title: Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids.
abstract: BACKGROUND
  Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD.
  
  
  OBJECTIVE
  To investigate whether expression of the sputum lipidome is affected by COPD or cigarette smoking.
  
  
  METHODS
  Lipid expression was investigated with liquid chromatography and high-resolution quadrupole time-of-flight mass spectrometry in induced sputum comparing smokers with and without COPD, and never-smokers. Changes in lipid expression after 2-month smoking cessation were investigated in smokers with and without COPD.
  
  
  RESULTS
  More than 1,500 lipid compounds were identified in sputum. The class of sphingolipids was significantly higher expressed in smokers with COPD than in smokers without COPD. At single compound level, 168 sphingolipids, 36 phosphatidylethanolamine lipids, and 5 tobacco-related compounds were significantly higher expressed in smokers with COPD compared with smokers without COPD. The 13 lipids with a high fold change between smokers with and without COPD showed high correlations with lower lung function and inflammation in sputum. Twenty (glyco)sphingolipids and six tobacco-related compounds were higher expressed in smokers without COPD compared with never-smokers. Two-month smoking cessation reduced expression of 26 sphingolipids in smokers with and without COPD.
  
  
  CONCLUSIONS
  Expression of lipids from the sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD. Considering their potential biologic properties, they may play a role in the pathogenesis of COPD.
authors.affiliation: 1 Department of Pulmonary Diseases.
authors.forename: Eef D
authors.initials: ED
authors.lastname: Telenga
authors.forename: Roland F
authors.initials: RF
authors.lastname: Hoffmann
authors.lastname: Ruben t'Kindt
authors.forename: Susan J M
authors.initials: SJ
authors.lastname: Hoonhorst
authors.forename: Brigitte W M
authors.initials: BW
authors.lastname: Willemse
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
authors.forename: Irene H
authors.initials: IH
authors.lastname: Heijink
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.forename: Lucie
authors.initials: L
authors.lastname: Jorge
authors.forename: Pat
authors.initials: P
authors.lastname: Sandra
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Koen
authors.initials: K
authors.lastname: Sandra
authors.forename: Nick H T
authors.initials: NH
authors.lastname: ten Hacken
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D016540:Smoking Cessation; D013107:Sphingolipids / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010714:Phosphatidylethanolamines; D013107:Sphingolipids
keywords: COPD; cigarette smoke; induced sputum; lipidomics