Search

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.

Background: Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy., Methods: The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1-67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose., Discussion: This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid., Trial Registration: German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de ., (© 2022. The Author(s).)

Food allergy is a collective term for several immune-mediated responses to food. IgE-mediated food allergy is the best-known subtype. The patients present with a marked diversity of clinical profiles including symptomatic manifestations, threshold reactivity and reaction kinetics. In-vitro predictors of these clinical phenotypes are evasive and considered as knowledge gaps in food allergy diagnosis and risk management. Peanut allergy is a relevant disease model where pioneer discoveries were made in diagnosis, immunotherapy and prevention. This review provides an overview on the immune basis for phenotype variations in peanut-allergic individuals, in the light of future patient stratification along emerging omic-areas. Beyond specific IgE-signatures and basophil reactivity profiles with established correlation to clinical outcome, allergenomics, mass spectrometric resolution of peripheral allergen tracing, might be a fundamental approach to understand disease pathophysiology underlying biomarker discovery. Deep immune phenotyping is thought to reveal differential cell responses but also, gene expression and gene methylation profiles (eg, peanut severity genes) are promising areas for biomarker research. Finally, the study of microbiome-host interactions with a focus on the immune system modulation might hold the key to understand tissue-specific responses and symptoms. The immune mechanism underlying acute food-allergic events remains elusive until today. Deciphering this immunological response shall enable to identify novel biomarker for stratification of patients into reaction endotypes. The availability of powerful multi-omics technologies, together with integrated data analysis, network-based approaches and unbiased machine learning holds out the prospect of providing clinically useful biomarkers or biomarker signatures being predictive for reaction phenotypes., Competing Interests: PS declares being a scientific advisor in RefLab ApS. CB-J declares being a Clinical Investigator for Novartis, Aimmune, Hal Allergy, Allakos, and Miltenyi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Czolk, Klueber, Sørensen, Wilmes, Codreanu-Morel, Skov, Hilger, Bindslev-Jensen, Ollert and Kuehn.)

Rationale: Food allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented., Methods: A questionnaire was developed evaluating allergists' management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK)., Results: Here, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (<50%). At initial diagnosis, oral food challenge was used less in DE (13%) and FR (14%) and very rarely in the UK (3%) to confirm diagnosis. Recognition of acute reactions, use of adrenaline auto-injectors and allergen avoidance were reported to be discussed with the patient/caregiver at the initial office visit by most allergists (>75%). Half of the responders reported assessing the patient's quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a 'very significant' barrier for optimal PA treatment, with allergists being less than 'moderately familiar' with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient's PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment., Conclusions: This survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare., Competing Interests: The authors have read the journal’s policy and have the following competing interests: SZ, RR, ST and RSM are or were employed by Aimmune Therapeutics Inc. during the course of the study. WC is an employee of CE Outcomes LLC, and JJ is an employee of Food Allergy Pros LLC. VS received speakers’ honoraria from Aimmune and is a principal investigator for Aimmune-sponsored ARC008 and ARC005 studies. VS held consultancy briefly with Novartis and Mead-Johnson and received sponsorship to attend and talk at educational events from other pharmaceutical companies. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Nut intake has been associated with reduced cancer-related mortality, but there is very limited evidence on total cancer risk. We investigated the associations of nut and peanut butter intake with the risk of total cancer and smoking- and alcohol-related cancer subgroups., Methods: In the prospective Netherlands Cohort Study, 120,852 men and women aged 55 to 69 years provided information on lifestyle and dietary habits at baseline in 1986. After 20.3 years of follow-up, 19,255 total cancer cases and 3,499 subcohort members were included in multivariable-adjusted Cox regression analyses, using a case-cohort approach., Results: No significant associations were found between total nut, tree nut, peanut, and peanut butter intake and total cancer risk in men and women. There were also no significant associations with smoking-(un)related and alcohol-(un)related cancers in both sexes., Conclusions: Our findings suggest that nut and peanut butter intake are not associated with a reduced risk of total cancer in men or women., Impact: Nut and peanut butter consumption are not related to the risk of total cancer., (©2020 American Association for Cancer Research.)

Background: It is not established whether the risk of anaphylaxis induced by peanuts or tree nuts in children increases at specific times of the year. We aimed to evaluate the risk of peanut-and tree-nut-induced anaphylaxis during certain cultural holidays in Canadian children., Methods: We collected data on confirmed pediatric cases of anaphylaxis presenting to emergency departments in 4 Canadian provinces as part of the Cross-Canada Anaphylaxis Registry. We assessed the mean number of cases per day and incidence rate ratio (IRR) of anaphylaxis induced by unknown nuts, peanuts and tree nuts presenting during each of 6 holidays (Halloween, Christmas, Easter, Diwali, Chinese New Year and Eid al-Adha) versus the rest of the year. We estimated IRRs and 95% confidence intervals (CIs) using Poisson regression., Results: Data were collected for 1390 pediatric cases of anaphylaxis between 2011 and 2020. Their median age was 5.4 years, and 864 (62.2%) of the children were boys. During Halloween and Easter, there were higher rates of anaphylaxis to unknown nuts (IRR 1.66, 95% CI 1.13-2.43 and IRR 1.71, 95% CI 1.21-2.42, respectively) and peanuts (IRR 1.86, 95% CI 1.12-3.11 and IRR 1.57, 95% CI 0.94-2.63, respectively) compared to the rest of the year. No increased risk of peanut- or tree-nut-induced anaphylaxis was observed during Christmas, Diwali, Chinese New Year or Eid al-Adha. Anaphylaxis induced by unknown nuts, peanuts and tree nuts was more likely in children aged 6 years or older than in younger children., Interpretation: We found an increased risk of anaphylaxis induced by unknown nuts and peanuts during Halloween and Easter among Canadian children. Educational tools are needed to increase awareness and vigilance in order to decrease the risk of anaphylaxis induced by peanuts and tree nuts in children during these holidays., Competing Interests: Competing interests: Judy Morris received a grant from AllerGen Canada (Allergy, Genes and Environment Network), a Networks of Centres of Excellence research network, to allow the data for the project to be collected at her university hospital. AllerGen Canada is a not-for-profit network based at McMaster University. Julia Upton received advisor fees from Food Allergy Canada, ALK-Abelló, Kaléo and Bausch Health; research grant support from the Toronto SickKids Food Allergy and Anaphylaxis fund, DBV Technologies, Regeneron, the Canadian Institutes of Health Research and ALK-Abelló; and an in-kind contribution from Novartis, outside the submitted work. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Introduction: Food allergy is increasing in prevalence and the severity of allergic reactions is unpredictable. Identifying food-allergic patients at high risk of severe reactions would allow us to offer a personalized and improved management for these patients., Areas Covered: We review the evidence for using the levels of specific IgE, the nature of the allergen, and cellular tests to identify patients at high risk of developing severe allergic reactions to foods., Expert Opinion: The evidence about whether the quantity of allergen-specific IgE reflects the severity of allergic reactions to foods is conflicting, with some positive and some negative studies. For some foods, specific IgE to individual components (e.g. Ara h 2 in peanut) can provide additional information. However, more important than the quantity of IgE is possibly the quality of IgE, which can be captured by individual measurements of affinity/avidity, diversity, and specific activity, but is best measured overall using the basophil and mast cell activation tests, which assess the function of IgE in its ability to induce cell activation, degranulation, and mediator release. Biomarkers look at a single aspect of the allergic response and should be interpreted in the broader clinical context for each individual patient assessed.

A 13-year-old boy presented to the hospital with a 3-month history of repeated vomiting and abdominal pain. Results of esophagogastroduodenoscopy revealed a diagnosis of eosinophilic gastroenteritis (EGE). We initiated a short-term six-food elimination diet (SFED) and reintroduction therapy over five days. On the third day of SFED, the patient's abdominal symptoms completely disappeared. However, he experienced unbearable abdominal pain six hours after the reintroduction of milk and peanuts. His symptoms remain completely controlled at present after eliminating milk and peanut products. The SFED and reintroduction therapy for EGE may be effective even for short-term treatments over a five-day period.

While peanut oral immunotherapy (POIT) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4-9.0; 27 studies, I 2  = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5-11.4; 26 studies, I 2  = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8-3.7; 15 studies, I 2  = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.

Background: Current laboratory tests are less than 50% accurate in distinguishing between people who have food allergies (FA) and those who are merely sensitized to foods, resulting in the use of expensive and potentially dangerous Oral Food Challenges. This study presents a purely-computational machine learning approach, conducted using DNA Methylation (DNAm) data, to accurately diagnose food allergies and potentially find epigenetic targets for the disease., Methods and Results: An unbiased feature-selection pipeline was created that narrowed down 405,000+ potential CpG biomarkers to 18. Machine-learning models that utilized subsets of this 18-feature aggregate achieved perfect classification accuracy on completely hidden test cohorts (on an 8-fold hidden dataset). Ensemble classification was also shown to be effective for this High Dimension Low Sample Size (HDLSS) DNA methylation dataset. The efficacy of these machine learning classifiers and the 18 CpGs was further validated by their high accuracy on a large number of hidden data permutations, where the samples in the training, cross-validation, and hidden sets were repeatedly randomly allocated. The 18-CpG signature mapped to 13 genes, on which biological insights were collected. Notably, many of the FA-discriminating genes found in this study were strongly associated with the immune system, and seven of the 13 genes were previously associated with FA., Conclusions: Previous studies have also created highly-accurate classifiers for this dataset, using both data-driven and a priori biological insights to construct a 96-CpG signature. This research builds on previous work because it uses a completely computational approach to obtain a perfect classification accuracy while using only 18 highly discriminating CpGs (0.005% of the total available features). In machine learning, simpler models, as used in this study, are generally preferred over more complex ones (other things being equal). Lastly, the completely data-driven methodology presented in this research eliminates the need for a priori biological information and allows for generalizability to other DNAm classification problems., Competing Interests: The author, Ayush Alag, is Founder and CEO of Allergezy Inc., a company developing a DNA-methylation based diagnostic test to detect if a person has a food allergy or is sensitized. Allergezy did not provide any financial support in the form of salaries for me (Ayush Alag), nor did it have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. My specific role is articulated in the ‘author contributions’ section. This does not alter my adherence to PLOS ONE policies on sharing data and materials.

Objective: To determine the incidence and temporal trends of food allergies., Patients and Methods: We performed a historical cohort study to describe the epidemiology of food allergies among residents of all ages in Olmsted County, Minnesota, during a 10-year period from January 2, 2002, through December 31, 2011, using the Rochester Epidemiology Project database. Overall incidence and trends in biannual incidence rates over time were evaluated., Results: During the 10-year study period, 578 new cases of food allergies were diagnosed. The average annual incidence rate was significantly higher among males compared with females (4.1 [95% CI, 3.6-4.5] vs 3.0 [95% CI, 2.7-3.4]; P<.001; per 10,000 person-years; 3.6 per 10,000 person-years overall). The pediatric incidence rate of food allergy increased from 7.0 (95% CI, 6.2-8.9) to 13.3 (95% CI, 10.9-15.7) per 10,000 person-years between the 2002-2003 and 2006-2007 calendar periods and then stabilized at 12.5 and 12.1 per 10,000 person-years in the last 2 calendar periods. Milk, peanut, and seafood were the most common allergen in infancy, in children between ages 1 and 4 years, and in the adult population, respectively., Conclusion: This is one of the first population-based studies to examine the temporal trends of food allergies. The incidence of food allergies increased markedly between 2002 and 2009, with stabilization afterward. Additional longitudinal studies are warranted to assess for epidemiological evidence of changes in food allergy incidence with changing recommendations for allergenic food introduction., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

This case series is about four different foreign bodies lodged in different locations of the aerodigestive tract. All four cases had delayed diagnosis due to inconspicuous history. Radiology in the form of computed tomography aided the appropriate diagnosis in most of these cases. Though all four patients have been successfully managed by removal of foreign body, not all of them have identical outcomes. A brief discussion about predictive factors in the fish bone foreign body has been included. The authors also discuss certain critical aspects of the management, which may aid in reducing the morbidity. We emphasise on the high index of suspicion in peculiar cases and on the low threshold for radiological investigation in doubtful clinical scenarios., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited [2018]. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dietary non-digestible oligosaccharides (NDOs) have a protective effect against allergic manifestations in children at risk. Dietary intervention with NDOs promotes the colonization of beneficial bacteria in the gut and enhances serum galectin-9 levels in mice and atopic children. Next to this, NDOs also directly affect immune cells and low amounts may reach the blood. We investigated whether pre-incubation of whole blood from peanut-allergic patients with NDOs or galectin-9 can affect basophil degranulation., Methods: Heparinized blood samples from 15 peanut-allergic adult patients were pre-incubated with a mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS), scFOS/lcFOS, or galectin-9 (1 or 5 µg/mL) at 37°C in the presence of IL-3 (0.75 ng/mL). After 2, 6, or 24 h, a basophil activation test was performed. Expression of FcεRI on basophils, plasma cytokine, and chemokine concentrations before degranulation were determined after 24 h., Results: Pre-incubation with scGOS/lcFOS, scFOS/lcFOS, or galectin-9 reduced anti-IgE-mediated basophil degranulation. scFOS/lcFOS or 5 µg/mL galectin-9 also decreased peanut-specific basophil degranulation by approximately 20%, mainly in whole blood from female patients. Inhibitory effects were not related to diminished FcεRI expression on basophils. Galectin-9 was increased in plasma after pre-incubation with scGOS/lcFOS, and both NDOs and 5 µg/mL galectin-9 increased MCP-1 production., Conclusion and Clinical Relevance: The prebiotic mixture scFOS/lcFOS and galectin-9 can contribute to decreased degranulation of basophils in vitro in peanut-allergic patients. The exact mechanism needs to be elucidated, but these NDOs might be useful in reducing allergic symptoms.

The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily oral treatment with quail egg attenuated mice symptomatology and immune response. Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues like oesophagus, lung, and digestive system. Quail egg treatment resulted in decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that were abnormally expressed in EoE. Other effects included increased IL-10, decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest that quail egg treatment may have therapeutic potential in attenuating the symptoms of food allergy induced EoE like disease through regulating PAR-2 downstream pathway by blocking the activation of the transcription factor NF-kB p65 activity.

Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show that although EPIT, OIT and SLIT were all able to effectively desensitize peanut-sensitized mice, they induced different subsets of Tregs. Foxp3+ Tregs were induced by the three treatment routes but with greater numbers induced by EPIT. EPIT and OIT also increased the level of LAP+ Tregs, whereas SLIT induced IL-10+ cells. The suppressive activity of EPIT-induced Tregs did not depend on IL-10 but required CTLA-4, whereas OIT acted through both mechanisms and SLIT was strictly dependent on IL-10. Moreover, the three routes influenced the homing properties of induced Tregs differently, with a larger repertoire of chemokine receptors expressed by EPIT-induced Tregs compared with OIT- and SLIT- induced cells, resulting in different protective consequences against allergen exposure. Furthermore, whereas OIT- or SLIT-induced Tregs lost their suppressive activities after treatment was discontinued, the suppressive activities of EPIT-induced Tregs were still effective 8 weeks after the end of treatment, suggesting the induction of a more long-lasting tolerance. In summary, EPIT, OIT and SLIT mediated desensitization through the induction of different subsets of Tregs, leading to important differences in the subsequent protection against allergen exposure and the possible induction of tolerance.

Controlled studies on the effect of exercise on intestinal uptake of protein are scarce and underlying mechanisms largely unclear. We studied the uptake of the major allergen Ara h 6 following peanut consumption in an exercise model and compared this with changes in markers of intestinal permeability and integrity. Ten overnight-fasted healthy non-allergic men ( n = 4) and women ( n = 6) (23 ± 4 years) ingested 100 g of peanuts together with a lactulose/rhamnose (L/R) solution, followed by rest or by 60 min cycling at 70% of their maximal workload. Significantly higher, though variable, levels of Ara h 6 in serum were found during exercise compared to rest (Peak p = 0.03; area under the curve p = 0.006), with individual fold changes ranging from no increase to an increase of over 150-fold in the uptake of Ara h 6. Similarly, uptake of lactulose (2-18 fold change, p = 0.0009) and L/R ratios (0.4-7.9 fold change, p = 0.04) were significantly increased which indicates an increase in intestinal permeability. Intestinal permeability and uptake of Ara h 6 were strongly correlated ( r = 0.77, p < 0.0001 for lactulose and Ara h 6). Endurance exercise after consumption may lead to increased paracellular intestinal uptake of food proteins., Competing Interests: The authors declare no conflict of interest.

Background: Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days., Results: All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions were sterile., Conclusions: Our results demonstrate that the used peanut-SLIT protocol is well tolerated and safe in healthy dogs. Further studies should evaluate tolerability, safety and efficacy in dogs with food allergy.

Studies suggest that children who start solid foods early are at risk for developing food allergies. Herein, we evaluated the effects of the introduction of peanuts to the diets of children on emerging peanut allergies. Children with allergic rhinitis and asthma were enrolled in the present study and evaluated in four stages. In the first stage, a clinical history was completed for all participants. In the second stage, skin tests were conducted to detect the sensitization to peanuts. In the third stage, the parents were interviewed about the peanut-eating habits of their children. In the fourth stage, children with a convincing history of allergy or a positive peanut skin test result were subjected to an open oral food challenge (OOFC). Three hundred children in four groups were included, 58.2% of the subjects were male, and the mean age was 7.3±3.9 years. The median age of first exposure to peanuts in patients with peanut allergies was greater than that in children without peanut allergies (2 years versus 1 year; p=0.009). The multivariate analysis, including only those children subjected to the OOFC, revealed that the consumption of peanuts after the age of ≥2 years is a risk factor for developing a peanut allergy (odds ratio=8.0, 95% confidence interval 1.3-50.0, p=0.026). The results of the present study showed that the late introduction of peanuts to children increases the risk of developing a peanut allergy.

Background: Nut intake has been associated with lower mortality, but few studies have investigated causes of death other than cardiovascular disease, and dose-response relationships remain unclear., Methods: We investigated the relationship of nut (tree nut, peanut) and peanut butter intake with overall and cause-specific mortality. In the Netherlands Cohort Study, 120,852 men and women aged 55-69 years provided information on dietary and lifestyle habits in 1986. Mortality follow-up until 1996 consisted of linkage to Statistics Netherlands. Multivariate case-cohort analyses were based on 8823 deaths and 3202 subcohort members with complete data on nuts and potential confounders. We also conducted meta-analyses of our results with those published from other cohort studies., Results: Total nut intake was related to lower overall and cause-specific mortality (cancer, diabetes, cardiovascular, respiratory, neurodegenerative diseases, other causes) in men and women. When comparing those consuming 0.1-<5, 5-<10 and 10+ g nuts/day with non-consumers, multivariable hazard ratios for total mortality were 0.88, 0.74 and 0.77 [95% confidence interval (CI), 0.66-0.89], respectively (Ptrend = 0.003). Cause-specific hazard ratios comparing 10+ vs 0 g/day varied from 0.56 for neurodegenerative to 0.83 for cardiovascular disease mortality. Restricted cubic splines showed nonlinear dose-response relationships with mortality. Peanuts and tree nuts were inversely related to mortality, whereas peanut butter was not. In meta-analyses, summary hazard ratios for highest vs lowest nut consumption were 0.85 for cancer, and 0.71 for respiratory mortality., Conclusions: Nut intake was related to lower overall and cause-specific mortality, with evidence for nonlinear dose-response relationships. Peanut butter was not related to mortality., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk., Methods/design: We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18-year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications., Discussion: This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life., Trial Registration: ClinicalTrial.gov: NCT02046083 (23 January 2014).

Background: Peanut allergy is one of the most severe class I food allergies with increasing prevalence. Especially lipophilic allergens, such as oleosins, were found to be associated with severe symptoms, but are usually underrepresented in diagnostic extracts. Therefore, this study focused on isolation, molecular characterization and assessment of the allergenicity of peanut oleosins., Methods and Results: A comprehensive method adapted for the isolation of peanut oil bodies of high purity was developed comprising a stepwise removal of seed storage proteins from oil bodies. Further separation of the oil body constituents, including the allergens Ara h 10, Ara h 11, the presumed allergen oleosin 3 and additional oleosin variants was achieved by a single run on a preparative electrophoresis cell. Protein identification realized by N-terminal sequencing, peptide mass fingerprinting and homology search revealed the presence of oleosins, steroleosins and a caleosin. Immunoblot analysis with sera of peanut-allergic individuals illustrated the IgE-binding capacity of peanut-derived oleosins., Conclusion: Our method is a novel way to isolate all known immunologically distinct peanut oleosins simultaneously. Moreover, we were able to provide evidence for the allergenicity of oleosins and thus identified peanut oleosins as probable candidates for component-resolved allergy diagnosis.

A new selective electrochemical genosensor has been developed for the detection of an 86-mer DNA peanut sequence encoding part of the allergen Ara h 2 (conglutin-homolog protein). The method is based on a sandwich format, which presents two advantages: it permits shortening the capture probe and avoids labeling of the target. Screen-printed gold electrodes have been used as platform for the immobilization of oligonucleotides by the well-known S-Au bond. Mixed self-assembled monolayers (SAM), including thiol-modified capture probe and mercaptohexanol, were prepared to achieve an organized, homogeneous and not too compact SAM in which unspecific adsorption of the capture probe would be prevented. The optimization of the sensing phase was carried out using the Design of Experiments (DoE) approach. Traditionally, response optimization is achieved by changing the value of one factor at a time until there is no further improvement. However, DoE involves regulating the important factors so that the result becomes optimal. Optimized conditions were found to be 1.34 µM for capture probe concentration and 3.15 mM for mercaptohexanol (spacer) concentration. When the optimal conditions were employed the analytical performance of the proposed genosensor improved significantly, showing a sensitivity as high as 3 µA/nM, with a linear range from 5×10(-11) to 5×10(-8) M and a detection limit of 10 pM., (Copyright © 2014 Elsevier B.V. All rights reserved.)

For most allergenic foods, limited availability of threshold dose information within the population restricts the advice on action levels of unintended allergenic foods which should trigger advisory labeling on packaged foods. The objective of this paper is to provide guidance for selecting an optimal sample size for threshold dosing studies for major allergenic foods and to identify factors influencing the accuracy of estimation. A simulation study was performed to evaluate the effects of sample size and dosing schemes on the accuracy of the threshold distribution curve. The relationships between sample size, dosing scheme and the employed statistical distribution on the one hand and accuracy of estimation on the other hand were obtained. It showed that the largest relative gains in accuracy are obtained when sample size increases from N=20 to N=60. Moreover, it showed that the EuroPrevall dosing scheme is a useful start, but that it may need revision for a specific allergen as more data become available, because a proper allocation of the dosing steps is important. The results may guide risk assessors in minimum sample sizes for new studies and in the allocation of proper dosing schemes for allergens in provocation studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In South East Asia, concerns exist about the acceptability of peanut-based Ready-to-Use-Therapeutic-Foods (RUTF) for the treatment of severe acute malnutrition (SAM). Therefore, an alternative, culturally acceptable RUTF made from locally available ingredients and complying with local food traditions and preferences was developed. The current study evaluated its acceptability and impact on anthropometry., Methods: The study was a randomized, two-arm, cross-over intervention trial to test the acceptability of the local product (bar) against a commercially available, peanut-based RUTF paste (Plumpy'nut®). Children (n = 67) from two kindergartens in a rural area of North Vietnam were recruited. The age of the children was between 3 and 5 years., Results: The Vietnamese RUTF was well-accepted, although overall acceptability was less than of Plumpy'nut®, with the latter scoring higher on palatability (P < 0.05). In contrast, reluctance to eat Plumpy'nut® was higher than for the Vietnamese RUTF (P < 0.05). Impact on anthropmetrical indices was similar for both RUTF. The nutritional status of the children who consumed the two RUTF over a 4 week period improved significantly, with a mean weight gain of 0.64 (SD 0.27) Kg, and increases in WHZ and HAZ z-scores of 0.48 (SD 0.30) and 0.05 (SD 0.13) respectively (P < 0.01 both). Weight gain was similar between the 2 products (0.32 kg per 2 weeks for both)., Conclusions: Both the commercial Plumpy'nut® and the local produced RUTF were accepted although the harder consistency of the local product might have caused the lower overall acceptance. The promising increase in nutritional status needs to be confirmed in a controlled trial in children with SAM.

Peanuts are one of the most relevant foods implicated in IgE-mediated adverse reactions in pediatric population. This study aimed to evaluate the pattern of sensitization towards five peanut allergenic components (rAra h 1, 2, 3, 8 and 9) in a population of Italian children and adolescents with specific IgE (sIgE) to peanut. rAra h 9 was the main allergen implicated in peanut sensitization (58%), followed by rAra h 8 (35%), rAra h 2 (27%), rAra h 3 (23%) and rAra h 1 (12.5%). rAra h 1, 2, and 3 were the main allergenic components in young children: 8/13 (62%) between 2 and 5 years, 8/23 (35%) between 6 and 11 years, and 3/12 (25%) between 1 and 16 years. No differences were found among the levels of sIgE towards rAra h 1, 2, 3, and 9 in the three groups; in contrast, the levels of sIgE against rAra h 8 showed an increasing trend according to age. In conclusion rAra h 1, 2, and 3 were the prevalent sensitizing allergens during the first years of life in Italian patients with sIgE to peanuts ("genuine" allergy); in contrast rAra h 9 and 8 were mainly involved in school-age children and adolescents with pollen allergy ("secondary" sensitization).

Background: Moderate and severe acute malnutrition affects 13% of children <5 y of age worldwide. Severe acute malnutrition affects fewer children but is associated with higher rates of mortality and morbidity. Supplementary feeding programs aim to treat moderate acute malnutrition and prevent the deterioration to severe acute malnutrition., Objective: The aim was to compare recovery rates of children with moderate acute malnutrition in supplementary feeding programs by using the newly recommended ration of ready-to-use supplementary food (RUSF) and the more conventional ration of corn-soya blend (CSB) in Ethiopia., Design: A total of 1125 children aged 6-60 mo with moderate acute malnutrition received 16 wk of CSB or RUSF. Children were randomly assigned to receive one or the other food. The daily rations were purposely based on the conventional treatment rations distributed at the time of the study in Ethiopia: 300 g CSB and 32 g vegetable oil in the control group (1413 kcal) and 92 g RUSF in the intervention group (500 kcal). The higher ration size of CSB was provided because of expected food sharing., Results: The HR for children in the CSB group was 0.85 (95% CI: 0.73, 0.99), which indicated that they had 15% lower recovery (P = 0.039). Recovery rates of children at the end of the 16-wk treatment period trended higher in the RUSF group (73%) than in the CSB group (67%) (P = 0.056)., Conclusion: In comparison with CSB, the treatment of moderate acute malnutrition with RUSF resulted in higher recovery rates in children, despite the large ration size and higher energy content of the conventional CSB ration.

There is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open-label pilot studies to larger randomized designs. Our data show that immunological changes associated with immunotherapy include reduction in mast cell reactivity, decreased basophil responses, decreased specific-immunoglobulin (Ig)E, increased IgG4 and induction of regulatory T cells. Immunotherapy has generated much excitement in the food allergy community; however, further studies are needed before it is ready for clinical use., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)

Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes., Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure., Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2)) and reduced villus/crypt ratios (1.6±0.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm(2), p<0.05), mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05), IL-5 (p<0.05), and IL-13 (p<0.05)--GATA-3 (p<0.05), and intestinal villus sub-atrophia (2.3±0.15). EPIT also increased specific IgG2a (p<0.05) and mRNA expression of Foxp3 (p<0.05) in the esophageal mucosa., Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

Background: Peanut allergy is relatively common among children in developed countries and may have severe outcomes, including anaphylaxis. However, few data about peanut allergy in developing countries are available. Meanwhile, formulated foods with peanuts as a major ingredient are being promoted to prevent and control malnutrition in developing countries., Objective: The objectives of the paper are to review the existing epidemiologic data about peanut allergy, to determine whether the prevalence of peanut allergy is lower in developing countries, and to explore the possible reasons for onset of peanut allergy., Methods: Publications relevant to peanut allergy were searched via Pubmed, and prevalence and etiological factors of peanut allergy were reviewed., Results: Data about peanut allergy were scarce in most developing countries. The existing data support the conclusion that peanut allergy is not as common in developing countries as in developed countries and may not be a major concern for programs promoting formulated food containing peanuts for control of malnutrition. However, plans for treatment of individuals with peanut allergy could be incorporated into these formulated food supplementation programs. A few risk factors (late introduction of peanuts to children, peanut processing technology, non-oral peanut exposure, and maternal peanut exposure during pregnancy and lactation) have been hypothesized to be associated with peanut allergy. However, more conclusive data are needed to verify or disprove these hypotheses., Conclusions: Peanut allergy is not as common in developing countries as in developed countries and may not be a major concern for programs promoting formulated food containing peanuts for control of malnutrition. However, more research about prevalence of peanut allergy is warranted in developing countries.

Family physicians play a central role in the suspicion and diagnosis of immunoglobulin E-mediated food allergies, but they are also critical in redirecting the evaluation for symptoms that patients are falsely attributing to allergies. Although any food is a potential allergen, more than 90 percent of acute systemic reactions to food in children are from eggs, milk, soy, wheat, or peanuts, and in adults are from crustaceans, tree nuts, peanuts, or fish. The oral allergy syndrome is more common than anaphylactic reactions to food, but symptoms are transient and limited to the mouth and throat. Skin-prick and radioallergosorbent tests for particular foods have about an 85 percent sensitivity and 30 to 60 percent specificity. Intradermal testing has a higher false-positive rate and greater risk of adverse reactions; therefore, it should not be used for initial evaluations. The double-blind, placebo-controlled food challenge remains the most specific test for confirming diagnosis. Treatment is through recognition and avoidance of the responsible food. Patients with anaphylactic reactions need emergent epinephrine and instruction in self-administration in the event of inadvertent exposure. Antihistamines can be used for more minor reactions.

Peanut allergens are both stable and potent and are capable of inducing anaphylactic reactions at low concentrations. Consequently, the consumption of peanuts remains the most common cause of food-induced anaphylactic death. Since accidental exposure to peanuts is a common cause of potentially fatal anaphylaxis in peanut-allergic individuals, we tested for the presence of peanut protein in chocolate bars produced in Europe and North America that did not list peanuts as an ingredient. Ninety-two chocolate bars, of which 32 were manufactured in North America and 60 were imported from Europe, were tested by the Veratox assay. None of the 32 North American chocolate products, including 19 with precautionary labeling, contained detectable peanut protein. In contrast, 30.8% of products from western Europe without precautionary labeling contained detectable levels of peanut protein. Sixty-two percent of products from eastern Europe without precautionary labeling contained detectable peanut protein at levels of up to 245 ppm. The absence of precautionary labeling and the absence of the declaration of "peanut" as an ingredient in chocolate bars made in eastern and central Europe were not found to guarantee that these products were actually free of contaminating peanut protein. In contrast, North American manufacturers have attained a consistent level of safety and reliability for peanut-allergic consumers.

Peanut allergy accounts for the majority of severe food-related allergic reactions. It tends to present early in life, and affected individuals generally do not outgrow it. In highly sensitized people, trace quantities can induce an allergic reaction. In this review, we will discuss the prevalence, clinical characteristics, diagnosis, natural history and management of peanut allergy.

Objective: Hepatocellular carcinoma (HCC) is one of the major cancers in the world. In Sudan the incidence is thought to be high and increasing. This study aims to assess the association between peanut butter intake, as a source of aflatoxins, and the GSTM1 genotype in the etiology of HCC., Method: A case control study was conducted among 150 patients and 205 controls from two regions in Sudan. Food habits with special reference to peanut butter consumption, as well as peanut storage systems, have been investigated, as well as confounders such as hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1 genotype was assessed in DNA extracted from blood samples (110 cases, 189 controls)., Results: A positive association was observed for highest vs. lowest quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI) being 3.0 (1.6-5.5) and 1.6 (1.1-2.5) respectively. The positive association with peanut butter intake was essentially limited to subjects with GSTM1 null genotype with OR for highest vs. lowest quartile 16.7 (2.7-105)., Conclusion: Peanut butter consumption has been identified as a strong risk factor of HCC in a region with endemic aflatoxin contamination in Sudan and was essentially limited to subjects with the GSTM1 null genotype.

Food anaphylaxis is now the leading single cause of anaphylactic reactions treated in emergency departments in Westernized countries. In the US, it is estimated that there are 29,000 anaphylactic reactions to foods treated in emergency departments and 125-150 deaths each year. Peanuts, tree nuts, fish and shellfish account for the vast majority of severe food anaphylactic reactions. Immunopathogenic mechanisms responsible for food anaphylaxis may differ somewhat from other forms of anaphylaxis, since elevation of serum tryptase is rarely seen following food anaphylactic reactions. Education regarding the strict avoidance of food allergens, the early recognition of anaphylactic symptoms, and the early use of self-injectable epinephrine remain the mainstays of therapy. However, clinical trials are now underway for the treatment of patients with peanut anaphylaxis utilizing anti-IgE antibody therapy and novel immunomodulatory therapies utilizing 'engineered' recombinant proteins, overlapping peptides, and immunostimulatory deoxyoligonucleotide sequences are being tested in animal models of anaphylaxis.

Objective: To compare findings of tests for nut allergy in children., Design: Retrospective survey of a clinical practice protocol., Setting: Children's hospital paediatric outpatient clinic., Subjects: 96 children referred by general practitioners and accident and emergency doctors over 27 months (1994-96)., Main Outcome Measures: Allergic manifestations (generalised urticarial rash, facial swelling, bronchospasm, anaphylactic shock, vomiting on three occasions) related to specific nut IgE concentrations and following touch, skin prick, or oral ingestion of nuts., Results: 16 children from a sample of 51 who were tested for nut allergy had no reaction to an oral challenge. Positive IgE against peanuts was found in nine of these 16 children., Conclusions: Skin prick testing and IgE measured by radioallergosorbent testing are inadequate tests for nut allergy. The definitive diagnostic test for nut allergy in the hospital setting is direct oral challenge.