Abstract
Chronic Obstructive Pulmonary Disease (COPD) is increasingly being recognized as systemic rather than only a pulmonary disease. Increasing amounts of activated inflammatory cells, mediators and oxidative stress are not restricted to the local compartment- including airways, lung parenchyma, and pulmonary vasculature - but are also present in the circulation and even more pronounced during exacerbations. The origin and consequences of the systemic inflammation and oxidative stress present in COPD patients remains still to be elucidated. The interactions between exercise stress and the immune system provide a unique opportunity to link basic and clinical physiology and to evaluate the role of underlying stress and immunophysiologic mechanisms. Hypothetically, increased exposure to inflammation and oxidative stress might negatively affect tissues, e.g. skeletal muscles, and thereby play a role in the ongoing and progressive systemic effects of COPD. This thesis aimed to investigate the effects of exercise on the immune response in patients with COPD. It was found that both high and moderate cycling exercise further increases chronic systemic inflammation and oxidative stress in patients with COPD. Especially within a subgroup of patients, namely muscle-wasted COPD patients, the exercise-induced systemic effects are elevated in comparison with healthy individuals and COPD patients without muscle wasting. Even six minutes walking was able to induce systemic responses in these muscle-wasted patients. Furthermore, the severity of muscle wasting was related to the increase of systemic inflammation and oxidative stress, suggesting a causative relation between these systemic effects. Finally, it was shown that cycling with supplemental exercise diminished exercise-induced systemic inflammation and prevented oxidative stress. Mechanistically, both activation of neutrophils and ATP degradation were involved in these effects. In summary, only modest exercise induces a systemic inflammatory and oxidative response in especially muscle-wasted COPD patients. Chronic exposure to these effects might be involved in the ongoing progression of the disease
