PURPOSE: Recent studies have shown that the cysteinyl leukotriene (cysLT) of exhaled breath condensate (EBC) could be predictive of inflammatory status and effectiveness of treatment in allergic disease. The aim of this study was to evaluate the inflammation and therapeutic effectiveness of cysLT in EBC in pediatric patients with allergic rhinitis (AR). METHODS: We enrolled 34 healthy children (median age, 4 years 10 months) and 67 AR children (median age, 5 years 1 month). All of the AR patients received intranasal steroid (fluticasone furoate) once daily for 2 weeks. After 2 week of fluticasone furoate treatment, they were classified into 2 groups: the fluticasone furoate (F) and montelukast (M) groups. We treated each group for another 8 weeks. To evaluate the therapeutic effectiveness, we used symptom score (SS) and EBC leukotriene E4 (LTE4). EBC samples were collected with RTube. Each parameter was checked at 0, 2, and 10 weeks of therapy. RESULTS: Most of the AR patients showed clinical improvement with 2- and 10-week fluticasone therapy (F group: 0-week SS, 5.6; 2-week SS, 3.6; 10-week SS, 2.1; P<0.01; M group: 0-week SS, 4.8; 2-week SS, 3.2; 10-week SS, 1.9: P<0.01). LTE4 levels were higher in AR patients than in control subjects (0 week: 87 pg/mL vs. 18 pg/mL) and were reduced after 2 weeks of fluticasone treatment (F group: 90→51.6 pg/mL, P<0.01; M group: 84→46.1 pg/mL, P<0.01). After 10 weeks of treatment, there was no significant difference in the LTE4 level between the F and M groups. CONCLUSION: LTE4 in EBC may be useful for evaluating inflammation and therapeutic effectiveness in patients with allergic rhinitis.
Child* ; Fluticasone ; Humans ; Inflammation* ; Leukotriene E4* ; Rhinitis, Allergic*

OBJECTIVETo observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis.

METHODSSeventy-five children who were diagnosed with bronchiolitis between June 2014 and December 2014 were randomly assigned into two groups, one with thirty-eight cases as the montelukast treatment group and another thirty-seven cases as the control group. All of the children were given routine medical treatment. The children in the montelukast treatment group were additionally given montelukast daily (4 mg once a day, for 7 days). The serum leukotriene B4 and urinary leukotriene E4 levels were measured using ELISA before and after treatment. The relationship between serum leukotriene B4 and urinary leukotriene E4 levels was analyzed by Peason correlation analysis.

RESULTSAfter 7 days of treatment, the serum leukotriene B4 and urinary leukotriene E4 levels in the montelukast treatment and control groups were significantly reduced compared with before treatment (P<0.05). The montelukast treatment group showed significantly lower serum leukotriene B4 and urinary leukotriene E4 levels than the control group (P<0.05). The remission time of cough, wheezing and lung wheezes and the length of hospital stay in the montelukast treatment group were significantly shortened compared with the control group (P<0.05). There was a positive correlation between serum leukotriene B4 and urinary leukotriene E4 levels (r=0.723, P<0.05).

CONCLUSIONSMontelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.

Acetates ; therapeutic use ; Bronchiolitis ; drug therapy ; metabolism ; Humans ; Infant ; Leukotriene B4 ; blood ; Leukotriene E4 ; urine ; Quinolines ; therapeutic use

PURPOSE: This study assessed the association between the ratio of leukotriene E4 (LTE4) to fractional exhaled nitric oxide (FENO) in the response of children with exercise-induced bronchoconstriction (EIB) enrolled in a therapeutic trial with montelukast or inhaled corticosteroid (fluticasone propionate [FP]). METHODS: Children aged 6 to 18 years with EIB were randomized in a 4-week, placebo-controlled, double-blinded trial with montelukast or FP. Before and after treatment, treadmill exercise challenges were performed. The LTE4 levels in the induced sputum and urine and the FENO levels were measured in subjects before and 30 minutes after the exercise challenges. The same tests were conducted after treatment. RESULTS: A total of 24 patients completed the study: 12 in the montelukast group and 12 in FP group. Both study groups displayed a similar postexercise maximum decrease in forced expiratory volume in one second (FEV1) before treatment as well as after treatment. However, there were significant differences in the magnitude of change between the two (Delta; -18.38+/-14.53% vs. -4.67+/-8.12% for the montelukast and FP groups, respectively; P=0.021). The Delta logarithmic sputum baseline and postexercise LTE4/FENO ratio were significantly lower in the montelukast group than in the FP group (baseline; -0.09+/-0.21 vs. -0.024+/-0.03, P=0.045; postexercise, -0.61+/-0.33 vs. -0.11+/-0.28, P=0.023). CONCLUSIONS: These data indicate that the efficacy of montelukast for preventing a maximum decrease in FEV1 after exercise is significantly higher than that of FP, and the high LTE4/FENO ratio is associated with a greater response to montelukast than to FP for EIB therapy. These results suggest that LTE4 may play an important role in EIB.
Acetates ; Aged ; Bronchoconstriction ; Child ; Diethylpropion ; Forced Expiratory Volume ; Humans ; Leukotriene E4 ; Nitric Oxide ; Quinolines ; Sputum

PURPOSE: Some studies report a role of leukotrienes in the pathogenesis of atopic dermatitis and suggest a rationale for the use of leukotriene receptor antagonist (LTRA) in the treatment of atopic dermatitis. This study aimed to evaluate the treatment effectiveness of montelukast in children with atopic dermatitis. METHODS: Fifty-four children between the ages of 2 and 6 years with moderate to severe atopic dermatitis were enrolled. Group A received montelukast for 8 weeks, followed by a crossover to 8 weeks of placebo after a 2-week washout period. Group B reversed the administration according to a randomized, double-blind, placebo-controlled, crossover design. The SCORing atopic dermatitis (SCORAD) index, urinary leukotriene E4 (LTE4), and eosinophil-derived neurotoxin (EDN) were assessed at every visit. RESULTS: Forty-three patients (21 males) completed the study. Although the SCORAD index was decreased in both groups, there was no statistically significant difference between montelukast and placebo (-3.0±11.2 vs -5.7±11.3, P=0.43). The level of urinary LTE4 was decreased after taking montelukast when compared to placebo, but there was no statistically significant difference (-65.9±556.2 vs 87.7±618.3, P=0.26). The changes in urinary EDN after taking montelukast and placebo had no significant difference (37.0±1,008.6 vs -195.8±916.7, P=0.10). When analyzing SCORAD indices, urinary LTE4, and EDN, we could not prove the effectiveness of montelukast in the atopic, non-atopic or high ECP (ECP ≥15 µg/L) subgroups. CONCLUSIONS: There was no statistically significant difference in clinical improvement or biomarkers between montelukast and placebo treatment. Therefore, conventional treatments with skin care and infection control might be more important strategies in the treatment of atopic dermatitis.
Biological Markers ; Child* ; Cross-Over Studies* ; Dermatitis, Atopic* ; Eosinophil-Derived Neurotoxin ; Humans ; Infection Control ; Leukotriene E4 ; Leukotrienes ; Receptors, Leukotriene ; Skin Care ; Treatment Outcome

PURPOSE: Atopic dermatitis (AD) is a genetically determined, chronic relapsing skin disease. The pathogenesis of AD is complex and the course is unpredictable. Atopy is an important risk factor for the development of AD. Cysteinyl leukotrienes (Cys-LTs) were implicated in the pathophysiology of allergic diseases, and are being targeted for their diagnosis and treatments. Early detection of tissue inflammation of target organ is important to enable early prevention and management of allergic diseases. The aim of our study is to evaluate the differences in urinary leukotrienes E4 (LTE4) levels, according to AD symptom score and aeroallergen sensitization in children with AD by using noninvasive techniques. METHODS: We recruited 46 children with AD, using predetermined criteria. Clinical features of AD were evaluated by a physician, using scoring atopic dermatitis (SCORAD) index. Aeroallergen sensitization was measured by using a skin prick test and UniCap. Urine samples were also collected on day of the 1st and 2nd visits, and were analyzed for LTE4 with an enzyme-linked immunoassay kit. RESULTS: SCORAD indeces of children with AD were correlated with urinary LTE4 levels. Total immunoglobulin E (IgE) and eosinophil counts also had significant correlation with urinary LTE4 levels. Especially, aeroallergen sensitization of atopic AD significantly correlated with urinary LTE4 of these patients. CONCLUSION: Urinary LTE4 levels significantly correlated with serum total IgE and number of sensitized aeroallergen in children with AD. Clinical features of AD evaluated with SCORAD index related with urinary LTE4 level. Urinary LTE4 might be a valuable, noninvasive marker for different pathogenesis of AD.
Child ; Dermatitis, Atopic ; Eosinophils ; Humans ; Immunoassay ; Immunoglobulin E ; Immunoglobulins ; Inflammation ; Leukotriene E4 ; Leukotrienes ; Risk Factors ; Skin ; Skin Diseases

OBJECTIVECysteinyl leukotriene (CysLTs) plays an important role in airway inflammation and remodeling in asthma. Measurement of urinary leukotriene E(4) (LTE(4)) is a sensitive and noninvasive method of assaying total body CysLTs level. This study aimed to evaluate the clinical significance of urinary leukotriene E(4) (LTE(4)) in childhood asthma.

METHODSSixty children with acute asthma were randomly divided into montelukast (leukotriene receptor antagonist) treatment and conventional treatment groups (n = 30 each). Urinary LTE(4) levels were measured using ELISA and the airway resistance Rint was assessed by the lung function instrument at the acute and the convalescence phases. Twenty healthy children were used as the control group.

RESULTSUrinary LTE(4) levels in asthmatic children at the acute and the convalescence phases were significantly higher than those in the control group (p<0.01). The urinary LTE(4) levels at the convalescence phase were significantly reduced compared with those at the acute phase in asthmatic children (p<0.01). More significantly decreased urinary LTE(4) levels were noted in the montelukast treatment group than the conventional treatment group at the convalescence phase (p<0.01). In the acute phase, there was no correlation between urinary LTE4 level and Rint in asthmatic children.

CONCLUSIONSUrinary LTE(4) level is significantly increased in children with acute asthma. Urinary LTE(4) is a useful marker for the diagnosis of asthma and can be as a predictor of asthma control and marker of susceptibility to treatment with leukotriene receptor antagonists.

Airway Resistance ; Asthma ; diagnosis ; physiopathology ; urine ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Leukotriene E4 ; urine ; Male

PURPOSE: Although early detection of airway inflammation is important to enable early prevention and treatment, it is not easy to differentiate clinically between respiratory virus- induced bronchiolitis and infantile asthma during a wheezing attack. Leukotriens (LTs) are known as a mediator of airway adhesions and inflammations, such as constricted airways and increased mucus secretions. Eosinophil cationic protein (ECP) is one of the cytotoxic proteins released from the granules of activated eosinophils, which have a role in the pathogenesis of airway inflammation. The aim of our study was to evaluate differences in urinary LTE4 and nasopharyngeal ECP levels between children with bronchiolitis and children with infantile asthma by using noninvasive techniques. METHODS: We recruited 32 children whose chief complaint was wheezing (20 non-atopic and 12 atopic children) and 18 controls without wheezing for this study. Urine and nasopharyngeal samples were collected on the day of admission. Samples were stored at -70degrees C until measurement. Nasopharyngeal ECP were measured by using UniCap (Pharmacia CAP FEIA, Pharmacia Diagostics, Uppsala, Sweden). Urine LTE4 level were measured by ACE enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI, USA). RESULTS: Children with infantile asthma have significantly higher LTE4 levels than children with bronchiolitis. Nasopharyngeal ECP levels were significantly different in children with/without wheezing. Furthermore, urinary LTE4 was significantly correlated with nasopharyngeal ECP, serum total eosinophil, serum IgE level, and respiratory symptoms. CONCLUSION: Urinary LTE4 and nasopharyngeal ECP were significantly different between children with bronchiolitis and infantile asthma. Further studies are needed to investigate the clinical application of our findings.
Asthma ; Bronchiolitis ; Child ; Eosinophil Cationic Protein* ; Eosinophils* ; Humans ; Immunoenzyme Techniques ; Immunoglobulin E ; Infant* ; Inflammation ; Leukotriene E4* ; Mucus ; Respiratory Sounds*

BACKGROUND: Exercise can aggravate asthmatic symptoms in many patients with bronchial asthma. It is caused by that inhaled air bypasses nasal cavity and goes directly to the lower airways through open mouth dring exercise. Although the pathogenetic mechanisms of exercise-induced asthma(EIA) have not been clarified yet, there is evidence that chemical mediators, released from the inflammatory cells triggered by airway cooling or drying, might be responsible for induction of bronchoconstriction. However, it has been controversial which chemical mediators or cells are involved in such process. Objectiye . The aim of this study was to evaluate the role of activated mast cells in the pathogenesis of EIA and find out whether or not sulfidopeptide leukotrienes (LTC4/d4/E4) are involved in the exercise-induced bronchoconstriction. MATERIAL AND METHOD: Eleven asthmatics with documented exercise-induced bronchoconstriction and 10 control subjects were studied. Before and 6 hours after free running for 6 minutes, forced expiratory volume in 1 second (FEV,) and the concentrations of N- methylhistamine, LTE4, and creatinine in unine collected for 6 hours after exercise were determined. RESULT: Urinary concentrations of N-methylhistamine(mean+SE, ng/mg creatinine) of EIA patients before and after exercise were 159+40 and 450+75, respectively. Those of control subjects were 208+ 54 and 275+ 62, respectively. Uninary N-methylhistamine levels of EIA group increased significantly after exercise, while those of control group did not change. Urinary concentrations of LTE,(mean+SE, pg/mg creatinine) of EIA patients before and after exercise were 15.6 k2.6 and 22.2+5.8, respectively. Those of control subjects were 10.4+ 4.0, 18.2 +7.0, respectively. The concentrations of LTE4 in the urine samples collected before exerise revealed no difference between EIA and control subjects (p=0.07). There was no change after exercise in both groups. Percent fall of FEV, was 29.1+8.0% (mean+SD) in EIA group and 3.4 + 4.0% in control group, respectively. There was no correlation between reduction of FEV, and change in urinary concentrations of N-methyl-histmine after exercise. CONCLUSTION: Chemical mediators of activated mast cells may be involved in exercise-induced bronchoconstriction, but there is little evidence for enhanced sulfidopeptide leukotriene generation as assessed by urinary LTE4.
Asthma ; Asthma, Exercise-Induced* ; Bronchoconstriction ; Creatinine ; Forced Expiratory Volume ; Humans ; Leukotriene E4 ; Leukotrienes ; Mast Cells ; Mouth ; Nasal Cavity ; Running

BACKGROUND: Cysteinyl leukotrienes are important inflammatory mediators in bronchial asthma because they enhance microvascular permeability, increase nonspecific bronchial hyperresponsiveness, and are potent bronchoconstrictor agents. Leukotriene E4 is a major metabolite of cysteinyl leukotriene excreted in urine and its concentration of urine can be a reliable marker of the overall leukotriene production in the body. OBJECTIVE: To determine whether clinical parameters of bronchial asthma are associated with production of cysteinyl leukotrienes, expressed by urinary leukotriene E4. METHOD: We measured the urinary concentration of leukotriene E4 in bronchial asthma(127 patients) and normal control(15 persons) group by ELISA method. Pulmonary function test, allergic skin test, measurement of peripheral eosinophil count and eosinophil cationic protein were undertaken in bronchial asthma patients. RESULTS: The concentrations of urinary leukotriene E4 were significantly higher in bronchial asthma patients than normal controls (p<0.05). The increased concentrations of leukotriene E4 had a significant correlation with FEV1/FVC or methacholine PC20(p<0.05). However, the concentration of leukotriene E4 did not have any correlation with the presence of atopy, peripheral blood eosinophil count, and eosinophil cationic protein level. CONCLUSION: The concentration of urinary leukotriene E4 that represents the overall leukotriene production in the body is correlated with the degree of airway obstruction and airway hyperresponsiveness. So, the concentration of urinary leukotriene E4 may be used as an adjunctive parameter of airway obstruction and hyperresponsiveness in bronchial asthma.
Airway Obstruction ; Asthma* ; Bronchoconstrictor Agents ; Capillary Permeability ; Enzyme-Linked Immunosorbent Assay ; Eosinophil Cationic Protein ; Eosinophils ; Humans ; Leukotriene E4* ; Leukotrienes ; Methacholine Chloride ; Respiratory Function Tests ; Skin Tests

It has been widely known that nasal mucosa shows reaction to neuromediators, to irritants, and to physical stimuli such as cold exposure. The mechanisms of hypersensitivity to cold were not fully understood. This study was performed to evaluate the relationship between thermal changes and releases of chemical mediators in mast cells. Mast cells were obtained from pleural and peritoneal fluids of 12 Sprague Dawley rats. They were stimulated with substance P and compound 48/80, known most powerful stimulant to mast cells, for 5 and 30 minutes under the temperature of 0degreesC, 10degreesC, 20degreesC, 25degreesC and 36degreesC. In control group, nontreated mast cells were incubated for 5 and 30 minutes under the same temperatures as experimental group. Histamine and leukotriene E4 were measured in supernatant of each culture tube by enzyme linked immunosorbent assay. Mast cells treated with compound 48/80 produced a marked increase in histamine release and the cells treated with substance P did an increased histamine too. The increases in substance P treated mast cells were less than those in compound 48/80 treated cells. However, there were statistically no difference of histamine release between substance P treated cells and compound 48/80 treated cells in 20degreesC. Contents of leukotriene E4 were too small to measure amounts in both control and compound 48/80 treated group. The cells treated with substance P showed a visible increase in leukotriene E4 release on 5 minutes incubation at 36degreesC and on 30 minutes incubation at 20degreesC. This study suggests that a thermal change has not an effect on releasing chemical mediators from mast cells and substance P could play an important role in release of chemical mediators at the environment of 20degreesC.
Animals ; Ascitic Fluid ; Enzyme-Linked Immunosorbent Assay ; Histamine Release ; Histamine* ; Hypersensitivity ; Irritants ; Leukotriene E4* ; Mast Cells* ; Nasal Mucosa ; Rats* ; Rats, Sprague-Dawley ; Substance P*