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Rationale: Chronic obstructive pulmonary disease (COPD) is thought to result in rapid and progressive loss of lung function usually expressed as mean values for whole cohorts., Objectives: Longitudinal studies evaluating individual lung function loss and other domains of COPD progression are needed., Methods: We evaluated 1,198 stable, well-characterized patients with COPD (1,100 males) recruited in two centers (Florida and Tenerife, Spain) and annually monitored their multidomain progression from 1997 to 2009. Patients were followed for a median of 64 months and up to 10 years. Their individual FEV(1) (L) and BODE index slopes, expressed as annual change, were evaluated using regression models for repeated measures. A total of 751 patients with at least three measurements were used for the analyses., Measurements and Main Results: Eighteen percent of patients had a statistically significant FEV(1) slope decline (-86 ml/yr; 95% confidence interval [CI], -32 to -278 ml/yr). Higher baseline FEV(1) (relative risk, 1.857; 95% CI, 1.322-2.610; P < 0.001) and low body mass index (relative risk, 1.071; 95% CI, 1.035-1.106; P < 0.001) were independently associated with FEV(1) decline. The BODE index had a statistically significant increase (0.55, 0.20-1.37 point/yr) in only 14% of patients and these had more severe baseline obstruction. Concordance between FEV1 and BODE change was low (κ Cohen, 16%). Interestingly, 73% of patients had no significant slope change in FEV1 or BODE. Only the BODE change was associated with mortality in patients without FEV(1) progression., Conclusions: The progression of COPD is very heterogeneous. Most patients show no statistically significant decline of FEV(1) or increase in BODE. The multidimensional evaluation of COPD should offer insight into response to COPD management.