Impact of using less objective symptoms to define tolerated dose during food challenges: A data-driven approach.

BACKGROUND: Food challenges (FCs) form the basis for assessing efficacy outcomes in interventional studies of food allergy; however, different studies have used a variety of similar but not identical criteria to define a challenge reaction, including subjective (nonobjective) symptoms occurring in a single-organ system as dose limiting. OBJECTIVE: Our aim was to undertake a secondary analysis of 4 interventional studies to assess the impact of using less objective criteria to determine challenge-stop on reaction thresholds and their reproducibility. METHODS: We analyzed individual participant data, including individual participant data meta-analysis, by using 3 different published challenge-stop criteria: (1) PRACTALL consesus criteria; (2) Consortium for Food Allergy Research version 3 (CoFAR v3) with at least 1 moderate- or severe-grade symptom; or (3) CoFAR v3 with at least 2 mild symptoms occurring in different organ systems. Reproducibility of challenge threshold was also assessed in participants undergoing subsequent repeat FCs. RESULTS: Four studies, with detailed challenge data from a total of 592 participants, were included. Applying CoFAR v3 definitions for dose-limiting symptoms resulted in an underestimate of reaction thresholds compared with those in PRACTALL (P < .001) that is equivalent to almost a single dosing increment when using a semi-log dosing regimen. Reproducibility was also reduced when applying CoFAR v3 (P < .001 [n = 223]). Using the least conservative interpretation of CoFAR v3 (≥2 mild symptoms occurring in different systems) resulted in a significant overestimate of 15% when assessing oral immunotherapy efficacy. Applying a data-driven minor modification to CoFAR v3 resulted in a new set of challenge-stop criteria with validity similar to that of PRACTALL but one that is simpler to implement and in which significant gastrointestinal discomfort with observable decreased activity remains a dose-limiting symptom. CONCLUSION: The use of less objective symptoms to define challenge-stop compromises the reproducibility of the FC as a tool to assess efficacy outcomes in interventional studies, and potentially overestimates the efficacy of the intervention tested.

Sesame eliciting and safe doses in a large sesame allergic population.

BACKGROUND: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. METHODS: All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe-dose challenges with 90-120 min intervals were also analyzed. RESULTS: Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3-6.3) and 0.7 mg (range 0.1-7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2-20.6) and 4.5 mg (range 1.2-28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4-7.5 mg) and ED05 (3.4, 1.2-22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe-dose OFCs. CONCLUSIONS: This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Reproducibility of food challenge to cow's milk: Systematic review with individual participant data meta-analysis.

BACKGROUND: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds. OBJECTIVE: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges in CM to determine the rate of anaphylaxis to low-level exposures and the reproducibility of reaction thresholds. METHODS: We performed a systematic review and IPD meta-analysis of studies reporting relevant data. Authors were contacted to provide additional data and/or clarification as needed. Risk of bias was assessed using the National Institute for Clinical Excellence methodologic checklists. RESULTS: Thirty-four studies were included, representing data from over 1000 participants. The cumulative ED01 and ED05 (cumulative doses causing objective symptoms in 1% and 5% of the at-risk allergic population) were 0.3 (95% confidence interval [CI], 0.2-0.5) and 2.9 (95% CI, 1.6-5.4) mg, respectively. At meta-analysis, 4.8% (95% CI, 2.0-10.9) and 4.8% (95% CI, 0.7-27.1) of individuals reacting to ≤5 mg and ≤0.5 mg of CM protein had anaphylaxis (minimal heterogeneity, I2 = 0%). Then 110 individuals underwent repeat double-blind, placebo-controlled food challenges; the intraindividual variation in reaction threshold was limited to a ½-log change in 80% (95% CI, 65-89) of participants. Two individuals initially tolerated 5 mg CM protein but then reacted to this dose at a subsequent challenge, although neither had anaphylaxis. CONCLUSIONS: About 5% of CM-allergic individuals reacting to ED01 or ED05 exposure might have anaphylaxis to that dose. This equates to 5 and 24 anaphylaxis events per 10,000 patients exposed to an ED01 or ED05 dose, respectively, in the broader CM-allergic population. Most of these anaphylactic reactions would be mild and respond to a single dose of epinephrine.

Using data from food challenges to inform management of consumers with food allergy: A systematic review with individual participant data meta-analysis.

BACKGROUND: Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown. OBJECTIVE: Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge. METHODS: We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists. RESULTS: A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis. CONCLUSION: Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.

Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

BACKGROUND: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow's milk of 0.5 mg protein. METHODS: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity. RESULTS: 172 children (median age 6.0 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single-dose challenge using 0.5 mg cow's milk protein. CONCLUSIONS: These data support an estimated ED05 for cow's milk of 0.5 mg protein. Values for ED05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed.

Subjective oral symptoms are insufficient predictors of a positive oral food challenge.

BACKGROUND: Subjective oral symptoms, especially if recurrent, might lead to termination of an oral food challenge (OFC) for fear of a subsequent severe reaction. METHODS: In a single-center retrospective cohort study, oral food challenges to milk, egg, peanut, sesame, or tree nuts performed between January 2016 and January 2018 in patients aged ≥3 years, at the Institute of Allergy, Immunology and Pediatric Pulmonology in Shamir Medical Center, were analyzed. Subjective oral symptoms during the challenge were documented, and their association with the challenge outcome was examined. RESULTS: A total of 323 patients underwent 652 oral food challenges to the investigated foods (milk, 71; egg, 22; peanut, 48; sesame, 24; and tree nuts, 487). Subjective oral symptoms were experienced in 237 (36.3%) of all OFCs performed, and their rate was comparable across most foods tested. The rate of positive challenges was significantly higher when subjective oral symptoms were experienced during the challenge than when they were not (69.6% vs 30.4%, respectively, P < .001). However, the false-positive rate of such symptoms in predicting a positive food challenge was 30.3% for all foods; peanut, 40%; sesame, 27.3%; milk, 35.5%; egg, 33%; and tree nuts, 28.4%. Overall, subjective oral symptoms (SOS) provided sensitivity of 56.7, specificity 80.4, PPV 69.6, and NPV 69.0 for predicting OFC outcome. Importantly, reactions during positive challenges with and without subjective oral symptoms were comparable to severity. CONCLUSIONS: Continuing OFCs with subjective oral symptoms is recommended for it will prevent false-positive results in a third of cases without increasing patients' risk.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

BACKGROUND: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). OBJECTIVE: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 µg, subjects who had received DBV712 250 µg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. RESULTS: Of 213 eligible subjects who had received DBV712 250 µg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). CONCLUSIONS: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Can my child with IgE-mediated peanut allergy introduce foods labeled with "may contain traces"?

Peanut IgE-mediated food allergy is one of the most common food allergies in children with a prevalence that has increased in the past decades in Westernized countries. Peanut allergies can trigger severe reactions and usually persist over time. Peanut-allergic children and their families are often confronted to processed foods with precautionary allergen labeling (PAL) such as "may contain traces of peanuts," which are frequently used by the food industry. Patients are generally confused as to whether eating such foods entails a risk of allergic reaction, which can ultimately lead to dietary restrictions and decreased quality of life. Thus, guidance toward eviction of foods with PALs such as "may contain traces of peanuts" is a recurring problem that peanut-allergic patients address during pediatric allergy consultations with varying attitudes among allergists. Many studies have evaluated peanut contamination in foods with PALs, with generally less than 10% of foods containing detectable levels of peanuts, albeit heterogeneous amounts, with in rare occasions levels that could trigger allergic reactions in certain patients. The risk of reacting to foods with traces varies significantly with threshold, with patients with the lowest reaction thresholds at highest risk, and a dramatic reduction of risk as threshold increases. Thus, risk stratification based on individual reaction threshold may help stratify patients' risk of reacting to foods with PAL. In clinical practice, a single-dose 30 mg peanut protein oral food challenge may be an option to stratify peanut-allergic patients' risk when introducing foods with PAL, as illustrated by three clinical cases.

Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens.

BACKGROUND: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. OBJECTIVE: We sought to develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders but particularly patients with food allergy. METHODS: Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges. If double-blind, placebo-controlled food challenge data are not available, data from widely used open food challenges using predefined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research and the Food Allergy Research and Resource Program at the University of Nebraska-Lincoln have been collecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens. RESULTS: In this article we provide in-depth insights into the methodology applied by the Netherlands Organisation for Applied Scientific Research and Food Allergy Research and Resource Program to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. More than 90 examples for determining individual allergic thresholds are presented. CONCLUSION: With the methodology presented in this article, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption.

Gender, prick test size and rAra h 2 sIgE level may predict the eliciting dose in patients with peanut allergy: Evidence from the Mirabel survey.

BACKGROUND: Peanut allergy management is based on active avoidance and access to emergency treatment including self-injectable adrenaline. Knowing the dose at which a patient is likely to react is crucial for risk assessment and could significantly improve management by integrating a personalized approach. OBJECTIVE: To develop a threshold dose distribution curve model from routinely collected data. METHODS: The MIRABEL survey is an observational study of 785 patients with peanut allergy/sensitization conducted in France, Belgium and Luxemburg. The current analysis included the 238 participants for whom medical and oral food challenge data were available. Several statistical models (Kaplan-Meier, Cox model, Weibull and Lognormal with predictive factors, basic Weibull and Lognormal) were compared to select the best model and predictive factor combination associated with the threshold doses. Inferences were made with a Bayesian approach. RESULTS: Patients were mainly children (mean age: 9 years [IQR: 6-11]; 87% < 16 years) and males (62%). Median Ara h2 s IgE was of 8kUA/L [IQR: 1-55] and median skin prick test size of 10 mm [IQR: 7-13]. OFC was positive in 204 patients (86%). The median threshold dose was of 67 mg of peanut protein [IQR: 16-244]. The dose at which 1% of the patients are likely to react with objective symptoms was 0.26 [0.03; 2.24] mg of peanut protein. Gender, size of the skin prick test (SPT) and Ara h 2 specific IgE level had a significant impact on the threshold dose distribution curve. The Cox model was the most effective to predict threshold doses with this combination of factors. Girls react to lower doses than boys with a beta coefficient associated to the risk and a 95% credible interval of 0.44 [0.04; 0.77]. The higher the size of the SPT and the Ara h 2 specific IgE level are, the higher the risk of reacting to a small amount of peanut, with beta coefficients associated to the risk and 95% credible intervals of 0.05 [0.02; 0.08] and 0.01 [0.01; 0.02], respectively. CONCLUSION AND CLINICAL RELEVANCE: According to the model, routinely collected data could be used to estimate the threshold dose. The consequences could be the identification of high-risk patients who are susceptible to react to small amounts of peanut and a personalized management of peanut allergy integrating the risk of allergic reaction. Limitations of this study are that assessors of OFC outcome were aware of SPT and Arah2 results, and a further validation study is required to confirm the predictive value of these parameters.

How does dose impact on the severity of food-induced allergic reactions, and can this improve risk assessment for allergenic foods?: Report from an ILSI Europe Food Allergy Task Force Expert Group and Workshop.

Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single-dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.

NUT Co Reactivity - ACquiring Knowledge for Elimination Recommendations (NUT CRACKER) study.

BACKGROUND: Ambiguities exist regarding the diagnosis of tree-nut allergy, necessitating either their elimination or the performance of oral food challenges (OFCs). OBJECTIVE: To examine the coincidences 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 (SPTs) 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 to 0.94. Knowledge of coincident 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.

Prediction of the severity of allergic reactions to foods.

BACKGROUND: There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. OBJECTIVE: To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. METHODS: The study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. RESULTS: A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P < .001), eliciting dose (B = -0.09, P < .001), level of specific immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = -0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P < .001), history of atopic dermatitis (B = -0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003). CONCLUSIONS: The severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.

Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy.

BACKGROUND: Eliciting doses (EDs) of allergenic foods can be defined by the distribution of threshold doses for subjects within a specific population. The ED05 is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED05 for peanut is 1.5 mg of peanut protein (6 mg of whole peanut). OBJECTIVE: We sought to validate the predicted peanut ED05 (1.5 mg) with a novel single-dose challenge. METHODS: Consecutive eligible children with peanut allergy in 3 centers were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used to identify ED05 single-dose reactors. RESULTS: Five hundred eighteen children (mean age, 6.8 years) were eligible. No significant demographic or clinical differences were identified between 381 (74%) participants and 137 (26%) nonparticipants or between subjects recruited at each center. Three hundred seventy-eight children (206 male) completed the study. Almost half the group reported ignoring precautionary allergen labeling. Two hundred forty-five (65%) children experienced no reaction to the single dose of peanut. Sixty-seven (18%) children reported a subjective reaction without objective findings. Fifty-eight (15%) children experienced signs of a mild and transient nature that did not meet the predetermined criteria. Only 8 (2.1%; 95% CI, 0.6%-3.4%) subjects met the predetermined criteria for an objective and likely related event. No child experienced more than a mild reaction, 4 of the 8 received oral antihistamines only, and none received epinephrine. Food allergy-related quality of life improved from baseline to 1 month after challenge regardless of outcome (η2 = 0.2, P < .0001). Peanut skin prick test responses and peanut- and Ara h 2-specific IgE levels were not associated with objective reactivity to peanut ED05. CONCLUSION: A single administration of 1.5 mg of peanut protein elicited objective reactions in fewer than the predicted 5% of patients with peanut allergy. The novel single-dose oral food challenge appears clinically safe and patient acceptable, regardless of the outcome. It identifies the most highly dose-sensitive population with food allergy not otherwise identifiable by using routinely available peanut skin prick test responses or specific IgE levels, but this single-dose approach has not yet been validated for risk assessment of individual patients.

Minimal impact of extensive heating of hen's egg and cow's milk in a food matrix on threshold dose-distribution curves.

We analyzed reaction threshold data from 352 children undergoing open food challenges to hen's egg or cow's milk, either fresh or extensively heated into a muffin. There was no significant shift in dose-distribution curves due to the baking process, implying that existing threshold data for these allergens can be applied to allergen risk management, even when these allergens are heat-processed into baked foods.