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BETA-ADRENERGIC RECEPTOR POLYMORPHISMS AFFECT RESPONSE TO TREATMENT FOR PEDIATRIC STATUS ASTHMATICUS

Connecticut Children's Medical Center, Hartford, CT

PURPOSE: ß2-adrenergic receptor (ß2-AR) agonists are the most important group of drugs used in the treatment of acute asthma exacerbations. Previous studies have found that genotypic differences in the ß2-AR, particularly at amino acid positions 16 and 27, affect response to chronic and single dose ß2-AR agonist therapy. Our hypothesis was that genotypic differences also contribute to response to acute ß2-AR agonist treatment during acute asthma exacerbations in children.

METHODS: Children admitted to the ICU for status asthmaticus between 2002-2005 were contacted and genetic samples obtained via saliva. Children hospitalized during this period had been treated with a protocol that titrated ß2-AR therapy (first nebulized, then intravenous) according to clinical asthma score. The charts of those who provided samples were retrospectively reviewed. Genotyping of the ß2-AR gene was performed by restriction fragment length polymorphism.

RESULTS: Thirty-two children hospitalized in the ICU during the study period were enrolled. At amino acid position 16, thirteen children were homozygous for the Gly16 allele (Gly/Gly), seven children were homozygous for the Arg16 allele (Arg/Arg), and 12 children were heterozygous (Arg/Gly). Despite similar clinical asthma scores on admission, children with the Gly/Gly genotype had significantly shorter ICU length of stay (43 ± 25 vs. 76 ± 37 hours; p=0.01), duration of continuous albuterol therapy (3.0 ± 0.9 vs. 5.2 ± 2.0 days; p=0.002), and were significantly less likely to require IV ß2-AR therapy (31% vs. 74%; p=0.02) compared to children with Arg/Arg and Arg/Gly genotypes. There was no association between polymorphisms at amino acid position 27 (Glu27Gln) and response to ß2-AR therapy during acute exacerbations. Haplotype analysis was also not significant.

CONCLUSION: Children homozygous for the Gly16 allele had a more rapid response to ß2-AR agonist treatment received during an acute exacerbation. A child's ß2-AR genotype significantly affected the response to acute ß2-AR agonist therapy.

CLINICAL IMPLICATIONS: Knowledge of a child's genotype could significantly impact treatment received for severe asthma exacerbations.

DISCLOSURE: Christopher Carroll, None.