Oral Food Challenge Research Articles

From bite to brain: Neuro-immune interactions in food allergy.

Immunoglobulin E (IgE)-mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity. While being the gold standard for diagnosis, oral food challenges are burdensome, and diagnostic tools based on specific IgE can be flawed. Furthering our understanding of the mechanisms behind food allergy onset, severity and persistence could help reveal immune profiles associated with the disease, to ultimately aid in diagnosis. Alterations to cytokine levels and immune cell ratios have been identified, though further research is needed to fully capture the heterogenous nature of food allergy. Moreover, the existence of such immune alterations also raises the question of potential wider systemic effects. For example, recent research has emphasised the existence and impact of neuro-immune interactions and implicated behavioural and neurological changes associated with food allergy. This review will provide an overview of such food allergy-driven neuro-immune interactions, with the aim of emphasising the importance of furthering our understanding of the immune mechanisms underlying IgE-mediated food allergy.

The Efficacy and Safety of Stepwise Oral Food Challenge in Children with Cow’s Milk Allergy

Plain Language SummaryStepwise oral food challenge (OFC) tests begin with low doses of allergens, progressing to full doses. This is one of the strategies used to avoid anaphylactic reactions to the reintroduction of allergens. We previously reported the safety and efficacy of hen egg OFC. In this study, we discuss it for cow’s milk (CM) allergy. We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When the participants reacted to low doses, they underwent very low-dose OFC using baked milk or <1 mL of CM. Positive reactions developed in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results and anaphylaxis. Multivariate analysis indicated that only in low-dose OFCs, higher CM-specific IgE (CM-sIgE) levels, younger age, and complete CM elimination were associated with positive OFC results. Food ladders, an approach to reintroduce allergens, are becoming increasingly popular. Although we believe that OFC is a safer strategy to reintroduce CM to children with CM allergy, our CM-OFCs appeared to develop more anaphylactic reactions than milk ladders. The stepwise OFC reintroduced small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at a younger age, preferably from infancy, with very low doses, similar to milk ladders, may facilitate the safe reintroduction of CM.

An overview of hidden food allergens: need for change to the priority food allergen lists?

Many food allergens not actually included in the European priority list of allergenic foods have the potential to cause severe allergic reactions and could escape correct identification and behave as "hidden allergens". Moreover, the adoption in recent years of novel diets based on plant products and new sustainable foods or the use of specific food additives have contributed to the onset of new emerging allergens of public health importance. The knowledge of hidden allergens is important both for physicians and for patients to improve the prevention, diagnosis and treatment of food allergies, in order to decrease eventual improper diagnosis of idiopathic anaphylaxis. In this review, the characteristics of the most frequent hidden allergens and their diagnostic tools are described. A detailed history with a careful review of the ingredient lists, an understanding of possible cross-reactions or contaminations with other foods, together with an allergological evaluation consisting of in vivo or in vitro tests and, where necessary, an oral food challenge, are recommended for the successful identification of the culprit allergen. In future, it will be very important to implement these diagnostic tools, especially in the field of molecular allergology, and reporting allergens on labels should become mandatory.

Recombinant Gad c 1 improves diagnostic efficacy of cod allergy but not horse mackerel allergy.

Parvalbumin Gad c1 is a major cod allergen used as a follow-up marker of fish-allergic children. However, the diagnostic efficacy of recombinant Gad c 1 (rGad c 1) for fish allergy diagnosis remains controversial. This study aimed to evaluate the efficacy of rGad c1 for diagnosing cod and horse mackerel allergy. This single-centered, retrospective study obtained oral food challenges (OFCs) information performed for cod and horse mackerel. Cod-, horse mackerel-, and rGad c1-specific immunoglobulins (sIgEs) were investigated. Diagnostic performances of these parameters were compared using areas under the curve (AUC). We enrolled 45 and 38 children with suspected cod and horse mackerel allergies, respectively. The median age (interquartile range) of children with suspected cod allergy was 5.7 (0.7-11.7) years and that of children with suspected horse mackerel allergy was 6.0 (1.0-12.3) years. Fourteen and 22 children reacted to OFCs with 25 (10-40) g of cooked pacific cod and 40 (10-40) g of cooked horse mackerel, respectively. The cod sIgE and rGad c 1 sIgE AUCs for cod allergy diagnosis were 0.85 and 0.90, respectively. For horse mackerel allergy diagnosis, AUCs of horse mackerel and rGad c 1 sIgE were 0.76 and 0.72, respectively. Both AUCs for cod and mackerel allergy were significantly different. rGad c 1 sIgE is more effective than cod sIgE as a diagnostic marker of cod allergy, but less effective than horse mackerel sIgE as a diagnostic marker of horse mackerel allergy. Further studies are warranted to explore the potential applications of rGad c 1 sIgE in the diagnosis of various fish allergies.

Low-dose oral food challenges.

Infants aged <1 year with confirmed food allergies generally need to avoid causative foods completely for a certain period. Low-dose oral food challenges (LD-OFCs) may be an effective strategy for safely introducing small amounts of causative foods to individuals with food allergies. This study clarified the safety of LD-OFCs in infants aged <1 year with food allergies. We retrospectively analyzed the clinical records of LD-OFCs performed in infants aged <1 year allergic to hen's egg, cow's milk, or wheat between April 2014 and October 2017. Approximately 1/25th-1/20th of the egg white from a heated whole hen's egg, 3 mL heated cow's milk, and 2 g wheat noodles (udon) were used as challenge foods. We examined the LD-OFC results, including the induced symptoms and treatment required for positive LD-OFC results. The LD-Egg, LD-Milk, and LD-Wheat OFC groups comprised 68, 42, and 13 participants, respectively. The positivity rates for the LD-Egg, LD-Milk, and LD-Wheat OFC groups were 7%, 24%, and 0%, respectively. Patients predominantly exhibited skin symptoms, and most were treated with oral antihistamines alone. None of the patients experienced anaphylaxis or required adrenaline injections. Infants aged <1 year with food allergies can safely undergo LD-OFCs by consuming low doses of causative foods. Avoiding the complete elimination of causative foods is an important strategy for managing infants with food allergies when initially introducing causative foods.

Air pollution is associated with persistent peanut allergy in the first 10 years.

The role of air pollution in eczema and food allergy development remains understudied. We aimed to assess whether exposure to air pollution is associated with eczema and food allergies in the first 10 years of life. HealthNuts recruited a population-based sample of 1-year-old infants who were followed up at ages 4, 6, and 10 years. Annual average fine particulate matter (particulate matter with diameter of 2.5 μm or less, or PM2.5) and nitrogen dioxide (NO2) exposures were assigned to geocoded residential addresses. Eczema was defined by parent report. Oral food challenges to peanut, egg, and sesame were used to measure food allergy. Multilevel logistic regression models were fitted, and estimates were reported as adjusted odds ratios. Those exposed to high concentration of NO2 (<10 ppb) at age 1 year had higher peanut allergy prevalence at ages 1 (adjusted odds ratio [95% confidence interval], 2.21 [1.40-3.48]) and 4 (2.29 [1.28-4.11]) years. High exposure to NO2 at 6 years old were associated with higher peanut allergy prevalence at age 6 (1.34 [1.00-1.82] per 2.7 ppb NO2 increase) years. Similarly, increased PM2.5 at age 1 year was associated with peanut allergy at ages 4, 6, and 10 years (respectively, 1.27 [1.01-1.60], 1.27 [1.01-1.56], and 1.46 [1.05-2.04] per 1.2 μg/m PM2.5 increase) years. We found that increased concentrations of NO2 or PM2.5 at age 1 year were associated with persistent peanut allergy at later ages. Little evidence of associations was observed with eczema or with egg allergy. Early-life exposure to PM2.5 and NO2 was associated with peanut allergy prevalence and persistence. Policies aiming at reducing air pollution could potentially reduce presence and persistence of peanut allergy.

Oral food challenge test results of patients with food allergy with specific IgE levels >100 UA/ml.

Specific IgE level (sIgE) is an important factor indicating sensitization status in children with food allergies (FAs). The present study aimed to clarify oral food challenge test (OFC) results in children with FAs with sIgE levels ≥100 UA/ml compared with those in children with sIgE <100. The retrospective study analyzed patients who underwent OFC with egg white, cow milk and wheat at Gifu Prefectural general medical center, Gifu, Japan between July 2017 and March 2023. Clinical history, total IgE (tIgE), sIgE and correlation between sIgE, sIgE/tIgE and eliciting dose as the amount of intake protein were examined. In the <100 group, positive OFC showed significantly higher sIgE for egg white, ovomucoid and casein than negative OFC (P<0.05); however, there was no significant difference between positive and negative OFC in the ≥100 group. In the <100 group, positive OFC showed significantly higher sIgE/tIgE for ovomucoid, milk and casein than negative OFC (P<0.05); however, there was no significant difference in sIgE/tIgE between positive and negative OFC in the ≥100 group. There was a significant negative correlation between eliciting dose and sIgE for egg white and wheat (P<0.05). For milk and wheat, there was no significant difference between ≥100 group and the <100 group with regard to positive rates in the OFC. Therefore, OFC may be safely performed by decreasing total challenge dose for the ≥100 group.

Oral Food Challenge in Children with Tree Nut and Peanut Allergy: The Predictive Value of Diagnostic Tests.

Food allergy (FA) affects approximately 6-8% of young children, with a peak prevalence at approximately one year of age. Tree nut and peanut allergies are among the main causes of anaphylaxis in the world. The gold standard for the diagnosis of FAs is the oral food challenge (OFC). Other diagnostic tests used in the clinical practice are skin prick tests (SPTs) and laboratory tests to measure out the presence of serum specific IgE (sIgE). In this narrative review, we collect the current evidence of the predictive value (PV) of SPTs and sIgE for the outcome of the OFCs. In literature, data are conflicting as to whether increasing sIgE concentration and wheal size in SPTs correlate with OFC outcomes. Most studies included in our review have shown that in vivo and in vitro tests may predict OFC outcomes with variable PV, but data are not conclusive; therefore, the OFC currently remains the gold standard for FA diagnosis.

Modern Approaches to the Diagnosis o Food Allergy in Children: Oral Food Challenges (Review)

The diagnosis of food allergies significantly impacts the lives of patients and their families, restricting diets and social activities. A misdiagnosis can lead to severe allergic reactions, making accurate diagnosis crucial. Immunoglobulin E (IgE)-mediated food allergies are diagnosed using skin tests or serum-specific IgE levels. However, for most allergens, the only reliable method for confirming the diagnosis remains the oral food challenge (OFC). Objective — elucidation of the importance of oral provocation tests in the diagnosis of food allergy and their relevance for the future treatment of food allergy. Materials and methods. A search for information on OFC was conducted in scientometric databases such as Web of Science, Scopus, Google Scholar, ScienceDirect and PubMed using the following keywords: «food allergy», «oral food challenge», «children». After reviewing the publications, professional sources that met the query criteria and were published between 2017 and 2024 were selected for the review. Results and discussion. OFCs help determine allergen sensitivity and reaction severity, which is useful for further management. They also have therapeutic value, reducing anxiety related to food allergies and improving quality of life. Psychological aspects play an important role in food allergies, as the fear of severe reactions often exceeds actual risks.One limitation of OFCs is the need for substantial resources and specialized knowledge, available only in specialized medical centers. This leads to long waiting lists and delays in food introduction, increasing the risk of developing allergies. Additionally, OFCs are often conducted in controlled environments, which may not reflect real-world accidental exposures.OFC results can include false positives, false negatives, and inconclusive outcomes. They are also time-consuming and may affect school or work attendance for patients and caregivers. It is essential to standar­dize doses for each food according to portion sizes and patient age. Conclusions. The frequency of food allergies is currently increasing in Ukraine, highlighting the need for allergists to master the technique and implement oral food challenges in general allergy practice to establish food allergies in children.

Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.

In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA). We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels. In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50. During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible. ClinicalTrials.gov, NCT06316414.

Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit.

The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children's Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow's-milk-free diet.

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting

Oral immunotherapy (OIT) for food allergy has been largely studied in older children within the context of clinical trials, and its availability has historically been limited for younger patients with food allergy. Data has shown that the most impact may actually be seen with the use of OIT in younger infants and toddlers. To evaluate the safety and feasibility of OIT in subjects younger than 24 months in a real-world setting using commercially available food products. This was a retrospective study of subjects 24 months and younger initiated on OIT for peanut, tree nut, or sesame allergy within the Scripps Clinic allergy department. Medical records were reviewed for data regarding initial oral food challenges (OFCs), OIT, and adverse outcomes. Fifty-two subjects under 24 months of age were initiated on OIT. Most subjects (84.6%) were on single food OIT, some (15.4%) were on multi-food OIT. No increased adverse outcomes were observed on multi-food OIT. Of the 59 initial OFCs, objective reactions occurred during 42 challenges, the majority being low grade reactions. During initial OFCs, 86.1% of peanut allergic children tolerated 1/8 of one Bamba stick with no reaction. The majority (73.1%) of subjects up-dosed at home and most (51.9%) had no reactions while up-dosing. Some had low grade cutaneous reactions, none requiring epinephrine or emergency evaluation. OIT in infants is safe and feasible to perform in a real-world setting using commercially available food products with at home up-dosing, thus increasing the availability of OIT for patients.

A Streamlined Strategy for Basophil Activation Testing in a Multicenter Phase III Clinical Trial

BackgroundThe basophil activation test (BAT) has been limited to research settings due to technical issues. Novel approaches using dry, ready-to-use reagents and streamlined protocols offer greater flexibility and may open opportunities for easier implementation in clinical research. ObjectiveUsing a streamlined BAT (sBAT) strategy and the settings of the baseline study of the EPITOPE trial of EPicutaneous ImmunoTherapy (EPIT™) for peanut allergy, we aimed to assess the feasibility of implementing BAT in a multicenter trial and to evaluate its utility in predicting the outcomes of peanut double-blind placebo-controlled food challenge (DBPCFC). MethodsWhole blood samples were collected from subjects aged 1-3 years (n=241) undergoing baseline eligibility DBPCFC in the EPITOPE study across 15 clinical sites in North America. After preparation with sBAT reagents, processed samples were analyzed in a single central laboratory within 5 days of collection and preparation. The eliciting dose (ED) at DBPCFC was determined using PRACTALL criteria. Using a machine learning (ML) approach which incorporated BAT-derived features, clinical characteristics, and peanut-specific IgE, the ability to predict outcomes of interest (ED [<300 mg or >300 mg] and use of epinephrine) was assessed using data randomly split into training (n=182) and validation (n=59) subsets. ResultsThe expression of basophil activation markers CD203c and CD63 correlated with ED and severity outcomes of DBPCFC. Most informative concentrations of peanut extract in the sBAT assay for these associations were 1 and 10 ng/ml. Using ML to assess the ability to predict the outcomes of DBPCFC, the best models using only the BAT-derived features provided relatively high sensitivities of 0.86 and 0.85 for predicting eliciting dose and epinephrine use, respectively, while specificities were lower, ranging from 0.60 to 0.80. While including specific IgE and SPT data in addition to those from sBAT did not improve the ability to identify individuals most at risk for severe reactions, it did improve the ability to identify patients with an eliciting dose above 300 mg. ConclusionIn addition to facilitating implementation in multicenter trials, sBAT retains the potential of BAT to characterize allergic patients and confirms its potential to contribute to predicting the outcome of oral food challenges.

Successful Introduction of Peanut in Sensitized Infants With Reported Reactions at Home

Background and objectivePrevious studies have shown efficacy of early introduction of peanut to prevent peanut allergy. It is currently unknown which diagnostic pathway is optimal after parental-reported reactions to peanut at home after early introduction. MethodsThe PeanutNL cohort study included high-risk infants that were referred for early introduction of peanut. A subgroup of 186 infants with reactions to peanut at home underwent peanut skin prick tests and a supervised open oral food challenge (OFC) at a median age of 8 months. After a negative OFC, peanut was introduced at home. ResultsSensitization to peanut was detected in 69% of 186 infants, of which 80% had > 4mm wheals in skin prick tests. An OFC with a cumulative dose of 4.4 gr peanut protein was performed in 163 infants with Sampson severity score grade I-III reactions at home; 120 challenges were negative. Peanut was subsequently introduced at home in infants with a negative challenge outcome. After 6 months, 96% were still eating peanut and 81% ate single portions of 3.0 gr peanut protein. One patient was considered to be peanut allergic after reintroduction of peanut at home. ConclusionThese data show that 65% of infants with reported reactions to peanut at home have negative OFCs. In those children, peanut could be introduced safely and 96% were able to consume peanut regularly without reactions. Challenging infants under 12 months of age prevents the misdiagnosis of peanut allergy, and enables safe continued exposure to peanut and the induction of long-term tolerance.

Efficacy and safety of low-dose sesame oral immunotherapy in paediatric patients: a protocol for a single-centre, randomised controlled trial

IntroductionSesame allergy, though with low prevalence, can result in severe, potentially life-threatening reactions and poses challenges in allergen avoidance due to hidden sources. In the majority of patients, sesame allergy...

Severe anaphylaxis requiring continuous adrenaline infusion during oral food challenge: A case series

Severe anaphylaxis requiring continuous adrenaline infusion during oral food challenge: A case series

Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy

BackgroundThe bead-based epitope assay (BBEA) has been used to identify epitope-specific (es) antibodies and successfully utilized to diagnose clinical allergy to milk, egg and peanut. ObjectiveThis study aimed to identify es-IgE, es-IgG4 and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the BBEA. MethodsChildren and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from alpha/beta-gliadin, gamma-gliadin (γ-gliadin), omega-5-gliadin (ω-5-gliadin), high and low molecular weight glutenin were commercially synthesized and coupled to LumAvidin beads. Machine learning (ML) methods were used to identify diagnostic epitopes and performance was evaluated using DeLong’s test. ResultsThe analysis includes 122 children (83 wheat-allergic and 39 wheat-tolerant, 57.4% male). ML coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1 to be most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis (WDEIA) showed lower es-IgG1 binding than all other groups. A set of 4 informative epitopes from ω-5-gliadin, and γ-gliadin were the best predictors of wheat allergy with an AUC of 0.908 (sensitivity=83.4%, specificity=88.4%), higher than the performance exhibited by wheat-specific IgE (AUC=0.646, p < 0.001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 non-allergic), with an AUC of 0.908 (sensitivity=75.9%, specificity=90.5%). ConclusionThe wheat BBEA demonstrated greater diagnostic accuracy compared to existing specific IgE tests for wheat allergy.

Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe.

Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies. To evaluate the association between the natural course of egg sensitization and FLG mutations. We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid-school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white-specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns. Three similar patterns of egg sensitization (persistent, early-onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four-fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2-16.0), p = .03 in CHIBA; 4.3 (1.3-14.7), p = .02 in MAAS). FLG loss-of-function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.

Fish and shellfish allergy: Presentation and management differences in the UK and US—analysis of 945 patients

Seafood allergy (SA), including allergy to shellfish (crustacean and mollusks) and fish, is among the 4 most common food allergies causing anaphylaxis, but there are limited data showing SA clinical management in different countries. We sought to characterize a large cohort of patients with fish and shellfish allergy and to facilitate standardization of future care for this increasingly common allergic disease. We performed a retrospective, observational, noninterventional study from 945 patients from 2015 to 2019 in 7 hospitals in the United States and the United Kingdom to evaluate SA. Achi-square test was used to detect differences in family history, medical history, and current symptoms between patients in 2 countries. Underdiagnosed anaphylaxis in patients with SA was associated with underuse of epinephrine (adrenaline) autoinjectors in both countries. Oral food challenge was used only when skin or serologic test results were negative. Asthma and allergic rhinitis were more common in the US patients withSA, but eczema was more common in UK patients with SA (P< .001). Respiratory, gastrointestinal, and neurological symptoms were higher in UK patients with SA than in US patients with SA (P< .001). In international multicenter cohorts of patients with fish and shellfish allergy, there are opportunities for improvement in management. Physician identification of anaphylaxis, use of diagnostic oral food challenges, and anaphylaxis treatment with epinephrine are areas with significant knowledge gaps in need of improvement in the United Kingdom and the United States. There is an opportunityfor the development of unified, standardized diagnostic protocols for SA with distribution for allergists and trainees.

Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. gov (NCT01906853). Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.