Q J Med 2003; 96: 435-440
© 2003 Association of Physicians
Airway-stabilizing effect of long-acting ß2-agonists as add-on therapy to inhaled corticosteroids
From the Asthma & Allergy Research Group, 1Department of Public Health & Epidemiology, Ninewells University Hospital & Medical School, University of Dundee, and 2Tayside Centre for General Practice, University of Dundee, Dundee, UK
Received 20 January 2003 and in revised form 26 March 2003
Background: The protection afforded by long-acting ß2-agonists against bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing effects on airway smooth muscle.
Aim: To determine the magnitude of residual bronchoprotection after chronic dosing with long-acting ß2-agonists.
Design: Retrospective meta-analysis
Methods: Medline, BIDS and Cochrane Library databases were searched from 1990. A meta-analysis was then performed of 13 eligible randomized placebo-controlled trials (596 patients) in which second-line treatment with a long-acting ß2-agonist (salmeterol or formoterol) was used for 1 week or more. The residual protection against bronchoconstrictor stimuli as doubling dose/dilution shift was the main outcome measure.
Results: Data were assessed according to Quorum criteria. Combining the results of the meta-analysis, the overall estimated protection amounted to a 0.79 (95%CI 0.63–0.96) doubling dose/dilution shift from placebo. Subgroup analysis showed greater protection at peak vs. trough, but no difference between formoterol vs. salmeterol, or between direct vs. indirect challenge. There was no evidence of significant heterogeneity across all the studies, or within any of the subgroups.
Discussion: When used as second-line treatment, the overall additive protective effect of long-acting ß2-agonists amounts to a 0.8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations.
Address correspondence to Professor B.J. Lipworth, Asthma & Allergy Research Group, Ninewells University Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK. e-mail: b.j.lipworth{at}dundee.ac.uk
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