Chest
Volume 127, Issue 3, March 2005, Pages 818-824
Journal home page for Chest

Clinical Investigations: COPD
Detrimental Effects of β-Blockers in COPD: A Concern for Nonselective β-Blockers

https://doi.org/10.1378/chest.127.3.818Get rights and content

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

Section snippets

Materials and Methods

Patients with stable mild-to-moderate COPD participated in the study.4 Inclusion criteria were as follows: age 40 to 70 years, FEV1 ≥ 1.5 L and from 60 to 80% predicted,12 FEV1/FVC ≤ 0.7, pulse rate ≥ 60 beats/min, ≥ 15 pack-years smoking history, and reversibility ≤ 12% of predicted FEV1 after inhalation of 400 μg salbutamol. Major exclusion criteria were a history of asthma, the use of β-blocking agents, and the presence of significant diseases other than COPD, which could have put the

Results

Between April 2001 and February 2002, 35 patients were recruited from our outpatient clinic. Twenty patients failed to fulfil all inclusion and exclusion criteria. Reasons for not entering the study were FEV1 out of range (n = 13), no methacholine threshold (n = 2), heart rate too slow (n = 1), reversibility (n = 1), and administrative reasons (n = 3)

The remaining 15 patients were randomized, and all completed the study. The compliance rate was 100%. Treatments were well tolerated, although

Discussion

In this study, we found evidence of the negative effects of β-blocker treatment on lung function (FEV1) and AHR in patients with mild-to-moderate, irreversible COPD. FEV1 deteriorated significantly during 4 days of propranolol treatment only, whereas AHR deteriorated both during propranolol and metoprolol treatment when compared to placebo.

In addition, the fast bronchodilating effect of the β2-adrenergic agonist formoterol was significantly impaired after propranolol treatment, but unaffected

Acknowledgments

We thank G. D. Nossent, I. P. Smit, E. F. Smit, L. H. Steenhuis, C. G. Tol, and S. H. Wills for their contribution for the clinical part of the study; and M. Boorsma and P. Gobbens for assistance with data analysis.

References (31)

  • EJ Ramsdale et al.

    Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis

    Thorax

    (1985)
  • EH Ramsdale et al.

    Bronchial hyperresponsiveness to methacholine in chronic bronchitis: relationship to air flow obstruction and cold air responsiveness

    Thorax

    (1984)
  • RJ Hancox et al.

    Tolerance of β agonists during acute bronchoconstriction

    Eur Respir J

    (1999)
  • Executive Summary NHLBI/WHO Workshop Report: Global Strategy for the Diagnosis, Management and Prevention of COPD....
  • R Aalbers et al.

    Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial

    Eur Respir J

    (2002)
  • Cited by (142)

    • Impact of Comorbidities on the Treatment of Chronic Obstructive Pulmonary Disease

      2018, American Journal of Medicine
      Citation Excerpt :

      Treatment with propranolol (80 mg) was also shown to significantly reduce bronchodilation and FEV1 in patients receiving the LABA formoterol.45 However, cardioselective metoprolol (100 mg) and celiprolol (200 mg) did not exhibit any detrimental effect on bronchodilation with formoterol, as measured by the increase in FEV1.45 It is interesting that this study found differing effects on airway hyper-responsiveness, with metoprolol causing an increase in airway hyper-responsiveness and celiprolol having no effect.45

    • Critical Care of the Thoracic Surgical Patient

      2022, Onco-critical Care: An Evidence-based Approach
    View all citing articles on Scopus

    This work was sponsored by an unconditional grant from AstraZeneca

    View full text