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

R. C. A. Dancer, D. Parekh, S. Lax, V. D'souza, S. Zheng, C. R. Bassford, D. Park, D. G. Bartis, Rahul Mahida, Alice Turner, E. Sapey, W. Wei, B. Naidu, P. M. Stewart, W. D. Fraser, K. B. Christopher, M. S. Cooper, F. Gao, D. M. Sansom, A. R. MartineauG. D. Perkins, D. R. Thickett

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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.
Original languageEnglish
Pages (from-to)617-624
JournalThorax
Volume70
Issue number7
Early online date22 Apr 2015
DOIs
Publication statusPublished - 1 Jul 2015

Keywords

  • ARDS
  • Innate Immunity

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