Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary.

Unintended allergens in precautionary labelled and unlabelled products pose significant risks to UK allergic consumers.

BACKGROUND: Allergens in food may pose a risk to allergic consumers. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary allergen labels to inform allergic individuals of a potential risk from UAPs. This study investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut- and peanut-allergic populations when ingesting UK foods across multiple product categories with and without precautionary allergen labelling. METHODS: Allergen risk assessment using probabilistic techniques enables the estimation of the residual risk after the consumption of a product that unintentionally contains an allergen. RESULTS: Within this selection of UK products, the majority that tested positive for an allergen contained a concentration of allergen predicted to cause a reaction in >1% of the allergic population. The concentrations of allergens measured were greater than the VITAL(®) 2.0 action levels and would trigger precautionary allergen labelling. This was found for products both with and without precautionary allergen labelling. CONCLUSIONS: The results highlight the need for the food industry and regulators to adopt a transparent, risk-based approach for the communication of the risk associated with potential cross-contact that could occur in the processing facility or production chain.

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.

Probabilistic risk assessment model for allergens in food: sensitivity analysis of the minimum eliciting dose and food consumption.

Previously, TNO developed a probabilistic model to predict the likelihood of an allergic reaction, resulting in a quantitative assessment of the risk associated with unintended exposure to food allergens. The likelihood is estimated by including in the model the proportion of the population who is allergic, the proportion consuming the food and the amount consumed, the likelihood of the food containing an adventitious allergen and its concentration, and the minimum eliciting dose (MED) distribution for the allergen. In the present work a sensitivity analysis was performed to identify which parts of the model most influence the output. A shift in the distribution of the MED reflecting a more potent allergen, and an increase in the proportion of the population consuming a food, increased the number of estimated allergic reactions considerably. In contrast, the number of estimated allergic reactions hardly changed when the MEDs were based on a more severe response, or when the amount of food consumed was increased. Development of this work will help to generate a more accurate picture of the potential public health impact of allergens. It highlights areas where research is best focused, specifically the determination of minimum eliciting doses and understanding of the food choices of allergic individuals.

Risk assessment and food allergy: the probabilistic model applied to allergens.

In order to assess the risk of unintended exposure to food allergens, traditional deterministic risk assessment is usually applied, leading to inconsequential conclusions as 'an allergic reaction cannot be excluded'. TNO therefore developed a quantitative risk assessment model for allergens based on probabilistic techniques resulting in a more exhaustive risk assessment and more detailed information. By now, this approach is recognized as the future approach in allergen risk assessment. A case study (hazelnut proteins in chocolate spread) is presented as a proof of concept.

Sesame allergy threshold dose distribution.

BACKGROUND: Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies. METHOD: Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used. RESULTS: Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein. CONCLUSION: This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis.

Socio-economic status, dietary intake and 10 y trends: the Dutch National Food Consumption Survey.

OBJECTIVE: To study differences in dietary intake between adults with different socioeconomic status (SES) and trends over time. DESIGN: Cross-sectional study based on data of three Dutch National Food Consumption Surveys (DNFCS-1 1987/88; DNFCS-2 1992; DNFCS-3 1997/98), obtained from a panel by a stratified probability sample of the non-institutionalized Dutch population. SUBJECTS: A total of 6008 men and 6957 women aged 19 y and over. METHODS: Dietary intake was assessed with a 2 day dietary record. Background information was obtained by structured questionnaire. Sociodemographic variables were available from panel information. SES, based on educational level, occupation and occupational position was categorized into (very) low, middle and high. Analysis of variance with age as covariable was used to explore the effects of SES on dietary intake and anthropometry. Statistical tests for trend were carried out with models in which week-weekend-day effects and an interaction term of time with SES were also included. RESULTS: The prevalence of obesity and skipping of breakfast was higher among people with a low SES. In all three surveys, subjects in the (very) low SES group reported having a higher consumption of potatoes, meat and meat products, visible fats, coffee and soft drinks (men only). Subjects with a high SES reported consuming more vegetables, cheese and alcohol. As regards nutrients, in all surveys a higher SES was associated with higher intake of vegetable protein, dietary fibre and most micronutrients. A higher SES was also associated with a lower fat intake but the differences between social classes were rather small and not consistent when the contribution of alcohol to energy intake was taken into account. CONCLUSION: In general, dietary intake among subjects in higher SES groups tended to be closer to the recommendations of the Netherlands Food and Nutrition Council and this phenomenon was quite stable over a period of 10 y.

Concentrations of undeclared allergens in food products can reach levels that are relevant for public health.

Food products can become contaminated with food allergens due to cross-contact. Precautionary 'may contain' labelling may alert to the possible presence of an allergen, but guidance for such labelling is lacking. As a result, allergy information on the packaging may not be reliable and allergic consumers might be at risk of allergic reactions after consuming unlabelled, but indeed contaminated, products. Recently, a cow's milk protein allergic patient experienced a severe allergic reaction to a dark chocolate product containing undeclared milk proteins. This case induced the authors to investigate to what extent allergen concentrations of unlabelled products reach levels that are of public health relevance. The concentrations of milk proteins in the complaint sample and a collection of products of other batches and brands purchased from different stores were analysed. Together with appropriate threshold and food consumption data, the risks of allergic reactions and the severity of these reactions within the adult milk-allergic population were determined using probabilistic risk assessment techniques. The results show that milk protein concentrations in unlabelled products reach levels that may elicit allergic reactions in up to 68% of the adult allergic consumers. Therefore, concentrations of allergens in unlabelled products could reach levels that are of public health relevance. Application of probabilistic risk assessment can be an aid in revealing the public health consequences of undeclared allergens in food, in risk management decision-making and developing guidance in terms of risk-based concentration limits for precautionary labelling.

Validation and sensitivity analysis of probabilistic models of dietary exposure to micronutrients: an example based on vitamin B6.

Probabilistic modelling can be used to get an insight into the variability and uncertainty of the nutrient intake in a population. When a probabilistic model is used, it is important that it is validated. Furthermore, a sensitivity analysis of the model output can give an insight into the most important input variables of the model and can be used as an aid to describe the reliability of the model. In this study, four models to estimate vitamin B(6) intake among males and females were validated using the method of Kaaks et al. This method compares the relationship between three different kind of measurements with the unknown 'true' intake. In each of these four models, only one input variable (concentration or bioavailability) was changed compared with a reference model. A sensitivity analysis was also performed. The results of the validation showed that for males, a model using a fixed bioavailability factor at the food group level was valid, while for females a model using either a fixed value or a distribution for the bioavailability factor was valid. Use of a distribution for the concentration of vitamin B(6) in supplements was not valid. The results of the sensitivity analysis showed that the concentration of vitamin B(6) in food and supplements was the key contributor to variability and uncertainty in the model estimates of vitamin B(6) intake, in both males and females. All results indicated that when taking variability and uncertainty into account by using probabilistic modelling, the effect on the nutrient intake for nutrients that are present in many common eaten foods, is small. For these broadly available nutrients, fixed concentrations and bioavailability factors give a good estimate of the nutrient intake in a population. When using probabilistic modelling, it is very important to collect more actual information about the concentration.

Development of databases for use in validation studies of probabilistic models of dietary exposure to food chemicals and nutrients.

The data currently available in the European Union in terms of food consumption and of food chemical and nutrient concentration data present many limitations when used for estimating intake. The most refined techniques currently available were used within the European Union FP5 Monte Carlo project to estimate, as accurately as possible, the intake of food additives, pesticide residues and nutrients. Databases of 'true' intakes of food additives (based on brand level food consumption records and additive concentration data), pesticide residues (based on duplicate diet studies) and nutrients (based on biomarker studies) have thus been generated. These kind of estimates are rarely repeatable because the databases generated and used to calculate them require an extraordinary expenditure of time and resources. The databases created served the purpose of estimating as accurately as possible 'true' chemical intakes for assessing the validity of additive, nutrient and pesticide probabilistic models.