Greiff L, Wollmer P, Andersson M, Svensson C, Persson C G
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
Thorax. 1998 Dec;53(12):1010-3. doi: 10.1136/thx.53.12.1010.
A number of studies have shown that beta 2 agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus in animal airways. Whether clinical doses of beta 2 agonists inhibit plasma exudation in human bronchial airways is unknown.
In order to explore the microvascular permeability and its potential inhibition by beta 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 micrograms) 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 alpha 2-macroglobulin were determined to indicate microvascular-epithelial exudation of bulk plasma.
Histamine induced plasma exudation 30 minutes after placebo was considerably greater than at baseline (median difference 11.3 micrograms/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) micrograms/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formoterol was not demonstrated.
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 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.
多项研究表明，包括福莫特罗在内的β2激动剂可抑制动物气道中炎症刺激诱导的血浆渗出。β2激动剂的临床剂量是否能抑制人支气管气道中的血浆渗出尚不清楚。
为了探究人支气管气道中的微血管通透性及其受β2激动剂的潜在抑制作用，开发了一种双重诱导方法：吸入组胺诱导血浆渗出，随后吸入高渗盐水（4.5%）诱导痰液生成。在一项安慰剂对照、双盲、交叉研究中，16名健康受试者接受了福莫特罗（18微克）。共进行了五次痰液诱导：一次在基线时，四次在组胺激发后（福莫特罗和安慰剂治疗后30分钟和8小时）。测定痰液中α2-巨球蛋白水平以指示大量血浆的微血管-上皮渗出。
安慰剂后30分钟，组胺诱导的血浆渗出明显高于基线水平（中位数差异为11.3微克/毫升（95%置信区间0.9至90.0））。与安慰剂相比，福莫特罗后30分钟，组胺的作用降低了5.1（0.9至61.9）微克/毫升。在8小时时，组胺引起的渗出较少，未显示福莫特罗有抑制作用。
本研究首次表明β2激动剂在健康人支气管气道中有抗渗出作用。通过其物理和生物学效应，血浆渗出在哮喘中具有多种潜在的致病重要性。如果目前的研究结果适用于疾病状态，则表明抗渗出作用可能有助于福莫特罗的抗哮喘活性。
