Exercise ventilatory inefficiency is an independent predictor of mortality in COPD

Background: An excessive ventilatory response to metabolic demand during exercise (“ventilatory inefficiency”) has been increasingly recognized as an important marker of disease severity in patients with COPD. The independent role of ventilatory inefficiency in predicting mortality, however, remains unclear. Methods: 288 patients with mild to end-stage COPD were followed-up during a median of 57 months for all-cause mortality. In addition to full pulmonary function tests, an incremental cardiopulmonary exercise test was performed on a cycle ergometer. Results: During the follow-up, there were 77 (26.7%) deaths: 36 (46.5%) had a COPD-related cause for death. Among the resting functional variables, inspiratory capacity/total lung capacity ratio (IC/TLC) - a measure of lung hyperinflation - had the largest area under the ROC curve (0.794, best cut-off ≤ 0.34). Similar analysis involving the main exercise variables showed that peak O 2 uptake and the ventilatory equivalent for CO 2 (VE/VCO 2 nadir) had the largest areas under the ROC curves (0.689, best cut-off ≤ 75% and 0.678, best cut-off u003e34, respectively). In a multivariate Cox regression analysis controlling for IC/TLC, only VE/VCO 2 nadir significantly contributed to predict mortality (Figure). Conclusion: Indirect measures of ventilation-perfusion mismatch during exercise and resting lung hyperinflation are additive in predicting poor survival across the spectrum of COPD severity.