Loss of Salmeterol Bronchoprotection against Exercise in Relation to ADRB2 Arg16Gly Polymorphism and Exhaled Nitric Oxide

Rationale: β2-Agonists are the treatment of choice for exercise-induced bronchoconstriction (EIB) and act through specific receptors (ADRB2). Arg16Gly polymorphisms have been shown to affect responses to regular use of β2-agonists.Objectives: To evaluate the influence of the Arg16Gly receptor polymorphism on salmeterol bronchoprotection in EIB and assess predictors of bronchoprotection.Methods: A prospective, genotype-blinded, randomized trial was performed in 26 subjects (12 Arg16Arg and 14 Gly16Gly) with EIB who were not on controller therapy. Subjects were administered salmeterol, 50 μg twice a day for 2 weeks, and underwent an exercise challenge 9 hours after the first and last drug dose. In addition to genotype, FEV1, response to salmeterol, degree of EIB, and exhaled nitric oxide (FeNO) at baseline were examined for their association with loss of bronchoprotection (LOB).Measurements and Main Results: The maximum exercise-induced FEV1 fall was 27.9 ± 1.4% during the run-in period, 8.1 ± 1.2% (70.3 ± ...