Thorax 1998;53:1010-1013 ( December )

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Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects Lennart Greiff,^a Per Wollmer,^c Morgan Andersson,^a Christer Svensson,^a Carl G A Persson^b

^a Department of Otorhinolaryngology, Head and Neck Surgery, ^b Department of Clinical Pharmacology, ^c University Hospital, S-221 85 Lund, Sweden Department of Clinical Physiology, University Hospital, Malmö, Sweden

Correspondence to: Dr L Greiff.

Received 26 May 1998; Returned to authors 27 July 1998; Revised version received 14 August 1998; Accepted for publication 3 September 1998

BACKGROUNDA number of studies have shown that ₂ agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus in animal airways. Whether clinical doses of ₂ agonists inhibit plasma exudation in human bronchial airways is unknown.
METHODSIn order to explore the microvascular permeability and its potential inhibition by ₂ 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 ₂-macroglobulin were determined to indicate microvascular-epithelial exudation of bulk plasma.
RESULTSHistamine 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.
CONCLUSIONThis study shows for the first time an anti-exudative effect of a ₂ 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.

Keywords: ₂ agonists; induced sputum; plasma exudation

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© 1998 by Thorax
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