Abstract
We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was used to determine the reliability of phenotype classification. Eighty-two percent of children exhibited a reliable histamine response phenotype [intraclass correlation coefficient 0.77 (95% CI 0.44–0.93]. These preliminary results suggest moderate reliability of HILD response phenotype in children. Further exploration is needed to determine contributions to phenotype variability.
Highlights
Histamine is a small molecule that is released by various cells throughout the body
The amine is most commonly associated with the allergic response whereby when binding to the Histamine-1 receptor (H1R) it sets off a cascade of responses that lead to itching, sneezing, mucous production, and bronchoconstriction
Nineteen children with asthma and/or allergic rhinitis were enrolled for this study
Summary
Histamine is a small molecule that is released by various cells throughout the body. Recently histamine has been discovered to have pervasive effects throughout the body which include the respiratory system, gastrointestinal tract, central nervous system, bone marrow, cardiovascular system, genitourinary system, as well as immunoregulatory effects (Huang and Thurmond, 2008; Thurmond et al, 2008). Due to the broadened understanding of histamine, it has been suggested that the amine plays a more significant role in the pathogenesis of diseases such as asthma and atopic dermatitis than previously believed. Evidence suggests that some patients with specific asthma phenotypes may benefit from antiallergic treatment in the management of the disease more than others (Warner and ETAC Study Group, 2001).
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