Association of Exercise Tolerance with Respiratory Health Outcomes in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

<b>Rationale:</b> Previous studies have identified exercise intolerance in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD). The association of exercise tolerance with lung function decline and acute exacerbation risk in mild-to-moderate COPD is unclear, especially in the community population. <b>Objectives:</b> We evaluated exercise tolerance in patients with mild-to-moderate COPD and analyzed its associations with respiratory health outcomes. <b>Methods:</b> We analyzed data from the community-based ECOPD (Early Chronic Obstructive Pulmonary Disease) study of patients with mild-to-moderate COPD (postbronchodilator forced expiratory volume in 1 second (FEV₁):forced vital capacity < 0.70 and FEV₁ ≥ 50% predicted). Patients who completed questionnaires, spirometry, and cardiopulmonary exercise testing at baseline were included. Annual exacerbation assessment and spirometry were conducted for 2 years consecutively. Exercise tolerance was defined as the percentage of predicted peak oxygen uptake ([Formula: see text]o_2peak% predicted). We analyzed the association between exercise tolerance, annual lung function decline, and acute exacerbation risk. <b>Results:</b> Overall, 338 patients were included in the baseline analysis, and 319 completed the 2-year follow up. The mean ± standard deviation of [Formula: see text]o_2peak% predicted was 79.8 ± 13.7%. Low [Formula: see text]o_2peak% predicted was associated with more chronic respiratory symptoms, worse lung function, severer emphysema, and air trapping at baseline. During the 2-year follow up, a decrease of 13.7% (1 standard deviation) in [Formula: see text]o_2peak% predicted was associated with a decline in prebronchodilator FEV₁:forced vital capacity (difference, 0.4% [95% confidence interval, 0.1-0.7%]; <i>P</i> = 0.003) and higher total exacerbation risk (relative risk, 1.25 [95% confidence interval, 1.08-1.46]; <i>P</i> = 0.004) after adjustment. <b>Conclusions:</b> Patients with mild-to-moderate COPD and exercise intolerance have worse respiratory health outcomes, for which low exercise tolerance is a prognostic marker. Clinical trial registered with www.chictr.org.cn (ChiCTR1900024643).