Search

Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed “reference doses,” below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure. Resumen: La legislación regional y nacional exige la divulgación de alérgenos "prioritarios" cuando están presentes como ingrediente en los alimentos, pero esto no se extiende a la presencia involuntaria de alérgenos debido a instalaciones de producción compartidas. Esto ha dado lugar a una proliferación de etiquetas de precaución para alérgenos ("pueden contener") (PAL) que los consumidores alérgicos a los alimentos suelen ignorar. Se han hecho intentos para mejorar la gestión del riesgo de alérgenos para informar mejor el uso de PAL, pero la falta de consenso ha llevado a una variedad de enfoques regulatorios y a la falta de uniformidad en el uso de PAL por parte de las empresas alimentarias. Una posible solución sería establecer “dosis de referencia” acordadas internacionalmente, por debajo de las cuales no se necesitaría PAL. Sin embargo, si se van a utilizar dosis de referencia para informar la necesidad de PAL, entonces es esencial caracterizar el peligro asociado con estas exposiciones de bajo nivel. Para el maní, ahora hay datos publicados relacionados con más de 3000 desafíos doble ciego controlados por placebo en individuos alérgicos, pero falta un nivel similar de evidencia para otros alérgenos prioritarios. Presentamos los resultados de una evaluación rápida de la evidencia y un metanálisis del riesgo deanafilaxia a una exposición a alérgenos de bajo nivel para alérgenos prioritarios. Sobre la base de este análisis, proponemos que el cacahuete puede y debe considerarse un alérgeno ejemplar para la caracterización del peligro en una exposición a un alérgeno de bajo nivel. Instituto de Investigación de Tecnología de Alimentos Fil: Turner, Paul J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Patel, Nandinee. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ballmer-Weber, Barbara K. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ballmer-Weber, Barbara K. Clínica de Dermatología y Alergología. Kantonsspital; Suiza. Fil: Baumert, Joe L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Blom, W. Marty. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brooke-Taylor, Simon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brough, Helen. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brough, Helen. King's College London. Departamento de Alergia Pediátrica; Reino Unido. Fil: Campbell, Dianne E. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Campbell, Dianne E. Tecnologías DBV. Montrouge; Francia. Fil: Chen, Hongbing. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Chinthrajah, R. Sharon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Crevel, René W.R. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Dubois, Anthony E.J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ebisawa, Motohiro. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Elizur, Arnon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Elizur, Arnon. Universidad de Tel Aviv. Facultad de Medicina Sackler. Departamento de Pediatría; Israel. Fil: Gerdts, Jennifer D. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Gowland, M. Hazel. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Houben, Geert F. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Hourihane, Jonathan O.B. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Knulst, André C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: La Vieille, Sébastien. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: López, María Cristina. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Mills, E.N. Clare. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Polenta, Gustavo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina. Fil: Polenta, Gustavo Alberto. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Purington, Natasha. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Said, María. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Sampson, Hugh A. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Sampson, Hugh A. Escuela de Medicina Icahn. División de Alergia e Inmunología Pediátricasen. Nueva York. Estados Unidos de América. Fil: Schnadt, Sabine. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Södergren, Eva. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Södergren, Eva. ThermoFisher Scientific; Suecia. Fil: Taylor, Stephen L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Remington, Benjamin C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Remington, Benjamin C. Grupo BV. Consultoría Remington; Holanda.

Background: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. Objective: We sought to develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders but particularly patients with food allergy. Methods: Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges. If double-blind, placebo-controlled food challenge data are not available, data from widely used open food challenges using predefined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research and the Food Allergy Research and Resource Program at the University of Nebraska-Lincoln have been collecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens. Results: In this article we provide in-depth insights into the methodology applied by the Netherlands Organisation for Applied Scientific Research and Food Allergy Research and Resource Program to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. More than 90 examples for determining individual allergic thresholds are presented. Conclusion: With the methodology presented in this article, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption. © 2019 American Academy of Allergy, Asthma & Immunology

Purpose Children with bronchopulmonary dysplasia often develop complications that affect them well into adult life. Very little is known about how this affects their quality of life, since no sensitive instrument is available to measure health-related quality of life in this population. In this study, a Dutch parent-proxy instrument was developed for this purpose. Methods A list of items was generated after literature search and interviews with both parents of patients and clinical experts. Clinically relevant items were selected with the clinical impact method and item analysis. Results of clinical tests to measure complications in children with bronchopulmonary dysplasia were correlated with these items to select the items that show construct validity. Cronbach’s alpha was calculated to estimate internal consistency of the items in the final questionnaire. Results In total, 92 children and their parents and 7 clinicians participated. Of 130 identified items, 47 showed clinical relevance. Spirometry, the Child Behavior Checklist, mean arterial pressure, and body mass index were used to determine construct validity of 33 items. These items were structured within five domains: pulmonary complaints, school functioning, growth and nutrition, exercise and locomotion, emotional functioning and health care concerns. The questionnaire showed excellent internal consistency with Cronbach’s alpha of 0.919. Conclusion This study developed a disease-specific parent-proxy instrument to measure health-related quality of life in children with bronchopulmonary dysplasia aged 4–8 years old, the BPD-QoL. All included items show construct validity and internal consistency reliability. Future research should focus on further validation and analysis of responsiveness and reliability. Electronic supplementary material The online version of this article (10.1007/s11136-018-2029-7) contains supplementary material, which is available to authorized users.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; PCONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

BackgroundThere is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted.ObjectiveTo identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact.MethodsThe study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions.ResultsA total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P ConclusionsThe severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.

_To the Editor:_ Previously, we identified the HLA region as a risk factor forpeanut allergy (PA); this observation is supported further by 2 independent genome-wide association studies (GWASs). The HLA class II genes (including HLA-DR, HLA-DQ, and HLADP) encode molecules involved in presentation of extracellular antigens, such as peanut allergens, to T lymphocytes, which in turn mediates B-cell antibody production.We used the Canadian Peanut Allergy Registry (CanPAR) and the Busselton Health Study to conduct the largest GWAS for PA to date. Here we report analysis of the HLA region and a meta-analysis with data from 6 additional studies, which confirms and narrows the region of interest to HLA-DQB1 and establishes independence from asthma loci. [...]

BACKGROUND/OBJECTIVES: Human breast milk is generally regarded as the best nutrition for infants in their first months of life. Whether breastfeeding has a protective effect on food allergy is a point of debate and the subject of this study.SUBJECTS/METHODS: This retrospective study was conducted in 649 children who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part of routine care in a tertiary care clinic. Food allergy was defined as having at least one positive DBPCFC to any food. The association between both "any" breastfeeding (yes/no) and its duration in months with food allergy was studied by logistic regression analysis with correction for confounding variables.RESULTS: The prevalence of food allergy was 58.9% (n = 382). Of all subjects, 75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no significant association between food allergy and breastfeeding versus bottle-feeding after correction for the confounding effect of increased breastfeeding by atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85-1.79, p = 0.27). However, in breastfed children, every additional month of breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93-0.99, p = 0.02). No confounders were identified in this association.CONCLUSION: These results show for the first time that in children investigated for possible food allergy, every additional month of breastfeeding is associated with a lower risk of developing clinical food allergy as diagnosed by DBPCFC. However, overall, there was no association between the prevalence of food allergy and breastfeeding versus bottle-feeding in this tertiary care population.

Background: Severe allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine.Objective: To evaluate the percentage of anaphylactic reactions treated with epinephrine during OFCs and to identify associated factors for the administration of epinephrine.Methods: Children who underwent an OFC with peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in the Netherlands were evaluated. Children with reactions meeting the criteria for anaphylaxis according to the European Academy of Allergy and Clinical Immunology guidelines for food allergy and anaphylaxis were included. Children with an anaphylactic reaction treated with vs without epinephrine were compared. Possible factors associated with the administration of epinephrine, such as age, sex, symptoms consistent with asthma, history of an allergic reaction to the tested allergen, and symptom types during the anaphylactic reaction, were evaluated using logistic regression analysis.Results: Eighty-three children in clinical and research settings (43% boys; median age, 7 years; range, 1-17) who met the criteria for anaphylaxis were included in this study. Thirty-two of 83 children (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during the OFC were treated significantly more often with epinephrine than gastrointestinal symptoms (P = .01).Conclusion: Only 39% of children with anaphylaxis, according to the guideline criteria, were treated with epinephrine during the OFC and most of these children had respiratory symptoms. There is need for an easy-to-use international guideline for the treatment of allergic symptoms during OFCs. (C) 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Background Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. Objective We sought to investigate genetic susceptibility to PA. Methods Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. Results An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA ( P = 1.80 × 10 −8 ), whereas SNPs associated with Src kinase–associated phosphoprotein 1 (SKAP1) , matrix metallopeptidase 12 (MMP12)/MMP13 , catenin α3 (CTNNA3) , rho GTPase–activating protein 24 (ARHGAP24) , angiopoietin 4 (ANGPT4) , chromosome 11 open reading frame (C11orf30/EMSY) , and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association ( P ≤ 1.49 × 10 −6 ). In the meta-analysis of PA, loci in or near ITGA6 , ANGPT4 , MMP12/MMP13 , C11orf30 , and EXOC4 were significant ( P ≤ 1.49 × 10 −6 ). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance ( P = 7.50 × 10 −11 ), whereas SNPs associated with ITGA6 , ANGPT4 , MMP12/MMP13 , and EXOC4 and additional C11orf30 SNPs were suggestive ( P ≤ 1.49 × 10 −6 ). Functional annotation indicated that SKAP1 regulates expression of CBX1 , which colocalizes with the EMSY protein coded by C11orf30. Conclusion This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes ( C11orf30 / EMSY , SKAP1 , and CTNNA3 ) identified by this study are involved in epigenetic regulation of gene expression.

BACKGROUND: Patients with indolent systemic mastocytosis (ISM) are at risk for severe anaphylactic reactions to yellow jacket (YJ) stings while demonstration of sensitization can be challenging because specific IgE (sIgE) levels are regularly below 0.35 kU(A)/L. The implication of missing YJ allergy is illustrated by a case of fatal anaphylaxis.OBJECTIVE: To explore the natural course of YJ venom allergy and the diagnostic accuracy and therapeutic consequence of YJ venom sIgE in patients with ISM.METHODS: All patients with ISM seen from 1981 to 2015 (n = 243) were evaluated on the number of YJ stings, reaction severity, and sensitivity and specificity of YJ venom sIgE. YJ venom allergic patients without mastocytosis served as control (n = 313).RESULTS: A total of 153 patients with ISM were stung during adult life. The first systemic reaction was more often severe in patients with ISM than in patients without mastocytosis (69.9% vs 22.0%) and reactions recurred in 40 of 41 re-stung patients with ISM. ISM reactors showed lower YJ venom sIgE levels than nonmastocytosis reactors (0.61 vs 4.83 kU(A)/L; P CONCLUSIONS: The high rate of severe reactions and the fatal case underscore the importance of adequate diagnostic sensitivity of sIgE in patients with ISM. The sensitivity of sIgE can be ameliorated by lowering the threshold to 0.17 kU(A)/L, retaining good specificity. We recommend sIgE screening in all patients with ISM and discussing immunotherapy when YJ venom sIgE exceeds 0.17 kU(A)/L.

Background It is challenging to define likely food allergy (FA) in large populations which limited the number of large studies regarding risk factors for FA. Objective We studied the prevalence and characteristics of self-reported FA (s-rFA) in the large, population-based Dutch Lifelines cohort and identified associated risk factors. Methods Likely food allergic cases (LikelyFA) were classified based on questionnaire reported characteristics consistent with FA. Subjects with atypical characteristics were classified as Indeterminate. We investigated 13 potential risk factors for LikelyFA such as birth mode and living on a farm and addressed health-related quality of life (H-RQOL). Results Of the 78, 890 subjects, 12.1% had s-rFA of which 4.0% and 8.1% were classified as LikelyFA and Indeterminate, respectively. Younger age, female sex, asthma, eczema and nasal allergy increased the risk of LikelyFA (p-value range −250–1.29*10−7). Living in a small city/large village or suburb during childhood was associated with a higher risk of LikelyFA than living on a farm (p-value = 7.81*10−4 and p = 4.84*10−4, respectively). Subjects classified as Indeterminate more often reported depression and burn-out compared to those without FA (p-value = 1.46*10−4 and p = 8.39*10−13, respectively). No association was found with ethnicity, (duration of) breastfeeding, birth mode and reported eating disorder. Mental and physical component scores measuring H-RQOL were lower in both those classified as LikelyFA and Indeterminate compared to those without FA. Conclusion The prevalence of s-rFA among adults is considerable and one-third reports characteristics consistent with LikelyFA. Living on a farm decreased the risk of LikelyFA. The association of poorer H-RQOL as well as depression and burn-out with questionable self-perceived FA is striking and a priority for future study.

Background: Allergic sensitisation towards cashew nut often happens without a clear history of eating cashew nut. IgE cross-reactivity between cashew and pistachio nut is well described; however, the ability of cashew nut-specific IgE to cross-react to common tree nut species and other Anacardiaceae, like mango, pink peppercorn, or sumac is largely unknown. Objectives: Cashew nut allergic individuals may cross-react to foods that are phylogenetically related to cashew. We aimed to determine IgE cross-sensitisation and cross-reactivity profiles in cashew nut-sensitised subjects, towards botanically related proteins of other Anacardiaceae family members and related tree nut species. Method: Sera from children with a suspected cashew nut allergy (n = 56) were assessed for IgE sensitisation to common tree nuts, mango, pink peppercorn, and sumac using dot blot technique. Allergen cross-reactivity patterns between Anacardiaceae species were subsequently examined by SDS-PAGE and immunoblot inhibition, and IgE-reactive allergens were identified by LC-MS/MS. Results: From the 56 subjects analysed, 36 were positive on dot blot for cashew nut (63%). Of these, 50% were mono-sensitised to cashew nuts, 19% were co-sensitised to Anacardiaceae species, and 31% were co-sensitised to tree nuts. Subjects co-sensitised to Anacardiaceae species displayed a different allergen recognition pattern than subjects sensitised to common tree nuts. In pink peppercorn, putative albumin- and legumin-type seed storage proteins were found to cross-react with serum of cashew nut-sensitised subjects in vitro. In addition, a putative luminal binding protein was identified, which, among others, may be involved in cross-reactivity between several Anacardiaceae species. Conclusions: Results demonstrate the in vitro presence of IgE cross-sensitisation in children towards multiple Anacardiaceae species. In this study, putative novel allergens were identified in cashew, pistachio, and pink peppercorn, which may pose factors that underlie the observed cross-sensitivity to these species. The clinical relevance of this widespread cross-sensitisation is unknown.

Regulators and risk managers in general need to decide whether an allergenic food or ingredient is of such public health importance that it needs to be actively managed. There is therefore a need to scale the relative allergenicity of foods and ingredients according to the hazards they pose. Objective criteria increase transparency and trust in this decision-making process and its conclusions. This paper proposes a framework that allows categorisation and prioritisation of allergenic foods according to their public health importance. The challenge is to find a basis on which the allergenicity of foods can best be described and a method to combine the relevant measures of allergenicity into a scoring system that prioritises allergenic foods on the basis of their public health relevance. The framework is designed in accordance with the generic risk analysis principles used in food safety and can be used by regulators to decide whether or not a specific allergenic food or ingredient is of sufficient public health importance that it warrants regulation (i.e. mandatory labelling) when used in the production of food products.

BackgroundGenetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals.MethodsWe performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS).ResultsGene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0mm vs 0.0mm for e-DR1, P=0.017 and 0.0mm for e-DR2, P=0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2mm vs 0.2mm for e-DR1, P=0.017 and 0.0mm for e-DR2, P=0.043). Only one subject (5%) remained symptom-free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2.ConclusionThese data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future.

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analyzed including 262 children (71.0%) with food allergy. Associations were tested by family based association testing (FBAT). The A alleles of both SNPs were associated with food allergy (p=0.036 and p=0.013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all p

Food allergy is a potentially life-threatening disease with a detrimental effect on the quality of life of caregivers and children.(1) Although many different types of food have been identified as potential elicitors of allergic reactions, only a small number of these foods cause the majority of reactions.(2) Food consists of a complex mixture of nutrient and non-nutrient components and their molecular interactions, which are known as the food matrix. Individual matrix components, or the matrix as a whole, may interact with a food allergen and may influence the clinical response to that allergen. This article is protected by copyright. All rights reserved.

Background: The allergy management support system (AMSS) was developed to assist general practitioners (GPs) to handle the increasing burden of allergic diseases and facilitates the diagnosis and management of allergy. The aim of this cluster-randomized controlled pilot study was to test the feasibility of this AMSS for primary care.Methods: GPs received diagnostic and management recommendations generated by the AMSS in addition to sIgE-test results (intervention) or GPs received sIgE-test results only (control). The AMSS recommendations are based on the previously developed patient-completed AMSS questionnaire and sIgE-test results. The AMSS was considered feasible when > 70% of the AMSS recommendations were sent to the GP within ten working days of sIgE-testing. GPs completed a questionnaire on their diagnosis and management before (T1) and after (T2) receiving sIgE test results. Agreement and disagreement concerning diagnosis, medication and referrals between GPs and AMSS was investigated at T1 and T2. A total agreement score between GPs and AMSS was calculated. GPs in the intervention group completed a questionnaire to evaluate the utility of the AMSS. Semi-structured interviews were used to explore the motivation of GPs who did not include patients in this pilot study.Results: Twenty-seven GPs included 101 patients. Forty-two patients (72%) completed the AMSS questionnaire in the intervention group. The majority of the AMSS recommendations (93%) were returned to the GP within 10 working days after sIgE-test results were known [mean (SD) 4.7 (4.0) working days]. GPs in the intervention group reported largely following the AMSS recommendations in 71% of cases. The total agreement scores concerning diagnosis were significantly higher (p Conclusion: The AMSS can be considered to be feasible for primary care. GPs tend to follow the AMSS recommendations. The AMSS may contribute to the empowerment of GPs to better manage allergy patients in primary care.Trial registration ISRCTN ISRCTN36780877. Registered 23 November 2017 (retrospectively registered).

Background: Diagnosis and management of allergic patients are often performed exclusively by general practitioners (GPs). Because of the increasing prevalence of allergic diseases and because of the limited knowledge of GPs on allergy, an allergy management support system (AMSS) was developed. The aim of this study was to test the feasibility of an AMSS for primary care in a pilot study. Method: Using a randomized controlled design, GPs in the intervention group received AMSS advice in addition to sIgE test results and GPs in the control group performed usual care based on sIgE test results only. The AMSS advice was based on the AMSS history questionnaire completed by patients and sIgE test results. The AMSS advice included probable diagnoses and recommendations for management. AMSS advice was also formulated for patients in the control group for evaluative purposes only. Patients were included by GPs when ordering an sIgE test. GPs in both groups completed a short questionnaire on diagnosis and management at the time of inclusion (T1) and after sIgE test outcomes were known (T2). A total agreement score between GP and AMSS was calculated as the number of concordant diagnoses minus the number of false negative and false positive diagnoses. The AMSS was considered feasible when >70% of the AMSS advice was sent to the GP within 10 workdays of sIgE testing. Results: Of the 75 GPs that agreed to participate, 27 GPs (37%) included one or more patients in the study. Together they included 101 patients of which 66 (67%) completed the AMSS history questionnaire. The majority of the AMSS advice (93%) was sent back to the GP within 10 workdays after sIgE test results were known (mean (SD) 4.7 (4.0) workdays). GPs in the intervention group reported that the AMSS advice was complete and to-the-point in 80% of cases, agreed for the most part with the AMSS advice in 80% of cases and followed the AMSS advice for the most part in 71% of cases. The difference in total agreement scores on diagnosis (T2 minus T1), was significantly higher in the intervention group than in the control group (mean (SD) 0.9 (1.8); -0.8 (1.0); P

Background Successful treatment of anaphylaxis in the community relies on early and correct use of epinephrine auto-injectors (EAI). In the Netherlands pharmacists supply EAIs to patients and have a crucial role in instructing patients in how and when to use EAI. However, there are currently no data in Europe on the quality of such instruction provided by pharmacists. Therefore, the aims of this study were to investigate the knowledge, attitudes, and beliefs regarding food allergy among pharmacists in the Netherlands, and to investigate the quality of EAI instructions and demonstrations to patients by pharmacists. Methods Pharmacists were asked to complete an online questionnaire. Quality of instructions and demonstration accuracy were assessed in mystery guest visits to randomly selected pharmacies. For the statistical analysis descriptive methods were used. Results In total 25 out of 115 questionnaires were completed. Only two (8%) respondents gave correct answers concerning the proper EAI demonstration. Twenty-one (84%) respondents thought that the provision of instructions was the responsibility of pharmacists. In total, ten pharmacies were included in simulated patient visits. Five of them (50%) demonstrated the EAI. None of them demonstrated the EAI use correctly. Conclusion Food-allergic patients at high risk for anaphylaxis who receive their EAI from a community pharmacy are often not instructed on how to use an EAI or receive incorrect instructions. Pharmacists show considerable gaps in knowledge about food allergy and its management. These data suggest that opportunities exist to improve the quality of care provided by pharmacies to high risk food-allergic patients. This article is protected by copyright. All rights reserved.

Background Cashew nut, pistachio nut and mango belong to the Anacardiaceae family and are botanically related. Therefore, cashew nut sensitised children are frequently advised to eliminate cashew nuts and pistachio nuts from their diet. The ‘Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572) study showed that cashew nut sensitised children were co-sensitised to pistachio nut in 98% of cases and to mango in 21% of cases. The aim of this follow-up study to IDEAL is to assess the clinical relevance of co-sensitisation to pistachio nut and mango in cashew nut sensitised children. Methods Children were recruited from the study: ‘Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572). Inclusion criterion for the IDEAL study was sensitization to cashew nut as demonstrated by either SPT or sIgE, and a clinical history of reactions to cashew nuts or no previous (known) exposure. Sensitized children who were tolerant to cashew nuts were excluded. Inclusion criterion for this IDEAL follow-up study was co-sensitization to pistachio nut, regardless the result of the DBPCFC with cashew nut. In this follow-up study a double-blind placebo-controlled food challenge with pistachio nut and an open food challenge with mango were performed. Results Twenty-nine children (mean age of 11.6 years, 62% male) were included. Pistachio nut sensitisation was clinically relevant in only 34% of cashew-sensitised children and only 31% of cashew challenge positive children. None of the children was challenge positive to mango. Conclusion Although co-sensitisation between cashew nut and pistachio nut was observed in 98%, pistachio nut sensitisation was only clinically relevant in 34% of the children. Therefore, a challenge test with pistachio nut is recommended in children with cashew nut and pistachio nut sensitisation. Trial registration The study was registered in the Dutch trial register (registration number 3572) on 10 August 2012 (retrospectively registered)

Bertine MJ Flokstra - deBlok,1,2 Thys van der Molen,1,2 Wianda A Christoffers,3 Janwillem WH Kocks,1,2 Richard L Oei,4 Joanne NG Oude Elberink,2,4 Emmy M Roerdink,5 Marie Louise Schuttelaar,3 Jantina L van der Velde,1,2 Thecla M Brakel,1,6 Anthony EJ Dubois2,5 1Department of General Practice, 2GRIAC Research Institute, 3Department of Dermatology, 4Department of Allergology, 5Department of Pediatric Pulmonology and Pediatric Allergy, University of Groningen, University Medical Center Groningen, 6Teaching Unit, Department of Social Psychology, University of Groningen, Groningen, The Netherlands Background: Management of allergic patients in the population is becoming more difficult because of increases in both complexity and prevalence. Although general practitioners (GPs) are expected to play an important role in the care of allergic patients, they often feel ill-equipped for this task. Therefore, the aim of this study was to develop an allergy management support system (AMSS) for primary care. Methods: Through literature review, interviewing and testing in secondary and primary care patients, an allergy history questionnaire was constructed by allergists, dermatologists, GPs and researchers based on primary care and specialists’ allergy guidelines and their clinical knowledge. Patterns of AMSS questionnaire responses and specific immunoglobulin E (sIgE)-test outcomes were used to identify diagnostic categories and develop corresponding management recommendations. Validity of the AMSS was investigated by comparing specialist (gold standard) and AMSS diagnostic categories. Results: The two-page patient-completed AMSS questionnaire consists of 12 (mainly) multiple choice questions on symptoms, triggers, severity and medication. Based on the AMSS questionnaires and sIgE-test outcome of 118 patients, approximately 150 diagnostic categories of allergic rhinitis, asthma, atopic dermatitis, anaphylaxis, food allergy, hymenoptera allergy and other allergies were identified, and the corresponding management recommendations were formulated. The agreement between the allergy specialists’ assessments and the AMSS was 69.2% (CI 67.2–71.2). Conclusion: Using a systematic approach, it was possible to develop an AMSS that allows for the formulation of diagnostic and management recommendations for GPs managing allergic patients. The AMSS thus holds promise for the improvement of the quality of primary care for this increasing group of patients. Keywords: allergy, development, diagnosis, management support system, primary care

BackgroundThe double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests.MethodsIn a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c).ResultsA total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p ConclusionThe major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children.

Instruments have been developed and validated for the measurement of health-related quality of life in patients with food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group. It draws on a systematic review of the literature on quality of life instruments for food allergy and the Appraisal of Guidelines for Research & Evaluation (AGREE II) guideline development process. Guidance is provided on the use of such instruments in research, and the current limitations of their use in clinical practice are described. Gaps in current knowledge as well as areas of future interest are also discussed. This document is relevant to healthcare workers dealing with food-allergic patients, scientists engaging in food allergy research and policy makers involved in regulatory aspects concerning food allergy and safety.

This is one of seven interlinked systematic reviews undertaken on behalf of the European Academy of Allergy and Clinical Immunology as part of their Guidelines for Food Allergy and Anaphylaxis, which focuses on instruments developed for IgE-mediated food allergy. Disease-specific questionnaires are significantly more sensitive than generic ones in measuring the response to interventions or future treatments, as well as estimating the general burden of food allergy. The aim of this systematic review was therefore to identify which disease-specific, validated instruments can be employed to enable assessment of the impact of, and investigations and interventions for, IgE-mediated food allergy on health-related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease-specific quality of life (QOL) tools relating to IgE-mediated food allergy. From the 17 eligible studies, we identified seven disease-specific HRQL instruments, which were then subjected to detailed quality appraisal. This revealed that these instruments have undergone formal development and validation processes, and have robust psychometric properties, and therefore provide a robust means of establishing the impact of food allergy on QOL. Suitable instruments are now available for use in children, adolescents, parents/caregivers, and adults. Further work must continue to develop a clinical minimal important difference for food allergy and for making these instruments available in a wider range of European languages.

To establish the effectiveness of interventions for the acute and long-term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series and - only in relation to adrenaline - case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty-five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1-antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long-term management interventions studied were anaphylaxis management plans and allergen-specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom-triggered anaphylaxis.

Recent studies on cashew nut allergy suggest that the prevalence of cashew nut allergy is increasing. Cashew nut consumption by allergic patients can cause severe reactions, including anaphylaxis. This review summarizes current knowledge on cashew nut allergy to facilitate timely clinical recognition and to promote awareness of this emerging food allergy amongst clinicians. The goal of this study is to present a systematic review focused on the clinical aspects of allergy to cashew nut including the characteristics of cashew nut, the prevalence, allergenic components, cross-reactivity, diagnosis and management of cashew nut allergy. The literature search yielded 255 articles of which 40 met our selection criteria and were considered to be relevant for this review. The 40 articles included one prospective study, six retrospective studies and seven case reports. The remaining 26 papers were not directly related to cashew nut allergy. The literature suggests that the prevalence of cashew nut allergy is increasing, although the level of evidence for this is low. A minimal amount of cashew nut allergen may cause a severe allergic reaction, suggesting high potency comparable with other tree nuts and peanuts. Cashew allergy is clearly an underestimated important healthcare problem, especially in children.

BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults.METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized.RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults.CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.

BACKGROUND: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts.METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized.RESULTS: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration.CONCLUSIONS: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority.

Patients with Oral Allergy Syndrome (OAS) to fresh apple may tolerate low allergenic apple cultivars. We aimed to investigate if the low allergenic properties of Elise and Santana, as previously identified in a Dutch population, could be generalised within North West Europe within the birch pollen region with regard to both the prevalence and degree of sensitization. Prick-to-prick tests (PTP) were performed in eighty-five adult patients with OAS to fresh apple in Great Britain, Switzerland and Northern Italy, before the birch pollen season, using the putatively low allergenic apple cultivars Elise, Santana, Granny Smith, Modi and Mcintosh, as well as the putatively high allergenic apple cultivars Golden Delicious and Kanzi. No significant differences in percentages of negative responses of PTPs were found between the three countries. Negative responses did not differ from negative responses to the different apple cultivars we previously found in 2006/2007 in the Netherlands. The size of the PTPs of all apple cultivars tested were correlated to the size of the skin prick tests with birch pollen. These results add to the indications for the low allergenic properties of the low allergenic apple cultivars Santana and Elise, as the number of negative responses were reproducible in three countries within the birch pollen region and were similar to previous results in the Netherlands. These results justify oral challenge studies with Elise and Santana within the birch pollen region, to establish the low allergenic properties for the benefit for apple allergic consumers for definite conclusions.

Food allergy (FA) is an important atopic disease although its precise burden is unclear. This systematic review aimed to provide recent, up-to-date data on the incidence, prevalence, time trends, and risk and prognostic factors for FA in Europe. We searched four electronic databases, covering studies published from 1 January 2000 to 30 September 2012. Two independent reviewers appraised the studies and qualified the risk of bias using the Critical Appraisal Skills Programme tool. Seventy-five eligible articles (comprising 56 primary studies) were included in a narrative synthesis, and 30 studies in a random-effects meta-analysis. Most of the studies were graded as at moderate risk of bias. The pooled lifetime and point prevalence of self-reported FA were 17.3% (95% CI: 17.0-17.6) and 5.9% (95% CI: 5.7-6.1), respectively. The point prevalence of sensitization to ≥1 food as assessed by specific IgE was 10.1% (95% CI: 9.4-10.8) and skin prick test 2.7% (95% CI: 2.4-3.0), food challenge positivity 0.9% (95% CI: 0.8-1.1). While the incidence of FA appeared stable over time, there was some evidence that the prevalence may be increasing. There were no consistent risk or prognostic factors for the development or resolution of FA identified, but sex, age, country of residence, familial atopic history, and the presence of other allergic diseases seem to be important. Food allergy is a significant clinical problem in Europe. The evidence base in this area would benefit from additional studies using standardized, rigorous methodology; data are particularly required from Eastern and Southern Europe.

Health-related quality of life (HRQL) has become an emerging focus of interest in food allergy. Food allergy is a disease characterized by low mortality and symptoms which only occur during an allergic reaction. However, food-allergic patients continuously need to be alert when eating in order to prevent potentially severe allergic reactions, which may be fatal. Fear of such reactions and the need to be continuously vigilant may seriously compromise their HRQL. During the last decade, numerous studies have been published on food allergy and HRQL. The development of reliable, valid and responsive instruments for measuring HRQL in food allergic patients has facilitated this research even further. Such instruments have given insight into the specific problems a patient may face and the impact of food allergy-related interventions from the patient's perspective. This paper focuses on the most significant findings regarding this topic since its first appearance in the literature in 2000.

Introduction: Food allergy is a recognized health problem, but little has been reported on its cost for health services. The EuroPrevall project was a European study investigating the patterns, prevalence and socio-economic cost of food allergy. Aims: To investigate the health service cost for food-allergic Europeans and the relationship between severity and cost of illness. Methods: Participants recruited through EuroPrevall studies in a case-control study in four countries, and cases only in five countries, completed a validated economics questionnaire. Individuals with possible food allergy were identified by clinical history, and those with food-specific immuno-globulin E were defined as having probable allergy. Data on resource use were used to estimate total health care costs of illness. Mean costs were compared in the case-control cohorts. Regression analysis was conducted on cases from all 9 countries to assess impact of country, severity and age group. Results: Food-allergic individuals had higher health care costs than controls. The mean annual cost of health care was international dollars (I$)2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95% confidence interval I$324-I$1530). A similar result was found for adults in each country, and for children, and was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. Conclusions: Food allergy is associated with higher health care costs. Severity of allergic symptoms is a key explanatory factor..

Background: Food allergic children are at least partially dependent on their parents tocare for their food allergy. In addition, parents are often responsible for the educationof others regarding food allergy, including the family, school, neighbors, and friends.The aim of this study was to investigate food allergy knowledge, attitudes, and beliefsof parents with food allergic children in the Netherlands. In addition, a cross-culturalcomparison was made between parents from the USA and parents from theNetherlands.Methods: The original Chicago Food Allergy Research Survey for Parents of Childrenwith Food Allergy (CFARS-PRNT) was translated into Dutch. Parents of childrenwith at least one doctor-diagnosed food allergy were included. Knowledge scores andattitude/beliefs scores were determined and compared with the data from 2945 parentsfrom the USA. Predictors of overall knowledge scores were investigated.Results: Dutch parents of children completed the translated CFARS-PRNT(n = 299). The mean overall knowledge score in the Netherlands was 9.9 afteradjusting for guessing, compared with 12.7 in the USA (p < 0.001). Attitudes andbeliefs regarding food allergy among parents from the Netherlands were generallymore optimistic. The overall knowledge scores could be predicted by country of origin,educational degree, being member of a patient organization, visiting an allergist, and ahistory of anaphylaxis.Conclusions: Food allergy knowledge among parents of food allergic children from theNetherlands is suboptimal when compared with their counterparts from the USA,although these parents tend to be more optimistic toward food allergy than parentsfrom the USA.The prevalence of food allergy in children from Europe and theUSA is considered to be 3–8% (1–4). Unfortunately, there is nocurative treatment available for food allergic patients. The keytreatment is avoidance of allergenic foods, education, andprescription of an epinephrine auto-injector (EAI) for emer-gency treatment in case of accidental ingestions (5–8). Foodallergic children are at least partially dependent on theirparents to seek medical care, to avoid culprit foods, and, in theevent of accidental allergic reactions, to determine the severityof the food allergic reaction and the need for emergencytreatment. In addition, parents often carry the responsibilityfor educating the family, school, neighbors, and friendsregarding their child’s food allergy.Previous studies have shown that having a child with a foodallergy has a significant impact on quality of life (9, 10).Parental anxiety about avoiding and responding to allergicreactions may play a role, particularly among parents educatedabout the potentially life-threatening nature of anaphylactic

Background Diagnostic and accidental food allergic reactions may be modified by the matrix containing the allergenic food. Previous studies of double-blind, placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the fat content of the challenge matrix on the severity of the challenge reactions.Objective The aim of this study was to examine whether the fat content of the food matrix is related to eliciting dose and reaction severity in DBPCFCs with heated hen's egg.Methods Sensitized egg allergic children (n=59) undergoing DBPCFCs with egg as a routine diagnostic procedure in our tertiary care centre were evaluated retrospectively. Three different recipes were used for the food matrix: vanilla pudding, pancake and minced meat, containing 22.8%, 31.9% and 52.7% fat (weighted average), respectively. The eliciting dose (i.e. the highest cumulative dose to which the child reacted) was analyzed by Kaplan-Meier log-rank statistic and by Cox regression. Reaction severity was quantified by using an index (range 1-12) and was analysed by multiple linear regression analysis.Results The overall influence of type of recipe on eliciting dose was not significant (P=0.12). The rate of response to minced meat (with the highest fat content) was not significantly different from pudding [HR=0.61 (0.26-1.45, P=0.26) or pancake (HR=1.41 (0.50-3.99), P=0.52] after adjustment for confounders. The type of recipe did not influence the severity of the challenge reaction. The severity of the challenge reaction for minced meat compared to pudding and pancake was 1.06 (0.52-2.16), P=0.87 and 0.81 (0.32-2.01), P=0.64, respectively, after correction for confounders.Conclusion and Clinical Relevance In contrast to similar research with peanut, no significant influence of the fat content of the matrix was found on the eliciting dose or severity of the reaction in 59 DBPCFCs with hen's egg. Matrix fat content differences comparable to those reported here may not be an important co-determinant of reaction severity for all allergenic foods.

The time during which children are observed following a double-blind, placebo-controlled food challenge (DBPCFC) varies in clinical practice. There are little data on late reactions (LRs) following DBPCFCs. Therefore, we determined the prevalence, severity and clinical characteristics of late reactions in food-allergic children and adolescents after DBPCFC, and ascertained which factors are associated with, and may predict, LRs. Logistic regression analyses were performed to investigate which factors were associated with LRs and to develop the association and prediction models. A total of 1142 children underwent DBPCFCs (child-test combinations). Of these 1142 child-test combinations, 400 reported LRs following the DBPCFC. LRs in food-allergic children after DBPCFC are poorly predictable and are generally not severe. All LRs, including those on the placebo day, are more frequently reported in younger children. Children who do not experience severe immediate reactions may be safely discharged home 2 h after a DBPCFC.

BACKGROUND: Atopic dermatitis (AD) and food allergy frequently coexist in children.OBJECTIVE: To examine the association between food allergy and AD.METHODS: Between 2001 and 2011, children referred to our tertiary care center underwent double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies as part of regular care. Immediate reactions were observed and recorded by allergy nursing staff, whereas late reactions were ascertained by semistructured telephone interview 48 hours after challenge. To test to which degree specific IgE results were predictive in the outcome of DBPCFCs in children with and without (previous and current) AD, logistic regression analysis was performed.RESULTS: A total of 1186 DBPCFCs were studied. Sensitization to foods occurred significantly more often in children with previous AD. The association between specific IgE results and the outcome of DBPCFCs was significant for children with and without (previous and current) AD but stronger for children without current AD. The positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food.CONCLUSION: Children with current AD are more frequently asymptomatically sensitized to the foods in question than those without AD. In addition, children suspected of food allergy should be considered for testing, regardless of the severity of their AD. Our results suggest that children with exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic.

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572

BackgroundFood-allergic patients at high risk of potential fatal anaphylaxis should carry an epinephrine auto-injector (EAI) at all times. This treatment may be perceived as burdensome and this may affect compliance and health-related quality of life (HRQL). The aims of the study were (1) to determine the burden of treatment (BoT) of an EAI, (2) to examine the relationship between this burden and compliance, and (3) to analyze which factors contribute to the BoT of the EAI as perceived by food-allergic adolescents and their parents.MethodsDutch food-allergic adolescents prescribed an EAI, and their parents completed a questionnaire package (n = 55). Relationships between BoT and HRQL, illness severity and perception, and anxiety measures were investigated.ResultsFood-allergic adolescents and their parents were (extremely) positive about the EAI (54.5%; 72.7%, respectively) (=low BoT). The BoT measure showed a significantly greater burden in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times than adolescents who reported they did. The BoT scores of both adolescents and their parents were not associated with HRQL, illness severity and perception, or trait anxiety.ConclusionsThe majority of food-allergic adolescents and their parents were positive about the EAI (=low BoT). However, the BoT was significantly associated with self-reported compliance with carrying the EAI. The BoT was higher in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times. The BoT measure seems to be a useful tool to study compliance with carrying an EAI. The BoT of an EAI is not associated with HRQL. The BoT measures a distinct concept related to compliance behavior.

Background: Previous studies showed that health-related quality of life (HRQL) significantly improved after the food challenge, with greater improvements in HRQL after a negative outcome than after a positive outcome. It is currently unknown whether this also occurs in patients undergoing DBPCFCs with cashew nut in the context of a clinical trial.Methods: Quality of life was studied in children enrolled in a cashew nut study using Food Allergy Quality of Life Questionnaires (FAQLQs). Children, teenagers and parents of the children completed the questionnaires before the challenge test and 6 months after the DBPCFC with cashew nut. The difference in the change in HRQL between the children with a positive and negative DBPCFC outcome was studied by Mann-Whitney U-test.Results: In total, 112 children (67 boys, median age of 9 years) were included. The children, teenagers and parents of the children completed 143 sets of questionnaires in total. There were no significant differences in baseline total and domain scores compared to the follow-up scores in the FAQLQ-CF, FAQLQ-TF and FAQLQ-PF. In children, the delta FAIM score in the negative DBPCFC tested group was significantly better than the delta FAIM score in the positive challenged group (p = 0.026). There were no significant differences in the changes in the scores of the FAQLQ-CF and FAQLQ-PF in the children with a positive challenge outcome, compared to the children with a negative challenge result. However, there was a significant difference in the change in score between the latter groups in the domain 'accidental exposure' of the FAQLQ-TF (p = 0.049).Conclusion: This study showed no difference in the change in HRQL scores after a DBPCFC with cashew nut in children participating in a clinical trial. The utility of HRQL as an outcome for clinical trials in food allergy may be limited if participant baseline HRQL is relatively unimpaired.

Background: While genetic factors are known to be important in the development of sensitization to foods, it is not known whether they also play a role in clinical allergic reactivity to foods. Objective: We aimed to determine whether parental atopic diseases are associated with a higher risk of a reaction to common allergenic foods when tested in a double-blind, placebo-controlled food challenge (DBPCFC). Methods: Parents of children suspected of being food allergic were interviewed about their own and their child’s atopic history. Specific IgE and skin prick tests to food allergens and the outcome of food challenges in the child were recorded. Results: Data from 553 double-blind food challenges performed in 396 children were analyzed. The foods tested were milk (n = 185), egg (n = 110), peanut (n = 198) and hazelnut (n = 60). Only parental eczema was significantly associated with positive outcomes for food challenges with milk after correction for age, sex, atopic comorbidity in the child and milk-specific IgE test results (odds ratio 3.1, 95% confidence interval 1.5–6.3). Conclusions: Children with a positive DBPCFC to milk more frequently have parents with eczema than children with a negative test. This effect of parental eczema was not seen in children challenged with egg, peanut or hazelnut. Clinical reactivity to milk may be caused by genetic factors which are shared with parental eczema to a greater extent than clinical reactivity to other foods.