Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies.

Carranza Rosenzweig JR.

University of Nevada School of Medicine, Reno, Nev, USA.

BACKGROUND: Improved adherence to inhaled corticosteroids (ICSs) has also been associated with decreased asthma-associated morbidity and mortality. OBJECTIVE: The purpose of this study was to assess patient medication refill persistence with fluticasone propionate (FP) and salmeterol combination in a single inhaler (FSC), FP and salmeterol in combination from 2 separate inhalers, FP and montelukast in combination, FP as monotherapy, and montelukast as monotherapy. METHODS: We performed a retrospective, observational, 24-month (12-month baseline and 12-month follow-up) database study using medical and pharmacy claims from a large managed care organization. We identified 2511 subjects 12 years of age or older with a claim for asthma (International Classification of Diseases, Ninth Revision: 493.XX): 563 patients receiving FSC, 224 receiving FP plus salmeterol, 75 receiving FP plus montelukast, 798 receiving FP only, and 776 receiving montelukast only. Refill rates of FP, as a measure of adherence, were compared for each FP-containing cohort during the 12-month follow-up period. In addition, refill rates were compared between FSC, an inhaler, and montelukast, an oral medication. RESULTS: Twelve-month baseline asthma medication use and patient demographics were comparable among cohorts. Patients in the FSC cohort obtained significantly more refills compared with the number of FP refills in the other FP-containing cohorts (4.06 for FSC vs 2.35 for FP plus salmeterol, 1.83 for FP plus montelukast, and 2.27 for FP alone) over the 12-month follow-up period. In addition, patients taking FSC had similar refill persistence compared with patients taking the oral leukotriene modifier montelukast (4.51). CONCLUSION: FSC might increase ICS refill persistence compared with FP alone in a single inhaler, FP in combination with salmeterol from 2 separate inhalers, and FP in combination with montelukast. In addition, FSC in a dry powdered inhaler had similar refill rates compared with an oral asthma agent, montelukast. Use of a single inhaler containing both an ICS (FP) and a long-acting bronchodilator (salmeterol) might increase the likelihood that patients are getting more optimal ICS therapy, as well as the benefits from the long-acting bronchodilator, with patient adherence comparable to an oral agent.

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Montelukast treatment does not affect peripheral blood neutrophil functions in asthma patients.

Heimer D.

Pulmonary Unit, Infectious Diseases Laboratory, Faculty of Health Sciences, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer Sheva, Israel.

BACKGROUND: Leukotriene receptor antagonists have become an integral part of asthma treatment as an add-on therapy for patients with moderate disease activity. OBJECTIVE: To determine whether in vivo treatment with montelukast, a leukotriene receptor antagonist, at the recommended therapeutic dose affects neutrophil functions which are essential for host defense. METHODS: Twenty nonsmoking patients between the ages of 18 and 70 with moderate asthma were recruited to the study. All of them were receiving inhaled corticosteroids for at least 6 months and beta2-agonist as needed. After the 2-week run-in period, in addition to the regular medication, each patient was treated with 10 mg of montelukast for a 6-week period. Pulmonary function test was performed and blood was tested for neutrophil activity twice during the run-in period and twice during the treatment period. Each assay was performed in parallel to a matched control. RESULTS: The 6-week treatment period with montelukast did not significantly affect neutrophil chemotaxis or phagocytosis nor the elevated superoxide production. However, at 2 weeks of treatment some of the patients showed a reduction in neutrophil function. CONCLUSIONS: The study demonstrated that the recommended dose of montelukast has no significant effect on peripheral blood neutrophil activities, indicating that montelukast treatment does not induce an inflammatory process and does not interfere with the first line of host defense. Copyright 2004 S. Karger AG, Basel

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Long-term montelukast therapy in moderate to severe COPD--a preliminary observation.

Schriever C.

Department of Medicine (MIC 719), College of Medicine, University of Illinois at Chicago, 840 South Wood Street, Room 173, Chicago, IL 60612-7323, USA. irubinst uic.edu

The purpose of this retrospective study was to determine the effects of long-term treatment with montelukast on chronic obstructive pulmonary disease (COPD) control in a cohort of patients with moderate to severe COPD. The medical records of 20 consecutive male patients (18 African-Americans) aged 71.2 +/- 10.7 years diagnosed with moderate to severe COPD at the VA Chicago Health Care System, Chicago, Illinois, USA, and treated with oral montelukast, 10 mg every night, for 23.6 +/- 7.3 months were reviewed. Information on demographics and COPD control was extracted from each record. In each patient, a comparable follow-up period in the clinic before and after initiating montelukast therapy was reviewed and tabulated so each patient served as his own control. There was a significant improvement in complaints of shortness of breath, sputum production wheezing and nocturnal symptoms during the observation period (P < 0.05). There was a significant reduction in the use of oral and inhaled corticosteroids, inhaled bronchodilators and supplemental oxygen (P < 0.05). In addition, there was a significant reduction in the number of visits to the emergency department, number of hospitalizations and duration of hospitalizations for acute exacerbations of COPD (P < 0.05). No significant changes in FEV1 (% predicted), FEV1/FVC ratio (% predicted) and peak expiratory flow rate were recorded during this time. No side effects where reported during the observation period and no patient discontinued the medication. Collectively, these data suggest that long-term treatment with montelukast is safe and improves COPD control in elderly patients with moderate to severe COPD.

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[Cardioprotective effect and influence on NOS expression of Montelukast sodium in rats]

[Article in Chinese]

Xu L.

NO. 2 Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China. Jinchenshan72 sina.com

AIM: To determine the protective effect and influence on NOS expression of Montelukast sodium--a leukotriene antagonist on myocardial necrosis in rats. METHODS: Myocardial ischemia and necrosis were induced in rats by isoproterenol (2 mg.kg-1, s.c., qd for 2 d). Serum activity of LDH, CK, MDA, NO content in myocardium and scope of myocardial necrosis were measured. nNOS, iNOS and eNOS were investigated by immunohistochemical evaluation. RESULTS: Decreased serum level of LDH, CK, MDA and attenuated myocardial necrosis area were found in rats pretreated with Montelukast sodium 10 and 30 mg.kg-1. Montelukast sodium 30 mg.kg-1 also enhanced NO content in myocardium. Montelukast sodium activated the eNOS expression and reduced the iNOS expression. CONCLUSION: Montelukast sodium is cardioprotective during myocardial injury in rats by halting the leukotrienes-induced inflammatory response and upregulating the eNOS expression as well as downregulating the iNOS expression. This may represent an approach to the treatment of myocardial ischemia with leukotriene antagonists.

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Recent innovations in asthma therapy.

Martin RJ.

Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

Guidelines for the diagnosis and management of asthma have been published since 1990 and already new versions are being published. The recommendations for the treatment of asthma were organized around four components of effective asthma management: i) use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy, ii) environmental control measures to avoid or eliminate factors that precipitate asthma symptoms or exacerbations, iii) comprehensive pharmacologic therapy for long-term management designed to reverse and prevent the airway inflammation characteristic of asthma as well as pharmacologic therapy to manage asthma exacerbations, and iv) patient education that fosters a partnership among the patient, family and clinicians. Newly released medications include anti-leukotriene (LTs) agents which function either by blocking the interaction of LTs with receptors (receptor antagonists) or by inhibiting leukotriene synthesis (synthesis inhibitors). Representatives of the antagonists discussed here are zafirlukast, pranlukast and montelukast. Zafirlukast (20 mg twice daily) improves pulmonary function indices and days without symptoms and decreases the asthma exacerbation frequency. Pranlukast, the first leukotriene receptor antagonist to be marketed, improves lung function and symptoms when 450 mg twice daily is used. A study with montelukast demonstrated similar positive results irrespective of the use of concomitant inhaled corticosteroid. This indicates that leukotriene receptor antagonists may have additive effects to steroid therapy. They may also be a potential alternative to inhaled steroids, although more studies need to be performed before defining the role of receptor antagonists in the treatment of asthma. Zileuton, a leukotriene synthesis inhibitor, has been shown to improve lung function, reduce symptoms and reduce use of beta-agonists and asthma exacerbations. These positive effects are dose-dependent and liver function abnormalities seem to be a relevant issue during zileuton use in some patients. Other compounds that inhibit LTs synthesis are in development and, like zileuton, need more tests. Phosphodiesterases (PDE), enzymes that break down cAMP and cGMP, have been a target for new compounds developed to treat asthma. Inhibition of PDE enzymes increases intracellular cAMP or cGMP which then produces bronchodilation. Recent studies have also shown antiinflammatory effects by suppressing some PDE isoenzymes, including PDE III and PDE IV. These effects were detected by studies in vitro and in animal models. Clinical trials are necessary to determine which PDE inhibitors can be useful for the treatment of asthma. (c) 1998 Prous Science. All rights reserved.

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