Effects of a Leukotriene Receptor Antagonist on Airway Remodeling in Asthmatic Mice via the Wnt/β -catenin Signaling Pathway / 中国医科大学学报

Objective To investigate the expression of Wnt7b, β -catenin, and c-Myc in asthmatic mice and the intervention of the leukotriene receptor antagonist montelukast on airway remodeling. Methods The asthma model was established by ovalbumin (OVA) induction. HE staining was used to observe the pathological changes in lung tissue. Serum OVA-sIgE levels were determined by ELISA. The level of Wnt7b, β -catenin, and c-Myc protein and mRNA in the lung tissue of mice was analyzed by Western blotting and real-time PCR. The basement membrane perimeter (PBM), wall area of bronchial tube (WAt), wall area of bronchial smooth muscle (WAm), and the number of smooth muscle cells were measured using medical image analysis software and standardized based on the PBM. Results The amount of OVA-slgE in the asthma group was significantly higher than in the control and montelukast groups (P ＜ 0. 05). Western blotting and real-time PCR showed that the expression of Wnt7b, β -catenin, and c-Myc in the asthma group was higher than the expression in the control and montelukast groups (P ＜ 0. 05). Image analysis showed that the WAt/PBM and WAm/PBM ratios in the montelukast group were significantly lower than those in the asthma group (P ＜ 0. 05). Conclusion The Wnt/ β -catenin signaling pathway may be an important factor in the pathogenesis of asthma; montelukast may attenuate airway remodeling in asthmatic patients by decreasing the expression of Wnt7b, β -catenin, and c-Myc.

Relationship between obstructive sleep apnea hypopnea syndrome and inflammation in children / 解放军医学杂志

Objective To investigate the clinical efficacy of anti-inflammatory therapy (intranasal corticosteroids combined with oral leukotriene receptor antagonist) in pediatric mild to moderate obstructive sleep apnea hypopnea syndrome (OSAHS),and analyze the relationship between OSAHS and inflammation factors.Methods Fifty patients with mild to moderate OSAHS,diagnosed by polysomnography (PSG) during Jan.to Nov.2016,were enrolled in present study.The patients' medical history,data of special physical examination,paryngorhinoscopy,PSG and OSA-18 questionnaire were collected.Patients received the therapy of intranasal corticosteroids combined with oral leukotriene receptor antagonist for 12 weeks.Special physical examination,paryngorhinoscopy,PSG and OSA-18 questionnaire were reviewed and the data before and after treatment were compared.Results Of the 50 subjects,37 were with mild OSAHS and 13 with moderate OSAHS.A total of 19 cases (38％) were cured including 17 mild OSAHS and 2 moderate cases.Other 19 cases (38％) got therapeutic effect but not be cured.Twelve cases (24％) were invalid or aggravated.There were 10 patients (20％) who received surgical treatment after drug treatment.The average values of obstructive apnea index (OAI) and mixed apnea index (MAI) decreased significantly in mild group and only OAI decreased in moderate group.After treatment,the average volumes of adenoids and tonsils were significantly reduced in mild OSAHS children but not in moderate OSAHS children.The OSA-18 questionnaire score declined only in mild group.No obvious correlation existed between the change of tonsil volume and the parameters of PSG.Conclusion Anti-inflammatory therapy of intranasal corticosteroids combined with oral leukotriene receptor antagonist may obviously reduce the volumes of adenoids and tonsils,improve the PSG indexes and the life quality of OSAHS patients,especially for those children with mild OSAHS.

Evaluación clínica de niños con rinitis alérgica tratados con montelukast / Clinical Evaluation in Children with Allergic Rhinitis Treated with Montelukast

Introducción: la rinitis alérgica es un trastorno sintomático, con inflamación de la mucosa nasal mediada por IgE e inducida por la exposición a alérgenos. Sus tres síntomas cardinales son la obstrucción nasal, los estornudos y la rinorrea. La rinitis alérgica es un problema global que va aumentando su prevalencia. Objetivo: evaluar la efectividad del montelukast en los niños con rinitis alérgica persistente perteneciente al Policlínico René Ávila Reyes de Holguín durante el periodo de octubre de 2012 a febrero de 2013. Método: se realizó un estudio analítico prospectivo en 20 pacientes pediátricos con rinitis alérgica persistente con edades entre los 6 y 19 años. Las variables estudiadas fueron sexo, edad, otras enfermedades alérgicas, síntomas nasales diurnos, síntomas nocturnos, síntomas oculares diurnos y valor total de eosinófilos. Se utilizó la prueba de McNemar con un p=0,01. Resultados: predominaron 12 pacientes del sexo masculino, (60,0%), 16 pacientes con asma bronquial (80,0%) y 8 con dermatitis atópica (40,0%). Antes del tratamiento 20 niños presentaban prurito nasal, luego del mismo solo un niño mantuvo esta condición (5,0%); 16 niños presentaban congestión nasal (80,0%) después del tratamiento solo un niño conservó esta condición (5,0%). Antes del tratamiento solo un paciente presentaba valores normales de la eosinófilos y luego del mismo esta cifra aumentó a 17 niños para el 85,0%. Conclusiones: en el grupo de estudio predominaron los pacientes masculinos, adolescentes y con asma bronquial. El montelukast fue efectivo en el manejo y control de los síntomas de los pacientes con rinitis alérgica.

Introduction: Allergic rhinitis is an IgE-mediated inflammation of the nasal mucosa induced after allergen exposure and presents with the 3 cardinal symptoms of sneezing, nasal obstruction, and rhinorrhea. Allergic rhinitis is a global health problem and is increasing in prevalence. Objective: to evaluate the effectiveness of montelukast in children with persistent allergic rhinitis in the Rene Avila Reyes Polyclinic, in Holguín, from October 2012 to February 2013. Methods: a prospective analytical study was performed including 20 patients aged from 6 to 19 years old. The variables analyzed in the study were: sex, age, other allergicdiseases, nasal symptoms in the day, symptoms in the night, and ocular symptoms in the day and total eosinophils. For comparative analysis we used the McNemar test p=0.01. Results: 12 patients (60.0%) of male sex were found, 16 (80.0%) with Bronchial Asthma and 8 (40.0%) with atopic dermatitis. Before the treatment 20 patients had nasal itch, 16 had nasal obstruction and 1 patient had normal levels of eosinophils. After treatment with montelukast 1 patient (5.0%) had nasal itch and nasal obstruction and 3 patients had high levels of eosinophils. Conclusions: in the population had prevalence of male patients, adolescents and with Bronchial Asthma. Montelukast was effective for managing and control of symptoms the patients with Allergic Rhinitis.

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Effects of leukotriene receptor antagonists on airway remodeling and Th17 cells/CD4+CD25+regulatory T cells expresson in asthma / 临床儿科杂志

The airway remodeling of bronchial asthma is the result of repeated airway inlfammation. Its occurrence is a complex process involving many cytokines, inlfammatory mediators and associated cellular components, of which leukotrienes are important mediators of inlfammation in the airway remodeling. Many factors inlfuence Airway remodeling. In recent years, effects of Th17 cells and CD4+CD25+regulatory T cells (CD4+CD25+treg cells) on airway remodeling is growing in importance. Leukotriene receptor antagonist is an effective drug in the treatment of asthma and can suppress airway remodeling. But the exact mechanisms and its impact on the proportion of Th17 cells/CD4+CD25+treg cells is not yet clear. Therefore, the clariifcation of the changes of Th17 cells/CD4+CD25+treg cells expression in airway remodeling and the speciifc pathways, biological effects, inlfuence of the proportion of Th17 cells/CD4+CD25+treg cells expression after leukotriene receptor antagonist intervene can provide a new target for prevention and the treatment of asthma in the future.

Integrating Evidence for Managing Asthma in Patients Who Smoke

Cigarette smoking among asthma patients is associated with worsening symptoms and accelerated decline in lung function. Smoking asthma is also characterized by increased levels of neutrophils and macrophages, and greater small airway remodeling, resulting in increased airflow obstruction and impaired response to corticosteroid therapy. As a result, smokers are typically excluded from asthma randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used by asthma RCTs limits the extent to which their findings can be extrapolated to the routine care asthma population and to reflect the likely effectiveness of therapies in subgroups of particular clinical interest, such as smoking asthmatics. The inclusion of smokers in observational asthma studies and pragmatic trials in asthma provides a way of assessing the relative effectiveness of different treatment options for the management of this interesting clinical subgroup. Exploratory studies of possible treatment options for smoking asthma suggest potential utility in: prescribing higher-dose ICS; targeting the small airways of the lungs with extra-fine particle ICS formulations; targeting leukotreines, and possibly also combinations of these options. However, further studies are required. With the paucity of RCT data available, complementary streams of evidence (those from RCTs, pragmatic trials and observational studies) need to be combined to help guide judicious prescribing decisions in smokers with asthma.

Bloqueio do receptor de leucotrieno CysLT1 em pacientes com fenômeno de Raynaud: evidência capilaroscópica do papel do leucotrieno / CysLT1 receptor inhibition in patients with Raynaud's phenomenon: capillaroscopic evidence of the role of leukotriene

OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste) nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95 por cento. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo), nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de Raynaud.

OBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast) on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes mellitus. All patients maintained their previous medications and started the use of montelukast, 10 mg/day, for 60 days. Naifold capillaroscopy of fingers was performed before the use of medication and after 30 and 60 days. Statistical analysis was performed with percentage, media, standard deviation, Fisher exact test, with 95 percent of confidence interval. RESULTS: The study assessed five Caucasian, female patients with Raynaud's phenomenon secondary to inflammatory connective tissue disease (three with scleroderma and two with mixed connective tissue disease), aged 42.4 ± 11.5 years, and with 9.6 ± 4.8 years of disease duration. Patients were on nifedipine and pentoxifylline, and those with mixed connective tissue disease were also on prednisone. The medications were maintained. After using montelukast for two months, nailfold capillaroscopy showed a reduction in edema and pallor, and normalization of capillary number, size, and distribution. CONCLUSION: The use of montelukast modified the capillary abnormalities observed on nailfold capillaroscopy of patients with Raynaud's phenomenon.

Tratamiento farmacológico para el control del asma en el niño

El presente artículo presenta las recomendaciones de un grupo de expertos venezolanos reunidos en Caracas en Octubre de 2009 por la Sociedad Venezolana de Puericultura y Pediatría en relación al tratamiento farmacológico del asma infantil. Se presentan los objetivos del tratamiento, los medicamentos recomendados, la terapia inicial y de mantenimiento y el tipo de dispositivo para la administración de drogas por vía inhalatoria, de acuerdo a la edad del paciente.

This article presents the recommendations made by a group of Venezuelan experts during a consensus meeting held in Caracas in October, 2009, under the auspices of the Venezuelan Society of Pediatrics, on the pharmacological treatment of childhood asthma. Goals of treatment, recommended medications, initial and maintenance therapy, and devices utilized for delivery of inhaled drugs according to patient’s age are presented.

Clinical efficacy of leukotriene receptor antagonists in treatment of chronic cough / 中国综合临床

Objective To explore the clinical efficacy of leukotriene receptor antagonists in treatment of chronic cough. Methods Eighty-one patients with chronic cough, defined by the diagnostic protocol of chronic cough, were recruited. The including criteria are complaining cough 8 weeks or longer, age ≥ 14, nonsmoking or had quitted smoking≥4 weeks, not taking ACEI medicine, not complicated with gastroesophageal reflux related cough, upper airway cough syndrome (besides allergic rhinitis), tuberculosis of bronchus and with normal chest X-ray. Those diagnosed as cough variant asthma(CVA),allergic rhinitis (AR),eosinophilic bronchitis(EB),post infectious cough(PIC) were treated with leukotriene 10 mg daily at night. Results The 81 patients includes:36 cases of CVA,30 cases of AR,5 cases with EB,10 cases with PIC. After treatment based on diagnosis, cough disappeared in 67 patients, symptoms improved in 12 patients, and 2 patients' cough did not improved. Conclusions Leukotriene receptor antagonists is an aggressive anti-inflammatory therapy, which can release the symptom of cough and is an important medicine in the treatment of chronic cough.

Clinical Efficacy Evaluation of Leukotriene Receptor Antagonists for Treatment of Coexisting Asthma and Allergic Rhinitis in Children / 国际儿科学杂志

Objective To evaluate the efficacy of Leukotriene receptor antagonists in treatment of patients with asthma and allergic rhinitis(AR).Methods This study was a 24-week,randomized,control open trial in which 100 children,who were diagnosed as mild to severe persistent coexisting asthma and AR,were enrolled.All cases were collected from pediatric out-patient department of the First Affiliated Hospital of Guangzhou Medical College from October 1st,2005 to April 30th,2006 and were divided into three groups.Montelukast group(1 group):inhated budesonide turbuhaler and oral singulair(5mg/Qn);Intranasal corticosteroids group(2 group):inhaled budesonide turbuhaler and intranasal budesonide nasal spray(64?g/Qd);Control group(Control group):only inhaled budesonide turbuhaler.Efficacy was assessed by recording daytime and nighttime symptom scores,nasal symptom scores,the times of acute episode,the symptomfree days,the requirement for the weekly beta 2-receptor agonist and the medication scores,using a daily diary card and the recording work were repeated per fo ur weeks in totally six months.Lung function(forced expiratory volume at 1 s inpredicted normal,FEV1%) and nasal eosinophil count had been tested three times:before treatment,after treatment of 8th and 24th week.Results 1 group and 2 group,compared with the prior treatment(P0.05);1 group was more statistically significant than 2 group in improving FEV1(P

MUC2/5AC Expression and Mucin Secretion through Leukotriene Receptor in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin production are highly increased during inflammatory airway disorders such as, asthma, chronic bronchitis and sinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators are related with secretion and production of mucin. However, among of inflammatory mediators, the relation of leukotrienes and mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC genes expression and mucin secretion through leukotriene receptor in human airway epithelial cells. SUBJECTS AND METHOD: The effect of Leukotriene D4 and leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion was observed in the human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS: Leukotriene D4 upregulated MUC2/5AC gene expression and mucin secretion on a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 micrometer) downregulated the leukotriene D4-mediated MUC2/5AC gene expression and mucin secretion. CONCLUSION: These results suggest that the leukotriene receptor system is one of the expression mechanisms of MUC2/5AC genes and mucin secretion.