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Leukotrienes comprise a family of products of the 5-lipoxigenase pathway of arachidonic acid metabolism. The cysteinil leukotrienes C4, D4 and E4 account for the biologic activity that was previously termed "slow-reacting substance of anaphylaxis". The proinflammatory effects of cysteinil leukotrienes (cys LTs) have been well described in asthma and rhinitis. The cys LTs induce broncospasm (1,000 times more potent than histamine), edema, mucus, hypersecretion, attract inflammatory cells like eosinophils, increase airway hyperreactivity, vascular leakage, and stimulate takikinins. The leukotriene synthesis can be inhibited in two different places; through inhibition of 5 lipooxigenase activating protein (FLAP) in the 5 lipooxigenase pathway, with the drug Zyleuton, or blocking the cysLT1 receptor with the drugs Montelukast, Pranlukast, Zafirlukast. The cysLTs play an important role in pathophysiology of allergic rhinitis and comorbid diseases like rhinosinusitis and nasal polyposis. Antileukotrienes are prescribed in the treatment of allergic rhinitis. Allergic rhinitis is a complex IgE inflammatory disease of the upper airways. It is the most common allergic disease ocurring in 10 to 20% of adults and up to 30% of children. It may be seasonal or perennial, intermittent or persistent. Sneezing, itching, watery rhinorrea and nasal obstruction are classic symptoms. Ocular itching, lacrimation and redness also occur frequently as almost 50% of the patients also have allergic conjunctivitis. Allergic rhinitis may be mild, moderate or severe disease. It may impair cognition, school and work performance. It affects productivity, behavior and mood changes, causes sleep disturbance and diminish the patient's quality of life. Allergic rhinitis is a common comorbid condition with asthma, sinusitis, otitis media, nasal polyposis and recurrent respiratory infections. The purpose of this rewiew article is to know the importante of leukotrienes, its receptors and the clinical efficacy of leukotriene antagonists in allergic rhinitis and comorbid diseases.
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We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.
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The efficacy and safety of a single-dose of Montelukast sodium for treating virus-related infantile wheezing are investigated in this study.
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All active treatments in both arms of the study resulted in the decrease of sICAM-1 and nasal eosinophilia, which correlated with the severity of nasal symptoms. In the montelukast/levocetirizine arm, montelukast decreased nasal eosinophilia more significantly than levocetirizine, whereas in reduction of sICAM-1 all active treatment options were equally effective. However, in the desloratadine/montelukast arm, the resulting improvement of combination therapy of sICAM-1 and the influx of eosinophils was not statistically significant.
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A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (> or = 15 years old) suffering from persistent asthma (pre-bronchodilator FEV1 > or = 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians.
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Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups.
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Sceptridium ternatum Lyon (ST), a common Chinese herb, has been used in treatment of allergic asthma and whooping cough. In the present study, we investigated the Th1/Th2 ratio of peripheral blood and mRNA levels of leukotriene receptors after the treatment of ST in allergic asthma mouse model.
Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control.
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A double-blind clinical study was carried out to evaluate the efficacy and the safety of montelukast, a cysteinyl leukotriene receptor 1 antagonist, 5 mg, 10 mg or placebo orally administered once daily at bedtime for 2 weeks, to Japanese patients with seasonal allergic rhinitis. The composite nasal symptom scores (average over the 2-week treatment period) were compared among the montelukast 5 mg and 10 mg groups with the placebo group.
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Asthma is a chronic inflammatory disorder of airways. It is characterised by bronchoconstriction, oedema and airways mucus hypersecretion. The main clinical features of asthma are dyspnea, cough, wheezing and heaviness in the chest. The pathology of asthma is characterised by presence of many inflammatory mediators, where the most important are cysteinyl leukotriens. Leukotriens C4, D4 and E4 are 1000 times more potent than histamine in contracting airways smooth muscles. Inhibitors of arachidonic acid metabolism have been used in asthma treatment. They can block the 5-lipoxygenase enzyme and/or 5-lipoxygenase-activating-proteine (FLAP), or can block the cysteinyl leukotriene receptors on the cell surface. Many inhibitors of arachidonic acid metabolism have been found during experimental trials. But only two are used as a drugs: zafirlukast and montelukast (leukotriene receptor inhibitors) montelukast and zileuton (5-lipoxygenase inhibitors) having the best efficacy in asthma treatment. Chronic treatment with these drugs results in a decrease of asthmatic symptoms, improvement of lung function (FEV1, PEF) and decreased usage of other medications--beta-adrenergic agonists and inhaled steroids. It has been proved that zafirlukast and zileuton show the high efficacy in mild-to-moderate asthma, exercise-induced asthma, allergen-induced asthma and aspirin-induced asthma. These oral drugs have been shown to course only mild adverse effects (such as temporary elevation in liver function tests, gastrointestinel disturbances, headache). Clinical usage of zafirlukast, montelukast and zileuton is limited in our country, they are hardly approachable on the market and the cost of treatment is high.
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Only randomised controlled trials conducted in adults or children with recurrent asthma where a LABA (for example, salmeterol or formoterol) or LTRA (for example, montelukast, pranlukast, zafirlukast) was added to ICS for a minimum of 28 days were considered for inclusion. Inhaled short-acting beta2-agonists and short courses of oral steroids were permitted as rescue medications. Other daily asthma treatments were permitted, providing the dose remained constant during the intervention period. Two reviewers independently reviewed the literature searches.
Patients with mild persistent asthma reported a substantial disease burden in the year before enrollment. The asthma burden experienced by these patients both before and during the run-in period was of sufficient severity to support the recommendation that mild persistent asthma should be managed with daily controller therapy.
We sought to determine whether the ratio of urinary leukotriene E(4) (LTE(4)) to fractional exhaled nitric oxide (FE(NO)) delineates children with preferential responsiveness to montelukast compared with fluticasone propionate (FP) therapy.
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Montelukast is a cysteinyl leukotriene receptor antagonist approved for the treatment of asthma for those ages 1 year old to adult. The purpose of this study was to evaluate the pharmacokinetic comparability of a 4-mg dose of montelukast oral granules in patients > or = 6 to < 24 months old to the 10-mg approved dose in adults. This was an open-label study in 32 patients. Population pharmacokinetic parameters included estimates of AUC(pop), C(max), and t(max). Results were compared with estimates from adults (10-mg film-coated tablet [FCT]). Dose selection criteria were for the 95% confidence interval (CI) for the AUC(pop) estimate ratio (pediatric/adult 10 mg FCT) to be within comparability bounds of (0.5, 2.00). The AUC(pop) ratio and the 95% CI for children compared with adults were within the predefined comparability bounds. Observed plasma concentrations were also similar. Based on systemic exposure of montelukast, a 4-mg dose of montelukast appears appropriate for children as young as 6 months of age.
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These results suggest that montelukast could effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38MAPK and NF-κB signaling pathways in spinal microglia.
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Our between the value reached by the PEF after treatment and the IgG values at the beginning of treatment (0.712). In lesser measurement for IgA values (0.660). For each 100 mg/ml of increase in the value of IgG, an increase of 10 l/min in the PEF measurement before and following treatment with Montelukast was produced.
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This prospective randomized controlled clinical study was conducted for 12 wk. Sixty patients of mild persistent asthma aged 2 to 18 y were randomly allocated to either oral Montelukast (n = 60) or inhaled Budesonide (n = 60) group. Outcomes measured were improvement in peak expiratory flow rate (PEFR), forced expiratory volume 1 s/forced vital capacity (FEV1/FVC), day time and night time symptoms and frequency of exacerbations and need to change medications.
Montelukast, 4-mg oral granules, was well tolerated over 6 weeks of treatment in children aged 6-24 months with asthma.
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These results confirm that LTD4 directly induces activation of eosinophils via the cysLT1 receptor. Furthermore, the results suggest that a beta2-agonist has no effect on eosinophil adhesion and activation induced by cysLTs. These results explain the differential effects of an LTRA and a beta2-agonist in the treatment of eosinophilic inflammation in asthma.
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A 16-year-old Caucasian female presented to the pulmonary clinic for a followup on her asthma. Due to the worsening of allergy-related symptoms, therapy with montelukast 10 mg daily was started and resulted in good relief of the patient's symptoms. In the nights following initiating therapy with montelukast, the patient's mother reported daily parasomnias in the form of sleeptalking and sleepwalking. Montelukast was discontinued, and that resulted in absence of the parasomnias. In a second attempt montelukast was reinstituted to control the patient's symptoms. Parasomnias were immediately reported after resuming therapy. Montelukast was then discontinued indefinitely. Our patient has never had any history of parasomnias, and since the discontinuation of montelukast, parasomnias were never reported again. Parasomnias in the form of sleeptalking or sleepwalking were not previously reported as adverse effects of montelukast. Alternative modalities to treat allergy-related symptoms in patients, who develop parasomnias while receiving montelukast, should be explored.
Leukotrienes are potent bronchoconstrictive and proinflammatory mediators in bronchial asthma. A randomized, cross-over study on 16 subjects assigned to two groups investigated whether premedication with the leukotriene antagonist montelukast (10 mg daily for 21 days) has a relevant effect on inhalational bronchial allergen provocation.
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At 2, 12, and 24 hours after dosing, the maximum decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for placebo, respectively (P < or = .001 at each time point). Postexercise recovery was quicker with montelukast than with placebo (P < or = .001); mean (95% confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), -16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes) at the 3 time points, respectively. At all time points, area under the curve for percentage decrease in FEV1 during 60 minutes after exercise was smaller after montelukast (P < or = .001); montelukast protected more patients against EIB (P < or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours after dosing with montelukast (P = .03).
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Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.
Human blood eosinophils were isolated by means of immunomagnetic separation. Upregulation of CD11b expression, active conformation of CD11b, and focal clustering of beta(2)-integrin caused by IL-5, eotaxin-1 or leukotriene (LT) B(4) was assessed by means of flow cytometry and confocal microscopy. The effect and mechanism of cysLT(1)R or 5-LO blockade on these components of beta(2)-integrin adhesion were determined.
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Our data suggest that human DCs may differentially respond to leukotriene, depending on their maturational stimuli.
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We recommend that medication with montelukast be discontinued before allergen provocation because it cannot be predicted in individual cases whether and to what extent montelukast suppresses the immediate reaction following inhalational bronchial allergen provocation.
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Sulfur dioxide (SO(2)) gas may induce acute asthmatic responses when inhaled by individuals in the setting of community or occupational air pollution during exercise. Some asthma medications mitigate the SO(2) response, which is not fully understood but appears to involve multiple mechanisms.