Dancer, R.C., Parekh, D., Lax, S. et al. (19 more authors) (2015) Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax, 70 (7). pp. 617-624. ISSN 0040-6376
Abstract
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.
TRIAL REGISTRATION: UKCRN ID 11994.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ |
Keywords: | ARDS; Innate Immunity; APACHE; Aged; Animals; Calcifediol; Calcitriol; Cells, Cultured; Disease Models, Animal; Epithelial Cells; Esophagectomy; Female; Gene Expression Regulation; Humans; Intensive Care Units; Male; Mice, Inbred C57BL; Middle Aged; Pulmonary Alveoli; Respiratory Distress Syndrome, Adult; Risk Factors; Survival Analysis; Vitamin D; Vitamin D Deficiency |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Department of Neuroscience (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Jul 2016 13:25 |
Last Modified: | 21 Jul 2016 13:25 |
Published Version: | http://dx.doi.org/10.1136/thoraxjnl-2014-206680 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1136/thoraxjnl-2014-206680 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101777 |