effects of long term treatment of asthma with the short acting β agonist fenoterol have been established in both epidemiological and
clinical studies. A study was undertaken to investigate the efficacy
and safety of long term treatment with salbutamol and salmeterol in
patients with mild to moderate bronchial asthma.
METHODS—In a two
centre double dummy crossover study 165 patients were randomly assigned
to receive salbutamol 400 µg qid, salmeterol 50 µg bid, or
placebo via a Diskhaler. All patients used salbutamol as required for
symptom relief. The study comprised a four week run in and three
treatment periods of 24 weeks, each of which was followed by a four
week washout. Asthma control was assessed by measuring mean morning and
evening peak expiratory flow rate (PEFR), a composite daily asthma
score, and minor and major exacerbation rates. Washout assessments
included methacholine challenge and bronchodilator dose response tests.
Analysis was by intention to treat.
RESULTS—Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR
increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not
change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p<0.001).
Salmeterol improved the asthma score compared to placebo (p<0.001),
but there was no overall difference with salbutamol. Only daytime
symptoms were improved with salbutamol. The minor exacerbation rates
were 0.29, 0.88, and 0.97 exacerbations/patient/year for salmeterol,
salbutamol and placebo, respectively (p<0.0001 for salmeterol).
The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p<0.03 for salmeterol). For salbutamol the asthma score
deteriorated over time (p<0.01), and the time spent in major
exacerbation was significantly longer compared with placebo (12.3 days
(95% CI 4.2 to 20.4)) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma
control, lung function, or bronchial hyperresponsiveness following
cessation of either active treatment, and no evidence of tolerance
to salbutamol or salmeterol.
treatment with salmeterol is effective in controlling asthma symptoms
and reduces minor more than major exacerbation rates. Salbutamol was
associated with improved daytime symptoms but subtle deterioration in
asthma control occurred over time. Salbutamol should therefore be used
only as required.