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

Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects
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DOI:
10.1136/thx.53.12.1010
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发表时间:
1998-12-01
期刊:
影响因子:
10
通讯作者:
Persson, CGA
Persson, CGA
中科院分区:
医学1区
文献类型:
--
作者:
Greiff, L;Wollmer, P;Persson, CGA

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背景-大量研究表明,包括福莫特罗在内的β 2受体激动剂可抑制动物气道炎症刺激诱导的血浆渗出。是否临床剂量的β(2)激动剂抑制血浆渗出在人类支气管airways. Methods,以探讨微血管通透性和其潜在的抑制β(2)激动剂在人类支气管airwaysA双诱导方法开发:血浆渗出诱导组胺吸入高渗盐水(4.5%)吸入痰诱导。在一项安慰剂对照、双盲、交叉研究中,16名健康受试者接受福莫特罗(18 μ g)。在五种情况下诱导痰:基线时一次,组胺激发后四次(福莫特罗和安慰剂治疗后30分钟和8小时)。α 2-巨球蛋白的痰液水平被确定为指示大量plasma.Results-Histamine诱导的血浆渗出30分钟后安慰剂是相当大的比在基线(中位数差异11.3 μ g/ml(95%置信区间0.9至90.0))。在福莫特罗给药后30分钟,与安慰剂相比,组胺的作用降低了5.1(0.9 - 61.9)μ g/ml。在8小时组胺产生较少的渗出和抑制福莫特罗没有demonstrated. Conclusib-This研究表明,第一次在健康的人支气管气道的β(2)激动剂的抗渗出作用。通过其物理和生物学效应,血浆渗出在哮喘中具有多潜在的致病重要性。如果目前的发现转化为疾病状况,则表明抗渗出作用可能有助于福莫特罗的抗哮喘活性。
Background-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.Methods-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 mu g) 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.Results-Histamine induced plasma exudation 30 minutes after placebo was considerably greater than at baseline (median difference 11.3 mu g/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) mu g/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formoterol 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 importance in asthma. if the present findings translate to disease conditions, it suggests that an antiexudative effect may contribute to the anti-asthmatic activity of formoterol.