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Semin Respir Crit Care Med 2002; 23(4): 399-410
DOI: 10.1055/s-2002-34333
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Leukotriene Receptor Antagonists

Marzena E. Krawiec1 , Nizar J. Jarjour2
  • 1Department of Pediatrics, University of Wisconsin, Madison, Wisconsin
  • 2Department of Medicine, University of Wisconsin, Madison, Wisconsin
Further Information

Publication History

Publication Date:
26 September 2002 (online)

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ABSTRACT

In the past decade, heightened emphasis has been placed on the importance of inflammation in the pathogenesis of asthma. Although corticosteroids have remained the primary anti-inflammatory agents in the management of the persistent asthmatic, new classes of drugs have recently been added. The leukotriene receptor antagonists (LTRAs) are the first new approach in asthma therapy in the past 25 years and the first class of drugs to target specific components of the inflammatory process. These drugs reverse the primary biological effects of the cysteinyl leukotrienes in relation to the pathogenesis of asthma including bronchoconstriction, mucus hypersecretion, and airway inflammation. The LTRAs have demonstrated efficacy against exercise- and allergen-induced bronchoconstriction, aspirin-sensitive asthma, and additive benefit in symptomatic moderate asthmatics on maintenance inhaled corticosteroids, as well as potential steroid-sparing effects. Finally, although evidence for their role as first-line controller agents for the management of mild persistent asthma has grown stronger in recent years, this role continues to evolve.

KEYWORDS

Asthma - leukotriene receptor antagonists - inflammation

REFERENCES

  • 1 Beasley R, Roche W R, Roberts J A, Holgate S T. Cellular events in the bronchi in mild asthma before and after bronchoprovocation.  Am Rev Respir Dis . 1989;  139 806-817
    PubMedGoogle Scholar
  • 2 Murphy R C, Hammerstrom S, Samuelsson B. Leukotriene C, a slow reacting substance (SRS) from mouse mastocytoma cells.  Proc Nat Acad Sci . 1979;  76 4275-4279
    PubMedGoogle Scholar
  • 3 Dahlen S E, Hedquist P, Hammarstrom S, Samuelsson B. Leukotrienes are potent constrictors of human bronchi.  Nature . 1980;  288 484-486
    CrossrefPubMedGoogle Scholar
  • 4 Weiss J W, Drazen J M, Coles N. Bronchoconstrictor effects of leukotriene C in humans.  Science . 1982;  15 196-198
    PubMedGoogle Scholar
  • 5 Griffin M, Weiss J W, Leitch A G. Effects of leukotriene D on the airways in asthma.  N Engl J Med . 1983;  308 436-439
    PubMedGoogle Scholar
  • 6 Smith L J, Greenberger P A, Patterson R, Krell R D, Bernstein P R. The effect of inhaled leukotriene D4 on humans.  Am Rev Respir Dis . 1985;  131 368-372
    PubMedGoogle Scholar
  • 7 Laitinen L A, Laitinen A, Haahtela T, Vilkka V, Spur B W, Lee T H. Leukotriene E(4) and granulocytic infiltration into asthmatic airways.  Lancet . 1993;  341 989-990
    CrossrefPubMedGoogle Scholar
  • 8 Kellaway C H, Trethewie E R. Liberation of slow-reacting smooth muscle stimulating substance of anaphylaxis.  J Exp Physiol . 1940;  30 121-148
    PubMedGoogle Scholar
  • 9 Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation.  Science . 1983;  220 568-575
    CrossrefPubMedGoogle Scholar
  • 10 Krawiec M E, Wenzel S E. Use of leukotriene antagonists in childhood asthma.  Curr Opin Pediatr . 1999;  11 540-547
    CrossrefPubMedGoogle Scholar
  • 10a Borgeat P, Hamberg M, Samuellsson B. Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monhydroxy acids from novel lipoxygenases.  J Biol Chem . 1976;  251 7816-7820
    PubMedGoogle Scholar
  • 11 Reid G K, Kargman S, Vickers P J. Correlation between 5-lipoxygenase activating protein, 5-lipoxygenase, and cellular leukotriene synthesis.  J Biol Chem . 1990;  265 19818-19823
    PubMedGoogle Scholar
  • 12 Williams J D, Czop J K, Austen K F. Release of leukotrienes by human monocytes on stimulation of their phagocytic receptor for particulate activators.  J Immunol . 1984;  30 34-40
    PubMedGoogle Scholar
  • 13 Goldyne M E, Burrish G F, Poubelle P, Borgeat P. Arachidonic acid metabolism among human mononuclear leukocytes: lipoxygenase-related pathways.  J Biol Chem . 1984;  259 8815-8819
    PubMedGoogle Scholar
  • 14 Jorg A, Henderson W R, Murphy R C, Klebanoff S J. Leukotriene generation by eosinophils.  J Exp Med . 1982;  155 390-402
    CrossrefPubMedGoogle Scholar
  • 15 Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T. A G-coupled receptor for leukotriene B4 that mediates chemotaxis.  Nature . 1997;  387 620-624
    CrossrefPubMedGoogle Scholar
  • 16 Lynch K R, O'Neill G P, Liu Q. Characterization of the human cysteinyl leukotriene cysLTI receptor.  Nature . 1999;  399 789-793
    CrossrefPubMedGoogle Scholar
  • 17 Heise C E, O'Dowd B F, Figueroa D J. Characterization of the human cysteinyl leukotriene 2 receptor.  J Biol Chem . 2000;  275 30531-30516
    CrossrefPubMedGoogle Scholar
  • 18 Shimizu T, Hirano H, Majima Y, Sakakura Y. A mechanism of antigen-induced mucus production in nasal epithelium of sensitized rats: a comparison with lipopolysaccharide-induced mucus production.  Am J Respir Crit Care Med . 2000;  161 1648-1654
    PubMedGoogle Scholar
  • 19 Barnes N C, Piper P J, Costello J F. Comparative actions of inhaled leukotriene C4, leukotriene D4 and histamine in normal human subjects.  Thorax . 1984;  39 500-504
    PubMedGoogle Scholar
  • 20 Adelroth E, Morris M M, Hargreave F E. Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls.  N Engl J Med . 1986;  315 480-484
    PubMedGoogle Scholar
  • 21 Holgate S T, Bradding P, Sampson A P. Leukotriene antagonists and synthesis inhibitors: new directions in asthma therapy.  J Allergy Clin Immunol . 1996;  98 1-13
    PubMedGoogle Scholar
  • 22 Marom Z, Shelhamer J H, Bach M K, Morton D R, Kaliner M. Slow-reacting substances, leukotrienes C4 and D4, increase the release of mucus from human airways in vitro.  Am Rev Respir Dis . 1982;  126 449-451
    PubMedGoogle Scholar
  • 23 Diamant Z, Hiltermann J T, van Rensen L E. Cell differentials in induced sputum after inhaled leukotriene D4 in subjects with mild asthma.  Am J Respir Crit Care Med . 1997;  155 1247-1253
    PubMedGoogle Scholar
  • 24 Martin T R, Pistorese B P, Chi E Y, Goodman R B, Matthay M A. Effects of leukotriene B4 in the human lung: recruitment of neutrophils into the alveolar spaces without a change in protein permeability.  J Clin Invest . 1989;  84 1609-1619
    PubMedGoogle Scholar
  • 25 Lee E, Lindo T, Jackson N. Reversal of human neutrophil survival by leukotriene B(4) receptor blockade and 5-lipoxygenase and 5-lipoxygenase activating protein inhibitors.  Am J Respir Crit Care Med . 1999;  160 2079-2085
    PubMedGoogle Scholar
  • 26 Hoover R L, Karnovsky M J, Austen K F, Corey E J, Lewis R A. Leukotriene B4 action on endothelium mediates augmented neutrophil/endothelial adhesion.  Proc Natl Acad Sci USA . 1984; 
    PubMedGoogle Scholar
  • 27 Yamaoka K A, Kolb J P. Leukotriene B4 induces interleukin 5 generation from human T lymphocytes.  Eur J Immunol . 1993;  23 2392-2398
    PubMedGoogle Scholar
  • 28 Smith L J, Geller S, Ebright L, Glass M, Thyrum P T. Inhibition of leukotriene D4-induced bronchoconstriciton in normal subjects by the oral LTD4 receptor antagonist ICI 204,219.  Am Rev Respir Dis . 1990;  141 988-992
    PubMedGoogle Scholar
  • 29 Smith L J, Glass M, Minkwitz M C. Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219.  Clin Pharmacol Ther . 1993;  54 430-436
    PubMedGoogle Scholar
  • 30 O'Shaughnessy T C, Georgiou P, Howland K, Dennis M, Comptom C H, Barnes N C. Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers.  Thorax . 1997;  52 519-522
    PubMedGoogle Scholar
  • 31 De Lepeleire I, Reiss T F, Rochette F. Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the airways of patients with asthma.  Clin Pharmacol Ther . 1997;  61 83-92
    CrossrefPubMedGoogle Scholar
  • 32 Smith L J, Hanby L A, Lavins B J, Simonson S G. A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy.  Ann Allergy Asthma Immunol . 1998;  81 43-49
    PubMedGoogle Scholar
  • 33 O'Byrne P M, Dolovich J, Hargreave F E. Late asthmatic responses.  Am Rev Respir Dis . 1987;  136 740-751
    PubMedGoogle Scholar
  • 34 Diamant Z, Grootendorst D C, Veselic-Charvat M. The effect of oral montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma.  Clin Exp Allergy . 1999;  29 42-51
    CrossrefPubMedGoogle Scholar
  • 35 O'Sullivan S, Roquet A, Dahlen B, Dahlen S, Kumlin M. Urinary excretion of inflammatory mediators during allergen-induced early and late phase asthmatic reactions.  Clin Exp Allergy . 1998;  28 1332-1339
    CrossrefPubMedGoogle Scholar
  • 36 Wenzel S E, Larsen G L, Johnston K, Voelkel N F, Westcott J W. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge.  Am Rev Respir Dis . 1990;  142 112-119
    PubMedGoogle Scholar
  • 37 Macfarlane A J, Dworski R, Sheller J R, Pavord I D, Barry Kay A, Barnes N C. Sputum cysteinyl leukotriene increase 24 hours after allergen inhalation in atopic asthmatics.  Am J Respir Crit Care Med . 2000;  161 1553-1558
    PubMedGoogle Scholar
  • 38 Rasmussen J B, Eriksson L O, Margolskee D J, Tagari P, Williams V C, Andersson K E. Leukotriene D4 receptor blockade inhibits the immediate and late bronchoconstrictor responses to inhaled antigen in patients with asthma.  J Allergy Clin Immunol . 1992;  90 193-201
    CrossrefPubMedGoogle Scholar
  • 39 Taylor I K, O'Shaughnessy K M, Fuller R W, Dollery C T. Effect of cysteinyl-leukotriene receptor antagonists ICI 204,219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects.  Lancet . 1991;  337 690-694
    CrossrefPubMedGoogle Scholar
  • 40 Taniguchi Y, Tamura G, Honma M. The effect of an oral leukotriene antagonist, ONO-1078, on allergen-induced immediate bronchoconstriction in asthmatic subjects.  J Allergy Clin Immunol . 1993;  92 507-512
    CrossrefPubMedGoogle Scholar
  • 41 Calhoun W J, Lavins B J, Minkwitz M C, Evans R, Gleich G J, Cohn J. Effect of zafirlukast (Accolate) on cellular mediators of inflammation. Bronchoalveolar lavage fluid findings after segmental antigen challenge.  Am J Respir Crit Care Med . 1998;  157 1381-1389
    PubMedGoogle Scholar
  • 42 Hamilton A, Faiferman I, Stober P, Watson M, O'Byrne P M. Pranlukast, a cysteinyl leukotriene receptor antagonist, attenuates allergen-induced early and late phase bronchoconstriction and airway hyperresponsiveness in asthmatic subjects.  J Allergy Clin Immunol . 1998;  102 177-183
    PubMedGoogle Scholar
  • 43 Anderson S D. Exercise-induced asthma: the state of the art.  Am Rev Respir Dis . 1985;  87 191-195
    PubMedGoogle Scholar
  • 44 Kikawa Y, Miyanomae T, Inoue Y. Urinary leukotriene E4 after exercise challenge in children with asthma.  J Allergy Clin Immunol . 1992;  89 1111-1119
    CrossrefPubMedGoogle Scholar
  • 45 Smith C M, Christie P E, Hawksworth R J, Thien F, Lee T H. Urinary leukotriene E4 levels after allergen and exercise challenge in bronchial asthma.  Am Rev Respir Dis . 1991;  144 1411-1415
    PubMedGoogle Scholar
  • 46 Reiss T F, Hill J B, Harman E. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.  Thorax . 1997;  52 1030-1035
    PubMedGoogle Scholar
  • 47 Finnerty J P, Wood-Baker R, Thomson H, Holgate S T. Role of leukotrienes in exercise-induced asthma: inhibitory effect of ICI 204,219, a potent leukotriene D4 receptor antagonist.  Am Rev Respir Dis . 1992;  145 746-749
    PubMedGoogle Scholar
  • 48 Manning P J, Watson R M, Margolskee D J, Williams V C, Schwartz J I, O'Byrne P M. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist.  N Engl J Med . 1990;  323 1736-1739
    PubMedGoogle Scholar
  • 49 Leff J A, Busse W W, Pearlman D. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction.  N Engl J Med . 1998;  339(3) 147-152
    CrossrefPubMedGoogle Scholar
  • 50 Dessanges J F, Prefaut C, Taytard A. The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness.  J Allergy Clin Immunol . 1999;  104 1155-1161
    PubMedGoogle Scholar
  • 51 Kemp J P, Dockhorn R J, Shapiro G G. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma.  J Pediatr . 1998;  133 424-428
    PubMedGoogle Scholar
  • 52 Pearlman D S, Ostrom N K, Bronsky E A, Bonuccelli C M, Hanby L A. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children.  J Pediatr . 1999;  134 273-279
    PubMedGoogle Scholar
  • 53 Robuschi M, Riva E, Fuccella L M. Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353): a double-blind study versus disodium cromoglycate and placebo.  Am J Respir Crit Care Med . 1992;  145 1285-1288
    PubMedGoogle Scholar
  • 54 Hofstra W B, Sterk P J, Neijens H J. Short-term treatment with zafirlukast, sodium cromoglycate or placebo in reducing exercise-induced bronchoconstriciton in adolescent asthmatics [abstract].  Eur Respir J . 1997;  10 220
    PubMedGoogle Scholar
  • 55 Coreno A, Skowronski M, Kotaru C, McFadden Jr R E. Comparative effects of the long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma.  J Allergy Clin Immunol . 2000;  106 500-506
    CrossrefPubMedGoogle Scholar
  • 56 Villaran C, O'Neill S J, Helbling A. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group.  J Allergy Clin Immunol . 1999;  104 547-553
    PubMedGoogle Scholar
  • 57 Edelman J M, Turpin J A, Bronsky E A. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction: a randomized, double-blind trial. Exercise Study Group.  Ann Intern Med . 2000;  132 97-104
    PubMedGoogle Scholar
  • 58 McFadden Jr R E, Gilbert I A. Exercise-induced asthma.  N Engl J Med . 1994;  330 1362-1367
    CrossrefPubMedGoogle Scholar
  • 59 Simons F ER, Gerstner T V, Cheang M S. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.  Pediatrics . 1997;  99 655-659
    CrossrefPubMedGoogle Scholar
  • 60 Ferreri N R, Howland W C, Stevenson D D, Spiegelberg H L. Release of leukotrienes, prostaglandins, and histamine into nasal secretions of aspirin-sensitive asthmatics during reaction to aspirin.  Am Rev Respir Dis . 1988;  137 847-854
    CrossrefPubMedGoogle Scholar
  • 61 Kumlin M, Dahlen B, Bjorck T, Zetterstrom O, Granstrom E, Dahlen S E. Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4 and histamine in asthmatics.  Am Rev Respir Dis . 1992;  146 96-103
    PubMedGoogle Scholar
  • 62 Daffern P J, Muilenburg D, Hugli T E, Stevenson D D. Association of urinary leukotriene E4 excretion during aspirin challenges with severity of respiratory responses.  J Allergy Clin Immunol . 1999;  104 559-564
    CrossrefPubMedGoogle Scholar
  • 63 Schmid M, Gode U, Schafer D, Wigand M E. Arachidonic acid metabolism in nasal tissue and peripheral blood cells in aspirin intolerant asthmatics.  Acta Otolaryngol . 1999;  119 277-280
    CrossrefPubMedGoogle Scholar
  • 64 Szczeklik A, Sladek K, Dworski R. Bronchial aspirin challenge causes specific eicosanoid response in aspirin-sensitive asthmatics.  Am J Respir Crit Care Med . 1996;  154 1608-1614
    PubMedGoogle Scholar
  • 65 Cowburn A S, Sladek K, Soja J. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma.  J Clin Invest . 1998;  101 834-846
    PubMedGoogle Scholar
  • 66 Yoshida S, Nakagawa H, Yamawaki Y. Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary leukotriene E4 excretion in patients with aspirin-intolerant asthma.  Int Arch Allergy Immunol . 1998;  117 146-151
    CrossrefPubMedGoogle Scholar
  • 67 Yamamoto H, Nagata M, Kuramitsu K. Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078.  Am J Respir Crit Care Med . 1994;  150 254-257
    PubMedGoogle Scholar
  • 68 Kuna P, Malmstrom K, Dahlen S E. Montelukast (MK-0476), a cyst1 receptor antagonist, improves asthma control in aspirin-intolerant asthmatic patients [abstract].  Am J Respir Crit Care Med . 1997;  155 D83
    PubMedGoogle Scholar
  • 69 Stevenson D C, Simon R A, Mathison D A, Christiansen S C. Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics.  Ann Allergy Asthma Immunol . 2000;  85 477-482
    PubMedGoogle Scholar
  • 70 Ishioka S, Hozawa S, Haruta Y. Effects of pranlukast, a cysteinyl leukotriene antagonist, on bronchial responsiveness to methacholine in aspirin-intolerant asthmatics treated with corticosteroids.  Hiroshima J Med Sci . 2000;  49 105-108
    PubMedGoogle Scholar
  • 71 Menendez R, Venzor J, Ortiz G. Failure of zafirlukast to prevent ibuprofen-induced anaphylaxis.  Ann Allergy Asthma Immunol . 1998;  80 225-226
    PubMedGoogle Scholar
  • 72 Enrique E, Garcia-Ortega P, Gaig P, San Miguel M M. Failure of montelukast to prevent anaphylaxis to diclofenac.  Allergy . 1999;  54 529-530
    CrossrefPubMedGoogle Scholar
  • 73 Foster A, Chan C C. Peptide leukotriene involvement and pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig.  Int Arch Allergy Appl Immunol . 1991;  96 279-284
    PubMedGoogle Scholar
  • 74 Turner C R, Smith W B, Andresen C J, Swindell A C, Watson J W. Leukotriene D4 receptor antagonism reduces airway hyperresponsiveness in monkeys.  Pulm Pharmacol . 1994;  7 49-58
    PubMedGoogle Scholar
  • 75 Virchow Jr C J, Faehndrich S, Nassenstein C, Bock S, Matthys H, Luttmann W. Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells.  Clin Exp Allergy . 2001;  31 836-844
    CrossrefPubMedGoogle Scholar
  • 76 Pizzichini E, Leff J A, Reiss T F. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized controlled trial.  Eur Respir J . 1999;  14 12-18
    CrossrefPubMedGoogle Scholar
  • 77 Ramsay C F, Li D, Wang D. Bronchial biopsy specimen variability: requirement for large sample size and repeated measurements to improve reliability [abstract].  Am J Respir Crit Care Med . 1999;  159 655
    PubMedGoogle Scholar
  • 78 Nakamura Y, Hoshino M, Sim J J, Ishii K, Hasaka K, Sakamoto T. Effect of the leukotriene receptor antagonist pranlukast on cellular infiltration in the bronchial mucosa of patients with asthma.  Thorax . 1998;  53 835-841
    PubMedGoogle Scholar
  • 79 Isogai S, Taniguchi M, Anzai K. Effect of peptide-leukotriene receptor antagonist pranlukast on eosinophil counts in peripheral blood and sputum in patients with chronic asthma [abstract].  Am J Respir Crit Care Med . 1998;  157 A412
    PubMedGoogle Scholar
  • 80 Kylstra J W, Sweitzer D E, Miller C J, Bonuccelli C M. Zafirlukast (Accolate) in moderate asthma: patient-reported outcomes and peripheral eosinophil data from a 13-week trial [abstract].  Am J Respir Crit Care Med . 1998;  157 A410
    PubMedGoogle Scholar
  • 81 Reiss T F, Chervinsky P, Dockhorn R J, Shingo S, Seidenberg B, Edwards T B. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma.  Arch Intern Med . 1998;  158 1213-1220
    CrossrefPubMedGoogle Scholar
  • 82 Fish J E, Kemp J P, Lockey R F, Glass M, Hanby L A, Bonuccelli C M. Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study.  Clin Ther . 1997;  19 675-690
    CrossrefPubMedGoogle Scholar
  • 83 Suissa S, Dennis R, Ernst P, Sheehy O, Wood-Dauphinee S. Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma: a randomized double-blind, placebo-controlled trial.  Ann Intern Med . 1997;  126 177-183
    PubMedGoogle Scholar
  • 84 Knorr B, Matz J, Bernstein J A. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial.  JAMA . 1998;  279 1181-1186
    CrossrefPubMedGoogle Scholar
  • 85 Pearlman D S, Lampl K L, Dowling Jr J P, Miller C J, Bonuccelli C M. Effectiveness and tolerability of zafirlukast for the treatment of asthma in children.  Clin Ther . 2000;  22 732-747
    CrossrefPubMedGoogle Scholar
  • 86 Volovitz B, Tabachnik E, Nussinovitch M. Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma.  J Allergy Clin Immunol . 1999;  104 1162-1167
    PubMedGoogle Scholar
  • 87 Nathan R A, Minkwitz M C, Bonuccelli C M. Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness.  Ann Allergy Asthma Immunol . 1999;  82 497-503
    PubMedGoogle Scholar
  • 88 Malmstrom K, Rodriguez-Gomez G, Guerra J. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Montelukast/beclomethasone study group.  Ann Intern Med . 1999;  130 487-495
    PubMedGoogle Scholar
  • 89 Bleecker E R, Welch M J, Weinstein S F. Low-dose fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma.  J Allergy Clin Immunol . 2000;  105 1123-1129
    CrossrefPubMedGoogle Scholar
  • 90 Busse W W, Raphael G D, Galant S. Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial.  J Allergy Clin Immunol . 2001;  107 461-468
    CrossrefPubMedGoogle Scholar
  • 91 Wenzel S E, Chervinsky P, Kerwin E. Oral pranlukast (Ultair) vs inhaled beclomethasone: results of a 12-week trial in patients with asthma [abstract].  Am J Respir Crit Care Med . 1997;  155 203
    PubMedGoogle Scholar
  • 92 Westbroek J, Pasma H R. The effect of inhaled fluticasone propionate 100 μg qd compared with oral zafirlukast 20 mg qd on bronchial hyperresponsiveness in mild to moderate asthmatics.  Eur Respir J . 1997;  8(suppl) 248
    PubMedGoogle Scholar
  • 93 Pauwels R, Lofdahl C G, Postma D. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.  N Engl J. Med . 1997;  337 1405-1411
    CrossrefPubMedGoogle Scholar
  • 94 Clark R A, Anderson P B. Combined therapy with salbutamol and beclomethasone inhalers in chronic asthma.  Lancet . 1978;  2 70-72
    PubMedGoogle Scholar
  • 95 Nassif E G, Weinberger M, Thompson R, Huntley W. The value of maintenance theophylline in steroid-dependent asthma.  N Engl J Med . 1981;  304 71-76
    PubMedGoogle Scholar
  • 96 Lofdahl C G, Reiss T F, Leff J A. Randomized, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients.  BMJ . 1999;  319 87-90
    PubMedGoogle Scholar
  • 97 Tamaoki J, Kondo M, Sakai N. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid.  Am J Respir Crit Care Med . 1997;  155 1235-1240
    PubMedGoogle Scholar
  • 98 Laviolette M, Malmstrom K, Lu S. Montelukast added to inhaled beclomethasone in treatment of asthma.  Am J Respir Crit Care Med . 1999;  160 1862-1868
    PubMedGoogle Scholar
  • 99 Virchow J C, Prasse A, Naya I, Summerton L, Harris A, The Zafirlukast Study Group. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids.  Am J Respir Crit Care Med . 2000;  162 578-585
    PubMedGoogle Scholar
  • 100 Simons F E, Villa J R, Lee B W. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study.  J Pediatr . 2001;  138 694-698
    CrossrefPubMedGoogle Scholar
  • 101 Nelson H S, Busse W W, Kerwin E. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.  J Allergy Clin Immunol . 2000;  106 1088-1095
    CrossrefPubMedGoogle Scholar
  • 102 Wechsler M E, Garpestad E, Flier S R. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast.  JAMA . 1998;  279 455-457
    CrossrefPubMedGoogle Scholar
  • 103 Wechsler M E, Finn D, Gunawardena D, Westlake R, Barker A, Haranath S P. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma.  Chest . 2000;  117 708-713
    CrossrefPubMedGoogle Scholar
  • 104 Kinoshita M, Shiraishi T, Koga T, Ayabe M, Rikimaru T, Oizumi K. Churg-Strauss syndrome after corticosteroid withdrawal in an asthmatic patient treated with pranlukast.  J Allergy Clin Immunol . 1999;  103 534-535
    PubMedGoogle Scholar
  • 105 Le Gall C, Pham S, Vignes S. Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.  Eur Respir J . 2000;  15 978-981
    CrossrefPubMedGoogle Scholar
  • 106 Bili A, Condemi J J, Bottone S M, Ryan C K. Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists.  J Allergy Clin Immunol . 1999;  104 1060-1065
    PubMedGoogle Scholar
  • 107 National Asthma Education Program Expert Panel Report. II: Guidelines for the Diagnosis and Management of Asthma Bethesda, MD: National Institutes of Health 1997
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