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      Chronic Obstructive Pulmonary Disease Is Associated with Low Levels of Vitamin D

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          Abstract

          Introduction

          COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.

          Methods

          Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40–76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO 2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.

          Results

          COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22).

          Conclusion

          COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

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          Most cited references19

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          Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.

          The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D(3) signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)(2)D(3) is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D(3)-dependent gene expression. 1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D(3) induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.
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            1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation.

            1 Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D3, is a potent immunomodulatory agent. Here we show that dendritic cells (DCs) are major targets of 1,25(OH)2D3-induced immunosuppressive activity. 1,25(OH)2D3 prevents the differentiation in immature DCs of human monocytes cultured with GM-CSF and IL-4. Addition of 1,25(OH)2D3 during LPS-induced maturation maintains the immature DC phenotype characterized by high mannose receptor and low CD83 expression and markedly inhibits up-regulation of the costimulatory molecules CD40, CD80, and CD86 and of class II MHC molecules. This is associated with a reduced capacity of DCs to activate alloreactive T cells, as determined by decreased proliferation and IFN-gamma secretion in mixed leukocyte cultures. 1, 25(OH)2D3 also affects maturing DCs, leading to inhibition of IL-12p75 and enhanced IL-10 secretion upon activation by CD40 ligation. In addition, 1,25(OH)2D3 promotes the spontaneous apoptosis of mature DCs. The modulation of phenotype and function of DCs matured in the presence of 1,25(OH)2D3 induces cocultured alloreactive CD4+ cells to secrete less IFN-gamma upon restimulation, up-regulate CD152, and down-regulate CD154 molecules. The inhibition of DC differentiation and maturation as well as modulation of their activation and survival leading to T cell hyporesponsiveness may explain the immunosuppressive activity of 1, 25(OH)2D3.
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              Serum vitamin D concentrations among elderly people in Europe.

              Vitamin D status decreases with age, mainly as a result of restricted sunlight exposure, reduced capacity of the skin to produce vitamin D, and reduced dietary vitamin D intake. We measured wintertime serum 25-hydroxyvitamin D [25(OH)D] concentrations in 824 elderly people from 11 European countries. 36% of men and 47% of women had 25(OH)D concentrations below 30 nmol/L. Users of vitamin D supplements and/or sunlamps had higher 25(OH)D (median 54 nmol/L) than non users (median 31 nmol/L). Surprisingly, lowest mean 25(OH)D concentrations were seen in southern European countries. Low 25(OH)D concentrations could largely be explained by attitudes towards sunlight exposure and factors of physical health status, after exclusion of users of vitamin D supplements or sunlamps. Problems with daily living activities and wearing clothes with long sleeves during periods of sunshine were strong predictors of low wintertime serum 25(OH)D concentrations. These findings show that free-living elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter and that dietary enrichment or supplementation with vitamin D should be seriously considered during this season.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                21 June 2012
                : 7
                : 6
                : e38934
                Affiliations
                [1 ]Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
                [2 ]Institute of Medicine, University of Bergen, Bergen, Norway
                [3 ]Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
                University of Tübingen, Germany
                Author notes

                Conceived and designed the experiments: LP PSB PSH TME. Performed the experiments: LP. Analyzed the data: LP MA PSB PSH TME. Contributed reagents/materials/analysis tools: LP MA PSB JAH TME. Wrote the paper: LP MA PSB JAH PSH TME.

                Article
                PONE-D-12-05304
                10.1371/journal.pone.0038934
                3380863
                22737223
                a37f5654-1b23-43d2-af8f-5f2a614bf54f
                Persson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 18 February 2012
                : 14 May 2012
                Page count
                Pages: 8
                Categories
                Research Article
                Medicine
                Clinical Immunology
                Immunity
                Inflammation
                Epidemiology
                Clinical Epidemiology
                Nutrition
                Obesity
                Vitamins
                Pulmonology
                Chronic Obstructive Pulmonary Diseases
                Environmental and Occupational Lung Diseases
                Smoking Related Disorders

                Uncategorized
                Uncategorized

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