Development of a tool predicting severity of allergic reaction during peanut challenge

Chinthrajah, R. Sharon; Purington, Natasha; Andorf, Sandra; Rosa, Jaime S.; Mukai, Kaori; Hamilton, Robert G.; Smith, Bridget; Gupta, Ruchi S.; Galli, Stephen J.; Desai, Manisha

doi:10.1016/j.anai.2018.04.020

Cited by 61 publications

(57 citation statements)

References 49 publications

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“…The severity of the reacting symptom is also of concern when conducting a food challenge. Similar to what we and others have shown, a concomitant history of asthma increases the risk of having a severe reaction ( 29 , 30 ). Not surprisingly, elevated specific IgEs and specific to total IgE ratios were associated with more severe symptoms.…”

Section: Discussionsupporting

confidence: 89%

“…The challenge of such subjects therefore was initiated at a lower dose (of 1 mg) due to safety concerns. Few studies have evaluated prognostic indicators for predicting OFC outcomes ( 29 ) and this is an area of ongoing research. In this study we attempted to identify potential prognostic indicators that may be associated with outcomes during OFC to a variety of foods, which could aid in risk stratification for allergists who may be considering a challenge.…”

Section: Discussionmentioning

confidence: 99%

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Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges

et al. 2018

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Background: Food allergy prevalence has continued to rise over the past decade. While studies have reported threshold doses for multiple foods, large-scale multi-food allergen studies are lacking. Our goal was to identify threshold dose distributions and predictors of severe reactions during blinded oral food challenges (OFCs) in multi-food allergic patients.Methods: A retrospective chart review was performed on all Stanford-initiated clinical protocols involving standardized screening OFCs to any of 11 food allergens at 7 sites. Interval-censoring survival analysis was used to calculate eliciting dose (ED) curves for each food. Changes in severity and ED were also analyzed among participants who had repeated challenges to the same food.Results: Of 428 participants, 410 (96%) had at least one positive challenge (1445 standardized OFCs with 1054 total positive challenges). Participants undergoing peanut challenges had the highest ED50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07 or 1.7 mg, respectively). The most common adverse event was skin related (54%), followed by gastrointestinal (GI) events (33%). A history of asthma was associated with a significantly higher risk of a severe reaction (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen-specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59], respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut challenges had more severe reactions as ED increased. In participants who underwent repeat challenges, the ED did not change (p = 0.66), but reactions were more severe (p = 0.02).Conclusions: Participants with a history of asthma, high sIgEr, and/or high values of sIgE were found to be at higher risk for severe reactions during food challenges. These findings may help to optimize food challenge dosing schemes in multi-food allergic, atopic patients, specifically at lower doses where the majority of reactions occur.Trials Registration Number: ClinicalTrials. gov number NCT03539692; https://clinicaltrials.gov/ct2/show/NCT03539692.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges

et al. 2018

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“…It can also relate to the severity of allergic reactions in that patients with more severe reactions show a greater proportion of activated basophils and patients reacting to trace amounts of the allergen show a greater basophil sensitivity, i.e. their basophils start reacting at lower allergen concentrations [ 51 , 52 , 53 ].…”

Section: Clinical Applications Of the Basophil Activation Testmentioning

confidence: 99%

Basophil Activation Test: Old and New Applications in Allergy

Hemmings

Kwok

McKendry

et al. 2018

Curr Allergy Asthma Rep

146

139

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Purpose of ReviewThe basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator release, and can be used for clinical applications as well as to explore the immune mechanisms of effector cell response to allergen. This review discusses the advancements made in clinical, diagnostic and laboratory research of allergy utilizing an ever-evolving BAT.Recent FindingsBeing an in vitro surrogate of the allergic reaction that happens in vivo in the sick patient, the BAT can be used to support the diagnosis of various allergic conditions, such as food, drug, respiratory and insect venom allergies, and the assessment of clinical response to allergen-specific immunotherapy and other immunomodulatory treatments. The BAT can also be used for research purposes to explore the mechanisms of allergy and tolerance at the level of the basophil, for instance by manipulating IgE and IgG and their receptors and by studying intracellular signalling cascade in response to allergen.SummaryThis review covers the applications of the BAT to the clinical management of allergic patients and the increased understanding of the mechanisms of immune response to allergens as well as technological advancements made in recent years.

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“…Gupta et al indicate that the sIgE/total IgE ratio is more accurate than sIgE alone in predicting outcomes of challenges performed to confirm PN tolerance . Another ratio which may be used to predict severity of reaction during peanut OFC is the BAT CD63 ratio (ratio of peanut‐stimulated basophils to anti‐IgE‐stimulated basophils), together with the history of exercise‐induced asthma, and FEV1/FVC ratio at the time of DBPCFC …”

Section: Oral Food Challengementioning

confidence: 99%

Peanut allergy diagnosis: Moving from basic to more elegant testing

Krogulska

Wood

2020

Pediatric Allergy Immunology

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Peanut allergy (PNA) is an IgE-mediated immune disorder, which merits particular attention due to its impact on the health and quality of life of millions of patients worldwide.Peanut allergy is particularly widespread in the younger population and affects almost ¼ of children with food allergy (FA). 1 Although PNA tends to develop in early life, it resolves in only 20% of children. 2 The overall prevalence of PNA is estimated as 0.4% in Europe and 0.6% in the United States. 3,4 The frequency of PNA by self-report is higher in the United States (1.2% to 8% of children) 5,6 than in Europe (from 0.5% to 2.5%). 3,7 Studies based on oral food challenge (OFC) have estimated the prevalence of PNA in Europe as 0.2%-1. 6%, 8,9 in Australia to be 3% at 12 months of age and 1.9% at 4 years. 10 On the basis of stringent criteria (peanut IgE > 14 kUA/L and prescribed epinephrine autoinjector), its prevalence among US school children was found to be 2%. 11Overall, the prevalence of PNA appears to be increasing, especially in developed countries. A large telephone-based survey found rates of PNA in US children rising from 0.6% in 1997 to 1.2% in 2002 and 2.1% in 2007. 2,5,6 Similar trends have been reported from the UK 8 ; however, studies from Canada 12 and a newer one from the UK suggest the prevalence has stabilized. 13 Peanut allergy also represents the most common cause of anaphylactic reactions in children, with its incidence increasing between five and sevenfold over the past 10 years. 14,15 It accounts for the majority of severe food-related allergic reactions and has the highest lifetime risk for both anaphylaxis and anaphylaxis mortalities. 16 Exposure to even trace amounts of peanut can induce a serious reaction, including anaphylactic shock.These facts result in significant effects on quality of life of patients and their families. In addition, the widespread distribution of peanuts (PN) in food products not only complicates their avoidance but also increases the risk of allergic reactions through accidental consumption. 2,16 Hence, an accurate diagnosis of PNA is vital. However, while the diagnosis is often obvious just based on the clinical history, in many cases it is far less clear given the imperfect nature of food allergy Abstract Peanut allergy (PNA) is an IgE-mediated immune disorder, which merits particular attention due to its impact on the health and quality of life of millions of patients worldwide. PNA tends to develop in early life and resolves in only 20% of peanutallergic children. It accounts for the majority of severe food-related allergic reactions.An accurate diagnosis of PNA is vital. In this review, we present the approach to the diagnosis of peanut allergy, starting from the history and proceeding to measures of overall sensitization and then to component-resolved diagnostics and oral food challenges as indicated. Additional testing in development includes basophil activation testing and determination of epitopes for peanut-allergic responses. Based on the literature, stepwise approaches and...

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Development of a tool predicting severity of allergic reaction during peanut challenge

Abstract: ClinicalTrials.gov identifier: NCT02103270.

Cited by 61 publications

References 49 publications

Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges

Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges

Basophil Activation Test: Old and New Applications in Allergy

Peanut allergy diagnosis: Moving from basic to more elegant testing

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