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  • The impact of exposure to desert dust on infants’ symptoms and countermeasures to reduce the effects
    Allergy (IF 6.771) Pub Date : 2020-01-17
    Toshiko Itazawa; Kumiko T. Kanatani; Kei Hamazaki; Hidekuni Inadera; Akiko Tsuchida; Tomomi Tanaka; Takeo Nakayama; Tohshin Go; Kazunari Onishi; Yoichi Kurozawa; Yuichi Adachi;
  • Legends of Allergy and Immunology: Philip S. Norman, M.D.
    Allergy (IF 6.771) Pub Date : 2020-01-17
    Peter Socrates Creticos

    At an early age, Philip S. Norman developed a keen interest in science – first with astronomy and mathematics, then with meteorology during his military training, and subsequently with a medical career that took him from the coal fields of Kansas to his eventual tenure at Johns Hopkins. Along the way, he had stops at Kansas State Teachers College, where he studied under a noted immunologist, J. Ralph Wells, who nurtured his growing interest in research; Washington University‐St. Louis, where he graduated cum laude; internship at Barnes Hospital; internal medicine residency at Vanderbilt; fellowship at the Rockefeller Institute‐New York, where he trained under Merrill Chase; and finally, in 1956 having joined the faculty at Johns Hopkins.

  • IL33 contributes to diesel pollution‐mediated increase in experimental asthma severity
    Allergy (IF 6.771) Pub Date : 2020-01-10
    Eric B. Brandt; Paige E. Bolcas; Brandy P. Ruff; Gurjit K. Khurana Hershey

    Exposure to traffic pollution, notably diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbations. The contribution of cytokines generated by stressed lung epithelial cells (IL25, IL33, TSLP) to DEP‐induced asthma severity remains poorly understood.

  • The need for clean air: the way air pollution and climate change affect allergic rhinitis and asthma
    Allergy (IF 6.771) Pub Date : 2020-01-09
    Ibon Eguiluz‐Gracia; Alexander G. Mathioudakis; Sabine Bartel; Susanne JH Vijverberg; Elaine Fuertes; Pasquale Comberiati; Yutong Samuel Cai; Peter Valentin Tomazic; Zuzana Diamant; Jørgen Vestbo; Carmen Galan; Barbara Hoffmann

    Air pollution and climate change have a significant impact on human health and well‐being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc.), tobacco smoke and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant‐ and fungal‐derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.

  • Profilin is a marker of severity in allergic respiratory diseases
    Allergy (IF 6.771) Pub Date : 2020-01-07
    Javier Ruiz‐Hornillos; M. Angeles López‐Matas; Pilar Berges Jimeno; Aythamy Henríquez; Sandra Blanco; Marta Seoane‐Rodríguez; Ignacio Mahíllo; Jerónimo Carnés
  • Dual blockade of IL‐4 and IL‐13 with dupilumab, an IL‐4Rα antibody, is required to broadly inhibit type 2 inflammation
    Allergy (IF 6.771) Pub Date : 2020-01-03
    Audrey Le Floc’h; Jeanne Allinne; Kirsten Nagashima; George Scott; Dylan Birchard; Seblewongel Asrat; Yu Bai; Wei Keat Lim; Joel Martin; Tammy Huang; Terra B. Potocky; Jee H. Kim; Ashique Rafique; Nicholas J. Papadopoulos; Neil Stahl; George D. Yancopoulos; Andrew J. Murphy; Matthew A. Sleeman; Jamie M. Orengo
  • Medical Algorithm: Diagnosis and Treatment of Pre‐school Asthma
    Allergy (IF 6.771) Pub Date : 2020-01-03
    Andrew Bush; Sejal Saglani

    Pre‐school children frequently present with respiratory symptoms. Parents use wheeze to describe many different noises, and it is important to determine what is actually being heard; indeed, until a physician has heard wheeze, diagnostic caution is wise. A thorough history and physical examination should focus on whether the child has normal airways, but recurrent viral colds; whether an airway or other disease is present; and the nature of any airway disease. Assessment of atopy will guide the likelihood of symptoms persisting.

  • Allergy: New editorial team, innovative content and achievements after two years
    Allergy (IF 6.771) Pub Date : 2020-01-03
    Cezmi A. Akdis

    Two years have passed since our team took over Allergy, stirring it into a new direction as a World journal with a dedicated team of Editors from all continents. We opened the Davos Office of Allergy with a Managing Editor, Graphics Editor and Social Media Editor. Together with our Copenhagen, Oxford, and Manila offices, Allergy is now an international enterprise with a strong team of highly focused and motivated Editors (Table 1).

  • Genetic Variants Associated with T‐Cell Mediated Cutaneous Adverse Drug Reactions: A Prisma‐Compliant Systematic Review – an EAACI Position Paper
    Allergy (IF 6.771) Pub Date : 2020-01-03
    Abderrahim Oussalah; Vincent Yip; Cristobalina Mayorga; Miguel Blanca; Annick Barbaud; Alla Nakonechna; Josefina Cernadas; Maia Gotua; Knut Brockow; Jean‐Christoph Caubet; Andreas Bircher; Marina Atanaskovic‐Markovic; Pascal Demoly; Luciana Kase‐Tanno; Ingrid Terreehorst; José Julio Laguna; Antonino Romano; Jean‐Louis Guéant; Pirmohamed Munir;

    Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell‐mediated reactions classically occur more than 6 hours after drug administration and include life‐threatening conditions such as toxic epidermal necrolysis, Stevens‐Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA‐B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA‐compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123,548 controls) have been included in the review reporting genetic associations with carbamazepine (n=31), other aromatic antiepileptic drugs (n=24), abacavir (n=11), nevirapine (n=14), trimethoprim‐sulfamethoxazole (n=11), dapsone (n=4), allopurinol (n=10), and other drugs (n=5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.

  • The role of drug, dose, and the tolerance/intolerance of new drugs in multiple drug hypersensitivity syndrome
    Allergy (IF 6.771) Pub Date : 2020-01-01
    Lukas Jörg; Daniel Yerly; Arthur Helbling; Werner Pichler
  • Follicular T cells: from stability to failure
    Allergy (IF 6.771) Pub Date : 2019-12-28
    Rodrigo Jiménez‐Saiz; Kelly Bruton; Manel Jordana

    The germinal centre (GC) reaction is key for adaptive immunity as it drives the generation of high affinity antibodies that mediate protection against extracellular pathogens. This process entails extensive B cell proliferation, somatic hypermutation of the B cell receptor and affinity maturation. While the GC reaction provides an evolutionary advantage, its dysregulation can trigger the development of diseases such as autoimmunity, hypersensitivity and cancer. Immune regulation, such as the one exerted by regulatory T cells, is a central immunological principle aimed at maintaining homeostasis and preventing pathological responses (1). At the level of the GC, the precise role of follicular regulatory T cells (TFR) has remained elusive, and even controversial, due to limitations of the current experimental systems.

  • Laser facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation
    Allergy (IF 6.771) Pub Date : 2019-12-27
    Evgeniia Korotchenko; Raquel Moya; Sandra Scheiblhofer; Isabella A Joubert; Jutta Horejs‐Hoeck; Michael Hauser; David Calzada; Víctor Iraola; Jerónimo Carnés; Richard Weiss

    Skin‐based immunotherapy of type 1 allergies has recently been re‐investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)‐induced lung inflammation to explore the potential of laser‐facilitated epicutaneous allergen‐specific treatment.

  • Immune dysregulation increases the incidence of delayed‐type drug hypersensitivity reactions
    Allergy (IF 6.771) Pub Date : 2019-12-23
    Dean J. Naisbitt; Anna Olsson‐Brown; Andrew Gibson; Xiaoli Meng; Monday O. Ogese; Arun Tailor; Paul Thomson

    Delayed‐type, T cell–mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug‐peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity.

  • 30 years of sublingual immunotherapy
    Allergy (IF 6.771) Pub Date : 2019-12-20
    Giovanni Passalacqua; Diego Bagnasco; Giorgio Walter Canonica

    Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable “alternative” option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not “class‐related,” as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities.

  • Impaired control of the contact system in hereditary angioedema with normal C1‐inhibitor
    Allergy (IF 6.771) Pub Date : 2019-12-20
    Maria Bova; Chiara Suffritti; Valeria Bafunno; Stefania Loffredo; Giorgia Cordisco; Stefano Del Giacco; Tiziana Maria Angela De Pasquale; Davide Firinu; Maurizio Margaglione; Vincenzo Montinaro; Angelica Petraroli; Anna Radice; Luisa Brussino; Andrea Zanichelli; Alessandra Zoli; Marco Cicardi

    Hereditary angioedema (HAE) comprises HAE with C1‐inhibitor deficiency (C1‐INH‐HAE) and HAE with normal C1‐INH activity (nl‐C1‐INH‐HAE), due to mutations in factor XII (FXII‐HAE), plasminogen (PLG‐HAE), angiopoietin 1 (ANGPT1‐HAE), kininogen 1 genes (KNG1‐HAE) or angioedema of unknown origin (U‐HAE). The Italian network for C1‐INH‐HAE (ITACA) created a registry including different forms of angioedema without wheals.

  • Interleukin‐5 drives glycolysis and reactive oxygen species‐dependent citric acid cycling by eosinophils
    Allergy (IF 6.771) Pub Date : 2019-12-19
    Nicholas Jones; Emma E. Vincent; Lindsey C. Felix; James G. Cronin; Louis M. Scott; Paul S. Hole; Paige Lacy; Catherine A. Thornton

    Eosinophils have been long implicated in anti‐parasite immunity and allergic diseases and, more recently, in regulating adipose tissue homeostasis. The metabolic processes that govern eosinophils, particularly upon activation, are unknown.

  • Deserters on the atopic march: Risk factors, immune profile and clinical outcomes of food sensitized‐tolerant infants
    Allergy (IF 6.771) Pub Date : 2019-12-19
    Lawrence E.K. Gray; Anne‐Louise Ponsonby; Fiona Collier; Martin O'Hely; Peter D. Sly; Sarath Ranganathan; Mimi L.K. Tang; John B. Carlin; Richard Saffery; Peter J. Vuillermin;

    Few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized‐tolerant phenotype may inform strategies for the prevention of food allergy.

  • Nasal epithelial barrier dysfunction increases sensitization and mast cell degranulation in the absence of allergic inflammation
    Allergy (IF 6.771) Pub Date : 2019-12-18
    Inge Kortekaas Krohn; Sven F. Seys; Gitte Lund; Anne‐Charlotte Jonckheere; Isabelle Dierckx de Casterlé; Jan L. Ceuppens; Brecht Steelant; Peter W. Hellings
  • Eosinophilic esophagitis and allergic comorbidities in a US‐population‐based study
    Allergy (IF 6.771) Pub Date : 2019-12-17
    Antonella Cianferoni; Christopher M. Warren; Terri Brown‐Whitehorn; Fallon Schultz‐Matney; Anna Nowak‐Wegrzyn; Ruchi S. Gupta

    Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in the esophagus

  • CARsomes inhibit airway allergic inflammation in mice by inducing antigen specific Th2 cell apoptosis
    Allergy (IF 6.771) Pub Date : 2019-12-17
    Huan‐Ping Zhang; Ying‐Xue Sun; Zhi Lin; Gui Yang; Jiang‐Qi Liu; Li‐Hua Mo; Xiao‐Rui Geng; Yan‐Nan Song; Hao‐Tao Zeng; Miao Zhao; Guo‐Shun Li; Zhi‐Gang Liu; Ping‐Chang Yang

    Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes.

  • TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice
    Allergy (IF 6.771) Pub Date : 2019-12-12
    Galber R. Araujo; Lorenz Aglas; Emília R. Vaz; Yoan Machado; Sara Huber; Martin Himly; Albert Duschl; Luiz R. Goulart; Fatima Ferreira
  • Antibody and T cell responses against avian and microbial antigens associate with hypersensitivity pneumonitis disease parameters in pigeon breeders
    Allergy (IF 6.771) Pub Date : 2019-12-13
    Sajidah F Hasan; Agnieszka Jozwik; Adrian Heaps; Nirupma Kakkar; Iona Donnelly; Sharon Cookson; Stephen J Bourke; Charles McSharry; Stephen M Todryk

    Pigeon Fancier’s Lung (PFL) is a form of Hypersensitivity Pneumonitis where lung pathology occurs due to an immune reaction to repeated inhalation of large amounts of feather‐derived and droppings‐derived dust [1]. The 1μm dust particles penetrate the lower respiratory tract, initiating characteristic granulomatous inflammation in distal airways and alveoli. The particles, which carry pigeon antigens, cause irritation, and likely contain microbial components, both of which enhance immunogenicity.

  • “Whole” vs. “Fragmented” approach to EAACI Pollen Season Definitions: A Multicenter Study in Six Southern European Cities
    Allergy (IF 6.771) Pub Date : 2019-12-13
    TM Hoffmann; A Acar Şahin; X Aggelidis; S Arasi; A Barbalace; A Bourgoin; B Bregu; MA Brighetti; E Caeiro; S Caglayan Sozmen; L Caminiti; D Charpin; M Couto; L Delgado; A Di Rienzo Businco; C Dimier; MV Dimou; JA Fonseca; O Goksel; A Guvensen; D Hernandez; DT Jang; F Kalpaklioglu; B Lame; R Llusar; M Makris; A Mazon; E Mesonjesi; A Nieto; A Öztürk; L Pahus; G Pajno; I Panasiti; Panetta; NG Papadopoulos; E Pellegrini; S Pelosi; AM Pereira; M Pereira; NM Pinar; O Pfaar; E Potapova; A Priftanji; F Psarros; C Sackesen; I Sfika; J Suarez; M Thibaudon; A Travaglini; S Tripodi; V Verdier; V Villella; P Xepapadaki; D Yazici; PM Matricardi; S Dramburg

    The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice and outcomes assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe.

  • A critical role for c‐Myc in group 2 innate lymphoid cell activation
    Allergy (IF 6.771) Pub Date : 2019-12-13
    Longyun Ye; Jiexue Pan; Mingwei Liang; Muhammad Asghar Pasha; Xiaofei Shen; Shanti S. D'Souza; Ivan Ting Hin Fung; Yinna Wang; Gargi Patel; Dale D Tang; Qi Yang

    Asthma is a complicated chronic inflammatory disorder characterized by airway inflammation and bronchial hyperresponsiveness. Group 2 innate lymphoid cells (ILC2) are tissue‐resident innate effector cells that can mediate airway inflammation and hyperresponsiveness through production of IL‐5, IL‐13 and VEGFA. ILC2 in asthma patients exhibit an activated phenotype. However, molecular pathways that control ILC2 activation are not well understood.

  • Diagnosis and treatment of radiocontrast media hypersensitivity
    Allergy (IF 6.771) Pub Date : 2019-12-11
    Knut Brockow

    Radiocontrast media (RCM) are concentrated solutions of tri‐iodinated benzene derivatives for enhancement of radiographic contrast. Adverse reactions associated with RCM administration can either be hypersensitivity reactions, toxic reactions (e.g. generalized pruritus, heat sensation, flushing, nausea), or events unrelated to RCM exposure (e.g. spontaneous urticaria).1 Hypersensitivity reactions are classified into immediate reactions (IHR) occurring within 1 hour after RCM administration, or non‐immediate reactions (NIHR) presenting > 1 hour after exposure.

  • Interleukin 31 in insect bite hypersensitivity – Alleviating clinical symptoms by active vaccination against itch
    Allergy (IF 6.771) Pub Date : 2019-12-09
    Florian Olomski, Victoria Fettelschoss, Sigridur Jonsdottir, Katharina Birkmann, Franziska Thoms, Eliane Marti, Martin F. Bachmann, Thomas M Kündig, Antonia Fettelschoss‐Gabriel

    Insect bite hypersensitivity (IBH) is the most common seasonal pruritic allergic dermatitis of horses occurring upon insect bites. In recent years, a major role for IL‐31 in allergic pruritus of humans, monkeys, dogs and mice was acknowledged.

  • Development of the Angioedema Control Test (AECT) ‐ a patient reported outcome measure that assesses disease control in patients with recurrent angioedema
    Allergy (IF 6.771) Pub Date : 2019-12-09
    Karsten Weller, Tamara Donoso, Markus Magerl, Emel Aygören‐Pürsün, Petra Staubach, Inmaculada Martinez‐Saguer, Tomasz Hawro, Sabine Altrichter, Karoline Krause, Frank Siebenhaar, Martin Metz, Torsten Zuberbier, Denise Freier, Marcus Maurer

    Recurrent angioedema (AE) is an important clinical problem in the context of chronic urticaria (mast cell mediator‐induced), ACE‐inhibitor intake and hereditary angioedema (both bradykinin‐mediated). To help patients obtain control of their recurrent AE is a major treatment goal. However, a tool to assess control of recurrent AE is not yet available. This prompted us to develop such a tool, the Angioedema Control Test (AECT).

  • Obesity/overweight and risk of allergic rhinitis: a meta‐analysis of observational studies
    Allergy (IF 6.771) Pub Date : 2019-12-09
    Jianbo Zhou, Fuqiang Luo, Yipeng Han, Hongfei Lou, Xingyao Tang, Luo Zhang

    Obesity/overweight has been shown to be associated with an increased risk of asthma in both adults and children in several meta‐analyses.

  • Subphenotypes of NSAID‐exacerbated respiratory disease identified by latent class analysis
    Allergy (IF 6.771) Pub Date : 2019-12-05
    Natalia Celejewska‐Wójcik, Krzysztof Wójcik, Maria Ignacak‐Popiel, Adam Ćmiel, Katarzyna Tyrak, Anna Gielicz, Aleksander Kania, Paweł Nastałek, Marek Sanak, Lucyna Mastalerz

    Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID‐exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation and increased production of proinflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous.

  • The quest for ingested peanut protein in human serum
    Allergy (IF 6.771) Pub Date : 2019-12-03
    Anja Pahlow Mose, Ejvind Mortz, Per Stahl Skov, Charlotte Gotthard Mortz, Esben Eller, Ulrik Sprogøe, Torben Barington, Carsten Bindslev‐Jensen
  • Can food allergy be cured? What are the future prospects?
    Allergy (IF 6.771) Pub Date : 2019-12-03
    Vanitha Sampath, Sayantani B. Sindher, Andres M. Alvarez Pinzon, Kari C. Nadeau

    Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6%‐13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine autoinjectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food‐allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen‐specific immunotherapy, vaccines, and non–allergen‐specific therapies (eg, monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.

  • Evaluating serum periostin levels in allergic bronchopulmonary aspergillosis
    Allergy (IF 6.771) Pub Date : 2019-12-03
    Jun Tanaka, Akira Hebisawa, Tsuyoshi Oguma, Katsuyoshi Tomomatsu, Junko Suzuki, Hiroshige Shimizu, Yoshinori Kawabata, Takashi Ishiguro, Noboru Takayanagi, Soichiro Ueda, Koichi Fukunaga, Masami Taniguchi, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Koichiro Asano
  • Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population‐based sample
    Allergy (IF 6.771) Pub Date : 2019-12-02
    Annemarie G. Hirsch, Cara Nordberg, Karen Bandeen‐Roche, Bruce K. Tan, Robert P. Schleimer, Robert C. Kern, Agnes Sundaresan, Jayant M. Pinto, Thomas L. Kennedy, Joseph Scott Greene, Jordan R. Kuiper, Brian S. Schwartz
  • Therapeutic and prophylactic deletion of IL‐4Rα‐signaling ameliorates established ovalbumin induced allergic asthma
    Allergy (IF 6.771) Pub Date : 2019-11-29
    Jermaine Khumalo, Frank Kirstein, Martyna Scibiorek, Sabelo Hadebe, Frank Brombacher

    Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. IL‐4Rα‐signaling is essential for driving TH2‐type immunity to allergens. Anti‐TH2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma.

  • State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: a position paper of the European Academy of Allergy and Clinical Immunology (EAACI)
    Allergy (IF 6.771) Pub Date : 2019-11-27
    E Jensen‐Jarolim, M Bachmann, S Bonini, L Jacobsen, M Jutel, L Klimek, V Mahler, R Mösges, P Moingeon, RE O´Hehir, O Palomares, O Pfaar, H Renz, C Rhyner, F Roth‐Walter, M Rudenko, J Savolainen, C Schmidt‐Weber, C Traidl‐Hoffmann, T Kündig

    Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre‐existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is pre‐sensitized to the allergen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilised in AIT redirect the Th2 immune response toward Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three‐to‐five‐year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.

  • Tolerance mechanisms of AIT
    Allergy (IF 6.771) Pub Date : 2019-11-23
    Willem van de Veen, Mübeccel Akdis

    Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. It induces immune tolerance together with the reduction of the symptoms of asthma and allergic rhinitis patients. The common routes for the application of AIT for respiratory allergens are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). SCIT improves the symptoms of asthma and rhinitis and increase the quality of life.

  • Is allergy immunotherapy with birch sufficient to treat patients allergic to pollen of tree species of the birch homologous group?
    Allergy (IF 6.771) Pub Date : 2019-11-22
    Jörg Kleine‐Tebbe, Torsten Zuberbier, Thomas Werfel, Matthias Krüll, Martin Wagenmann, Niels Johansen, Peter Adler Würtzen, Hendrik Wolf, Victoria Mücke, Eike Wüstenberg, Tilo Biedermann

    Pollen from various Fagales tree species prolong the season and make tree pollen allergy a major health problem. Despite involving the same causative allergens, allergy immunotherapy (AIT) treatment habits differ significantly across different geographical regions. Diagnosis and treatment with AIT in patients allergic to tree pollen were discussed by a group of German medical experts who give practical recommendations based on the available data.

  • Macrophage‐derived progranulin promotes allergen‐induced airway inflammation
    Allergy (IF 6.771) Pub Date : 2019-11-22
    Jun‐Pyo Choi, So Young Park, Keun‐Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk‐Soo Kwon, Tae‐Bum Kim, Hae‐Sim Park, Hee‐Bom Moon, Woo‐Jung Song, You Sook Cho

    Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, we investigated the role of PGRN in allergic airway inflammation.

  • Towards a more precise diagnosis of hypersensitivity to beta‐lactams – an EAACI position paper
    Allergy (IF 6.771) Pub Date : 2019-11-21
    A Romano, M Atanaskovic‐Markovic, A Barbaud, AJ Bircher, K Brockow, JC Caubet, G Celik, J Cernadas, AM Chiriac, P Demoly, LH Garvey, C Mayorga, A Nakonechna, P Whitaker, MJ Torres

    A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation.

  • Cross‐reactivities of non‐homologous allergens
    Allergy (IF 6.771) Pub Date : 2019-11-20
    Merima Bublin, Heimo Breiteneder

    Allergen cross‐reactivities occur when IgE antibodies, originally raised against a specific allergen, bind to identical or highly similar surface areas of another related allergen. It is a commonly held view that cross‐reactivity requires more than 70% sequence identity, while proteins that share less than 50% sequence identity are rarely cross‐reactive. This also implies that cross‐reactive proteins have a similar 3D fold and belong to the same protein family. At first, the existence of cross‐reactivity between non‐homologous allergens was not expected because it was contrary to the above described concepts. Now, several lines of evidence demonstrate that IgE cross‐reactivity also exists between unrelated allergens. In this Editorial, we aim to summarize the existing literature on IgE cross‐reactivity between non‐homologous allergens.

  • Medical Algorithm: Diagnosis and Treatment of NSAIDs Hypersensitivity
    Allergy (IF 6.771) Pub Date : 2019-11-19
    Inmaculada Doña, Natalia Pérez‐Sánchez, Gádor Bogas, Esther Moreno, María Salas, María José Torres

    Diagnosis in suspected hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) is complex as different mechanisms are involved: specific (selective responders, SRs) and non‐specific immunologically mediated (cross‐intolerants, CIs) (1‐3) (Table 1).

  • Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study
    Allergy (IF 6.771) Pub Date : 2019-07-29
    Nicole Schoepke, Riccardo Asero, André Ellrich, Marta Ferrer, Ana Gimenez‐Arnau, Clive E. H. Grattan, Thilo Jakob, George N. Konstantinou, Ulrike Raap, Per Stahl Skov, Petra Staubach, Arno Kromminga, Ke Zhang, Carsten Bindslev‐Jensen, Alvaro Daschner, Tamar Kinaciyan, Edward F. Knol, Michael Makris, Nadine Marrouche, Peter Schmid‐Grendelmeier, Gordon Sussman, Elias Toubi, Martin K. Church, Marcus Maurer
  • Toll‐like receptor 2 stimulation augments esophageal barrier integrity
    Allergy (IF 6.771) Pub Date : 2019-07-25
    Melanie A. Ruffner, Li Song, Kelly Maurer, Lihua Shi, Margaret C. Carroll, Joshua X. Wang, Amanda B. Muir, Jonathan M. Spergel, Kathleen E. Sullivan
  • Risk of adult‐onset asthma increases with the number of allergic multimorbidities and decreases with age
    Allergy (IF 6.771) Pub Date : 2019-07-24
    Sanna Toppila‐Salmi, Sebastien Chanoine, Jussi Karjalainen, Juha Pekkanen, Jean Bousquet, Valérie Siroux
  • Regulation of Immunity and allergy by helminth parasites
    Allergy (IF 6.771) Pub Date : 2019-07-18
    Rick M. Maizels

    There is increasing interest in helminth parasite modulation of the immune system, both from the fundamental perspective of the “arms race” between host and parasite, and equally importantly, to understand if parasites offer new pathways to abate and control untoward immune responses in humans. This article reviews the epidemiological and experimental evidence for parasite down‐regulation of host immunity and immunopathology, in allergy and other immune disorders, and recent progress towards defining the mechanisms and molecular mediators which parasites exploit in order to modulate their host. Among these are novel products that interfere with epithelial cell alarmins, dendritic cell activation, macrophage function and T‐cell responsiveness through the promotion of an immunoregulatory environment. These modulatory effects assist parasites to establish and survive, while dampening immune reactivity to allergens, autoantigens and microbiome determinants.

  • Risk factors and indicators of severe systemic insect sting reactions
    Allergy (IF 6.771) Pub Date : 2019-07-16
    Johanna Stoevesandt, Gunter J. Sturm, Patrizia Bonadonna, Joanna N.G. Oude Elberink, Axel Trautmann

    Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one‐quarter of sting‐induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long‐term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta‐blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline‐directed antihypertensive treatment. The absence of urticaria/angioedema during sting‐induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom‐allergic patients. Measurement of platelet‐activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.

  • EUFOREA consensus on biologics for CRSwNP with or without asthma
    Allergy (IF 6.771) Pub Date : 2019-07-15
    Wytske J. Fokkens, Valerie Lund, Claus Bachert, Joaquim Mullol, Leif Bjermer, Jean Bousquet, Giorgio W. Canonica, Lauren Deneyer, Martin Desrosiers, Zuzana Diamant, Joseph Han, Enrico Heffler, Claire Hopkins, Roger Jankowski, Guy Joos, Andrew Knill, Jivianne Lee, Stella E. Lee, Gert Mariën, Benoit Pugin, Brent Senior, Sven F. Seys, Peter W. Hellings

    Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2‐targeting biologics such as anti‐IgE, anti‐IL4Rα, anti‐IL5, and anti‐IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways.

  • Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis
    Allergy (IF 6.771) Pub Date : 2019-07-15
    Thomas Bieber

    Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)‐driven disease. Interleukin (IL)‐4 and IL‐13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor‐associated signal transduction machinery such as Janus kinases. Recently, IL‐13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL‐4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL‐13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL‐13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD.

  • Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens
    Allergy (IF 6.771) Pub Date : 2019-07-11
    Alain Jacquet, Clive Robinson

    House dust mites (HDMs) are sources of an extensive repertoire of allergens responsible for a range of allergic conditions. Technological advances have accelerated the identification of these allergens and characterized their putative roles within HDMs. Understanding their functional bioactivities is illuminating how they interact with the immune system to cause disease and how interrelations between them are essential to maximize allergic responses. Two types of allergen bioactivity, namely proteolysis and peptidolipid/lipid binding, elicit IgE and stimulate bystander responses to unrelated allergens. Much of this influence arises from Toll‐like receptor (TLR) 4 or TLR2 signalling and, in the case of protease allergens, the activation of additional pleiotropic effectors with strong disease linkage. Of related interest is the interaction of HDM allergens with common components of the house dust matrix, through either their binding to allergens or their autonomous modulation of immune receptors. Herein, we provide a contemporary view of how proteolysis, lipid‐binding activity and interactions with polysaccharides and polysaccharide molecular recognition systems coordinate the principal responses which underlie allergy. The power of the catalytically competent group 1 HDM protease allergen component is demonstrated by a review of disclosures surrounding the efficacy of novel inhibitors produced by structure‐based design.

  • Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?
    Allergy (IF 6.771) Pub Date : 2019-07-09
    Laure Castan, Katrine L. Bøgh, Natalia Z. Maryniak, Michelle M. Epstein, Sahar Kazemi, Liam O'Mahony, Marie Bodinier, Joost J. Smit, Jolanda H. M. van Bilsen, Carine Blanchard, Robert Głogowski, Hana Kozáková, Martin Schwarzer, Mario Noti, Nicole de Wit, Grégory Bouchaud, Shanna Bastiaan‐Net

    Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory‐to‐laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.

  • Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care
    Allergy (IF 6.771) Pub Date : 2019-06-04
    Heimo Breiteneder, Zuzana Diamant, Thomas Eiwegger, Wytske J. Fokkens, Claudia Traidl‐Hoffmann, Kari Nadeau, Robyn E. O’Hehir, Liam O’Mahony, Oliver Pfaar, Maria J. Torres, De Yun Wang, Luo Zhang, Cezmi A. Akdis

    The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.

  • The challenge of de‐labeling penicillin allergy
    Allergy (IF 6.771) Pub Date : 2019-05-26
    Cosby A. Stone, Jason Trubiano, David T. Coleman, Christine R. F. Rukasin, Elizabeth J. Phillips

    Even though 8%‐25% of most populations studied globally are labeled as penicillin allergic, most diagnoses of penicillin allergy are made in childhood and relate to events that are either not allergic in nature, are low risk for immediate hypersensitivity, or are a potential true allergy that has waned over time. Penicillin allergy labels directly impact antimicrobial stewardship by leading to use of less effective and broader spectrum antimicrobials and are associated with antimicrobial resistance. They may also delay appropriate antimicrobial therapy and lead to increased risk of specific adverse healthcare outcomes. Operationalizing penicillin allergy de‐labeling into a new arm of antimicrobial stewardship programs (ASPs) has become an increasing global focus.

  • Drug‐induced IgG‐neutrophil‐mediated anaphylaxis in humans: uncovered!
    Allergy (IF 6.771) Pub Date : 2019-11-17
    Rodrigo Jiménez‐Saiz

    Seminal work by Oettgen et al.1 in the early 90's revealed the existence of alternative pathways of anaphylaxis (non IgE‐mediated) in IgE‐deficient mice. These are mediated by IgG‐immune complexes which, depending on their nature, signal on a number of myeloid cells including macrophages/monocytes, basophils, mast cells and neutrophils. While extensively characterized in mice, conclusive evidence of the existence of alternative pathways of anaphylaxis in humans have remained elusive.

  • Allergen immunotherapy for asthma: looking “Back to the Future”
    Allergy (IF 6.771) Pub Date : 2019-07-20
    Matteo Bonini, Marek Jutel

    Asthma is a heterogeneous chronic syndrome which represents a relevant socioeconomic burden in both adults and children. Global asthma prevalence has been reported to be of approximately 300 million people, with an estimate of increasing figures up to 400 million by 20251. Among the identified distinct phenotypes and endotypes2, allergic asthma represents one of the most well‐characterized and relevant nosologic entity, with atopy playing a key role in the disease risk, onset and progression.

  • Cross‐reactivity in allergy: a double‐edged sword
    Allergy (IF 6.771) Pub Date : 2019-07-19
    Anna Pomés, Véronique Schulten

    Ragweed is a plant from the Asteraceae family and a major source of pollen allergens in late summer and autumn, especially in the US and Central and Southern Europe. In the US, most Ambrosia species are native, with a prevalence of ~45% in atopic individuals. Sensitization is spreading in Europe where Ambrosia artemisiifolia (short ragweed) was imported through Hungary at the beginning of the last century.1

  • Legends in allergy‐Immunology: Lawrence M. Lichtenstein, M.D., Ph.D
    Allergy (IF 6.771) Pub Date : 2019-05-10
    David B.K. Golden

    Legends in Allergy‐Immunology have influenced us as inquirers, observers, discoverers, educators, visionaries, leaders, mentors, organizers, and collaborators. Larry Lichtenstein is a living legend because he was all of these things and more. His legacy is one of enlightenment and enthusiasm for scientific dissection of the mechanisms of the allergic response.(1) Larry's enthusiasm begat enthusiasm, and he was able to both focus and unleash the enthusiasm of his fellows and colleagues.

  • Do NERDy eosinophils accelerate nasal polyp growth?
    Allergy (IF 6.771) Pub Date : 2019-05-08
    Bruce K. Tan, De Yun Wang

    Since its description by Widal in 1922 and Max Samter in 1967, significant efforts have been made to understand the molecular underpinnings of NSAID‐exacerbated respiratory disease (NERD), which comprises the pathognomonic triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and respiratory sensitivity to NSAID ingestion.[1] An intriguing aspect of this syndrome is that it is typically acquired in adulthood and only a minority of patients with nasal polyps, asthma or both conditions has sensitivity to NSAIDs. These observations would suggest the pathogenesis is neither a germ line metabolic syndrome nor a synergistic systemic manifestation of the component respiratory ailments.

  • Legends of Allergy/Immunology: Clemens von Pirquet
    Allergy (IF 6.771) Pub Date : 2019-11-16
    Heimo Breiteneder, Petra‐Natascha Hendler, Dietrich Kraft

    Clemens Peter Freiherr (= Baron) von Pirquet (Figure 1) was born in Hirschstetten near Vienna on 12 May 1847 into a patrician family originally from Liège. His father Peter Zeno was a member of parliament. His mother Flora Freiin (= Baroness) von Pereira‐Arnstein came from an assimilated Jewish banking family but had been brought up Catholic.

  • Pollen season is reflected on symptom load for grass and birch pollen‐induced allergic rhinitis in different geographic areas ‐ an EAACI Task Force Report
    Allergy (IF 6.771) Pub Date : 2019-11-13
    O Pfaar, K Karatzas, K Bastl, U Berger, J Buters, U Darsow, P Demoly, SR Durham, C Galán, R Gehrig, R Gerth van Wijk, L Jacobsen, N Katsifarakis, L Klimek, A Saarto, M Sofiev, M Thibaudon, B Werchan, KC Bergmann

    The effectiveness of allergen immunotherapy (AIT) in seasonal and perennial allergic rhinitis (AR) depends on the definition of pollen exposure intensity or time period. We recently evaluated pollen and symptom data from Germany to examine the new definitions of the European Academy of Allergy and Clinical Immunology (EAACI) on pollen season and peak pollen period start and end. Now we aim to confirm the feasibility of these definitions to properly mirror symptom loads for grass and birch pollen‐induced allergic rhinitis in other European geographical areas such as Austria, Finland and France, and therefore their suitability for AIT and clinical praxis support.

  • Pulmonary IL‐33 orchestrates innate immune cells to mediate RSV‐evoked airway hyperreactivity and eosinophilia
    Allergy (IF 6.771) Pub Date : 2019-11-12
    Yi‐Hsiu Wu, Alan Chuan‐Ying Lai, Po‐Yu Chi, Christina Li‐Ping Thio, Wei‐Yu Chen, Ching‐Hui Tsai, Yungling Leo Lee, Nicholas W. Lukacs, Ya‐Jen Chang
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