Mechanisms of exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation.