The study by Rutten et al7 in this issue (see page 245) provides evidence of intestinal compromise and, importantly, evidence of an associated mechanism for intestinal dysfunction in patients with COPD. They proposed that the increased metabolic demands that are associated with the physical activities of patients with COPD result in a reduction in intestinal perfusion causing ischemia in these tissues. The authors demonstrated increased intestinal permeability in patients with COPD at rest, compared with healthy individuals. However, physical exertion, represented by day-to-day activities, significantly increased the intestinal permeability of the small intestine in patients with COPD, which was assessed by measurement of the excretion of orally ingested sugar probes. This increased permeability was associated with acute enterocyte damage, which occurs rapidly during physical exertion and continues after the completion of activities. Importantly, there was no evidence of increased enterocyte damage in patients with COPD at rest, suggesting that the physical activity itself precipitates the epithelial damage. Of note, the authors demonstrated that performing the study exercise activities placed a higher metabolic demand on patients with COPD, and that metabolic load, measured as serum lactic acid, correlated with intestinal permeability in these patients. Thus, an intriguing hypothesis presents whereby patients with COPD, unable to cope with the metabolic demand of daily activities, are susceptible to intestinal ischemia and associated enterocyte damage.