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Am. J. Respir. Crit. Care Med., Vol 150, No. 2, Aug 1994, 381-387.

Nonbronchodilator effects of inhaled beta 2 agonists. Greater protection against adenosine monophosphate- than methacholine-induced bronchoconstriction in asthma

BJ O'Connor, RW Fuller and PJ Barnes
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.

There has been controversy about possible beneficial effects of beta agonists on airway function in asthma, in addition to their effects on airway smooth muscle. We compared the protective effects of terbutaline on bronchoconstrictor responses to methacholine, which constricts smooth muscle directly, adenosine 5'-monophosphate (AMP), which acts indirectly by mast cell activation, and sodium metabisulfite (MBS), which stimulates sensory nerves, in 15 mild asthmatic subjects in a randomized double-blind study carried out in two phases. In the first phase 12 subjects inhaled two doses of 0.5 and 2.5 mg terbutaline or placebo administered as a dry power (Tubohaler) 20 min before challenge with methacholine and AMP. Each subject received increasing doubling doses of methacholine and AMP nebulized from a dosimeter. Challenges were terminated when FEV1 fell by 20% from baseline (PC20). In the second phase 10 subjects (seven of whom had participated in Phase 1) inhaled 0.5 mg terbutaline or placebo before similar challenge with methacholine and MBS. In Phase 1 terbutaline inhibited the bronchoconstrictor response to methacholine by 2.1 and 3.3 doubling doses but caused a significantly greater inhibition of the response to AMP of 3.4 and 4.8 doubling doses after 0.5 and 2.5 mg, respectively. In the second phase 0.5 mg terbutaline had equivalent effects on responses to both methacholine and MBS of 2.6 and 2.2 doubling dilutions, respectively. This effect on methacholine and MBS implies functional antagonism of airway smooth muscle. The enhanced effect on AMP implies an additional non-smooth muscle action that may involve suppression of airway mast cell function.


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