There is a critical need for validated objective biomarkers that predict therapeutic response for asthma therapies in children. Children who require daily asthma treatment with a controller medication such as an inhaled steroid are defined to have persistent asthma. Approximately 60% of children with asthma in the United States have persistent disease. Variability in treatment response to standard guideline supported medications (e.g. inhaled steroids, leukotriene modifiers, mono-clonal antibodies) exist among children with persistent asthma. Clinical markers such as IgE level, exhaled nitric oxide level, eosinophil and neutrophil counts have not been validated to predict treatment response to asthma medications in children. It is not possible to optimize currently available treatments for asthma in achieving therapeutic efficacy and limiting exposure to adverse effects from non-efficacious medications without robust non-invasive biomarkers that can drive therapeutic decision making. The long-term goal is to advances and improve therapeutic intervention for pediatric patients with asthma. The objective in this particular application is to establish the utility of Histamine Iontophoresis with Laser Doppler monitoring (HILD) as biomarker for accurate prediction of therapeutic response to low cost and low side-effect antihistamine treatment in children with allergic asthma. The central hypothesis is that ?HILD is predictive of treatment response to an antihistamine in children with asthma?. This hypothesis has been formulated by the applicant's strong preliminary data and supporting literature. The rationale for the proposed research is that HILD is able to identify distinct histamine pharmacodynamic response types that predict treatment response to antihistamine medications in asthma. Guided by strong preliminary data, this hypothesis will be tested by two specific aims: 1) to determine HILD prediction of therapeutic response to an antihistamine among children with allergic asthma; 2) to develop a robust predictive model of therapeutic response to an antihistamine among children with allergic asthma.
The first aim will compare change in Asthma Control Test (ACT) scores by histamine response type in a six week, 2x2 cross-over, add-on trial of Levocetirizine (LTZ) among children with uncontrolled allergic asthma.
The second aim will determine the best predictive model (incorporating HILD and clinical variables) for change in ACT scores after LTZ treatment among children with allergic asthma. The proposed research is significant because it has the potential to alter the current treatment paradigms for children with asthma where response to treatment is predicted a priori; and is innovative in testing and validating a first biomarker accurately predicting response to an asthma treatment in children. The knowledge gained will make available the first validated biomarker to predict treatment response in children with asthma and will improve therapeutic efficacy and outcomes in these children.
These studies will validate and test Histamine Iontophoresis with Laser Doppler monitoring in the prediction of treatment response to an antihistamine in pediatric asthma. These studies will validate the first biomarker for use in guiding asthma treatment in children. The success of this research will allow personalized guidance to asthma treatment and ultimately lead to overall improved asthma outcomes in children.
