Beta-adrenergic receptor polymorphisms associated with length of ICU stay in pediatric status asthmaticus

摘要

Background During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous β 2- adrenergic receptor (ADRβ 2) agonist therapy. Genetic polymorphisms have been identified within the ADRβ 2 that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADRβ 2 agonist treatment during severe asthma exacerbations in children. Methods Children aged 2-18 years admitted to the ICU (intensive care unit) with a severe asthma exacerbation between 2006 and 2008 were eligible. Genotyping of the ADRβ 2 was performed. Results Eighty-nine children consented and were enrolled. Despite similar clinical asthma scores on admission, children with the Gly 16Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) and hospital LOS, compared to children with Arg 16Arg and Arg 16Gly genotypes. Children with either the Gln 27Glu or Glu 27Glu genotype at amino acid position 27 also had significantly shorter ICU LOS and hospital LOS compared to children with the Gln 27Gln genotype. The Arg 16Gly-Gln 27Gln haplotype was associated with the longest ICU LOS, but this was not statistically different from other haplotypes. Conclusions In this cohort of children with severe asthma exacerbations, ADRβ 2 polymorphisms were associated with responses to therapy. Knowledge of the genetic profile of children with asthma may allow for targeted therapy during acute exacerbations.