Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation Anthony P. Sampson, PhDa, Emilio Pizzichini, MD, PhDb,

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Presentation transcript:

Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation Anthony P. Sampson, PhDa, Emilio Pizzichini, MD, PhDb, Hans Bisgaard, MDc Journal of Allergy and Clinical Immunology Volume 111, Issue 1, Pages S49-S61 (January 2003) DOI: 10.1067/mai.2003.24 Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 1 Percent change in blood eosinophil counts after treatment of asthmatic adults and children with oral montelukast. Studies included are (1) Altman et al. J Allergy Clin Immunol 1998;102:50-6; (2) Noonan et al. Eur Respir J 1998;11:1232-9; (3) Malmstrom et al. Ann Intern Med 1999;130:487-95; (4) Reiss et al. Arch Intern Med 1998;158:1213-20; (5) Leff et al. N Engl J Med 1998;339:147-52; (6) Pizzichini et al. Eur Respir J 1999;14:12-8; (7) Knorr et al. JAMA 1998;279:1181-6. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 2 LTC4 synthase genotype and pulmonary function response to zafirlukast in patients with severe asthma. Pulmonary function responses to 2 weeks of treatment with oral zafirlukast (20 mg twice daily for 2 weeks) in 23 persons with chronic severe asthma, stratified by their wild-type (AA) (white bars, n = 10) or mutant (AC/CC) (black bars, n = 13) genotype for the LTC4 synthase A-444C promoter polymorphism. From Sampson et al. Thorax 2000;55(Suppl 2):S28-31. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 3 Diagram showing 3 models to investigate the anti-inflammatory effects of intervention using examination of induced sputum. Activated airway inflammation can be presented spontaneously (uncontrolled asthma) or induced by an allergen challenge or by a controlled reduction of therapy. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 4 Sputum cell counts for eosinophils (black bars) and neutrophils (white bars) in healthy subjects and in subjects with asthma of varying severities. Results are the mean values from the results of several studies. Dashed line represents the upper limit (+90% CI) of the mean for eosinophils from healthy subjects, 1.1%. Higher proportions of eosinophils and neutrophils were measured in asthmatic patients compared with healthy subjects. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 5 Time course of effects of prednisone reduction on markers of airway functional inflammation. Blue indicates symptoms; gray, FEV1; green, blood eosinophils; black, sputum eosinophils. Adapted from data in Pizzichini et al. Eur Respir J 1999;13:15-21. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 6 NO in exhaled air (Feno, in parts per billion) was significantly reduced after treatment with montelukast and budesonide as compared with placebo. Such treatment effects were independent of concurrent treatment with inhaled steroid (circles, solid lines) or no concurrent treatment with inhaled steroid (squares, dashed lines) . From Bisgaard H, et al. Am J Respir Crit Care Med 1999;160:1227-31. Journal of Allergy and Clinical Immunology 2003 111, S49-S61DOI: (10.1067/mai.2003.24) Copyright © 2003 Mosby, Inc. Terms and Conditions