Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene
Thorax 2010;65:215-220 doi:10.1136/thx.2009.120659
1. Wim Janssens1, 2. Roger Bouillon2, 3. Bart Claes3, 4. Claudia Carremans1, 5. An Lehouck1, 6. Ian Buysschaert3,
7. Johan Coolen4, 8. Chantal Mathieu5, 9. Marc Decramer1, 10. Diether Lambrechts3
* Received 29 May 2009, * Accepted 21 October 2009,
* Published Online First 8 December 2009
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 (FEV1) (r=0.28, 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; p=0.009).
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.
Is vitamin D deficiency important in the natural history of COPD?
Editorial in same issue
Thorax 2010;65:192-194 doi:10.1136/thx.2009.129619
Vitamin D consists of a group of fat-soluble prohormones, the most important of which are vitamin D2 and D3, with measurement of 25-hydroxyvitamin D (25-OHD) closely representing a person's vitamin D2 and D3 status. D2 (ergocalciferol) is plant and fungal derived, while vitamin D3 (cholecalciferol) is made from 7-dehydrocholesterol in the skin. This conversion of 7-dehydrocholesterol to previtamin D3 is governed by both the intensity and appropriate wavelength of the ultraviolet (UV) B irradiation reaching 7-dehydrocholesterol. Adequate amounts of vitamin D3 can be made in the skin after only 10–15 min of sun exposure at least twice a week without sunscreen. However, with longer exposure to UVB rays, equilibrium is achieved in the skin and the vitamin degrades as fast as it is generated. Serum concentrations of vitamin D have been found to vary with age, race, sex, season and geographic location, and subclinical deficiency is common, particularly in temperate climates.1
Once in its physiologically active form vitamin D is released into the circulation, binds to a carrier protein in the plasma (vitamin D-binding protein (DBP)) and is transported to various target organs. The hormonally active form of vitamin D mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. This VDR is constitutively expressed in monocytes, activated macrophages, dendritic cells, natural killer cells, and T and B cells. Activation has potent antiproliferative, prodifferentiative and immunomodulatory functions; both immune enhancing and immunosuppressive.2 It is these immunomodulatory properties of vitamin D that have particularly attracted interest in recent years with regards …
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