期刊
THORAX
卷 70, 期 7, 页码 617-624出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/thoraxjnl-2014-206680
关键词
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资金
- Wellcome trust
- QEHB charities
- Medical Research Council UK
- NIHR
- ERS
- Marie Curie Intra-European Fellowship
- MRC [MR/L008335/1, G1100196, MR/J011266/1, MR/L002736/1] Funding Source: UKRI
- Medical Research Council [MR/L008335/1, MR/L002736/1, G1100196, MR/J011266/1] Funding Source: researchfish
- National Institute for Health Research [ACF-2012-09-002, DHCS/06/06/010, NF-SI-0514-10139, PB-PG-0408-16104, NF-SI-0508-10356] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [PB-PG-0408-16104] Funding Source: National Institutes of Health Research (NIHR)
Rationale Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated. Objectives To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity. Methods Human, murine and in vitro primary alveolar epithelial cell work were included in this study. Findings Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients. Conclusions Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.
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