NULL HYPOTHESIS

The regularly scheduled administration of inhaled albuterol or placebo (2 puffs four times a day) will have similar effects on asthma control, as defined by AM PEF, in patients with mild to moderate asthma who bear the B16-Arg/Arg genotype or the B16-Gly/Gly genotype at the ß₂-adrenergic receptor.

DESIGN

Patients with mild asthma, not using a controller medication, were enrolled in FEV₁-matched pairs based on whether they harbored the Arg/Arg or Gly/Gly genotype. Regularly scheduled treatment with albuterol or placebo was administered, in a blinded, crossover, fashion, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. AM PEF was the primary outcome indicator. The primary comparisons were between treatments within each genotype and the secondary outcome was a treatment-by-genotype effect.

RESULTS

Enrollment for the BARGE trial began in August 1999 and the last patient visits occurred in July 2002. There were 78 randomized patients (37 Arg/Arg and 41 Gly/Gly). Patients with the Gly/Gly genotype had an increase in AM peak flow during treatment with regularly scheduled albuterol as compared with placebo, 14 L/min (3-25; p = 0.0175). Patients with the Arg/Arg genotype had decreased AM peak flow during treatment with albuterol as compared to treatment with placebo, –10 L/min (−19- −2, p = 0.0209). The treatment-by-genotype interaction was −24 L/min (−37- −12, p = 0·0003). Similar genotype-specific effects were observed in FEV₁, and symptoms. Thus, genotype at the 16^th amino acid locus of the b₂-adrenergic receptor affects the long-term response to albuterol use. These data suggest that bronchodilator treatments avoiding albuterol may be appropriate for patients bearing the Arg/Arg genotype. The major publication appeared in Lancet:

Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, Deykin A, Fagan JK, Fahy JV, Fish J, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF, Jr, Liggett SL, Martin RJ, Mitra N, Peters SP, Silverman E, Sorkness CA, Szefler SJ, Wechsler ME, Weiss ST, Drazen JM. Genotype stratified prospective cross-over trial of regularly scheduled albuterol treatment in asthma. Lancet 2004; 364:1505-1512.