Chronic obstructive pulmonary disease (COPD) exacerbations are episodes of symptom worsening that have major impacts on a variety of health outcomes, including quality of life, hospital admission and death [1]. Exacerbation reduction is now a key outcome for pharmacological therapies in COPD and, thus, if exacerbation can be prevented how does this affect disease progression and lung function decline?
The issue of the importance of lung function decline in COPD first arose when Fletcher and Peto [2] explored lung function in a cohort of 792 male British postal workers. These subjects were studied over 8 years and it was found that exacerbations were associated with the ratio of forced expiratory volume in 1 s (FEV1) to the cube of the height, although the exacerbation definition was limited at that time. This work was followed in close succession by a study from Utah in which Kanner et al. [3] showed that exacerbation frequency was related to COPD severity, thus implicating exacerbation frequency as a factor in FEV1 decline. However, detecting the relationship proved elusive until the Lung Health Study showed that in smokers and intermittent quitters each additional exacerbation reported to physicians caused a greater annual decline of 7 mL [4]. The following …