EAACI Guidelines on Allergen Immunotherapy: IgE‐mediated Food Allergy.
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.
Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions. Nature communications.
Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanutallergic reactions using serial peripheral blood samples obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4+ T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.
Detection of IgE reactivity to a handful of allergen molecules in early childhood predicts respiratory allergy in adolescence.
BACKGROUND: Sensitization in early childhood may precede respiratory allergy in adolescence. METHODS: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11years (N=248) and the outcome was studied at 11years. FINDINGS: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules. INTERPRETATIONS: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.
Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction.
Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.
Simultaneous Analysis of Multiple Allergens in Food Products by LC-MS/MS.
There is currently no cure for food allergies, and sufferers can only rely on the correct labeling of foods toavoid allergens. Hence, it is important that analytical methods are sensitive and accurate enough to screen for the presence of multiple allergens in food products. In this study, we developed an LC-tandem MS method that is able to simultaneously screen or quantify the signature tryptic peptides of multiple allergen commodities. This method is capable of screening and identifying egg white, skim milk, peanut, soy, and tree nuts (almond, Brazil nut, cashew, hazelnut, pecan, pine nut, pistachio, and walnut) at a detection limit of 10 ppm in incurred bread and cookies. It was further tested for the quantitative analysis of whole-egg, whole-milk, peanut butter, and hazelnut commodities, which are incurred or spiked into selected food matrixes as defined in AOAC INTERNATIONAL Standard Method Performance Requirement (SMPR®) 2016.002. The method demonstrated excellent sensitivity with a Method quantitative limit of 3 ppm for whole egg and 10 ppm for the remaining three allergen commodities. It also demonstrated good recovery (60‒119%) and repeatability (RSDr <20%), with an analytical range of 10-1000 ppm for each allergen commodity and was able to meet the minimum performance requirements of the SMPR.
Undeclared Food Allergens and Gluten in Commercial Food Products Analyzed by ELISA.
Undeclared allergen(s) in commercial food products are responsible for many food recalls, as reported by regulatory agencies in various countries, including the United States. Correct allergen labeling practices are essential for the safety of food-allergic consumers. However, this practice may be hindered by the introduction of allergens all along the food supply chain, including unintentionally through cross-contact. To understand the pervasiveness of undeclared allergen(s) in commercial food products, the objective of this review is to summarize the prevalence of undeclared milk, egg, hazelnut, peanut, soy, and gluten as detected by ELISA from previously published surveys. The prevalence of undeclared allergen(s) in products with or without an advisory statement was also summarized and compared. As compiled by this review, there are some food categories that may be at higher risk for containing undeclared allergen(s). However, the data on prevalence and amount of allergen present may vary widely within any particular allergen or food category. Factors, such as food survey product selection, geography, awareness of allergen/gluten issues, and/or the choice of ELISA method, may be responsible for such differences.
Integrating Allergen Analysis Within a Risk Assessment Framework: Approaches to Development of Targeted Mass Spectrometry Methods for Allergen Detection and Quantification in the iFAAM Project.
Allergen analysis is central to implementing and monitoring food allergen risk assessment and management processes by the food industry, but current methods for the determination of allergens in foods give highly variable results. The European Union-funded "Integrated Approaches to Food Allergen and Allergy Risk Management" (iFAAM) project has been working to address gaps in knowledge regarding food allergen management and analysis, including the development of novel MS and immuno-based allergen determination methods. Common allergenic food ingredients (peanut, hazelnut, walnut, cow's milk [Bos domesticus], and hen's egg [Gallus domesticus]) and common food matrixes (chocolate dessert and cookie) have been used for both clinical studies and analytical method development to ensure that the new methods are clinically relevant. Allergen molecules have been used as analytical targets and allergenic ingredients incurred into matrixes at levels close to reference doses that may trigger the use of precautionary allergen labeling. An interlaboratory method comparison has been undertaken for the determination of peanut in chocolate dessert using MS and immuno-based methods. The iFAAM approach has highlighted the need for methods to report test results in allergenic protein. This will allow food business operators to use them in risk assessments that are founded on clinical study data in which protein has been used as a measure of allergenic potency.
Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents.
BACKGROUND: Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. METHODS: We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. RESULTS: Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). CONCLUSIONS: Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions.
Allergenic food introduction and risk of childhood atopic diseases.
BACKGROUND: The role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. OBJECTIVE: To examine whether timing and diversity of allergenic food introduction are associated with allergic sensitization, allergy and eczema in children until age 10 years. MATERIALS AND METHODS: This study among 5,202 children was performed in a population-based prospective cohort. Timing (age ≤6 months vs. >6 months) and diversity (0, 1, 2 and ≥3 foods) of allergenic food (cow's milk, hen's egg, peanut, tree nuts, soy and gluten) introduction were assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by questionnaire. Data on parental-reported physician-diagnosed eczema were obtained from birth until age 10 years. RESULTS: Children introduced to gluten at age ≤6 months had a decreased risk of eczema (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at age >6 months. However, timing of allergenic food introduction was not associated with allergic sensitization or physician-diagnosed allergy. Children introduced to ≥3 allergenic foods at age ≤6 months had a decreased risk of physician-diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not introduced to any allergenic food at age ≤6 months. However, diversity of allergenic food introduction was not associated with allergic sensitization, physician-diagnosed food allergy or eczema. CONCLUSION: Neither timing nor diversity of allergenic food introduction was consistently associated with childhood allergic sensitization, allergy or eczema.
Health benefits of pistachios consumption.
The health benefits of nuts, mainly in relation to the improvement of dysmetabolic conditions such as obesity, type 2 diabetes mellitus and the related cardiovascular diseases, have been widely demonstrated. Compared to other nuts, pistachios have a lower fat and caloric content, and contain the highest levels of unsaturated fatty acids, potassium, γ-tocopherol, phytosterols and xanthophyll carotenoids, all substances that are well known for their antioxidant and anti-inflammatory actions. This variety of nutrients contributes to the growing body of evidence that the consumption of pistachios improves health, leading to a greater potential of healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. The present review examines the nutrients and phytochemicals present in pistachios as well as the potential health benefits of including pistachios in a diet.