吸入速尿对哮喘患者气道对缓激肽和5'-单磷酸腺苷反应的影响。

Effect of inhaled frusemide on responses of airways to bradykinin and adenosine 5'-monophosphate in asthma.

作者信息

Rajakulasingam K, Polosa R, Church M K, Howarth P H, Holgate S T

机构信息

Immunopharmacology Group, University of Southampton, Southhampton General Hospital, UK.

出版信息

Thorax. 1994 May;49(5):485-91. doi: 10.1136/thx.49.5.485.

DOI:10.1136/thx.49.5.485

PMID:8016771

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC474871/

Abstract

BACKGROUND

Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma. This effect could be caused by interference with neural pathways. The effect of inhaled frusemide on bronchoconstriction induced by inhaled bradykinin, which is thought to cause bronchoconstriction via neural mechanisms, was studied and compared with the effects of adenosine 5'-monophosphate (AMP) which probably produces its airway effects by augmenting mast cell mediator release and interfering with neural pathways.

METHODS

Patients first underwent AMP and bradykinin challenges. They were then studied in a randomised, placebo controlled, double blind fashion. Ten atopic asthmatic subjects, studied on four days, were pretreated with inhaled frusemide (40 mg) or placebo for 10 minutes, five minutes before challenge with increasing concentrations of nebulised AMP or bradykinin.

RESULTS

On the open visit days the provocative concentrations required to reduce forced expiratory volume in one second (FEV1) by 20% from baseline (PC20) for AMP and bradykinin were 16.23 (1.42-67.16) and 2.75 (0.81-6.6) mg/ml. There was a significant correlation between baseline AMP and bradykinin PC20 values. For AMP the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 80.97 (9.97- > 400.0) and 14.86 (2.6-104.6) mg/ml respectively (95% CI 0.49 to 0.98). For bradykinin the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 13.22 (2.53- > 16.0) and 2.52 (0.45-5.61) mg/ml respectively (95% CI 0.43 to 1.01). Frusemide afforded 5.45 and 5.24 fold protection against AMP and bradykinin-induced bronchoconstriction respectively. Furthermore, there was a significant correlation between protection afforded to the airways against AMP and bradykinin.

CONCLUSIONS

These data suggest that inhaled frusemide affords protection against bradykinin-induced bronchoconstriction which is comparable to that against AMP, supporting a common mechanism of action for frusemide.

摘要

背景

吸入速尿对哮喘中几种间接刺激诱导的支气管收缩具有保护作用。这种作用可能是由于干扰神经通路所致。研究了吸入速尿对吸入缓激肽诱导的支气管收缩的影响，缓激肽被认为是通过神经机制引起支气管收缩的，并将其与5'-单磷酸腺苷（AMP）的作用进行了比较，AMP可能通过增加肥大细胞介质释放和干扰神经通路来产生气道效应。

方法

患者首先接受AMP和缓激肽激发试验。然后以随机、安慰剂对照、双盲方式进行研究。10名特应性哮喘受试者，在4天内进行研究，在使用递增浓度雾化AMP或缓激肽激发前5分钟，用吸入速尿（40mg）或安慰剂预处理10分钟。

结果

在开放访视日时，使一秒用力呼气容积（FEV1）从基线降低20%所需的AMP和缓激肽激发浓度（PC20）分别为16.23（1.42 - 67.16）mg/ml和2.75（0.81 - 6.6）mg/ml。基线AMP与缓激肽PC20值之间存在显著相关性。对于AMP，吸入速尿和匹配安慰剂预处理后的几何平均PC20值分别为80.97（9.97 - >400.0）mg/ml和14.86（2.6 - 104.6）mg/ml（95%CI 0.49至0.98）。对于缓激肽，吸入速尿和匹配安慰剂预处理后的几何平均PC20值分别为13.22（2.53 - >16.0）mg/ml和2.52（0.45 - 5.61）mg/ml（95%CI 0.43至1.01）。速尿对AMP和缓激肽诱导的支气管收缩分别提供了5.45倍和5.24倍的保护。此外，气道对AMP和缓激肽的保护作用之间存在显著相关性。