Food Allergy Diagnostic Test Response to Previous Oral Challenge Response

Patients usually discover they have food allergies after consuming a given food and
experiencing a subsequent allergic reaction. The majority of patients (75%) will then consult
a food allergist for formal diagnosis and treatment information.1 With respect to patient
quality of life, there is tremendous benefit in having a confirmed diagnosis of food allergy
as often patients are unsure of the source of their reaction outside the office. Allergists
will conduct Skin Prick Test (SPT) and assess serum specific IgE levels to screen for
specific food protein sensitivities. However, a positive response in SPT and specific IgE
will confirm only sensitivity, and in more than 70% of cases patients that respond positively
to SPT and specific IgE testing will NOT manifest an allergic response to food consumption.2
To address this issue, most food allergists will recommend an oral food challenge in a
controlled setting to confirm the allergic response from consuming the suspected foods. The
oral food challenge (OFC) consists of consuming escalating levels of the suspect food,
(usually mixed in applesauce or controlled baked goods), until either a reaction manifests or
until the challenge is complete with no reaction. The food challenge process poses
significant risk to the patient. In 5% of cases, the patient experiences a severe allergic
response which requires the use of epinephrine.2,3 These responses typically consist of
severe reactions in GI or respiratory and arise from challenging patients with higher doses
of food allergen then is necessary to prove a mild allergic response. The reason an allergist
would give an increased dose that the patient reacts to with severity results from
misdiagnosing the mild forms of the reaction during the titrated challenge. It is this
shortcoming in diagnosis that could be addressed by identifying high-risk patient populations
through conjunctival allergen challenge and through the development of additional objective
diagnostic endpoints.

We hypothesize that conjunctival allergen challenge (CAC) may be able to predict which
patients are likely to experience an adverse event during a food allergen challenge. The
appearance of severe ocular response following CAC (level II on a 0-2 Scale) has been shown
to correlate well with a positive food response during escalating food challenge, and
represented a better predictor of food allergen than skin test and serum specific IgE
combined.4 We hypothesize that the severity of the ocular response to CAC titration, or the
appearance of related non-ocular signs and symptoms of systemic response to CAC (itchy
palate, wheezing, FEV1 reduction) could correlate with the likelihood of experiencing a
severe adverse event during food challenge. In order to mitigate the occurrence of severe
adverse events during food challenge, and to determine if the CAC response can serve as a
useful tool for informing the clinician of anticipated patient response patterns to oral food
allergen challenge, we will perform CAC titration on a population of food allergy patients
that previously underwent oral food escalating challenge. Any patterns in CAC response will
be compared to historical food allergen reactivity and occurrence of severe adverse responses
to evaluate the potential of the CAC as a predictive tool that could add value to the oral
food challenge model.

Inclusion Criteria:

- Be male or female of any race, at least 5 years of age with documented food challenge
in the past 12 months;

- Have provided verbal and written informed consent. If under 18, a parent/guardian must
provide consent for the subject;

- Negative pregnancy test for women of childbearing potential;

- Be willing and able to follow instructions, including participation in study
assessments, and can be present for the required study visits for the duration of the
study;

Exclusion Criteria:

- Be a woman who is pregnant or nursing an infant;

- Be unable to discontinue short-acting antihistamines for three days or long-acting
antihistamines for five to seven days (depending on half-life) prior to CAC;

- Have asthma that has evolved and now fulfills any of the criteria defined as follows:

1. uncontrolled persistent asthma by National Asthma Education and Prevention
Program Asthma guidelines (2007) or by Global Initiative for Asthma (2011) or
being treated with combination therapy of medium dose inhaled corticosteroid with
a long acting inhaled β2-agonists.

2. at least two systemic corticosteroid courses for asthma in the past year or one
oral corticosteroid course for asthma in the past three months.

3. prior intubation for asthma in the past year;

- Be receiving β-blocking agents, angiotensin-converting enzyme inhibitors,
angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant
therapy;

- Be receiving or planning to receive anti-tumor necrosis factor drugs or anti-IgE drugs
(such as omalizumab) or any biologic immunomodulatory therapy;

- Be receiving or planning to receive any type of immunotherapy to any food (e.g. oral
immunotherapy, sublingual immunotherapy, specific oral tolerance induction) during
their participation in the study;

- Be receiving or planning to receive any aeroallergen immunotherapy during their
participation in the study;

- Be suffering from generalized dermatologic disease (e.g. severe atopic dermatitis,
uncontrolled generalized eczema, ichthyosis vulgaris);

- Have any new disorder in which epinephrine is contraindicated such as coronary artery
disease, uncontrolled hypertension, or serious ventricular arrhythmias;

- Have experienced severe anaphylaxis resulting in emergency hospitalization;