This project aims to explore the relationship between Vitamin D deficiency and COPD progression via a prospective randomized placebo-controlled study. For this purpose, study was powered to 120 patients hospitalized with an exacerbation of COPD randomly assigned to a monthly oral dose of Vitamin D versus placebo. Taking into account dropouts, 182 patients are randomized during the course of the study

Principal objective: To define the therapeutic effect of Vitamin D in the chronic maintenance treatment of COPD by means of a prospective randomized placebo-controlled double blind study of 182 patients with a follow-up of at least one year. Primary endpoint is the median time to next exacerbation. Secondary endpoints are total number of exacerbations per group, number of exacerbations per patient per year, percentage of patients with one or more exacerbations per year, days of antibiotics and oral steroids, quality of life, FEV1, muscle force and survival.

Other objectives: First, to investigate the role of local and systemic levels of 25-OHD and 1,25-(OH)2D on the intensity and prevalence of bacterial colonisation, inflammatory markers, proteases and markers of oxidative stress in induced sputa and exhaled air. Second, to explore whether correction of Vitamin D deficiency by the oral supplementation of Vitamin D triggers the VDR-mediated cathelicidin pathway and increases local or systemic concentrations of the natural antimicrobial polypeptide cathelicidin with enhanced eradication of bacteria.

Inclusion Criteria:

• Primary diagnosis of COPD exacerbation
• Smoking history of at least ten pack years
• GOLD stage II, III and IV as assessed by a post-bronchodilator spirometry
• Informed consent

Exclusion Criteria:

• Tiffeneau index >70% or FEV1 >80%
• Hypercalcemia
• Sarcoidosis
• Newly discovered symptomatic osteoporosis (proven by DEXA and RX )
• Active cancer