COPD exacerbations: defining their cause and prevention

Abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.

Figure 1

Triggers of COPD exacerbations and associated pathophysiological changes leading to increased exacerbation symptoms

Figure 2

Effect of COPD exacerbations in the group with frequent exacerbations

Figure 3

Time course of a COPD exacerbation over 51 days of time spent indoors (open circles) and symptom count (solid circles) for 136 patients who were monitored daily and had an exacerbation Reproduced with permission from Fletcher and colleagues.

Figure 4

Effect of salmeterol (100 μg/day), fluticasone (1000 μg/day), both (combination), or placebo on the mean number of moderate and severe exacerbations of COPD per year, over 3 years *p<0·001 vs placebo. †p=0,002 vs salmeterol. ‡p=0·024 vs fluticasone. Adapted with permission from Calverley and colleagues.

Figure 5

Kaplan-Meier estimates of the rate of first treatment failure at 6 months for the first COPD exacerbation treated with either tiotropium (continuous line) or placebo (dotted line) Reproduced with permission from Niewoehner and colleagues.