A protocol for a systematic review to identify allergenic tree nuts and the molecules responsible for their allergenic properties.
Food regulations require that tree nuts and derived ingredients are included on food labels in order to help individuals with IgE-mediated allergies to avoid them. However, there is no consensus regarding which tree nut species should be included in this definition and specified on food labels. Allergen detection methods used for monitoring foods target allergen molecules, but it not clear which are the most relevant molecules to choose. A modified population-exposure-comparators-outcome (PECO) approach has been developed to systematically review the evidence regarding (1) which allergenic tree nuts should be included in food allergen labelling lists and (2) which are the clinically relevant allergens which should be used as analytical targets. A search strategy and criteria against which the evidence will be evaluated have been developed. The resulting evidence will be used to rank tree nuts with regards their ability to cause IgE-mediated allergies, and allergen molecules regarding their capacity to elicit an allergic reaction. The results of the systematic review will enable risk assessors and managers to identify tree nut species that should be included in food allergen labelling lists and ensure analytical methods for determination of allergens in foods are targeting appropriate molecules.
Prevalence of food allergies and intolerances documented in electronic health records.
BACKGROUND: Food allergy prevalence is reported to be increasing, but epidemiological data using patients' electronic health records (EHRs) remain sparse. OBJECTIVE: We sought to determine the prevalence of food allergy and intolerance documented in the EHR allergy module. METHODS: Using allergy data from a large health care organization's EHR between 2000 and 2013, we determined the prevalence of food allergy and intolerance by sex, racial/ethnic group, and allergen group. We examined the prevalence of reactions that were potentially IgE-mediated and anaphylactic. Data were validated using radioallergosorbent test and ImmunoCAP results, when available, for patients with reported peanut allergy. RESULTS: Among 2.7 million patients, we identified 97,482 patients (3.6%) with 1 or more food allergies or intolerances (mean, 1.4 ± 0.1). The prevalence of food allergy and intolerance was higher in females (4.2% vs 2.9%; P < .001) and Asians (4.3% vs 3.6%; P < .001). The most common food allergen groups were shellfish (0.9%), fruit or vegetable (0.7%), dairy (0.5%), and peanut (0.5%). Of the 103,659 identified reactions to foods, 48.1% were potentially IgE-mediated (affecting 50.8% of food allergy or intolerance patients) and 15.9% were anaphylactic. About 20% of patients with reported peanut allergy had a radioallergosorbent test/ImmunoCAP performed, of which 57.3% had an IgE level of grade 3 or higher. CONCLUSIONS: Our findings are consistent with previously validated methods for studying food allergy, suggesting that the EHR's allergy module has the potential to be used for clinical and epidemiological research. The spectrum of severity observed with food allergy highlights the critical need for more allergy evaluations.
An update on the impact of food allergy on anxiety and quality of life.
PURPOSE OF REVIEW: Food allergies have become more common, and management involves dietary avoidance that can impair quality of life. Patients and families must manage the daily risk of anaphylaxis at each meal. The purpose of this review is to describe the impact of food allergies on quality of life and to provide an update on new developments in food allergy management, particularly peanut allergy. RECENT FINDINGS: Food allergy requires careful avoidance of common and ubiquitous dietary allergens. Living with food allergy is associated with annual economic costs in excess of $4000 per child, in addition to risks of anxiety and depressive symptoms. An expert panel sponsored by the 2017 National Institute of Allergy and Infectious Diseases published addendum guidelines for the prevention of peanut allergy, which suggest three separate approaches to peanut protein introduction for infants at various levels of risk. SUMMARY: Clinicians must be aware of underappreciated burdens faced by children and families with food allergies. Management involves a partnership between primary and specialty care. Mitigation strategies to improve quality of life for patients include efforts to avoid overdiagnosis in synergy with balanced counseling about the risks of food allergies. Experimental food allergen desensitization can improve quality of life but remains investigational at this time. For patients with significant anxiety, interdisciplinary management involving professional counseling may be helpful. Risk stratification and early introduction of peanut protein can help prevent the development of peanut allergy.
Specific allergen profiles of peanut foods and of diagnostic or therapeutic allergenic products.
RATIONALE: 'Generic' immunoassays for peanut cannot discriminate between allergen levels in peanut derived food products or therapeutics. Clinical trials of oral immunotherapy are strengthened by using standardized peanut preparations, with defined doses of major allergens. OBJECTIVE: This paper describes measurement of Ara h 1, Ara h 2 and Ara h 6 in peanut foods and in peanut flour extracts used for allergy diagnosis and oral immunotherapy. METHODS: Monoclonal antibody-based enzyme immunoassays for Ara h 1, Ara h 2 and Ara h 6 were used to compare allergen levels in peanut (n=19) and tree nut (n=16) butter, peanut flour (n=11); oils (n=8); extracts used for diagnosis and oral immunotherapy (n=5); and the National Institute for Standards and Technology Peanut Butter Standard Reference Material® 2387. RESULTS: Roasted peanut butters contained 991-21,406μg/g Ara h 1 and exceeded Ara h 2 and Ara h 6 levels by 2-4 fold. Similarly, NIST SRM 2387 contained 11,275μg/g Ara h 1; 2,522μg/g Ara h 2 and 2,036μg/g Ara h 6. In contrast, peanut flours contained 787-14,631μg/g Ara h 2 and exceeded Ara h 1 levels by 2-20 fold. Flour extracts used for oral immunotherapy contained 394-505μg/ml Ara h 1, 1,187-5,270μg/ml Ara h 2 and 1,104-8,092μg/ml Ara h 6. In most cases, specific peanut allergens were not detected in tree nut butters or peanut oils. CONCLUSIONS: The results show marked differences in specific peanut allergen profiles in peanut butter, flour and peanut preparations for clinical use. Roasting may increase Ara h 1 levels in peanut butter. Variability in allergen levels could affect the outcome of clinical trials of peanut oral immunotherapy, especially with respect to Ara h 1. Specific allergen measurements will improve standardization and provide accurate dosing of peanut preparations that are being used for oral immunotherapy.
Low Food Allergy Prevalence Despite Delayed Introduction of Allergenic Foods—Data from the GUSTO Cohort.
BACKGROUND: There is mounting evidence that early introduction of allergenic food decreases the risk of food allergy development, especially in high-risk infants with eczema. However, there is a lack of data to suggest whether this association holds true in Asian populations. OBJECTIVE: To investigate the relationship between the timing of introduction of allergenic foods and food allergy outcomes in infants in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. METHODS: The GUSTO cohort recruited 1152 mothers of Chinese, Malay, and Indian ethnicity who had singleton, naturally conceived pregnancies and followed their offspring prospectively. Information on demographic characteristics, child health, infant feeding practices, and a convincing history of IgE-mediated food allergy was obtained from interviewer-administered questionnaires at multiple time points. Corroborative skin prick tests to food allergens were performed at 18 and 36 months. RESULTS: Most of the infants were introduced to egg (49.6%), peanut (88.7%), and shellfish (90.2%) after age 10 months. Food allergy prevalence was, however, very low between age 12 and 48 months: egg, 0.35% to 1.8%; peanut allergy, 0.1% to 0.3%; and shellfish, 0.2% to 0.9%. There were no significant associations between the timing of introduction of allergenic foods and the development of food allergy, adjusted for confounders including breast-feeding and eczema. CONCLUSIONS: Food allergy rates in Singapore are low despite delayed introduction of allergenic foods. Early introduction of allergenic foods may thus not be necessary in populations in which overall food allergy prevalence is low, and thus infant feeding recommendations should be carefully tailored to individual populations.
Methods in Allergy/Immunology: Food Challenges.
Since there is no in vitro test, which can accurately predict the clinical relevance of a sensitization to food, the oral food challenge still remains the most reliable procedure to confirm or exclude food allergy and to assess the development of tolerance in children with potentially transient food allergies such as to cow's milk, hen's egg, wheat or soy. Although in the last few years component-resolved diagnostic has improved the food allergy diagnostics, especially in peanut and tree nut allergy, the majority of patients still need to undergo oral food challenge. The following paper will describe in whom and how to perform an oral food challenge as well as its interpretation of the results with a focus on suspected IgE-mediated food allergy.
The role of environmental exposure to peanut in the development of clinical allergy to peanut.
The presence of peanut allergy has increased over the years and still remains one of the most common causes of food-related anaphylaxis. The way in which peanut sensitization occurs has been explored, such as via maternal consumption in pregnancy, via breast milk and through a disrupted skin barrier. It has previously been shown that environmental exposure to aeroallergens in household dust can be a risk factor for the development of allergic asthma. However, it is likely that the combination of cutaneous sensitisation via a disrupted skin barrier (i.e. children with eczema especially those with filaggrin mutations) and the interaction with environmental peanut exposure influences the development of peanut allergy. This review aims to explore the current evidence of how environmental exposure to peanut affects the development of peanut allergy.
The concordance between component tests and clinical history in British adults with suspected pollen-food syndrome to peanut and hazelnut.
BACKGROUND: Mild oropharyngeal symptoms to peanut/hazelnut occur in ~30% of patients with pollen-food syndrome (PFS). Component tests are considered a useful adjunct to the diagnosis and may help differentiate PFS from those at a risk of anaphylaxis due to storage protein/lipid transfer protein (LTP) sensitisation. AIMS: To assess concordance between component tests and clinical history in suspected PFS to peanut/hazelnut in a specialist clinic. METHODS: Adult patients were classified into PFS (group 1, n=69) and PFS with mild systemic symptoms (group 2, n=45) based on clinical history. Specific IgE (sIgE) of ≥0.35 kUA/L was considered positive as per manufacturers’ recommendation. Kappa (κ) inter-rater agreement was calculated for concordance between clinical classification and test profiles. RESULTS: Group 1 hazelnut: 85% monosensitised to Cor a1, 12% to storage protein/s or LTP and 3% negative to all components. Group 1 peanut: 41% monosensitised to Ara h8, 44% to storage protein/s or ±LTP and 15% negative to all components. Group 2 hazelnut: 67% monosensitised to Cor a1, 16% sensitised to storage protein/s and 17% negative to all components. Group 2 peanut: 19% monosensitised to Ara h8, 62% sensitised to storage protein/s and/or LTP and 19% negative to all components. SIgE to Ara h8 and Cor a1 were greater in group 1 versus group 2: (median (IQR) kUA/L; hazelnut: 12.1 (7.8-25.2) vs 2.4 (0.36-6.3), p<0.001; peanut: 2.4 (0.10-21.1) vs 0.3 (0-3), p<0.01)). CONCLUSION: Concordance between component tests and clinical history for adults with PFS was good for hazelnut (κ=0.63) but poor for peanut (κ=âˆ'0.12). Food challenges are warranted in discordant cases for an accurate diagnosis.
Food allergen detection by mass spectrometry: the role of systems biology.
Food allergy prevalence is rising worldwide, motivating the development of assays that can sensitively and reliably detect trace amounts of allergens in manufactured food. Mass spectrometry (MS) is a promising alternative to commonly employed antibody-based assays owing to its ability to quantify multiple proteins in complex matrices with high sensitivity. In this review, we discuss a targeted MS workflow for the quantitation of allergenic protein in food products that employs selected reaction monitoring (SRM). We highlight the aspects of SRM method development unique to allergen quantitation and identify opportunities for simplifying the process. One promising avenue identified through a comprehensive survey of published MS literature is the use of proteotypic peptides, which are peptides whose presence appears robust to variations in food matrix, sample preparation protocol, and MS instrumentation. We conclude that proteotypic peptides exist for a subset of allergenic milk, egg, and peanut proteins. For less studied allergens such as soy, wheat, fish, shellfish, and tree nuts, we offer guidance and tools for peptide selection and specificity verification as part of an interactive web database, the Allergen Peptide Browser (http://www.AllergenPeptideBrowser.org). With ongoing improvements in MS instrumentation, analysis software, and strategies for targeted quantitation, we expect an increasing role of MS as an analytical tool for ensuring regulatory compliance.
The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4-year follow-up.
BACKGROUND: The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse. OBJECTIVE: This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years. METHODS: HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires. RESULTS: The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life. CONCLUSIONS: Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high.