Predictors of poor response during asthma therapy differ with definition of outcome.
OBJECTIVE
To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma, based independently on lung function changes or asthma exacerbations.


METHODS
We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children (aged 5-12 years) randomized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program (CAMP).


RESULTS
Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response. A history of prior asthma exacerbations, younger age and a higher IgE level (p < 0.05) are associated with recurrent exacerbations. By contrast, lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206C in FCER2 (p < 0.05) are associated with poor lung function response. Poor lung function response does not increase the risk of exacerbations and vice versa (p = 0.72).


CONCLUSIONS
Genetic and phenotypic predictors of a poor long-term response to inhaled corticosteroids differ markedly depending on definition of outcome (based on exacerbations vs lung function). These findings are important in comparing outcomes of clinical trials and in designing future pharmacogenetic studies.
Rogers
Angela J
AJ
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. reajr@channing.harvard.edu
Tantisira
Kelan G
KG
Fuhlbrigge
Anne L
AL
Litonjua
Augusto A
AA
Lasky-Su
Jessica A
JA
Szefler
Stanley J
SJ
Strunk
Robert C
RC
Zeiger
Robert S
RS
Weiss
Scott T
ST
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics*; D012008:Recurrence; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D000099052:CRF Receptor, Type 1
D000305:Adrenal Cortex Hormones; C546930:FCER2 protein, human; D037181:Lectins, C-Type; D018019:Receptors, Corticotropin-Releasing Hormone; D017455:Receptors, IgE; D000099052:CRF Receptor, Type 1