Introduction of Complementary Foods to Infants.
While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance. Many international infant feeding guidelines already recommend complementary foods, including allergenic foods, to be introduced from 4 to 6 months of age irrespective of family history risk. Interim guidelines from 10 International Pediatric Allergy Associations state that healthcare providers should recommend the introduction of peanut-containing products into the diets of infants at high risk of allergic disease in countries where peanut allergy is prevalent. Direct translation of the results obtained from a cohort of high-risk infants to the general population has proved difficult, and issues regarding feasibility, safety, and cost-effectiveness have been raised. Five randomized placebo-controlled trials have assessed the effects of early egg exposure in infancy with varying results. In a recent comprehensive meta-analysis, there was moderate-certainty evidence that early versus late introduction of egg was associated with a reduced egg allergy risk. Although promising, optimal timing, doses, and if the feeding regimen should be stratified according to infant allergy risk remain to be determined. The single study that assessed introduction of multiple foods from 3 months whilst breastfeeding compared with exclusive breastfeeding until 6 months of age showed no reduction in food allergy prevalence. Future research should aim at optimizing infant feeding regimens and support a tolerogenic gastrointestinal microenvironment during the period of food allergen introduction.
Changes in patient quality of life during oral immunotherapy for food allergy.
BACKGROUND: Quality of life is (QOL) impaired in patients with food allergy and improves following oral immunotherapy (OIT). However, the treatment itself is prolonged and demanding. We examined changes in patient QOL during OIT for food allergy. METHODS: The FAQLQ-PF was administered to children aged 4-12 years undergoing OIT for milk, peanut or egg allergy, at the beginning and after 4 months of treatment. Patients were categorized as improved, unchanged, or diminished FAQLQ-PF (>0.5 point decrease, a change of ≤0.5 points, or >0.5 increase, respectively) and compared. Food-allergic patients not undergoing OIT served as controls. RESULTS: The Food Anxiety, Social and Dietary limitation and total FAQLQ-PF scores improved significantly during the study period (p=0.001, p=0.018 and p=0.01, respectively) in treated but not in control patients, while the Emotional Impact did not. The change in the FAQLQ-PF was independent of the maximal tolerated dose at baseline or following four months of treatment, the pace of dose-increase or of number or severity of reactions experienced. The total FAQLQ-PF score was inversely associated with the score at baseline on multi-variate analysis (regression coefficient = -0.56, p<0.001). That was driven primarily by improvement in QOL scores in patients with high score (worse QOL) at baseline. Some patients with low FAQLQ-PF score (better QOL) at baseline, deteriorated. CONCLUSIONS: QOL of patients with food allergy improves in some but deteriorates in others during OIT. Patients with impaired QOL at baseline, improve significantly despite the treatment-burden. Some patients with better QOL at baseline, might deteriorate during OIT.
A Survey of Self-Reported Food Allergy and Food-Related Anaphylaxis among Young Adult Students at Kuwait University, Kuwait.
OBJECTIVES: To conduct a survey on self-reported food allergy to milk, egg, peanuts, tree nuts, fish, shellfish, wheat, and sesame, as well as reported food-related anaphylaxis and epinephrine prescription practices among Kuwaiti students attending Kuwait University. SUBJECTS AND METHODS: One thousand questionnaires that included data on age, gender, presence of food allergies, and associated details were distributed. All participants reporting an allergy were categorized as having a perceived food allergy. Those with a convincing clinical history and history of undergoing diagnostic food allergy testing were further categorized as having a probable food allergy. RESULTS: Of the 1,000 questionnaires, 865 (86.5%) were completed. Of the 865 students, 104 (12.02%) reported food allergy (perceived), and 47 of these (45.19%) were probable food allergies. For milk (46.7%), peanut (35.7%), fish (60%), and sesame (50%), probable food allergy occurred in early childhood (≤5 years) while those of egg (44.4%) and wheat (57.1%) occurred in late childhood (6-10 years), and shellfish (40%) occurred in early adolescence (11-15 years). Of the 47 students with a probable food allergy, 28 (59.6%) were moderate to severe: 20 (71%) of these moderate-to-severe allergy cases reported at least 1 food-related anaphylactic episode while 8 (29%) denied such episodes. Equally important, of the 28 students, 6 (21%) received an autoinjectable epinephrine prescription, while 22 (79%) did not receive any. CONCLUSIONS: In this study the reported occurrence of perceived food allergy was low and probable food allergy occurred mostly in early childhood. Milk, egg, and nut allergies were the most commonly reported in both groups.
IgE-mediated food allergies in children: prevalence, triggers, and management
Food allergy (FA) is a serious health problem, and severe FA such as food-induced anaphylaxis can often be life threatening. The incidence of FA has been increasing especially in children. They usually develop early in life and affect up to 10% of children. The 2 most common food allergens worldwide are milk and eggs, while the third one varies depending on the countries: peanuts in the United States and Switzerland, wheat in Germany and Japan, tree nuts in Spain, sesame in Israel, and walnuts in Korea. These common food allergens are different and difficult to identify because of differing study methodologies, population, geography, age, and dietary exposure patterns. The current management of FA relies on the strict avoidance of culprit allergens, the prompt treatment of allergic reactions, including epinephrine use for food-induced anaphylaxis, monitoring, and education to prevent further reactions. Newer approaches for tolerance induction to FA and FA immunotherapy have been under investigation but are not yet ready for real-world application. Thus, consistent and systematic education of patients, caregivers, and food-handling people is of primary importance for the management and prevention of FA reactions. This review assesses and compares IgE-mediated FA in children in Korea and other countries, with a focus on summarizing the prevalence, common triggers, and management of FA.
Elimination diet and the development of multiple tree-nut allergies.
BACKGROUND: Despite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nuts allergies. METHODS: Patients (n=60, aged 4-15 years), recruited for a multiple food (tree-nuts, peanut, milk, egg, soy, sesame and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFC) to foods still eliminated. RESULTS: There was significantly less evidence for eliminating tree-nuts compared to other foods, as reflected by lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20-40% for other foods, respectively P<0.001), or later in life (14.5% vs. 38-75%, respectively P=0.001), and a higher rate of negative SPT/sIgE at initial diagnosis (25 vs. <10%, P<0.001). SPT/sIgE increased significantly from past initial levels to present for tree-nuts (P<0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive. CONCLUSIONS: Tree-nuts are often eliminated from the diet of multiple food-allergic patients, despite low probability for allergy. Sensitization and allergy to most tree-nuts exist years later suggesting it developed during the period of elimination.
A prospective microbiome‐wide association study of food sensitization and food allergy in early childhood.
BACKGROUND: Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. METHODS:
Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high dose Vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; p-values were adjusted for multiple comparisons. RESULTS: Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, p=0.003), Dialister (log2 fold change -2.22, p=0.009), Dorea (log2 fold change -1.65, p=0.02) and Clostridium (log2 fold change -1.47, p=0.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, p=0.03), Oscillospira (log2 fold change -2.80, p=0.03), Lactococcus (log2 fold change -3.19, p=0.05) and Dorea (log2 fold change -3.00, p=0.05) were underrepresented among subjects with food allergy. CONCLUSIONS: The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.
Peanut digestome: Identification of digestion resistant IgE binding peptides.
Stability to proteolytic degradation in the digestive tract is considered a general feature shared by most food allergens. Current digestibility models exclusively utilize purified allergen proteins, neglecting the relevant effects of matrix that occur for foodstuff systems. In the present study, we investigated digestion stability of the major peanut allergens directly in the natural matrix using an in vitro static model that simulates the gastrointestinal digestion including the oral, gastric, duodenal and intestinal (brush border membrane enzymes) phases. Immunogenicity was evaluated by Western Blot using N=8 pooled sera of peanut allergic pediatric subjects. Immunoreactive, large-sized and fragments of Ara h 2, Ara h 6 and Ara h 3 survived hydrolysis as assessed by SDS-PAGE. Smaller resistant peptides mainly arising from Ara h 3 and also Ara h 1 were detected and further identified by LC-high resolution-MS/MS. RP-HPLC purification followed by dot-blot analysis and MS/MS-based identification demonstrated that stable IgE-binding peptides derived from Ara h 3. These results provide a more realistic picture of the potentially allergenic determinants of peanuts that survived the human digestion, taking into account the role of the food matrix, which may significantly affect gastrointestinal breakdown of peanut allergens.
Indole-3-carbinol, a plant nutrient and AhR-Ligand precursor, supports oral tolerance against OVA and improves peanut allergy symptoms in mice.
In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
Quantitative Assessment of the Safety Benefits Associated with Increasing Clinical Peanut Thresholds Through Immunotherapy.
BACKGROUND: Peanut immunotherapy studies are conducted with the aim to decrease the sensitivity of patients to peanut exposure with the outcome evaluated by testing the threshold for allergic response in a double-blind placebo-controlled food challenge. The clinical relevance of increasing this threshold is not well characterized. OBJECTIVE: We aimed to quantify the clinical benefit of an increased threshold for peanut-allergic patients. METHODS: Quantitative risk assessment was performed by matching modeled exposure to peanut protein with individual threshold levels. Exposure was modeled by pairing US consumption data for various food product categories with potential contamination levels of peanut that have been demonstrated to be present on occasion in such food products. Cookies, ice cream, doughnuts/snack cakes, and snack chip mixes were considered in the risk assessment. RESULTS: Increasing the baseline threshold before immunotherapy from 100 mg or less peanut protein to 300 mg peanut protein postimmunotherapy reduces the risk of experiencing an allergic reaction by more than 95% for all 4 food product categories that may contain trace levels of peanut residue. Further increase in the threshold to 1000 mg of peanut protein had an additional quantitative benefit in risk reduction for all patients reacting to 300 mg or less at baseline. CONCLUSIONS: We conclude that achieving thresholds of 300 mg and 1000 mg of peanut protein by peanut immunotherapy is clinically relevant, and that the risk for peanut-allergic patients who have achieved this increased threshold to experience an allergic reaction is reduced in a clinically meaningful way.
A comparative study on basophil activation test, histamine release assay and passive sensitization histamine release assay in the diagnosis of peanut allergy.
BACKGROUND: Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR) and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. METHODS: BAT, HR, and passive HR were performed on eleven peanut allergic and fourteen non-allergic subjects. Blood was incubated with peanut extract or anti-IgE and tests performed as follows: BAT - CD63-upregulation assessed by flow cytometry; HR - released histamine quantified by a glass fiber-based fluorometric method; Passive HR - IgE-stripped donor basophils were incubated with participants' serum and histamine release quantified as HR. RESULTS: CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1 ± 17.4) compared to HR (23.4 ± 10.31) and passive HR (11.1 ± 2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82%, and specificity of 100%, 100%, and 100%, respectively when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10 and passive HR 9. Likewise, BAT recognized 12 of 14 non-allergic subjects, HR 10 and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, non-releasers in HR but not in BAT had lower basophil count compared to releasers (249 vs. 630 counts/min). CONCLUSION: BAT displayed a significant higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.