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Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration.

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords

Cholecalciferol

Cystic fibrosis

Metabolomics

Pulmonary exacerbation

Vitamin D

Journal Title metabolism: clinical and experimental
Publication Year Start




PMID- 28403943
OWN - NLM
STAT- In-Process
DA  - 20170413
LR  - 20170413
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 70
DP  - 2017 May
TI  - Plasma metabolomics in adults with cystic fibrosis during a pulmonary
      exacerbation: A pilot randomized study of high-dose vitamin D3 administration.
PG  - 31-41
LID - S0026-0495(17)30053-7 [pii]
LID - 10.1016/j.metabol.2017.02.006 [doi]
AB  - 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 D3 administration on systemic metabolism in adults
      with CF with an acute pulmonary exacerbation. DESIGN: Twenty-five hospitalized
      adults with CF were enrolled in a randomized trial of high-dose vitamin D3
      (250,000IU vitamin D3 bolus) 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 D3
      supplementation. 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 D3
      treatment. CONCLUSIONS: Numerous metabolic pathways detected by HRM varied in
      association with vitamin D status and high-dose vitamin D3 supplementation in
      adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data
      suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical
      setting.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Alvarez, Jessica A
AU  - Alvarez JA
AD  - 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: [email protected]
FAU - Chong, Elizabeth Y
AU  - Chong EY
AD  - Department of Biostatistics and Bioinformatics, Rollins School of Public Health, 
      Emory University, Atlanta, GA, USA.
FAU - Walker, Douglas I
AU  - Walker DI
AD  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of
      Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Chandler, Joshua D
AU  - Chandler JD
AD  - 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.
FAU - Michalski, Ellen S
AU  - Michalski ES
AD  - 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.
FAU - Grossmann, Ruth E
AU  - Grossmann RE
AD  - College of Nursing, The University of Iowa, Ames, IA, USA.
FAU - Uppal, Karan
AU  - Uppal K
AD  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of
      Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Li, Shuzhao
AU  - Li S
AD  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of
      Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Frediani, Jennifer K
AU  - Frediani JK
AD  - 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.
FAU - Tirouvanziam, Rabindra
AU  - Tirouvanziam R
AD  - 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.
FAU - Tran, ViLinh T
AU  - Tran VT
AD  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of
      Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Tangpricha, Vin
AU  - Tangpricha V
AD  - 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.
FAU - Jones, Dean P
AU  - Jones DP
AD  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of
      Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Ziegler, Thomas R
AU  - Ziegler TR
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20170211
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
OTO - NOTNLM
OT  - Cholecalciferol
OT  - Cystic fibrosis
OT  - Metabolomics
OT  - Pulmonary exacerbation
OT  - Vitamin D
EDAT- 2017/04/14 06:00
MHDA- 2017/04/14 06:00
CRDT- 2017/04/14 06:00
PHST- 2016/10/17 [received]
PHST- 2017/01/07 [revised]
PHST- 2017/02/05 [accepted]
AID - S0026-0495(17)30053-7 [pii]
AID - 10.1016/j.metabol.2017.02.006 [doi]
PST - ppublish
SO  - Metabolism. 2017 May;70:31-41. doi: 10.1016/j.metabol.2017.02.006. Epub 2017 Feb 
      11.

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