Assessing the exercise response to a bronchodilator in COPD

P rogressive irreversible airway obstruction is the defining characteristic of chronic obstructive pulmonary disease (COPD). However, people with COPD do not complain of airway obstruction but, more usually, about the associated restriction of physical activity. The disability resulting from COPD may also be compounded by peripheral muscle dysfunction that further limits exercise capacity. Traditionally, we have used tests of whole body exercise performance to reflect this process. However, as we learn more about COPD, it is revealed as a complex condition where apparently straightforward truths are neither pure nor simple. The relationship between airway function and exercise capacity is a good example of this complexity, since it may naively be expected that the decline in physical activity may mirror the progression of airway obstruction. Furthermore, it might also be reasonable to expect that an improvement in airway function may lead to a similar gain in physical activity. In fact, neither of these phenomena is necessarily observed. The relationship between static lung function and exercise capacity is not predictive in COPD and, in addition, the forced expiratory volume in 1 s (FEV1) alone cannot be used to judge disability. Furthermore, the effects of short-term improvements in airway function by bronchodilation do not reliably lead to improved exercise capacity. This is clearly a source of frustration—both for patients whose performance may not improve and for those who seek to demonstrate the benefits of a therapeutic intervention. There are several possible explanations for the apparent disconnection between changes in lung function and exercise performance. One explanation lies in understanding the nature of exercise capacity limitation in COPD, which may vary with the stage of the disease. Another factor may be the method chosen to assess activity limitation. We usually use formal, standardised whole body exercise tests as a proxy for domestic physical activity. However, not all exercise tests assess the same physiological activity and may not always be the most appropriate or sensitive investigation to demonstrate therapeutic change. Some of these factors are explored by Pepin and co-workers in this issue of Thorax (see page 291) where they begin to address the subject with the degree of sophistication that it deserves. Advancing airway obstruction in COPD is associated with exercise limitation, but the factors that limit maximal incremental (peak) performance may be different from those limiting endurance (constant load) exercise. In health, maximal capacity is usually defined by the oxygen uptake of the respiring muscle mass. This is generally the product of oxygen delivery and muscle mass. Neither ventilation nor gas exchange are normally factors in maximal limitation, although peripheral muscle fatigue may be a complication. In contrast, submaximal constant workload exercise is limited by factors that affect endurance capacity. In health these include substrate usage, the state of peripheral muscle conditioning, motivation and thermoregulation. As COPD develops, two further factors become evident. First, ventilatory limitation begins to impede the exercise response and maximal exercise may eventually be terminated prematurely through the phenomenon of dynamic hyperinflation, although this is not universal. 3 Second, deconditioned peripheral muscles may result in subjective or physiologically limiting fatigue. Both of these factors will clearly play a major role in the termination of maximal exercise and may also curtail endurance exercise if the relative workload is sufficient for them to develop. An endurance or constant workload exercise test is usually set at a proportion of the maximal performance. In health, the sustainable fraction of maximal capacity that can be maintained as an endurance task is of the order of 75% and can be improved by training or diet. Ironically, people with COPD can sustain a slightly higher fraction of their peak capacity because the latter may be artificially reduced by the ventilatory limitation. The exploration of exercise pathophysiology in COPD has naturally taken place in the laboratory where motorised treadmills or cycle ergometers have been used as the exercise testing platform. Such laboratory-based studies have provided invaluable insight into the exercise responses in COPD. However, there are details in the methodology of these explorations that have created some misconceptions now that exercise testing is routinely used as an outcome for therapeutic intervention. Most studies have used the cycle ergometer as the exercise platform for two reasons. First, the cycle ergometer is a stable and safe platform from which it is easier to take samples or perform measurements while exercising. Second, the ergometer provides a direct measurement of workload. However, cycling is not the same as walking, and the two platforms are not interchangeable. Cycling uses less muscle mass but may produce a greater lactate response because of the unfamiliar use of the leg muscles. For the last couple of decades it has been perceived wisdom that maximal exercise in COPD is limited as much by the legs as by dyspnoea. However, this does not fit with patients’ descriptions of their symptoms where breathlessness predominates. More recently a repetition of the comparison of limiting factors in COPD suggests that, when a walking test is used, dyspnoea is indeed the limiting symptom. When exercise tests are used as an outcome measure for therapeutic interventions in COPD, it is important—when interpreting the response—to understand the nature of the test that is being used. Tests of maximal capacity may provide insights into pathphysiology but, in COPD, they are unlikely to change much with a therapeutic intervention. Constant workload or endurance tests, by contrast, are more likely to be responsive to treatment for two reasons: (1) the factors that limit endurance exercise are more amenable to intervention and (2) because even a minor change in maximal capacity will reduce the relative workload of the constant workload test and amplify the response. We have become used to seeing reliable improvements in exercise capacity following exercise training in COPD in the context of pulmonary rehabilitation. In this situation, small improvements occur in maximal capacity but much greater benefits are evident on tests of exercise endurance. However, demonstration of a similar improvement in exercise capacity following administration of a bronchodilator has been inconsistent. EDITORIALS 281