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

Salmeterol (SM) is a novel beta(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 beta(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-mu-g) and SB (200-mu-g) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both beta(2)-agonists (p < 0.005), when reduction was expressed either in terms of maximum fall in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/- 4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 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 FEV1, 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 LTE4 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 beta(2)-agonists in allergen challenge is relaxation of airway smooth muscle and not the inhibition of mediator release from pulmonary inflammatory cells.