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 E 4 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 < 0.005), when reduction was expressed either in terms of maximum fall in FEV 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 < 0.005, SM versus SB; p < 0.02, SM versus placebo). Expressed in terms of AUC, only SM significantly reduced bronchoconstriction in the period 120 to 240 minutes after allergen ( p < 0.01). The changes in airway reactivity 4 hours after allergen were (doubling doses of histamine, median, and range) −1.34 (−4.06 to 0.56) placebo; −0.20 (−3.29 to 1.14) SB; and 1.39 (−1.22 to 5.60) SM ( p < 0.005, SB and SM versus placebo; p < 0.005, SM versus SB). There were no differences between groups in urinary LTE 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.