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Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1786-1790

Differential Effect of Formoterol on Adenosine Monophosphate and Histamine Reactivity in Asthma

JULIA A. NIGHTINGALE, DUNCAN F. ROGERS, and PETER J. BARNES

Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom

Short-acting beta 2-agonists provide greater protection against bronchoconstriction induced by adenosine 5'-monophosphate (AMP) than by direct-acting bronchoconstrictors such as histamine and methacholine. AMP is thought to cause bronchoconstriction via release of mediators from mast cells, which suggests that these drugs stabilize mast cells in vivo. This in vivo property has not yet been demonstrated for long-acting beta 2-agonists. We undertook a double-blind, randomized, placebo-controlled, cross-over study to investigate the effects of a single dose of formoterol inhaled via Turbuhaler (12 µg) and of albuterol inhaled via Turbuhaler (200 µg) on airway responsiveness to AMP and histamine in 16 subjects with mild atopic asthma. Albuterol reduced airway responsiveness to AMP and histamine by 4.1 ± 0.5 and 3.5 ± 0.4 doubling doses, respectively. In contrast, formoterol caused a greater protective effect against AMP than against histamine challenge, decreasing airway responsiveness by 6.0 ± 0.8 and 4.2 ± 0.4 doubling doses, respectively (p < 0.05). Thus, the long-acting beta 2-agonist formoterol appears to have a mast cell-stabilizing effect in vivo in mild asthma.




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