Prediction of food challenge outcome in children

At present, the double blind placebo controlled food challenge (DBPCFC)
represents the gold standard for the definitive diagnose of food allergy. The
DBPCFC is terminated and considered positive when objective symptoms occur.
However, there are several pitfalls in performing and interpreting food
challenges. Food challenges are expensive due to the time consuming procedure
and the need of trained staff. Moreover challenges can be dangerous by bearing
the risk of a severe allergic reaction. In children, also the portion size and
total volume of the challenge food can be a problem. Furthermore, especially in
young children, symptoms during challenge can be difficult to interpret.
Subjective symptoms (abdominal complaints, oral allergy syndrome, and change of
behaviour) are difficult to objectify and less obvious objective symptoms (as
mild broncho-constriction or change in blood pressure) are easily missed. As a
result false-negative tests do occur and negative challenges are sometimes
followed by an allergic reaction upon the reintroduction of the allergen.
Markers of the IgE mediated immune response could provide more specific and
objective diagnostic tools to determine the presence of peanut allergy. The
Basophil Activation Test (BAT), a flow cytometry based functional assay that
assesses the degree of cell activation after exposure to an allergen in vitro,
has shown promising results as a diagnostic tool in atopic diseases. A high
sensitivity and specificity was found in exploratory studies in children with
food allergy and non allergic controls. The aim of this study is to evaluate
the diagnostic value of the BAT to predict the presence of a clinical relevant
peanut allergy in children. Hereby we tend to improve the diagnostic process in
children with suspected peanut allergy and reduce the amount of food challenges
by at least 50%. More insight in the presence of a systemic inflammatory
response after the ingestion of peanut could improve the diagnostic value of
the food challenge test. As a secondary aim in this study we will therefore
also evaluate whether we can identify determinants of the cytokine level during
food challenges in children.

Evaluate the diagnostic value of the Basophil Activation Test in determining
the presence of peanut allergy in children.
Domain: Children with suspected peanut allergy
Determinant: The Basophil Activation Test
Outcome: The presence of clinically relevant peanut allergy

As a secondary aim we will evaluate whether we can identify determinants of the
cytokine response during food challenges.

In this observational diagnostic study we will evaluate the diagnostic value of
the basophil activation test (BAT) in detecting the presence of peanut allergy.
For this study children will undergo food allergy diagnostics according to the
current international guidelines including the standardized DBPCFC. The DBPCFC
will be extended in children with negative / inconclusive challenge with an
extensive follow-up period of four weeks to determine our outcome, the presence
of a clinically relevant food allergy, in all children. During follow-up in
which patients will reintroduce peanut at home by a reintroduction program,
reactions will be monitored and objectified in hospital when necessary. An
expert panel will review and classify the symptoms during DBPCFC and follow-up
and determine the final outcome (presence of peanut allergy) in all children.
We draw blood before and during the DBPCFC to perform the BAT and as a
secondary aim measure the systemic cytokine response during challenge.

Peanut allergy is a largely disabling diagnosis during childhood and later
life. We will study children because it is important to diagnose food allergy
accurately to prevent unnecessary restricted diets further in live. Moreover,
especially in children false negative tests occur due to subjective symptoms
during challenge. There are no risks associated with participation to this
study. The burden is limited to some additional blood drawing at moments that
children have intravenous lines in situ. The total amount of blood drawn for
this study will be 10 ml (in a 2 week period) which is below the local clinical
guidelines for blood sample volume limits in children. The follow-up period of
children without objective symptoms during DBPCFC will be short and
non-invasive and consist of a diary, additional telephonic interviews to ensure
reintroduction at home and a hospital visit with open re-challenge when
necessary to confirm and objectify symptoms. There are no individual patient
benefits for the participation of this study. The results of this study will
improve food allergy diagnostics and reduce the amount of food challenges. It
can lead to a considerable decrease of unnecessary food avoidance on one hand
and a decrease in the occurrence of reintroduction problems on the other hand
with resulting improvement of quality of life in children with suspected peanut
allergy.