Background:Perioperative anaphylaxis (POA) is a life-threatening condition with substantial variability in evaluation and management practices. Objective:To assess current practices, perceived barriers, and regional differences in POA management among allergists worldwide. Methods:A cross-sectional online survey was distributed to World Allergy Organization (WAO) members from March to June 2024. The 39-question survey addressed demographics, clinical practices, diagnostic tools, perceived challenges, and future needs. Results:A total of 249 respondents from 50 countries completed the survey (median age 49 years, 49% female, 94% allergists, and 57% with >15 years of clinical experience). While 70% had access to acute serum tryptase (sAT), only 46% obtained it within the recommended 2-h window. Guideline adherence was low: 63% did not perform skin testing 4-6 weeks post-reaction, and fewer than half routinely tested for latex or chlorhexidine. Regional differences were observed: routine latex and chlorhexidine testing was most common in Europe and United States/Canada and least frequent in Africa and Asia (p = 0.0001); tryptase availability was lower in Africa and Latin America. Most respondents identified a culprit in <65% of cases, with antibiotics reported most frequently in Europe and United States/Canada, followed by neuromuscular blocking agents and non-steroidal anti-inflammatory drugs (NSAIDs). Major barriers included limited access to anesthesia records, testing reagents, and resource-related contrainsts in low-income regions. Respondents expressed the need for guidelines on alternative agents and validated non-irritating skin test concentrations. Conclusions:This international survey highlights substantial regional differences and global barriers in POA evaluation. Improving access to diagnostic resources, enhancing interdisciplinary collaboration, and providing clear guidance on alternative agents and standardized testing methods are essential to optimize worldwide POA management.

Health care providers across settings must be trained to manage anaphylaxis by (1) removing the offending allergen if still present; (2) positioning the patient with legs elevated, and if respiratory distress is present, allow the patient to sit upright with legs extended and elevated; (3) immediately administering epinephrine (adrenaline) intramuscularly (IM) or intranasally (IN) every 5 to 15 minutes for persistent anaphylaxis; and (4) optimizing airway, breathing, and cardiovascular (ABC) resuscitation. This may include supplemental oxygen, noninvasive or invasive positive-pressure ventilation, and intravenous fluid resuscitation. For life-threatening or refractory presentations, (5) IM/IN epinephrine should be administered every 5 minutes while addressing ABC derangements; this includes aggressive intravenous fluid resuscitation for patients in anaphylactic shock. Providers may continue IM or IN epinephrine or switch to the other, as both routes are considered equally efficacious based on pharmacokinetic data. An intravenous epinephrine infusion should be prepared for patients with persistent anaphylaxis after 2 doses of IM/IN epinephrine and initiated after the third dose, or earlier at the provider's discretion. In settings without epinephrine infusions, repeat IM/IN epinephrine should be administered every 5 minutes, along with other ABC interventions, and the patient should be transferred quickly to a setting equipped to provide advanced resuscitative care.

Seafood allergy is complex due to extensive species diversity, posing major challenges in food safety assessments, clinical diagnosis and dietary management. However, the absence of established workflows to resolve allergenomes limits correlations between allergen abundance, clinical sensitisation, and consumer risk. Mass spectrometry (MS)-based proteomics overcomes limitations of conventional immunoassay allergen detection by enabling unbiased protein identification and quantification, including allergen isoforms and low-abundance proteins within complex matrices. An integrated workflow combining immunological analyses, liquid chromatography-MS/MS proteomics, and bioinformatics was developed to characterise allergenomes across eight commonly consumed Asia-Pacific fish species. Comprehensive allergen profiles were established using in silico allergenicity predictions with AllerCatPro, combined with immunological validations using allergen-specific antibody and pooled patient sera. Across eight species, 529-1012 protein groups were identified, including all 11 fish muscle allergens, with pronounced interspecies differences in allergen composition and isoform distribution. The major fish pan-allergen parvalbumin was the most abundant allergen of most species and varied in abundance by up to 7-fold. Mackerel displayed a distinct low-parvalbumin profile with enriched metabolic allergens. Tissue heating induced a consistent shift toward enrichment of heat-stable and tissue-retained allergens, particularly parvalbumin, tropomyosin, and collagen. In contrast, heating of raw extracts generated more variable and species-specific retention of selected proteins, including heat-labile metabolic enzymes. In silico analysis predicted 14 proteins with strong allergenicity evidence for further validation. Fish allergenomes are species-specific and processing-dependent, positioning quantitative proteomics as a powerful platform for improved molecular risk assessment, and the development of representative diagnostic and food safety reference materials.

Peanut allergies continuously present urging public health challenges. Oral immunotherapy (OIT) is an important treatment option for peanut allergies, but its effectiveness varies, in terms of inducing desensitization (DS) or achieving long-term sustained unresponsiveness (SU). Identifying biomarkers to predict OIT outcomes is thus of great translational interests. We thoroughly analyzed data from the POISED trial and our in-house OPIA trial, with a particular focus on the peanut-reactive T cells, in an attempt to identify potential biomarkers at baseline before OIT to distinguish DS and SU outcomes. In both the POISED trial and OPIA trial, we found that functional profiles of peanut-reactive T cells at baseline before OIT, such as their type II T helper (Th2) cell cytokine productions, including IL-4, were associated with the DS versus SU outcomes after OIT cessation. Baseline peanut-reactive T cell functional profiles might provide new possibilities for biomarker discovery to predict peanut allergy OIT outcomes.

BACKGROUND:The prevalence of allergic diseases across the Australian population, in all regions and age groups, is not well documented. This study aimed to describe the prevalence and distribution of five allergic diseases (allergic rhinitis, asthma, drug allergy, eczema, and food allergy) and examine differences by sociodemographic factors. METHODS:This study used data from the 2022 cross-sectional Australian National Health Survey. The survey randomly selected a sample of 13,095 households (with 17,093 participants) living in private dwellings in all Australian states and territories. Questionnaires were completed via face-to-face interviews. Allergic rhinitis, asthma, drug allergy, eczema, and food allergy were captured as self- or parent-reported long-term health conditions. Weighted estimates and relative standard errors were extracted and analysed. Prevalence was calculated using population data from the Australian 2021 Census. RESULTS:The prevalence of self-reported current allergic rhinitis in Australia was 23.9% (95% CI: 23.1%-24.8%), food allergy was 7.0% (95% CI: 6.5%-7.5%), drug allergy was 5.2% (95% CI: 4.7%-5.6%), eczema was 1.6% (95% CI: 1.3%-1.9%), and diagnosed asthma was 10.8% (95% CI: 10.2%-11.5%). Food allergy and asthma prevalence were similar across childhood and adulthood, whereas the prevalence of allergic rhinitis increased sharply during early adulthood. Eczema was more common in childhood, while drug allergy was more common in later adulthood. Higher rates of allergic rhinitis, food allergy, and eczema were reported among individuals with more advantaged socio-economic status. In general, allergic diseases were less commonly reported by Indigenous Australians compared to non-Indigenous Australians, and by individuals born overseas compared to those born in Australia; however, prevalence varied markedly by region of birth, with some regions exhibiting higher reported rates. CONCLUSIONS:We identified a high overall prevalence of allergic diseases in Australia, with variations across populations. The differences across populations may reflect actual prevalence or disparities in disease recognition, reporting, or access to diagnostic services.

BACKGROUND:There is a high prevalence rate of atopic comorbidities, including atopic dermatitis (AD), asthma, and concomitant food allergy (CFA), in children with peanut allergy. OBJECTIVE:To evaluate whether concomitant atopic comorbidities affect the safety and efficacy of VIASKIN peanut patch (patch containing 250 µg peanut protein [VP250]). METHODS:EPITOPE was a phase 3, double-blind, placebo-controlled trial designed to assess treatment response to VP250, as measured by eliciting dose at 12 months, in children with peanut allergy aged 1 to 3 years. This subgroup analysis assessed response rates for prespecified subgroups, including children with asthma, AD/eczema, and CFA. The safety profile of VP250 was evaluated by atopic condition in all randomized participants who received at least 1 dose. RESULTS:Responder rates were significantly greater with VP250 vs placebo, irrespective of the presence of atopic conditions. There was no significant interaction effect between participants with an atopic comorbidity and those without. The safety profile was generally similar across subgroups without any additional safety signals. There was no clinically meaningful change in severity of AD in those receiving VP250, regardless of baseline AD status. Rates of anaphylaxis were higher in those with AD or CFA receiving VP250 vs those without; however, these imbalances were also observed in the placebo group. CONCLUSION:The results suggest that 12 months of treatment with VP250 was effective in desensitizing children with peanut allergy aged 1 to 3 years, with no difference in efficacy and a favorable safety profile, regardless of the presence of atopic comorbidities. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03211247.

INTRODUCTION:The predisposition to food allergy development and the induction of allergen-specific immune responses appears to be initiated early in infancy. Early exposure to food allergens, such as peanut and cashew nut, via human milk is likely important in initiating oral tolerance and reducing risk of food allergy development. This trial aims to determine if the risk of developing peanut and cashew nut allergy during infancy can be reduced by a high peanut and cashew nut maternal diet during lactation. METHODS AND ANALYSIS:This is a multisite, parallel, two-arm (1:1 allocation), single-blinded (outcome assessors, statistical analyst and investigators), randomised controlled trial. Target sample size is 4412 participants (2206 per group). Women (aged 18-50 years) with a singleton pregnancy, who are planning to breastfeed and do not have peanut and/or cashew nut allergies are eligible to participate. After obtaining written informed consent, participants are randomised to either a high peanut and cashew nut diet (at least 60 peanuts and 40 cashew nuts per week) or a low peanut and cashew nut diet (no more than 20 peanuts and 12 cashew nuts per week). Participants are asked to follow their allocated diet from birth to 6 months postnatal. Individual lactation consultant advice and support is provided as required. The study's primary outcome is food challenge proven IgE-mediated peanut and/or cashew nut allergy during infancy (0-18 months). Key secondary outcomes include infant sensitisation to peanut and/or cashew nut. Analyses will be performed on an intention-to-treat basis according to a prespecified statistical analysis plan. ETHICS AND DISSEMINATION:Ethical approval has been granted from the Western Australian Child and Adolescent Health Service Human Research Ethics Committee (approval number RGS0000006685). Trial results will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry (ACTRN ACTRN12624000134527).

Coeliac disease and food allergy management primarily relies on the strict avoidance of dietary antigens. This approach is challenging to maintain in real-world settings and in food allergy carries the risk of life-threatening anaphylaxis. Despite their distinct pathogenesis, both disorders are driven by maladaptive responses to dietary proteins, creating opportunities for shared treatment strategies. In food allergy, desensitisation therapies such as oral, sublingual, and epicutaneous immunotherapy are well-established, complemented by biologics like omalizumab and dupilumab. However, the induction of sustained tolerance remains challenging. In contrast, therapeutic advancements for coeliac disease are still in their early stages. Current efforts focus on gluten detoxification or modification, immune blockade or modulation, tolerogenic approaches, and barrier restoration. Emerging therapies, including JAK and BTK inhibitors and microbiome-targeted interventions, support further targeted treatment options for both conditions. Biomarkers tracking gluten-specific T cells have emerged as valuable tools for immunomonitoring and symptom assessment in coeliac disease, although standardisation of patient-reported outcome measures and gluten challenge protocols is still needed. Food allergy trials are reliant on double-blind placebo-controlled food challenges to measure allergen reactivity, but these are time-consuming, carry risks, and underscore the need for surrogate biomarkers. The successful development of immune-targeted therapies will require building an immune toolset to optimally assess systemic responses to antigens in both conditions. Clinically, this could lead to better outcomes for patients who might otherwise remain undiagnosed or untreated due to the absence of significant enteropathy or allergen-specific symptoms.

The skin is a large and sophisticated organ populated by innate and adaptive immune effector cells. These immune cells provide a critical first line of defense against pathogens, but genetic and environmental factors can lead to inappropriate signaling that may manifest as hypersensitivity. The most common cutaneous allergic disorders in children include atopic dermatitis, urticaria/angioedema, and contact dermatitis. In this review, we will briefly review these conditions, with a focus on recent developments in our understanding of the diagnosis and management of these disorders.

BACKGROUND:Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy. OBJECTIVE:This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial. METHODS:REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months. RESULTS:Of the 392 participants (male 54.8%; median age 7.2 y) who received at least 1 dose of treatment, 77.8% completed the 36-month active treatment. Mean adherence to treatment was high at 96.4%. Most participants (98.7%) experienced at least 1 treatment-emergent adverse event (TEAE); the majority were mild or moderate and decreased in frequency and severity over time. Most participants (94.6%) experienced at least 1 treatment-related TEAE. Local skin reactions were the most common treatment-related TEAE with the incidence decreasing from year 1 (87.8%) to year 3 (19.2%). Serious treatment-related TEAEs were reported in 2 participants. No specific safety signals were identified in the 14 participants enrolled with a history of severe anaphylaxis (Anaphylaxis Staging System grade 3). CONCLUSION:Consistent with previous phase 3 studies, long-term EPIT with VIASKIN peanut patch 250 μg was well tolerated with high adherence in peanut-allergic children aged 4 through 11 years (clinicaltrials.gov; NCT: NCT02916446).

OBJECTIVES:We compared the effect of a heterologous wP/aP/aP primary series (hereafter mixed wP/aP) versus a homologous aP/aP/aP primary schedule (hereafter aP-only) on antibody responses to co-administered vaccine antigens in infants and toddlers. METHODS:We randomised Australian infants in a 1:1 ratio to receive either a mixed wP/aP schedule (pentavalent diphtheria-tetanus-wP-hepatitis B-Haemophilus influenzae type b; DTwP-HepB-Hib vaccine at 6 weeks old, followed by hexavalent DTaP-inactivated poliovirus vaccine (IPV)-HepB-Hib vaccine at 4 and 6 months old) or aP-only priming doses of hexavalent DTaP-IPV-HepB-Hib vaccine at the same ages. All infants received 13-valent pneumococcal conjugate vaccine (13vPCV) at 6 weeks, 4 and 12 months of age and DTaP-IPV and Hib vaccine boosters at 18 months. We assessed whether the wP/aP schedule is non-inferior to the aP-only schedule for co-administered vaccine antigens (geometric mean ratio [GMR] >2/3). REGISTRATION:ACTRN12617000065392p. RESULTS:Between March 2018 and January 2020, 150 infants were randomised (75 per arm). Responses to all 13vPCV serotypes and Hib-PRP at 6, 7, 18, and 19 months old, as well as HBsAg at 6 and 7 months old, were non-inferior (>90% probability). CONCLUSION:A mixed wP/aP schedule resulted in non-inferior IgG responses to co-administered vaccine antigens compared to the standard aP-only schedule for pertussis primary immunisation.

Oral immunotherapy (OIT) is an important treatment option for food allergy but achieving sustained unresponsiveness (SU) via OIT is challenging. Improving SU for OIT with adjuvants is of great interest but little progress has been made so far. Gut microbiota-derived metabolites like short-chain fatty acids (SCFAs) protect against food allergy in mouse models via promoting regulatory T cells (Treg) generation. We thus aim to investigate the impacts from metabolite-based dietary supplement as an adjuvant in food allergic children receiving peanut OIT. Based on a prior phase 2 single centre open label interventional randomized controlled trial Oral Peanut Immunotherapy with Short Chain Fatty Acid Adjuvant (OPIA, ACTRN12617000914369), gut microbiota and immune profiles from food allergic children receiving peanut OIT supplemented with butyrylated high-amylose maize starch (HAMSB) or with low amylose maize starch (LAMS) were comprehensively profiled. HAMSB conferred minimal effects on gut microbiota, except transiently increasing their SCFA production like propionate and butyrate. HAMSB skewed CD4 + FOXP3 + Treg towards a tolerogenic phenotype and strikingly increased anti-inflammatory CD4 - FOXP3 + Treg, even after cessation of OIT and HAMSB. We present the first report of the potent immune modulatory effects of dietary butyrate supplementation via HAMSB over an extended period of 1 year in food allergic children. Our findings highlight the tolerance inducing effects of HAMSB and its potential as immunotherapy adjuvant for food allergy and/or autoimmune diseases.

BACKGROUND:The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years. OBJECTIVE:To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study. METHODS:Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results. RESULTS:A total of 266 EPITOPE participants enrolled in the OLE study; 244 underwent month 24 DBPCFC (n = 166 VP250; n = 78 placebo). After 24 months of VP250, 81.3% reached an eliciting dose (ED) ≥1000 mg, 63.8% reached an ED ≥2000 mg, and 55.9% completed the DBPCFC (cumulative dose: 3444 mg) without meeting stopping criteria. No treatment-related anaphylaxis or serious treatment-related adverse events occurred during year 2 in this treatment arm. Local application-site reactions occurred less frequently in year 2 versus year 1. In placebo-treated EPITOPE participants, outcomes after 1 year of open-label VP250 were consistent with EPITOPE treatment results: 62.7% reached an ED ≥1000 mg, 36.5% reached an ED ≥2000 mg, and 28.4% completed the DBPCFC without meeting stopping criteria; and there was 1 treatment-related anaphylaxis event. CONCLUSIONS:Two years of VP250 in young peanut-allergic children demonstrated continued increases in treatment effect without new safety signals. This supports the potential of VP250 as a safe and effective treatment for peanut allergy in young children. CLINICALTRIALS:GOV: NCT03859700.

SummaryBackgroundWhole-cell pertussis (wP) and acellular pertussis (aP) vaccines evoke different immune responses to pertussis vaccine antigens. We compared the effect of a heterologous wP/aP/aP primary series (hereafter mixed wP/aP) versus a homologous aP/aP/aP primary schedule (hereafter aP-only) on antibody responses to co-administered vaccine antigens in infants and toddlers.MethodsWe randomised Australian infants in a 1:1 ratio to receive either a mixed wP/aP schedule (pentavalent diphtheria-tetanus-wP-hepatitis B-Haemophilus influenzaetype b; DTwP-HepB-Hib vaccine at 6 weeks old followed by hexavalent DTaP-inactivated poliovirus vaccine (IPV)-HepB-Hib vaccine at 4 and 6 months old) or to aP-only priming doses of hexavalent DTaP-IPV-HepB-Hib vaccine at the same ages. All infants received 13-valent pneumococcal conjugate vaccine (13vPCV) at 6 weeks, 4 and 12 months of age and DTaP-IPV and Hib vaccine boosters at 18 months. We estimated the ratio (GMR) of IgG geometric mean concentrations (GMCs) in the wP/aP and aP-only groups for the serotypes included in the 13vPCV, for Hib capsular polysaccharide polyribosylribitol phosphate (PRP), and for hepatitis B surface antigen (HBsAg) at 6, 7, 18, and 19 months. We assessed whether the wP/aP schedule is non-inferior to the aP-only schedule for co-administered vaccine antigens (GMR>2/3). Trial registration: ACTRN12617000065392p.ResultsBetween March 2018 and January 2020, 150 infants were randomised (75 per study arm). Responses to all 13vPCV serotypes and Hib-PRP at 6, 7, 18, and 19 months old, as well as HBsAg at 6 and 7 months old were non-inferior (>90% probability). Sera GMCs were higher for each 13vPCV serotype, Hib-PRP, and HBsAg at each timepoint in the wP/aP group than in the aP-only group.InterpretationA mixed wP/aP schedule resulted in non-inferior IgG responses to co-administered vaccine antigens compared to the standard aP-only schedule for pertussis primary immunisation.FundingTelethon New Children’s Hospital Research Fund and National Health and Medical Research Council.Research in contextEvidence before this studyCombination vaccines incorporate antigens that protect against multiple diseases into a single injection. Most low- and middle-income countries (LMICs) currently use wP combination vaccines. Due to the need for periodic boosters to protect older children, adolescents, and adults, these countries may consider moving to the less reactogenic aP combination vaccines that are routinely used in most high-income countries. We searched for evidence about whether a mixed wP/aP primary schedule impacts the immunogenicity of co-administered vaccines. We were particularly interested in evidence for impacts on 13vPCV 2 + 1 schedule and other pneumococcal dose-sparing schedules. We searched PubMed on May 23, 2024, for randomised controlled trials using the following search terms “pneumococcal”, “routine vaccin*”, and “pertussis” combined with Boolean operators, without date or language restrictions. We failed to identify any head-to-head randomised comparisons of the effect of heterologous (mixed) versus homologous pertussis vaccine primary series on co-administered vaccine antigens. Our previous meta-analysis reviewed 15 randomised controlled studies that compared serious adverse events among infants receiving wP versus aP as a first dose before 6 months of age. Few studies reported immune responses to non-DTP co-administered antigens. These findings suggest enhanced Hib responses among recipients of a three-dose primary series of wP compared to those who received three primary aP doses, non-inferior Hib-PRP seroprotection among aP compared to wP vaccinees, and mixed results regarding HBsAg-IgG levels post-wP priming. Both wP and aP groups exhibited weaker Hib-PRP IgG responses when DTP-Hib vaccines were co-administered with meningococcal serogroup C vaccine conjugated to cross-reactive material 197 (CRM197) compared to the meningococcal serogroup C vaccine conjugated to tetanus toxoid (TT).Added value of this studyThis paper is the first reported evidence of a mixed wP/aP schedule resulting in non-inferior IgG responses to co-administered vaccine antigens compared to the standard homologous aP-only schedule for pertussis primary immunisation. In addition, enhanced immune responses were observed to all serotypes included in the 13vPCV and Hib-PRP vaccines in children receiving the mixed wP/aP vaccination strategy versus those vaccinated with a standard aP-only schedule.Implications of all the available evidenceIn settings transitioning from using wP to aP multi-component vaccines, infants receiving a mixed schedule (with wP as the first dose) can be expected have non-inferior, and possibly superior, antibody responses to concomitant vaccine antigens. To better understand the underlying mechanisms of our findings, the assessment of opsonophagocytic activity response rates and serotype-specific memory B cell immune responses to PCV antigens is required. Large population-based studies, particularly in countries where pneumococcal and Hib disease burdens remain high, should be conducted to determine if the observed effects on immune responses translate into differences in protection against disease.

BACKGROUND:Sustained unresponsiveness (SU) remains a major challenge for peanut OIT. The short chain fatty acid (SCFA) butyrate has the potential to upregulate regulatory T cells (Tregs) to improve long term tolerance. We conducted a superiority randomised controlled trial to assess the efficacy and safety of the addition of daily oral butyrate to peanut OIT. METHODS:Peanut allergic children (aged 10-16 years) were recruited in a single-centre randomised double-blind placebo-controlled trial and randomised 2:2:1 to receive 12 months daily peanut OIT with HAMSB (OIT + butyrate), peanut OIT with LAMS (OIT + placebo) or no OIT (control) following an entry DBPCFC. Allocation of HAMSB and LAMS was blinded. Peanut OIT was open. Exit DBPCFC was performed after at least 6 weeks of treatment cessation. The primary outcome was the proportion of participants who tolerated ≥ 1000 mg of peanut protein (cumulative dose 1449 mg) at exit DBPCFC. Adverse events and compliance were recorded. Blood Treg responses and stool SCFA analysis were performed. RESULTS:A total of 65 participants were enrolled (male 57%, median age 12 years). Of these 26 participants received OIT + butyrate, 26 received OIT + placebo, and 13 received standard care with no OIT (control). After 6 weeks of treatment cessation, 73% (19/26) of OIT + butyrate, 69% (18/26) of OIT + placebo (OR 95% CI = 1.21 (0.36-4.0) for OIT + butyrate relative to OIT + placebo, p = 0.76) and 0% (0/13) of the control group tolerated at least 1000 mg (cumulative dose 1449 mg) of peanut protein. The most common adverse events observed in OIT + butyrate and OIT + placebo were gastrointestinal related (73%). Treatment-related anaphylaxis occurred in eight participants; four in each OIT group (15%). There was no statistically significant difference in AE rate between OIT + butyrate and OIT + placebo. INTERPRETATION:In a first in food allergy clinical trial setting, the addition of oral butyrate to peanut OIT was well tolerated but did not enhance SU rate in our cohort. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12617000914369; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000914369; Trial was registered on 22 June 2017.

Background: Limited research exists on when to administer epinephrine (adrenaline) or activate emergency medical services (EMS) during acute allergic reactions in community settings. This contributes to suboptimal patient care, including both the underuse and overuse of epinephrine, as well as potentially unnecessary emergency department visits. Objective: We developed consensus recommendations for administering epinephrine and activating EMS during acute allergic reactions. Methods: From January 2024 to May 2025, we assembled a 34-member international panel of experts to develop clinical scenarios reflecting varying severity levels within and across organ systems, candidate modifiers that may lower the threshold for epinephrine administration (eg, history of asthma), and candidate EMS activation recommendations. In phase 1, the panel engaged in a modified Delphi process to reach consensus on these outputs. In phase 2, we tested each consensus modifier by embedding it into scenarios where epinephrine was not recommended or lacked consensus, to assess potential impacts on treatment decisions. Results: The expert panel developed 24 clinical scenarios, 9 candidate modifiers, and 12 candidate EMS activation recommendations. During the first phase, 21 statements reached consensus to recommend epinephrine, 2 reached consensus not to recommend it, and 1 did not reach a consensus. There were 5 consensus modifiers and 10 consensus EMS activation recommendations. In the second phase, 2 of the 15 clinical scenarios reached consensus to recommend epinephrine administration. Conclusion: We developed consensus recommendations for administering epinephrine and activating EMS during acute allergic reactions in community settings. Integrating them into technology-based decision support tools may enhance reaction management, improve patient outcomes, optimize health care utilization, and empower patient and caregiver self-efficacy.