The Key Events Dose-Response Framework: A Foundation for Examining Variability in Elicitation Thresholds for Food Allergens

Food allergies are caused by immunological reactions in individuals sensitized to normal protein components of foods. For any given sensitized individual, the severity of a reaction is generally assumed to be proportional to the dose of allergenic protein. There is substantial clinical evidence that “threshold” doses exist for the elicitation of an allergic reaction; however, the threshold (i.e., lowest dose that elicits a reaction) varies substantially across the sensitized population. Current approaches to protecting sensitized individuals from exposure to food allergens are highly qualitative (i.e., they rely on food avoidance). The Key Events Dose-Response Framework is an analytical approach for refining understanding of the biological basis of the dose-response. Application of this approach to food allergy provides a foundation for a more rigorous quantitative understanding of variability in allergic response. This study reviews the allergic disease process and the current approaches to identifying thresholds for food allergens. The pathway of key biological events occurring between food intake and allergic response is considered, along with factors that may determine the nature and severity of response to food allergens. Data needs, as well as implications for identifying thresholds, and for characterizing variability in thresholds, are also discussed

Accidental allergic reactions to food in adolescents and adults: An overview of the factors involved and implications for prevention

Accidental allergic reactions to food are one of the major problems in adult patients diagnosed with food allergy. Such reactions occur frequently, are often severe and are associated with higher medical and non-medical costs. The aim of this Perspective is to provide insight into the different factors involved in the occurrence of accidental allergic reactions and to present an overview of practical implications for effective preventive measures. Several factors affect the occurrence of accidental reactions. These factors are related to the patient, health care, or food. The most important patient-related factors are age, social barriers to disclosing their allergy and non-adherence to the elimination diet. With regards to healthcare, the degree to which clinical practice is tailored to the individual patient is an important factor. The major food-related factor is the absence of adequate precautionary allergen labeling (PAL) guidelines. Since many factors are involved in accidental allergic reactions, different preventive strategies are needed. It is highly recommended that health care be tailored to the individual patient, with regard to education about the elimination diet, support on behavioral and psychosocial aspects, usage of shared decision-making and taking into account health literacy. In addition, it is crucial that steps are taken to improve policies and guidelines for PAL

Updated full range of Eliciting Dose values for Cow’s milk for use in food allergen risk assessment

Access to Eliciting Doses (ED) for allergens enables advanced food allergen risk assessment. Previously, the full ED range for 14 allergenic foods, including milk, and recommendations for their use were provided (Houben et al., 2020). Additional food challenge studies with cow’s milk-allergic patients added 247 data points to the original dataset. Using the Stacked Model Averaging statistical method for interval-censored data on the 697 individual NOAELs and LOAELs for milk generated an updated full ED distribution. The ED01 and ED05, the doses at which 1% and 5% of the milk-allergic population would be predicted to experience any objective allergic reaction, were 0.3 and 3.2 mg milk protein for the discrete and 0.4 mg and 4.3 mg milk protein for the cumulative dose distribution, respectively. These values are slightly higher but remain within the 95% confidence interval of previously published EDs. We recommend using the updated EDs for future characterization of risks of exposure of milk-allergic individuals to milk protein. This paper contributes to the discussion on the Reference Dose for milk in the recent Ad hoc Joint FAO/WHO Expert Consultation on Risk Assessment of Food Allergens. It will also benefit harmonization of food allergen risk assessment and risk management globally

The role of hazard- and risk-based approaches in ensuring food safety

AbstractBackgroundFood legislation in the European Union and elsewhere includes both hazard- and risk-based approaches for ensuring safety. In hazard-based approaches, simply the presence of a potentially harmful agent at a detectable level in food is used as a basis for legislation and/or risk management action. Risk-based approaches allow consideration of exposure in assessing whether there may be unacceptable risks to health.Scope and approachThe advantages and disadvantages of hazard- and risk-based approaches for ensuring the safety of food chemicals, allergens, ingredients and microorganisms were explored at an ILSI Europe workshop.Key findings and conclusionsIt was concluded that both types of approach have their place, depending on the context. However, problems can arise when both types of approach are used in regulation by separate agencies that address different aspects of the same agent/substance present in food. This separation of decision-making can result in hazard-based restrictions on marketing and use, whereas risk-based assessments for those exposed show there is reasonable certainty no harm will result. This in turn can lead to contradictory, confusing and ultimately unnecessary actions. Use of hazard-based approaches for foods also means that comparisons with benefits for nutrition and food security cannot be undertaken. This has the potential to lead to bias in the overall conclusions of regulators and risk managers, who may not have been presented with the benefits of particular foods. The value of risk-based approaches is becoming increasingly recognised

Low dietary adherence after a positive food challenge in food allergic adults

Background: After a positive food challenge (FC), patients receive dietary advice regarding avoidance of the culprit food. We examined the frequency and variables associated with dietary adherence after a positive FC in adults. Methods: In this prospective daily practice study, adults with a positive FC were included. After every FC, dietary advice was given consisting of three options: (1) strict avoidance, (2) avoidance but products with precautionary allergen labelling (PAL) allowed and (3) (small) amounts allowed. Questionnaires about dietary adherence and associated variables were completed prior to and 6 months after the FC(s). Results: 41 patients (with 58 positive FCs) were included. Overall, patients adhered to the advised diet after 31% of the FCs. After 33 FCs, the advice was strict avoidance, whereof 82% followed a less strict diet. After 16 FCs, the advice was avoidance but products with PAL allowed, whereof 19% followed a less strict and 25% a stricter diet. In 9 FCs with the least strict advice, “(small) amounts allowed’’, 67% followed a stricter diet. Three variables were associated with adherence: misremembering dietary advice, impaired health-related quality of life (HRQL) on domain “Emotional impact’’ and the need for dietary change after the FC. Conclusion: After one third of the positive FCs, patients adhered to the dietary advice. Variables associated with adherence were misremembering dietary advice, impaired HRQL on domain “Emotional impact’’ and the need for dietary change after the FC. It seems important that healthcare professionals should more frequently apply adherence-enhancing strategies to improve dietary adherence

Consensus on gut feelings in general practice

Contains fulltext : 81134.pdf (publisher's version ) (Open Access)BACKGROUND: General practitioners sometimes base clinical decisions on gut feelings alone, even though there is little evidence of their diagnostic and prognostic value in daily practice. Research to validate the determinants and to assess the test properties of gut feelings requires precise and valid descriptions of gut feelings in general practice which can be used as a reliable measuring instrument. Research question: Can we obtain consensus on descriptions of two types of gut feelings: a sense of alarm and a sense of reassurance? METHODS: Qualitative research including a Delphi consensus procedure with a heterogeneous sample of 27 Dutch and Belgian GPs or ex-GPs involved in academic educational or research programmes. RESULTS: After four rounds, we found 70% or greater agreement on seven of the eleven proposed statements. A "sense of alarm" is defined as an uneasy feeling perceived by a GP as he/she is concerned about a possible adverse outcome, even though specific indications are lacking: There's something wrong here. This activates the diagnostic process by stimulating the GP to formulate and weigh up working hypotheses that might involve a serious outcome. A "sense of alarm" means that, if possible, the GP needs to initiate specific management to prevent serious health problems. A "sense of reassurance" is defined as a secure feeling perceived by a GP about the further management and course of a patient's problem, even though the doctor may not be certain about the diagnosis: Everything fits in. CONCLUSION: The sense of alarm and the sense of reassurance are well-defined concepts. These descriptions enable us to operationalise the concept of gut feelings in further research

Updated threshold dose-distribution data for sesame

Sesame is classified as a “major” food allergen for which mandatory disclosure is required. Understanding reaction thresholds and how these vary within the allergic population is crucial in providing appropriate dietary advice to patients, providing guidance to the food industry, and informing dosing regimens for oral food challenges (FC). However, the largest data series used to derive a threshold dose-distribution for sesame included blinded challenge data from just 40 individuals.1 Data from low-dose, open FC can be used to supplement that from blinded FC, reducing uncertainty in estimating threshold dose-distributions for allergenic foods which otherwise lack sufficient data.2 We, therefore, undertook a systematic search of the literature and performed dose-distribution modelling of individual patient FC data (including open FC) to update estimated eliciting doses for sesame

Ad hoc Joint FAO/WHO Expert Consultation on Risk Assessment of Food Allergens Part 2: Review and establish threshold levels in foods of the priority allergens

The main purpose of this second meeting was to establish threshold levels in foods of the priority allergens. Based on the defined approach, the Expert Committee discussed and agreed on the safety objective, which could be described as “to minimise, to a point where further refinement does not meaningfully reduce health impact, the probability of any clinically relevant objective allergic response, as defined by dose distribution modelling of minimum eliciting doses (MEDs) and supported by data regarding severity of symptoms in the likely range of envisioned Reference Doses (RfD)”. The Committee further identified several important considerations to guide decision-making. These included a clear definition of criteria to be met by quantitative data on which reference doses (RfD) are based, supporting data on health manifestations (severity) at the proposed RfD, quality, quantity, availability and accessibility of data (for priority allergens), as well as how to deal with priority allergens for which information supporting one or more of those considerations was lacking.El objetivo principal de esta segunda reunión fue establecer niveles umbral en los alimentos de los alérgenos prioritarios. Sobre la base del enfoque definido, el Comité de Expertos discutió y acordó el objetivo de seguridad, que podría describirse como “minimizar, hasta un punto en el que un mayor refinamiento no reduzca significativamente el impacto en la salud, la probabilidad de cualquier respuesta alérgica objetiva clínicamente relevante, como definido por el modelo de distribución de dosis de dosis mínimas provocadoras (MED) y respaldado por datos sobre la gravedad de los síntomas en el rango probable de dosis de referencia previstas (RfD) ”. El Comité identificó además varias consideraciones importantes para orientar la toma de decisiones. Estos incluyeron una definición clara de los criterios que deben cumplir los datos cuantitativos en los que se basan las dosis de referencia (RfD), datos de apoyo sobre manifestaciones de salud (gravedad) en la RfD propuesta, calidad, cantidad, disponibilidad y accesibilidad de los datos (para alérgenos prioritarios). , así como cómo tratar los alérgenos prioritarios para los que faltaba información que respaldara una o más de esas consideraciones.Instituto de Investigación de Tecnología de AlimentosFil: Baumert, Joseph. Universidad de Nebraska-Lincoln. Departamento de Ciencia y Tecnología de Alimentos; Estados UnidosFil: Brooke-Taylor, Simon. Brooke-Taylor & Co. Consultor australiano de regulación alimentaria y análisis de riesgos (Pty Ltd); Australia.Fil: Crevel, René W.R. René Crevel Consulting Limited; Reino Unido.Fil: Houben, Geert F. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Jackson, Lauren. Administración de Alimentos y Medicamentos de los Estados Unidos. División de Ciencia y Tecnología del Procesamiento de Alimentos. Ingeniería de Procesos; Estados UnidosFil: Kyriakidis, Symeon. Laboratorio Estatal de Química General (GCSL).Autoridad Independiente de Ingresos Públicos (IAPR); Grecia.Fil: La Vieille, Sébastien. Universidad Laval. Departamento de Ciencias de los Alimentos; Canadá.Fil: Lee, N Alice. Universidad de Nueva Gales del Sur. Escuela de Química e Ingeniería. Ciencia e ingeniería de los alimentos; Australia.Fil: López, María Cristina. Universidad Nacional de San Martín. Ingeniería de Alimentos; Argentina.Fil: Luccioli, Stefano. Administración de Alimentos y Medicamentos de los Estados Unidos. Centro de Seguridad Alimentaria y Nutrición Aplicada; Estados UnidosFil: O’Mahony, Patrick. Autoridad de Seguridad Alimentaria de Irlanda; Irlanda.Fil: O’Mahony, Patrick. Universidad College Dublin; Irlanda.Fil: Polenta, Gustavo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina.Fil: Polenta, Gustavo Alberto. Instituto de Ciencia y Tecnología de los Sistemas Alimentarios Sustentables (ICyTeSAS) UEDD INTA-CONICET; Argentina.Fil: Pöpping, Bert. Food Consulting Strategically (FOCO); Alemania.Fil: Pöpping, Bert. Comités de Normalización ISO - CEN. Grupo de trabajo CEN Alérgenos Alimentarios (CEN TC 275 WG 12).); Alemania.Fil: Remington, Benjamin C. Remington Consulting Group B.V.; Holanda.Fil: Remington, Benjamin C. Universidad de Nebraska–Lincoln. Programa de Recursos e Investigación de Alergias Alimentarias. Estados UnidosFil: Srikulnath, Sirinrat. Universidad de Kasetsart (UKaset). Instituto de Investigación y Desarrollo de Productos Alimentarios. Centro de Servicio de Aseguramiento de la Calidad de los Alimentos. Unidad de Alérgenos Alimentarios; Tailandia.Fil: Taylor, Stephen L. Universidad de Nebraska-Lincoln. Departamento de Ciencia y Tecnología de Alimentos; Estados UnidosFil: Turner, Paul J. Colegio Imperial de Ciencia, Tecnología y Medicina. Alergia e Inmunología Pediátricas; Inglaterra