The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform

DR Thickett - One of the best experts on this subject based on the ideXlab platform.

  • Churg-Strauss syndrome and Leukotriene Antagonist use: a respiratory perspective
    THORAX, 2008
    Co-Authors: DR Thickett
    Abstract:

    Background: Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene Antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.Methods: Systematic review searching Medline from database inception to August 2007 to identify cases with a possible association between LTAs and CSS. Hill's criteria of causation were used to assess strength of causality.Results: 62 cases in which CSS developed after the introduction of LTA therapy were identified. Patients were divided into three groups: group 1 had received no previous steroid therapy; group 2 had been treated with oral and/or inhaled corticosteroids, but had no change in steroid therapy following LTA introduction; and group 3 had a clear reduction in steroid therapy following introduction of LTA therapy. The majority of patients from each group exhibited a clear temporal relationship between initiation of LTA and development of CSS, with no evidence of pre-existing disease.Conclusions: Currently available evidence suggests an association between LTA and CSS that may be causal.

Sven-erik Dahlén - One of the best experts on this subject based on the ideXlab platform.

  • Improvement of aspirin-intolerant asthma by montelukast, a Leukotriene Antagonist: a randomized, double-blind, placebo-controlled trial.
    American journal of respiratory and critical care medicine, 2002
    Co-Authors: Sven-erik Dahlén, Kerstin Malmstrom, E. Nizankowska, Barbro Dahlén, Piotr Kuna, Marek L. Kowalski, W.r. Lumry, César Picado, Donald D. Stevenson, Jean Bousquet
    Abstract:

    Leukotriene Antagonists block the proinflammatory actions of Leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of Leukotrienes. We therefore tested whether addition of the Leukotriene receptor Antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a Leukotriene receptor Antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.

  • The Leukotriene-Antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics
    The European respiratory journal, 1994
    Co-Authors: B. Dahlén, Olle Zetterström, Björck T, Sven-erik Dahlén
    Abstract:

    The hypothesis that cysteinyl-Leukotrienes (LTC4, LTD4 and LTE4) are mediators of allergen-induced airway obstruction in asthmatics was tested with the specific receptor Antagonist ICI-204,219, in a double-blind, placebo-controlled, randomized, cross-over bronchoprovocation study. On three occasions, cumulative bronchial challenge with specific allergen was performed in 10 males with mild allergic asthma. The first control session established the baseline provocative dose of allergen producing a decrease in forced expiratory volume in one second (FEV1) by 20% (PD20FEV1). The two rechallenges were performed 2 h after oral administration of placebo or 20 mg of ICI-204,219. The allergen dose-response relations were highly reproducible, producing PD20 values at the control session and after placebo treatment which varied by no more than 0.7-1.3 fold (95% confidence interval (95% CI)). After ICI-204,219, the median cumulated allergen dose was 5.5 fold higher, and the group geometric mean PD20 was increased 2.5 times. Furthermore, the recovery time after the immediate bronchoconstriction was shorter (40 vs 60 min). The wheal and flare responses to intradermally injected LTD4 were somewhat inhibited by ICI-204,219, whereas responses to histamine were unaffected. However, the findings suggest that skin testing with LTD4 is unlikely to predict the degree of Leukotriene-antagonism in the airways. The findings confirm and extend the indications that cysteinyl-Leukotrienes are important mediators of allergen-induced airway obstruction, and that Leukotriene-Antagonists should be evaluated as a potential new therapy in allergic asthma.

  • effect of the Leukotriene receptor Antagonist mk 0679 on baseline pulmonary function in aspirin sensitive asthmatic subjects
    Thorax, 1993
    Co-Authors: Barbro Dahlén, D J Margolskee, O Zetterstrom, Sven-erik Dahlén
    Abstract:

    BACKGROUND--The cysteinyl Leukotrienes (LTC4, LTD4, and LTE4) have been shown to mediate airway obstruction evoked by several factors which trigger asthmatic reactions--for example, allergen and exercise. Accordingly, drugs which block the action or formation of these Leukotrienes are being evaluated as a new treatment of asthma. Elevated production of Leukotrienes has been reported in asthmatic subjects who are intolerant to aspirin and related nonsteroidal anti-inflammatory drugs. In this study the influence of the specific Leukotriene receptor Antagonist MK-0679 was tested on basal airway function in asthmatic patients with documented aspirin intolerance. METHODS--The eight subjects in the study had a mean baseline FEV1 of 78% predicted (range 58-99%) and six required treatment with inhaled glucocorticosteroids (400-1200 micrograms budesonide/beclomethasone daily). On two separate days the subjects received either 825 mg MK-0679 or placebo, orally in a double blind, randomised, crossover design. RESULTS--The Leukotriene Antagonist MK-0679 caused bronchodilation which lasted for at least nine hours. The average peak improvement in FEV1 was 18% above the predrug baseline, but the bronchodilator response varied between 34% and 5% and was found to correlate strongly with the severity of asthma and aspirin sensitivity. CONCLUSIONS--The findings indicate that ongoing Leukotriene production may be one cause of persistent airway obstruction in aspirin sensitive asthmatic subjects and that they may benefit from treatment with a Leukotriene receptor Antagonist.

David E. Cohen - One of the best experts on this subject based on the ideXlab platform.

  • The Leukotriene Antagonist zafirlukast as a therapeutic agent for atopic dermatitis
    Archives of dermatology, 1998
    Co-Authors: John A. Carucci, Kenneth Washenik, Alan Weinstein, Jerome L. Shupack, David E. Cohen
    Abstract:

    A 42-year-old man presented with a 10-year history of atopic dermatitis that was refractory to treatment with UV light, oral antihistamines, and high-potency topical corticosteroids. On presentation, he denied any other medical problems and was taking no medicines. His condition improved with the use of cyclosporine; however, this regimen was discontinued secondary to transaminitis due to hepatitis C infection, which was treated with interferon alfa. His atopic dermatitis flared after discontinuation of cyclosporine therapy. A physical examination showed erythroderma involving more than 70% of his body surface area approximately 2 weeks after cyclosporine therapy was discontinued.

Brian J Lipworth - One of the best experts on this subject based on the ideXlab platform.

  • comparative efficacy and anti inflammatory profile of once daily therapy with Leukotriene Antagonist or low dose inhaled corticosteroid in patients with mild persistent asthma
    The Journal of Allergy and Clinical Immunology, 2002
    Co-Authors: Owen J Dempsey, Gwen Kennedy, Brian J Lipworth
    Abstract:

    Abstract Background: Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma. Objective: We compared the efficacy and anti-inflammatory profiles of a Leukotriene receptor Antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma. Methods: Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 μg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment. Results: At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV 1 ) in comparison with placebo ( P P P P P Conclusion: Once-daily inhaled corticosteroid and Leukotriene Antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree. (J Allergy Clin Immunol 2002;109:68-74.)

  • Comparative efficacy and anti-inflammatory profile of once-daily therapy with Leukotriene Antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma
    The Journal of allergy and clinical immunology, 2002
    Co-Authors: Owen J Dempsey, Gwen Kennedy, Brian J Lipworth
    Abstract:

    Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma. We compared the efficacy and anti-inflammatory profiles of a Leukotriene receptor Antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma. Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment. At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin. Once-daily inhaled corticosteroid and Leukotriene Antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree.

  • effects of adding a Leukotriene Antagonist or a long acting beta2 agonist in asthmatic patients with the glycine 16 beta2 adrenoceptor genotype
    The American Journal of Medicine, 2000
    Co-Authors: Brian J Lipworth, Owen J Dempsey, Imran Aziz, Andrew M Wilson
    Abstract:

    Abstract PURPOSE: In the United Kingdom, about 40% of patients with asthma are homozygous for the glycine-16 beta 2 -adrenoceptor polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the beta 2 -adrenoceptor. We assessed the effects of adding treatment with either a long-acting beta 2 -agonist (inhaled formoterol, 12 μg twice daily) or a Leukotriene receptor Antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid therapy in patients with this genotype. SUBJECTS AND METHODS: We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids. Patients were randomly assigned to receive one of three treatments (placebo, zafirlukast, or formoterol in addition to inhaled corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week placebo run-in and washout period. Measurements of bronchoprotection (measured as the provocative dose of methacholine that produced a 20% decline in forced expiratory volume in 1 second [FEV 1 ]), exhaled nitric oxide (a surrogate marker of airway inflammation), and symptoms were made before each treatment and 12 hours after the last dose of each treatment. RESULTS: Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo: the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and 1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo, zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed significant ( P CONCLUSIONS: Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta 2 -agonists. The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids.

H. Halis Ünlü - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of Leukotriene Antagonists as concomitant therapy in allergic rhinitis
    The Laryngoscope, 2010
    Co-Authors: Cemal Cingi, Kivanc Gunhan, Linda Gage-white, H. Halis Ünlü
    Abstract:

    Objectives/Hypothesis: The symptoms of allergic rhinitis result from an immunoglobulin E-dependent mast cell activation cascade, marked by the release of inflammatory mediators, including histamine. Patients with perennial allergic rhinitis also have elevated levels of cysteinyl Leukotrienes (CysLTs) in nasal lavage fluid. Histamine and CysLTs produce different responses in the pathogenesis of allergic rhinitis, and this study tested the hypothesis that the effects of combined antihistamine and Leukotriene Antagonist therapy would be more effective than antihistamine alone. Study Design: Multicentered, prospective, randomized, placebo-controlled, parallel-group. Methods: Three groups totaling 275 patients using: 1) fexofenadine alone, 2) fexofenadine with montelukast, or 3) fexofenadine with placebo, participated in a 21-day trial conducted during the spring pollen season. Objective analysis included pre- and poststudy physical examination findings and nasal resistance measurements. Subjective data gathered included a daily patient diary and pre- and poststudy patient satisfaction measurements. Results: The group using both fexofenadine and montelukast showed significantly better control of nasal congestion both subjectively, using patient diary and visual analog scale evaluations, and objectively, using rhinomanometry and physical examination, compared to groups using antihistamine alone or with placebo. Conclusions: Our data provided both objective and subjective evidence that Leukotriene receptor Antagonist-antihistamine combination therapy is more effective than antihistamine alone in the control of allergic rhinitis symptoms. Laryngoscope, 2010

  • Efficacy of Leukotriene Antagonists as concomitant therapy in allergic rhinitis
    The Laryngoscope, 2010
    Co-Authors: Cemal Cingi, Kivanc Gunhan, Linda Gage-white, H. Halis Ünlü
    Abstract:

    The symptoms of allergic rhinitis result from an immunoglobulin E-dependent mast cell activation cascade, marked by the release of inflammatory mediators, including histamine. Patients with perennial allergic rhinitis also have elevated levels of cysteinyl Leukotrienes (CysLTs) in nasal lavage fluid. Histamine and CysLTs produce different responses in the pathogenesis of allergic rhinitis, and this study tested the hypothesis that the effects of combined antihistamine and Leukotriene Antagonist therapy would be more effective than antihistamine alone. Multicentered, prospective, randomized, placebo-controlled, parallel-group. Three groups totaling 275 patients using: 1) fexofenadine alone, 2) fexofenadine with montelukast, or 3) fexofenadine with placebo, participated in a 21-day trial conducted during the spring pollen season. Objective analysis included pre- and poststudy physical examination findings and nasal resistance measurements. Subjective data gathered included a daily patient diary and pre- and poststudy patient satisfaction measurements. The group using both fexofenadine and montelukast showed significantly better control of nasal congestion both subjectively, using patient diary and visual analog scale evaluations, and objectively, using rhinomanometry and physical examination, compared to groups using antihistamine alone or with placebo. Our data provided both objective and subjective evidence that Leukotriene receptor Antagonist-antihistamine combination therapy is more effective than antihistamine alone in the control of allergic rhinitis symptoms.