leukotriene-e4 and Sleep-Apnea--Obstructive

Topics: C-Reactive Protein; Child; Humans; Leukotriene E4; Longitudinal Studies; Malocclusion, Angle Class II; Orthodontic Appliances, Removable; Prospective Studies; Retrognathia; Sleep Apnea, Obstructive; Treatment Outcome

Obstructive sleep apnea (OSA) characterized by nocturnal intermittent hypoxia (IH) is associated with atherosclerosis and cysteinyl-leukotrienes (CysLT) pathway activation. We aimed to identify the determinants of CysLT pathway activation and the role of CysLT in OSA-related atherosclerosis.. Determinants of the urinary excretion of LTE. IH-related CysLT pathway activation contributes to OSA-induced atherogenesis. In the era of personalized medicine, U-LTE

Topics: 5-Lipoxygenase-Activating Proteins; Acetates; Adult; Animals; Arachidonate 5-Lipoxygenase; Atherosclerosis; Case-Control Studies; Cyclopropanes; Cysteine; Disease Models, Animal; Disease Progression; Female; Humans; Leukotriene Antagonists; Leukotriene E4; Leukotrienes; Male; Mice, Knockout, ApoE; Middle Aged; Plaque, Atherosclerotic; Quinolines; Receptors, Leukotriene; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Sulfides

Antileukotriene has been used for alleviating disease severity in children with adenotonsillar hypertrophy (ATH) and mild obstructive sleep apnea (OSA). Previous study showed the relationship between urinary cysteinyl leukotriene E₄ (uLTE₄) level and therapeutic response to montelukast in asthmatic adults. However, this relationship has never been investigated in pediatric OSA.. To determine the relationship between uLTE₄ level and therapeutic response to montelukast in children with ATH and mild OSA.. Children aged 3-15 yrs who had ATH and mild OSA were enrolled. All had quality of life (assessed by Thai version OSA-18 QoL questionnaire) and uLTE₄ levels measured prior to start a 6-week course of montelukast treatment. Overnight polysomnography (PSG) and QoL reassessment were performed after completing the treatment. Those who demonstrated a large improvement of mean total QoL score or ≥ 50% decrease of obstructive apnea-hypopnea index (OAHI) after the treatment were defined as responders.. Twenty-six children were enrolled (mean age 7.5 ± 2.9 yrs, 38.5% male). After 6-week course of montelukast, nine (34.6%) children showed significant improvement. The mean uLTE₄ level from the responders was higher comparing to the non-responders (2,952.56 ± 966.9 vs. 978.6 ± 460.8 pg/mg creatinine; p < 0.001). uLTE₄ level of ≥ 1,457 pg/mg creatinine had 100% sensitivity and 88.2% specificity in identifying the responders.. We found the association between ULTE4 and therapeutic response to monteleukast. The uLTE₄ level of ≥ 1,457 pg/mg creatinine could predict the therapeutic response to montelukast in children who had ATH and mild OSA.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Biomarkers, Pharmacological; Child; Child, Preschool; Creatinine; Cyclopropanes; Disease Progression; Female; Humans; Leukotriene E4; Male; Predictive Value of Tests; Prognosis; Quinolines; Sleep Apnea, Obstructive; Sulfides

Obstructive sleep apnea (OSA) is a common problem in children and is associated with increased cardiovascular, neurobehavioral and somatic growth consequences. Cysteinyl leukotrienes (CysLTs) play a major role with local and systemic relations to the pathophysiology of OSA. The level of CysLTs in urine, blood, exhaled breath and adenotonsillar tissue of OSA children are increased. However it remains unclear whether inflammatory marker levels are alleviated after adenotonsillectomy. Therefore, we compare the urine leukotriene E4 (uLTE4) levels in children before and after adenotonsillectomy and evaluate clinical outcomes on resolution of OSA.. Children under 15 years who suspected OSA with planned adenotonsillectomy were recruited. Sleep questionnaires, quality of life assessment by OSA-18, physical examination, lateral neck radiographs, overnight SpO. Adenotonsillectomy remains an effective treatment for SDB children that not only alleviated the severity of SDB and improved quality of life; it also decreased levels of the systemic inflammatory marker, uLTE4. However, benefits were more obvious in non-obese children.

Topics: Adenoidectomy; Biomarkers; Child; Child, Preschool; Cysteine; Female; Humans; Leukotriene E4; Leukotrienes; Male; Obesity; Prognosis; Quality of Life; Sleep Apnea, Obstructive; Surveys and Questionnaires; Tonsillectomy; Treatment Outcome

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.. 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.. We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry.. 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.. Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.

Topics: 5-Lipoxygenase-Activating Proteins; Adult; Carrier Proteins; Chromatography, Liquid; Female; Humans; Hypoxia; Leukotriene E4; Male; Membrane Proteins; Middle Aged; Obesity; Polysomnography; Prospective Studies; RNA, Messenger; Sleep Apnea, Obstructive; Tandem Mass Spectrometry; Thromboxane B2