Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Dundee, UK.
Br J Clin Pharmacol. 2012 May;73(5):717-26. doi: 10.1111/j.1365-2125.2011.04143.x.
β-adrenoceptor blockers are avoided in asthma due to concerns of bronchoconstriction. We investigated the safety of acute exposure to propranolol in asthmatics, sequentially challenged with histamine to mimic an asthma exacerbation and evaluated the role of intravenous hydrocortisone in potentiating salbutamol reversibility.
Persistent atopic asthmatics, requiring ≤ 1000 µg day(-1) budesonide, performed a randomized double-blind placebo-controlled crossover study. Following 10 mg or 20 mg of oral propranolol, patients received 400 mg intravenous hydrocortisone or placebo, followed by histamine challenge with nebulized salbutamol 5 mg and ipratropium 500 µg recovery.
Thirteen patients completed per protocol. Hydrocortisone did not potentiate salbutamol recovery post propranolol and histamine challenge vs. placebo (mean difference in FEV(1) 0.04 ml, 95% CI -0.07, 0.15, P= 0.417). β-adrenoceptor blocker induced bronchoconstriction was demonstrated by spirometry and impulse oscillometry. For the placebo visit, FEV(1) fell 4.7% 2 hours post propranolol (95% CI 1.8, 7.5, P= 0.008) whilst total airway resistance (R5%) increased 31.3% (95% CI 15.6, 47.0, P= 0.04). On both visits FEV(1) % and R5% returned to baseline after salbutamol post histamine.
Nebulized salbutamol and ipratropium produced a full recovery after propranolol and histamine induced bronchoconstriction, independent of hydrocortisone use. Since the greatest risk of β-adrenoceptor blockade is after first dose, our findings offer reassurance to those undertaking further evaluation of chronic β-adrenoceptor blockade as a potential treatment for mild-to-moderate asthma.
由于担心支气管收缩,β-肾上腺素受体阻滞剂在哮喘中被避免使用。我们研究了急性暴露于普萘洛尔在哮喘患者中的安全性,这些患者先后接受组胺挑战以模拟哮喘加重,并评估静脉注射氢化可的松在增强沙丁胺醇逆转中的作用。
需要≤1000μg 布地奈德/天的持续性特应性哮喘患者进行了一项随机、双盲、安慰剂对照交叉研究。口服普萘洛尔 10mg 或 20mg 后,患者接受 400mg 静脉注射氢化可的松或安慰剂,随后用雾化沙丁胺醇 5mg 和异丙托溴铵 500μg 进行组胺挑战以恢复。
13 名患者按方案完成。与安慰剂相比,氢化可的松并没有增强普萘洛尔和组胺挑战后的沙丁胺醇恢复(FEV1 的平均差异为 0.04ml,95%CI-0.07,0.15,P=0.417)。通过肺量计和脉冲振荡测量法证实了β-肾上腺素受体阻滞剂引起的支气管收缩。在安慰剂就诊时,FEV1 在普萘洛尔后 2 小时下降了 4.7%(95%CI 1.8,7.5,P=0.008),而总气道阻力(R5%)增加了 31.3%(95%CI 15.6,47.0,P=0.04)。在两次就诊中,在组胺后用沙丁胺醇后,FEV1%和 R5%均恢复至基线。
在普萘洛尔和组胺引起的支气管收缩后,雾化沙丁胺醇和异丙托溴铵产生了完全恢复,与氢化可的松的使用无关。由于β-肾上腺素受体阻滞剂的最大风险是在第一次给药后,我们的发现为那些正在进一步评估慢性β-肾上腺素受体阻滞剂作为轻度至中度哮喘潜在治疗方法的人提供了保证。