Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline

Abstract

The onset of bronchoprotection as obtained by various b 2 -agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting b 2 -agonists formoterol and salmeterol and the shortacting b 2 -agonist terbutaline were measured.Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 mg Turbuhaler1), salmeterol (50 mg Diskus1), terbutaline (500 mg Turbuhaler1) or placebo.Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (pv0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (pv0.05).These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three b 2 -agonists.

Paradoxal effect of salbutamol in an in vitro model of bronchoprotection

“…Inhaled β 2 ‐agonists are widely prescribed in the treatment of asthma and are the most effective bronchodilator on human airways [1,2]. In addition to their bronchodilator effect, bronchoprotective properties have also been demonstrated against various stimuli including exercise [3], cold air, methacholine or histamine‐induced bronchoconstriction [4]. The interest in this bronchoprotective effect of β 2 ‐agonists has grown with the introduction of long acting β 2 ‐agonists such as salmeterol or formoterol [5,6] that are taken morning and evening to prevent an asthma crisis.…”

Onset and Duration of Action of Formoterol and Tiotropium in Patients with Moderate to Severe COPD

“…Formoterol has a fast onset of action, in both asthma [2, 3] and COPD [4,] with a 12-hour effect on spirometry [5, 6]. Studies with the long-acting anticholinergic compound tiotropium demonstrated that an 18-µg dose is safe and provides effective bronchodilation suitable for maintenance therapy in COPD with once-daily dosing [7,8,9,10].…”

Prevention of Exercise-induced Asthma by a Fixed Combination of Disodium Cromoglycate plus Reproterol Compared with Montelukast in Young Patients

“…Being conservative, we hypothesised that the combination of DSCG/REP would be superior to MON even when comparing with the last level pre-exercise, although the reliever (reproterol) might have already enlarged the airways after inhalation at that time. In fact, this "adjusted approach" was also chosen sometimes in the literature on EIA, particularly if the duration of the effect was assessed [22][23][24]. However, other investigations [9,25] used the last value pre-inhalation as baseline (unadjusted approach).…”