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The present study aimed to investigate whether a fixed combination of salmeterol and fluticasone (SFC) from a single inhaler provides sufficient asthma control comparable to that achieved with standard treatment (inhaled steroid in a dose of 1,000 mcg BDP- (beclomethasone dipropionate) equivalent plus a LABA and/or theophylline and/or montelukast).
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Monitoring noninvasive biomarkers of inflammation is an important adjunct in asthma therapy.
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Leukotrienes are key mediators in asthma. Over the last 5 years, several antileukotrienes, including three receptor antagonists (montelukast, pranlukast and zafirlukast) and one 5-lipoxygenase inhibitor (zileuton), have been marketed and, to date, this class of drugs is being used widely. Still, their definite place in the asthma treatment algorithm is not yet established. These novel drugs have not yet all been evaluated in the same depth, but they have all been shown to possess anti-inflammatory properties and to be effective in chronic asthma treatment. Zafirlukast and montelukast are particularly efficacious in exercise-induced asthma and zileuton appears valuable for treating aspirin-intolerant asthmatics. Clinical comparisons to other anti-asthma drugs are still sparse. The corticosteroid-sparing effect of antileukotrienes is fairly well established except for zileuton, even though this drug has been evaluated most thoroughly in terms of its anti-inflammatory effects. Montelukast is the antileukotriene most extensively evaluated in children and zafirlukast has recently been approved for use in children in the USA, although not yet in Europe. Therapeutic regimes are quite variable depending on the drug, but all of the antileukotrienes marketed to date are taken orally; hence, compliance is usually greater than that with inhaled medication. Response to antileukotrienes appears to depend on the individual patients' characteristics, in particular on genetic polymorphisms related to leukotriene metabolism. All drugs of this class are well tolerated and only in the case of zileuton is there potential for hepatic adverse effects. The diagnosis of Churg-Strauss syndrome made among patients taking antileukotrienes seems to be more related to the withdrawal of corticosteroids than to the antileukotrienes themselves.
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A 24-month, retrospective, pre-post cohort study using a pharmacy claims database of children (age < 16 years) with 2 or more consecutive asthma controller prescriptions and 1 or more allergy prescription (within 12 months before initial controller prescription). Children taking inhaled corticosteroids (ICSs) and montelukast were matched one to one based on age, days of prior allergic rhinitis therapy supply, duration of controller therapy, and propensity score. Differences in costs of rescue or acute asthma medications, prescription allergy medications, other respiratory medications, and the number of days of rescue or acute asthma medication use and allergy medication use were calculated.
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The study aims to assess medication adherence and asthma management behaviors and their modifiable predictors in low-income children with persistent asthma.
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The mean total area under the plasma concentration-time curve of zafirlukast during the gemfibrozil phase was 102% (geometric mean ratio; 95% confidence interval 89-116%) of that during the placebo phase. Furthermore, there were no statistically significant differences in the peak plasma concentration, time of peak concentration, or elimination half-life of zafirlukast between the phases.
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The 4 studies had a total of 1,910 patients 15 years or older with symptomatic asthma previously treated with inhaled short-acting beta2-agonists alone. At the end point, there were significantly greater increases in forced expiratory volume in 1 second with fluticasone propionate-salmeterol (0.57 L; P < or = .004) vs fluticasone propionate (0.48 L) and montelukast (0.31 L) and significantly greater increases in morning peak expiratory flow rate (84.9 L/min; P < .001) vs fluticasone propionate (56.0 L/min) and montelukast (36.1 L/min). Fluticasone propionate-salmeterol significantly increased the percentage of symptom- and rescue-free days and significantly reduced albuterol use vs fluticasone propionate and montelukast (P < or = .04 for both). Patients treated with fluticasone propionate and montelukast had 2.6 and 3.6 greater risk, respectively, of having an asthma-related exacerbation vs fluticasone propionate-salmeterol users. In addition, mean daily exacerbation costs per treated patient were dollars 0.41 for fluticasone propionate-salmeterol, dollars 4.60 for fluticasone propionate, and dollars 7.57 for montelukast, whereas mean daily costs per patient exacerbation for fluticasone propionate-salmeterol, fluticasone propionate, and montelukast were dollars 29, dollars 128, and dollars 154, respectively.
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Human ILC2s expressed the LT receptor CysLT1, levels of which were increased in atopic subjects. CysLTs, particularly LTE4, induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro. LTE4 enhanced the effect of PGD2, IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE4 was inhibited by montelukast, a CysLT1 antagonist. Interestingly, addition of IL-2 to LTE4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25.
Of 50 possible candidates, we recruited 46 children with polysomnographically diagnosed OSA. In this prospective, double-blind, randomized trial, children received daily oral montelukast at 4 or 5 mg (<6 or >6 years of age, respectively) or placebo for 12 weeks. Polysomnographic assessments, parent questionnaires, and radiographs to assess adenoid size were performed before and after therapy.
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The addition of montelukast as postoperative therapy may be beneficial for patients with eCRSwNP and AFS.
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Allergic diseases include a variety of different illnesses (rhinitis, conjunctivitis, asthma, urticaria, and dermatitis) in which the physiological and pathological basis is the release of chemical mediators such as histamine; platelet-activating factor; metabolites of arachidonic acid; and chemotactic factors from mastocytes, basophils, and eosinophils. The numerous drugs used for allergy treatment now include the new pharmacologic category of cysteinyl leukotriene (LT) antagonists. LTs are released from eosinophils, mast cells, and macrophages, interacting functionally in allergic reactions against a background of an imbalance between T-cell clones and resulting in preferential cytokine production following the T-helper 2 profile. Anti-LTs also have been used successfully by some authors to control rhinitis, atopic dermatitis, and urticaria. although additional controlled testing will be required, these applications broaden the possible range of treatments for allergic disease in all its many aspects.
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Relevant and appropriately controlled clinical studies on the efficacy of anti-LTs were used. Only literature in the English language was reviewed.
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The most common clinical adverse experiences were upper respiratory tract infection, asthma, fever, diarrhea, and vomiting occurring with similar frequencies between treatment groups. There were no clinically meaningful differences between the two treatment groups in clinical or laboratory adverse experiences and no significant differences in frequency of patients with elevated serum transaminases. Differences between the montelukast and placebo treatment groups in the exploratory efficacy endpoints of days without beta-agonist use, oral corticosteroid rescues, emergency care, asthma attacks, and discontinuations due to worsening asthma were not significant.
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Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis.
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Thirty patients were identified, mean age 33 years, 90% men. Solid food dysphagia was present in all. Twenty-seven patients (90%) were diagnosed with EoE during the index dilation; 17% underwent dilation for known, but symptomatic EoE. The median initial bougie size was 11. The median final bougie size was 15 mm; 24 patients (80%) had resultant mucosal tears. One patient complained of postprocedure chest pain requiring opioids. There were no perforations or hospitalizations. After dilation, patients were placed on swallowed fluticasone for 6 weeks (87%), maintenance montelukast (90%), or a prednisone taper (7%). Six patients (20%) underwent repeat dilation for recurrent dysphagia. All except one of these patients were on medical therapy for EoE.
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Sixteen children fulfilled criteria of EGIDs. Mucosal type was the most common finding type (12 out of 16 cases) (75%). Muscular and serosal type was found in equal numbers (2 of each in 16 cases) (12.5% each). Ages ranged from 6 months to 13 years. The male: female ratio was 1: 1.2. Abdominal pain was the most common presenting symptom followed by diarrhea. Allergic history was detected in 68.75% of all patients. Peripheral eosinophilia was found in only 37.5% of all cases. Radiographic findings showed non-specific findings. Endoscopy was performed in 14 out of 16 cases (87.5%). Lymphoid hyperplasia was the most common endoscopic finding especially in mucosal type. Eosinophil (more than 20 per high power field) was found from biopsied tissues obtained from the esophagus, stomach, colon or from ascitic fluid. Prednisolone was used in 13 out of 16 cases with satisfactory results in 11 cases. The two resisted cases responded to ketotifen in one and the other in combination with montelukast. One out of 16 cases subsided with only proton pump inhibitor The last two cases improved by allergic food elimination.
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28 Wistar-Albino rats were enrolled into 4 groups with 7 rats per group. The healthy control group was exposed to fresh air while all rats in the 3 experimental groups were exposed to cigarette smoke for 20 weeks for 2 hours per day. After histopathological verification of smoke induced lung injury, montelukast (0.1 mg/kg) dissolved in Na2CO3 was given in one group (MON), Na2CO3 only was given in another group (MON control) and placebo was injected in the third group (COPD control) intraperitoneally for 21 days. At the end of this period blood samples were obtained for serum TNF-α assessment and light and electron microscopy analyses were performed on the lung tissues of sacrificed rats.
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This study demonstrated a decrease in P-ET levels in children with mild asthma receiving montelukast. This indicates a reduction in the severity of the inflammatory response and, hence, provides evidence for the anti-inflammatory effect of montelukast. Monitoring both ET-1 and ECP levels at regular follow-up may be useful in assessing these two facets of activity of chronic inflammation in bronchial asthma.
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Arachidonic acid metabolism via 5-lipoxygenase gives rise to a group of biologically active lipids known as leukotrienes: leukotriene B(4), which is a potent activator of leukocyte chemotaxis, and cysteinyl leukotrienes (leukotriene C(4), D(4)and E(4)) which account for the spasmogenic activity previously described as slow-reacting substance of anaphylaxis. The biological actions of leukotrienes and the observations that leukotrienes are synthesised in the lung following antigen provocation and are elevated in asthma, stimulated considerable activity in the pharmaceutical industry to find drugs that modulate the synthesis or actions of leukotrienes. Three cysteinyl leukotriene antagonists (zafirlukast [Accolate], montelukast [Singulair] and pranlukast) and one 5-lipoxygenase inhibitor (zileuton) have received regulatory approval for the treatment of asthma. The clinical data obtained from using these drugs are generally consistent and complimentary. As a class the leukotriene modulators produce a rapid improvement in lung function after the first oral dose. Lung function improvements are maintained on chronic administration and are associated with reductions in a variety of asthma symptom scores. All of the available data are consistent with the hypothesis that all the leukotriene modulators exert their clinical benefit primarily through interference with cysteinyl leukotrienes. There are no compelling clinical data for an additional contribution by leukotriene B(4)in human asthma. In other respiratory conditions such as COPD, which are characterised by pronounced neutrophil infiltration, it may be that the chemotactic properties of leukotriene B(4)are more important and therefore evaluation of 5-lipoxygenase inhibitors in this condition is warranted. The introduction of the leukotriene modulators into clinical practice is the culmination of over 60 years of research since the initial discovery of the slow-reacting substances. The leukotriene modulators, and in particular the cysteinyl leukotriene antagonists, provide respiratory physicians with an oral therapeutic option and have set an efficacy standard which new oral anti-inflammatory approaches will have to beat.
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Montelukast (Singulair, MSD) has been shown to have a beneficial effect on the clinical symptoms of asthma. We aimed to investigate the effect of montelukast treatment on the production of eosinophil survival-enhancing cytokines by peripheral blood mononuclear cells (PBMNC).
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After switching treatment from a low-dose ICS, montelukast maintained control of asthma symptoms in 75% of patients. High sEos before the treatment change was the strongest exacerbation risk factor. In patients with asthma controlled by low-dose ICS and low inflammatory markers, treatment could be safely switched to montelukast.
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Previous studies suggested that leukotrienes (LT) were involved in the pathogenesis of Henoch-Schönlein purpura (HSP). This study investigated the efficacy of an add-on therapy with montelukast in the treatment of HSP.
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Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC(4), LTD(4), and LTE(4) are important mediators of asthma, and LTB(4) has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC(4) synthase (LTC(4)S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme responsible for the biosynthesis of LTB(4), are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC(4)S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB(4). Furthermore, challenge of AAA wall tissue with exogenous LTD(4) increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC(4)S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA.
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A novel chemiluminescence method using β - cyclodextrins coated on CoFe2O4 magnetic nanoparticles is proposed for the chemiluminometric determination of montelukast in plasma. The effect of coated β - cyclodexterinon CoFe2O4 magnetic nanoparticles in the chemiluminescence of luminol-H2O2 system was investigated. It was found that β - cyclodexterin coated on CoFe2O4 magnetic nanoparticles could greatly enhance the chemiluminescence of the luminol-H2O2 system. Doehlert design was applied in order to optimize the number of experiments to be carried out to ascertain the possible interactions between the parameters and their effects on the chemiluminescence emission intensity. This design was selected because the levels of each variable may vary in a very efficient way with few experiments. Doehlert design and response surface methodology have been employed for optimization pH and concentrations of the components. Results showed under the optimized experimental conditions, the relative CL intensity (ΔI) is increased linearly in the concentration range of 0.003-0.586 μgml(-1) of montelukast with limit of detection (LOD) 1.09 × 10(-4) μgml(-1) at S/N ratio of 3, limit of quantitative (LOQ) 3.59 × 10(-4) μgml(-1) and the relative standard deviation 2.63 %. The method has been successfully applied to the determination of montelukast in plasma of human body. Results specified that relative chemiluminescence intensity (ΔI) has good proportional with the montelukast concentration with R(2) = 0.99979. The test of the recovery efficiency for known amounts of montelukast was also performed, the recoveries range obtained from 98.2 to 103.3 %, with RSDs of <4 % indicated that the proposed method was reliable.
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Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.