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Project

The vitamin D axis in COPD role in skeletal muscle function and exacerbations.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease which imposes huge burden on our society. So far no treatment, except for smoking cessation, has been clearly shown to affect disease progression. It is accepted that repetitive infections and chronic inactivity play a detrimental role in the progressive course of the disease as they may respectively trigger exacerbations with further decline of pulmonary function or may cause skeletal muscle weakness with enhanced functional limitation. A recent study made it clear that a phenotype of frequent-exacerbation is present in COPD patients. A key question is to unravel why this subgroup of COPD patients are more prone to exacerbations. Similarly, it is unknown why two third of COPD patients develop muscle dysfunction. The vitamin D pathway is involved in bacterial defense and healthy muscular function. We have linked severe vitamin D deficiency and genetic polymorphisms in the vitamin D pathway to COPD and have recently performed a randomized controlled trial to explore the effect of long-term and high dose vitamin D supplements in moderate to very severe COPD. We showed that only in very deficient patients, substitution alters the susceptibility to infections. Moreover, supplementation resulted in a significant additional improvement of maximal exercise capacity and muscle force in the subgroup of patients who followed active rehabilitation during our intervention trial. All together, this suggests that the vitamin D pathway, by its interaction with infection and inactivity, may partly explain the existing heterogeneity of COPD phenotypes. As vitamin D deficiency can easily and cost effectively be reversed by oral supplementation in almost every individual, the present concept deserves further studies. The current research project aims to explore the above-mentioned clinical observations in more detail in the laboratory: 1) We will study bacterial defense and muscular properties in vitro on cells isolated from COPD patients, smoking and non-smoking controls. 2) A smoking mouse model will be used to explore the same interactions and their clinical outcomes prospectively in vivo. Overall, the present proposal will clarify the potential role of the vitamin D pathway in COPD with regard to infection and disease progression, inactivity and skeletal muscle weakness.
Date:1 Oct 2011 →  30 Sep 2015
Keywords:Vitamin D, Skeletal muscles, Inactivity, Repetitive infections, Chronic obstructive pulmonary disease