© 2008 American Thoracic Society doi: 10.1164/rccm.200712-1792ED
Understanding Breathlessness in Mild Chronic Obstructive Pulmonary Disease
Clinical Sciences Centre Dyspnea remains the symptom most feared by patients with chronic obstructive pulmonary disease (COPD). It limits their ability to exercise, can precipitate hospitalization, and is an independent marker for premature death (1). In the last decade, we have made significant progress in understanding the factors that lead to dyspnea, particularly during exercise, in moderate to severe COPD. Building on ideas developed in the early 1970s (2), O'Donnell and colleagues demonstrated that end-expiratory lung volume rises progressively during exercise in patients with COPD rather than remaining constant or falling, as is the case in healthy subjects (3, 4). As a result of this dynamic hyperinflation (DH), the work of breathing is greater and the respiratory muscles in the chest wall operate less efficiently, contributing to the neuromechanical disassociation that these authors have proposed as the principal mechanism for breathlessness in COPD (5). Changes in end-expiratory lung volume at rest after bronchodilators explain the improved exercise performance with these drugs, although the rate of increase of DH is generally not affected (6). This is in contrast to situations in which respiratory drive and the metabolic load on the respiratory system are reduced—for example, after oxygen treatment, where baseline mechanics are unaffected but hyperinflation is delayed. Combining these treatments has additive beneficial effects that were again associated with improved lung mechanics during exercise (7). Studies measuring chest wall volume noninvasively have complemented and confirmed these findings. However, sometimes lung mechanics can improve but the patient may adopt a less effective breathing pattern, and this may explain why they become breathless prematurely and stop exercising (8). Changes in lung volume track breathlessness during the recovery from exacerbation (9), but the degree of hyperinflation is not as predictive of the degree of breathlessness in the recovery period from exercise (10). All of these observations have been made in relatively severe COPD, and specifically in individuals with significant resting hyperinflation of the lungs. There is a paucity of data in patients with less severe disease. The basis of breathlessness in milder COPD is not a trivial issue as there are real concerns in identifying patients with only modest spirometric abnormalities, specifically GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I, where the FEV1 is above 80% predicted (11). There is a risk of believing disease to be present when this is not the case, a particular problem in the elderly in whom the FEV1/FVC ratio in healthy subjects tends toward 0.7 (12). The article by Ofir and colleagues in this issue of the Journal (pp. 622–629) is particularly welcome as it presents for the first time a detailed analysis of the mechanisms contributing to breathlessness in a group of patients with very mild COPD (13). Twenty-one patients with a mean age of 64 years and an FEV1 of 91% predicted (FEV1/FVC, 0.6) were recruited into Ofir and colleagues' study. All complained of some degree of breathlessness, with most having a Medical Research Council rating of 2 without another condition that could explain this. Although the patients' spirometry was preserved, the residual volume was somewhat increased as was the functional residual capacity, and some showed evidence of emphysema. These patients underwent an incremental cardiopulmonary exercise test recording symptoms of leg discomfort and breathlessness every minute and measurement of inspiratory capacity at the end of each 2-minute interval. The data were compared with an age-matched group of healthy subjects who completed the same protocol. The patients with COPD tended to be limited by breathlessness, whereas leg discomfort stopped exercise in the control subjects. The patients with COPD stopped sooner, had a lower anaerobic threshold, and exhibited a significant fall of inspiratory capacity by end-exercise of over 0.5 L, although there was some intersubject variability in this result. By contrast, inspiratory capacity was unchanged in the healthy control subjects. The patients with COPD had higher minute ventilation for any given degree of carbon dioxide production and adopted a more rapid shallow breathing pattern during exercise. However, their cardiovascular response to exercise was normal and they did not show oxygen desaturation. The authors reasonably conclude that increased breathlessness in mild COPD is multifactorial, reflecting a combination of increased ventilatory demand, dynamic hyperinflation, and the impact of a rapid shallow breathing pattern, although this is more likely to be the consequence of the former factors rather than an independent cause of breathlessness. Some of the mechanisms identified have been recognized before. The lower anaerobic threshold of the patients with COPD may be associated with a lower level of physical activity and this has certainly been demonstrated in patients with more severe disease. Ventilation–perfusion abnormalities and the effects of increased dead space help explain the higher ventilatory equivalent during exercise, which was clearly sufficient to prevent oxygen desaturation. However, the striking abnormality resulting from all these factors which increased minute ventilation for a given workload was the increase in end-expiratory lung volume, which, by the end of exercise, was similar to that in patients with much more severe disease. The patients with COPD studied here did have evidence of small airway disease; such small airway disease, together with accompanying emphysema, may explain the prolonged mechanical time constant necessary to favor dynamic hyperinflation. Previous data suggest that true expiratory flow limitation is uncommon in patients with such well-preserved spirometry; this should be formally tested in patients, such as those reported here, using more robust methods of detection (14). It is important not to overstate findings of this study. They do not demonstrate that all patients with mild COPD show these abnormalities and would have limited exercise performance. In general clinical practice, other factors could be contributory and there are good data suggesting that heart failure, in particular, is underdiagnosed in patients with milder COPD managed in the community (15). Nonetheless, the present results provide clear evidence that even mild airflow obstruction can be associated with considerable physiological abnormalities during exercise and that such abnormalities are present early in the natural history of COPD, with worsening disease severity serving to accelerate the speed with which hyperinflation occurs. Understanding these mechanisms helps us explain to our patients why symptoms occur and plan more sensibly the management strategies we adopt. Future studies investigating the relative efficacy of treatment in patients with COPD, such as those described by Ofir and colleagues, are clearly justified. FOOTNOTES Conflict of Interest Statement: P.C. has received funding from GlaxoSmithKline (GSK), Altana, and Chiesi to conduct clinical research trials for COPD; has led several large sponsored studies including those by GSK, Roche, Chiesi and Altana; and has spoken at meetings supported by these companies and by AstraZeneca, Pfizer/Boehringer Ingelheim, and BOC/Linde. REFERENCES
Related articles in AJRCCM:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
