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.

Development of the BELANA questionnaire for the analysis of economic burdens of food allergy and intolerance.

INTRODUCTION: Patients affected by food allergies and intolerance need to apply dedicated avoidance strategies and also prevent the consequences of unbalanced diets. In most countries, the health economic costs for these patients are unknown. METHODS: To measure temporal and financial burdens of the patients in multinational settings, the BELANA questionnaire (Burdens and Expenses of Living as an Adult with Nutrition based Allergy or Intolerance) has been developed. For the complementary measurement of Health Related Quality of Life (HR-QoL), a combined appliance of the disease-specific FAQLQ-AF (Food Allergy Quality of Life Questionnaire - Adult Form) and the generic SF-12v1 (Short Form-12 Health Survey) has been chosen. RESULTS: BELANA collects six economic items while avoiding questions, which are already included in the HR-QoL questionnaires or could lead to denial tendencies. In a web-based pilot survey with 51 patients, the practicability of using BELANA together with the complementary quality of life instruments was investigated. The electronic data collection offers real time plausibility checks and limits the workload for completion and data evaluation. DISCUSSION: The response rates at BELANA health-economic items (76 - 100%) and the high amount of completed questionnaires (50 of 51) confirm the patients acceptance of the chosen methodology. Within the web-based survey, the combination of BELANA, FAQLQ-AF and SF-12v1 was completed in an average of 22 minutes. An age-related selection bias was not been confirmed in this pilot application. The median age in the pilot trial was 37.9 years (minimum age to participate was 18 years, range from 19 to 72 years, Standard Deviation (SD) = 12.4 years). Most of the participants were female (44 of 50). CONCLUSION: It is assumed that the BELANA questionnaire should be a useful tool for the evaluation of health-economic burden for patients with food allergy and intolerance.

A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

BACKGROUND: The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). METHODS: A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. RECOMMENDATIONS: A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. CONCLUSION: The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening 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.

A new framework for the interpretation of IgE sensitization tests.

IgE sensitization tests, such as skin prick testing and serum-specific IgE, have been used to diagnose IgE-mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi-quantified from an IgE sensitization test results. This relationship varies though according to the patients' age, ethnicity, nature of the putative allergic reaction and coexisting clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patient's presenting features (pretest probability). The presence of each of these patient-specific factors may mean that a patient is more or less likely to have clinical allergy with a given test result (post-test probability). We present two approaches to include pretest probabilities in the interpretation of results. These approaches are currently limited by a lack of data to allow us to derive pretest probabilities for diverse setting, regions and allergens. Also, cofactors, such as exercise, may be necessary for exposure to an allergen to result in an allergic reaction in specific IgE-positive patients. The diagnosis of IgE-mediated allergy is now being aided by the introduction of allergen component testing which may identify clinically relevant sensitization. Other approaches are in development with basophil activation testing being closest to clinical application.

Precautionary allergen labelling: perspectives from key stakeholder groups.

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk-taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision-making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.

Detection of relevant amounts of cow's milk protein in non-pre-packed bakery products sold as cow's milk-free.

BACKGROUND: Currently, there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterize allergic reactions to non-pre-packed foods and to investigate whether staff in bakery shops were able to give advice regarding a safe product choice. METHODS: Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 bakery shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as 'cow's milk-free' were bought, and cow's milk protein levels were measured using ELISA. RESULTS: A total of 104 of 200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from bakery shops and 20% from ice cream parlours. Sixty percent of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. Eighty four percent of the staff felt able to advise food-allergic consumers regarding a safe product choice. Seventy three 'cow's milk-free' products were sold in 44 bakery shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving. CONCLUSION: Staff in bakery shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as 'cow's milk-free'. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk-allergic children will show clinical relevant symptoms.

Effects of a structured educational intervention on knowledge and emergency management in patients at risk for anaphylaxis.

BACKGROUND: Structured educational programmes for patients at risk for anaphylaxis have not yet been established. Patients and caregivers often lack adequate skills in managing the disease. METHODS: To investigate effects of structured patient education intervention on knowledge, emergency management skills and psychological parameters in patients with previous episodes of anaphylaxis and caregivers of affected children 95 caregivers (11 male, 84 female, mean age 37 years) of affected children and 98 patients (32 male, 66 female, mean age 47.5 years) were randomly assigned to an intervention (IG) or control group (CG) in a multicentre randomized controlled trial. The IG received two 3-h schooling modules of group education; the CG received standard auto-injector training only. Knowledge of anaphylaxis and emergency management competence in a validated training anaphylaxis situation as main outcome measures as well as secondary psychological parameters were assessed at baseline and 3 months after intervention. RESULTS: In comparison with controls, the intervention led to significant improvement of knowledge from baseline to 3-month follow-up (caregivers: IG 3.2/13.2 improvement/baseline vs CG 0.7/12.6; P < 0.001; patients: IG 3.9/10.8 vs 1.3/12.6; P < 0.001). Moreover, emergency management competence was increased after intervention as compared to controls (caregivers: IG 8.6/11.2 vs CG 1.2/10.8; P < 0.001; patients: 7.1/11.0 vs 1.1/11.1; P < 0.001). Intervention showed significant reduction of caregiver anxiety (-1.9/8.4 vs -0.7/7.5; P < 0.05). There were no significant changes in the depression scores. CONCLUSION: Structured patient education programmes may be beneficial in the management of anaphylaxis by increasing patients' empowerment to prevent and treat the disease.

EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs.

Individuals suffering from IgE-mediated food allergy usually have to practise life-long food allergen avoidance. This document aims to provide an overview of recent evidence-based recommendations for allergen risk assessment and management in the food industry and discusses unmet needs and expectations of the food allergic consumer in that context. There is a general duty of care on the food industry and obligations in European Union legislation to reduce and manage the presence of allergens alongside other food hazards. Current evidence enables quantification of allergen reference doses used to set-up reliable food safety management plans for some foods. However, further work is required to include a wider variety of foods and to understand the impact of the food matrix as well as additional factors which affect the progression and severity of symptoms as a function of dose. Major concerns have been raised by patients, carers and patient groups about the use of precautionary 'may contain' labelling to address the issue of unintended presence of allergens; these therefore need to be reconsidered. New and improved allergen detection methods should be evaluated for their application in food production. There is an urgent requirement for effective communication between healthcare professionals, patient organizations, food industry representatives and regulators to develop a better approach to protecting consumers with food allergies.

EAACI food allergy and anaphylaxis guidelines: managing patients with food allergy in the community.

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level.

[Hidden allergens in processed food. The consumer perspective]. / Problematik "versteckter Allergene" in Lebensmitteln aus Sicht des allergischen Verbrauchers.

Despite improved allergen-labeling and careful avoidance strategies, hidden allergens in food are a substantial risk for unintended reactions in food allergy sufferers. Unpublished data from a survey of the German Allergy and Asthma Association (Deutscher Allergie- und Asthmabund, DAAB) show that 85% of 738 questioned food allergic patients have experienced at least one allergic reaction from each prepacked products as well as food sold loose. Almost half of the participants said to have not received information of a food allergen as an ingredient or possible trace on the label. Different possibilities are discussed under which food allergens can be hidden in processed products, like incomprehensible labeling, labeling gaps, unexpected occurrence of allergens as well as cross contaminations or allergens in loose products. To each of the seven highlighted sources of hidden allergens in food, practical examples are given as well as proposals for the improvement of the situation from consumer view. The aim is to indicate possibilities and measures for politics and industry by which allergic consumers and their social circle are able to make an informed choice concerning the safe consumption of a certain product and to protect themselves from unintentional reactions.

Can we define a tolerable level of risk in food allergy? Report from a EuroPrevall/UK Food Standards Agency workshop.

BACKGROUND: There is an emerging consensus that, as with other risks in society, zero risk for food-allergic people is not a realistic or attainable option. Food allergy challenge data and new risk assessment methods offer the opportunity to develop quantitative limits for unintended allergenic ingredients which can be used in risk-based approaches. However, a prerequisite to their application is defining a tolerable level of risk. This requires a value judgement and is ultimately a 'societal' decision that has to involve all relevant stakeholders. OBJECTIVE: The aim of the workshop was to bring together key representatives from the stakeholders (regulators, food industry, clinical researchers and patients), and for the first time ever discuss the definition of a tolerable level of risk with regard to allergic reactions to food. RESULTS: The discussions revealed a consensus that zero risk was not a realistic option and that it is essential to address the current lack of agreed action levels for cross-contamination with allergens if food allergen management practice is to be improved. The discussions also indicated that it was difficult to define and quantify a tolerable level of risk, although both the clinical and the industry groups tried to do so. A consensus emerged that doing nothing was not a viable option, and there was a strong desire to take action to improve the current situation. CONCLUSIONS AND CLINICAL RELEVANCE: Two concrete actions were suggested: (1) Action levels should be derived from the data currently available. Different scenarios should be examined and further developed in an iterative process. On the basis of this work, a tolerable level of risk should be proposed. (2) 'One-dose' clinical trial with a low challenge dose should be performed in multiple centres to provide additional information about the general applicability of dose-distribution models and help validate the threshold levels derived.