A flexible pragmatic approach to establishing individual food allergic thresholds
Published online: August 22, 2019
For more than 20 years, the Netherlands Organisation for Applied Scientific Research (TNO), The Food Allergy Research and Resource Program (FARRP) at the University of Nebraska-Lincoln, and their clinical collaborators across the globe have been collecting data from oral food challenges in an effort to refine knowledge regarding the sensitivity of the allergic population to food allergens. The resulting food-allergic population-based threshold dose distributions have been previously published by The Journal of Allergy and Clinical Immunology (JACI) and others for a number of priority, regulated food allergens (https://doi.org/10.1016/j.jaci.2012.10.034, https://doi.org/10.1016/j.jaci.2013.06.042, https://doi.org/10.1016/j.jaci.2014.10.047). How individual threshold values are derived from the clinical raw data for this purpose is critical, but has not been previously systematically discussed, to our knowledge.
In an effort to standardize individual food challenge data reporting and reduce variability in subsequent population dose distribution results, Westerhout and colleagues have published a transparent framework in The Journal of Allergy and Clinical Immunology (JACI) which can be utilized to derive individual maximum doses tolerated without reaction and minimum eliciting doses during oral food challenges. The framework guides food challenge data interpretation with over 90 examples and different scenarios for determining individual allergic thresholds.
In theory, an individual’s objective symptoms threshold dose is based on the first appearance of objective symptoms. However, in reality, food challenges and the occurrence or interpretation of clear, clinically unequivocal challenge-stopping symptoms are seldom straightforward. Symptoms can be transient in nature, appearing and disappearing again, or symptoms can be subjective and need to be confirmed over multiple (increasing) doses. In many cases, a food challenge is continued by the clinician after the observation of objective symptoms, possibly because the investigator requires stronger evidence to confirm the diagnosis of food allergy. The methodology presented by Westerhout and colleagues deals with these issues and can be considered as a conservative, pragmatic and practical approach to balance data analysis from individual diagnostic food challenges for population risk assessment and risk management purposes without overcorrecting in the presence of transient or repeated symptoms.
The framework presented by Westerhout and colleagues provides a transparent, flexible template for interpretation of food challenge results. It provides a step forward towards harmonized food allergy risk assessment & risk management and the framework can be updated in the future based on potential changes in stakeholder opinions/requirements.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.