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with very high food allergen IgE serum titers are often excluded. Thus, food challenge studies may not include subpopulations of those allergic individuals who may be the most sensitive to allergen exposure.

Individuals with allergies to a specific food have different genetic backgrounds and express a wide distribution of sensitivity and reactivity. Studies have shown that there may be a range of as much as one-million-fold (106) in eliciting doses from the least sensitive to the most sensitive individuals (Leung et al., 2003; Wensing et al., 2002b; Bindslev-Jensen et al., 2002). Moreover, sensitivity and reactivity may change with age for individuals within a population. For example, unpublished challenge data described in Moneret-Vautrin and Kanny (2004) show that 83% of wheat allergic children reacted to less than 2 g of wheat flour compared to 18% of wheat allergic adults. Therefore, the inclusion or exclusion of data for highly sensitive individuals can greatly affect the NOAEL determination for the population. To add to this uncertainty, the most sensitive individuals also may have more severe reactions (Wensing et al., 2002b; Perry et al., 2004). The thresholds measured for populations that exclude these individuals may not apply to those with severe allergic disease.

3. Testing Materials Food challenges vary in the type of testing material used (e.g., peanut flour versus ground peanut), oral challenge vehicle (e.g., whole food versus capsules), and in the efficacy of blinding. Differences in these variables could modify the distribution or concentration of allergen within the test material, affect digestibility and absorption, influence false- positive subjective reactions, and therefore, affect interpretation of the dose-response data.

The nature of the testing material is very important, as this can enhance or diminish the overall immunogenicity of the native allergen (Beyer et al., 2001; Maleki et al., 2003). The matrix used (e.g., fatty substances) can delay absorption, thus affecting the time interval to a reaction, or may affect the intrinsic allergenic properties of the food. Also, gustatory differences in the challenge doses (because of the food matrix used) may influence subjective reactions due to poor taste or fear of consuming the allergen. The use of capsules eliminates problems caused by taste, but bypasses the oral cavity. Because the oral cavity plays an important role in the initial contact and metabolism of food allergens, this may affect the subsequent severity or character of response to the challenge dose.

4. Subjective Versus Objective Reactions There are two types of physiologic reactions or effects that can occur during a food challenge – subjective symptoms, those reported by the subject, and objective signs, those observed by the researcher. Because subjective symptoms may be the result of non-immunological mechanisms, elicitation of objective signs is believed to be the more reliable indicator of clinical reactivity to the food allergen (Taylor et al., 2004).

The signs of a severe allergic reaction are associated with life-threatening conditions, e.g., anaphylaxis. However, there is no consensus as to which of the less serious signs or

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