Intercept of minute ventilation versus carbon dioxide output relationship as an index of ventilatory inefficiency in chronic obstructive pulmonary disease

Background Ventilatory inefficiency contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V˙E) vs. carbon dioxide output (V˙ CO2) plot is a key ventilatory inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate correlations between the V˙E/V˙ CO2 intercept and LH and airflow limitation to determine its physiological interpretation as an index of functional impairment in COPD. Methods We conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls who performed incremental cardiopulmonary exercise tests (CPETs) and resting pulmonary function assessment. Ventilatory inefficiency was represented by parameters reflecting the V˙E/V˙ CO2 nadir and slope (linear region) and the intercept of V˙E/V˙ CO2 plot. Their correlations with measures of LH and airflow limitation were evaluated. Results Compared to control, the slope (30.58±3.62, P<0.001) and intercept (4.85±1.11 L/min, P<0.05) were higher in COPDstages1-2, leading to a higher nadir (31.47±4.47, P<0.01). Despite an even higher intercept in COPDstages3-4 (7.16±1.41, P<0.001), the slope diminished with disease progression (from 30.58±3.62 in COPDstages1-2 to 26.84±4.96 in COPDstages3-4, P<0.01). There was no difference in nadir among COPD groups and higher intercepts across all stages. The intercept was correlated with peak V˙E/maximal voluntary ventilation (MVV) (r=0.489, P<0.001) and peak V˙ O2/Watt (r=0.354, P=0.003). The intercept was positively correlated with residual volume (RV) % predicted (r=0.571, P<0.001), RV/total lung capacity (TLC) (r=0.588, P<0.001), peak tidal volume (VT)/FEV1 (r=0.482, P<0.001) and negatively correlated with rest inspiratory capacity (IC)/TLC (r=-0.574, P<0.001), peak VT/TLC (r=-0.585, P<0.001), airflow limitation forced expiratory volume in 1 s (FEV1) % predicted (r=-0.606, P<0.001), and FEV1/forced vital capacity (FVC) (r=-0.629, P<0.001). Conclusions V˙E/V˙ CO2 intercept was consistently correlated with worsening static and dynamic LH, pulmonary gas exchange, and airflow limitation in COPD. The V˙E/V˙ CO2 intercept emerged as a useful index of ventilatory inefficiency in COPD patients.