Charlotte Bernhard Madsen

The prevalence of plant food allergies: A systematic review

BACKGROUND There is uncertainty regarding the prevalence of allergies to plant food. OBJECTIVE To assess the prevalence of allergies to plant food according to the different subjective and objective assessment methods. METHODS Our systematic search of population-based studies (since 1990) in the literature database MEDLINE focused on fruits, vegetables/legumes, tree nuts, wheat, soy, cereals, and seeds. Prevalence estimates were categorized by food item and method used (food challenges, skin prick test, serum IgE, parent/self-reported symptoms), complemented by appropriate meta-analyses. RESULTS We included 36 studies with data from a total of over 250,000 children and adults. Only 6 studies included food challenge tests with prevalences ranging from 0.1% to 4.3% each for fruits and tree nuts, 0.1% to 1.4% for vegetables, and < 1% each for wheat, soy, and sesame. The prevalence of sensitization against any specific plant food item assessed by skin prick test was usually < 1%, whereas sensitization assessed by IgE against wheat ranged as high as 3.6% and against soy as high as 2.9%. For fruit and vegetables, prevalences based on perception were generally higher than those based on sensitization, but for wheat and soy in adults, sensitization was higher. Meta-analyses showed significant heterogeneity between studies regardless of food item or age group. CONCLUSION Population-based prevalence estimates for allergies to plant products determined by the diagnostic gold standard are scarce. There was considerable heterogeneity in the prevalence estimates of sensitization or perceived allergic reactions to plant food.

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE‐mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low‐dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult.

The prevalence, cost and basis of food allergy across Europe

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.

Adverse reactions to food additives in children with atopic symptoms.

In a multicenter study conducted at four Danish hospital pediatric departments, the parents of 472 consecutive children were informed of this project to determine the incidence of intolerance of food additives among children referred to an allergy clinic with symptoms of asthma, atopic dermatitis, rhinitis, or urticaria. After a 2‐week period on an additive‐free diet, the children were challenged with the eliminated additives. The food additives investigated were coloring agents, preservatives, citric acid, and flavoring agents. Carbonated “lemonade” containing the dissolved additives was used for the open challenge. Two doses were used: a low dose and a 10‐fold higher dose. Gelatin capsules were used for a double‐blind challenge. The children were 4–15 years old, and they were attending an outpatient pediatric clinic for the first time. Of the 379 patients who entered the study, 44 were excluded and 335 were subjected to open challenge. A total of 23 children developed positive reactions after the open challenge. Sixteen of these patients accepted the double‐blind challenge, and six showed a positive reaction to preservatives (atopic dermatitis, asthma, rhinitis), coloring agents (atopic dermatitis, asthma, urticaria, gastrointestinal symptoms), and citric acid (atopic dermatitis, gastrointestinal symptoms). The incidence of intolerance of food additives was 2% (6/335), as based on the double‐blind challenge, and 7% (23/335), as based on the open challenge with lemonade. Children with atopic skin symptoms had a statistically increased risk of a positive reaction. This may have consequences for the future clinical investigation of children with atopic cutaneous symptoms.

Information provision for allergic consumers – where are we going with food allergen labelling?

As the current treatment for food allergy involves dietary exclusion of the problem food, information for food‐allergic consumers provided on food labels about the nature of allergenic ingredients is important to the management of their condition. The members of an EU‐funded networking project, InformAll, focusing on developing strategies for the provision of credible, reliable sources of information for food allergy sufferers, regulators and the food industry, have been considering these matters with respect to food labelling. This paper presents an overview of the genesis of the new EU directive on food labelling, its relevance to food‐allergic consumers and the problems that might arise if precautionary labelling becomes more widespread in response to concerns regarding inadvertent allergen contamination in foods. International efforts to define threshold levels of allergens able to trigger a reaction coupled with validated allergen detection methods are essential if the food industry is to implement effective hazard control procedures and address the problems of cross‐contact allergens without devaluing the information provided to consumers on food labels.

Approaches to risk assessment in food allergy: Report from a workshop ‘‘developing a framework for assessing the risk from allergenic foods” ☆

A workshop was organised to investigate whether risk assessment strategies and methodologies used in classical/conventional toxicology may be used for risk assessment of allergenic foods, to discuss the advantages and limitations of different approaches and to determine the research needed to move the area forward. Three possible approaches to safety assessment and risk assessment for allergenic foods were presented and discussed: safety assessment using NOAEL/LOAEL and uncertainty factors, safety assessment using Benchmark Dose and Margin of Exposure (MoE), and risk assessment using probabilistic models. The workshop concluded that all the three approaches to safety and risk assessment of allergenic foods should continue to be considered. A particular strength of the MoE and probabilistic approaches is that they do not rely on low-dose extrapolations with its inherent issues. Probabilistic modelling is considered to be the most promising approach for use in population risk assessment (which is a particular focus for risk managers). For all approaches, further improvement of input data is desirable, particularly data on consumption patterns/food choices in food allergic consumers, data on minimum eliciting doses and data that can be used to evaluate whether the whole population at risk has been modelled accurately. Specific research topics were identified.

Immunotoxicity of the pyrethroid insecticides deltametrin and α-cypermetrin

Abstract The synthetic pyrethroids deltametrin and α-cypermetrin were studied for effects on the immune system in 28-day studies in F344 male rats. Sixteen rats per group were dosed with either deltametrin 0, 1, 5, or 10 mg/kg body wt./day or α-cypermetrin 0, 4, 8, or 12 mg/kg body wt./day in soy bean oil by gavage. Haematology, bone marrow cell counts, tests for natural killer (NK) cell activity and mitogen response (Con A and STM) as well as quantitation of lymphocyte subpopulations were performed. Spleen cells from immunized animals (six animals/group) were tested for antibody production (SRBC-PFC). Volumes of lymphoid compartments of mesenteric lymph nodes and thymus were estimated using stereological methods. In the deltametrin study an effect was found in the groups receiving 5 or 10 mg/kg body wt. The effects were: increased weight of mesenterial lymph nodes, decreased thymus weight in immunized animals and an increase in numbers of SRBC-PFC and splenic NK cell activity. An effect on relative adrenal weight was seen in the 10 mg/kg body wt. group. No severe effects on the immune system was found. The lowest effect level of α-cypermetrin was 12 mg/kg body wt./day based on increased relative adrenal weight.

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

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.

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.

Digested Ara h 1 has sensitizing capacity in Brown Norway rats.

Background Food allergies are a public health issue of growing concern, with peanuts in particular being associated with severe reactions. The peanut allergen, Ara h 1, belongs to the cupin plant food allergen family, which, unlike other structural families, appears to be broken down rapidly following gastrointestinal digestion.