Treatment of COPD: from pharmacological to instrumental therapies

Abstract

T he two main goals of the current management of chronic obstructive pulmonary disease (COPD) are: 1) to reduce the impact of the disease on daily activities; and 2) to reduce the risk of future events (exacerbations, lung function decline and death) [1]. The first measure is obviously smoking cessation; however, we will not discuss this.Treatment guidelines are mainly based on randomised clinical trials that include a small and highly selected fraction of the COPD population [2]. Therefore, it is questionable as to whether these evidence-based guidelines can be extrapolated to the overall COPD population in the everyday practice. Indeed, less than one in five or 10 patients with COPD could fit into inclusion or exclusion criteria commonly used in clinical trials evaluating efficacy of pharmacological treatments [2,3]. In addition, COPD is a heterogeneous disease and patients with similar forced expiratory volume in 1 s (FEV1) may show very different functional status, underlying lung pathology and comorbidities. For most treatments, differences in the responsiveness of COPD subgroups are not yet established and large, long clinical trials, along with high-quality meta-analyses, remain the basis of the current treatment guidelines and the evaluation of the benefit/risk ratio of the main therapeutic classes used in COPD management. However, even the large therapeutic trials may suffer from methodological limitations in the design or analysis [4].The most important outcomes in clinical trials are patientcentred outcomes. Exacerbations, health-related quality of life and mortality are logical major outcomes in COPD trials [4]. In addition, exercise performance and lung function decline are other important targets for therapeutic intervention in COPD [5]. Lung function and biological markers reliably predicting individual response to treatments would be useful. PHARMACOLOGICAL INTERVENTIONS BronchodilatorsBronchodilators are the mainstay of the current pharmacological management of COPD. Long-acting bronchodilators reduce exacerbations and improve health-related quality of life [6][7][8][9][10][11]. The inconsistencies in the definitions or statistical analyses of exacerbations hamper comparison of efficacy data on this outcome between trials performed with different long-acting bronchodilators [4,12]. A clinical trial has been designed to compare the effect of tiotropium and salmeterol on exacerbations and would require the inclusion of 6,800 patients in order to potentially detect a difference in efficacy between the two long-acting bronchodilators [13]. The reduction of lung function decline by bronchodilators is a matter of debate [11]. A post hoc analysis of the TORCH study suggested that salmeterol reduces the rate of decline in post-bronchodilator FEV1 versus placebo [8]. A post hoc analysis of two 1-yr trials with tiotropium versus placebo also showed an improvement in the rate of decline of FEV1 [14]. Except in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II COPD [10], t...

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