Repeatability of response to asthma medications

BackgroundPharmacogenetic 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.ObjectiveTo determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, FEV1, and PC20.MethodsThe 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.ResultsThe 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 FEV1 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 PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates.ConclusionThe within–treatment group repeatability of FEV1 and PC20 is high; thus, these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma.