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Background: Food allergy is a leading cause of anaphylaxis worldwide. Allergen‐specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short‐lived efficacy. Allergen‐derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T‐cell epitopes of major peanut allergens for treatment of peanut allergy. Methods: Pre‐clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first‐in‐human, randomized, double‐blind, placebo‐controlled trial in peanut‐allergic adults (46 active, 21 placebo). The repeat‐dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre‐dose, Week 21 and Month 18 after treatment. Results: PVX108 induced negligible activation of peanut‐sensitised basophils. PVX108 was safe and well tolerated in peanut‐allergic adults. There were no treatment‐related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2+ Th2A:CCR6+ Th17‐like cells within the peanut‐reactive Th pool which strengthened following treatment. Conclusion: This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut‐specific T‐cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof‐of‐concept for using peptides to treat food allergy. [ABSTRACT FROM AUTHOR]

Background: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg. Methods: One hundred and fifty children underwent double‐blind placebo‐controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC. Results: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non‐severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid‐sIgE (p =.009) and higher BAT to BE (p =.001). Patients with lower threshold to BE had higher IgE‐specific activity (p =.027) and BAT to egg (p =.007) but lower severity score (p =.008). Optimal cut‐offs for ovomucoid‐sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut‐offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients. Conclusions: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy. [ABSTRACT FROM AUTHOR]

Background: Double‐blind placebo‐controlled food challenges (DBPCFC) are the gold‐standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE). Methods: Children aged 6 months to 15 years were assessed for possible egg allergy as part of the BAT2 study (NCT03309488). They underwent clinical assessment, skin prick test (SPT), specific IgE (sIgE) and basophil activation test (BAT). The results of the tests were compared with DBPCFC outcomes to both BE and LCE. Results: A total of 150 children underwent DBPCFC to BE, 60 (40%) reacted to and 85 (57%) tolerated BE and 5 (3%) had inconclusive oral food challenges (OFC). Seventy‐seven children tolerant to BE had DBPCFC to LCE and 16 reacted. The test within each modality with the best diagnostic performance for BE allergy was as follows: SPT to egg white (EW) (AUC = 0.726), sIgE to EW (AUC = 0.776) and BAT to egg (AUC = 0.783). BAT (AUC = 0.867) was the best test in the younger than 2 years age group. Applying 100% sensitivity and 100% specificity cut‐offs, followed by OFC, resulted in 100% diagnostic accuracy. BAT enabled the greatest reduction in OFC (41%). Using sIgE followed by BAT allowed to reduce the number of BATs performed by about 30% without significantly increasing the number of OFC. Conclusions: The best diagnostic test was BAT to egg in terms of diagnostic accuracy and reduction in number of OFC. Using sIgE to EW followed by BAT required fewer BATs with sustained OFC reduction and diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well‐developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA. [ABSTRACT FROM AUTHOR]

Predicted number of peanut-allergic patients needed to treat with epicutaneous immunotherapy (EPIT) to prevent one allergic reaction: A novel approach to assessing relevance In order to estimate the proportion of allergic reactions occurring due to accidental peanut consumption, which would result in a moderate and/or severe allergic reaction, a review of the relevant literature was performed. The model predicts an average of 182 objective allergic reactions prevented per year for 1000 patients treated and prevention of106 moderate/severe reactions per 1000 patients treated. [Extracted from the article]

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual‐allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL‐33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome. [ABSTRACT FROM AUTHOR]

Background: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. Objective: To identify differences in IgE and IgG4 binding to peanut peptides between peanut‐allergic (PA) and peanut‐sensitized but tolerant (PS) children. Methods: PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15‐mer peptides of peanut allergens (Ara h 1‐11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood‐ratio tests between each specified nominal logistic regression models. Results: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2‐specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. Conclusions: Ara h 2 peptide‐specific IgE added diagnostic value to Ara h 2‐specific IgE. Ability of peptide‐specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance. [ABSTRACT FROM AUTHOR]

Background: The prevention of food allergy is a key priority for reducing the burden of allergic disease. Environmental exposures modulate the risk of developing food allergy and some of this may be mediated by the infants' developing microbiome. However, the role of potentially protective environmental exposures, such as pet ownership, is largely uninvestigated with respect to food allergy. Methods: We performed a secondary cohort analysis in the Enquiring About Tolerance (EAT) study, which enrolled 1303 three‐month infants onto a randomized trial to prevent food allergy. A survey elicited domestic animal ownership and participants were examined for atopic dermatitis (AD) at enrolment. Sensitization to foods and aeroallergens were elicited by skin and serum testing at 3, 12 and 36 months. Food allergy status was determined by double‐blind placebo‐controlled food challenges between 1 and 3 years. Results: Food allergy was diagnosed amongst 6.1% (68/1124) of participants with complete data. No significant relationships were demonstrated between food allergy and caesarean delivery, infections or antibiotic exposure in early life. After adjusting for familial atopic disease, maternal dog/cat sensitization and participant AD, living with dogs was associated with a 90% reduction in the odds of infants developing food allergy (adjusted odds ratio (aOR) 0.10 (confidence interval (CI) 0.01‐0.71), P = 0.02). None of the 49 infants living with at least two dogs developed food allergy, suggesting a dose‐response relationship (each dog owned aOR 0.12 (CI 0.02‐0.81), P = 0.03). No relationship was demonstrated between owning dogs or cats and the development of AD. Conclusion: Dog ownership in infancy may prevent food allergy. [ABSTRACT FROM AUTHOR]

Oral food challenge (OFC) is the gold-standard to diagnose food allergy; however, it is a labour and resource-intensive procedure with the risk of causing an acute allergic reaction, which is potentially severe. Therefore, OFC are reserved for cases where the clinical history and the results of skin prick test and/or specific IgE do not confirm or exclude the diagnosis of food allergy. This is a significant proportion of patients seen in Allergy clinics and results in a high demand for OFC. The basophil activation test (BAT) has emerged as a new diagnostic test for food allergy. With high diagnostic accuracy, it can be particularly helpful in the cases where skin prick test and specific IgE are equivocal and may allow reducing the need for OFC. BAT has high specificity, which confers a high degree of certainty in confirming the diagnosis of food allergy and allows deferring the performance of OFC in patients with a positive BAT. The diagnostic utility of BAT is allergen-specific and needs to be validated for different allergens and in specific patient populations. Standardisation of the laboratory methodology and of the data analyses would help to enable a wider clinical application of BAT. [ABSTRACT FROM AUTHOR]

The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology. [ABSTRACT FROM AUTHOR]

Despite efforts to prevent food allergy (FA) in children, IgE-mediated FAs are increasing in westernized countries. Previous preventive strategies, such as prolonged exclusive breast-feeding and delayed weaning onto solid foods, have recently been called into question. The present review considers possible risk factors and theories for the development of FA. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure to food allergen induces tolerance. Novel interventional strategies to prevent the development of FA are also discussed. [ABSTRACT FROM AUTHOR]

We reviewed the evidence linking otitis media with effusion (OME) and atopy, with the goal of clarifying the possible role of intranasal corticosteroids (INSs) in OME treatment. In August 2009, the MEDLINE database was searched for primary studies on OME epidemiology, pathophysiology, and treatment. Relevant clinical guidelines were obtained. Interpreting OME research is complicated by variable disease definitions, patient populations, methodologies, and outcomes assessments, along with the possibility of spontaneous resolution. However, evidence links OME with atopic conditions including allergic rhinitis; observed prevalence of allergic rhinitis in patients with chronic or recurrent OME ranges from 24% to 89%. Such findings have prompted evaluations of common allergy medications for OME treatment. While short-term use of INSs alone or combined with antibiotics has shown benefit in some studies, more prolonged treatment protocols and long-term clinical outcomes will require critical assessment. Evidence suggesting epidemiologic and pathophysiologic links between allergy and OME has prompted investigation into a potential role for INSs in OME management, with promising initial results. Benefits of considering medical treatment in patients with OME prior to surgery include both the potential reductions in allergic inflammation and the naturally occurring spontaneous resolution of OME in these patients. [ABSTRACT FROM AUTHOR]

Background: Most children with peanut allergy (PA) react on first known oral exposure to peanut. Recent data suggest cutaneous exposure as a route of sensitization. Objectives: This study aimed to establish the relevant route of peanut exposure in the development of allergy. Methods: Questionnaires were administered to children with PA and to high-risk controls (with egg allergy) and controls without allergy. Questionnaires were completed before subjects were aware of their PA status, avoiding recall bias. Questionnaires recorded maternal peanut consumption during pregnancy, breast-feeding, and the first year of life. Peanut consumption was determined among all household members, allowing quantification of environmental household exposure (household peanut). Results: Median weekly household peanut in the 133 PA cases was significantly elevated (18.8 g) compared with 150 controls without allergy (6.9 g) and 160 high-risk controls (1.9 g). There were no differences in infant peanut consumption between groups. Differences in maternal peanut consumption during pregnancy (and lactation) were significant but become nonsignificant after adjusting for household peanut. A dose-response relationship was observed between environmental (nonoral) peanut exposure and the development of PA, which was strongest for peanut butter. Early oral exposure to peanut in infants with high environmental peanut exposure may have had a protective effect against the development of PA. Conclusions: High levels of environmental exposure to peanut during infancy appear to promote sensitization, whereas low levels may be protective in atopic children. No effect of maternal peanut consumption during pregnancy or lactation is observed, supporting the hypothesis that peanut sensitization occurs as a result of environmental exposure. [Copyright &y& Elsevier]

Atopy is common and the prevalence amongst children is rising. Measurements in early childhood that can predict subsequent development of atopy could be clinically useful for targeting preventive measures. We used the Children in Focus (CiF) subgroup of a large population-based birth cohort study (the Avon Longitudinal Study of Parents and Children) to investigate whether total immunoglobulin E (IgE) measured at 12 and 18 months could predict subsequent development of atopy at 5 yr of age. Atopy was determined by positive skin prick test (≥3 mm wheal) to one or more of 14 inhalant and food allergens. Prevalence of skin prick positivity to any allergen was 14.5% (104 of 715; 95% CI: 12.0–17.1%). Total IgE levels were significantly higher at 12 months of age (p < 0.0005) but not 18 months of age in those children subsequently atopic. The highest positive predictive value was 41% with an IgE measurement of >51 kU/l, with a sensitivity of 13.5% and a specificity of 95.8%. Although significant differences in early life IgE measurements were seen, the extent of overlap was great, such that the overall performance of IgE at 12 months as a screening test for atopy was poor. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the use of specific immunotherapy (SIT) for childhood seasonal allergic asthma. Objective: We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen (Phleum pratense Alutard SQ; ALK-Abelló, Hørsholm, Denmark) in children with seasonal allergic asthma. Methods: A randomized, double-blind, placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16 years) with a history of seasonal allergic asthma sensitized to grass pollen (P pratense) and requiring at least 200 μg of inhaled beclomethasone equivalent per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded. The primary outcome measure was a combined asthma symptom-medication score during the second pollen season. Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen, sputum eosinophilia, exhaled nitric oxide, and adverse events. Results: Thirty-nine subjects were enrolled. Thirty-five subjects provided data for analysis. The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo (P = .04). There were also significant reductions in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P = .01) reactivity to allergen after SIT compared with that after placebo. The 2 groups had similar levels of airway inflammation, despite a trend toward less inhaled steroid use in the active group. No serious adverse events were reported, and no subjects withdrew because of adverse events. Conclusion: The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen. [Copyright &y& Elsevier]

The main concerns about adverse effects of genetically modified (GM) foods on health are the transfer of antibiotic resistance, toxicity and allergenicity. There are two issues from an allergic standpoint. First, the transfer of a known allergen may occur from a crop into a non-allergenic target crop. The second scenario is the creation of a neo-allergen where de novo sensitisation occurs in the population. The first scenario occurred in 1996 when the 2S albumen protein from Brazil nut was transferred into soy bean (N. Engl. J. Med. 334 (1996) 688). 2S albumen was found to be a major Brazil nut allergen and the newly expressed protein in transgenic soy retained its allergenicity. Patients allergic to Brazil nuts and not to soy bean now showed an IgE mediated response towards GM soy bean. We argue that it is possible to prevent such occurrences by doing IgE-binding studies and taking into account physico-chemical characteristics of proteins and referring to known allergen databases. The second possible scenario of de novo sensitisation does not easily lend itself to risk assessment. We compare GM technology to traditional plant breeding and food processing methods. There is no evidence that the technology used for the production of GM foods poses an allergic threat per se compared to other methodologies widely accepted in the food industry. We need to proceed cautiously in the future, assessing individual GM foods on the basis of their individual merits and risks prior to introducing them into the market. [Copyright &y& Elsevier]

The National Academies of Sciences, Engineering, and Medicine convened an expert, ad hoc committee to examine critical issues related to food allergy. The authors of the resulting report, "Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy," evaluated the scientific evidence on the prevalence, diagnosis, prevention, and management of food allergy and made recommendations to bring about a safe environment for those affected. The committee recommended approaches to monitor prevalence, explore risk factors, improve diagnosis, and provide evidence-based health care. Regarding diagnostics, emphasis was placed on utilizing allergy tests judiciously in the context of the medical history because positive test results are not, in isolation, diagnostic. Evidence-based prevention strategies were advised (for example, a strategy to prevent peanut allergy through early dietary introduction). The report encourages improved education of stakeholders for recognizing and managing as well as preventing allergic reactions, including an emphasis on using intramuscular epinephrine promptly to treat anaphylaxis. The report recommends improved food allergen labeling and evaluation of the need for epinephrine autoinjectors with a dosage appropriate for infants. The committee recommended policies and guidelines to prevent and treat food allergic reactions in a various settings and suggested research priorities to address key questions about diagnostics, mechanisms, risk determinants, and management. Identifying safe and effective therapies is the ultimate goal. This article summarizes the key findings from the report and emphasizes recommendations for actions that are applicable to pediatricians and to the American Academy of Pediatrics. [ABSTRACT FROM AUTHOR]

Background: The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors. Methods: We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life). Results: Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of prenatal sensitization from the maternal diet, and peanut-specific IgE was not detectable in the cord blood. Peanut allergy was independently associated with intake of soy milk or soy formula (odds ratio, 2.6; 95 percent confidence interval, 1.3 to 5.2), rash over joints and skin creases (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 5.0), and oozing, crusted rash (odds ratio, 5.2; 95 percent confidence interval, 2.7 to 10.2). Analysis of interview data showed a significant independent relation of peanut allergy with the use of skin preparations containing peanut oil (odds ratio, 6.8; 95 percent confidence interval, 1.4 to 32.9). Conclusions: Sensitization to peanut protein may occur in children through the application of peanut oil to inflamed skin. The association with soy protein could arise from cross-sensitization through common epitopes. Confirmation of these risk factors in future studies could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy. N Engl J Med 2003;348:977-85. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the proposed strategies for the prevention of peanut allergies among infants and recommends the appropriate strategy. Topics include a description of the Learning Early about Peanut Allergy (LEAP) program used to acquire the relevant population data , the use of statistical tools such as the two-tailed chi-square test in the analysis, and the study's conclusion about early introduction of peanuts and the decreased risk of developing the allergy.