Abstract
INTRODUCTION:
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.
OBJECTIVE:
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.
DESIGN:
A double-blind, placebo-controlled, randomized, cross-over study.
SETTING:
An ambulatory, hospital outpatient clinic of pulmonary diseases.
PATIENTS:
Patients with mild-to-moderate irreversible COPD and AHR.
INTERVENTION:
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.
RESULTS:
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).
CONCLUSIONS:
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.