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沙美特罗和丙酸氟替卡松单独及联合用药对哮喘患者气道血流的急性影响。

Acute effects of salmeterol and fluticasone propionate alone and in combination on airway blood flow in patients with asthma.

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.

出版信息

Chest. 2012 May;141(5):1184-1189. doi: 10.1378/chest.11-0685. Epub 2011 Oct 6.

Abstract

BACKGROUND

The airway contains airway smooth muscle and airway vascular smooth muscle. The acute effects of inhaled long-acting β(2)-adrenergic agonists (LABAs) alone, or in combination with an inhaled glucocorticoid (ICS), on airway smooth muscle tone in asthma are known; however, to the best of our knowledge, their effect on airway vascular smooth muscle tone has not been investigated previously. The objective of this study was to investigate the immediate effects of a LABA and an ICS alone and in combination on airway blood flow (Qaw) as an index of airway vascular smooth muscle tone in patients with stable asthma.

METHODS

Fourteen subjects with moderate asthma inhaled single doses of salmeterol (50 μg), fluticasone propionate (250 μg), salmeterol/fluticasone propionate (50/250 μg), or placebo; Qaw was measured before and serially for 240 min after drug administration.

RESULTS

Mean Qaw increased after salmeterol and salmeterol/fluticasone propionate, with peaks at 60 min of 34% and 40%, respectively, and returned to baseline by 240 min after inhalation. Fluticasone propionate alone caused a transient decrease in mean Qaw. The maximal changes in Qaw, which occurred at different times, were 60% for salmeterol, 67% for salmeterol/fluticasone propionate, and -19% for fluticasone propionate (P < .05 vs placebo for all).

CONCLUSIONS

The LABA salmeterol has an acute vasodilator action on the airway of subjects with stable asthma. The addition of fluticasone propionate, which by itself causes vasoconstriction, does not attenuate the salmeterol-induced vasodilation, suggesting that fluticasone propionate potentiates the vasodilator effect of salmeterol. The vasodilation could be of clinical benefit by promoting the vascular clearance of inflammatory mediators including spasmogens from the airway.

TRIAL REGISTRY

ClinicalTrials.gov; No.: NCT01231230; URL: www.clinicaltrials.gov.

摘要

背景

气道包含气道平滑肌和气道血管平滑肌。已知吸入长效β2-肾上腺素能激动剂(LABA)单独或与吸入糖皮质激素(ICS)联合使用对哮喘患者气道平滑肌张力的急性作用;然而,据我们所知,以前尚未研究它们对气道血管平滑肌张力的影响。本研究的目的是研究 LABA 和 ICS 单独和联合使用对气道血流(Qaw)的即时影响,作为稳定哮喘患者气道血管平滑肌张力的指标。

方法

14 名中度哮喘患者吸入单剂量沙美特罗(50μg)、丙酸氟替卡松(250μg)、沙美特罗/丙酸氟替卡松(50/250μg)或安慰剂;在给药前和给药后 240 分钟内连续测量 Qaw。

结果

沙美特罗和沙美特罗/丙酸氟替卡松后平均 Qaw 增加,峰值分别为 60 分钟时的 34%和 40%,吸入后 240 分钟恢复至基线。单独使用丙酸氟替卡松会导致平均 Qaw 短暂下降。Qaw 的最大变化发生在不同时间,沙美特罗为 60%,沙美特罗/丙酸氟替卡松为 67%,丙酸氟替卡松为-19%(与所有安慰剂相比,均 P<0.05)。

结论

LABA 沙美特罗对稳定哮喘患者的气道具有急性血管扩张作用。单独使用会引起血管收缩的丙酸氟替卡松的添加不会减弱沙美特罗引起的血管扩张,这表明丙酸氟替卡松增强了沙美特罗的血管扩张作用。血管扩张可能通过促进血管清除气道中的炎症介质(包括痉挛剂)而具有临床益处。

试验注册

ClinicalTrials.gov;编号:NCT01231230;网址:www.clinicaltrials.gov。

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