title: Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.
abstract: BACKGROUND
  Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.
  
  
  OBJECTIVE
  This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.
  
  
  METHODS
  Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.
  
  
  RESULTS
  Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.
  
  
  CONCLUSIONS
  Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.
authors: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
authors: Susanna L
authors: SL
authors: Lundström
authors: Bettina
authors: B
authors: Levänen
authors: Malin
authors: M
authors: Nording
authors: Anna
authors: A
authors: Klepczynska-Nyström
authors: Magnus
authors: M
authors: Sköld
authors: Jesper Z
authors: JZ
authors: Haeggström
authors: Johan
authors: J
authors: Grunewald
authors: Magnus
authors: M
authors: Svartengren
authors: Bruce D
authors: BD
authors: Hammock
authors: Britt-Marie
authors: BM
authors: Larsson
authors: Anders
authors: A
authors: Eklund
authors: Åsa M
authors: ÅM
authors: Wheelock
authors: Craig E
authors: CE
authors: Wheelock
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054883:Oxylipins / Q000378:metabolism*; D011890:Railroads; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D054883:Oxylipins