Thorax 1998;53:744-752 ( September )

Asthma control during long term treatment with regular inhaled salbutamol and salmeterol

D Robin Taylor, G Ian Town, G Peter Herbison, David Boothman-Burrell, Erin M Flannery, Bob Hancox, Elizabeth Harré, Keith Laubscher, Vivienne Linscott, Catriona M Ramsay, Geoff Richards, with the technical assistance of J Cowan, N Holbrook, C McLachlan, S Rigby

Otago and Canterbury Respiratory Research Groups, Dunedin and Christchurch Schools of Medicine, University of Otago Medical School, New Zealand

Correspondence to: Dr D R Taylor, Department of Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.

Received 17 November 1997; Returned to authors 31 March 1998; Revised version received 5 May 1998; Accepted for publication 6 May 1998

BACKGROUNDThe adverse effects of long term treatment of asthma with the short acting  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.
METHODSIn 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.
RESULTSData 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.
CONCLUSIONSRegular 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.

Keywords: asthma therapy; salbutamol; salmeterol

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© 1998 by Thorax
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