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


METHODS
A double-blind, placebo-controlled, randomized, cross-over study.


METHODS
An ambulatory, hospital outpatient clinic of pulmonary diseases.


METHODS
Patients with mild-to-moderate irreversible COPD and AHR.


METHODS
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.
van der Woude
Hanneke J
HJ
Department of Pulmonary Diseases, Martini Hospital, Van Ketwich Verschuurlaan 82, 9721 SW Groningen, the Netherlands. jvbhw@home.nl
Zaagsma
Johan
J
Postma
Dirkje S
DS
Winter
Trea H
TH
van Hulst
Marinus
M
Aalbers
René
R
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use; D017272:Celiprolol / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D016210:Methacholine Chloride; D011433:Propranolol; D017272:Celiprolol; D008790:Metoprolol; D000068759:Formoterol Fumarate