EFFECTS OF LONG-ACTING AND SHORT-ACTING BETA-AGONISTS ON METHACHOLINEDOSE-RESPONSE CURVES IN ASTHMATICS

Regular use of short-acting beta-agonists may decrease control of asth ma and increase airway responsiveness to bronchoconstrictor stimuli. T he aim of this study was to determine the effects of regular treatment with the long-acting beta-agonist, salmeterol, on the methacholine do se-response curve (DRC) in mild-to-moderate asthmatics. Changes in met hacholine airway responsiveness were measured in 14 stable adult asthm atics, randomized in a double-blind, three-way cross-over design to re ceive salmeterol 50 mu g, salbutamol 200 mu g or placebo, each twice d aily for 4 days. Two baseline methacholine DRC, mere performed, one wi thout premedication and one following a single dose of 200 mu g salbut amol. Following 4 days of regular treatment, methacholine DRC to plate au were carried out commencing 15 min after the final dose of trial me dication. There were no significant differences in mean baseline force d expiratory volume in one second (FEV(1)) between treatments. Four da ys treatment with salmeterol and salbutamol shifted the DRC to the rig ht, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling d oses, respectively, compared to placebo (p less than or equal to 0.001 ), and the provocative concentration of methacholine required to produ ce a 20% fall in FEV(1) (PC20) increased 1.6 and 3.1 doubling doses, r espectively (p less than or equal to 0.001). The slope of the DRC was increased slightly by both beta-agonists compared to placebo (log slop e 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respecti vely). This effect of regular salmeterol on slope was more marked in s ubjects with lower baseline FEV(1). Maximal response plateaus did not differ between the three treatments.These results suggest that regular use either of short- or long-acting beta-agonists could increase the risk, of a more precipitous asthma episode associated with ''breakthro ugh'' bronchoconstrictor responses, particularly in those with more se vere initial airflow obstruction, if subjects are exposed to a suffici ently potent stimulus.