[Effect of the leukotriene receptor antagonist montelukast therapy on asthma in childhood]

[Article in Hungarian]

Kosa L.

Svabhegyi Allami Gyermekgyogyintezet, Budapest.

The authors have summed up the survey results for children with asthma below 14 years of age participating in the Hunair II. surveillance program. This program proves the efficiency of montelucast 5mg treatment in cases of childhood asthma bronchiale. The 255 patients participating in the survey have received 5 mg montelucast therapy for 8 weeks. During the surveillance period they have used questionnaires to record the change of day and night symptoms, decrease of different restrictions and the quantity change of long- and short-acting beta agonists and inhaled steroids. The use of short-acting agonists decreased from 5 inhalations to 1 in 4 weeks. During the leukotriene antagonist montelucast treatment according to symptom scores 61% of the patients have experienced improvements after the 4th week, 80% after the 8th week. To sum up all the survey results--after the 8th week of treatment the daytime restrictions in the everyday lives of children with asthma have decreased by 88.1%, nighttime restrictions by 80.1%. After the 2nd month of the HUNAIR II. surveillance program it could be deduced that montelucast 5 mg therapy used in child populations less then 14 years of age with asthma has proven useful.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15638037&dopt=Abstract montelukast, Singulair




Biological effects of montelukast, a cysteinyl-leukotriene receptor-antagonist, on T lymphocytes.

de Benedictis FM.

Laboratory of Experimental Immunology and Allergy, Department of Clinical and Experimental Medicine, University of Perugia, I-06122 Perugia, Italy. spinozzi unipg.it

BACKGROUND: Montelukast (MNT), a cysteinyl-leukotriene receptor (Cys-LTR) antagonist, has anti-inflammatory activity in the treatment of allergic diseases. If this effect is due only to blocking leukotrienes or also owing to inhibiting proliferation and survival of inflammatory cells, is actually unknown. OBJECTIVE: Testing the hypothesis that MNT could influence T lymphocyte functional behaviour in vitro. METHODS: Normal T lymphocytes were analysed for surface expression of Cys-LTR(1) and Cys-LTR(2) by means of monoclonal antibodies (mAbs), in the resting state and after activation with T helper type 2 cytokine or T cell receptor (TcR) stimulation. Proliferative activity, as well as IL-4 andIFN-gamma production, were simultaneously determined in samples exposed to molar concentrations of MNT from 10(-8) to 10(-5). Programmed cell death in cultured samples was evaluated by means of propidium iodide and fluorescein isothiocyanate-conjugated anti-Annexin V mAb staining. The complementary DNA microarray technique was adopted to identify gene products involved in apoptosis induction. RESULTS: Resting T cells expressed low levels of Cys-LTR. Upon anti-CD3 mAb activation, a progressive increase in Cys-LTR(1) and -LTR(2) expression was observed. Exposure to MNT reduced proliferative response to TcR engagement, increased IFN-gamma production and led to apoptosis at minimal concentrations of 10(-6) M. A progressive loss in BAD and B cell lymphoma/leukaemia-2 activities, and an increase in the expression of CD27, TRAF3, TRAIL, p53 and Fas genes were also observed. CONCLUSIONS: Biological effects of MNT delineate a complex picture of gene activation and repression, probably induced by Cys-LTR blockade. The induction of apoptosis in allergen-specific T cell population, as a final result, appears fundamental in the treatment of asthma.

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[Effects of montelukast on apoptosis and Fas mRNA expression of eosinophils in airway of asthmatic guinea pigs]

[Article in Chinese]

Zhang HQ.

Medical and Pharmacological Institute of Yangzhou University, Yangzhou 225001, China.

AIM: To study the effect of montelukast on apoptosis and Fas mRNA expression of eosinophils in airway of asthmatic guinea pigs. METHODS: Experimental asthma model of guinea pigs was induced by ovalbumin. The eosinophils in broncho-alveolar lavage fluid (BALF) were separated by density gradient centrifugation. The apoptosis of eosinophils was labeled by TdT-mediated dUTP nick end labeling (TUNEL) technique. Fas mRNA expression of eosinophils was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After treatment with montelukast, the number of eosinophils in BALF of asthmatic guinea pigs decreased significantly. The apoptosis index as well as Fas mRNA expression of eosinophils were elevated significantly. There were statistical differences between the therapeutic group and the model group. CONCLUSION: Apoptosis of eosinophils is highly correlated with the increased expression of Fas mRNA. Enhancing expression of Fas mRNA and promoting apoptosis of eosinophils subsequentely may be an important mechanism for montelukast to antagonize airway inflammation of asthma.

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The effect of montelukast on exhaled nitric oxide and lung function in asthmatic children 2 to 5 years old.

Wildhaber JH.

Division of Respiratory Medicine, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. daniel.straub kispi.unizh.ch

OBJECTIVE: The study was undertaken to investigate the influence of once-daily treatment with montelukast (Singulair; MSD; Glattbrugg, Switzerland) on levels of exhaled nitric oxide (eNO) and lung function in preschool children with asthma. METHODS: A total of 30 children (19 girls), 2 to 5 years of age, in whom asthma had been newly diagnosed, who had a positive first-degree family history of asthma and a positive allergy test result, were allocated to undergo a 1-week run-in period of montelukast treatment. eNO and airway resistance were measured in all patients before (visit 1) and after the run-in period (visit 2), and after treatment with montelukast (4 mg once daily) for 4 weeks (visit 3). RESULTS: There were no significant differences in all parameters before and after the run-in period. However, the mean (SD) levels of eNO and the mean (SD) levels of airway resistance after treatment at visit 3 were 11.6 parts per billion (ppb) [9.5 ppb] and 1.15 kPa/L/s (0.26 kPa/L/s), respectively, and were significantly lower compared to values of 33.1 ppb (12.0 ppb) and 1.28 kPa/L/s (0.23 kPa/L/s), respectively, before treatment (p < 0.001) and at visit 2 (p = 0.01). There was no significant change in mean bronchodilator responsiveness between visit 3 (13.2%; SD, 6.8%) and visit 1/visit 2 (13.3%; SD, 7.0%; p = 0.47). CONCLUSION: We have shown that montelukast has a positive effect on lung function and airway inflammation as measured by nitric oxide level in preschool children with allergic asthma.

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Effects of antileukotriene among asthmatic patients.

Saenghirunvattana S.

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

STUDY OBJECTIVE: To determine the effect of antileukotriene (montelukast) 10 mg once daily for the treatment of mild to moderate asthma. DESIGN: Open label, prospective. PATIENTS: Thirty asthmatic patients > or = 18 years of age with baseline FEV1 > 60 per cent and < or = 80 per cent of predicted values and evidence of reversible airway obstruction, as defined by an increase in FEV1 of > or = 20 per cent. INTERVENTIONS: Montelukast 10 mg once daily orally for 12 weeks, back up beta-2 agonist inhaler was available. MEASUREMENT AND RESULTS: Spirometry was performed during the screening period, and every month after starting antileukotriene. Subjects recorded asthma-related symptoms and use of supplement beta-2 agonists daily on diary cards. Over 12 weeks of treatment, the FEV1 increased 10 per cent, 14 per cent and 19 per cent respectively, compared to the baseline (p < 0.05). The physician and patients evaluation scores were quite good in the study. CONCLUSION: Oral montelukast once daily gave a favorable effect in management of mild to moderate asthmatic patients.

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