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Genetics of the Beta-Adrenergic Receptor and Response to Albuterol in Children With Bronchiolitis FREE TO VIEW

Christopher L. Carroll, MD; Kathleen A. Sala, MPH; Aaron R. Zucker, MD; Craig M. Schramm, MD
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Connecticut Children’ s Medical Center, Hartford, CT

Chest. 2010;138(4_MeetingAbstracts):869A. doi:10.1378/chest.9840
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PURPOSE: Bronchiolitis is a common cause of critical illness in children. Despite no clear evidence of their efficacy, inhaled bronchodilators, such as β2-adrenergic receptor (ADRβ2) agonists, are frequently used as part of treatment. Our hypothesis was that genotypic differences within the ADRβ2 are associated with response to ADRβ2 agonist treatment in children with bronchiolitis.

METHODS: We conducted a prospective study of 54 children mechanically ventilated for bronchiolitis between 2007-2010. Before and for 30 minutes following scheduled albuterol treatment, sequential measurements of pulmonary resistance (Rrs) were made using the interrupter technique on repeated consecutive breaths. A positive response to albuterol was defined as having an improvement in Rrs > 30% of baseline. Genotype of the ADRβ2 was determined using DNA obtained from blood samples.

RESULTS: At amino acid position 16, 26 children (48%) were homozygous for the Gly allele (Gly16Gly), 6 children (11%) were homozygous for the Arg allele (Arg16Arg), and 22 children (44%) were heterozygous (Arg16Gly). At amino acid position 27, 19 children (35%) were homozygous for the Gln allele (Gln27Gln), 7 children (13%) were homozygous for the Glu allele (Glu27Glu), and 28 children (52%) were heterozygous (Gln27Glu). Measurements of pulmonary mechanics were assessed a median of 27 hours following intubation (range 2-71 hours), using a median of 360 mcg albuterol (range 360-900 mcg) delivered via MDI. Fourteen (26%) of the 54 children responded to albuterol treatment. There were no significant differences in the age, gender, race or ethnicity between the responders and non-responders. However, children with the Glu/Glu genotype were significantly more likely to respond to albuterol than children of other genotypes (OR 5.0; 95% CI 1.0-25.7; p=0.04).

CONCLUSION: Children with the Glu/Glu genotype of the ADRβ2 were 5 times more likely to respond to albuterol during acute bronchiolitis.

CLINICAL IMPLICATIONS: Some of the variation in response to albuterol during acute bronchiolitis may be explained by ADRβ2 polymorphisms.

DISCLOSURE: Christopher Carroll, No Financial Disclosure Information; No Product/Research Disclosure Information

08:00 AM - 09:15 AM




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