Children vary significantly in their response to high-dose continuous β2-adrenergic receptor (ADRβ2) agonist therapy given during severe asthma exacerbations. Genetic polymorphisms have been identified within the ADRβ2 that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with response to ADRβ2 agonist treatment during severe asthma exacerbations in children.
We conducted a prospective observational study of all children admitted to the ICU with a severe asthma exacerbation between 2006–2008. Children were treated with guidelines that titrated ADRβ2 agonist therapy (first nebulized, then intravenous) according to a validated clinical asthma score. Genetic samples were obtained via saliva or blood sampling.
Eighty-nine consecutive children were enrolled. At amino acid position 16, 25 children (28%) were homozygous for the Gly allele (Gly16Gly), 13 children (15%) were homozygous for the Arg allele (Arg16Arg), and 51 children (57%) were heterozygous (Arg16Gly). At amino acid position 27, 50 children (56%) were homozygous for the Gln allele (Gln27Gln), 5 children (6%) were homozygous for the Glu allele (Glu27Glu), and 34 children (38%) were heterozygous (Glu27Gln). Despite similar clinical asthma scores on admission, children with the Gly16Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) (47 ± 34 vs. 91 ± 128 hours; p=0.015) and hospital LOS (93 ± 54 vs. 157 ± 180 hours; p=0.01), compared to children with Arg16Arg and Arg16Gly genotypes. Children with the Gln27Glu genotype also had significantly shorter ICU LOS (50 ± 40 vs. 102 ± 144 hours; p=0.02) and hospital LOS (99 ± 54 vs. 172 ± 205 hours; p=0.02) compared to children with the Gln27Gln genotype. The Arg16Gly-Gln27Gln haplotype was associated the longest ICU LOS (124 ± 177 hours), but this was not statistically significant.
ADRβ2 polymorphisms are related to response to therapy in children admitted to the ICU with severe asthma exacerbations.
Knowledge of a child's genotype could allow for personalized therapy in this population.
Christopher Carroll, No Financial Disclosure Information; No Product/Research Disclosure Information