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Detrimental Effects of β-Blockers in COPD

A Concern for Nonselective β-Blockers

      Introduction

      β-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring β-blocker treatment

      Objective

      To determine the effects of β-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20]), FEV1, 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, FEV1 and PC20 were assessed. Immediately hereafter, formoterol (12 μg) was administered and FEV1 was measured for up to 30 min

      Results

      PC20 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). FEV1 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 FEV1 at 3 min, 6.7 ± 8.9%) but was unaffected by the other β-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 FEV1 and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of β-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a β-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV1, AHR, and response to additional β2-agonists

      Key words

      Abbreviation:

      AHR (airway hyperresponsiveness), PC20 (provocative concentration of methacholine causing a 20% fall in FEV1)
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