Pharmacotherapy for mortality reduction in chronic obstructive pulmonary disease

Despite rapid advances in our understanding of its pathophysiology, chronic obstructive pulmonary disease (COPD) remains incurable. Although bronchodilators and theophyllines are commonly used to treat symptoms of dyspnea and cough and to acutely improve lung function, they do not modify the long-term decline in FEV(1). The principal goals of current COPD pharmacotherapy are to reduce exacerbations, improve health status, and prolong survival. There is strong evidence, including data from randomized clinical trials, that indicates inhaled corticosteroids alone, or in combination with a long-acting beta(2)-adrenoceptor agonist, improve patient symptoms, reduce morbidity, and perhaps even prolong survival in COPD. A recent individual patient-based meta-analysis of randomized, placebo-controlled trials of inhaled corticosteroids in COPD indicated that mortality over 3-4 yr was 27% lower in the group that received inhaled corticosteroids compared with the group that received placebo. Several short-term follow-up trials have also suggested a reduction in mortality with a combination of long-acting beta(2)-agonist and inhaled corticosteroids, and a large, long-term study that is currently ongoing (the Toward a Revolution in COPD Health [TORCH] study) will provide data on the effects of fluticasone propionate and salmeterol in combination on all-cause mortality. This article reviews some of the relevant epidemiologic and pathophysiologic processes that affect mortality in COPD and critically examines the effect of current COPD therapies on mortality.