Cardioselective beta-blockers for reversible airway disease

Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.

To assess the effect of cardioselective beta1-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component.

A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to May 2001. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language.

Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta1-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta2-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta2-agonist administration, or the presence of asthma as defined by the American Thoracic Society.

Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta1-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta1-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug.

Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta1-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta2-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta1-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta2-agonist response compared to placebo, a response not seen with beta1-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]).

Cardioselective beta1-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta1-blockers should not be withheld from patients with mild-moderate reversible airway disease.