Design of the Intervention to Reduce Early Peanut Allergy in Children (iREACH): A practice-based clinical trial.

BACKGROUND: Introducing peanut products early can prevent peanut allergy (PA). The "Addendum guidelines for the prevention of PA in the United States" (PPA guidelines) recommend early introduction of peanut products to low and moderate risk infants and evaluation prior to starting peanut products for infants at high risk for PA (those with severe eczema and/or egg allergy). Rapid adoption of guidelines could aid in lowering the prevalence of PA. The Intervention to Reduce Early (Peanut) Allergy in Children (iREACH) trial was designed to promote PPA guideline adherence by pediatric clinicians. METHODS: A two-arm, cluster-randomized, controlled clinical trial was designed to measure the effectiveness of an intervention that included clinician education and accompanying clinical decision support tools integrated in electronic health records (EHR) versus standard care. Randomization was at the practice level (n = 30). Primary aims evaluated over an 18-month trial period assess adherence to the PPA guidelines using EHR documentation at 4- and 6-month well-child care visits aided by natural language processing. A secondary aim will evaluate the effectiveness in decreasing the incidence of PA by age 2.5 years using EHR documentation and caregiver surveys. The unit of observation for evaluations are individual children with clustering at the practice level. CONCLUSION: Application of this intervention has the potential to inform the development of strategies to speed implementation of PPA guidelines.

Optimising the management of peanut allergy by targeting immune plasticity.

Randomised controlled trials investigating the efficacy of oral tolerance induction to peanut have enabled detailed comparison of their clinical and immunological success. They have demonstrated that the regular consumption of peanut for at least 2 years by babies who are not allergic enables protection from developing peanut allergy. The LEAP study intervention tested the impact of regular peanut consumption for 4 years and demonstrated a sustained protection against the development of peanut allergy even after 12 months of peanut avoidance from 5 to 6 years of age. The PreventADALL trial introduced multiple allergens into babies' diets from early infancy and reduced the prevalence of food allergy at 3 years, especially by protecting against peanut allergy. Immunological studies from the LEAP cohort demonstrated that regular peanut consumption was associated with a prompt induction of peanut-specific IgG4 and reduced manufacture of peanut and Ara h 2-specific IgE. Even after stopping peanut consumption for 5 years, there continued to be a significant fall in peanut-specific Ara h 2 IgE in the consumption group from 5 to 6 years of age (p < .01). Children who developed peanut allergy by 5 years started to develop increasing sensitisation to linear sequential peanut epitopes from 2.5 years of age, suggesting that putative disease-modifying interventions should commence before 3 years. Data comparing clinical outcomes between children undergoing peanut immunotherapy from infancy suggest that younger children can consume higher portions of peanut without reaction on challenge whilst taking immunotherapy, have fewer side effects and are more likely to enjoy remission of PA. Peanut oral immunotherapy modulates T-cell populations in order to bring about hypo-responsiveness of allergy effector cells. Studies are now needed to characterise and compare different states of immunological tolerance. This will accelerate the design of interventions which can promote primary, secondary and tertiary levels of PA prevention across a range of age groups.

Risk subgroups and intervention effects among infants at high risk for peanut allergy: A model for clinical decision making.

BACKGROUND: The Learning Early About Peanut Allergy (LEAP) trial showed that early dietary introduction of peanut reduced the risk of developing peanut allergy by age 60 months in infants at high risk for peanut allergy. In this secondary analysis of LEAP data, we aimed to determine risk subgroups within these infants and estimate their respective intervention effects of early peanut introduction. METHODS: LEAP raw data were retrieved from ITNTrialShare.org. Conditional random forest was applied to participants in the peanut avoidance arm to select statistically important features for the classification and regression tree (CART) analysis to group infants based on their risk of peanut allergy at 60 months of age. Intervention effects were estimated for each derived risk subgroup using data from both arms. Our main model was generated based on baseline data when the participants were 4-11 months old. Specific IgE measurements were truncated to account for the limit of detection commonly used by laboratories in clinical practice. RESULTS: The model found infants with higher predicted probability of peanut allergy at 60 months of age had a similar relative risk reduction, but a greater absolute risk reduction in peanut allergy with early introduction of peanut, than those with lower probability. The intervention effects were significant across all risk subgroups. Participants with baseline peanut sIgE ≥0.22 kU/L (n = 78) had an absolute risk reduction of 40.4% (95% CI 27.3, 51.9) whereas participants with baseline peanut sIgE<0.22 kU/L and baseline Ara h 2 sIgE <0.10 kU/L (n = 226) had an absolute risk reduction of 6.5% (95% CI 2.6, 11.0). These findings were consistent in sensitivity analyses using alternative models. CONCLUSION: In this study, risk subgroups were determined among infants from the LEAP trial based on the probability of developing peanut allergy and the intervention effects of early peanut introduction were estimated. This may be relevant for further risk assessment and personalized clinical decision-making.

Food allergies: Updates for nurses.

ABSTRACT: Food allergies are on the rise; the incidence and types of foods implicated have increased worldwide. While peanut allergies are the most well-known, allergies exist to almost all types of foods. This article discusses various types of food allergies along with the most recent prevention and treatment strategies.

Screening of probiotic Lactobacillus to reduce peanut allergy and with potential anti-allergic activity.

BACKGROUND: Peanut is a significant source of nutrition and a valuable oilseed crop. It is also a serious allergy source, which poses a threat to 1.1% of the population. This study aimed to screen lactic acid bacteria (LAB) with the capacity to alleviate peanut allergenicity and exhibit anti-allergic properties. RESULT: The results show that LAB can make use of substances in peanuts to reduce the pH of peanut milk from 6.603 to 3.593-4.500 by acid production and that it can utilize the protein in peanuts to reduce the allergenic content (especially Ara h 1) and improve biological activity in peanut pulp. The content of Ara h 1 peanut-sensitizing protein was reduced by 74.65% after fermentation. The protein extracted from fermented peanut pulp is more readily digestible by gastrointestinal juices. The inhibitory activity assay of hyaluronidase (an enzyme with strong correlation to allergy) increased from 46.65% to a maximum of 90.57% to reveal that LAB fermentation of peanut pulp exhibited a robust anti-allergic response. CONCLUSION: The strains identified in this study exhibited the ability to mitigate peanut allergenicity partially and to possess potential anti-allergic properties. Lactobacillus plantarum P1 and Lactobacillus salivarius C24 were identified as the most promising strains and were selected for further research. © 2023 Society of Chemical Industry.

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

BACKGROUND: Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD: The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS: A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS: Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.

Reaching Communities Through Food Allergy Advocacy, Research, and Education: A Comprehensive Analysis.

This article explores the multifaceted approach of food allergy (FA) advocacy, research, and education to address the diverse challenges associated with FA, such as disparities in socioeconomic status, food security, quality of life, and the overall burden of the disease. Advocacy initiatives are instrumental in driving policy changes, raising public awareness, and directing substantial research funding, with a focus on reducing disparities. They have influenced allergen labeling regulations and improved access to epinephrine, emphasizing the importance of school-based management plans, especially in underserved communities. Research in FA informs medical practices and offers them hope for improved treatments. Recent breakthroughs in peanut allergy prevention and oral immunotherapy trials exemplify the potential for advancements while highlighting the need to address disparities in health care access. Education is a critical tool for prevention, raising awareness, and reducing the risk of allergic reactions. Efforts should be tailored to reach marginalized communities, particularly in schools where education on FA management is essential. Collaborating directly with communities is imperative to ensure inclusivity and address disparities. Barriers such as mistrust, language and cultural differences, and lack of diversity among researchers must be overcome to encourage diverse participation in research studies. This article concludes by emphasizing the significance of a comprehensive approach to FA research that prioritizes equity and inclusivity. The call to action highlights the need for global initiatives to reshape the landscape of FA care and address disparities in health care access and outcomes.

Early Peanut Immunotherapy in Children (EPIC) trial: protocol for a pragmatic randomised controlled trial of peanut oral immunotherapy in children under 5 years of age.

INTRODUCTION: Food allergy is a major public health challenge in Australia. Despite widespread uptake of infant feeding and allergy prevention guidelines the incidence of peanut allergy in infants has not fallen, and prevalence of peanut allergy in school-aged children continues to rise. Therefore, effective and accessible treatments for peanut allergy are required. There is high-quality evidence for efficacy of oral immunotherapy in children aged 4-17 years old; however, few randomised trials have investigated peanut oral immunotherapy (OIT) in young children. Furthermore, the use of food products for OIT with doses prepared and administered by parents without requiring pharmacy compounding has the potential to reduce costs associated with the OIT product. METHODS AND ANALYSIS: Early Peanut Immunotherapy in Children is an open-label randomised controlled trial of peanut OIT compared with standard care (avoidance) to induce desensitisation in children aged 1-4 years old with peanut allergy. n=50 participants will be randomised 1:1 to intervention (daily peanut OIT for 12 months) or control (peanut avoidance). The primary outcome is the proportion of children in each group with a peanut eliciting dose >600 mg peanut protein as assessed by open peanut challenge after 12 months, analysed by intention to treat. Secondary outcomes include safety as assessed by frequency and severity of treatment-related adverse events, quality of life measured using age-appropriate food allergy-specific questionnaires and immunological changes during OIT. ETHICS: The trial is approved by the Child and Adolescent Health Service Human Research Ethics Committee and prospectively registered with the Australia and New Zealand Clinical Trials Registry. DISSEMINATION: Trial outcomes will be published in a peer-review journal and presented and local and national scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12621001001886.

Early Peanut Introduction in Infants: Improving Guideline Adherence With EMR Standardization.

OBJECTIVES: Peanut allergy in children is a population health problem. Evidence suggests early peanut introduction (EPI) for infants can reduce the development of peanut allergy. Primary care settings have not widely adopted guidelines recommending EPI. Peanut allergy prevention depends on primary care providers incorporating EPI guidelines into well-child check (WCC) encounters. We aimed to improve guideline adherence in a primary care setting by implementing a bundle of clinical decision support (CDS) tools. METHODS: Using quality improvement methodology, the team developed a standardized work protocol and CDS tools within an electronic medical record (EMR) at 4, 6, and 9-month WCC encounters. The team executed changes and modifications through plan-do-study-act cycles and analyzed results with statistical process control charts. RESULTS: We collected data from 445 WCC encounters from baseline through sustainability. EMR documentation of EPI guidance at 4, 6, and 9-month WCCs shifted from 13.9% to 83.5% over 12 months. Provider adoption of smart lists and templates increased from 2% to 73%, the distribution of home peanut introduction handouts increased from 5.2% to 54.1%, and caregiver-reported peanut ingestion increased from 0% to 34.6%. Diphtheria-tetanus-acellular pertussis vaccination rates remained at 100% for 6-month visits, and patient in-room time remained at 65 minutes. CONCLUSIONS: Quality improvement methodology improved documentation of EPI guidance and increased reported peanut ingestion at routine WCC encounters without impacting other measures. Broader use of bundled CDS tools and EMR standardization could further improve guideline adherence and increase early peanut introduction to prevent peanut allergy in infants.

Updates in Food Allergy Prevention in Children.

Although significant evidence exists that feeding early has a role in the prevention of food allergy, this intervention in isolation may not be sufficient. Recent evidence highlights that early introduction of peanut specifically has had no significant impact on the populational prevalence of peanut allergy. Other factors that may contribute to food allergy prevention include regularity of ingestion once an allergen is introduced and consideration to the form in which the allergen is introduced (such as baked versus cooked egg). There are also many practicalities to early feeding and some discrepant viewpoints on these practicalities, which has led to poor implementation of early feeding strategies. In general, preemptive screening before food introduction is not recommended by most international allergy societies. Although there is little guidance to inform early introduction of allergens other than milk, egg, and peanut, the mechanism of sensitization is thought to be similar and there is no harm to early introduction. In terms of frequency and duration of feeding, there is little evidence to inform any concrete recommendations.

Food Allergies: Diagnosis, Treatment, and Prevention.

In the United States, approximately 2% to 3% of adults and 8% of children have a food allergy. Allergic reactions range from minor pruritus to life-threatening anaphylaxis. These allergies often lead to significant anxiety and costs for patients and caregivers. Common food allergies include peanuts, cow's milk, shellfish, tree nuts, egg, fish, soy, and wheat. Peanut allergy, the most common, is the leading cause of life-threatening anaphylaxis. Children with asthma, allergic rhinitis, atopic dermatitis, or an allergy to insect venom, medications, or latex are at an increased risk of developing food allergies. Diagnosis of food allergy starts with a detailed, allergy-focused history. Serum immunoglobulin E and skin prick testing provide reliable information regarding food allergy diagnoses. Primary treatment involves elimination of the offending food from the diet. Prevention strategies proven to decrease the risk of developing a food allergy include restricting exposure to cow's milk in the first three days of life and early sequential exposure to allergenic foods starting between four and six months of age. Exclusive breastfeeding for three to four months reduces the likelihood of developing eczema and asthma but does not reduce development of food allergies. Most children eventually outgrow allergies to cow's milk, egg, soy, and wheat. However, allergies to tree nuts, peanuts, and shellfish are more likely to be lifelong.

Early Peanut Introduction Awareness, Beliefs, and Practices Among Parents and Caregivers.

BACKGROUND AND OBJECTIVES: The 2017 Prevention of Peanut Allergy Guidelines recommend incorporating peanut protein into infants' diets to prevent peanut allergy. The goal of this study was to explore US caregivers' awareness, beliefs, practices, and outcomes around peanut introduction. METHODS: A parent-report survey was administered between January and February 2021 to a population-based sample of 3062 US parents/caregivers of a child between age 7 months and 3.5 years. The survey evaluated awareness, beliefs, feeding practices, primary care provider (PCP) interactions, and food reactions. RESULTS: Overall, 13.3% of parents/caregivers reported Prevention of Peanut Allergy Guidelines awareness. Caregivers who reported being white, 30 to 44 years of age, educated, high income, or cared for a child with food allergy or eczema were more likely to be guideline-aware (P < .001). Among US parents/caregivers, 47.7% believed that feeding peanuts early prevented peanut allergy; 17.2% first offered peanut-containing foods before age 7 months and 41.8% did so between ages 7 and 12 months. Peanut introduction occurred earlier among guideline-aware parents/caregivers: 31% offered it before 7 months (P < .001). Overall, 57.8% of parents/caregivers reported discussing peanut introduction with their PCP. PCP counseling was the most common facilitator for peanut introduction before 7 months (odds ratio 16.26 [9.49-27.85]), whereas fear of reactions was the most common reason for delaying peanut introduction beyond 7 months (32.5%). Actual reactions during peanut introduction were reported by 1.4%. CONCLUSIONS: Early peanut feeding practices are gaining traction among US parents/caregivers; however, disparities exist. Future efforts to increase guideline adherence need to address disparities, provide support for medical providers, and educate about the true incidence of reactions.

A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis.

BACKGROUNDIgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy.METHODSAfter undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut protein to elicit an objective clinical reaction.RESULTSAt baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range 444-4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious.CONCLUSIONAcalabrutinib pretreatment achieved clinically relevant increases in patients' tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials.TRIAL REGISTRATIONClinicalTrials.gov NCT05038904FUNDINGAstraZeneca Pharmaceuticals, the Johns Hopkins Institute for Clinical and Translational Research, the Ludwig Family Foundation, and NIH grants AI143965 and AI106043.

A Survey of Canadian Dietitians on Identification of Infants at High Risk of Food Allergy and Frequency of Allergenic Food Consumption.

Purpose: To assess knowledge of Canadian dietitians on the topics of food allergy and food allergy prevention guidelines, including introduction of allergenic solids to infants at risk of food allergy.Methods: An online survey was distributed via email listservs targeting Canadian dietitians.Results: In total, 144 of 261 dietitians completed the survey (60.5%). Respondents recommend introduction of peanut (89.5%) and allergenic solids (91.2%) within the recommended age of 4-6 months for infants at high risk of food allergy, but only 26.2% recommend offering peanut three times per week once it has been introduced. In identifying what constitutes an infant at high risk of developing peanut allergy, dietitians expressed lower comfort levels and lower number of correct responses.Conclusions: Dietitians demonstrated they are up to date regarding the timing of introduction of allergenic solids, but not the frequency of consumption once introduced, for infants at high risk of food allergy. They also expressed low comfort level identifying risk factors for peanut allergy. There are opportunities for further education of dietitians, as well as potential to further utilize dietitian services for the benefit of patients with food allergy or who are at risk for food allergy.

Feasibility and safety of introducing cashew nut spread in infant diets-A randomized trial.

BACKGROUND: To reduce peanut allergy prevalence, infant feeding guidelines now recommend introducing peanuts in an age-appropriate form (such as peanut butter) as part of complementary feeding. However, due to a lack of randomized trial evidence, most infant feeding and food allergy prevention guidelines do not include tree nuts. The aims of this trial were to determine safety and feasibility of dosage consumption recommendations for infant cashew nut spread introduction. METHODS: This is a parallel, three-arm (1:1:1 allocation), single-blinded (outcome assessors), randomized controlled trial. General population term infants were randomized at 6-8 months of age to either a one teaspoon (Intervention 1 n = 59) or increasing dosage regime of one teaspoon at 6-7 months, two teaspoons at 8-9 months, and three teaspoons from 10 months of age onwards (Intervention 2 n = 67) cashew nut spread, both three times per week, or no specific advice on cashew introduction (Control n = 70). At 1 year of age, food challenge proven IgE-mediated cashew nut allergy was assessed. RESULTS: Compliance in Intervention 1 (92%) was higher than Intervention 2 (79%), p = .04. Only one infant had delayed (at 5 h) facial swelling and eczema flare to cashew introduction at 6.5 months, but no cashew allergy at 1 year. Only one infant (Control) had cashew allergy at 1 year, and this infant had not been introduced to cashew prior to 12 months of age. CONCLUSION: Regular infant consumption of one teaspoon of cashew nut spread three times per week from 6 to 8 months of age was found to be feasible and safe.

Environmental Exposure to Foods as a Risk Factor for Food Allergy.

PURPOSE OF REVIEW: Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy. RECENT FINDINGS: Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy.