Improved diagnostics in food allergy (ID-in-FA) Study

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Food allergy is an increasing public health issue, affecting up to 2% of adults and 6% of children in the UK. It is the most common cause of life-threatening allergic reactions (anaphylaxis). An allergic reaction is a consequence of an interaction between allergen-specific Immunoglobulin E (IgE) antibodies and a food allergen, causing activation of immune cells including mast cells found throughout the body. The "gold standard" test for diagnosis is a formal food challenge, in which increasing doses of food are given under medical supervision. However, food challenges are time-consuming, costly, and not without risk, due to the potential for inducing severe or even fatal anaphylaxis. In practice, IgE-mediated food allergy is usually diagnosed using a surrogate: the detection of specific IgE to the implicated food (called "sensitisation"), either in the skin (through skin prick testing) or blood. Unfortunately, these measures over-estimate the rate of true clinical allergy. In large, population-based studies, over 50% of those with a positive skin test to a food can eat that food without clinical symptoms ie. the antibody is present, but does not result in mast cell activation. The use of tests which assess sensitisation alone results in over-diagnosis, causing unnecessary dietary/social restrictions and anxiety which can impair nutrition and quality of life: the adverse impact of food allergy in children is greater than that caused by diabetes and other chronic illnesses. This, in turn, increases demand for food challenges which become necessary to clarify the diagnosis. Safer and less burdensome diagnostics which can be performed in the outpatient setting are therefore an important goal.In this proposal, we will assess the ability of 2 novel, complementary tests to accurately diagnose food allergy. We will recruit children and young people with indeterminate allergic status despite conventional allergy testing, who have been recruited from our specialist allergy clinic and are due to undergo formal food challenge to clarify a diagnosis of food allergy to peanut, egg or cow's milk.In addition to undertaking conventional allergy tests immediately prior to the food challenge, we will perform:1. Mast cell activation test - in which mast cells (generated from precursor cells in donated blood) are incubated with a small amount of blood from the patient and then exposed to the food allergen, and the mast cell response measured. Our pilot data indicates this is a robust test, with excellent ability to distinguish between true allergy and sensitisation alone.2. Intranasal food challenge - a quick and straightforward procedure in which very small amounts of food protein are administered into the nose, causing a mild hay fever-like response in allergic, but not non-allergic individuals. The technique is identical to that used for the intranasal influenza vaccine given in primary care as part of the UK National Immunisation Schedule. Feedback from participants who participated in a pilot study reported that they found the lack of clinical symptoms at intranasal challenge to be reassuring, reducing both their own and their families' concern over subsequently eating the food to demonstrate no clinical allergy.We will assess how these tests compare to conventional allergy testing, to determine the best strategy to accurately diagnose food allergy without the need for formal food challenge.Our preliminary data indicates that both techniques may confer significant diagnostic accuracy over existing allergy tests. This study will provide the necessary validation to secure follow-on translational funding and commercial investment, to accelerate product development through to regulatory approvals and, ultimately, clinical use. This will assist healthcare professionals in providing more accurate diagnoses, reassurance to patients and parents alike, as well as delivering economic savings to the NHS.