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

Background-A number of studies have shown that beta(2) agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus i n animal airways. Whether clinical doses of beta(2) agonists inhibit plasma exudation in human bronchial airways is unknown. Methods-In order to explore the microvascular permeability and its potentia l inhibition by beta(2) agonists in human bronchial airways a dual inductio n method was developed: plasma exudation induced by histamine inhalation fo llowed by sputum induction by hypertonic saline (4.5%) inhalation. Sixteen healthy subjects received formoterol (18 mu g) in a placebo controlled, dou ble blind, crossover study. Sputum was induced on five occasions: once at b aseline and four times after histamine challenge (30 minutes and eight hour s after both formoterol and placebo treatments). Sputum levels of alpha(2)- macroglobulin were determined to indicate microvascular-epithelial exudatio n of bulk plasma. Results-Histamine induced plasma exudation 30 minutes after placebo was con siderably greater than at baseline (median difference 11.3 mu g/ml (95% con fidence interval 0.9 to 90.0)). At 30 minutes after formoterol the effect o f histamine was reduced by 5.1 (0.9 to 61.9) mu g/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formote rol was not demonstrated. Conclusibn-This study shows for the first time an anti-exudative effect of a beta(2) agonist in healthy human bronchial airways. Through its physical and biological effects, plasma exudation is of multipotential pathogenic im portance in asthma. if the present findings translate to disease conditions , it suggests that an antiexudative effect may contribute to the anti-asthm atic activity of formoterol.