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Limits to ventilation (for sure!) and exercise (maybe?) in mild chronic obstructive pulmonary disease.

The physiological basis for limitation of maximum exercise performance has long been debated (1, 2). In health, O2 transport (CaO2$Q : ) is the likely major candidate, and in turn, limitations on the maximum obtainable stroke volume and cardiac output are the key limitations to O2 transport. In disease states such as chronic obstructive pulmonary disease (COPD), exercise performance becomes symptom limited, and many links in the chain of O2 transport to and use by locomotor muscles are compromised to varying degrees (3–5). In this issue of the Journal, Chin and colleagues (pp. 1315–1323) have addressed this complex problem in patients with “mild” COPD, characterized by reduced lung elastic recoil and increased gas trapping, but who experience no exerciseinduced arterial hypoxemia (6). Their peak exercise capacity is reduced, as is their peak V : E, but whether the lungs’ mechanical properties play a role in this exercise limitation is unclear because (1) bronchodilation does not improve V : E or exercise performance or reduce dyspnea; (2) the major exercise-limiting symptom expressed by the patient is leg discomfort; and (3) the maximum exercise V : E is well short of the usual index of maximum available ventilation, the maximum voluntary ventilation (MVV). Accordingly, Chin and colleagues have used dead space loading to provide a more direct interventional approach to this question. During air breathing exercise at all intensities, the patients showed a normal, tight control of end-tidal (partial) carbon dioxide pressure (PETCO2) at all workloads, indicating an adequate overall ventilatory response that not only was in proportion to the rising CO2 production but also provided a higher than normal V : E/V : CO2 to accommodate their higher VD/VT. This “isocapnic hyperpnea” in mild COPD is similar to that achieved in the healthy fit elderly, who—in comparison to younger fit adults—also have a raised VD/ VT but maintained normocapnia during exercise (7). Exactly what mechanisms are capable of “sensing” both the rising V : CO2 (or accompanying locomotor-linked stimuli) and the elevated VD/VT are unknown—as of course is the basic mechanism for the hyperpnea itself (8). This homeostatic response in the elderly and to an even greater extent in patients with mild COPD does come at the cost of an exaggerated work of breathing and dyspnea. At peak work rates, dead space loading did not elicit further increases in VT or V : E in either the patients with mild COPD or the age-matched control subjects, but importantly this ventilatory limitation to equivalent increase in PETCO2 was reached in the patients at a much lower work rate and ventilation than in the control subjects. The ventilatory limitation to added VD in the patients was attributed to an inability to further increase end inspiratory lung volume or VT. Their progressive hyperinflation (secondary to expiratory flow limitation) and a reduced ventilatory response slope to increased PETCO2 began to appear even in submaximal exercise. Dyspneic ratings were also increased in the patients at any given work rate or ventilation, and leg discomfort was also increased at any given work rate. We note that ventilatory limitation was achieved at peakwork rates in both the healthy elderly (at 90–95 L/min V : E) and in mild COPD at w50–60 L/min. Ventilatory limitation to added chemical stimuli is also reached in many young highly fit males coincident with the onset of expiratory flow limitation at or near peak exercise (but at 160–180 L/min) (9) and at a lower V : E in fit females (10, 11), but does not occur in normally fit subjects working at lower levels of V : O2max and V : Emax. Chin and colleagues (6) are to be congratulated on their clever experimental design and especially in its adaptation to these very difficult-to-study patients. They have clearly documented ventilatory limitation in these patients with mild COPD at lower work rates than in health and in so doing have uncovered a fallacy in the traditional use of MVV as a standard for “maximum available V : E.” This misleading practice should be abandoned! However, it is not entirely clear that we can also interpret these data to mean that the ventilatory limitation and its associated dyspnea are the only or even the major cause of the impaired exercise performance in these patients. First, the traditional means of using the patient’s self-selection of “dyspnea” versus “limb discomfort” as their dominant exerciselimiting symptom does not take into account the dependence of the latter on a major determinant of the former, that is, respiratory mechanics. For example, their high sustained levels of respiratory muscle work may cause sympathetically mediated vasoconstriction of limb musculature (12), and increased intrathoracic pressures accompanying expiratory flow limitation can reduce stroke volume and cardiac output (13, 14). Both of these effects will limit O2 transport to working muscle, leading to metabolite accumulation and increased sensation of limb