Comparison of the dose response to levalbuterol with and without pretreatment with S-albuterol after methacholine-induced bronchoconstriction.
OBJECTIVE
To determine the effect of S-albuterol on the dose response to levalbuterol in patients with moderate bronchoconstriction induced by a methacholine challenge.


METHODS
Prospective, randomized, double-blind, placebo-controlled, crossover study.


METHODS
University-affiliated clinical trial center.


METHODS
Twenty-two adults with mild, stable asthma.


METHODS
At the screening visit, patients were switched from their beta2-agonist to ipratropium bromide for use as an as-needed rescue therapy. At the baseline visit 2-6 days later, the provocative concentration of methacholine to induce a 30% decrease in forced expiratory volume in 1 second (FEV(1) PC(30)) was determined, followed by a nebulized racemic albuterol dose-response study with three doses of albuterol, to familiarize patients with the procedures. At visits 2 and 3, patients were randomly assigned to receive nebulized normal saline placebo or S-albuterol 5 mg before the methacholine challenge and were administered three escalating doses of levalbuterol after the challenge.


RESULTS
Area under the curve for FEV(1) over 40 minutes (AUC(0-40)) after administration of levalbuterol was the primary outcome, with slope of FEV(1) as the secondary outcome. In addition, the fraction of exhaled nitric oxide (FeNO) was measured before and after the challenges. In the 17 patients who met criteria for completion, no deleterious effect for S-albuterol was found for FEV(1) PC(30), AUC(0-40) FEV(1), or the FEV(1) slope(0-40). However, S-albuterol reduced the provocative concentration of methacholine to induce a 20% decrease in FEV(1) (PC(20) 0.52 +/- 2.06 vs 0.39 +/- 1.58 mg/ml, placebo vs S-albuterol, p=0.044) but did not affect FeNO.


CONCLUSIONS
A single high dose of S-albuterol did not alter the bronchodilator response to levalbuterol. The effect on bronchial responsiveness requires further study.
Raissy
Hengameh H
HH
School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA.
Harkins
Michelle
M
Esparham
Anna
A
Kelly
H William
HW
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy*; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004336:Drug Antagonism; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use; D016210:Methacholine Chloride; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011446:Prospective Studies; D013237:Stereoisomerism
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D016210:Methacholine Chloride; D009569:Nitric Oxide; D009241:Ipratropium; D000420:Albuterol