Exercise ventilation-CO2 output relationship in COPD and heart failure: a tale of two abnormalities.

Ventilatory gas exchange measurements have been increasingly accepted as an integral part of cardiopulmonary exercise testing by pulmonologists1-3 and more recently by cardiologists.4,5 A particularly useful measure is the total ventilation (minute ventilation [V̇E]) versus metabolic CO2 output (V̇CO2) relationship obtained with incremental exercise from rest to maximal exercise. In healthy subjects, the V̇E-V̇CO2 relationship from rest to moderate exercise is remarkably linear (y mx b, where m is the slope and b is the y intercept), with PaCO2 and arterial pH being closely regulated homeostatically within narrow limits. For more severe exercise, the relationship becomes curvilinear when V̇E increases disproportionately with respect to V̇CO2 as lactic acidosis sets in, resulting in hypocapnia.6 Patients with chronic heart failure also demonstrate a similar biphasic linear-curvilinear V̇E-V̇CO2 relationship but with an earlier onset of lactic acidosis and a lower peak O2 uptake attained compared with normal depending on the severity of the disease.4 Remarkably, the V̇E-V̇CO2 relationship in chronic heart failure is significantly steeper than normal in compensation for the increase in alveolar dead-space fraction (dead-space-to-tidal volume ratio) due to ventilationperfusion mismatching. The augmentation in the slope of the V̇E-V̇CO2 relationship heightens with increasing alveolar dead-space fraction and is an indicator of poor prognosis in these patients.7 By contrast, the scenario for patients with COPD is less well defined except that peak O2 uptake is typically also reduced. Part of the difficulties in delineating the diseasedependent changes in the exercise V̇E-V̇CO2 relationship in COPD is that the latter is a multidimensional disease affecting not only pulmonary gas exchange but also respiratory mechanics to varying degrees, with potential development of expiratory flow limitation and consequent dynamic lung hyperinflation, which may severely limit exercise V̇E. The attendant ventilation-perfusion mismatching in COPD is likely to predispose these patients to an augmented V̇E-V̇CO2 slope as with chronic heart failure. On the other hand, increasing ventilatory limitation during exercise may constrain the patient’s ability to augment V̇E in compensation for the dead-space ventilation. How these contrasting chemical and mechanical factors play out in determining the resultant exercise V̇E-V̇CO2 relationship may vary greatly depending on the severity of the disease. Indeed, although expiratory flow limitation could also occur in chronic heart failure, it is generally less prohibitive than in severe COPD and can be largely circumvented by switching to a rapid and shallow breathing pattern without compromising ventilation.9 How do patients with COPD defend exercise V̇E compared with chronic heart failure in the face of increased ventilatory limitation? In this issue of RESPIRATORY CARE, Teopompi et al10 report that the slopes of the exercise V̇E-V̇CO2 relationship were similar in subjects with COPD and chronic heart failure provided that