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 t...
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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 mu g 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 [FEV1]), 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% CT: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% Cl: 0.8- to 1.9-fold). Diary cards showed significant (P < 0.05) improvements in the peak flow with formoterol (morning and evening) and zafirlukast (evening) as compared with placebo. CONCLUSIONS: Formoterol and zafirlukast maintained asthma control in pa
The prevalence of asthma is increasing dramatically despite major changes in monitoring and treatment of this disease. currently available bronchodilators and anti-inflammatory drugs are effective in most patients, al...
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The prevalence of asthma is increasing dramatically despite major changes in monitoring and treatment of this disease. currently available bronchodilators and anti-inflammatory drugs are effective in most patients, although these can have side effects and are mainly symptomatic. Many drugs are now in development for the treatment of asthma. Most of these new therapies are aimed at inhibition of the inflammatory components, with better safety profiles than steroids.
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