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We hypothesized that fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy.
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KP-496 produced parallel rightward shifts of the LTD(4) and U46619 concentration-response curves in a concentration-dependent manner. Schild plot analyses of the antagonistic activities of KP-496 demonstrated that it is a competitive antagonist for LTD(4) and TXA(2) receptors with pA(2) values of 8.64 and 8.23, respectively. The LTD(4) antagonistic activity of KP-496 was comparable to that of pranlukast and zafirlukast but was more potent than that of montelukast. The TXA(2) antagonistic activity of KP-496 was comparable to that of seratrodast. KP-496 and seratrodast also inhibited the prostaglandin (PG) D(2)- and PGF(2alpha)-induced contractions of the isolated guinea pig trachea. KP-496 had no effect on the histamine-, acetylcholine-, serotonin- and substance P-induced contractions of the isolated guinea pig trachea.
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Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression.
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The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.
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This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 4. See the HTA programme website for further project information.
Asthma is a complex process that results from airway inflammation and manifests as bronchoconstriction. Infiltration of the airway mucosa and lumen by activated inflammatory cells, along with release of mediators, can occur extensively. Chemical mediators known as leukotrienes are believed to play a major role in this process. At present, inhaled corticosteroids (ICS) are the pharmacologic cornerstone of asthma management. However, asthma control may remain suboptimal when relying on ICS because of problems with compliance, poor inhaler technique and concerns about the side effects of steroids; additional agents are often required to control symptoms. Leukotriene receptor antagonists (LTRA), namely montelukast, provide a safe and effective additional anti-inflammatory treatment option. There is particular benefit for patients with asthma and concomitant allergic rhinitis.
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The effect of inhaled glucocorticosteroids (ICS) on bone metabolism and subsequent osteoporosis is controversial. Explanations for this controversy include various study designs, duration of use, outcome measures, and population demographics of research studies with intranasal or inhalational ICS. Patients with poorly controlled asthma are at greatest risk of osteoporosis because they are commonly treated with intermittent or continuous systemic corticosteroids (SCS) or high-dose ICS. A 45-year-old Caucasian woman presents with moderate-to-severe asthma with frequent albuterol use and nighttime awakenings at least once weekly. She is on fluticasone/salmeterol 500/50 μg one inhalation twice daily and montelukast 10 mg/day. She requires prednisone 15 mg three times per day for 5 days up to three times a year. Is this patient at greater risk of osteopenia, characterized by a T-score between -1.0 and -2.5, and subsequent osteoporosis and an increased risk of fractures? If she has osteopenia, should she be treated with a bisphosphonate? The risk of osteoporosis and fracture increases significantly with frequent administration of SCS, and patients on such medications should undergo preventative measures and treatment. This study discuses factors that contribute to an increased risk of osteoporosis/osteopenia in patients with asthma and suggests recommendations based on the current literature.
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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.
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Montelukast is used in the treatment of allergic rhinitis and asthma. It has been used as adjuvant therapy in patients with chronic rhinosinusitis (CRS), but its effectiveness has not been evaluated. This study evaluates the efficacy of adjuvant leukotriene receptor antagonism in CRS and subtypes.
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To examine whether outpatient post-stabilization therapy with montelukast produces more treatment failures than prednisolone.
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We conclude that the dose of montelukast and the dosing interval does not need to be modified if the goal is to mimic the serum concentration used to treat asthma. The effectiveness of these concentrations for the inflammatory lung disease of patients with CF is unknown.
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We investigated the role of montelukast (ML), a cysteinyl leukotriene-1 receptor antagonist, on the water avoidance stress (WAS)-induced degeneration of the rat gastric, ileal and colonic mucosa. One group of Wistar albino rats were exposed to chronic WAS (WAS group) 2h daily for 5 days. Another group was administered ML (10mg/kg; i.p.; WAS+ML group) following every WAS exposure for 5 days. Control rats were injected with the vehicle solution only. The stomach, ileum and colon were dissected and investigated for histopathological changes with a light microscope as well as for topographical changes with a scanning electron microscope. The levels of malondialdehyde (MDA, a biomarker of oxidative damage) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. In the WAS group, the stomach epithelium showed ulceration in some areas, dilatations of the gastric glands, degeneration of gastric glandular cells, and prominent congestion of the capillaries. In a similar fashion, degenerated epithelium and severe vascular congestions were observed in the ileum and colon. In all the tissues dense inflammatory cell infiltration and mast cell degranulation in mucosa were observed. The levels of MDA were significantly increased whereas those of GSH were significantly decreased in all test tissues in the WAS group compared to the control group. The morphology of gastric, ileal and colonic mucosa in WAS+ML group showed a significant amelioration showing a reduction in inflammatory cell infiltration and mast cell degranulation. Increased MDA and decreased GSH levels in the WAS group were also ameliorated with ML treatment. Based on the results, ML supplement seems attenuated inflammatory effects of WAS induction in gastrointestinal mucosa.
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Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast.
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Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.
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Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma.
Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed. Efficacy end points included (1) symptom-free days (SFDs) during the 12-week period and (2) a 12% or greater increase in forced expiratory volume in 1 second (FEV1) from baseline. The economic analysis was performed from a payer's perspective, and hence only direct costs were included in the analysis. The incremental cost-effectiveness ratio (ICER), which is the mean difference in average costs divided by the mean difference in average effectiveness, was calculated for both effectiveness outcomes (SFDs and FEV1).
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Montelukast treatment after CP injection exerted therapeutic effects against CP-induced acute kidney damage.
To evaluate the therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma.
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We used a C57BL/6 mouse model of allergic airway disease and murine tracheal epithelial cells to examine the effects of cysLTs on the regulation of IL-11 expression.
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Of the 166,686 subjects, 445 carried out self-harm during a mean (SD) follow-up period of 5.84 (2.35) years. Asthma (hazard ratio=1.70, 95% CI: 1.35-2.14), age, residence, episode of psychiatric disease and Charlson comorbidity index were independent risks on self-harm in the fully adjusted model.
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In patients with CVA, 2-week treatment with montelukast, clenbuterol, and montelukast plus clenbuterol all significantly decreased cough scores and treatment with montelukast plus clenbuterol was superior to treatment with montelukast alone. In the montelukast plus clenbuterol group, PEF values in the morning and evening significantly increased after 2 weeks compared with values before treatment. In patients with AC, scores on the cough scale did not differ significantly between the montelukast group and the placebo group.
Allergic rhinitis (AR) is the single most common allergic disease and one of the most common chronic diseases. It affects approximately 25-30% of the population, and can substantially worsen patients' medical conditions, reduce quality of life, and contribute to absenteeism from work or school. It is also responsible for substantial direct and indirect economic burdens on the health care system. The medical management of allergic rhinitis includes several available pharmacotherapies, such as α-sympathomimetics, anticholinergic drugs, natural saline or other nasal rinses, mast cell-stabilizing agents, topical and systemic antihistamines, topical and systemic glucocorticosteroids, leukotriene-receptor antagonists and the new monoclonal antibodies following a stepwise approach. Allergen-specific immunotherapy is the only treatment option that interferes with the natural course of the disease and, besides allergen elimination, is thought to be the only causative treatment option. Nasal glucocorticosteroids (nGCS) are thought to be the most effective treatment choice for controlling the symptoms of AR. Double-blind, randomized clinical trials have demonstrated greater efficacy of nGCSs versus placebo, antihistamines or montelukast for relief of all nasal symptoms, especially congestion. Therefore, especially in the management of AR-related nasal inflammation and congestion, nGCSs are considered the most appropriate treatment. Patients should be informed that symptom improvement can be expected after 2-4 days for intermittent rhinitis and after up to 2-3 weeks for persistent rhinitis. The medication has to be taken regularly and not as "on-demand" treatment. Adherence to treatment also affects outcomes, and this may be influenced by patient preferences for the sensory attributes of an individual drug and the awareness of possible side effects. More recently, safety studies have shown that the newer nGCS agents have improved safety profiles compared with older nGCS agents. The newer nGCS drugs have been found to have minimal adverse effects on growth and hypothalamic-pituitary-adrenal-axis function in children. This review will discuss the pathophysiology of allergic inflammation in the nasal mucosa and the mechanism of action of nGCSs; also the efficacy and safety of nGCSs will be discussed by focusing on clinical evidence.
To evaluate the effects of montelukast in smoke-induced lung injury.
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Eosinophilic Gastroenteritis (EG) is a rare condition, caused by eosinophilic inflammatory infiltrates in the gastrointestinal tract. It is usually treated successfully with systemic glucocorticoids. Because of frequent relapses, however, there is need for alternatives. We describe a 38-year old man with steroid-dependent EG, who was successfully treated with montelukast, a leukotriene receptor antagonist. It inhibits leukotriene D4, an important cytokine in the inflammatory cascade. Although montelukast could not replace steroid therapy, it acted as a steroid sparing agent in our patient. Review of the literature shows that montelukast is efficient in the treatment of EG in a part of the patients. The low cost, the low number of side effects and its efficiency make it an interesting alternative in relapsing or steroid dependent EG. There is need for multicentric studies regarding the treatment of EG.
Anaphylaxis induced by exercise after the intake of certain foods is referred to as food-dependent exercise-induced anaphylaxis (FDEIA). Only the preventive medication such as oral sodium cromoglycate and oral combined cetirizine-montelukast was tried in FDEIA. Specific oral tolerance induction (SOTI) using IFN-gamma was tried in 2 cases of FDEIA for wheat. Merely, exercise accompanied every treatment just after the intake of allergenic foods during treatment. Patients acquired tolerance for wheat in both cases successfully. After treatment, two patients take wheat in their food living freely. Conclusively, SOTI using IFN-gamma was effective as the causative treatment for allergenic foods in FDEIA.
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The obtained results in both groups showed that the serum IL-13 before the start of therapy were much higher and after 6 months of treatment significantly reduces their value, which in the second group were more expressed. The difference in the average value of FEV1 in both groups before and after therapy was statistically significant.
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These findings suggest that high doses of montelukast modulate the production of IL-6, TNF-alpha, and MCP-1 through the inhibition of NF-kappaB activation. However, the anti-inflammatory effect of montelukast at therapeutic doses in patients with asthma needs to be further investigated.