Am. J. Respir. Crit. Care Med.,
Volume 156, Number 3, September 1997, 988-991
Effect of Regular Salmeterol Treatment on
Albuterol-induced Bronchoprotection in Mild Asthma
DEBORAH H.
YATES,
MIIN
WORSDELL,
and
PETER J.
BARNES
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom
There is increasing evidence for the development of tolerance to the bronchoprotective effects of
inhaled 
2-agonists against bronchoconstrictor stimuli in asthma. With short-acting 2-agonists, this
is more readily demonstrable using indirectly acting agents such as adenosine monophosphate
(AMP), which may act via mast cell degranulation, than using methacholine (MCh), implying more rapid mast cell than smooth muscle desensitization. Desensitization may be greater with the long-acting 2-agonist, salmeterol, given its greater duration of receptor occupancy. In a double-blind, placebo-controlled crossover study, we investigated the effect of regular salmeterol on the protection
conferred by albuterol using MCh- and AMP-induced bronchoconstriction. Sixteen mild asthmatic subjects not using inhaled glucocorticoids were randomized to treatment for 2 wk with inhaled salmeterol (50 µg b.i.d. via diskhaler) or identical placebo. Provocative concentrations of MCh and AMP causing a 20% fall in FEV1 (PC20) were measured 15 min after 200 µg albuterol, both before and after
treatment. Mean MCh PC20 after albuterol decreased significantly after 2 wk of salmeterol treatment (mean 2.2 mg/ml before to 1.1 ± 1.2 mg/ml after) compared with placebo (2.9 ± 1.3 mg/ml before
to 2.6 ± 1.3 mg/ml after; p < 0.05), but this fell just short of statistical significance when analyzed as
change in doubling dilutions (1.1 ± 0.4 versus 0.18 ± 0.4; p = NS). Mean PC20 to AMP was not significantly affected (mean 27.5 ± 1.5 mg/ml prior to salmeterol treatment and 9.5 ± 1.5 mg/ml after
treatment; p = NS compared with placebo). Thus, regular salmeterol treatment led to loss of bronchoprotection by albuterol to MCh but not to AMP challenge, implying an absence of mast cell 2-adrenoceptor downregulation with regular salmeterol therapy.
