Skeletspierdysfunctie in COPD, effect van (in-)activiteit.

Chronic obstructive pulmonary disease (COPD) is a disease with high clinical and economic burden. By the year 2030 COPD will be among the top five chronic diseases in terms of global mortality and morbidity. In subjects older than 40 years of age the prevalence of moderate COPD has recently been estimated to be 10.1% in a large multinational population study. Smoking is the main risk factor to develop COPD in Western countries. In 2006 a world wide panel of experts, assembled in the Global initiative for Chronic Obstructive Lung Disease (GOLD), defined COPD as a preventable and treatable pulmonary disease with significant extra-pulmonary effects that may contribute to the disease severity in individual patients. The recognition of the systemic consequences in this international statement is important and opens new avenues for research. Examples of the systemic consequences are depression, endocrinological abnormalities, insuline resistance, anemia, osteoporosis, and skeletal muscle weakness. The latter has been a research interest of our group for many years. Skeletal muscle dysfunction is surely worthy studying. We showed that muscle weakness is related to exercise intolerance and excessive utilization of health care resources. In addition, muscle weakness can be restored by exercise training, as our group convincingly showed in previous years. Interestingly, although all experts agree that systemic consequences are important, the development of these systemic consequences is poorly understood. Full understanding is further complicated by the occurrence of comorbidity, which develops as a consequence of shared risk factors such as smoking and systemic inflammation. Since systemic inflammation indeed has been associated with much of these systemic effects and co-morbid conditions it has been recently suggested that COPD may evolve into a chronic inflammatory syndrome. Physical inactivity is another factor intimately linked to the development of the systemic consequences. Physical inactivity is now well established as an important factor leading to morbidity in the population. In fact, next to smoking, physical activity is claimed to be the second most important reason of preventable mortality. We have suggested that inactivity may be present even in early stages of the disease. Several epidemiological studies suggest that inactivity may reinforce systemic inflammation and regular physical activity attenuates the inflammatory cytokine production upon plasma LPS-stimulation. It should be noted that no studies have investigated physical activity levels in patients not yet referred to a specialized center. In early stages COPD, however, patients are followed in general practice and many are even undiagnosed. It is unclear whether these patients are physicaly inactive and whether they have, or develop systemic consequences.. Patients with COPD experience periodic deteriorations of their symptoms, which are often secondary to viral or bacterial infections. These exacerbations are associated to significant mortality and they accelerate lung function decline, decline in functional status and decline in health related quality of life. They are also associated with very low physical activity levels. Several lines of evidence point at inactivity, during and following exacerbations, as a major cause of the increased morbidity after exacerbations. First, we found acute reductions in skeletal muscle strength during exacerbations of COPD. Others have reported a rapid onset of insulin resistance with 5 days of bed rest in healthy volunteers, which may further contribute to the systemic consequences of an exacerbation. Second, epidemiological studies suggest a role for inactivity in readmission to the hospital. This was confirmed in our lab with formal activity monitoring. Patients readmitted within the year had 12min of walking time per day at home, whereas those not readmitted walked 30 min at home, one month after the initial hospital admission. Third, at the molecular level, we found in the skeletal muscle a decreased expression of Insulin Growth Factor-I and the muscle regulatory factor MyoD, in the absence of up-regulated muscle inflammation. Lastly, the muscle weakness observed during exacerbations can be blocked by increasing skeletal muscle activity with resistance training (see below). This further strengthens the hypothesis that inactivity is causally related to the long term deleterious effects of an exacerbation. From the above, two target populations emerge. First, patients with mild disease, or those newly diagnosed where the prevalence and incidence of systemic consequences of the disease and factors contributing to the development of systemic consequences should be explored. Second, patients suffering from acute exacerbations who, if subjected to current best clinical practice will suffer from significance worsening of physical activity levels, muscle weakness and will remain at high risk for readmission and even death.

Trefwoorden:Skeletal muscle dysfunction