title: Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3administration.
abstract: BACKGROUND
  Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown.
  
  
  OBJECTIVE
  We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation.
  
  
  METHODS
  Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3(250,000IU vitamin D3bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3supplementation.
  
  
  RESULTS
  Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways-predominantly representing amino acid pathways-differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3treatment.
  
  
  CONCLUSIONS
  Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3in this clinical setting.
authors.affiliation: Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: jessica.alvarez@emory.edu.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Alvarez
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Chong
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Walker
authors.affiliation: Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Chandler
authors.affiliation: Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Michalski
authors.affiliation: College of Nursing, The University of Iowa, Ames, IA, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grossmann
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Shuzhao
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Frediani
authors.affiliation: Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Tirouvanziam
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: ViLinh T
authors.initials: VT
authors.lastname: Tran
authors.affiliation: Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Section of Endocrinology, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Section of Endocrinology, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000494:pharmacology; D002952:Citric Acid Cycle; D003550:Cystic Fibrosis / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D008171:Lung Diseases; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D014808:Vitamin D Deficiency
chemical_list: D000596:Amino Acids; D002762:Cholecalciferol
keywords: Cholecalciferol; Cystic fibrosis; Metabolomics; Pulmonary exacerbation; Vitamin D