Introduction Vitamin D deficiency has been associated with many chronic illnesses, but little is known about its relationship with chronic obstructive pulmonary disease (COPD). Objectives Serum 25-hydroxyvitamin D (25-OHD) levels were measured in 414 (ex)-smokers older than 50 years and the link between vitamin D status and presence of COPD was assessed. The rs7041 and rs4588 variants in the vitamin D-binding gene (GC) were genotyped and their effects on 25-OHD levels were tested. Results In patients with COPD, 25-OHD levels correlated significantly with forced expiratory volume in 1 s (FEV 1 ) (r¼0.28, p<0.0001). Compared with 31% of the smokers with normal lung function, as many as 60% and 77% of patients with GOLD (Global Initiative for Obstructive Lung Disease) stage 3 and 4 exhibited deficient 25-OHD levels <20 ng/ml (p<0.0001). Additionally, 25-OHD levels were reduced by 25% in homozygous carriers of the rs7041 at-risk T allele (p<0.0001). This correlation was found to be independent of COPD severity, smoking history, age, gender, body mass index, corticosteroid intake, seasonal variation and rs4588 (p<0.0001). Notably, 76% and 100% of patients with GOLD stage 3 and 4 homozygous for the rs7041 T allele exhibited 25-OHD levels <20 ng/ml. Logistic regression corrected for age, gender and smoking history further revealed that homozygous carriers of the rs7041 T allele exhibited an increased risk for COPD (OR 2.11; 95% CI 1.20 to 3.71; p¼0.009). Conclusion Vitamin D deficiency occurs frequently in COPD and correlates with severity of COPD. The data warrant vitamin D supplementation in patients with severe COPD, especially in those carrying at-risk rs7041 variants.

Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

The discovery that the vitamin D endocrine system regulates a very large number of genes and their associated biological processes improves our insight into the fundamental role of vitamin D and sun exposure for human health. Accumulating epidemiological data are linking a low vitamin D nutritional status to highly prevalent diseases such as cancer, autoimmune diseases, and chronic infections. Approximately half of the world's elderly, and to a lesser extent the adult population, have insufficient to deficient 25-hydroxyvitamin D (25-OHD) serum levels, and several intervention studies are being undertaken to study the impact of adequate vitamin D supplementation in chronic diseases. In this perspective we claim that chronic obstructive pulmonary disease (COPD) is a candidate disease for which vitamin D supplementation might be beneficial. Epidemiological studies revealed a dose-dependent association between serum 25-OHD levels and pulmonary function so that adequate vitamin D supplementation may extend beyond its protection against osteoporotic fractures. In line with the novel insights on its immune function, it is tempting to speculate that vitamin D may down-regulate the inflammatory immune response in the airways while boosting innate immune defense against different microorganisms. Apart from its affects on osteoporosis, vitamin D may also interfere with other comorbidities of COPD such as skeletal muscle weakness, cardiovascular disease, and cancer. Because respiratory treatments in COPD fail to reverse disease progression, interventional trials that may exploit the broader potential of vitamin D are warranted. A further challenge of such studies is to define optimal serum 25-OHD levels for such noncalcemic endpoints.

We conclude that similar to single breath exhaled NO, exhaled NO at different flow rates does not contribute to the diagnosis of COPD in standard respiratory practice.

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