Repeatability of response to asthma medications

Abstract

Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients; however, no formal studies have demonstrated this. To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, FEV(1), and PC(20). The Childhood Asthma Management Program was a multicenter clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over a period of 4 years in the Childhood Asthma Management Program by using mixed-effects regression models. We adjusted for the covariates age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV(1) was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC(20) was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. The within-treatment group repeatability of FEV(1) and PC(20) is high; thus, these phenotypes are heritable. FEV(1) and PC(20) may be better phenotypes than bronchodilator response for studies of treatment response in asthma.