Cross-tolerance to albuterol occurs independently of β 2-adrenoceptor genotype-16 in asthmatic patients receiving regular formoterol or salmeterol

Abstract

Rationale We evaluated the Arg-16 and Gly-16 genotypes for the acute albuterol response following methacholine challenge, after the first and last doses of combination inhalers containing formoterol (FM) and salmeterol (SM). Methods Parallel groups of matched 10 homozygous Arg-16 and 10 homozygous Gly-16 asthmatics completed a randomized, double-blind, double-dummy, cross-over study. During a 1-week washout period prior to each randomized treatment, patients continued on their usual inhaled corticosteroid therapy. Patients received 2 weeks of either budesonide (BUD) 200 μg + FM 6 μg, 2 puffs bid, or fluticasone propionate (FP) 250 μg + SM 50 μg, 1 puff bid. After washouts and randomized treatments, 1 hour post first and last dose of combination inhalers, a methacholine challenge was performed followed by albuterol 200 μg, with recovery over 30 minutes (the primary outcome). Results Washout values for FEV 1, methacholine PC 20 and albuterol recovery were all similar for both treatments and genotypes. Pre-challenge FEV 1 values for both genotypes were not significantly different comparing first vs. last doses of each treatment. Albuterol recovery as area under the 30-minute time-response curve (%.min) was significantly delayed ( p<0.05) equally in both genotypes and treatments, comparing the first doses of BUD+FM (Arg-16: 386, Gly-16: 352) or FP+SM (Arg-16: 363, Gly-16: 289), vs. the last doses respectively of BUD+FM (Arg-16: 591, Gly-16: 491) or FP+SM (Arg-16: 529, Gly-16: 466). There were no differences in albuterol recovery comparing either genotypes or treatments. Conclusion Acute albuterol recovery in methacholine constricted airways was significantly delayed to a similar degree in both genotypes, due to cross-tolerance induced by FM or SM.