Detrimental Effects of β-Blockers in COPD

A Concern for Nonselective β-Blockers


      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


      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


      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, FEV1 and PC20 were assessed. Immediately hereafter, formoterol (12 μg) was administered and FEV1 was measured for up to 30 min


      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)


      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


      AHR (airway hyperresponsiveness), PC20 (provocative concentration of methacholine causing a 20% fall in FEV1)
      To read this article in full you will need to make a payment


      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Murray CJ
        • Lopez AD
        Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study.
        Lancet. 1997; 349: 1498-1504
        • Salpeter SR
        • Ormiston TM
        • Salpeter EE
        • et al.
        Cardioselective β-blockers for chronic obstructive pulmonary disease: a meta-analysis.
        Respir Med. 2003; 97: 1094-1101
        • Hospers JJ
        • Postma DS
        • Rijcken B
        • et al.
        Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study.
        Lancet. 2000; 356: 1313-1317
        • Postma DS
        • De Vries K
        • Koeëter GH
        • et al.
        Independent influence of reversibility of air-flow obstruction and nonspecific hyperreactivity on the long-term course of lung function in chronic air-flow obstruction.
        Am Rev Respir Dis. 1986; 134: 276-280
        • Tashkin DP
        • Altose MD
        • Connett JE
        • et al.
        Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.
        Am J Respir Crit Care Med. 1996; 153: 1802-1811
        • Ramsdale EJ
        • Roberts RS
        • Morris MM
        • et al.
        Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis.
        Thorax. 1985; 40: 422-426
        • Ramsdale EH
        • Morris MM
        • Roberts RS
        • et al.
        Bronchial hyperresponsiveness to methacholine in chronic bronchitis: relationship to air flow obstruction and cold air responsiveness.
        Thorax. 1984; 39: 912-918
        • Hancox RJ
        • Aldridge RE
        • Cowan JO
        • et al.
        Tolerance of β agonists during acute bronchoconstriction.
        Eur Respir J. 1999; 14: 283-287
      1. Executive Summary NHLBI/WHO Workshop Report: Global Strategy for the Diagnosis, Management and Prevention of COPD. Bethesda, MD: National Heart, Lung and Blood Institute 2001; NIH Publication No 2701A

        • Cazzola M
        • Centanni S
        • Regorda C
        • et al.
        Onset of action of single doses of formoterol administered via Turbuhaler in patients with stable COPD.
        Pulm Pharmacol Ther. 2001; 14: 41-45
        • Aalbers R
        • Ayres J
        • Backer V
        • et al.
        Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial.
        Eur Respir J. 2002; 19: 936-943
      2. Quanjer PH, Tammeling GJ, Cotes JE, et al. Lung volumes and forced ventilatory flows: Report Working Party Standardisation of Lung Function Tests European Community of Steel and Coal; Official Statement of the European Respiratory Society. Eur Respir J 1993; 6(Suppl):5–40

      3. Farmacotherapeutisch Compas. Medische Farmaceutische Voorlichting. Ziekenfondsraad 2004 Amstelveen, the Netherlands

        • Van der Woude HJ
        • Winter TH
        • Aalbers R
        Decreased bronchodilating effect of salbutamol in relieving methacholine induced moderate to severe bronchoconstriction during high dose treatment with long-acting β2agonists.
        Thorax. 2001; 56: 529-535
        • Perks WH
        • Chatterjee SS
        • Croxson RS
        • et al.
        Comparison of atenolol and oxprenolol in patients with angina or hypertension and co-existent chronic airways obstruction.
        Br J Clin Pharmacol. 1978; 5: 101-106
        • Clague HW
        • Ahmad D
        • Carruthers SG
        Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade.
        Eur J Clin Pharmacol. 1984; 27: 517-523
        • Hansen EF
        • Phanareth K
        • Laursen LC
        • et al.
        Reversible and irreversible airflow obstruction as predictor of overall mortality in asthma and chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 1999; 159: 1267-1271
        • Salpeter S
        • Ormiston TM
        • Salpeter EE
        Cardioselective β-blockers in patients with reactive airway disease: a meta-analysis.
        Ann Intern Med. 2002; 137: 715-725
        • Politiek MJ
        • Boorsma M
        • Aalbers R
        Comparison of formoterol, salbutamol and salmeterol in methacholine induced severe bronchoconstriction.
        Eur Respir J. 1999; 13: 918-922
        • Macdonald AG
        • Ingram CG
        • McNeill RS
        The effect of propranolol on airway resistance.
        Br J Anaesthesiol. 1967; 39: 919-926
        • Sterk PJ
        • Fabbri LM
        • Quanjer PH
        • et al.
        Airway responsiveness: standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal: Official Statement of the European Respiratory Society.
        Eur Respir J Suppl. 1993; 16: 53-83
      4. COPD guidelines Group of the Standards of Care Committee of the BTS. BTS guidelines for the management of chronic obstructive pulmonary diseases. Thorax 1997; 52(suppl):S1–S28

        • Siafakas NM
        • Vermeire P
        • Pride NB
        • et al.
        Optimal assessment and management of chronic obstructive pulmonary disease (COPD).
        Eur Respir J. 1995; 8: 1398-1420
        • American Thoracic Society
        Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 1995; 152: S77-S120
        • Calverley PMA
        • Burge PS
        • Spencer S
        • et al.
        Bronchodilator reversibility testing in chronic obstructive pulmonary disease.
        Thorax. 2003; 58: 659-664
        • Gross NJ
        Responses to steroids and bronchodilators in COPD in the ISOLDE trial: the fat lady sings on.
        Thorax. 2003; 58: 647-648
        • Norris RJ
        Anti-hypertensive therapy with celiprolol: a new cardioselective β-blocker.
        Am J Cardiol. 1988; 61: 14C-22C
        • Cazzola M
        • Noschese P
        • D'Amato G
        • et al.
        The pharmacological treatment of uncomplicated arterial hypertension in patients with airway dysfunction.
        Chest. 2002; 121: 230-241
        • Dart RA
        • Gollub S
        • Lazar J
        • et al.
        Treatment of systemic hypertension in patients with pulmonary diseases: COPD and asthma.
        Chest. 2003; 123: 222-243
        • Kendall MJ
        Clinical relevance of pharmacokinetic differences between β-blockers.
        Am J Cardiol. 1997; 80: 15J-19J
      5. Kendall MJ. Possible mechanism of action in the positive effect of β blockers in heart failure. Heart 1999; 82(suppl): IV5–IV7