van der Woude Hanneke J, Zaagsma Johan, Postma Dirkje S, Winter Trea H, van Hulst Marinus, Aalbers René
Department of Pulmonary Diseases, Martini Hospital, Van Ketwich Verschuurlaan 82, 9721 SW Groningen, the Netherlands.
Chest. 2005 Mar;127(3):818-24. doi: 10.1378/chest.127.3.818.
beta-Blockers are known to worsen FEV(1) and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment.
To determine the effects of beta-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), FEV(1), and response to formoterol in patients with COPD.
A double-blind, placebo-controlled, randomized, cross-over study.
An ambulatory, hospital outpatient clinic of pulmonary diseases.
Patients with mild-to-moderate irreversible COPD and AHR.
Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >/= 3 days. On day 4 of treatment, FEV(1) and PC(20) were assessed. Immediately hereafter, formoterol (12 microg) was administered and FEV(1) was measured for up to 30 min.
PC(20) was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV(1) deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV(1) at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively).
Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV(1) and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a beta-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV(1), AHR, and response to additional beta(2)-agonists.
已知β受体阻滞剂会使哮喘患者的第一秒用力呼气容积（FEV₁）和气道高反应性（AHR）恶化。这两个特征决定了慢性阻塞性肺疾病（COPD）的病情转归，COPD是一种常伴有心脏合并症且需要使用β受体阻滞剂治疗的疾病。
确定β受体阻滞剂对COPD患者AHR（使FEV₁下降20%时的乙酰甲胆碱激发浓度[PC₂₀]）、FEV₁以及对福莫特罗反应的影响。
一项双盲、安慰剂对照、随机、交叉研究。
一家门诊肺部疾病医院诊所。
轻至中度不可逆性COPD且伴有AHR的患者。
15名患者接受普萘洛尔（80毫克）、美托洛尔（100毫克）、塞利洛尔（200毫克）或安慰剂治疗4天，随后有一个≥3天的洗脱期。在治疗的第4天，评估FEV₁和PC₂₀。此后立即给予福莫特罗（12微克）并测量FEV₁长达30分钟。
与安慰剂（3.16毫克/毫升）或塞利洛尔（3.41毫克/毫升）相比，普萘洛尔和美托洛尔治疗后PC₂₀显著降低（p<0.01）（几何均值分别为2.06毫克/毫升和2.02毫克/毫升）。仅普萘洛尔治疗后FEV₁恶化（2.08±0.31升）[均值±标准差]，而安慰剂组为（2.24±0.37升）。普萘洛尔阻碍了福莫特罗的快速支气管扩张作用（3分钟时FEV₁的平均增加量为6.7±8.9%），但其他β受体阻滞剂未产生影响（安慰剂、美托洛尔和塞利洛尔组分别为16.9±9.8%、22±11.6%和16.9±9.0%）。
塞利洛尔未产生肺部效应。只有普萘洛尔降低了FEV₁以及福莫特罗的支气管扩张作用。美托洛尔和普萘洛尔均增加了AHR。因此，不同类别的β受体阻滞剂具有不同的肺部效应。β受体阻滞剂预期的有益心血管效应必须与可能的有害肺部效应相权衡，即对FEV₁、AHR以及对额外β₂激动剂反应的影响。
