β-Adrenoceptor modulation in chronic obstructive pulmonary disease: present and future perspectives

The common coexistence of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) presents several therapeutic constraints that have not been comprehensively investigated. Pharmacologic modulation of β-adrenoceptor (β-AR) function is one of the critical issues in the treatment of these patients because inhaled β(2)-AR agonists may induce adverse events in patients with COPD, mainly in those with coexisting CVD. Moreover, the use of β-AR blockers has traditionally been contraindicated in COPD, mainly because of the potential for acute bronchospasm and increased airway hyperresponsiveness after their administration. However, there now appears to be good evidence that β-AR blockers are not only safe but may have benefits in COPD that extend beyond a reduction in cardiovascular mortality. This article starts with a succinct outline of the evolution in our understanding of β-AR modulation in COPD, touching on treatment of COPD with β-AR agonists and the issues of β-AR blockade and cardioselectivity in patients with comorbid CVD. We then summarize the current evidence for a COPD benefit from β-AR blockers and hypothesize on the mode of action. Finally, we provide a view of the future landscape in terms of therapeutic possibilities and what still needs to be resolved, based on our opinion.