Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers

Chest. 2005 Mar;127(3):818-24. doi: 10.1378/chest.127.3.818.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use
  • Adrenergic beta-Antagonists / adverse effects*
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / physiopathology
  • Bronchial Provocation Tests
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use
  • Celiprolol / adverse effects
  • Celiprolol / therapeutic use
  • Cross-Over Studies
  • Double-Blind Method
  • Ethanolamines / therapeutic use
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate
  • Humans
  • Male
  • Methacholine Chloride
  • Metoprolol / adverse effects
  • Metoprolol / therapeutic use
  • Middle Aged
  • Propranolol / adverse effects
  • Propranolol / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Ventilation / drug effects*


  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Bronchodilator Agents
  • Ethanolamines
  • Methacholine Chloride
  • Propranolol
  • Celiprolol
  • Metoprolol
  • Formoterol Fumarate