Oral Food Challenge Research Articles

Cashew and Shrimp Oral Immunotherapy-Induced Changes in Allergen-Reactive CD4+ T Cells

A better understanding of immune underpinnings of food allergy and interventional desensitization is imperative to design effective oral immunotherapy (OIT) protocols for varied food allergens. To this end, we probed immune changes in participants of our open label cashew and shrimp OIT trial- MOTIF (NCT03504774). In this study, the participants were treated with increasing dose of cognate allergen for 52 weeks followed by 6 weeks of avoidance. Participants successfully desensitized post-OIT were classified into two groups, namely SU4043 (n=23) and SU2043 (n=5) based on the cumulative tolerated allergen protein dose of 4043 mg and 2043 mg respectively during the post-avoidance (i.e., week 58) oral food challenge.

Baked Egg Oral Food Challenges: Modifying Decision Points for Success

Including baked egg into the diet for children with egg allergy has nutritional and quality of life benefits. Current data on recommended IgE decision points for baked egg challenges are variable. We investigated whether specific egg white IgE and age are associated with passing a baked egg food challenge and if our institutional decision point of 10-15 kU/L should be modified.

Single Center Oral Food Challenges: A Five Year Retrospective Review

Single Center Oral Food Challenges: A Five Year Retrospective Review

Systemic Reactions in Infants and Toddlers: A Prospective Study of Oral Food Challenge Outcomes

Systemic Reactions in Infants and Toddlers: A Prospective Study of Oral Food Challenge Outcomes

Fatal and near-fatal anaphylaxis: The Allergy-Vigilance® Network data (2002-2020).

Having a better understanding of the risk factors of severe anaphylaxis is a crucial challenge for physicians. To retrospectively analyse fatal/near-fatal anaphylaxis cases recorded by the Allergy-Vigilance® Network (2002-2020) and evaluate the characteristics associated with survival, age and allergens. Among the 3510 anaphylaxis cases documented in the network, 70 (2%) patients (males: 57%; mean age: 35.4y) presented grade 4 (Ring-Messmer) anaphylaxis and 25 died (19 food-related); 33% had a history of asthma. The main allergens were food (60%; peanut, 20%; milks, 11%) involved in 25/26 cases in children and in 17/44 (39%) cases in adults. Non-food anaphylaxis was related to drugs/latex (24%; neuromuscular blocking agents, 10%; betalactamins, 6%), Hymenoptera (16%). Three food-related cases (one death) occurred during oral food challenge in children. Patients with a food allergy were younger (22.2 years vs. 55 years, p < .001), had more likely a history of asthma (50% vs. 7%; p < .001), a pre-existing allergy (62% vs. 18%; p < .001) compared with other allergies. A cofactor was identified in 35 cases (50%) but predominantly in adults as opposed to children (64% vs. 27%; p=.01). The patients who died were younger (25.6 vs. 40.8 years; p=.01) than the survivors and mostly presented bronchospasm (56% vs. 29%; p=.05). Gaps in the prevention and management of anaphylaxis were noted in 15 cases (21%). Severe food anaphylaxis has specific features compared with other causes such as young age, asthma history and exercise. Food is also involved in severe anaphylaxis in adults that should not be underestimated.

Molecular allergy diagnostics in predicting oral cow's milk challenge outcome in Finnish children.

Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy. A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergyunderwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4),beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes. Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alphalactalbumin, and BSA than did children with mild reactions. Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.

Cow’s milk allergy skin tests: fresh milk, commercial extracts, or both?

BackgroundThe diagnosis of food allergy is based on a history of immediate allergic reaction following food ingestion, and skin prick test (SPT) demonstrating sensitization with commercial extracts (CE) or fresh food (FF). For most food allergens, the SPT with FF is considered more accurate and predictive. Regarding cow’s milk, the results are inconclusive. This retrospective study aimed to evaluate the accuracy of SPT with fresh milk compared to CE (cow’s milk and casein) for evaluation of cow’s milk allergy (CMA).MethodsThis study summarized the medical records of children, diagnosed with CMA. The data include demographics, skin tests and oral food challenge results, as well as atopic comorbidities.ResultsRecords of 698 patients with the diagnosis of CMA were reviewed, 388 fulfilled the inclusion criteria. Overall, 134 patients (34.54%) had an additional atopic disease. The SPT wheal size with fresh milk was significantly larger than with CE (cow's milk and casein) at first evaluation or before oral food challenge (OFC). Combination of SPT results (CE and FF) gave the maximal odds ratio for reaction during OFC and SPT with fresh milk alone gave the minimal OR (34.18 and 4.74, respectively).ConclusionsSPT with CE for CMA evaluation is more reliable than SPT performed with fresh milk. In patients suspected of having IgE-mediated CMA, before deciding on performing OFC, it is advised to perform SPT with at least two different extracts, and always include casein. Fresh milk can serve as a backup if commercial extracts are not available. In cases that the SPT with fresh milk is 3 mm or less, there is 93.3% chance that the OFC will pass without reaction.Trial registration This study protocol was reviewed and approved by the Ethics Committee of Meir Medical Center, IRB Number 0083-18 MMC.

Geographical discrepancy in oral food challenge utilization based on Canadian billing data

BackgroundOral food challenges (OFC) confer the highest sensitivity and specificity in diagnosis; however, uptake has been variable across clinical settings. Numerous barriers were identified in literature from inadequate training to resource access. OFC utilization patterns using billing data have not been previously studied.ObjectiveThe objective of this study is to explore the geographic differences in utilization of OFCs across Ontario and Québec using anonymized billing data from 2013 to 2017.MethodsAnonymized OFC billing data were obtained between 2013 and 2017 from Ontario Health Insurance Plan (OHIP) and Régie de l'Assurance Maladie du Québec (RAMQ). The number of OFCs was extracted by location, billings, and physician demographics for clinic and hospital-based challenges.ResultsOver the period studied, the number of OFCs increased by 92% and 85% in Ontario clinics and Québec hospitals, respectively. For Ontario hospitals, the number of OFCs increased by 194%. While Québec performed exclusively hospital-based OFCs, after controlling for the population, the number of OFCs per 100,000 residents annually were similar to Ontario at 50 and 49 OFCs, respectively. The number of OFCs varied across the regions studied with an annual rate reaching up to 156 OFCs per 100,000 residents in urban regions and as low as 0.1 in regions furthest from city centers.ConclusionOFC utilization has steadily increased over the last decade. There has been marked geographical discrepancies in OFC utilization which could be driven by the location of allergists and heterogeneity in their practices. More research is needed to identify barriers and propose solutions to them.

ANTIGENICITY OF SOY PROTEIN IN SOY-BASED INFANT FORMULA BONLACT® i

The purpose of this study was to compare the antigenicity of Bonlact® i (BL) with that of defatted soy protein (SP) and soy protein isolate (SPI), which is the original source of BL, using sera from patients with soybean allergy. Proteins were extracted from SP, SPI, and BL using PBS. Proteins in each sample were analyzed for antigenicity using inhibition ELISA with SP-specific IgE (sIgE), SDS-PAGE, and immunoblotting. Sere from patients with soybean allergy confirmed by an oral food challenge (OFC) (n=6, OFC+ Pt), and from patients who were positive for soy-sIgE without symptoms ( n = 7, sIgE+ Pt) were used for these assays. The cross-antigenicity of SP and BL with cow's milk (CM) proteins was also analyzed in the sera from patients with CM allergy using inhibition ELISA. SDS-PAGE showed that the proteins in BL produced a smear-like band in the low-molecular-weight region compared with that in SP and SPI. Inhibition ELISA against SP-sIgE showed that BL had a significantly lower inhibition rate than that of SP in both OFC+ Pt and sIgE+ Pt. Immunoblotting analysis showed that the bands of BL were thinner than those of SP and SPI. Additionally, SP and BL showed no cross-antigenicity with CM proteins. The proteins in BL was partially digested, and its antigenicity was lower than that of SP and SPI.

A potential role of gliadin extract skin prick test in IgE-mediated wheat allergy.

Wheat extracts containing both water/salt and alcohol soluble proteins may increase extract's accuracy for diagnosing IgE-mediated wheat allergy. This study aimed to determine the performance of new invented in-house prepared wheat extracts for skin prick test (SPT). Children aged 1-18 years with history of immediate wheat allergy were recruited. Four in-house prepared wheat extracts (wheat-Coca-10%EtOH, and 3 new invented extracts, wheat-salt, gliadin, and glutenin) and a commercial wheat extract were used for SPT. Serum specific IgE (sIgE) to wheat and omega-5 (ω-5) gliadin were also determined. Oral food challenge (OFC) with wheat flours was performed in all patients except those with history of wheat-induced anaphylaxis or with recent symptoms within the past 6 months. Thirty-one children were recruited. Of those, 14 were excluded from OFC (12 with history of anaphylaxis and 2 with recent symptom). OFC was positive in 8 of 17 children. Of the 5 extracts and sIgE to wheat and ω-5 gliadin, gliadin extract provided the best SPT performance with 84.2% sensitivity, 88.9% specificity, 94.1% positive predictive value (PPV), 72.7% negative predictive value (NPV), 7.59 positive likelihood ratio (LR), 0.18 negative LR, and 85.7% accuracy. Compared to other in-house and commercial wheat extracts and sIgE to wheat and ω-5 gliadin, SPT with an in-house gliadin extract yielded the highest performance for the diagnosis IgE-mediated wheat allergy.

Food Protein-induced Enterocolitis Syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food allergy. FPIES is characterized by repetitive vomiting without classic IgE-mediated allergic skin or respiratory symptoms 1-4 h after causative food ingestion. The condition may be classified as acute or chronic, typical or atypical, and liquid or solid according to the course of symptoms, presence of IgE antibodies, and causative food, respectively. Since the development of international consensus guidelines in 2017, epidemiological studies have been conducted in many countries. FPIES is a relatively rare disease, with a prevalence of 0.015%-0.7%. However, the number of patients has been increasing in recent years. Most patients develop the disease in infancy. The natural history of FPIES is generally favorable, with most FPIES cases resolving before school age. FPIES is diagnosed using symptoms such as vomiting or diarrhea, or via an oral food challenge (OFC). Currently, no validated biomarker is available for diagnosis, and the mechanisms related to gastrointestinal manifestations and immune system involved in the development of FPIES have not yet been elucidated. Treatment with intravenous fluids and ondansetron is recommended in the acute phase. Long-term management consists of complete causative food elimination and periodic OFC to confirm tolerance. Given that many diagnoses are delayed because of a lack of awareness of the condition, FPIES must be widely recognized by healthcare providers. In the future, it is expected that FPIES pathogenesis will be further clarified, and more objective diagnostic criteria will be developed.

Efficacy and safety of low- and high-dose slow oral egg immunotherapy for hen's egg allergy: Single-center non-inferiority randomized trial.

Low-dose oral immunotherapy (OIT) is a safe treatment for hen's egg allergy; however, comparison of its therapeutic effects with those of high-dose OIT has not been reported. To compare the efficacy of low- and high-dose boiled egg-white (EW) OIT for hen's egg allergy. Patients with hen's egg allergy were randomly assigned to two groups: OIT using hard-boiled EW with a maximum maintenance dose of 2 and 20 g in the low-dose (L-D) and high-dose (H-D) groups, respectively. The intake dose was ingested twice a week, increased by approximately 20% per week until reaching the target maintenance dose (2 or 20 g hard-boiled EW), and maintained thereafter according to the schedule. The threshold was confirmed via oral food challenge (OFC) after 6 months, and the difference in the proportion of subjects passing the exit OFC between groups was evaluated. Fifty-two patients (L-D, n = 23; H-D, n = 29) were enrolled. Thirty-three patients (L-D, n = 17; H-D, n = 16) completed the 6-month OIT and underwent an exit OFC. In total, three (L-D, 3/17; H-D, 3/16) patients in each group tested negative for an exit OFC with a 20-g reactive dose (p = 1.000). EW-specific IgE levels in both groups decreased significantly after OIT (L-D, p < 0.001; H-D, p = 0.002). A threshold-elevating effect was observed in the L-D group, not inferior to that in the H-D group. Low-dose OIT may be appropriate to treat hen's egg allergy for the first 6 months.

Awareness or neglecting the diagnosis of cow milk protein allergy in the neonatal period.

Cow milk protein allergy (CMPA) can mimic surgical disease, gastroenteritis, sepsis, and necrotizing enterocolitis in the neonatal period. For this reason, we aimed to evaluate the clinical features, differential diagnosis, and treatment methods of neonates with CMPA. The charts of twenty-six breastfed full-term and preterm newborns presenting with CMPA between October 2018 and February 2021 were retrospectively reviewed. The clinical symptoms, laboratory findings, and methods used in diagnosis and treatment were analyzed. CMPA was diagnosed in preterm infants 50% (n=13) at the same rate as in full-term infants 50% (n=13) between 32 to 38 weeks corrected age (median 36 weeks). Among patients with CMPA, 69.2% (n=18) had blood in the stool at the onset. Cow's Milk-related Symptom Score score was found to be significantly higher prior to diagnosis vs. after treatment with the cow milk protein-free mom's milk diet [12(11-13) vs. 4(3-5), p<0.001]. Seventy-two hours after the commencement of the mothers' elimination diet, macroscopic blood in stool disappeared in all patients except one patient. Oral food challenge (OFC) for the diagnosis of CMPA was carried out on all (n=26) neonates. Eosinophilia was seen in 46.2% of patients (n=12). The methemoglobin concentration was 1.1 to 1.5% (median 1.3%). CMPA should be kept in mind for well-appearing preterm and full-term infants suspected of necrotizing enterocolitis and gastroenteritis, respectively, presenting with bloody stool and eosinophilia. The use of OFC can be implemented since neonates were very well monitored in the neonatal intensive care unit. Treatment is possible by continuing breastfeeding.

Oral food challenge: a Brazilian panorama

Oral food challenge: a Brazilian panorama

Food Sensitivity in Children Diagnosed with Atopic Dermatitis in The First 2 Years: How Many of These Patients Are Truly Allergic?

In this study, it was aimed to examine food sensitivity in patients with atopic dermatitis (AD) and to investigate the frequency of food allergy in patients with food sensitivity. Patients aged 0-2 years who were followed up with the diagnosis of AD were included in the study. The characteristics of demographic and clinical and laboratory findings of the patients were recorded retrospectively. Patients were classified as mild, moderate, and severe using the SCORing AD index according to the severity of AD. The presence of food sensitivity was evaluated by skin prick test and serum-specific immunoglobulin (Ig)E results. Food allergy was diagnosed by oral food challenge (OFC) test. Of the 72 patients included in the study, 62.5% (n=45) were male, and the mean age was 9±4.8 months. When the disease severity was evaluated, it was mild in 40 patients (55.6%); moderate/severe AD was present in 32 patients (44.4%). The frequency of moderate/severe AD was higher in patients who were younger (p=0.01), whose symptoms started in the first 6 months (p=0.03), who had a family history of allergic disease (p=0.001), who breastfed for <6 months (p=0.01), who had a higher median serum total IgE level, and a higher percentage of serum eosinophils (p=0.005 and p=0.01, respectively). Food sensitivity in 45.8% of patients; food allergy was detected in 41.7% of them. The most common sensitivities and allergies were eggs white/yolk and cow's milk, respectively. The rate of food sensitivity was found to be higher in male gender (p=0.03) and breastfed patients (p=0.03), whereas it was similar in patients with mild and moderate/severe AD. In the investigation of food sensitivity in patients with AD, it is important to evaluate other demographic and clinical characteristics such as gender and breastfeeding, apart from the severity of disease. The OFC test should be performed to confirm the food allergy in patients with food sensitivity before the recommendation of an elimination diet.

Oral mite anaphylaxis (pancake syndrome) caused by storage mite Acarus siro and its treatment with allergen immunotherapy

A 10-year-old atopic patient with asthma, peanut, and house dust mite allergy developed frequent episodes with symptoms including abdominal pain, nausea, vomiting, dizziness, drop of blood pressure, and occasionally shortness of breath and wheezing. After detailed diagnostics including an ISAC test and several other specific IgE blood tests, which could not explain the symptoms, the patient tested positive for specific IgE to Acarus siro (flour mites) (9.2 kU/L). As no oral food challenge with Acarus siro was available, the patient's family implemented avoidance measures by storing food containing flour in the refrigerator, and the patient started subcutaneous immunotherapy (SCIT) with Depigoid Acarus siro. The implementation of avoidance measures led to an immediate improvement of symptoms, and after 3 years of treatment, products containing flour, stored at room temperature, are tolerated again.

Children with wheat anaphylaxis and with low wheat specific IgE have a different IgE immunoblot pattern than those with high wheat specific IgE.

Children with wheat anaphylaxis can present with a wide range of wheat-specific IgE (sIgE). To identify differences in clinical features and predominant wheat allergens sensitized by these patients. Children with history of wheat anaphylaxis were recruited. Skin prick test (SPT) to wheat, sIgE to wheat, omega-5 gliadin (ω5G), lipid transfer protein (LTP) were investigated. Profiles of IgE-bound wheat allergens were studied to identify predominant wheat allergens. Twenty-nine children (17 males) aged 1-18 years were enrolled. Sixteen patients (55.2%) had wheat-sIgE > 100 kUA/L (WAhi) and 13 patients (44.8%) had wheat-sIgE < 34 kUA/L (WAlo). The median of peak wheat-sIgE in WAhi and WAlo were 340.5 kUA/L (IQR 184.3, 564.5) and 12.2 kUA/L (IQR 1.4, 41.3), respectively. Oral food challenge test (OFC) was carried out in 12 of 13 patients in the WAlo group, all of which had positive results. Eight of these 12 patients developed anaphylaxis during OFC despite having wheat-sIgE less than 10 kUA/L. There were no differences in clinical characteristics and atopic history between WAhi vs. WAlo. Medium to low molecular weight gliadin (< 40 kDa) and glutenin (< 60 kDa) were commonly recognized by patients with WAhi. IgE immunoblot pattern among the WAlo group was more widely dispersed than those with WAhi. Wheat anaphylaxis can occur in patients with low wheat-sIgE. Predominant wheat allergens recognized by patients with WAlo were different than those with WAhi. Such difference could be responsible for anaphylaxis at even low levels of wheat-sIgE.

Phenotypes of persistent hen`s egg allergy in children and adolescents.

Optimum management of food allergy (FA) includes consideration of co-allergies and multimorbidities and tolerance assessment. Documentation of FA practices may pave the way for better practice. Patients aged 3-18 years, with persistent IgE-mediated hen`s egg allergy were reviewed. A total of 102 children with a median age of 59 months (IQR= 40-84) (72.2% males) were included. All were diagnosed during infancy and the initial symptoms were atopic dermatitis (65.6%), urticaria (18.6%), and anaphylaxis (5.9%). Of the total population, 21 (20.6%) experienced anaphylaxis with hen`s eggs, and 79.4%, 89.2%, and 30.4% had multiple FAs (≥2 food categories), ever atopic dermatitis, and asthma, respectively. The most common co-allergies were tree nuts, cow`s milk, and seeds, respectively. From 52 heated egg yolk and 47 baked egg oral food challenges, 48 (92.3%) and 41 (87.2%) were found as tolerant, respectively. The baked egg nontolerant group had a greater egg white skin prick test diameter [9 mm (IQR: 6-11.5) vs. 6 mm (IQR: 4.5-9); (p=0.009)] and specific IgE [12.6 kU/L (IQR: 4.11-45.4) vs. 6.2 kU/L (IQR: 1.9-12.4) (p=0.009)], respectively. In the multivariate analysis, baked egg tolerance was more likely in those with egg yolk-tolerant subgroup (OR: 6.480, 95% CI: 2.524-16.638; p < 0.001) and heated egg tolerance in those with baked egg tolerance (OR: 6.943, 95% CI: 1.554-31.017; p=0.011). Persistent hen`s egg allergy is characterized by multiple food allergies and age-related multimorbidities. Baked egg and heated egg yolk tolerance were more likely to be considered in a subgroup with a high expectation for finding a way to eliminate their allergy.

Синдром острого энтероколита, индуцированного пищевыми белками (FPIES), как проявление множественной пищевой аллергии

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifested by delayed onset of gastrointestinal symptoms (1–4 hours after allergen consumption), which can lead to severe life-threatening conditions. The absence of specific laboratory markers of FPIES allowing to determine the trigger and confirm the diagnosis, unclear clinical features often masked by acute intestinal infections and other gastrointestinal diseases create significant difficulties in identifying patients with FPIES, choosing the right tactics for their management, and prescribing an adequate elimination diet. This article presents a clinical case of a patient who had multiple episodes of severe clinical manifestations of FPIES since the age of 6 months, requiring emergency hospitalization. The diagnosis of FPIES was first suspected at the age of 1.5 years; subsequently, the diagnosis was clinically confirmed, and a plan for further management of the child was developed. Key words: food protein-induced enterocolitis syndrome (FPIES), children, diagnosis, food allergy, trigger, oral food challenge test, cow’s milk protein allergy, meat allergy

Comparison of perennial and preseasonal allergoid immunotherapy in grass pollen allergic patients.

Few studies have examined the effect of atopic dermatitis (AD) on the resolution of food allergies in Asia, and the predictors of egg allergy resolution are not yet well defined. We evaluated whether AD severity could predict the resolution of egg allergy. This retrospective cohort study included infants under 24 months of age diagnosed with IgE-mediated egg white allergy. We included subjects who completed a 60-month follow-up. Open oral food challenges (OFCs) and serologic tests were performed at the time of initial diagnosis and at 36 ± 3 and 60 ± 3 months. We analyzed 68 patients (39 boys and 29 girls). OFCs were performed in 88.2% of the patients. The egg allergy remission rates were 23.5% and 47.1% by 3 and by 5 years of age, respectively. Persistent egg allergy was significantly associated with moderate to severe AD and house dust mite sensitization. Kaplan-Meier curve analysis revealed that patients with moderate to severe AD had higher persistent egg allergy rates than patients with no and mild AD (p = 0.012). Multivariable analysis identified moderate to severe AD as strongly associated with persistent egg allergy (p = 0.001). In this study, 47.1% of infants had resolved egg white allergies at 60 months. Moderate to severe AD may be a practical and important prognostic factor for persistent egg allergy in clinical settings.