Dancer, Rachel C AParekh, DhruvLax, SianD'Souza, VijayZheng, ShengxingBassford, Chris RPark, DanielBartis, D GMahida, RahulTurner, Alice MSapey, ElizabethWei, WenbinNaidu, BabuStewart, Paul MFraser, William DChristopher, KennethCooper, Mark SGao, FangSansom, David MMartineau, Adrian RPerkins, Gavin DThickett, David R2015-08-032015Dancer, R. C. A., D. Parekh, S. Lax, V. D'Souza, S. Zheng, C. R. Bassford, D. Park, et al. 2015. “Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).” Thorax 70 (7): 617-624. doi:10.1136/thoraxjnl-2014-206680. http://dx.doi.org/10.1136/thoraxjnl-2014-206680.0040-6376http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820680Rationale: 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.en-USARDSInnate ImmunityJournal Article2015-08-0310.1136/thoraxjnl-2014-206680