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

Thorax. 2015 Jul;70(7):617-24. doi: 10.1136/thoraxjnl-2014-206680. Epub 2015 Apr 22.

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.

Keywords: ARDS; Innate Immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Aged
  • Animals
  • Calcifediol / blood
  • Calcifediol / pharmacology
  • Calcitriol / blood
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Esophagectomy / adverse effects
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Intensive Care Units
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects
  • Respiratory Distress Syndrome, Adult / blood
  • Respiratory Distress Syndrome, Adult / etiology*
  • Respiratory Distress Syndrome, Adult / prevention & control
  • Risk Factors
  • Survival Analysis
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / drug therapy

Substances

  • Vitamin D
  • Calcitriol
  • Calcifediol