Repeatability of response to asthma medications.
BACKGROUND
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.


OBJECTIVE
To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, FEV(1), and PC(20).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wu
Ann Chen
AC
Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Mass, USA.
Tantisira
Kelan
K
Li
Lingling
L
Schuemann
Brooke
B
Weiss
Scott
S
D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D019819:Budesonide