Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease Results from the CanCOLD Study

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V_ E/V_ CO2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high V_ E/V_ CO2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort. Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir V_ E/V_ CO2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2–4 COPD. Participants with V_ E/V_ CO2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale>2; odds ratio [5–95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak V_ O2 (V_ O2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The KCO had a stronger correlation with nadir V_ E/V_ CO2 (r=20.38; P,0.001) than other relevant lung function and computed tomography metrics. The prevalence of V_ E/V_ CO2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: V_ E/V_ CO2 above the ULN was associated with greater dyspnea and low V_ O2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.