A comparative study in atopic subjects with asthma of the effects of salmeterol and salbutamol on allergen-induced bronchoconstriction, increase in airway reactivity, and increase in urinary leukotriene E4 excretion

Abstract Salmeterol (SM) is a novel β 2 -adrenoceptor agonist with a duration of action in excess of 12 hours. Evidence from in vitro studies has also demonstrated that, unlike the short-acting β 2 -agonists, such as salbutamol (SB), it may have some anti-inflammatory properties. With a randomized, double-blind, crossover design, we have compared the inhibitory effects of SM (50 μg) and SB (200 μg) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E 4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both β 2 -agonists ( p 1 at 15 minutes after allergen (percent fall in FEV 1 , mean ± SEM: 6.2 ± 4.9, SM; 5.7 ± 2.5, SB; 40.4 ± 6.3, placebo) or the area under the FEV 1 time curve (AUC) for the first 120 minutes after allergen. Four hours after challenge, results in the SB-treated and placebo-treated groups were not significantly different and demonstrated a small persistent bronchoconstriction compared to bronchodilatation in the SM-treated group (percent fall in FEV 1 , respectively, 9.3 ± 3.7, 14.3 ± 7.1, and −6.3 ± 2.7; p p p p p 4 excretion for either the 0 to 120-, 120 to 240-, or total 0 to 240 minute collection periods after allergen inhalation ( p > 0.1). Therefore, although both drugs have inhibitory effects on allergen-induced bronchoconstriction, neither drug significantly reduced allergen-induced cysteinyl leukotriene production. This finding suggests that the major effect of inhaled β 2 -agonists in allergen challenge is relaxation of airway smooth muscle and not the inhibition of mediator release from pulmonary inflammatory cells.