Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications

There is well established evidence that the minute ventilation (V′(E))/carbon dioxide output (V′(CO(2))) relationship is relevant to a number of patient-related outcomes in COPD. In most circumstances, an increased V′(E)/V′(CO(2)) reflects an enlarged physiological dead space (“wasted” ventilation), although alveolar hyperventilation (largely due to increased chemosensitivity) may play an adjunct role, particularly in patients with coexistent cardiovascular disease. The V′(E)/V′(CO(2)) nadir, in particular, has been found to be an important predictor of dyspnoea and poor exercise tolerance, even in patients with largely preserved forced expiratory volume in 1 s. As the disease progresses, a high nadir might help to unravel the cause of disproportionate breathlessness. When analysed in association with measurements of dynamic inspiratory constraints, a high V′(E)/V′(CO(2)) is valuable to ascertain a role for the “lungs” in limiting dyspnoeic patients. Regardless of disease severity, cardiocirculatory (heart failure and pulmonary hypertension) and respiratory (lung fibrosis) comorbidities can further increase V′(E)/V′(CO(2)). A high V′(E)/V′(CO(2)) is a predictor of poor outcome in lung resection surgery, adding value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of disease severity. Considering its potential usefulness, the V′(E)/V′(CO(2)) should be valued in the clinical management of patients with COPD.