Longitudinal peanut and Ara h 2 specific-IgE, -IgG4, and -IgG4/-IgE ratios are associated with the natural resolution of peanut allergy in childhood.

BACKGROUND: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. OBJECTIVES: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. METHODS: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG4 to peanut and Ara h 2. RESULTS: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG4 (p < .001), Ara h 2 sIgG4 (p = .01), peanut sIgG4/sIgE (p < .001) and Ara h 2 sIgG4/sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. CONCLUSION: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

Characterization of Adverse Outcomes from Legacy-Contaminated Groundwater Exposure to Early Life Stages of Fathead Minnow.

Complex mixtures of chemicals present in groundwater at legacy-contaminated industrial sites can pose significant risks to adjacent surface waters. The combination of short-term molecular and chronic apical effect assessments is a promising approach to characterize the potential hazard of such complex mixtures. The objectives of this study were to: (1) assess the apical effects (survival, growth, development, and liver histopathology) after chronic exposure of early life stages (ELSs) of fathead minnows (FHM; Pimephales promelas) to contaminated groundwater from a legacy-contaminated pesticide manufacturing and packaging plant, and (2) identify possible molecular mechanisms responsible for these effects by comparing results to mechanistic outcomes previously determined by a short-term reduced transcriptome assay (EcoToxChips). This study revealed a significant increase in mortality and prevalence of spinal curvatures, as well as a significant reduction in the length of FHMs exposed to the groundwater mixtures in a concentration-dependent manner. There was an increasing trend in the prevalence of edema in FHMs, though not significantly different from controls. Additionally, no histopathological effects were observed in the liver of FHMs exposed to the groundwater mixtures. Short-term molecular outcomes determined in a parallel study were found to be informative of chronic apical outcomes, including cardiotoxicity, spinal deformities, and liver toxicity. Overall, the results observed in this study demonstrated that short-term transcriptomics analyses could support the hazard assessment of complex contaminated sites.

Epigenomic variability is associated with age-specific naïve CD4 T cell response to activation in infants and adolescents.

Childhood is a critical period of immune development. During this time, naïve CD4 (nCD4) T cells undergo programmed cell differentiation, mediated by epigenetic changes, in response to external stimuli leading to a baseline homeostatic state that may determine lifelong disease risk. However, the ontogeny of epigenetic signatures associated with CD4 T cell activation during key developmental periods are yet to be described. We investigated genome-wide DNA methylation (DNAm) changes associated with nCD4 T activation following 72 h culture in media+anti-CD3/CD28 beads in healthy infants (aged 12 months, n = 18) and adolescents (aged 10-15 years, n = 15). We integrated these data with transcriptomic and cytokine profiling from the same samples. nCD4 T cells from both age groups show similar extensive epigenetic reprogramming following activation, with the majority of genes involved in the T cell receptor signaling pathway associated with differential methylation. Additionally, we identified differentially methylated probes showing age-specific responses, that is, responses in only infants or adolescents, including within a cluster of T cell receptor (TCR) genes. These encoded several TCR alpha joining (TRAJ), and TCR alpha variable (TRAV) genes. Cytokine data analysis following stimulation revealed enhanced release of IFN-γ, IL-2 and IL-10, in nCD4 T cells from adolescents compared with infants. Overlapping differential methylation and cytokine responses identified four probes potentially underpinning these age-specific responses. We show that DNAm in nCD4T cells in response to activation is dynamic in infancy and adolescence, with additional evidence for age-specific effects potentially driving variation in cytokine responses between these ages.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

TreEAT trial: Protocol for a randomized controlled trial investigating the efficacy and safety of early introduction of tree nuts for the prevention of tree nut allergy in infants with peanut allergy.

INTRODUCTION: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy; however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. METHODS AND ANALYSIS: TreEAT is a 2-armed, open-label, randomized, controlled trial (RCT). Infants (n = 212) aged 4-11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut, and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy-related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention-to-treat basis. ETHICS AND DISSEMINATION: TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT04801823.

Early peanut introduction: To test or not to test?

OBJECTIVE: To review recent evidence and international guidelines on early peanut introduction for preventing peanut allergy and provide an update on the status of the debate around testing before early peanut introduction. DATA SOURCES: Review of published literature documenting: infant feeding guidelines; impact of early peanut introduction on peanut allergy; risk factors for peanut allergy; and impact of early peanut introduction guidelines on infant feeding practices and allergy. STUDY SELECTION: We used a narrative approach and present both pro and con arguments for testing before peanut introduction. Data from randomized controlled trials and post-hoc analyses of these trials and observational studies were included. RESULTS: Allergy prevention guidelines around the world now consistently recommend introducing peanut into an infant's diet before 12 months of age for countries with high peanut allergy prevalence. In the US, guidelines recently shifted away from recommending allergy testing before introduction for those at risk of peanut allergy. There is evidence primarily from Australia that recommending early introduction without prior testing is safe and effective in increasing early peanut introduction for both high and low-risk infants, although the subsequent reduction in peanut allergy prevalence at the population level was less than expected. CONCLUSION: Current evidence supports recommending early peanut introduction without routinely testing for peanut allergy. If testing is offered, this should be based on shared decision making between families and practitioners and only be undertaken where there is provision for rapid access to definitive diagnosis including oral food challenges.

Epidemiology of eczema in South-Eastern Australia.

BACKGROUND/OBJECTIVES: Eczema is a common chronic debilitating skin condition in childhood. Data on the epidemiology and natural history of eczema across the life course are lacking. This analysis aimed to describe these epidemiological features in Australian children and adults. METHODS: Data collected on eczema from four Australian cohort studies were analysed: namely HealthNuts, Melbourne Atopic Cohort Study (MACS), Tasmanian Longitudinal Health Study (TAHS) and the Australian arm of the European Community Respiratory Health Survey (ECRHS). RESULTS: Among children aged under 6 years, 28.8%-35.6% have ever-had eczema, and 16.7%-26.6% had 'current eczema'. Among those aged 6-12 years, 14.6%-24.7% had 'current eczema' with 12.0%-18.5% of those at ages of 6 and 10 years classified as having moderate-to-severe eczema according to the Scoring of Atopic Dermatitis (SCORAD) index. In adults, the prevalence of 'eczema ever' ranged between 13.8% and 48.4%. The 12-month period prevalence of eczema was 15.1% at age 18, while current eczema was 8.5% at an average age of 51, and 8.8% at an average age 53 years. Eczema was more common among young boys, but this difference became non-significant for older children and early adolescents. In contrast, eczema was more common for adult women than men. CONCLUSIONS: Eczema is common both in children and adults. The proportion of severe eczema in children was substantial.

The natural history of peanut and egg allergy in children up to age 6 years in the HealthNuts population-based longitudinal study.

BACKGROUND: Prospectively collected data on the natural history of food allergy are lacking. OBJECTIVE: We examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood. METHODS: The HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up. RESULTS: New-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52]). CONCLUSION: Most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg.

Climate change and global health: A call to more research and more action.

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

A pragmatic approach to infant feeding for food allergy prevention.

Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2-driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.

The association between environmental greenness and the risk of food allergy: A population-based study in Melbourne, Australia.

BACKGROUND: While exposure to environmental greenness in childhood has shown mixed associations with the development of allergic disease, the relationship with food allergy has not been explored. We investigated the association between exposure to environmental greenness and challenge-confirmed food allergy in a large population-based cohort. METHODS: The HealthNuts study recruited 5276 12-month-old infants in Melbourne, Australia, who underwent skin prick testing to peanut, egg, and sesame; infants with a detectable wheal underwent food challenges to determine food allergy status. Environmental greenness was estimated using the normalized difference vegetation index (NDVI) for five buffer zones around the infant's home address: at the home, 100 m, 500 m, 800 m, and 1600 m radial distances. Environmental greenness was categorized into 3 tertiles and mixed effects logistic regression models quantified the association between greenness and the risk of food allergy, adjusting for confounding and accounting for clustering at the neighborhood level. RESULTS: NDVI data were available for n = 5097. For most buffer zones, medium and high greenness, compared to low greenness, was associated with an increased risk of peanut allergy (eg, 100 m tertile 2 aOR 1.89 95% CI 1.22-2.95, tertile 3 aOR 1.78 95% CI 1.13-2.82). For egg allergy, the effect sizes were smaller (100 m tertile 2 aOR 1.52 95% CI 1.16-1.97, tertile 3 aOR 1.38 95% CI 1.05-1.82). Socioeconomic status (SES) modified the association between greenness and peanut allergy, but not egg allergy; associations were apparent in the low SES group but not in the high SES group (p for interaction 0.08 at 100 m). Air pollution (PM2.5) also modified the associations between environmental greenness and food allergy, with associations present in high air pollution areas but not low (p for interaction at 100 m 0.05 for peanut and 0.06 for egg allergy.) CONCLUSION: Increased exposure to environmental greenness in the first year of life was associated with an increased risk of food allergy. Increased greenness may correlate with higher pollen levels which may trigger innate immune responses skewing the immune system to the Th2-dependent allergic phenotype; additionally, some pollen and food allergens are cross-reactive. Given the mixed data on greenness and other allergies, the relationship appears complex and may also be influenced by confounding variables outside those that were measured in this study.

Out-of-hospital health care costs of childhood food allergy in Australia: A population-based longitudinal study.

BACKGROUND: Australia has one of the highest prevalence of childhood food allergy in the world, but there are no data on its economic burden in Australia. METHODS: We used data from the HealthNuts study, a population-based longitudinal study undertaken in Melbourne, Australia. Infants were recruited at age 12 months between Sept 2007 and Aug 2011 with food allergy diagnosed using oral food challenges. Health care costs of out-of-hospital services were collected through data linkage to Australia's universal health insurance scheme Medicare. Two-part model was used to compare costs after controlling for potential confounders. RESULTS: 2919 children were included, and 390 (13.4%) had challenge-confirmed food allergy at age 1 year. Compared with children without food allergy, children with food allergy had significantly higher costs for GP visits, specialist visits, tests, and prescriptions in the first four years of life. The total Medicare cost associated with food allergy from age 1 to 4 years was estimated to be AUD$889.7 (95% CI $566.1-$1188.3) or €411.0 (95% CI €261.5-€549.0) per child. This was projected into an annual Medicare cost of AUD$26.1 million (95% CI $20.1-$32.3 million) or €12.1 (95% CI €9.3-€14.9 million) based on population size in 2020. CONCLUSIONS: Childhood food allergy causes considerable Medicare costs for out-of-hospital services in the first four years after birth in Australia. These findings can help anticipate the financial impact on the health care system associated with childhood food allergy, act as a useful costing resource for future evaluations, and inform management of childhood food allergy internationally.

Protocol for a systematic review of the diagnostic test accuracy of tests for IgE-mediated food allergy.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30 September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. METHODS: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1 October 2012 to 30 June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluations will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. RESULTS: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. DISCUSSION: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.

Ana o 3 sIgE testing increases the accuracy of cashew allergy diagnosis using a two-step model.

BACKGROUND: Measurement of cashew-specific IgE (sIgE) is often used to confirm sensitization but does not reliably diagnose clinical allergy. Ana o 3 is the dominant cashew allergen detected in 75-100% of patients with cashew allergy but not currently used in clinical practice. OBJECTIVES: To determine if component-resolved diagnostics using specific IgE to the 2 S albumin from cashew, Ana o 3, improves the accuracy of diagnosing cashew allergy, thereby circumventing the need for an oral food challenge (OFC) in some patients. METHODS: A population-based sample of 5276 children was recruited at age 1 year and followed up at age 6 years. Children with positive cashew skin prick test at age 6 underwent an OFC to clarify allergy status. Forty-seven children (mean age 5.02 ± 0.2) (33 cashew-allergic and 14 cashew-tolerant) had cashew sIgE and Ana o 3 sIgE quantified by ImmunoCAP System FEIA. RESULTS: A cutoff of >0.32 kUA/L for Ana o 3 sIgE provided 95% specificity and 90% sensitivity and correctly identified 90% of clinical cashew allergy. At the same specificity, the sensitivity for cashew sIgE (>8.5 kUA/L) was only 26%. Sequential measurement of cashew sIgE followed by Ana o 3 sIgE diagnosed 90% of children with cashew allergy without the need for an OFC. CONCLUSION: Ana o 3 sIgE testing provides higher diagnostic accuracy than cashew sIgE. Sequential measurement of cashew sIgE followed by Ana o 3 removed the need for a food challenge from 66% down to 12.8% (5-fold) of children compared with cashew sIgE testing alone.

The role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children.

BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

Immuno-epigenomic analysis identifies attenuated interferon responses in naïve CD4 T cells of adolescents with peanut and multi-food allergy.

BACKGROUND: IgE-mediated food allergies have been linked to suboptimal naïve CD4 T (nCD4T) cell activation in infancy, underlined by epigenetic and transcriptomic variation. Similar attenuated nCD4T cell activation in adolescents with food allergy have also been reported, but these are yet to be linked to specific epigenetic or transcriptional changes. METHODS: We generated genome-wide DNA methylation data in purified nCD4 T cells at quiescence and following activation in a cohort of adolescents (aged 10-15 years old) with peanut allergy (peanut only or peanut + ≥1 additional food allergy) (FA, n = 29), and age-matched non-food allergic controls (NA, n = 18). Additionally, we assessed transcriptome-wide gene expression and cytokine production in these cells following activation. RESULTS: We found widespread changes in DNA methylation in both NA and FA nCD4T cells in response to activation, associated with the T cell receptor signaling pathway. Adolescents with FA exhibit unique DNA methylation signatures at quiescence and post-activation at key genes involved in Th1/Th2 differentiation (RUNX3, RXRA, NFKB1A, IL4R), including a differentially methylated region (DMR) at the TNFRSF6B promoter, linked to Th1 proliferation. Combined analysis of DNA methylation, transcriptomic data and cytokine output in the same samples identified an attenuated interferon response in nCD4T cells from FA individuals following activation, with decreased expression of several interferon genes, including IFN-γ and a DMR at a key downstream gene, BST2. CONCLUSION: We find that attenuated nCD4T cell responses from adolescents with food allergy are associated with specific epigenetic variation, including disruption of interferon responses, indicating dysregulation of key immune pathways that may contribute to a persistent FA phenotype. However, we recognize the small sample size, and the consequent restraint on reporting adjusted p-value statistics as limitations of the study. Further study is required to validate these findings.

Time trends in adrenaline auto-injector dispensing patterns using Australian Pharmaceutical Benefits Scheme data.

AIM: Adrenaline auto-injector (AAI) dispensing data, a community-based proxy for number of individuals at risk of anaphylaxis, provides complementary information on time trends of anaphylaxis risk in addition to hospital admission data. We examined trends of AAI dispensing over a 10-year period (from January 2005 to December 2014) in Australia. METHODS: Individuals with dispensed AAI were identified from a 10% random sample of Australian Pharmaceutical Benefits Scheme (PBS) data. PBS is the Australian national drug subsidy programme covering all Australians. Cumulative incidence and incidence rates of individuals with AAI were calculated. We assessed difference by age, sex, state and time trends. RESULTS: The cumulative incidence of individuals with AAI in 2005-2014 was 75.43/100 000 (95%CI 75.07-75.80/100 000). Incidence rate of individuals with AAI increased from 2005 to 2014 (from 71.47 to 82.07 per 100 000 person-years) although this varied by state. Over the time assessed, there was a shift to more prescriptions being provided by general practitioners (GP) rather than specialists. Children (0-19 years) were more likely to have been prescribed an AAI from a specialist and adults from a GP. CONCLUSION: Overall, an increase in dispensed AAI mirrored other evidence for a rising prevalence of allergy. This increase could also reflect changes in prescribing practices or increased awareness and education of health-care professionals on anaphylaxis and indications for prescribing AAI. The rising rate of AAI prescribed by GPs compared to decreasing rates by specialists suggests a changing response of the Australian health-care system to the increased burden of anaphylaxis.

Anaphylaxis to foods purchased from food establishments in Australia.

AIM: Food establishments that sell non-packaged foods are not required to have a food label directly on the food product detailing the ingredients. This practice could increase the risk of anaphylaxis among individuals with food allergy. The aim of the study is to understand whether anaphylaxis occurs commonly in individuals with food allergy as a consequence of eating food products purchased from food establishments. METHODS: We undertook an anonymous on-line cross-sectional survey of food allergic individuals over a 9-month period. Anaphylaxis was defined as reported symptoms consistent with the Australasian Society of Clinical Immunology and Allergy definition of anaphylaxis. RESULTS: A total of 268 responses were received over the study period and 264 consented and completed the questionnaire. Among our survey participants, the rate of anaphylaxis to food purchased from establishments was 27% (n = 67/246, 95% confidence interval 21.8-33.3%). Of those who reported an anaphylaxis (n = 67), 87% reported informing staff of their/their dependents food allergy/s. Most (81%) reported that they would like to see additional information, such as listing of allergen information next to dishes on the menu and 61% reported that staff pro-actively asking about food allergies would be beneficial. CONCLUSION: Anaphylaxis from food purchased at food establishments is not uncommon despite a high proportion of individuals declaring their food allergy to staff. Consumers with food allergy would like to see allergen information listed on the menus and for staff to proactively enquire about food allergies. A food allergen matrix that is regularly checked/updated so staff and consumers have easy access to information on menu items and common allergens is required.

Infant pacifier sanitization and risk of challenge-proven food allergy: A cohort study.

BACKGROUND: Environmental microbial exposure plays a role in immune system development and susceptibility to food allergy. OBJECTIVE: We sought to investigate whether infant pacifier use during the first postnatal year, with further consideration of sanitization, alters the risk of food allergy by age 1 year. METHODS: The birth cohort recruited pregnant mothers at under 28 weeks' gestation in southeast Australia, with 894 families followed up when infants turned 1 year. Infants were excluded if born under 32 weeks, with a serious illness, major congenital malformation, or genetic disease. Questionnaire data, collected at recruitment and infant ages 1, 6, and 12 months, included pacifier use and pacifier sanitization (defined as the joint exposure of a pacifier and cleaning methods). Challenge-proven food allergy was assessed at 12 months. RESULTS: Any pacifier use at 6 months was associated with food allergy (adjusted odds ratio, 1.94; 95% CI, 1.04-3.61), but not pacifier use at other ages. This overall association was driven by the joint exposure of pacifier-antiseptic use (adjusted odds ratio, 4.83; 95% CI, 1.10-21.18) compared with no pacifier use. Using pacifiers without antiseptic at 6 months was not associated with food allergy. Among pacifier users, antiseptic cleaning was still associated with food allergy (adjusted odds ratio, 3.56; 95% CI, 1.18-10.77) compared with no antiseptic use. Furthermore, persistent and repeated antiseptic use over the first 6 months was associated with higher food allergy risk (P = .029). CONCLUSIONS: This is the first report of a pacifier-antiseptic combination being associated with a higher risk of subsequent food allergy. Future work should investigate underlying biological pathways.