β2-adrenergic receptor (AR) agonists are the mainstay of treatment for severe asthma exacerbations, one of the most common causes of critical illness in children. Genotypic differences in the β2-AR gene, particularly at amino acid positions 16 and 27, have been shown to affect the response to β2-AR agonist therapy. Our hypothesis is that genotypic differences contribute to patient response to β2-AR agonist treatment during severe asthma exacerbations in children.
Children admitted to the hospital ICU for a severe asthma exacerbation between 2002 and 2005 were located, and genetic samples were obtained from saliva. Children hospitalized during this period were treated with a protocol that titrated β2-AR therapy (first nebulized, then IV) according to a validated clinical asthma score.
Thirty-seven children hospitalized during the study period were enrolled into the study. At amino acid position 16 in the β2-AR gene, 13 children were homozygous for the glycine (Gly) allele (Gly/Gly), 8 were homozygous for the arginine (Arg) allele (Arg/Arg), and 16 were heterozygous (Arg/Gly). Despite similar clinical asthma scores on hospital admission, the children with the Gly/Gly genotype had significantly shorter hospital ICU length of stay and duration of continuously nebulized albuterol therapy and were significantly less likely to require IV β2-AR therapy than those with Arg/Arg or Arg/Gly genotypes. No association existed among polymorphisms at amino acid position 27 and response to β2-AR therapy.
In this cohort of children with severe asthma exacerbations, children whose genotypes were homozygous for Gly at amino acid position 16 of the β2-AR gene had a more rapid response to β2-AR agonist treatment. The β2-AR genotype appears to influence the response to therapy in this population.