Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS)

• Published in: Thorax Vol. 70; no. 7; pp. 617 - 624
• Main Authors: Dancer, Rachel C A, Parekh, Dhruv, Lax, Sian, D'Souza, Vijay, Zheng, Shengxing, Bassford, Chris R, Park, Daniel, Bartis, D G, Mahida, Rahul, Turner, Alice M, Sapey, Elizabeth, Wei, Wenbin, Naidu, Babu, Stewart, Paul M, Fraser, William D, Christopher, Kenneth B, Cooper, Mark S, Gao, Fang, Sansom, David M, Martineau, Adrian R, Perkins, Gavin D, Thickett, David R
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.07.2015; BMJ Publishing Group
• Series: Original article
• Subjects: Aged; Animals; APACHE; Apoptosis; Calcifediol - blood; Calcifediol - pharmacology; Calcitriol - blood; Cells, Cultured; Critical Care; Disease Models, Animal; Epithelial Cells - drug effects; Esophagectomy - adverse effects; Female; Gene Expression Regulation - drug effects; Gram-positive bacteria; Humans; Intensive Care Units; Male; Mice, Inbred C57BL; Middle Aged; Mortality; Patients; Physiology; Pulmonary Alveoli - cytology; Pulmonary Alveoli - drug effects; Respiratory distress syndrome; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - etiology; Respiratory Distress Syndrome - prevention & control; Risk Factors; Studies; Survival Analysis; Vitamin D; Vitamin D - therapeutic use; Vitamin D Deficiency - blood; Vitamin D Deficiency - complications; Vitamin D Deficiency - drug therapy; Vitamin deficiency; ARDS; Innate Immunity
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2014-206680

RationaleVitamin 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.ObjectivesTo 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.MethodsHuman, murine and in vitro primary alveolar epithelial cell work were included in this study.FindingsVitamin 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.ConclusionsVitamin 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 registrationUKCRN ID 11994.