title: Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia.
abstract: BACKGROUND
  Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of intermittent hypoxia and confounders, such as obesity, is still debated.
  
  
  OBJECTIVE
  To monitor urinary leukotriene E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE(4) concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE(4) concentrations.
  
  
  METHODS
  We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  The U-LTE(4) concentrations were increased (P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI (P = .001; regression coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001; regression coefficient, 1.01) as independent predictors of U-LTE(4) concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI.
  
  
  CONCLUSIONS
  Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.
authors: Institut National de la Santé et de la Recherche Médicale, Grenoble, France. FStanke@chu-grenoble.fr
authors: Françoise
authors: F
authors: Stanke-Labesque
authors: Magnus
authors: M
authors: Bäck
authors: Blandine
authors: B
authors: Lefebvre
authors: Renaud
authors: R
authors: Tamisier
authors: Jean-Philippe
authors: JP
authors: Baguet
authors: Nathalie
authors: N
authors: Arnol
authors: Patrick
authors: P
authors: Lévy
authors: Jean-Louis
authors: JL
authors: Pépin
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000328:Adult; D002352:Carrier Proteins / Q000032:analysis; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000652:urine*; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000652:urine*; D017286:Polysomnography; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000652:urine*; D053719:Tandem Mass Spectrometry; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4