ABSTRACT
BACKGROUND: COPD exacerbations are responsible for the morbidity and mortality of this disease. The relationship between exacerbations and patient-related clinical outcomes is not clearly understood. METHODS: A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 microg daily was conducted to examine relationships between exacerbations and other clinical outcomes. The relationship between FEV(1), St. George's Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2). RESULTS: 921 patients participated in the trials (mean age 65 years, mean FEV(1) = 1.02 L (39% predicted). The percent change from baseline in FEV(1) in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was -3.4%, -3.4%, -5.7% and -6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively. Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations. In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores. A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments. CONCLUSIONS: In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV(1), TDI, and SGRQ. A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes.
