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Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of foodtriggered anaphylactic reactions are not life-threatening. Nonetheless, severe lifethreatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

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The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow us to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities.

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Clinical records of 286 consecutive patients reacting positively with objective symptoms to double-blind, placebo-controlled oral peanut challenges at University Hospital, Nancy, France were examined for individual No Observed Adverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels (LOAELs). After fitting to a log-normal probability distribution model, the ED(10) and ED(05) were 14.4 and 7.3mg (expressed as whole peanut), respectively, with 95% lower confidence intervals of 10.7 and 5.2mg, respectively. Compared to results from a previous study where the ED(10) was based upon individual peanut thresholds gleaned from 12 publications, a statistically significant difference was observed between the ED(50)'s, but not the ED(10)'s of the two probability distribution curves. The Nancy patient group contains more sensitive subjects than the group from the published literature thus contributing to the observed differences. Minimum eliciting dose-distributions for patients with histories of more severe reactions (grade 4 or 5; 40 subjects) did not differ significantly from those of patients with histories of less severe reactions (grades 1-3; 123 subjects). These data and this modeling approach could be used to establish population thresholds for peanut-allergic consumers and thereby provide a sound basis for allergen control measures in the food industry.