title: Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting β2-agonists: results of the PACMAN cohort.
abstract: BACKGROUND
  Current evidence suggests that asthma patients with the ADRB2 Arg16 genotype have a poorer response to long-acting β2-agonists (LABA), but the results remain inconsistent.
  
  
  OBJECTIVE
  This study assessed the association between Arg16 variants and treatment outcome in children treated with inhaled corticosteroids (ICS) and LABA.
  
  
  METHODS
  ADRB2 Arg16 was genotyped in 597 children (4-12 years of age) participating in the PACMAN cohort study. A questionnaire was used to assess asthma control, frequency of asthma-related emergency department visits and use of oral corticosteroids in the past year.
  
  
  RESULTS
  Arg/Arg carriers with a reported use of ICS and LABA had an increased risk of oral corticosteroid use (odds ratio: 14.9; 95% CI: 1.59-140.1) and emergency department visits in the past year (odds ratio: 11.9; 95% CI: 1.22-115.8) compared to Gly/Gly carriers. This effect was not observed in Arg/Arg genotype carriers reporting ICS use only.
  
  
  CONCLUSIONS
  Children who are homozygous for ADRB2 Arg16 have an increased risk of exacerbations when treated with combined LABA and ICS.
authors.affiliation: Utrecht University, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherland>
authors.forename: Miranda J L
authors.initials: MJ
authors.lastname: Zuurhout
authors.forename: Susanne J H
authors.initials: SJ
authors.lastname: Vijverberg
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Raaijmakers
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Anke Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C553443:ADRB2 protein, human; D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D018343:Receptors, Adrenergic, beta-2