Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia.
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.
Stanke-Labesque
Françoise
F
Institut National de la Santé et de la Recherche Médicale, Grenoble, France. FStanke@chu-grenoble.fr
Bäck
Magnus
M
Lefebvre
Blandine
B
Tamisier
Renaud
R
Baguet
Jean-Philippe
JP
Arnol
Nathalie
N
Lévy
Patrick
P
Pépin
Jean-Louis
JL
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
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