Discrepant clinical responses and blood chemokine profiles between two non-steroidal anti-inflammatory medications for children with mild persistent asthma.

Yang KD.

Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. ped mail.ndmctsgh.edu.tw

In a randomized study, two oral medications, ketotifen and montelukast, were compared for children with mild persistent asthma. Montelukast revealed faster clinical responses than ketotifen, showing improved exhaled nitric oxide, peak expiratory flow, and asthma scores in 1 wk. After 8-wk of medication, both ketotifen and montelukast revealed improved clinical responses. However, 8 wk of ketotifen, but not montelukast, decreased plasma serum thymus and activation-regulated chemokine (317.854 +/- 207.906 vs. 181.348 +/- 167.109, p < 0.05), macrophage-derived chemokine (355.11 +/- 174.30 vs. 169.19 +/- 62.42, p < 0.05) levels. In conclusion, different oral non-steroidal anti-inflammatory drugs revealed faster or slower treatment responses due to different mechanisms.

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A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy.

Luskin AT.

Dean Foundation for Health, Research, and Education, Dean Medical Center, Madison, Wisconsin 53590, USA.

BACKGROUND: The prevalence of asthma is increasing, and this chronic condition imposes a substantial economic burden worldwide. It is not known whether newer therapies, such as leukotriene receptor antagonists (LTRAs), can ease this burden. OBJECTIVE: This analysis examined the association between choice of first-line asthma control therapy and health care resource utilization and expenditures in patients with mild asthma. METHODS: A retrospective cohort analysis of claims data for patients who started therapy with fluticasone propionate or montelukast between January 1, 1997, and February 28, 1999, was performed, adjusting for baseline differences. RESULTS: Data from 343 patients (229 fluticasone; 114 montelukast) were analyzed. Patients starting therapy with fluticasone were significantly older (33.3 vs 27.6 years; P = 0.015) and significantly less likely than patients starting therapy with montelukast to have been started on control therapy by an asthma specialist (52.0% vs 69.3%; P = 0.007). There were no significant differences in mean changes in total asthma-related health care expenditures, oral steroid and antibiotic prescriptions, hospitalizations, or emergent care visits. The mean increase in total asthma-related pharmacy expenses was significantly greater for patients who were prescribed montelukast than for those prescribed fluticasone (P < 0.001). Treatment adherence was better in patients prescribed montelukast versus fluticasone (5.1 vs 3.1 prescriptions filled per year, respectively; P < 0.001). Montelukast patients had a significantly lower increase in the number of beta-agonist prescriptions filled per year than fluticasone patients (0.19 vs 0.66; P = 0.03). In the subsequent year, 4% (10/229) of fluticasone patients added or switched to an LTRA. No montelukast patients added to or switched control therapy. CONCLUSION: The mean change in total asthma-related health care expenditures was not significantly different in patients started on fluticasone propionate versus montelukast. Montelukast patients had better adherence to their treatment regimen and required fewer beta-agonist prescriptions, which is an indicator of asthma control and possibly therapeutic effectiveness.

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Inflammatory Basis of Exercise-induced Bronchoconstriction.

Aitken ML.

Department of Medicine, University of Washington, Seattle, WA, USA.

Rationale: Exercise-induced bronchoconstriction is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of exercise-induced bronchoconstriction differ regarding the inflammatory basis of this condition. Objectives: Our goals were to establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during exercise-induced bronchoconstriction and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during exercise-induced bronchoconstriction. Methods: Induced sputum was used to measure mast cell mediators and eicosanoids at baseline and 30 min after exercise challenge in 25 asthmatics with exercise-induced bronchoconstriction. In a randomized, double-blind, crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine or 2 matched placebos were administered for 2 doses before exercise challenge. Main Results: The percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of exercise-induced bronchoconstriction. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin E2 and thromboxane B2 significantly decreased in the airways and there was an increase in columnar epithelial cells in the airways. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways. Conclusions: These data indicate that epithelial cells, mast cell mediators, and eicosanoids are released into the airways during exercise-induced bronchoconstriction supporting an inflammatory basis for exercise-induced bronchoconstriction.

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Effect of the cysteinyl leukotriene antagonist pranlukast on transendothelial migration of eosinophils.

Kanazawa M.

Department of Respiratory Medicine, Saitama Medical School, Japan. favre4mn saitama-med.ac.jp

BACKGROUND: Evidence shows that leukotriene receptor antagonist (LTRA) can cause a partial reduction of eosinophils in the asthmatic airway. Although cysteinyl leukotrienes (CysLTs) can regulate the development of eosinophilic inflammation, LTRA might modulate the eosinophilic response to other inflammatory molecules involved in allergic inflammation. Montelukast is an LTRA that inhibits eosinophil transendothelial migration (TEM) in response to platelet-activating factor (PAF). The present study evaluates whether pranlukast (an LTRA) modifies eosinophil TEM in response to chemoattractants including PAF and C-C chemokines. METHODS: Eosinophils isolated from the blood of healthy individuals were incubated with or without pranlukast. We then evaluated eosinophil transmigration across human umbilical vein endothelial cells in response to LTD(4), eotaxin, RANTES and PAF. RESULTS: Pranlukast did not modify the spontaneous transmigration of eosinophils (n = 5). As reported, eosinophil TEM was significantly augmented by 0.1 microM LTD(4) and this enhancement was blocked by 1 microM pranlukast (p < 0.001; n = 6). On the other hand, pranlukast did not modify eosinophil transmigration in response to eotaxin, RANTES, or PAF (p > 0.1; n = 5). CONCLUSION: The inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the CysLT1-dependent pathway. Copyright 2005 S. Karger AG, Basel.

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State and trait anxiety in patients affected by nasal polyposis before and after medical treatment.

Coen Tirelli G.

Department of Otorhinolaryngology, S. Eugenio Hospital, Rome, Italy. ldirienzo businco.net

The present study aimed to establish whether anxiety and depression in nasal polyposis play a role in genesis of the disease, or are a consequence of symptoms. Anxiety levels were evaluated in state and trait forms, and depression, in 30 consecutive patients presenting nasal polyposis before and after effective 7 months' medical treatment with nasal mometasone, loratadine and montelukast. Before and at the end of treatment, patients were asked to fill in the State and Trait Anxiety Inventory and the Zung self-rating depression scale. In 63.15% of patients with high levels of state anxiety before therapy, these were reduced (p < 0.004) after treatment. In 61.9% of patients with high levels of trait anxiety before treatment, these were reduced (p < 0.002) after treatment. There were no significant differences in depression. Anxiety in nasal polyposis is present both as a state and as a trait, and is significantly reduced after effective medical treatment, showing that anxiety is a reversible consequence of nasal polyposis in most cases.

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