Effect of long-term salmeterol treatment on exercise-induced asthma.
BACKGROUND
With long-term administration of salmeterol, the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease. Whether this effect extends to a clinically relevant stimulus such as exercise is unknown.


METHODS
We performed a random-order, double-blind, crossover trial in 20 patients with exercise-induced asthma. Each patient received inhaled salmeterol or placebo twice daily for a month, with a one-week washout period between treatments. The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st, 14th, and 29th study days. The primary end point was the extent of the decrease in forced expiratory volume in 1 second (FEV1) 10 minutes after exertion.


RESULTS
With placebo, significant airway narrowing developed at all times (mean [+/-SE] decrease from base line in FEV1, 19+/-2 percent in the morning and 18+/-2 percent in the evening). The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times (decrease in FEV1 on day 1, 5+/-2 percent; on day 14, 10+/-3 percent; and on day 29, 9+/-3 percent; P=0.10). Its ability to act throughout the day, however, decreased with long-term administration (decrease in FEV1 from morning to evening on day 1, 6+/-2 percent; on day 14, 15+/-3 percent; and on day 29, 14+/-3 percent; P=0.003).


CONCLUSIONS
Protection against exercise-induced asthma is maintained with long-term administration of salmeterol, but the length of time that the drug remains active after a single dose decreases.
Nelson
J A
JA
Division of Pulmonary and Critical Care Medicine, University Hospitals of Cleveland, OH 44106-5067, USA.
Strauss
L
L
Skowronski
M
M
Ciufo
R
R
Novak
R
R
McFadden
E R
ER
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001250:Asthma, Exercise-Induced / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D000068299:Salmeterol Xinafoate; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol