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Background: Food allergy is common in childhood with some children having a low threshold and being difficult to protect from accidental ingestion of the offending food. Therapies for this potentially life-threatening condition are highly needed. The aim of this study was to evaluate the efficacy of Omalizumab in food-allergic children., Methods: This is a single-center, double-blind, placebo-controlled study. Food allergic children with a cumulative threshold ≤443 mg food protein at DBPCFC were randomized to Omalizumab (asthma dose) or placebo (3:1). After 3 months, a second DBPCFC was performed (steps 3, 10, 30, 100, 300, 1000, and 3000 mg food protein), followed by a separate open challenge up to 10,000 and 30,000 mg food protein if negative. Responders were defined as ≥2-step increases in threshold. Non-responders received high-dose Omalizumab. A third DBPCFC was performed after 6 months. Skin testing, blood samples, and the severity of atopic co-morbidity were registered during the study and 3 months after treatment., Results: In total, 20 children were evaluated at 3 months (14 Omalizumab, 6 placebo). All treated with Omalizumab increased their threshold at least two steps and with a significant difference between the Omalizumab and the placebo group (p = .003), although the intended number of included children was not reached. The threshold before Omalizumab treatment was 13-443 mg food protein while the threshold after 3 months of treatment increased up to 44,000 mg (1143-44,000). In the placebo group, two children improved threshold during the study., Conclusion: An increase in the threshold level during Omalizumab treatment significantly improve patient safety and protected all children against small amount of allergen., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Exacerbations of asthma are thought to be strongly dependent on reactivation of allergen-induced lung tissue-resident and circulatory memory CD4 T cells. Strategies that broadly inhibit multiple T cell populations might then be useful to limit asthma. Accordingly, we tested whether targeting CD3 during exposure to inhaled allergen could prevent the accumulation of lung-localized effector memory CD4 T cells and block exacerbations of asthmatic inflammation., Methods: House dust mite-sensitized and repetitively challenged BL/6 mice were transiently treated therapeutically with F(ab')2 anti-CD3ε and memory T cell responses and lung inflammation were assessed. PBMCs from HDM-allergic donors were examined for the effect of anti-CD3 on expansion of allergen-reactive T cells., Results: Allergen-sensitized mice undergoing exacerbations of asthma were protected from lung inflammation by transient therapeutic treatment with F(ab')2 anti-CD3. Regardless of whether sensitized mice underwent a secondary or tertiary recall response to inhaled allergen, anti-CD3 inhibited all phenotypes of effector memory CD4 T cells in the lung tissue and lung vasculature by 80%-90%, including those derived from tissue-resident and circulatory memory T cells. This did not depend on Treg cells suggesting it was primarily a blocking effect on memory T cell signaling. Correspondingly, anti-CD3 also strongly inhibited proliferation of human allergen-reactive memory CD4 T cells from allergic individuals. In contrast, the number of surviving tissue-resident memory CD4 T cells that were maintained in the lungs at later times was not robustly reduced by anti-CD3., Conclusion: Anti-CD3 F(ab')2 administration at the time of allergen exposure represents a viable strategy for limiting the immediate activity of allergen-responding memory T cells and asthma exacerbations., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Recent studies pointed to a crucial role for apolipoproteins in the pathogenesis of inflammatory diseases. However, the role of apolipoprotein-IV (ApoA-IV) in allergic inflammation has not been addressed thoroughly thus far., Objective: Here, we explored the anti-inflammatory effects and underlying signaling pathways of ApoA-IV on eosinophil effector function in vitro and in vivo., Methods: Migratory responsiveness, Ca 2+ -flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen-driven airway inflammation was assessed in a mouse model of acute house dust mite-induced asthma. ApoA-IV serum levels were determined by ELISA., Results: Recombinant ApoA-IV potently inhibited eosinophil responsiveness in vitro as measured by Ca 2+ -flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev-ErbA-α and induced a PI3K/PDK1/PKA-dependent signaling cascade. Systemic application of ApoA-IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA-IV levels were decreased in serum from allergic patients compared to healthy controls., Conclusion: Our data suggest that ApoA-IV is an endogenous anti-inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA-IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil-driven disorders., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Background: The mechanisms of work-related asthma (WRA) are incompletely delineated. Nasal cell samples may be informative about processes in the lower airways. Our aim was to determine the nasal protein expression profiles of WRA caused by different kind of exposures., Methods: We collected nasal brush samples from 82 nonsmoking participants, including healthy controls and WRA patients exposed to (i) protein allergens, (ii) isocyanates and (iii) welding fumes the day after relevant exposure. The proteome changes in samples were analysed by two-dimensional difference gel electrophoresis, and the differentially regulated proteins found were identified by mass spectrometry. Immunological comparison was carried out using Western blot., Results: We detected an average of 2500 spots per protein gel. Altogether, 228 protein spots were chosen for identification, yielding 77 different proteins. Compared to the controls, exposure to protein allergens had the largest effects on the proteome. Hierarchical clustering revealed that protein allergen- and isocyanate-related asthma had similar profiles, whereas asthma related to welding fumes differed. The highly overrepresented functional categories in the asthma groups were defence response, protease inhibitor activity, inflammatory and calcium signalling, complement activation and cellular response to oxidative stress. Immunological analysis confirmed the found abundance differences in galectin 10 and protein S100-A9 between the groups., Conclusions: Work-related asthma patients exposed to protein allergens and isocyanates elicit similar nasal proteome responses and the profiles of welders and healthy controls were alike. Revealed biological activities of the protein expression changes are associated with allergic inflammation and asthma., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Allergens in food may pose a risk to allergic consumers. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary allergen labels to inform allergic individuals of a potential risk from UAPs. This study investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut- and peanut-allergic populations when ingesting UK foods across multiple product categories with and without precautionary allergen labelling., Methods: Allergen risk assessment using probabilistic techniques enables the estimation of the residual risk after the consumption of a product that unintentionally contains an allergen., Results: Within this selection of UK products, the majority that tested positive for an allergen contained a concentration of allergen predicted to cause a reaction in >1% of the allergic population. The concentrations of allergens measured were greater than the VITAL(®) 2.0 action levels and would trigger precautionary allergen labelling. This was found for products both with and without precautionary allergen labelling., Conclusions: The results highlight the need for the food industry and regulators to adopt a transparent, risk-based approach for the communication of the risk associated with potential cross-contact that could occur in the processing facility or production chain., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization)., Methods: Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables., Results: A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5., Conclusions: These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with/without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma., Methods: Data from randomized, double-blind, placebo-controlled trials of Timothy grass SLIT-tablet MK-7243 (2800 BAU/75 000 SQ-T, Merck/ALK-Abelló) were pooled for post hoc analyses. Subjects with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment-emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma-related treatment-related AEs (TRAEs) were calculated., Results: Among adults (n = 3314) and children (n = 881), 24% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT-tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children with asthma treated with grass SLIT-tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma-related TRAEs assessed as severe with grass SLIT-tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively)., Conclusions: In the AR/C subjects with reported well-controlled mild asthma included in these studies, grass SLIT-tablet did not increase TEAE frequency, severe local allergic swelling, or systemic allergic reactions versus subjects without asthma. There was no indication that treatment led to acute asthma worsening., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sensitization to food allergens indicates the production of food-specific IgE; however, sensitization is not a definite indicator of allergic reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol, 120, 2007, 491). Currently, food challenge is the best approach to identify the presence or absence of allergy. While 95% positive predictive values (PPVs) thresholds for sIgE can assist with identifying increased likelihood of allergy among those who are sensitized, there are no specific biological markers that differentiate between allergic and sensitized individuals., Objectives: To determine whether plasma serum cytokine profiles predict (i) sensitization to peanut and egg and (ii) food allergy among sensitized infants., Methods: Peanut-sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized controls enrolled in HealthNuts, a population-based study of food allergy, underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC. Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by multiplex assay., Results: Food-sensitized infants had significantly higher plasma IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants. IL-10 and IL-6 levels were significantly higher in sensitized compared with allergic infants. Egg-allergic infants had significantly higher IL-13 and IL-12p70 levels compared to peanut-allergic (PA) infants., Conclusion: Levels of Th2-related cytokines in plasma are higher in food-sensitized infants, irrespective of clinical food allergy status. In contrast, IL-10 levels appear to predict food allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg- and peanut-allergic infants could help explain the different resolution rates of the allergies., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This placebo-controlled study assessed the effects of the once-daily inhaled corticosteroid (ICS) fluticasone furoate (FF) and long-acting beta(2) -agonist (LABA) vilanterol (VI) on early and late asthmatic responses (EAR/LAR) and airway hyper-responsiveness (AHR)., Methods: Patients (n = 27) were randomized to FF (100 μg), VI (25 μg), FF/VI (100/25 μg), and placebo for 21 days (four periods). Allergen challenge was performed 1 h post-dose on day 21. AHR was assessed on day 22 using methacholine., Results: Allergen challenge caused an early change (0-2 h) in minimum forced expiratory volume in 1 s (FEV(1)) of -1.091 l (95% CI: -1.344; -0.837) following placebo therapy; changes were -0.955 l (-1.209; -0.702), -0.826 l (-1.070; -0.581), and -0.614 l (-0.858; -0.370) following VI, FF, or FF/VI therapy, respectively. Treatment differences were significant for all comparisons between therapies. Mean changes in 0-2 h %FEV(1) were as follows: -28.05 (placebo), -23.10 (VI), -22.33 (FF), and -16.10 (FF/VI). Following placebo, the late change (4-10 h) in weighted mean FEV(1) was -0.466 l (-0.589; -0.343) and -0.298 l (-0.415; -0.181) after VI, and was +0.018 l with both FF/VI (-0.089; 0.124) and FF (-0.089; 0.125). Treatment differences were significant for all comparisons between therapies except FF/VI vs FF. Mean changes in 4-10 h %FEV(1) were as follows: -21.08 (placebo), -14.30 (VI), -5.02 (FF), and -5.83 (FF/VI). AHR 24 h after allergen challenge was significantly reduced with FF/VI and FF vs placebo, and FF/VI was superior to either component., Conclusion: Combined treatment with FF/VI provides additive protection from the EAR relative to its components, significant protection over VI alone from the LAR, and confers sustained protection from hyper-responsiveness 24 h post-dose., (© 2013 The Authors. Allergy published by John Wiley & Sons Ltd.)

Background: Patients allergic to pollen have been known to become more symptomatic during pollen season compared with the nonpollen season. However, there are few studies regarding whether higher exposure to pollen might increase the prevalence of allergic diseases., Methods: An ecological analysis was conducted to evaluate whether pollen exposure is associated with the prevalence of allergic diseases in schoolchildren. Pollen count data of Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), which are the major pollen allergens in Japan, were obtained from each prefecture. The prevalence of allergic diseases in schoolchildren in each prefecture was based on a nationwide cross-sectional survey using the International Study of Asthma and Allergies in Childhood questionnaire., Results: After omitting three prefectures where pollen data were not available, data of 44 prefectures were analysed. The prevalence of allergic rhinoconjunctivitis in children aged 6-7 years was positively associated with both cedar and cypress pollen counts (P = 0.01, both), whereas the prevalence of allergic rhinoconjunctivitis in children aged 13-14 years was positively associated with only cypress pollen counts (P = 0.003). Furthermore, the prevalence of asthma was positively associated with cedar pollen counts in 6- to 7-year-old children (P = 0.003) but not cypress pollen counts in either age group., Conclusions: There are ecological associations between pollen counts and the prevalence of allergic diseases in Japanese schoolchildren. Further studies are needed to determine whether the difference between the effects of cedar and cypress pollens is attributable to pollen counts or allergenicity., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Airway epithelial cells are the first to encounter aeroallergens and therefore have recently become an interesting target of many studies investigating their involvement in the modulation of allergic inflammatory responses. Disruption of a passive structural barrier composed of epithelial cells by intrinsic proteolytic activity of allergens may facilitate allergen penetration into local tissues and additionally affect chronic and ongoing inflammatory processes in respiratory tissues. Furthermore, the ability of rhinoviruses to disrupt and interfere with epithelial tight junctions may alter the barrier integrity and enable a passive passage of inhaled allergens through the airway epithelium. On the other hand, epithelial cells are no longer considered to act only as a physical barrier toward inhaled allergens, but also to actively contribute to airway inflammation by detecting and responding to environmental factors. Epithelial cells can produce mediators, which may affect the recruitment and activation of more specialized immune cells to the local tissue and also create a microenvironment in which these activated immune cells may function and propagate the inflammatory processes. This review presents the dual role of epithelium acting as a passive and active barrier when encountering an inhaled allergen and how this double role contributes to the start of local immune responses., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

The immune system is regulated to protect the host from exaggerated stimulatory signals establishing a state of tolerance in healthy individuals. The disequilibrium in immune regulatory vs effector mechanisms results in allergic or autoimmune disorders in genetically predisposed subjects under certain environmental conditions. As demonstrated in allergen-specific immunotherapy and in the healthy immune response to high-dose allergen exposure models in humans, T regulatory cells are essential in the suppression of Th2-mediated inflammation, maintenance of immune tolerance, induction of the two suppressive cytokines interleukin-10 and transforming growth factor-β, inhibition of allergen-specific IgE, and enhancement of IgG4 and IgA. Also, suppression of dendritic cells, mast cells, and eosinophils contributes to the construction of peripheral tolerance to allergens. This review focuses on mechanisms of peripheral tolerance to allergens with special emphasis on recent developments in the area of immune regulation., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: Alcohol, exercise or non-steroidal anti-inflamatory drugs (NSAID) are frequently mentioned as amplifiers of food allergic reactions but only individual cases or small series have been previously published., Methods: Descriptive study including 74 cases of suspected co-factor enhanced food allergy, assessed by skin-prick tests, specific IgE and oral challenges., Results: Anaphylaxis accounted for 85.1% of reactions. In 99% of cases culprit food allergens were plant-derived, mainly vegetables and cereals. NSAID were involved in 58%, exercise in 52.7% and alcohol in 12.2%. Lipid transfer protein was the most frequently involved allergen., Conclusions: Co-factor enhanced food allergy should be considered when assessing food, alcohol, exercise and NSAID allergic reactions., (© 2012 John Wiley & Sons A/S.)

Background: Evidence demonstrates the existence of local allergic rhinitis (LAR) in nonatopic patients, although its prevalence in the rhinitis population remains unknown. The aim, therefore, of this study was to evaluate the prevalence, clinical characteristics, and severity of LAR in a Spanish rhinitis population, compared with patients having classical allergic rhinitis (AR) with systemic atopy or nonallergic rhinitis (NAR)., Methods: A group of 452 adult rhinitis patients were randomly selected from a total of 3860 who attended our allergy service over 1 year. A clinical questionnaire, skin prick test (SPT), spirometry, and serum total and specific IgE (sIgE) were evaluated. A nasal allergen provocation test with multiple aeroallergens (NAPT-M), including Dermatophagoides pteronyssinus, pollens, alternaria, and dog epithelia, was performed in patients with negative SPT and serum sIgE., Results: A total of 428 patients completed the study; 24 were excluded because of nasal hyper-reactivity. LAR was diagnosed in 25.7%, AR in 63.1%, and NAR in 11.2%. The LAR and AR patients had a similar clinical profile: a nonsmoking woman with severe, persistent perennial rhinitis frequently associated with conjunctivitis and asthma. More than 36% of LAR patients reported rhinitis onset in childhood. NAPT-M detected aeroallergen polysensitization in 37.3% of the LAR patients. Dermatophagoides pteronyssinus was the main sensitizing aeroallergen in LAR and AR (60% vs 54%, P > 0.05)., Conclusions: Local allergic rhinitis is a prevalent entity in patients evaluated with rhinitis. Persistent and severe symptoms associated with conjunctivitis and/or asthma and polysensitization were likely to be detected in LAR and AR., (© 2012 John Wiley & Sons A/S.)

Background: The aim of this study was to determine the safety of sublingual immunotherapy in pregnancy, which has not yet been reported., Methods: One hundred and fifty-five patients received sublingual immunotherapy with either house dust mite (D. farinae) or a mixture of up to five allergens during 185 pregnancies. Twenty-four patients received sublingual immunotherapy for the first time during pregnancy. Follow-up data were analysed with regard to abortion, perinatal mortality, prematurity, toxaemia and congenital malformation. Two control groups did not receive immunotherapy; group A (85 patients) received budesonide 400 μg twice daily and group B (40 patients) received rescue salbutamol inhalation. All three groups were on appropriate avoidance measures., Results: Six-year follow-up data for the sublingual immunotherapy group revealed an incidence of complications less than that in the general population and a higher incidence of complications in both control groups., Conclusions: This study concludes that sublingual immunotherapy is safe during pregnancy and is also safe when initiated for the first time in a pregnant patient., (© 2012 John Wiley & Sons A/S.)

Background: Anaphylaxis is the most severe manifestation of an IgE-dependent allergy. Standardized acquired clinical data from large cohorts of well-defined cases are not available. The aim of this study was to analyse the symptom profile and risk factors of anaphylaxis in a large Central European cohort., Methods: We acquired data from patients in Germany, Austria and Switzerland who experienced a severe allergic reaction defined by the onset of severe pulmonary and/or severe cardiovascular symptoms. The data were gained via an online questionnaire from 83 medical centres specialized in allergy. Data were collected from 2006 to 2010 and analysed by using a multinomial regression model., Results: A total of 2012 paediatric and adult patients were included into the present analysis. The skin (84%) was the most frequently affected organ followed by the cardiovascular (72%) and the respiratory (68%) system. The regression model analysing the onset of cardiovascular versus respiratory symptoms revealed a strong impact of age (adjusted OR = 6.08; 95% CI, 3.35-11.01; P < 0.001). Furthermore, the elicitor food (adjusted OR = 0.29; 95% CI, 0.21-0.41, P < 0.001) and the presence of atopic diseases (adjusted OR = 0.54; 95% CI, 0.40-0.73, P < 0.001) were significantly associated with the onset of respiratory symptoms., Conclusion: Data from individuals who experienced anaphylaxis can support the identification of risk factors. The present study indicates that age, the elicitor itself and the presence of atopic diseases have an impact on the symptom profile of anaphylaxis. Identifying further risk factors of anaphylaxis is of significant importance for clinical practice in the future., (© 2012 John Wiley & Sons A/S.)

Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 40-75% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further., (© 2011 John Wiley & Sons A/S.)

Background: The assessment of allergen immunotherapy (AIT) efficacy in the treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms., Methods: Study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high tertiles). The difference observed in the average score in each tertile in active vs placebo-treated patients was assessed. This allowed an estimation of the efficacy that could be achieved in patients from sites where symptoms were high during the pollen season., Results: An increased treatment effect was observed in the most severe patients and was independent of the study analysed and symptom score used., Conclusions: The use of a tertile approach to analyse efficacy in AIT in SAR clinical studies can give a more accurate assessment of potential clinical benefit., (© 2011 John Wiley & Sons A/S.)

Background: Food allergy may present with a plethora of gastrointestinal and extraintestinal symptoms such as abdominal pain, diarrhea, cardiocirculatory symptoms, cutaneous reactions, or rhinitis. Macropathological lesions like lymphofollicular hyperplasia and erosive or ulcerative lesions have seldom been described in gastroscopy and colonoscopy previously., Methods: Fifteen patients presenting with unspecific abdominal symptoms in which food allergy was detected in due course were included. During the examination process, those patients showed various indications for small-bowel capsule endoscopy, such as weight loss and anemia., Results: Fourteen (93.3%) of the 15 small-bowel capsule endoscopies could be assessed, showing nonerosive lesions such as erythema, swelling, and lymphoid hyperplasia in 8 patients (57.1%) and erosive lesions such as aphthoid lesions, erosions, and petechiae in 4 patients (28.6%) with food allergy., Conclusion: In 15 patients with confirmed food allergy and after exclusion of other diseases, 12 (85.7%) showed various unspecific nonerosive or erosive mucosal lesions within the small bowel, resulting, however, partially in grave consequences such as anemia. Lymphoid hyperplasia was the most prominent finding in 7 patients (50%), albeit infectious disease had been excluded. Anemia improved within 1 year after adequate antiallergic treatment., (© 2011 John Wiley & Sons A/S.)

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries., (© 2011 John Wiley & Sons A/S.)

Background: Kiwifruit is an important cause of food allergy. A high amount of a protein with a molecular mass compatible with that of Bet v 1 was observed in the kiwifruit extract., Objective: To identify and characterize kirola, the 17-kDa protein of green kiwifruit (Act d 11)., Methods: Act d 11 was purified from green kiwifruit. Its primary structure was obtained by direct protein sequencing. The IgE binding was investigated by skin testing, immunoblotting, inhibition tests, and detection by the ISAC microarray in an Italian cohort and in selected Bet v 1-sensitized Austrian patients. A clinical evaluation of kiwi allergy was carried out., Results: Act d 11 was identified as a member of the major latex protein/ripening-related protein (MLP/RRP) family. IgE binding to Act d 11 was shown by all the applied testing. Patients tested positive for Act d 11 and reporting symptoms on kiwifruit exposure were found within the Bet v 1-positive subset rather than within the population selected for highly reliable history of allergic reactions to kiwifruit. Epidemiology of Act d 11 IgE reactivity was documented in the two cohorts. IgE co-recognition of Act d 11 within the Bet v 1-like molecules is documented using the microarray IgE inhibition assay., Conclusions: Act d 11 is the first member of the MLP/RRP protein family to be described as an allergen. It displays IgE co-recognition with allergens belonging to the PR-10 family, including Bet v 1., (© 2011 John Wiley & Sons A/S.)

Background: Avoidance of occupational allergens or reduction in exposure has been advocated as the mainstay of the management of occupational rhinitis. Sparse data to the effect of allergen avoidance are available., Objective: To identify factors that may lead to leaving work and to address the effect of subsequent allergen avoidance on quality of life., Methods: A survey to the prevalence of occupational allergy to bell pepper performed in 1999 comprised 472 employees, of which 254 had work-related rhinitis and 228 completed the Rhinitis-related Quality of Life Questionnaire. After 8-year follow-up in 2007, 91 workers with rhinitis in 1999 were available to fill out the questionnaire again and were used to evaluate the course of nasal disease in terms of perceived severity and impact on daily life., Results: Workers with rhinitis at baseline were more likely to leave their job in bell pepper cultivation for another job (OR = 1.62, 95% CI 0.95-2.75). Among the 91 workers, 58 subjects were still at work, whereas 33 subjects had left work. The subjects who left jobs reported substantial improvement in quality of life. The magnitude of the changes ranged from -0.31 to -1. The effect of quitting work on the mean quality of life score amounted -0.76 ± 0.15., Conclusions: The current study is the first large longitudinal studies showing that leaving work and subsequent occupational allergen avoidance have a beneficial effect on rhinitis-related quality of life. The study suggests that occupational rhinitis can be a reason to leave work., (© 2011 John Wiley & Sons A/S.)

Background: Multinational time-trend analyses of atopic disease have shown that the East-West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy and atopic diseases in Finnish and Russian Karelia during the past 10 years have diminished and how the prevalence of atopy has evolved with successive years of birth., Methods: Two surveys with identical methodology were performed in 1997/1998 and 2007. The study population comprised randomly selected adults, aged 25-54 years, from Finnish and Russian Karelia. Serum samples were collected for total and specific IgE measurements. Clinical data were obtained by questionnaires., Results: Sensitization rates to birch pollen increased from 7.8% to 14.8% (P < 0.001) and to cat from 6.1% to 10.8% (P < 0.001) in Finland. In Russia, no significant increase was found. Contrary to this, total IgE remained stable in Finland but decreased significantly (P < 0.001) in Russia. Analyses based on years of birth revealed that the prevalence of sensitization to allergens increased with successive birth years in Finland, but remained stable in Russia. Over the 10 years, self-reported physician-diagnosed asthma increased from 5.5% to 8.1% (P = 0.05) and hay fever from 8.1% to 13.2% (P < 0.001) in Finland., Conclusions: Disparities in the prevalence of atopy and atopic disease between Finnish and Russian Karelia have further grown. The 'allergy epidemic' continues in Finland and is mainly attributable to the years of birth effect shown in atopy prevalence. In Russia, no signs of the epidemic are discernible, although the decrease in total IgE may indicate a change in environmental exposure., (© 2011 John Wiley & Sons A/S.)

Background: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume., Methods: Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test., Results: For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs., Conclusions: All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children., (© 2011 John Wiley & Sons A/S.)

Allergen extracts for subcutaneous specific immunotherapy (SCIT) may be adsorbed to aluminium hydroxide for adjuvant effect and to delay allergen discharge. A product with an optimised allergen-to-aluminium hydroxide ratio enables a lower allergen dose and shorter introduction phase. The new therapeutic product Avanz (ALK, Denmark) has an optimised allergen-to-aluminium hydroxide ratio. A multicentre, randomised, phase II clinical trial evaluated the immunological effects and tolerability of two different five-step updosing schedules for Avanz in 400 patients with grass pollen-induced rhinoconjunctivitis with or without asthma, randomised into two groups. Group 1 were administered weekly, and group 2 were administered every 3 to 4 days. After updosing, patients received two maintenance injections after 2 and 4 weeks. In the updosing phase, local and systemic reactions were significantly more frequent in group 2 than group 1. In the maintenance phase, adverse reactions were less common in both groups. No generalised reactions with hypotension or fatal reactions occurred. An increase in allergen-specific immunoglobulin G(4) (IgG(4) ) and IgE antibodies was established one week after the last injection. Avanz is a SCIT product with an optimised allergen-to-aluminium hydroxide ratio that enables a shorter updosing phase. We established an improved safety profile with weekly updosing compared with 3-4-day intervals. Clinical trials are needed to confirm clinical efficacy., (© 2011 John Wiley & Sons A/S.)

The studies on the mechanisms of specific immunotherapy (SIT) point out its targets that decide on the efficacy of SIT and hence might be used for its further improvement. Several mechanisms have been proposed to explain the beneficial effects of immunotherapy. The knowledge of the mechanisms underlying allergic diseases and curative treatment possibilities has experienced exciting advances over the last three decades. Studies in several clinical trials in allergen-SIT have demonstrated that the induction of a tolerant state against allergens in many ways represents a key step in the development of a healthy immune response against allergens. Several cellular and molecular mechanisms have been demonstrated: allergen-specific suppressive capacities of both inducible subsets of CD4(+) CD25(+) forkhead box P3(+) T-regulatory and IL-10-secreting type 1 T-regulatory cells increase in peripheral blood; suppression of eosinophils, mast cells, and basophils; Ab isotype change from IgE to IgG4. This review aims at the better understanding of the observed immunological changes associated with allergen SIT., (© 2011 John Wiley & Sons A/S.)

Anaphylaxis is a clinical emergency, and recent reports suggest increased prevalence. A diverse set of primary genetic and environmental influences may confer susceptibility to anaphylactic reactions. Anaphylaxis presents diagnostic and therapeutic challenges. It often manifests with a broad array of symptoms and signs that might be similar to other diseases. The management of anaphylaxis consists of emergency treatment of acute episodes as well as preventive strategies to avoid recurrences. Treatment is complicated by its rapid onset and progression, presence of concurrent diseases or medications, and need for long-term allergen avoidance. Health care professionals must be able to recognize the signs of anaphylaxis, treat an episode promptly and appropriately, and provide preventive recommendations. Recognizing the gaps in our understanding and management of anaphylaxis may help identify promising targets for future treatment and prevention and areas that require further study., (© 2010 John Wiley & Sons A/S.)

Background: Previous studies suggest that pre/probiotics can be used in the prevention and treatment of early allergic disease in newborns and young children., Objective: To determine the effect of treatment with synbiotics (90% short-chain galacto-oligosaccharides, 10% long-chain fructo-oligosaccharides: Immunofortis(®) and Bifidobacterium breve M-16V) on allergic responses in adults with established allergic asthma. Primary outcome was allergen-induced bronchial inflammation as represented by eosinophil counts., Methods: Twenty-nine patients with asthma and house dust mite (HDM) allergy were randomized in a double-blind, parallel design to receive placebo or synbiotics for 4 weeks. At study entry and after treatment, a bronchial allergen challenge with HDM was performed, followed by lung function tests, collection of blood (in/ex vivo IL-5) and induced sputum (inflammatory parameters). During treatment, a diary was kept with peak expiratory flow (PEF) and asthma scores., Results: Treatment did not affect the allergen-induced increase in sputum eosinophils at 6 and 24 h after challenge. Likewise, other parameters for bronchial inflammation and early and late changes in lung function did not differ upon treatment. Both the morning and evening PEF, however, significantly increased during synbiotics treatment (morning P = 0.003, evening P = 0.011). Also, the increase in serum IL-5 after allergen challenge was significantly inhibited by synbiotics (P = 0.034), as was ex vivo allergen-induced Th2-cytokine (IL-5 and IL-4+ IL-13) production by PBMCs (P = 0.046). In vivo (24 h) and ex vivo IL-5 production were associated., Conclusion: Four-week treatment with synbiotics had no effect on bronchial inflammation and LAR, but did significantly reduce systemic production of Th2-cytokines after allergen challenge and improved PEF., (© 2010 John Wiley & Sons A/S.)

Background: Rhinoconjunctivitis because of tree pollen sensitization is common in Northern Europe. Specific subcutaneous immunotherapy (SCIT) is the only disease-modifying treatment, but unmodified allergen extracts carry a risk of allergic side-effects. Our objective was to examine efficacy and safety of a depigmented-polymerized mixed tree pollen extract., Methods: A double-blind, placebo-controlled trial of 184 tree pollen allergic adults was performed. SCIT consisted of four increasing doses at 7-day intervals, then maintenance injections every 6 weeks for 18 months. Primary outcome was combined symptom and medication score during the 2008 season. Secondary outcomes included analysis at different levels of pollen exposure and a responder analysis. Adverse events were classified using the EAACI scale. Birch pollen-specific IgE and IgG(4) were measured before and after treatment., Results: The combined symptom and medication score of actively treated patients was significantly lower than those on placebo (P < 0.04). Increased efficacy was seen at high pollen exposure (median score 2.1 for active [IQR 0.7-3.4] vs 4.2 [IQR 2.4-5.3] for placebo for days with 500 or more pollen grains per m(3) , a 50% reduction, P < 0.01). A modified responder analysis revealed 64% responders in the active and 32% in the placebo group (P < 0.01). There were 17 systemic reactions. All were mild (grade 1 or 2) and required no treatment. Serum birch-specific IgG(4) increased in the SCIT group (P < .01)., Conclusions: SCIT with depigmented- polymerized tree pollen extract was clinically effective and well tolerated. Responder analysis suggested that one-third of patients treated with immunotherapy may not respond., (© 2010 John Wiley & Sons A/S.)

Background: To investigate the associations between clinical obstetric factors during birth and doctor-diagnosed wheezing and allergic sensitization during early childhood., Methods: We followed 410 Finnish women from late pregnancy until 18 months age of their children. All children were delivered at term. Doctor-diagnosed wheezing among children was established by questionnaires, while specific immunoglobulin E antibodies to inhalant and food allergens were measured in 388 children at 1 year of age. Data on maternal obstetric variables were recorded at the time of delivery., Results: Children of mothers with longer duration of ruptured fetal membranes before birth had significantly higher risk of doctor-diagnosed wheezing during early childhood compared to those children with shorter period of ruptured fetal membranes (III vs I quartile; aOR 6.65, 95% CI 1.99-22.18; P < 0.002 and IV vs I quartile; aOR 3.88, 95% CI 1.05-14.36, P < 0.043). Children who were born by Cesarean delivery had significantly less allergic sensitization at the age of 1 year compared to those who were born by vaginal route (16.0%vs 32.2%; aOR 0.34, 95% CI 0.14-0.80; P < 0.013). Furthermore, allergic sensitization tended to be more common in children with longer duration of labor before birth. No other birth-related obstetric factors, such as induction, the type of fetal membrane rupture during birth or quality of amniotic fluid were associated significantly with the examined outcomes., Conclusion: The longer duration of the ruptured fetal membranes possibly reflected the higher risk of intrapartum infection at birth, and further increased the risk of doctor-diagnosed wheezing among offspring.

Background: Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods., Methods: Sera from the 'random sample' of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix., Results: Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country., Conclusions: Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization.

Background: Several clinical and experimental observations suggest that allergen deposition in the nose may partially be responsible for the induction of conjunctival symptoms in allergic rhinitis. The aims of this study were to evaluate the induction of conjunctival symptoms by selective nasal allergen provocation and to assess the feasibility of the different tools for evaluation of conjunctival allergic inflammation., Methods: Grass pollen allergic subjects with rhinoconjunctivitis symptoms during the pollen season (n = 12) underwent a nasal sham and grass pollen provocation extra-seasonally. Nasal and conjunctival symptoms were scored using the Visual Analogue Scale (VAS) system at baseline, 15 min, 1 h and 24 h after provocation. In addition to Peak Nasal Inspiratory flow (PNIF) measurements, conjunctival inflammation and vascular congestion were evaluated and histamine and substance P levels in tear fluid were measured., Results: Selective nasal grass pollen provocation induced ocular pruritus, lacrimation and conjunctival vascular congestion. PNIF values correlated inversely with lacrimation (r = -0.71, P < 0.001) and ocular pruritus (r = -0.41, P < 0.05). Four out of 11 patients showed a conjunctival eosinophilic inflammation and levels of histamine (r = 0.73, P < 0.05) and substance P (r = 0.67, P = 0.05) in tear fluid correlated with conjunctival symptoms., Conclusion: Selective nasal grass pollen provocation induced conjunctival inflammation, ocular pruritus and lacrimation, which correlated with histamine and substance P levels in tear fluid and inversely with the PNIF values. These data show a naso-ocular interaction in allergic rhinitis and offer objective tools for evaluation of conjunctival inflammation in allergic rhinoconjunctivitis.

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe., Aims: The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel., Methods: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres., Results: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe., Conclusion: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

Background: Allergic and nonallergic rhinitis are common childhood disorders., Objective: To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses., Methods: We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage., Results: Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) (P = 0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis (P = 0.000) and nonallergic rhinitis (P = 0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis., Conclusion: Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis.

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64:1427-1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life-time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence-based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Specific inhalation challenge can help differentiate occupational asthma from allergic alveolitis caused by malt.

Background: Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention., Aims of the Study: The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein., Methods: Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment., Results: Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5-50 mg (1/40-1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects., Conclusions: We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion.

Background: For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross-reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT)., Objectives: The aim of this study was to test whether Na2[PdCl4] is also more sensitive for diagnosing Pd allergy with a standardized LTT., Patients/methods: After determining optimal nontoxic and nonmitogenic concentrations for Na2[PdCl4], blood samples from 105 patients with clinical suspicion of metal allergy were tested with an LTT called memory lymphocyte immuno stimulation assay for Na2[PdCl4], PdCl2 and NiCl2. Reaction profiles were analysed for concordant positive reactions., Results: Using the conventional cut-off of stimulation index > or = 3, 74.3% showed a positive reaction to NiCl2, 15.2% to PdCl2 and 28.6% to Na2[PdCl4]. All positive results to PdCl2 were covered by Na2[PdCl4]. From the 30 positive reactions to Na2[PdCl4], 26 (87%) were concordant for NiCl2 reactivity., Conclusion: In LTT, the use of Na2[PdCl4] results in more positive reactions in Pd allergy testing which are in concordance with positive reactions to PdCl2 and NiCl2.