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Original article
Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS)
  1. Rachel C A Dancer1,
  2. Dhruv Parekh1,
  3. Sian Lax1,
  4. Vijay D'Souza1,
  5. Shengxing Zheng1,
  6. Chris R Bassford1,
  7. Daniel Park1,
  8. D G Bartis1,
  9. Rahul Mahida1,
  10. Alice M Turner1,
  11. Elizabeth Sapey1,
  12. Wenbin Wei2,
  13. Babu Naidu1,
  14. Paul M Stewart3,
  15. William D Fraser4,
  16. Kenneth B Christopher5,
  17. Mark S Cooper6,
  18. Fang Gao1,
  19. David M Sansom7,
  20. Adrian R Martineau8,
  21. Gavin D Perkins9,
  22. David R Thickett1
  1. 1Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
  2. 2School of Cancer Sciences, University of Birmingham, Birmingham, UK
  3. 3Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
  4. 4Norwich Medical School, University of East Anglia, Norwich, UK
  5. 5Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  6. 6Department of Medicine, Concord Medical School, University of Sydney, Sydney, New South Wales, Australia
  7. 7Institute of Immunity and Transplantation, University College London, London, UK
  8. 8Blizard Institute, Queen Mary University of London, London, UK
  9. 9Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK
  1. Correspondence to Professor David Thickett, Centre for Translational Inflammation and Fibrosis Research, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TH, UK; d.thickett{at}


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.

  • ARDS
  • Innate Immunity

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