ABSTRACT: BACKGROUND:Exercise capacity is an important feature in patients with COPD. Its impairment drives disability and dependency for daily activities performance. This study evaluated the six years change in exercise capacity in subjects with airflow obstruction and compared this to subjects without airflow obstruction, with and without a smoking history. METHODS:Cardiopulmonary exercise tests (CPET) were repeatedly performed during a six years follow up period. Peak oxygen uptake (VO2peak), work rate (WRpeak), heart rate (HRpeak), minute ventilation (VEpeak), respiratory exchange ratio (RERpeak) and ventilatory reserve (VE/MVV) were collected as effort dependent outcomes. The slopes of oxygen uptake, ventilatory and mechanical efficiency (OUES, ?VE/?VCO2 and ?VO2/?WR) were collected as effort independent outcomes. RESULTS:One hundred and thirty-eight subjects were included. Thirty-eight presented airflow obstruction (63±6 years, 74% men, FEV1 90±15%pred), 44 had a smoking history but no airflow obstruction (61±5 years, 61% men, FEV1 105±15%pred) and 56 had never smoked (61±7 years, 57% men, FEV1 117±18%pred). At baseline, the airflow obstruction group had slightly worse exercise capacity in comparison to the never smoking control group, in absolute terms and expressed as percentage of the predicted value (VO2peak = 27±5 versus 32±8 ml/min/kg, p<0.01; 112±29 versus 130±33%pred, p = 0.04). Most exercise variables showed a statistically significant yearly deterioration, with exception of VE/MVV, ?VE/?VCO2 and ?VO2/?WR. The yearly decline in VO2peak and OUES was not faster in subjects with airflow obstruction than in smoking and never smoking controls (VO2peak -67 (9) versus -76 (9) ml/min, p = 0.44 and versus -58 (9), p = 0.47; OUES -32 (11) versus -68 (10), p = 0.03 and versus -68 (13), p = 0.03). CONCLUSIONS:With exception of VO2peak, effort dependent variables deteriorated faster in subjects with airflow obstruction compared to never smoking controls. The deterioration of effort independent variables, however, was not accelerated in the airflow obstruction group compared to controls.