title: Impact of the Arg 16 allele of the B2AR gene on the effect of withdrawal of LABA in patients with moderate to severe asthma.
abstract: BACKGROUND
  Long-acting beta agonists (LABAs) are effective for controlling asthma, however questions about their safety have led to concerns over use. Genetic polymorphisms at the 16 amino acid position of the beta-2 adrenergic receptor gene (B2AR) may be associated with increased risk.
  
  
  METHODS
  A randomized, double blind study was conducted in patients with moderate to severe asthma being treated with combined inhaled corticosteroids/LABA (ICS/LABA), comparing the effect of LABA continuation versus withdrawal on asthma outcomes among patients stratified by B2AR genotype (Arg/Arg vs. Gly/Gly at the 16th amino acid position).
  
  
  RESULTS
  67 participants (31 Arg/Arg, 36 Gly/Gly) were randomized to receive fluticasone alone (F) or continue combined fluticasone/salmeterol (F/S) after a run-in period on F/S. Among Gly/Gly subjects, those in the F/S treatment group showed improvement in AM PEFR (+ 8.4 L/s) whereas those receiving F alone experienced a reduction in AM PEFR over the study period (-14.4 L/s), (p = 0.06). There was no significant difference in morning peak expiratory flow rate (AM PEFR) in Arg/Arg participants randomized to receive F/S (-15.7L) vs F alone (-5.6 L/s) (p = 0.61). There was no significant difference in exacerbations in the Arg/Arg subjects treated with F/S compared with those treated with F (p = 0.65).
  
  
  CONCLUSIONS
  Withdrawal of LABA therapy in asthmatics with the Arg/Arg genotype at the 16th amino acid position of B2AR did not lead to significant improvement in AM PEFR. LABA withdrawal in the Gly/Gly genotype however led to a borderline significant decline in AM PEFR.
authors.affiliation: a Department of Medicine , Columbia University , New York , NY , USA.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Slankard
authors.affiliation: b Department of Medicine and Pediatrics , Hackensack University Medical Center , Hackensack , NJ , USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Michelis
authors.affiliation: c Department of Pathology , Columbia University , New York , NY , USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mansukhani
authors.affiliation: d Hackensack University Medical Center , Department of Medicine , Hackensack , NJ , USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: McGoey
authors.affiliation: e Mailman School of Public Health , Columbia University , New York , NY , USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Paige
authors.affiliation: e Mailman School of Public Health , Columbia University , New York , NY , USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Andrews
authors.affiliation: a Department of Medicine , Columbia University , New York , NY , USA.
authors.forename: David
authors.initials: D
authors.lastname: Lederer
authors.affiliation: a Department of Medicine , Columbia University , New York , NY , USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Canfield
authors.affiliation: a Department of Medicine , Columbia University , New York , NY , USA.
authors.forename: Emily
authors.initials: E
authors.lastname: DiMango
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000483:Alleles; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D000068299:Salmeterol Xinafoate / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D001120:Arginine; D000068298:Fluticasone; D005998:Glycine
keywords: Pharmacotherapy; genetics/genotypes; management/control; quality of life; treatment