Leukotriene E4 Levels Research Articles

Urine Leukotriene E4 Levels in Children with Nonspecific Isolated Chronic Dry Cough.

Chronic cough is the most common complaint during childhood. Various pathophysiologic mechanisms may cause cough. Knowledge of the mechanisms underlying chronic cough plays an important role in the choice of treatment to evaluate the role of leukotrienes in children with nonspecific isolated chronic dry cough. The patient group consisted of children with isolated chronic dry cough persisting for >4 weeks and the control group included healthy children. Medical histories were elicited and physical examinations were performed, then respiratory function testing was done and chest X-rays were obtained. Patients were given inhaled corticosteroid. The urine leukotriene E4 (uLTE4) levels in the patient and control groups was measured by enzyme immunoassay. The patient group included 55 patients, 25 of them were males between 6 and 12 years old. The control group included 25 healthy children between 6 and 12 years old, 12 of them were males. There were no pathologic findings on physical examinations, pulmonary function testing, and chest X-rays. The complaints of cough in 50 patients were resolved after treatment. The median level of uLTE4 was 73.1 ng/mmol creatinine (range, 15.59-787.55 ng/mmol creatinine) in the patient group, and 64.2 ng/mmol creatinine (range, 12-282 ng/mmol creatinine) in the control group. No significant difference was detected between the 2 groups with respect to age, gender, and uLTE4 levels. Different pathophysiologic mechanisms are known to influence nonspecific isolated chronic dry cough. Various mechanisms, other than leukotrienes, may also give rise to dry cough.

Effect of Zileuton and Celecoxib on Urinary LTE4 and PGE-M Levels in Smokers

COX-2 and 5-lipoxygenase (5-LO) use arachidonic acid for the synthesis of eicosanoids that have been implicated in carcinogenesis and cardiovascular disease. The ability of celecoxib, a selective COX-2 inhibitor, to redirect arachidonic acid into the 5-LO pathway can potentially reduce its efficacy as a chemopreventive agent and increase the risk of cardiovascular complications. Levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E4 (LTE4), biomarkers of the COX and 5-LO pathways, are elevated in smokers. Here, we investigated the effects of zileuton, a 5-LO inhibitor, versus zileuton and celecoxib for 6 ± 1 days on urinary PGE-M and LTE4 levels in smokers. Treatment with zileuton led to an 18% decrease in PGE-M levels (P = 0.03); the combination of zileuton and celecoxib led to a 62% reduction in PGE-M levels (P < 0.001). Levels of LTE4 decreased by 61% in subjects treated with zileuton alone (P < 0.001) and were unaffected by the addition of celecoxib. Although zileuton use was associated with a small overall decrease in PGE-M levels, increased PGE-M levels were found in a subset (19 of 52) of subjects. Notably, the addition of celecoxib to the 5-LO inhibitor protected against the increase in urinary PGE-M levels (P = 0.03). In conclusion, zileuton was an effective inhibitor of 5-LO activity resulting in marked suppression of urinary LTE4 levels and possible redirection of arachidonic acid into the COX-2 pathway in a subset of subjects. Combining celecoxib and zileuton was associated with inhibition of both the COX-2 and 5-LO pathways manifested as reduced levels of urinary PGE-M and LTE4.

Leptin and urinary leukotriene E4 and 9α,11β-prostaglandin F2 release after exercise challenge

BackgroundLeptin-related effects on inflammation and bronchial hyperresponsiveness (BHR) in the human airway have not been demonstrated. ObjectivesTo investigate the relationship between the levels of serum leptin and BHR and urinary leukotriene E4 (LTE4) and 9α,11β-prostaglandin F2 (9α,11β-PGF2) release after exercise challenge in asthmatic children. MethodsEighty-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. ResultsSerum 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. ConclusionThe serum levels of leptin were significantly associated with BHR and urinary LTE4 and 9α,11β-PGF2 release induced by exercise challenge in asthmatic children.

Passive Smoking Induces Leukotriene Production in Children: Influence of Asthma

Background. Passive smoking is associated with poor asthma control in children, but the mechanism is unknown. Leukotrienes are involved in the asthma pathogenesis and their synthesis is increased in adult subjects who actively smoke. Objective. To evaluate whether passive smoking, as assessed by urinary cotinine levels, increases leukotriene production in children with or without asthma. Methods. This was a prospective, cross-sectional study in which children with stable intermittent asthma (without exacerbation) and healthy control children were studied through spirometry and urinary concentrations of cotinine and leukotriene E4 (LTE4). Both groups were balanced to include children with and without passive smoking. Results. Ninety children (49 with asthma and 41 controls, 54.4% females) aged 9 years (range, 5–13 years) were studied. Urinary LTE4 concentrations were progressively higher as cotinine levels increased (rS = 0.23, p = .03). LTE4 also correlated with body mass index (BMI) (rS = 0.30, p = .004), and multiple regression analysis revealed that BMI was even more influential than cotinine for determining LTE4 levels. LTE4 concentrations were unrelated with gender, age, or spirometry. In turn, cotinine inversely correlated with forced expiratory volume in one second (FEV1) (rS = −0.22, p = .04) and forced vital capacity (FVC) (rS = −0.25, p = .02), but when analyzed by groups, these relationships were statistically significant only in children with asthma. Conclusions. Exposure to environmental tobacco smoke, as assessed by urinary cotinine levels, was associated with an increased urinary concentration of LTE4, although BMI exerted more influence in determining its concentration. Urinary cotinine was associated with decreased lung function, mainly in children with asthma.

Cysteinyl leukotrienes in exhaled breath condensate of smoking asthmatics

Cysteinyl leukotrienes (CysLTs) are among important inflammatory mediators in asthma pathogenesis. In this study, we aimed to determine leukotriene D₄ (LTD₄) and leukotriene E₄ (LTE₄) levels in exhaled breath condensate (EBC) in asthmatics and to evaluate the effect of smoking upon CysLTs levels and to speculate the importance of adding leukotriene receptor antagonists in smoking asthmatics. A total of 88 participants were included in the study. Of them, 59 were asthmatics; 30 of the 59 asthmatics were smokers (Group I) and the others were non-smokers (Group II). As a control group (Group III), 29 healthy non-smokers were enrolled. EBC samples were collected (EcoScreen, Jaeger, Hoechberg, Germany) and pulmonary function tests (PFTs) were performed in each case, and an asthma control questionnaire (ACQ) was completed by the asthmatics. LTD₄ and LTE₄ levels in EBC samples were analyzed by using ELISA. LTD₄ levels were found to be higher in Group I than other groups and similar in Group II and Group III. LTE₄ levels were lower in Group III than other groups and similar in Group I and Group II. PFTs were different between Group I and Group III and there was a significant negative correlation between LTE₄ levels and forced expiratory volume in one second and forced vital capacity ratio in Group I. LTD₄, but not LTE₄, concentrations in EBC were higher in asthmatic smokers than asthmatic nonsmokers. LTE₄ concentrations in EBC were higher in asthmatics than healthy non-smokers. In smoking asthmatics usage of agents that block the effects of LTD₄ can be beneficial; however, new clinical studies are required.

Exercise-Induced Bronchoconstriction in Children with Asthma: Is There an Association with Urinary Leukotriene E4 or Exhaled Nitric Oxide

Cysteinyl leukotrienes (LT) and airway inflammation are thought to affect exercise-induced bronchoconstriction (EIB). The aim of this study was to investigate the relations between EIB and urinary leukotriene E4 (LTE4) levels and other noninvasive measures of airways inflammation markers in a sample of children with asthma. Pre-exercise urinary LTE4, fractional concentration of exhaled nitric oxide (FeNO) and blood eosinophil count and pulmonary function were measured in 32 children with asthma (mean age±SD, 11.2±2.9 years). Change in forced expiratory volume in one second (FEV1) was determined at 5, 10, and 15 min following 6 min of exercise on a cycle ergometer. Fifteen of the 32 subjects experienced EIB (≥10% decrease in FEV1). The urinary LTE4, FeNO, and blood eosinophil count were significantly related to the maximal percentage decrease in FEV1 after exercise (r=0.44, P<0.05; r=0.36, P<0.05, and r=0.40, P<0.05, respectively). By multiple linear regression, after adjusting for age, gender, and treatment with inhaled corticosteroids, only the pre-exercise urinary LTE4 level was correlated with the maximal percentage decrease in FEV1 after exercise (β=32, P<0.05). Bronchoconstriction after exercise is related to the pre-exercise urinary LTE4 in children with asthma.

Advances in pediatric asthma in 2012: Moving toward asthma prevention

Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.

Urinary levels of leukotriene E4 in acute asthmatic children

Background and Aims: Increased production of cysteinyl leukotrienes (CysLTs) within the airways causes acute asthma. Leukotriene E4 (LTE4) is a potent constricting mediator and is excreted in urine. This study hypothesized that urinary LTE4 (uLTE4) levels would be increased in acute asthma in Egyptian children. The study measured uLTE4 in children with acute asthma and compared them to a matched healthy control group. Material and Methods: The study included 40 acute Egyptian asthmatic children and 40 age-and sex-matched controls. All candidates were subjected to a complete clinical study (thorough history and physical examination); with emphasis on severity of asthma attack according to Global Initiative for Asthma Guidelines. Measurement of urinary creatinine was performed for all study candidates. Measurement of uLTE4 (pg/mg creatinine) was performed using commercial ELISA kit. Results: Levels of uLTE4 were significantly higher in cases compared to controls (305.48 ± 34 pg/mg creatinine versus 175.55 ± 79 pg/mg creatinine respectively, 95% CI (17.7; 242.1), p=0.024).Levels of uLTE4 were significantly higher in cases with moderate and severe attacks in comparison to those with mild attacks. There was a significant positive correlation between severity of the attack and uLTE4 levels (Spearman's rho = 0.446, p=0.004). Conclusion: Levels of uLTE4 are significantly elevated during acute asthma episodes in children. The significant direct correlation between severity of these attacks and uLTE4 levels make uLTE4 a possible marker for monitoring acute asthma exacerbations in children.

Measurement of Bronchoconstrictive Eicosanoids in Chronic Obstructive Pulmonary Disease

The aim of the study was the evaluation of the concentration of 9α11β prostaglandin F(2) - a stable metabolite of prostaglandin D(2) (PGD(2)) and leukotriene E(4) (LTE(4)) in stable and exacerbated COPD patients. 29 COPD patients aged 73 ± 8.34, mean FEV1 = 48.64 ± 15.75% of predictive value and 29 healthy controls aged 57.48 ± 10.86, mean FEV1 = 97.17 ± 13.81% of predictive value participated in this study. Samples of urine and blood were taken from COPD patients during exacerbation and in stable state of the disease; LTE(4) was determined in urine using commercial enzyme immunoassay (EIA) and 9α11β prostaglandin F(2) (9α11βPGF(2)) - stable metabolite of PGD(2) was evaluated in blood and urine using GC/MS. LTE(4) concentration in urine (677.15 vs. 436.4 pg/mg of creatinine; p = 0.035) and 9α11βPGF(2) in blood serum (5.35 vs. 3.07 pg/ml; p = 0.007) were significantly higher in exacerbated COPD patients than in control group. There was no difference in LTE(4) level in urine and 9α11βPGF2 in blood serum between exacerbated and stable COPD. The urinary 9α11βPGF(2) concentration did not differ between all studied groups. We found a positive correlation between smoking history and the urine LTE(4) level (r = 0.395; p = 0.002) as well as blood 9α11βPGF(2) concentration (r = 0.603; p = 0.001) in COPD patients. 9α11βPGF(2) and LTE(4) level in urine did not differ between the stable COPD group and the control group. We also did not find any difference between LTE4 level in urine and 9α11βPGF(2) in blood and urine between exacerbated and stable COPD. Finally, LTE(4) concentration in urine and 9α11βPGF(2) in blood occurred to be significantly higher in exacerbated COPD patients than in control group.

Ambient Particulate Air Pollution, Environmental Tobacco Smoking, and Childhood Asthma: Interactions and Biological Mechanisms

Ambient Particulate Air Pollution, Environmental Tobacco Smoking, and Childhood Asthma: Interactions and Biological Mechanisms

Efficacy of Montelukast on Treatment of Wheezing Lower Respiratory Tract Infection (LRI) in Young Children with Risk of Asthma

Background and Aims: Leukotrienes are major inflammatory mediators in wheezing-LRI and leukotriene antagonist has been reported to be effective in asthmatic children. This randomized double-blind, placebo-controlled trial study was performed to evaluate the efficacy of montelukast in the treatment of wheezing-LRI and in prevention of recurrent wheezing among previously healthy children under 5 years of age with risk of asthma. Methods: The enrolled patients were randomly allocated into the studied group (receiving 4-mg montelukast once daily while being hospitalized) and the control group (receiving placebo). The 2 groups were compared in terms of clinical severity scores, duration of oxygen use, length of hospital stay, chest X-ray, viral study and urine leukotriene E4 levels. All patients were followed up for 6 months to evaluate their recurrent wheezing episodes and pulmonary function tests. Results: 21 patients (mean age 23 months) were recruited. 11 patients received montelukast, 10 patients received placebo. There were no differences in clinical severity scores, duration of O2 therapy, length of hospital stay and urine leukotriene E4 levels between the two groups. During the 6-month-follow up period, the montelukast group had lower recurrent wheezing episodes and inhaled corticosteroid use but not statistically significant. The airway resistance was significantly decreased after 6 months in the montelukast group (mean of difference = -0.14, p = 0.004). Conclusion: In wheezing-LRI children with risk of asthma, montelukast was ineffective in improving acute outcomes and prevention of recurrent wheezing. However; montelukast might be beneficial in decreasing airway resistance.

Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) (‘classic’ BPD) and with minimal early lung disease (‘atypical’ BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1st, 3rd and 7th day of life and measured the levels of leukotriene E4 (LTE4) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3rd day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7th day were the independent risk factor for developing moderate/severe BPD. In ‘classic’ BPD, the 8-OHdG values on the 3rd day were higher than those of ‘atypical’ BPD. In ‘atypical’ BPD, the LTE4 values on the 7th day were higher than the values in ‘classic’ BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in ‘atypical’ BPD.

Effects of physical exercise on lung injury and oxidant stress in children with asthma

Background The aim of this study was to investigate the influence of exercise training on oxidative stress and markers of lung inflammation in children with asthma. Methods Thirty children aged 8-13 years diagnosed with asthma were enrolled in the study as well as 13 healthy children. One group received only pharmacological treatment and the other group was also enrolled in an exercise programme. Venous blood and 24-hour urine samples were obtained from the children enrolled in the study at the beginning and end of the study. Leukotriene E4 and creatinine levels were measured in the urine and matrix metallopeptidase (MMP-9), endothelin-1(ET-1), malnodialdehyde (MDA), IgE and specific IgE levels were measured in blood samples. Results Leukotriene E4, MDA and MMP9 levels decreased significantly with treatment in both groups (p<0.001). However, ET-1 levels decreased significant only in the exercise group (26.5 ± 3.6 vs 21.3 ± 2.4pg/ml respectively, p=0.001). Moreover, ET-1 levels were found to be significantly lower in the exercise group compared to the only pharmacotherapy group (24.2 ± 3.1 vs 21.3 ± 2.4pg/ml, p=0.007). Conclusions Positive influences of exercise training in children with asthma may be mediated by decrease in ET-1 levels.

Polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein are associated with chronic spontaneous urticaria and urinary leukotriene E4

The mechanisms of chronic spontaneous urticaria (CSU) continue to be unknown. Our working hypothesis is that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be involved in the pathways leading to CSU. We examined five candidate polymorphisms of cyclo-oxygenases 1 and 2 and of 5-lipo-oxygenase-activating protein in 109 controls and in 94 CSU patients from Northern Italy. We also examined the levels of urinary leukotriene E4 (LTE4) before and after challenge with ASA. A multiple regression model was found to show that COX-2 5'UTR T/G, COX-2 Exon 10 T/C, and FLAP -336 G/A polymorphisms were significantly associated with CSU, with the minor allele more represented in CSU group. Similar results were obtained as regards the specific association with ASA-tolerated CSU and ASA-exacerbated CSU. Evaluating a polygenic model, reflecting the sum of the concomitant alleles associated with CSU (i.e. COX-2 5'UTR G allele, COX-2 Exon 10 C allele, and FLAP -336 G/A allele), the proportion of CSU patients increased progressively with the increasing number of unfavourable alleles. Finally, in a linear regression model after adjustment for disease status COX-1 22 T carriership remained a significant predictor of post-challenge high urinary LTE4 levels. Our results support the hypothesis that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be associated with CSU.

Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge.

Serum Interleukin -4 and urinary leukotriene E4 level hi children with bronchiolitis

目的 探讨毛细支气管炎患儿血清IL4及尿白三烯E4(LTFA)水平变化与病情分度的关系.方法 选择2006年12月至2008年12月我院小儿呼吸科住院毛细支气管炎患儿100例,按病情程度分为轻度、中重度两组,轻度组52例,中重度组48例.另选择健康体检儿50例为对照组.采用酶联免疫吸附法测定血清IL-4及尿LIFA水平.结果 毛细支气管炎患儿发病急性期血清IL-4水平为(11.34±7.56)ng/L,尿LTFA(20.3±4.75)pmol/μmol Cr;恢复期血清IL-4(6.84±5.64)ng/L及尿LTE4(3.6±1.12)pmol/μmol Cr;健康组IL-4(5.72±2.24)ng/L及尿LTFA(1.43±0.14)pmol/μmolCr.毛细支气管炎患儿发病急性期血清IL-4及尿LTE4明显增高(P 0.01).血清IL-4与尿LTE4检测结果呈正相关,r值分别为0.628、0.564(P<0.01).结论 血清IL-4及尿LTE4水平可作为毛细支气管炎病情严重程度的指标之一,有利于指导临床诊治。

CIRCADIAN STUDY OF DECOMPRESSION SICKNESS SYMPTOMS AND RESPONSE-ASSOCIATED VARIABLES IN RATS

In order to study circadian rhythms and decompression sickness (DCS), we determined: 1) the baseline circadian time structure in noncompressed rats of potential response variables to compression/decompression (C/D), and 2) whether rats subjected to C/D display a circadian time-dependent difference in inflammatory response intensity and biological tolerance. Subgroups of male rats, standardized to a 12 h light/12 h dark schedule, were evaluated every 4 h over 24 h after they were either compressed to 683 kPa (group E) or remained at sea level (group C). During 60 min recovery, evaluation included gross DCS symptoms and pulmonary edema in all E rats, and cell counts, nitric oxide, protein, thromboxane B2, and leukotriene E4 levels in survivors. Chi-square, ANOVA, and 24 h cosinor analyses were used to test for time-of-day effects. C/D exposures near the end of dark/activity or during light/resting were generally better tolerated, with lowest signs of DCS symptoms and lowest responses by most of the variables monitored. More deaths were observed in the first half of the dark/activity span. Of the 16 subsets of inflammatory-associated variables, overall increases were observed in 13 and decreases in 2. Significant or borderline significant circadian time effects were found in 14 variables in group C, 12 variables in group E, and 13 variables in response (E%C). Thus, nearly all baseline indices of DCS demonstrated circadian time-dependencies in the sea-level exposed control rats (group C), and nearly all were modified by the circadian time of C/D. Such time-of-day effects of DCS are potentially relevant to the operational concerns of occupations involving decompression exposures and the investigation of prevention and treatment intervention strategies of DCS. (Author correspondence: Bruce.D.Butler@uth.tmc.edu).

Hışıltılı Çocuklarda Lökotrien E4 ve Endotelin-1 Düzeyleri, Tedaviye Yanıt, Gastroösefageal Reflü ve Süt Çocuğu Astımı Gelişmesi ile Potansiyel İlişkileri

Objective: Wheezing is a common symptom among children and is proposed to be associated with inflammatory cell infiltration, cytokines production, and with some risk factors such as gastro esophageal reflux (GER). The aim of the present study was to investigate endotheline-1 (ET-1) and leukotriene-E4 (LTE-4) levels, their response to steroid and ?2-agonist therapy, and to establish if these parameters can be used as a diagnostic tool for infantile asthma and assess their relation with GER during acute attack of wheezy infants (WI). Material and Methods: Thirty WI and 12 healthy infants were enrolled in the present study. Serum IgE, ET-1, urine LTE-4 levels, and eosinophil percentage were measured prior to and 5 days after the treatment (systemic or inhaled steroid therapy and inhaled ?2-agonist) in children with WI. In addition, esophageal pH was monitored for 24 hours. Results: Serum IgE, ET-1, and urine LTE-4 levels were significantly higher in the patients compared to the controls before and five days after the treatment (p= 0.009; p= 0.039, p= 0.032; p= 0.014, p= 0.017, respectively). The serum IgE and urine LTE-4 levels prior to and 5 days after the treatment were higher in the patients with GER when compared to the controls (p= 0.021, p= 0.016 and p= 0.039). Moreover, the systemic or inhaled steroid therapy did not influence the serum ET-1 and urine LT-E4 levels. We found that the serum IgE and ET-1 levels on 5^th day of the treatment and LTE-4 levels at the beginning and 5th day of the treatment were notably different in patients with higher likelihood for developing infantile asthma when compared to the controls. Finally, increased serum IgE levels were present in patients with good response to inhaled ?2-agonist with regard to those with poor response to inhaled ?2-agonist (p= 0.031). Conclusion: The present study indicated that IgE, ET-1 and LTE-4 levels were related to airway inflammation in WI while LTE-4 and IgE levels were associated with GER. LTE-4 and IgE levels could be novel parameters for determining the risk factor for developing asthma in child with WI. Inhaled ?2-agonist therapy seemed to be beneficial only in patients with high serum IgE levels.

Levels of Prostaglandin E Metabolite and Leukotriene E4 Are Increased in the Urine of Smokers: Evidence that Celecoxib Shunts Arachidonic Acid into the 5-Lipoxygenase Pathway

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Urinary cysteinyl leukotriene E4 significantly increases during pain in children and adults with sickle cell disease

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.