Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.
BACKGROUND
The protection afforded by long-acting beta(2)-agonists against bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing effects on airway smooth muscle.


OBJECTIVE
To determine the magnitude of residual bronchoprotection after chronic dosing with long-acting beta(2)-agonists.


METHODS
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 beta(2)-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.


CONCLUSIONS
When used as second-line treatment, the overall additive protective effect of long-acting beta(2)-agonists amounts to a 0.8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations.
Currie
G P
GP
Asthma & Allergy Research Group, Department of Public Health & Epidemiology, Ninewells University Hospital & Medical School, University of Dundee, UK.
Jackson
C M
CM
Ogston
S A
SA
Lipworth
B J
BJ
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001249:Asthma / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004983:Ethanolamines / Q000627:therapeutic use; D000068759:Formoterol Fumarate; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012137:Respiratory System / Q000187:drug effects*; D012189:Retrospective Studies; D000068299:Salmeterol Xinafoate
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate