title: Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  BACKGROUND
  UKCRN ID 11994.
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Rachel C A
authors.initials: RC
authors.lastname: Dancer
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Parekh
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Lax
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: D'Souza
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Shengxing
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Bassford
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: D G
authors.identifier: http://orcid.org/0000-0003-2301-3704
authors.initials: DG
authors.lastname: Bartis
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mahida
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Turner
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sapey
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Babu
authors.initials: B
authors.lastname: Naidu
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Christopher
authors.affiliation: Department of Medicine, Concord Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cooper
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.affiliation: Institute of Immunity and Transplantation, University College London, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Sansom
authors.affiliation: Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
mesh_terms: D018806:APACHE; D000368:Aged; D000818:Animals; D002112:Calcifediol / Q000097:blood / Q000494:pharmacology; D002117:Calcitriol / Q000097:blood; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D016629:Esophagectomy / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D012307:Risk Factors; D016019:Survival Analysis; D014807:Vitamin D / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000188:drug therapy
chemical_list: D014807:Vitamin D; D002117:Calcitriol; D002112:Calcifediol
keywords: ARDS; Innate Immunity