Reducing airways inflammation to prevent exacerbations in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is amajor cause of handicap, mortality and health careexpenses (1). Altered quality of life (QOL) is a hallmarkof the disease, and relates mainly to dyspnoea andexacerbations: both QOL at steady-state and its rate ofdecline over time correlate to the frequency of acuterespiratory events (2, 3). In parallel, hospitalizations forexacerbations in the most severe patients are importantdeterminants of health care costs (4). Thus, preventingexacerbations is a major goal of care for COPD patients,both from an individual and collective point of view.Inflammation and COPD exacerbationsIn most cases, COPD occurs in smokers and ex-smokers,in whom airflow limitation is the consequence of variousdegrees of emphysema, chronic bronchiolitis and mucusplugging (5). These components of the disease have beenlinked to inflammatory and remodelling processes in theairways and lung parenchyma, involved inflammatorycells being mainly neutrophils, B and T lymphocytes andmacrophages (5, 6). Airways inflammation is moreintense during exacerbations, as shown by increases inthe levels of (i) expression of neutrophil elastase, CXCL-5, CXCL-8 and CXCR1/2 in biopsies (7), (ii) exhaledLTB4 and 8-isoprostane in breath condensates (8), (iii)interleukin (IL)-8 and tumour necrosis factor (TNF)-a insputum (9).Infections are a leading cause of exacerbations andfurther amplify airway inflammation (10). However,about one half of exacerbations occur in the absence ofany detectable infective pathogen, which may not preventinflammation from increasing (11). Besides, higher levelsof inflammatory markers in the airways of patients atsteady-state are also associated with more frequentexacerbations (12). Studies of the East London COPDcohort even suggest the existence of a particular subgroupof COPD patients called frequent exacerbators, whoconsistently have more than 2–3 exacerbations per year(13). In these patients, QOL is more altered, forcedexpiratory volume at 1 s (FEV