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Background: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission)., Methods: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic)., Results: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001)., Conclusion: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort., Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point., Results: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time., Conclusions: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

(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: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy., Methods: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension., Results: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group., Conclusions: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)., (Copyright © 2024 Massachusetts Medical Society.)

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., (© 2023 Aravax Pty Ltd. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The patient was in his 70s. He was addmitted to our hospital because of obstructive pneumonia for 3 months. Chest computed tomography( CT) showed a nodule at the base of the right B8, obstructing the basal branch, with consolidation of the peripheral lung. Bronchoscopy revealed the right basal trunk obstruction by a tumorous lesion. FDG-PET showed heterogeneous FDG uptake at the right hilum and the lower lobe suggesting malignancy, and a thoracoscopic right lower lobectomy was performed. Pathology showed a granulation-like nodule and a brown oval foreign body incarcerated in the peripheral bronchus, which was later revealed to be a peanut, and no obvious malignant findings were observed.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown., Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo., Results: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group., Conclusions: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo., Aims: To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA)., Methods: Children with a positive (OFC + , n = 16) or a negative (OFC - , n = 10) OFC-outcome were included (controls, n = 7). Single-cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC., Results: Peripheral immune profiles correlated with OFC outcome. OFC + -profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC - -profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2-shifted CD4 + T cells and Treg cells. Low versus high threshold reactivity-groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8 + T cells and reduced memory cells (central memory [CM] CD4 + [Th2] T cells, CM CD8 + T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types., Conclusion: We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Peppermint oil capsules are prescribed to manage abdominal colic and distension, a common complaint in postcaesarean section patients. Arachis (peanut) oil is contained within one frequently prescribed peppermint formulation: Colpermin. This ingredient is contraindicated in patients with peanut and soya allergy; however, this is not stated in the side effects or contraindications section of the British National Formulary, or present on the medication packaging. A postpartum woman in her early 30s had an unexpected allergic reaction to the capsules, in the form of a generalised body rash, fortunately with no anaphylactic features. The patient reported the same reaction to soya in the past. After review of the patient's clinical and medication history, Colpermin capsules were thought to be responsible for the patient's symptoms. This case highlights the necessity for clearer documentation in prescribing formularies and on medication packaging to ensure patient safety., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Peanut allergy affects 1%-3% of children in Western countries. Boiling peanuts has been demonstrated to result in a hypoallergenic product that may provide a safer way of inducing desensitization in peanut-allergic patients by first inducing tolerance to boiled peanut. We aimed to assess the efficacy and safety of oral immunotherapy (OIT) using sequential doses of boiled peanuts followed by roasted peanuts for treating peanut allergy in children., Methods: In this open-label, phase 2, single-arm clinical trial, children aged 6-18 years with a positive history of peanut allergy and positive peanut skin prick test ≥ 8 mm and/or peanut-specific IgE ≥ 15 kU/L at screening underwent OIT involving sequential up-dosing with 12-hour boiled peanut for 12 weeks, 2-hour boiled peanut for 20 weeks and roasted peanut for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily., Primary Outcome: proportion of children passing open-label oral food challenge involving cumulative administration of 12 roasted peanuts (12 g peanuts; approximately 3000 mg peanut protein) 6-8 weeks after reaching the target maintenance dose. Secondary outcomes included treatment-related adverse events and use of medications for treating allergy symptoms., Results: Between 1 July 2017 and 22 June 2018, 70 participants were enrolled and commenced OIT. Desensitization was successfully induced in 56 of 70 (80%) participants. Withdrawal due to treatment-related adverse events was infrequent (n = 3). Treatment-related adverse events were reported in 43 (61%) participants, corresponding to a rate of 6.58 per 1000 OIT doses. Medication use associated with treatment-related adverse events was infrequent, with rescue epinephrine use reported by three (4%) participants (0.05 per 1000 doses)., Conclusion: Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitization and is associated with a favourable safety profile., (© 2023 John Wiley & Sons Ltd.)

Background: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose., Methods: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis., Results: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC., Conclusions: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Peanut oral immunotherapy (POIT) has emerged as an active management option for peanut allergy, with an FDA-approved product now available for therapy. Allergic reactions, including anaphylaxis, can occur during therapy and their management is key in optimizing this treatment and patient outcomes., Purpose of Review: In this manuscript, we will review the rates of allergic reactions and anaphylaxis in seminal peanut oral immunotherapy research studies. We will examine factors that can alter the risk of anaphylaxis and describe various strategies, including adjunct therapies, that have the potential to mitigate anaphylaxis risk based on published evidence., Recent Findings: Rates of anaphylaxis and epinephrine administration vary in different research studies, but there is consensus that most POIT-related allergic reactions are mild or moderate and not severe. Certain external factors (for example, tiredness, exercise, viral illness) as well as uncontrolled allergic co-morbidities (asthma, allergic rhinitis) have been shown to increase the risk of anaphylaxis during OIT. The search of biomarkers who may predict who is at risk for severe allergic reactions is ongoing. Adjunct therapies have shown promise, but further studies are required to optimize their use alongside POIT. Our understanding of anaphylaxis during POIT has increased in recent years, resulting in better management strategies. However, future plans will need to involve all stakeholders, including physicians, patients and families, researchers, public health authorities, and the food, hospitality, and catering industries., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment., Objective: To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data., Methods: RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary end point for RAMSES and ARC011 was the frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES and ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE and ARTEMIS trials., Results: In 506 patients randomized to study treatment, baseline characteristics appeared balanced among groups. Proportion of participants with at least 1 AE was 55% for PTAH vs 33.9% for placebo during initial dose escalation and 98.8% vs 94.0% during updosing, respectively. Most participants with AEs had mild or moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data revealed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable., Conclusion: Safety data from clinically selected children with peanut allergy receiving PTAH do not seem different from those in phase 3 trials requiring DBPCFC to enter trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: IgE-epitope profiling can accurately diagnose clinical peanut allergy., Objective: We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing., Methods: Sixty four ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay. A pair of ses-IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope-based predictor was validated on 331 subjects from five independent cohorts (ages 4-25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated., Results: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses-IgE-based predictor, subjects were assigned into "high," "moderate," or "low" dose-reactivity groups. On average, subjects in the "high" group were four times more likely to tolerate a specific dose, compared with the "low" group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the "low" group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the "high" group., Conclusions: Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study-specific challenge protocols. Despite these limitations, an epitope-based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Exposure to mycotoxins in food is largely unavoidable, and concerns about their health effects are growing. Consumption of vegetable oils such as peanuts oil has increased, hence several studies have been conducted on concentration of aflatoxins (AFs) in peanuts oil. Search was performed in Scopus and PubMed databases on prevalence and concentration of AFs in peanuts oil from 1 January 2005 to 15 April 29, 2022. Prevalence and concentration of AFs in peanuts oil was meta-analyzed based on country and type of AFs subgroups. In addition, health risk was calculated using monte carlo simulation method. Pooled prevalence of AFB1 in peanuts oil was 47.9%; AFB2, 46.45%; AFG1, 46.92% and AFG2, 54.01%. The Overall prevalence of AFTs was 49.30%, 95%CI (35.80-62.84%). Pooled concentration of AFB1 in peanuts oil was 2.30 μg/kg; AFB2, 0.77 μg/kg; AFG1, 0.07 μg/kg; AFG1, 0.28 μg/kg. The sort of country based on mean of MOEs in the adults consumers was Japan (47,059) > China (17,670) > Ethiopia (7,398) > Sudan (6,974) > USA (1,012) and sort of country based on mean of MOEs in the children was Japan (120,994) > China (46,991) > Ethiopia (19,251) > Sudan (18,200) > USA (2,620). Therefore, adults consumers were in considerable health risk in Ethiopia, Sudan and USA and for children in USA (MOE < 10,000)., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Importance: Randomized clinical trials showed that earlier peanut introduction can prevent peanut allergy in select high-risk populations. This led to changes in infant feeding guidelines in 2016 to recommend early peanut introduction for all infants to reduce the risk of peanut allergy., Objective: To measure the change in population prevalence of peanut allergy in infants after the introduction of these new guidelines and evaluate the association between early peanut introduction and peanut allergy., Design: Two population-based cross-sectional samples of infants aged 12 months were recruited 10 years apart using the same sampling frame and methods to allow comparison of changes over time. Infants were recruited from immunization centers around Melbourne, Australia. Infants attending their 12-month immunization visit were eligible to participate (eligible age range, 11-15 months), regardless of history of peanut exposure or allergy history., Exposures: Questionnaires collected data on demographics, food allergy risk factors, peanut introduction, and reactions., Main Outcome and Measures: All infants underwent skin prick tests to peanut and those with positive results underwent oral food challenges. Prevalence estimates were standardized to account for changes in population demographics over time., Results: This study included 7209 infants (1933 in 2018-2019 and 5276 in 2007-2011). Of the participants in the older vs more recent cohort, 51.8% vs 50.8% were male; median (IQR) ages were 12.5 (12.2-13.0) months vs 12.4 (12.2-12.9) months. There was an increase in infants of East Asian ancestry over time (16.5% in 2018-2019 vs 10.5% in 2007-2011), which is a food allergy risk factor. After standardizing for infant ancestry and other demographics changes, peanut allergy prevalence was 2.6% (95% CI, 1.8%-3.4%) in 2018-2019, compared with 3.1% in 2007-2011 (difference, -0.5% [95% CI, -1.4% to 0.4%]; P = .26). Earlier age of peanut introduction was significantly associated with a lower risk of peanut allergy among infants of Australian ancestry in 2018-2019 (age 12 months compared with age 6 months or younger: adjusted odds ratio, 0.08 [05% CI, 0.02-0.36]; age 12 months compared with 7 to less than 10 months: adjusted odds ratio, 0.09 [95% CI, 0.02-0.53]), but not significant among infants of East Asian ancestry (P for interaction = .002)., Conclusions and Relevance: In cross-sectional analyses, introduction of a guideline recommending early peanut introduction in Australia was not associated with a statistically significant lower or higher prevalence of peanut allergy across the population.

Background: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years., Objective: We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment., Methods: Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed., Results: Of the 944 individuals receiving ≥1 PTAH dose, median exposure was ∼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis])., Conclusion: The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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).)

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life., Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores., Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life., Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response., (© 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: To assess the impact of anaphylaxis on health-related quality of life (HRQL) and self-efficacy in food-allergic patients undergoing in-hospital food challenge., Design: Secondary analysis of a randomised controlled trial., Setting: Specialist allergy centre., Patients: Peanut-allergic young people aged 8-16 years., Interventions: Double-blind, placebo-controlled food challenge to peanut, with HRQL and self-efficacy assessed using validated questionnaire, approximately 2 weeks prior to and 2 weeks after challenge. Where possible, anaphylaxis was treated with self-injected adrenaline (epinephrine)., Main Outcome Measures: Change in HRQL and self-efficacy., Results: 56 participants had reactions at food challenge, of whom 16 (29%) had anaphylaxis. Overall, there was an improvement in HRQL (mean 2.6 points (95% CI 0.3 to 4.8); p=0.030) and self-efficacy (mean 4.1 points (95% CI 2.4 to 5.9); p<0.0001), independent of whether anaphylaxis occurred. Parents also reported improved HRQL (mean 10.3 points (95% CI 5.9 to 14.7); p<0.0001). We found evidence of discordance between the improvement in HRQL and self-efficacy as reported by young people and that perceived by parents in their child., Conclusions: Anaphylaxis at food challenge, followed by self-administration of injected adrenaline, was associated with an increase in HRQL and self-efficacy in young people with peanut allergy. We found no evidence that the occurrence of anaphylaxis had a detrimental effect. Young people should be encouraged to self-administer adrenaline using their autoinjector device to treat anaphylaxis at in-hospital challenge., Trial Registration Number: NCT02149719., Competing Interests: Competing interests: PT has received research funding for studies of food desensitisation from the Medical Research Council, Imperial/NIHR Biomedical Research Centre, Jon Moulton Charity Trust and Action Medical Research and has acted a principle investigator for commercial studies of food immunotherapy sponsored by Aimmune Therapeutics and DBV Technologies. DC is an employee of DBV Technologies. The other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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.)

Background: Bioaccessibility of food allergens may be a key determinant of allergic reactions., Objective: To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut-allergic volunteers., Methods: A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut-allergic patients) at various time-points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in-house immunoassay., Results: An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies-Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300-1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut-allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non-allergic volunteers., Conclusions and Clinical Relevance: The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut-allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

The US Food and Drug Administration's approval of a peanut oral immunotherapy product in January 2020 is a landmark development in the field of food allergy therapy. While food allergy prevalence has been increasing, this product is the first approved therapy for food allergy. Oral immunotherapy has many similarities to subcutaneous immunotherapy and drug desensitization protocols, but does not lead to sustained unresponsiveness. The studies leading to approval of the Palforzia product demonstrated increase in the amount of peanut protein able to be consumed, with 67% of subjects randomized to the treatment arm able to consume 600 mg of peanut protein in double-blind placebo-controlled food challenge at study exit. However, side effects are an important consideration, and dropout rates in studies of Palforzia ranged from 11% to 21%. Postmarketing surveillance of this product will be critical in assessing its long-term risks and benefits., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Peanut allergy is one of the most common food allergies in children, with increasing prevalence over time. The dual-allergen exposure hypothesis now supports transcutaneous sensitization to peanut as a likely pathophysiologic mechanism for peanut allergy development. As a result, there is emerging evidence that early peanut introduction has a role in peanut allergy prevention. Current first-line diagnostic tests for peanut allergy have limited specificity, which may be enhanced with emerging tools such as component-resolved diagnostics. Although management of peanut allergy includes avoidance and carrying an epinephrine autoinjector, risk of fatal anaphylaxis is extremely low, and there is minimal risk related to cutaneous or inhalational exposure. Quality of life in children with peanut allergy requires significant focus. Moving forward, oral and epicutaneous immunotherapy are emerging and exciting tools that may have a role to play in desensitization to peanut., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Abrams is a member of the scientific advisory board for Food Allergy Canada. Dr Chan has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, and Kaleo; is a member of the scientific advisory board for Food Allergy Canada; and was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored guidelines for peanut allergy prevention. Dr Sicherer reports royalty payments from UpToDate and from Johns Hopkins University Press; grants to his institution from the National Institute of Allergy and Infectious Diseases, from Food Allergy Research and Education, and from HAL Allergy; and personal fees from the American Academy of Allergy, Asthma, and Immunology outside of the submitted work. He was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored guidelines for peanut allergy prevention., (Copyright © 2020 by the American Academy of Pediatrics.)

Peanut allergy (PNA) is an IgE-mediated immune disorder, which merits particular attention due to its impact on the health and quality of life of millions of patients worldwide. PNA tends to develop in early life and resolves in only 20% of peanut-allergic children. It accounts for the majority of severe food-related allergic reactions. An accurate diagnosis of PNA is vital. In this review, we present the approach to the diagnosis of peanut allergy, starting from the history and proceeding to measures of overall sensitization and then to component-resolved diagnostics and oral food challenges as indicated. Additional testing in development includes basophil activation testing and determination of epitopes for peanut-allergic responses. Based on the literature, stepwise approaches and predictive models for diagnosing PNA are also presented., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: To estimate the proportion of infants introduced to peanut and other common food allergens by 12 months of age; to collect information about parent-reported reactions to food., Design, Setting: Observational cohort study, applying the SmartStartAllergy SMS protocol and online questionnaire to parents of 12-month-old infants attending 69 Australian general practices between 21 September 2018 and 3 May 2019., Participants: 3374 parents recruited via the 69 participating general practices., Main Outcome Measures: Proportions of infants who had eaten peanut and other common food allergens; proportions with parent-reported reactions to food., Results: 1940 of 3374 invited parents participated in the study (response rate, 57%), of whom 836 (46%) completed the online questionnaire. At 12 months of age, 1673 of 1940 infants had eaten peanut-including foods (86.2%; 95% confidence interval [CI], 84.6-87.7%); 235 of 1831 parents (12.8%; 95% CI, 11.3-14.5%) reported food-related reactions. Questionnaire responses indicated that dairy was the food type most frequently reported to cause a food-related reaction (72 of 835 exposed infants, 8.6%; 95% CI, 6.8-11%); peanut-related reactions were reported for 20 of 764 exposed children (2.6%; 95% CI, 1.6-4.0%). 97 of 250 parent-reported reactions to food (39%) did not include symptoms that suggested an IgE-mediated allergic reaction., Conclusion: Infant feeding practices in Australia have changed over the past decade; a large majority of infants are now fed peanut before 12 months of age. The SmartStartAllergy program allows monitoring of infant feeding practices in primary care, as well as of parent-reported reactions to food in infants., (© 2020 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Foreign body aspiration is a true medical emergency and is the fifth most common cause of mortality due to unintentional injury in the United States. Children who have aspirated a foreign body may present with a variety of symptoms, from mild irritation and cough to respiratory failure. Treatment is removal of the foreign body, often via rigid bronchoscopy. Clinicians must have a high degree of suspicion to ensure a foreign body aspiration is not missed on initial presentation.

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.