Allergenic food introduction and risk of childhood atopic diseases.
BACKGROUND: The role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. OBJECTIVE: To examine whether timing and diversity of allergenic food introduction are associated with allergic sensitization, allergy and eczema in children until age 10 years. MATERIALS AND METHODS: This study among 5,202 children was performed in a population-based prospective cohort. Timing (age ≤6 months vs. >6 months) and diversity (0, 1, 2 and ≥3 foods) of allergenic food (cow's milk, hen's egg, peanut, tree nuts, soy and gluten) introduction were assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by questionnaire. Data on parental-reported physician-diagnosed eczema were obtained from birth until age 10 years. RESULTS: Children introduced to gluten at age ≤6 months had a decreased risk of eczema (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at age >6 months. However, timing of allergenic food introduction was not associated with allergic sensitization or physician-diagnosed allergy. Children introduced to ≥3 allergenic foods at age ≤6 months had a decreased risk of physician-diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not introduced to any allergenic food at age ≤6 months. However, diversity of allergenic food introduction was not associated with allergic sensitization, physician-diagnosed food allergy or eczema. CONCLUSION: Neither timing nor diversity of allergenic food introduction was consistently associated with childhood allergic sensitization, allergy or eczema.
Influence of enzymatic hydrolysis on the allergenic reactivity of processed cashew and pistachio.
Cashew and pistachio allergies are considered a serious health problem. Previous studies have shown that thermal processing, pressurization and enzymatic hydrolysis may reduce the allergenic properties of food by changing the protein structure. This study assesses the allergenic properties of cashew and pistachio after thermal treatment (boiling and autoclaving), with or without pressure (autoclaving), and multiple enzymatic treatments under sonication, by SDS-PAGE, western blot and ELISA, with serum IgE of allergic individuals, and mass spectroscopy. Autoclaving and enzymatic hydrolysis under sonication separately induced a measurable reduction in the IgE binding properties of pastes made from treated cashew and pistachio nuts. These treatments were more effective with pistachio allergens. However, heat combined with enzymatic digestion was necessary to markedly lower IgE binding to cashew allergens. The findings identify highly effective simultaneous processing conditions to reduce or even abolish the allergenic potency of cashew and pistachio.
The allergen-specificity of early peanut consumption and the impact on the development of allergic disease in the LEAP Study Cohort.
BACKGROUND: Early introduction of dietary peanut in high-risk infants with severe eczema and/or egg allergy prevented peanut allergy at 5 years of age in the LEAP Study; the protective effect persisted after 12 months of avoiding peanuts in the LEAP-On Study. It is unclear whether this benefit is allergen and allergic-disease specific. OBJECTIVE: To assess the impact of early introduction of peanut on the development of allergic disease, food sensitization and aeroallergen sensitization. METHODS: Asthma, eczema and rhinoconjunctivitis were diagnosed by clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food and aeroallergens was determined by skin prick testing and specific IgE measurement. RESULTS: A high and increasing burden of food and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least one allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts; levels were higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants; this was not affected by peanut consumption. CONCLUSION: Early consumption of peanut in infants at high risk of peanut allergy is allergen-specific and does not prevent the development of other allergic disease, sensitization to other foods and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.
NUT Co Reactivity‐Acquiring Knowledge for Elimination Recommendations (NUT CRACKER) Study.
BACKGROUND: Ambiguities exist regarding the diagnosis of tree-nut allergy, necessitating either elimination or performance of oral food challenges (OFC). OBJECTIVE: To examine the co-incidences of allergies among tree-nuts and improve diagnostic testing to minimize the need for OFC. METHODS: Eighty three patients prospectively evaluated for walnut, pecan, cashew, pistachio, hazelnut and almond allergy. A history of previous reactions was obtained and standardized skin prick tests (SPT) using finely ground tree-nut solution and basophil activation tests (BAT) were performed. Patients underwent OFC for each tree-nut they eliminated and to which a reaction in the previous 2 years was not documented. RESULTS: While most patients were sensitized to 5-6 tree-nuts, over 50% were allergic to only 1-2 tree-nuts. The highest rate of allergy in sensitized patients was observed for walnut (74.6%) and cashew (65.6%). The rate of co-allergy for most tree-nuts was < 30%. Two thirds of walnut- and cashew-allergic patients were also allergic to pecan and pistachio, respectively, while all pecan- and pistachio-allergic patients were allergic to walnut and cashew, respectively. Receiver operating characteristic analysis for SPT and BAT was tree-nut dependent and yielded area under the curve (AUC) values ranging from 0.75-0.94. Knowledge of co-incident allergies in these pairs along with the combination of SPT and BAT correctly distinguished allergic from tolerant patients for walnut (87%), pecan (66%), cashew (71%) and pistachio (79%). CONCLUSION: The data presented here should assist in differentiating between allergic and tolerant patients, decrease the need for OFC and allow for appropriate elimination recommendations.
Liquid chromatography coupled to tandem mass spectrometry for detecting ten allergens in complex and incurred foodstuffs.
Food allergy is a considerable heath problem, as undesirable contaminations by allergens during food production are still widespread and may be dangerous for human health. To protect the population, laboratories need to develop reliable analytical methods in order to detect allergens in various food products. Currently, a large majority of allergen-related food recalls concern bakery products. It is therefore essential to detect allergens in unprocessed and processed foodstuffs. In this study, we developed a method for detecting ten allergens in complex (chocolate, ice cream) and processed (cookie, sauce) foodstuffs, based on ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Using a single protocol and considering a signal-to-noise ratio higher than 10 for the most abundant multiple reaction monitoring (MRM) transition, we were able to detect target allergens at 0.5mg/kg for milk proteins, 2.5mg/kg for peanut, hazelnut, pistachio, and cashew proteins, 3mg/kg for egg proteins, and 5mg/kg for soy, almond, walnut, and pecan proteins. The ability of the method to detect 10 allergens with a single protocol in complex and incurred food products makes it an attractive alternative to the ELISA method for routine laboratories.
Detection of the Peanut Allergens Ara h 2 and Ara h 6 in Human Breast Milk: Development of 2 Sensitive and Specific Sandwich ELISA Assays.
BACKGROUND: Little is known about breast milk as a vehicle for tolerance development or sensitization to peanuts very early in life. Thus, well-characterized and highly sensitive detection systems for the reliable determination of peanut allergens in breast milk are mandatory. METHODS: For the quantification of the marker allergens Ara h 2 and Ara h 6 in the low nanogram per milliliter range in breast milk samples of a German cohort, sensitive and highly specific sandwich ELISAs were optimized and validated. RESULTS: The Ara h 2 ELISA revealed a limit of detection (LOD) of 1.3 ng Ara h 2/mL and a quantification range of 2.3-250 ng/mL, the Ara h 6 ELISA showed an LOD of 0.7 ng/mL and a working range of 1.1-14.4 ng/mL. The assays showed no relevant cross-reactivity against other potentially cross-reactive legume, seed, and tree nut extracts (<0.01%, except for Ara h 1 in the Ara h 2 ELISA <0.1%). Ara h 2 was detectable in breast milk samples from 14/40 (35%) of the participants in concentrations from 2.3 to 184 ng/mL, Ara h 6 appeared in 9/40 (22.5%) of the lactating mothers between 1.1 and 9.7 ng/mL, and 1 highly positive sample with 79 ng/mL. Both allergens appeared at the same time points, but Ara h 6 in lower concentrations than Ara h 2. CONCLUSIONS: Sensitive and specific diagnostic tools for the determination of Ara h 2 and Ara h 6 in human breast milk were established. The kinetics of secreted Ara h 2 and Ara h 6 seem to be similar but with a difference in concentration. Follow-up investigations on their tolerogenic or sensitizing properties in breast milk become now accessible.
Age-Based Causes and Clinical Characteristics of Immediate-Type Food Allergy in Korean Children.
PURPOSE: Age-based causes and clinical characteristics of immediate-type food allergy (FA) have not been sufficiently studied. Therefore, we investigated age-dependent clinical profiles of FA in Korean children through an extensive multicenter investigation. METHODS: Using a case report form developed by the authors, a retrospective medical record review was performed of patients (0-18 years old) diagnosed with immediate-type FA between September 2014 and August 2015 in 14 tertiary hospitals in Korea. RESULTS: A total of 1,353 children and adolescents, 93% younger than 7 years, were enrolled in the present study, and 1,661 cases of immediate-type FA were recorded in these patients. The 7 major causative foods were cow's milk (28.1%), hen's eggs (27.6%), wheat (7.9%), walnuts (7.3%), peanuts (5.3%), buckwheat (1.9%), and shrimps (1.9%). Categorizing the patients into 4 age groups revealed that the most common causative food was different for each age group: cow's milk (<2 years), walnuts (2-6 years), walnuts (7-12 years), and buckwheat (13-18 years). The onset time of symptoms was less than 10 minutes in 49%, between 10 and 30 minutes in 17%, and between 30 minutes and 2 hours in 34% of cases. Food-induced anaphylaxis was reported in 506 (30.5%) out of 1,661 cases, and the 7 major causes of food-induced anaphylaxis was cow's milk (27.5%), hen's eggs (21.9%), wheat (11.3%), walnuts (10.5%), peanuts (5.9%), buckwheat (4.2%), and pine nuts (3.0%). The proportion of anaphylaxis was highest in the patients allergic to buckwheat (67.7%), followed by those allergic to pine nuts (57.7%), walnuts (43.8%), wheat (43.5%), and peanuts (34.1%). CONCLUSIONS: The 5 major causative foods of immediate-type FA in Korean children were cow's milk, hen's eggs, wheat, walnuts, and peanuts. The distribution of causative foods was considerably distinctive according to different age groups. Anaphylaxis was reported in 30.5% of immediate-type FA cases.
CRD and beyond: multivariable regression models to predict severity of hazelnut allergy.
BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n=423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during DBPCFC) were categorized in mild, moderate and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (OR) and areas under receiver operating characteristic (ROC) curves (AUC) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1 respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk), increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3% and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.
Effects of industrial cashew nut processing on anacardic acid content and allergen recognition by IgE.
Cashew nuts are important both nutritionally and industrially, but can also cause food allergies in some individuals. The present study aimed to assess the effect(s) of industrial processing on anacardic acids and allergens present in cashew nuts. Sample analyses were performed using liquid chromatography coupled with mass spectrometry, SDS-PAGE and immunoassay. The anacardic acid concentration ranged from 6.2 to 82.6mg/g during processing, and this variation was attributed to cashew nut shell liquid incorporation during storage and humidification. Dehydrated and selected samples did not significantly differ in anacardic acid content, having values similar to the raw sample. SDS-PAGE and immunoassay analysis with rabbit polyclonal sera and human IgE indicated only minor differences in protein solubility and antibody binding following processing steps. The findings indicate that appreciable amounts of anacardic acid remain in processed nuts, and that changes to cashew allergens during industrial processing may only mildly affect antibody recognition.
Small percentage of anaphylactic reactions treated with epinephrine during food challenges in Dutch children.
BACKGROUND: Severe allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine. OBJECTIVE: To evaluate the percentage of anaphylactic reactions treated with epinephrine during OFCs and to identify associated factors for the administration of epinephrine. METHODS: Children who underwent an OFC with peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in the Netherlands were evaluated. Children with reactions meeting the criteria for anaphylaxis according to the European Academy of Allergy and Clinical Immunology guidelines for food allergy and anaphylaxis were included. Children with an anaphylactic reaction treated with vs without epinephrine were compared. Possible factors associated with the administration of epinephrine, such as age, sex, symptoms consistent with asthma, history of an allergic reaction to the tested allergen, and symptom types during the anaphylactic reaction, were evaluated using logistic regression analysis. RESULTS: Eighty-three children in clinical and research settings (43% boys; median age, 7 years; range, 1-17) who met the criteria for anaphylaxis were included in this study. Thirty-two of 83 children (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during the OFC were treated significantly more often with epinephrine than gastrointestinal symptoms (P = .01). CONCLUSION: Only 39% of children with anaphylaxis, according to the guideline criteria, were treated with epinephrine during the OFC and most of these children had respiratory symptoms. There is need for an easy-to-use international guideline for the treatment of allergic symptoms during OFCs.