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Smoking caused more breathing problems in those (mice) with low vitamin D – Sept 2015

Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice

Respiratory Research 2015, 16:110 doi:10.1186/s12931-015-0271-x
Nele Heulens1†, Hannelie Korf2†, Nele Cielen1, Elien De Smidt2, Karen Maes1, Conny Gysemans2, Erik Verbeken3, Ghislaine Gayan-Ramirez1, Chantal Mathieu2† and Wim Janssens1 wim.janssens at uzleuven.be †  † Equal contributors
1 Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium
2 Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium
3 Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Minderbroederstraat 12, Leuven, 3000, Belgium

VitaminDWiki Summary
Vitamin D deficient diet <100 IU
/kg of feed
17–20 ng/ml.
Control diet 1000 IU
/kg of feed
75–90 ng/ml

Mice exposed to the smoke were second generation mice on the diet
Mice with ~20 ng had far more lung problems than those with ~ 80 ng
From Background
Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive expiratory airflow limitation and is associated with chronic inflammation in the airways and lung parenchyma . In the majority of cases, this inflammatory response in COPD is initiated by long-term exposure to cigarette smoke (CS), which triggers a series of events that damage the airways and terminal airspaces, leading to lung function decline and emphysema.

A great many charts and microphotographs in the PDF
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Background
Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways. Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression. Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored.

Methods
In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics. Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic). Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages.

Results
Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice. Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung. Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice. Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-α) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice. Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect.

Conclusions
Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD. As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed.

Attached files

ID Name Comment Uploaded Size Downloads
5929 Smoke mice.pdf PDF 2015 admin 16 Sep, 2015 22:59 2.90 Mb 331
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