Physical activity and chronic obstructive pulmonary disease.

Physical activity, not to be confused with exercise tolerance, is an essential component of human life. Defined as any movement of the body produced by skeletal muscles that consumes oxygen (1), physical activity allows normal functioning during daily life, both at home and at work. In healthy subjects, regular physical activity improves health and prognosis. In patients, reduced physical activity is a marker of disease severity, often a poor prognostic marker, and always a key contributor to reduced health status. Thus, a better understanding of the mechanisms contributing to reduced physical activity in disease, as well as to improved wellbeing in healthy subjects, is a matter of great interest. Physical activity has only recently begun to be studied rigorously in patients with chronic obstructive pulmonary disease (COPD). We now know that, compared with healthy subjects, physical activity is reduced in patients with moderate to severe COPD (2, 3). We also know that physical activity is only modestly correlated with the degree of airflow obstruction (2, 3), the functional hallmark of COPD, indicating that other factors must be involved in limiting physical activity in these patients (4). Recently, Garcia-Aymerich and colleagues showed that physical activity reduces hospital admissions, the rate of lung function decline, and even mortality in patients with COPD (5, 6). However, many questions still remain unanswered, including the contribution of different mechanisms to reduced physical activity in these patients, or the effect of therapy on physical activity. In this issue of the Journal (pp. 743–751), Watz and coworkers present novel data that help to better understand the contribution of different pulmonary and extrapulmonary factors to reduced physical activity in COPD (7). Traditionally, physical activity has been estimated from questionnaires and clinical interviews. Modern technology allowed Watz and colleagues to estimate physical activity much more precisely by using multisensor accelerometer armbands that record ‘‘steps per day’’ and calculate ‘‘energy expenditure’’ (7). Physical activity levels were estimated by dividing total daily energy expenditure by whole-night sleeping energy expenditure (7). Using this technique, the authors confirmed previous data (2, 3) and showed that more than two-thirds of a relatively large cohort (n 5 170) of patients with stable COPD, covering the whole range of GOLD (Global Initiative for Chronic Obstructive Lung Disease) severity, have low physical activity (7). More interestingly, however, they used multivariate analysis to explore the relationship between a number of pulmonary and extrapulmonary factors and reduced physical activity in these patients (7). They found that their ‘‘best’’ model was able to explain only 37% of the total variance of physical activity (7), suggesting that factors not included in the analysis contribute significantly to reduced physical activity in COPD. The degree of airflow obstruction accounted for about two-thirds of this 37% of variance, whereas the combination of two extrapulmonary factors (systemic inflammation and left cardiac dysfunction) explained the remaining third (7). Finally, and contrary to what might have been expected, the authors found that the presence of nutritional depletion, depression, anemia, peripheral arterial disease, pulmonary hypertension, and/or peripheral muscle strength did not contribute significantly to physical activity in these patients (7). The study by Watz and colleagues (7) provides interesting data that permit better understanding of the mechanisms contributing to reduced physical activity in patients with COPD. However, as any good piece of research, this study also raises many questions. For instance, despite the fact that a relatively large number of pulmonary and extrapulmonary factors that can potentially reduce physical activity in these patients were included in the analyses, as well as a number of potential lifestyle confounders (e.g., the level of education, regular alcohol consumption, and smoking status, among others), these could explain less than 50% of the total physical activity variance. What other pulmonary or extrapulmonary factor(s) are we missing? To name only a few, and just to stimulate further thoughts, I would suggest that future studies consider including in the model the following: the degree of lung hyperinflation, which has prognostic value in these patients (8), can limit oxygen delivery to tissues (9), and may contribute to systemic inflammation (10); the presence of systemic endothelial dysfunction (11); other inflammatory markers (e.g., IL-6, a cytokine involved in the sense of ‘‘fatigue’’ in athletes [12]); and/or the possibility of abnormal oxidative metabolism in the mitochondrial of skeletal muscle (13). Likewise, diastolic left heart dysfunction (as assessed by echocardiography and N-terminal pro–B-type natriuretic peptide levels) and systemic inflammation (as assessed by the plasma values of C-reactive protein and fibrinogen) contributed, independently of the degree of airflow limitation, to physical activity in COPD (7). We know that left heart failure occurs in about 20% of elderly patients with COPD, and that in about a half of these patients this is of the diastolic type (14). Have Watz and coworkers identified a new form of ‘‘cardiac dysfunction,’’ similar to the skeletal muscle dysfunction known to occur in COPD (15) and also believed to be related to systemic inflammation (16)? The answer to these and others questions that investigators in the field may raise from the findings of Watz and coworkers (7) may be important because they may identify domains of COPD amenable to therapeutic intervention.