In an attempt to establish the protection afforded by regular salmeterol use against induced bronchoconstriction in asthmatic patients, a meta-analysis was conducted on nine double-blind clinical trials that fulfilled the inclusion criteria.
In each trial, subjects were randomly assigned to receive either salmeterol 50 μg twice daily or a comparator (placebo or salbutamol). Two hundred and twenty-five asthmatic subjects had at least one PC20 or PD20 (histamine or methacholine concentration or dose producing 20% fall in forced expiratory volume in 1 s) measurement recorded within 1 h to 16 weeks after the first dose, and up to 31 days after the last dose, of medication.
One hour after the first dose of salmeterol, there was a 3·5-fold increase in doubling dose compared to baseline. Within 12 h of the first dose, the level of protection was 1·5 doubling doses, and protection was maintained at 0·5–1·5 doubling doses over 16 weeks' treatment. This level of protection was maintained for up to 60 h after the last dose. At no time during the washout period did the level of protection fall below zero. Salmeterol afforded significantly greater protection at all time points during the treatment period than comparator agents, but there was no significant difference during the washout period.
In conclusion, salmeterol affords protection against bronchoconstrictor stimuli, and any reduction in this bronchoprotective effect occurred during the first few days of treatment. During long-term salmeterol treatment, there was maintained significant protection that showed no evidence of attenuation after 16 weeks' treatment. Furthermore, there was no evidence of rebound deterioration in bronchial responsiveness after cessation of salmeterol treatment.
