leukotriene-e4 and Obesity

Topics: Adult; Body Mass Index; Breast Feeding; Child Development; Correlation of Data; Dinoprostone; Fatty Acids, Omega-3; Female; Humans; Infant, Newborn; Leukotriene E4; Milk, Human; Mothers; Obesity

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

Leptin-related effects on inflammation and bronchial hyperresponsiveness (BHR) in the human airway have not been demonstrated.. To investigate the relationship between the levels of serum leptin and BHR and urinary leukotriene E4 (LTE4) and 9α,11β-prostaglandin F2 (9α,11β-PGF(2)) release after exercise challenge in asthmatic children.. Eighty-six prepubertal children between 6 and 10 years old were enrolled and divided into 4 groups: 19 obese asthmatic children, 25 normal-weight asthmatic children, 21 obese nonasthmatic children, and 21 healthy controls. We measured serum leptin levels and urinary LTE4 and 9α,11β-PGF2 levels in children before and 30 minutes after the exercise challenge.. Serum leptin levels were significantly higher in obese asthmatic children compared with normal-weight asthmatic children. Significant increases in urinary levels of LTE4 and 9α,11β-PGF2 were observed in obese asthmatic children after the exercise challenge. Although smaller than in obese asthmatic children, significant increases in the urinary levels of LTE4 and 9α,11β-PGF2 were also observed in the normal-weight. Asthmatic children Logarithmic serum leptin values were significantly associated with the logarithmic maximum percentage change in forced expiratory volume in 1 second, the logarithmic urinary LTE4 change, and the logarithmic urinary 9α,11β-PGF2 change from baseline to after exercise in both obese and normal-weight asthmatic children.. The serum levels of leptin were significantly associated with BHR and urinary LTE4 and 9α,11β-PGF2 release induced by exercise challenge in asthmatic children.

Topics: Asthma, Exercise-Induced; Child; Dinoprost; Exercise Test; Female; Humans; Leptin; Leukotriene E4; Male; Obesity

Sleep disordered breathing (SDB) has been associated with increased inflammatory responses. Changes in the level of pro-inflammatory leukotrienes (LTs) may initiate or exacerbate pediatric SDB and may play a major role in end-organ morbidity. The objective of the study was to investigate the relationship of LT productions with severity of SDB, obesity, and adenotonsillar hypertrophy in children.. Prospective, observational study that included standard questionnaires, physical examinations, overnight polysomnography (PSG), and urinary leukotriene E(4) (LTE(4)) assay.. Sleep Center and Laboratory of Nutriology.. 282 children with SDB and 94 healthy control subjects were recruited.. Urinary LTE(4) levels were elevated in children with SDB compared to the controls, and LTE(4) productions emerged disease severity- and obesity-dependent increases. In stepwise multiple regression analysis, the independent predictors of the apnea-hypopnea index (AHI) included LTE(4) level and adenotonsillar-size sum score (P < 0.001 respectively; adjusted R(2)=0.318). A positive relationship between LTE(4) urinary level and adenotonsillar-size sum scores was present in the underweight/normal weight SDB subjects (r=0.276; P < 0.001), but not in the overweight/obese children (P > 0.05).. Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE(4) is significantly related to the severity of SDB and obesity. However, a correlation between LTE(4) concentration and adenotonsillar size is present only among nonobese children.

Topics: Adenoids; Child, Preschool; China; Cohort Studies; Female; Humans; Hypertrophy; Leukotriene E4; Male; Obesity; Palatine Tonsil; Polysomnography; Prospective Studies; Severity of Illness Index; Sleep Apnea Syndromes; Surveys and Questionnaires

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

We investigated the effects of fish oil and vitamin E on the endogenous leukotriene production. 10 healthy volunteers were supplemented for 1 week with fish oil (containing 40 mg/kg body weight per day of eicosapentaenoic and docosahexaenoic acid), vitamin E (540 mg, i.e., 800 IU of D-alpha-tocopherol per day), or with both agents. Treatment resulted in a significant increase in the eicosapentaenoate concentration in red blood cell membranes and/or in the vitamin E concentration in serum. In addition, nine obese patients were investigated who were on a hypocaloric diet including 10 mg vitamin E/day for 8 weeks. This diet was associated with a significant decrease in serum vitamin E concentration. The urinary concentration of leukotriene E4 plus N-acetylleukotriene E4 served as a measure for the endogenous leukotriene production. Fish oil reduced leukotriene production in eight of the 10 healthy individuals. After vitamin E supplementation, urinary leukotrienes were significantly reduced in all of the healthy volunteers. The combination of vitamin E plus fish oil had no synergistic effect on leukotriene production in the individuals tested. The decrease in serum vitamin E concentration during the hypocaloric, 10 mg vitamin E/day diet was associated with an increase in urinary leukotrienes in 8 of the 9 obese patients. Urinary prostaglandin metabolites, determined as tetranorprostanedioic acid, increased or decreased in parallel with urinary leukotrienes in most individuals; however, changes were less pronounced than those observed with leukotrienes. We conclude that the endogenous leukotriene production can be reduced effectively by high doses of fish oil or vitamin E, whereas vitamin E depletion is associated with an increase in leukotriene generation.

Topics: Adult; Diet; Diet, Reducing; Docosahexaenoic Acids; Drug Synergism; Eicosapentaenoic Acid; Erythrocyte Membrane; Fatty Acids; Fish Oils; Humans; Leukotriene E4; Leukotrienes; Male; Obesity; Vitamin E