Assessment of leukotriene E4 in exhaled breath condensate as a marker of inflammation and therapeutic effect in allergic rhinitis children

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.

A Double-Blind, Randomized, Crossover Study to Compare the Effectiveness of Montelukast on Atopic Dermatitis in Korean Children

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.

Clinical efficacy of montelukast for the treatment of bronchiolitis in infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis.</p><p><b>METHODS</b>Seventy-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.</p><p><b>RESULTS</b>After 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).</p><p><b>CONCLUSIONS</b>Montelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.</p>

Ratio of Leukotriene E4 to Exhaled Nitric Oxide and the Therapeutic Response in Children With Exercise-Induced Bronchoconstriction

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.

Association of SCORAD Index and Aeroallergen Sensitization on Urinary Leukotriene E4 in Children with Atopic Dermatitis / 소아알레르기및호흡기학회지

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.

Changes of prostaglandin D2,carboxypeptidase A3 and platelet activating factor in guinea pig in anaphylactic shock / 法医学杂志

OBJECTIVE@#To detect the changes of leukotriene E4(LTE4), prostaglandin D2(PGD2), carboxypeptidase A3(CPA3) and platelet activating factor (PAF) in guinea pigs died from anaphylactic shock.@*METHODS@#Guinea pigs were used for establishing anaphylactic shock models. The levels of LTE4, PGD2 and CPA3, and PAF were detected in urine, plasma, and brain tissues with ELISA kit, respectively. The significant biomarkers were selected comparing with control group. The changes of PGD2, CPA3 and PAF in the guinea pigs at time zero, 12 and 24 hours after death were observed and compared respectively. The effect of platelet activating factor acetylhydrolase (PAF-AH) to PAF in guinea pig brain was examined and compared.@*RESULTS@#There were no statistically differences of LTE4 levels in urine observed between experimental group and control group. The levels of CPA3, PGD2 and PAF in the experimental group were significantly higher than that in the control group at 0 h. The levels of PAF at 12 and 24 hours after anaphylactic shock were significantly higher than that in the control group. The levels of PAF decreased significantly after pretreatment with PAF-AH.@*CONCLUSION@#LTE4 in urine cannot be selected as a biomarker to determine the anaphylactic shock. PGD2 and CPA3 in plasma, and PAF in brain tissue may be used as biomarkers to determine the anaphylactic shock. PAF-AH may be potentially useful for clinical treatment of anaphylactic shock.

Urinary leukotrience E(4) level in children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Cysteinyl 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.</p><p><b>METHODS</b>Sixty 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.</p><p><b>RESULTS</b>Urinary 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.</p><p><b>CONCLUSIONS</b>Urinary 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.</p>

Relationship between the efficacy of inhaled corticosteroids and the leukotriene expression in children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between leukotriene expression in blood polymorphonuclear leukocytes (PMNL) and the efficacy of inhaled corticosteroids (ICS) in children with asthma.</p><p><b>METHODS</b>Thirty-two children with asthma (5-12 years) and ten healthy children (control group) were enrolled. The asthmatic children were subdivided into ICS well-controlled and ICS poorly-controlled groups based on their clinical symptoms and lung function. The level of leukotriene C4 synthase (LTC4S) mRNA in PMNL was detected by fluorescence quantitative polymerase chain reaction. The level of LTC4S mRNA was expressed by the value of qCt, and the value of qCt was diversely correlated with the level of LTC4S mRNA expression. The concentration of urinary leukotriene E4 (LTE4) was measured using ELISA.</p><p><b>RESULTS</b>The expression of LTC4S mRNA in PMNL was significantly higher in children with asthma (qCt: 1.12+/-0.27) than that in the control group (qCt: 1.42+/-0.12; P< 0.05). The expression of LTC4S mRNA in PMNL in the ICS poorly-controlled group (qCt: 1.03+/-0.17) was significantly higher than that in the ICS well-controlled group (qCt: 1.24+/-0.33; P< 0.05) and the control group(1.42+/-0.12; P< 0.01). There was no significant difference in the level of urinary LTE4 among the the ICS poorly-controlled, the ICS well-controlled and the control groups.</p><p><b>CONCLUSIONS</b>LTC4S mRNA expression in PMNL in asthmatic children increases, and the LTC4S mRNA expression in the ICS poorly-controlled group is higher than that in the ICS well-controlled group. This suggests that an increased leukotriene expression might be associated with poorly-controlled asthma.</p>

Role of urinary leukotriene E4 in the pathogenesis of atopic dermatitis

This study was meant to evaluate the importance of LTs in atopic dermatitis [AD] and to study the correlation of urinary LTE4 with disease severity and some commonly altered parameters in AD. The study included 30 children and adolescents diagnosed to have atopic dermatitis. Ten age and sex matched healthy children and adolescents were enrolled for comparison. They were subjected to clinical evaluation and measurement of urinary LTE4, absolute eosinophilic count, serum IgE and IL-4 and IL-5 in peripheral blood mononuclear cell culture [PBMC] supernatant. The patients were categorized into mild [n = 5], moderate [n = 16] and severe [n = 9] AD subgroups. The study revealed a significant increase in absolute eosinophilic count. Urinary LTE4, serum IgE and IL-4 and IL-5 in PBMC culture supernatant in the patients as compared to controls. Moreover, urinary LTE4 levels were significantly increased in moderate and severe cases of AD as compared to the control group, whereas mild cases had levels that were comparable to the controls. Urinary LTE4 levels were higher in severe and moderate cases when compared to mild cases. Significant positive correlations could be elicited between urinary LTE4 and PBMC IL-4, disease severity scale, absolute eosinophilic count and serum total IgE. However, urinary LTE4 could not be correlated statistically with PBMC IL-5

Study of Urinary Leukotriene E4 and Eosinophil Cationic Protein in Nasopharyngeal Aspiration from Wheezing Infants / 소아알레르기및호흡기학회지

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.

Effects of leukotriene receptor antagonist on chronic obstructive correction of obstractive pulmonary disease induced pulmonary hypertension / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.</p><p><b>METHODS</b>Eleven cases of chronic cor pulmonale at acute exacerbation were examined using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E(4) (LTE(4)) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Arterial and mixed venous blood gas analyses were done correspondingly.</p><p><b>RESULTS</b>The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE(4) and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP.</p><p><b>CONCLUSIONS</b>Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.</p>

Urinary leukotriene E[4] in asthmatic children with and without nocturnal exacerbations

Nocturnal exacerbations of bronchial asthma are very common and disturbing signs with serious consequences on patient's quality of life. The exact mechanism of these exacerbations is not known but inflammatory mediators may play an important role. To study the role of leukotriene E[4] [LTE[4]] in the pathogenesis of nocturnal exacerbations of bronchial asthma. The study was conducted on 50 asthmatic children who used to attend the outpatient clinics of the Pediatric and Chest Departments of Tanta University Hospital. Their ages ranged 8-14 years. The study was carried out over 10 months from October 1, 2000 to July 31, 2001. They were classified into two groups. Group A included 25 asthmatic children without nocturnal symptoms, and group B comprised 25 children who used to have nocturnal asthma exacerbations. Twenty non-asthmatic children of comparable ages were included in the study as controls. All of the children were subjected to full history taking, clinical examination, pulmonary function tests [PFTs], methacholine bronchial challenge test, and measurement of LTE[4] in urine. Values of morning drop of peak expiratory flow [PEFR] in children with nocturnal symptoms [Group B] was significantly higher than those in the asthmatic children without nocturnal exacerbations [Group A] [P<0.05]. The PC[20] FEV[1] was significantly lower in group B than in group A [P<0.05]. Urinary LTE4 levels were found to be significantly higher in group B than in group A [P<0.05]. In asthmatic children with nocturnal exacerbations [group B], urinary LTE[4] levels were found significantly higher at night more than at day hours [P<0.05]. Also, in this same group B, there were significant positive correlations between urinary LTE[4] levels and morning drop in PEFR values and significant negative correlation between urinary LTE[4] levels and PC[20] FEV[1] [P<0.05]. There was no significant difference in urinary LTE[4] levels between atopic and non-atopic asthmatic children. Measurement of urinary LTE[4] levels may represent a non-invasive method for assessment of airway inflammation and for predicting the outcome of nocturnal exacerbations that disturb the life of asthmatic children

Clinical application of urinary leukotriene E4 in bronchial asthma / 천식및알레르기

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.

The Difference between the Concentrations of Arachidonic Acid Metabolites in the Cholesterol Granuloma and Granulation Tissues in Chronic Otitis Media / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Both the granulation tissue and cholesterol granuloma can erode the surrounding bone and ossicles. However, the etiology of bone resorption in the granulation tissue and cholesterol granuloma has not been evident. The aim of this study was to assay the concentrations of arachidonic acid metabolites (AAMs) in cholesterol granuloma and the mastoid granulation tissue in order to better understand the possible role of AAMs in the pathophysiology of cholesterol granuloma in comparison with the granulation tissue. MATERIALS AND METHOD: Cholesterol granuloma tissues were obtained from eight patients who had underwent tympanomastoidectomy. Granulation tissues, which served for comparison, were taken from 12 patients who had underwent tympanomastoidectomy. Tissue concentrations of prostagladin (PG)E2, 6-keto-PGF1alpha, leukotriene (LT)C4, LTD4, LTE4, 15-hydro xyeicosatetraenoic acid (HETE), 12-HETE, 5-HETE, and thromboxane (TXB)2 were calculated using high performance liquid chromatography and compared between cholesterol granuloma and granulation tissue. RESULT: The level of 12-HETE was higher in cholesterol granuloma than in the granulation tissue. Among the PGs, the tissue concentration of PGE2 was particularly high in cholesterol granuloma than in the granulation tissue. LTD4 was the only LT detectable in cholesterol granuloma. In comparison to the AAMs in cholesterol granuloma, the lipoxygenase pathway products such as 12-HETE, 15-HETE, and 5-HETE were present in lower concentrations in the granulation tissue. LT was undetectable in the granulation tissues. CONCLUSION: Our results suggest that cholesterol granuloma and the granulation tissue is different not only in terms of histology, but also in terms of biochemical properties such as arachidonic acid metabolism.

Asma por ejercicio: utilidad de marcadores en orina / Exercise induced asthma: utility of urinaria markers

Antecedentes: los metabolitos estables de la Prostaglandina D2 (PGD2) mastocitaria 9 Ó11ß Prostaglandina F2 (9 Ó11ßPGF2) y de los cis-leucotrienos (LTE4) medidos en orina reflejan la producción de estos mediadores. Objetivos: determinar el rol de los leucotrienos y de la Prostaglandina D2 a través de la relación existente entre la provocación del asma por ejercicio (AIE) y los niveles urinarios de Laucotrieno E4 (LTE4) y 9 Ó11ßPGF2. Materiales y métodos: fueron estudiados 24 niños con asma (6-14 años) y 9 niños sanos como control. En todos los asmáticos y en 5 controles se evaluó la presencia de AIE mediante prueba de carrera libre durante 7 min, alcanzando el 80 por ciento de frecuencia cardíaca máxima para la edad. Se realizaron espirometrías basales y post prueba (secuenciales) y se colectó orina inmediatamente antes y 45 minutos despues de la prueba. LTE4 y 9 Ó11ßPGF2 fue evaluada por enzimainmunoensayos específicos. Resultados: Los 5 controles normales no presentaron asma por ejercicio, de los 24 pacientes asmáticos 12 no presentaron AIE y en 12 la prueba fue posititva (VEF1s cae > 15 por ciento). Las medias de los valores basales y post ejercicio de LTE4 y 9 Ó11ßPGF2 en pg/mg creatinina se tabulan a continuación: Asma por ejercicio: 9 Ó11ßPGF2: Basal: 3,39; Post: 7,95; p=0,001; LTE4: Basal: 4,00; Post: 9,39; p=0,002. Asma sin ejercicio: 9 Ó11ßPGF2: Basal: 3,98; Post: 6,28; p=0,02; LTE4: Basal: 5,91; Post: 7,04; p=0,242. Los niveles de 9 Ó11ßPGF2 y LTE4 de los controles normales no variaron significativamente post ejercicio. Conclusión: en los pacientes con asma por ejercicio se verifica activación mastocitaria con liberación de PGD2 que se demuestra como aumento de 9 Ó11ßPGF2 urinaria, y de los leucotrienos aumento del LTE4. El aumento de LTE4 es específico para asma por ejercicio en tanto que la 9 Ó11ßPGF2 aumenta en ambos grupos

Urinary N-methylhistamine and sulfidopeptide leukotriene in exercise-induced asthma / 천식및알레르기

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.

Effects of Substance P on Histamine and Leukotriene E4 Release from Rat Mast Cells according to Temperature Changes / 대한이비인후과학회지

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.

Cambios metabólicos del ácido araquidónico en la desensibilización a la aspirina / Aspirin, metabolic change in arachidonic acid in the desensitization

La sensibilización de la aspirina se presenta en acerca del 10 por ciento de todos los pacientes asmáticos. En esta clase de asmáticos la congestión nasal y el broncoespasmo ocurren entre los 30 a 180 minutos después de la ingestión de la aspirina. Luego de la reacción respiratoria a la aspirina todos los pacientes pueden ser desensibilizados a la misma mediante la introducción repetida de pequeñas a grandes cantidades de aspirina hasta que los sujetos asmáticos pueden ingerir 650 mg del fármaco sin ningún efecto adverso. Los mecanismos de la sensibilidad a la aspirina no están totalmente esclarecidos, y las razones por las cuales la desensibilización en los pacientes asmáticos sensibles a la aspirina (ASA) ocurre de manera universal se desconocen. En este estudio, pacientes ASA y testigos asmáticos no ASA se expusieron a dosis provocadoras de aspirina. Se colectaron muestras de orina antes, durante el broncoespasmo inducido, y después de la ingestión de 650 mg de aspirina, cuando los efectos adversos habían desaparecido (fenómeno de desensibilización). Se dertminaron los niveles de los productos tipo y cicloxigenados en las muestras de orina. En este trabajo se analizan los resultados y se expone una explicación del probable mecanismo de la desensibilización