Exacerbation frequency and course of COPD

Background: Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial. Methods: This retrospective analysis of data from the 4-year UPLIFT ® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0>0–1, >1–2, and>2). Spirometry and the St George's Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry). Results: In total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV 1 ) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV 1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations. Conclusion: Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death. Keywords: chronic obstructive pulmonary disease, exacerbations, forced expiratory volume in one second, health status, tiotropium