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Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes.
Russell P Bowler1, Sean Jacobson, Charmion Cruickshank
11 National Jewish Health, Denver, Colorado.
American Journal of Respiratory and Critical Care Medicine
|December 11, 2014
Summary
Specific sphingolipids are linked to chronic obstructive pulmonary disease (COPD) subphenotypes. Sphingomyelins are associated with emphysema, while glycosphingolipids are linked to COPD exacerbations, indicating metabolic dysregulation.
Area of Science:
- Pulmonary Medicine
- Metabolomics
- Lipidomics
Background:
- Chronic obstructive pulmonary disease (COPD) affects a subset of smokers, presenting with exacerbations and distinct subphenotypes like emphysema and chronic bronchitis.
- While sphingolipids are implicated in COPD pathogenesis, specific species linked to subphenotypes remain unidentified.
Purpose of the Study:
- To identify plasma sphingolipid species associated with COPD subphenotypes using mass spectrometry.
- To investigate the relationship between sphingolipid metabolism and COPD subphenotypes.
Main Methods:
- Targeted and untargeted mass spectrometry analyzed 69 sphingolipid species in plasma from 129 COPDGene cohort participants.
- Regression analysis, false discovery rate correction, and meta-analysis were employed to assess associations.
- Peripheral blood mononuclear cells were used to correlate sphingolipid gene expression with plasma sphingolipid levels.
Main Results:
- Five sphingomyelins were associated with emphysema.
- Four trihexosylceramides and three dihexosylceramides were linked to COPD exacerbations.
- Fifteen sphingolipid gene/metabolite pairs showed differential regulation between COPD cases and controls.
Conclusions:
- Systemic dysregulation of sphingolipid metabolism is evident in COPD patients.
- Sphingomyelins are strongly associated with the emphysema subphenotype.
- Glycosphingolipids are associated with COPD exacerbations, suggesting distinct roles in disease presentation.
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