Association between COPD exacerbations and lung function decline during maintenance therapy

Background Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods The study population included patients with mild to moderate COPD, aged >= 35 years, with a smoking history, who were followed up for >= 3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV(1)decline. Effect modification by blood eosinophils was studied through interaction terms. Results Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC >= 350 cells/mu L not on ICS, each exacerbation was associated with subsequent acceleration of FEV(1)decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC >= 350 cells/mu L treated with ICS. Conclusion Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as >= 350 cells/mu L, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.