Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects

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Abstract
BACKGROUND A number of studies have shown that β2 agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus in animal airways. Whether clinical doses of β2 agonists inhibit plasma exudation in human bronchial airways is unknown. METHODS In order to explore the microvascular permeability and its potential inhibition by β2 agonists in human bronchial airways a dual induction method was developed: plasma exudation induced by histamine inhalation followed by sputum induction by hypertonic saline (4.5%) inhalation. Sixteen healthy subjects received formoterol (18 μg) in a placebo controlled, double blind, crossover study. Sputum was induced on five occasions: once at baseline and four times after histamine challenge (30 minutes and eight hours after both formoterol and placebo treatments). Sputum levels of α2-macroglobulin were determined to indicate microvascular-epithelial exudation of bulk plasma. RESULTS Histamine induced plasma exudation 30 minutes after placebo was considerably greater than at baseline (median difference 11.3 μg/ml (95% confidence interval 0.9 to 90.0)). At 30 minutes after formoterol the effect of histamine was reduced by 5.1 (0.9 to 61.9) μg/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formoterol was not demonstrated. CONCLUSION This study shows for the first time an anti-exudative effect of a β2 agonist in healthy human bronchial airways. Through its physical and biological effects, plasma exudation is of multipotential pathogenic importance in asthma. If the present findings translate to disease conditions, it suggests that an anti-exudative effect may contribute to the anti-asthmatic activity of formoterol.