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      The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis

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          Abstract

          Background

          In recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases. However, the association between serum vitamin D and COPD is not well studied. This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD.

          Methods

          A systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases. The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency. Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method.

          Results

          A total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included. Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002). Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326). Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk.

          Conclusion

          Serum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation. Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation. It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD.

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          Most cited references 52

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          Update in vitamin D.

          The past decade, particularly the last 18 months, witnessed a vigorous increase in interest in vitamin D from both the lay and biomedical worlds. Much of the growing interest in vitamin D is powered by new data being extracted from the National Health and Nutrition Examination Survey (NHANES). The newest statistics demonstrate that more than 90% of the pigmented populace of the United States (Blacks, Hispanics, and Asians) now suffer from vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml), with nearly three fourths of the white population in this country also being vitamin D insufficient. This represents a near doubling of the prevalence of vitamin D insufficiency seen just 10 yr ago in the same population. This review attempts to provide some explanation for: 1) the rapid decline in vitamin D status in the United States; 2) the adverse impact of vitamin D insufficiency on skeletal, infectious/inflammatory, and metabolic health in humans; and 3) the therapeutic rationale and reliable means for vigorous supplementation of our diets with vitamin D.
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            High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

            Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) University Hospitals Leuven, Leuven, Belgium. 182 patients with moderate to very severe COPD and a history of recent exacerbations. 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). This was a single-center study with a small sample size. High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).
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              Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes.

              There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process-be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process. In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue. Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2016
                19 October 2016
                : 11
                : 2597-2607
                Affiliations
                Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China
                Author notes
                Correspondence: Yulin Ji, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, People’s Republic of China, Tel/fax +86 28 8542 2571, Email huaxijiyulin@ 123456163.com
                Article
                copd-11-2597
                10.2147/COPD.S101382
                5079694
                © 2016 Zhu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                meta-analysis, copd, risk, severity, exacerbation, vitamin d

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