that overall there is only little evidence for breastfeeding being protective against allergic disorders. As these reviews last searched for relevant studies on 2 October 2014, the aim of our review is to shed light on the association between breastfeeding and allergic disorders (asthma, eczema, allergic rhinitis) recently published. These recent studies are varied and differ in size, settings, design, depth of data collecting, and quality of the study. Thus far, the results on the association between nonexclusive and exclusive breastfeeding with regards to asthma are mixed especially in young ages. Additionally, if eczema and allergic rhinitis are the outcomes of interest, this recent review does not provide a clearer picture. The current guidelines by WHO and European Academy of Allergy and Clinical Immunology (EAACI) on breastfeeding till 6 months and exclusively breastfeeding for 4-6 months, respectively, for the prevention of allergies are not supported by the recent study results. Nevertheless, breastfeeding should be strongly recommended for other beneficial health effects than allergy prevention.