Advertisement

Anti-Leukotriene Therapy for Asthma

  • Zuzana Diamant
  • Anthony P. Sampson
Chapter
  • 85 Downloads
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Human bronchial asthma is a chronic disorder of the airways, associated in most cases with atopy (i.e. specific immunoglobulin E responses to allergens), and characterised by a range of abnormalities on various levels. Early definitions of asthma stressed the aspects of variable lung function, reversible spontaneously or with treatment, but more recent definitions also place emphasis on the underlying airway inflammation that is thought to promote bronchial hyperresponsiveness [1]. The asthma syndrome comprises firstly, clinical symptoms, such as chest tightness, dyspnoea, coughing, and/or wheeze, secondly, pathophysiological features, such as variable airway obstruction and bronchial hyperresponsiveness (BHR) to a variety of stimuli which may be physical (e.g. cold dry air, hyper/hypotonic saline), pharmacological (e.g. histamine, methacholine), chemical (e.g. SO2), or physiological (e.g. exercise), and thirdly, pathohistological parameters, particularly eosinophilic airway inflammation, resulting in structural changes within the airways (“airway remodelling”) [2, 3]. Asthma may occur in varying degrees of severity ranging from intermittent to severe persistent forms [1].

Keywords

Airway Smooth Muscle Allergy Clin Immunol Respir Crit Persistent Asthma Bronchial Hyperresponsiveness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Global initiative for asthma (1995) National Institutes of Health, National Heart, Lung, and Blood InstituteGoogle Scholar
  2. 2.
    Djukanovic R, Roche WR, Wilson JW, Beasley CRW, Twentyman OP, Howarth PH, Holgate ST (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142: 434–457PubMedGoogle Scholar
  3. 3.
    Ebina M, Takahashi T, Chiba T, Motomiya M (1993) Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. Am Rev Respir Dis 148: 720–726PubMedCrossRefGoogle Scholar
  4. 4.
    Barnes PJ, Jonsson B, Klim JB (1996) The costs of asthma. Eur Respir J 9: 636–642PubMedCrossRefGoogle Scholar
  5. 5.
    Sterk PJ, Fabbri LM, Quanjer PhH, Cockcroft DW, O’Byrne PM, Anderson SD, Juniper EF, Malo J-L (1993) Airway responsiveness. Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Eur Respir J 6 (Suppl 16): 53–83Google Scholar
  6. 6.
    Cockcroft DW, Murdock KY, Kirby JG, Hargreave FE (1987) Prediction of airway responsiveness to allergen from skin sensitivity to allergen and airway responsiveness to histamine. Am Rev Respir Dis 135: 264–267PubMedGoogle Scholar
  7. 7.
    Weersink EJM, Postma DS, Aalbers R, De Monchy JG (1994) Early and late asthmatic reaction after allergen challenge. Respir Med 88: 103–114PubMedCrossRefGoogle Scholar
  8. 8.
    Diaz P, Gonzalez MC, Galleguillos FR, Ancic P, Cromwell O, Shepherd D, Durham SR, Gleich GJ, Kay AB (1989) Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions. Am Rev Respir Dis 139: 1383–1389PubMedGoogle Scholar
  9. 9.
    Bentley AM, Kay AB, Durham SR (1997) Human late asthmatic reactions. Clin Exp Allergy 27 (Suppl 1): 71–86PubMedCrossRefGoogle Scholar
  10. 10.
    Holgate ST, Bradding P, Sampson AP (1996) Leukotriene antagonists and synthesis inhibitors: new directions in asthma therapy. J Allergy Clin Immunol 98: 1–13PubMedCrossRefGoogle Scholar
  11. 11.
    Holtzman MJ (1991) Arachidonic acid metabolism. Am Rev Respir Dis 143: 188–203PubMedGoogle Scholar
  12. 12.
    Lewis RA, Austen KF, Soberman RJ (1990) Leukotrienes and other products of the 5-lipoxygenase pathway: biochemistry and relation to pathobiology in human diseases. N Engl J Med 323: 645–655PubMedCrossRefGoogle Scholar
  13. 13.
    Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA (1988) Cloning of the cDNA for human 5-lipoxygenase. Proc Natl Acad Sci USA 85: 416–420PubMedCrossRefGoogle Scholar
  14. 14.
    Brock TG, McNish RW, Bailie MB, Peters-Golden M (1997) Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence. J Biol Chem 272: 8276–8280PubMedCrossRefGoogle Scholar
  15. 15.
    Dixon RA, Diehl RE, Opas E, Rands E, Vickers PJ, Evans JF, Gillard JW, Miller DK (1990) Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature 343: 282–284PubMedCrossRefGoogle Scholar
  16. 16.
    Miller DK, Gillard JW, Vickers PJ, Sadowski S, Leveille C, Mancini JA, Charleson P, Dixon RA, Ford-Hutchinson AW, Fortin R et al (1990) Identification and isolation of a membrane protein necessary for leukotriene production. Nature 343: 278–281PubMedCrossRefGoogle Scholar
  17. 17.
    Samuelsson B, Funk CD (1989) Enzymes involved in the biosynthesis of leukotriene B4. J Biol Chem 264: 19469–19472PubMedGoogle Scholar
  18. 18.
    Yoshimoto T, Soberman RJ, Lewis RA, Austen KF (1985) Isolation and characterization of leukotriene C4 synthetase of rat basophilic leukemia cells. Proc Natl Acad Sci USA 82: 8399–8403PubMedCrossRefGoogle Scholar
  19. 19.
    Lam BK, Penrose JF, Freeman GJ, Austen KF (1994) Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci USA 91: 7663–7667PubMedCrossRefGoogle Scholar
  20. 20.
    Lam BK, Owen WFJ, Austen KF, Soberman RJ (1989) The identification of a distinct export step following the biosynthesis of leukotriene C4 by human eosinophils. J Biol Chem 264: 12885–12889PubMedGoogle Scholar
  21. 21.
    Conroy DM, Piper PJ (1991) Metabolism and generation of cysteinyl-containing leukotrienes by human lung preparations. Ann NY Acad Sci 629: 455–457.PubMedCrossRefGoogle Scholar
  22. 22.
    Zakrzewski JT, Sampson AP, Evans JM, Barnes NC, Piper PJ, Costello JF (1989) The biotransformation in vitro of cysteinyl leukotrienes in blood of normal and asthmatic subjects. Prostaglandins 37: 425–444PubMedCrossRefGoogle Scholar
  23. 23.
    Keppler D, Huber M, Hagmann W, Ball HA, Guhlmann A, Kastner S (1988) Metabolism and analysis of endogenous cysteinyl leukotrienes. Ann NY Acad Sci 524: 68–74PubMedCrossRefGoogle Scholar
  24. 24.
    Shak S, Goldstein IM (1984) Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes. J Biol Chem 259: 10181–10187PubMedGoogle Scholar
  25. 25.
    Maltby NH, Taylor GW, Ritter JM, Moore K, Fuller RW, Dollery CT (1990) LTC4 elimination and metabolism in man. J Allergy Clin Immunol 85: 3–9PubMedCrossRefGoogle Scholar
  26. 26.
    Williams JD, Czop JK, Austen KF (1984) Release of leukotrienes by human monocytes on stimulation on their phagocytic receptor for particulate activators. J Immunol 132: 3034–3040PubMedGoogle Scholar
  27. 27.
    Fels AO, Pawlowski NA, Cramer EB, King TKC, Cohn ZA, Scott WA (1982) Human alveolar macrophages produce leukotriene B4. Proc Natl Acad Sci USA 79: 7866–7870PubMedCrossRefGoogle Scholar
  28. 28.
    Bochner BS, Undem BJ, Lichtenstein LM (1994) Immunological aspects of allergic asthma. Annu Rev Immunol 12: 295–335PubMedCrossRefGoogle Scholar
  29. 29.
    Peters SP, MacGlashan DW, Schulman ES, Schulman ES, Schleimer RP, Hayes EC, Rokach J, Adkinson NF, Lichtenstein LM (1984) Arachidonic acid metabolism in purified human lung mast cells. J Immunol 132: 1972–1879PubMedGoogle Scholar
  30. 30.
    Shaw RJ, Cromwell O, Kay AB (1984) Preferential generation of leukotriene C4 by human eosinophils. Clin Exp Immunol 56: 716–722PubMedGoogle Scholar
  31. 31.
    Borgeat P, Fruteau de Laclos B, Rabinovitch H, Picard S, Braquet P, Hébert J, Laviolette M (1984) Eosinophil-rich human polymorphonuclear leukocyte preparations characteristically release leukotriene C4 on ionophore A-23187 challenge. J Allergy Clin Immunol 74: 310–315PubMedCrossRefGoogle Scholar
  32. 32.
    Sampson AP (1996) The leukotrienes: mediators of chronic inflammation in asthma. Clin Exp Allergy 26: 995–1004PubMedCrossRefGoogle Scholar
  33. 33.
    Drazen JM, Evans JF, Stevens RL, Shipp MA (1995) Inflammatory effector mechanisms in asthma. Am J Respir Crit Care Med 152: 403–407PubMedGoogle Scholar
  34. 34.
    Martin TR, Pistorese BP, Chi EY, Goodman RB, Matthay MA (1989) Effects of leukotriene B4 in the human lung. J Clin Invest 84: 1609–1619PubMedCrossRefGoogle Scholar
  35. 35.
    Spada CS, Nieves AL, Krauss AH-P, Woodward DF (1994) Comparison of leukotriene B4 and D4 effects on human eosinophil and neutrophil motility in vitro. J Leukoc Biol 55: 183–191PubMedGoogle Scholar
  36. 36.
    Gardiner PJ, Cuthbert NJ (1988) Characterisation of the leukotriene receptor(s) on human isolated lung strips. Agents Actions Suppl 23: 121–128PubMedGoogle Scholar
  37. 37.
    Weiss JW, Drazen JM, Coles N, McFadden ER, Lewis R, Weiler P, Corey EJ, Austen KF (1982) Bronchoconstrictor effects of leukotriene C in humans. Science 216: 196–198PubMedCrossRefGoogle Scholar
  38. 38.
    Barnes NC, Piper PJ, Costello JF (1984) Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. Thorax 39: 500–504PubMedCrossRefGoogle Scholar
  39. 39.
    Holroyde MC, Altounyan REC, Cole M, Dixon M, Elliott EV (1981) Bronchoconstriction produced in man by leukotrienes C and D. Lancet ii: 17–18CrossRefGoogle Scholar
  40. 40.
    Griffin M, Weiss JW, Leitch AG, McFadden ERJ, Corey EJ, Austen KF, Drazen JM (1983) Effects of leukotriene D on the airways in asthma. N Engl J Med 308: 436–439PubMedCrossRefGoogle Scholar
  41. 41.
    Coles SJ, Neill KH, Reid LM, Austen KF, Nii Y, Corey EJ, Lewis RA (1983) Effects of leukotrienes C4 and D4 on glycoprotein and lysozyme secretion by human bronchial mucosa. Prostaglandins 25: 155–170PubMedCrossRefGoogle Scholar
  42. 42.
    Woodward DF, Weichman BM, Gill CA, Wasserman MA (1983) The effect of synthetic leukotrienes on tracheal microvascular permeability. Prostaglandins 25: 131–142PubMedCrossRefGoogle Scholar
  43. 43.
    Foster A, Chan CC (1991) Peptide leukotriene involvement in pulmonary eosinophil migration upon challenge in the actively sensitized guinea-pig. Int Arch Allergy Appl Immunol 96: 279–284.PubMedCrossRefGoogle Scholar
  44. 44.
    Laitinen LA, Laitinen A, Haahtela T, Vilkka V, Spur B, Lee TH (1993) Leukotriene E4 and granulocytic infiltration into asthmatic airways. Lancet 341: 989–990PubMedCrossRefGoogle Scholar
  45. 45.
    Diamant Z, Hiltermann JT, Van Rensen EL, Callenbach PM, Veselic-Charvat MA, Van der Veen H, Sont JK, Sterk PJ (1997) The effect of inhaled leukotriene D4 and methacholine on cell differentials in sputum from patients with asthma. Am J Crit Respir Care Med 155: 1247–1253Google Scholar
  46. 46.
    Gorenne I, Norel X, Brink C (1996) Cysteinyl leukotriene receptors in the human lung: what’s new? Trends Pharmacol Sci 17: 342–345PubMedCrossRefGoogle Scholar
  47. 47.
    Diamant Z, Timmers MC, van der Veen H, Booms P, Sont JK, Sterk PJ (1994) Effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responsiveness to leukotriene D4 in normal and asthmatic subjects in vivo. Eur Respir J 7: 459–466PubMedCrossRefGoogle Scholar
  48. 48.
    Krell RD, Tsai BS, Berdoulay A, Barone M, Giles RE (1983) Heterogeneity of leukotriene receptors in guinea pig trachea. Prostaglandins 25: 171–178PubMedCrossRefGoogle Scholar
  49. 49.
    Israel E, Robin JL, Drazen JM (1987) Differential effects of calcium channel blockers on leukotriene C4-and D4-induced contractions in guinea pig pulmonary parenchymal strips. J Pharmacol Exp Ther 243: 424–429PubMedGoogle Scholar
  50. 50.
    Mong S, Wu HL, Stadel JM, Clark MA, Crooke ST (1986) Solubilisation of [3H]-leukotriene D4 receptor complex from guinea pig lung membranes. Mol Pharmacol 29: 235–243.PubMedGoogle Scholar
  51. 51.
    Buckner CK, Krell RD, Laravuso, Coursin DB, Bernstein PR, Will JA (1986) Pharmacological evidence that human intralobar airways do not contain different receptors that mediate contractions to leukotriene C4 and leukotriene D4. J Pharmacol Exp Ther 237: 558–562PubMedGoogle Scholar
  52. 52.
    Gardiner PJ, Abram TS, Tudhope SR, Cuthbert NJ, Norman P, Brink C (1994) Leukotriene receptors and their selective antagonists. Adv Prostaglandin Thromboxane Leukot Res 22: 49–61PubMedGoogle Scholar
  53. 53.
    Wenzel SE, Larsen GL, Johnston K, Voelkel NF, Westcott JY (1990) Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis 142: 112–119PubMedGoogle Scholar
  54. 54.
    Taylor G, Taylor I, Black P, Maltbey NH, Turner N, Fuller RW, Dollery CT (1989) Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet i: 584–588CrossRefGoogle Scholar
  55. 55.
    Turnbull LS, Turnbull LW, Leitch AG, Crofton JW, Kay AB (1977) Mediators of immediate-type hypersensitivity in sputum from patients with chronic bronchitis and asthma. Lancet i: 526–529CrossRefGoogle Scholar
  56. 56.
    Jarjour NN, Calhoun WJ, Schwartz LB, Busse W (1991) Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction. Am Rev Respir Dis 144: 83–87PubMedCrossRefGoogle Scholar
  57. 57.
    Liu MC, Bleecker ER, Lichtenstein LM, Kagey-Sobotka A, Niv Y, Mclemore TL, Permutt S, Proud D, Hubbard WC (1990) Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airway of subjects with mild asthma. Am Rev Respir Dis 142: 126–132PubMedGoogle Scholar
  58. 58.
    Stenton SC, Court EN, Kingston WP, Goadby P, Kelly CA, Duddridge M, Ward C, Hendrick DJ, Walters EH (1990) Platelet activating factor in bronchoalveolar lavage fluid from asthmatic subjects. Eur Respir J 3: 408–413PubMedGoogle Scholar
  59. 59.
    Lam S, Chan H, LeRiche JC, Chan-Yeung M, Salari H (1988) Release of leukotrienes in patients with bronchial asthma. J Allergy Clin Immunol 81: 711–717PubMedCrossRefGoogle Scholar
  60. 60.
    Sampson AP, Thomas RU, Costello JF, Piper PJ (1992) Enhanced leukotriene synthesis in leukocytes of atopic and asthmatic subjects. Br J Clin Pharmacol 33: 423–430PubMedCrossRefGoogle Scholar
  61. 61.
    Shindo K, Miyakawa K, Fukumura M (1993) Plasma levels of leukotriene B4 in asthmatic patients. Int J Tissue React 15: 181–184PubMedGoogle Scholar
  62. 62.
    Okubo T, Takahashi H, Sumitomo M, Shindo K, Suzuki S (1987) Plasma levels of leukotrienes C4 and D4 during wheezing attack in asthmatic patients. Int Arch Allergy Appl Immunol 84: 149–155PubMedCrossRefGoogle Scholar
  63. 63.
    Wardlaw AJ, Hay H, Cromwell O, Collins JV, Kay AB (1989) Leukotrienes LTC4 and LTB4 in bronchoalveolar lavage in bronchial asthma and other respiratory diseases. J Allergy Clin Immunol 84: 19–26PubMedCrossRefGoogle Scholar
  64. 64.
    Becher G, Winsel K, Beck E, Neubauer G, Stresemann E (1997) Breath condensate as a method of noninvasive assessment of inflammation mediators from the lower airways. Pneumologie 51(2): 456–459PubMedGoogle Scholar
  65. 65.
    Kidney JC, Ridge SM, Chung KF, Barnes PJ (1993) Inhibition of platelet-activating factor-induced bronchoconstriction by the leukotriene D4 receptor antagonist ICI 204,219. Am Rev Respir Dis 147: 215–217PubMedCrossRefGoogle Scholar
  66. 66.
    Abraham WM, Burch RM, Farmer SG, Sielczak MW, Ahmed A, Cortes A (1991) A bradykinin antagonist modifies allergen-induced mediator release and late bronchial responses in sheep. Am Rev Respir Dis 143: 787–796PubMedGoogle Scholar
  67. 67.
    Broide DH, Eisman S, Ramsdell JW, Ferguson P, Schwartz LB, Wasserman SI (1990) Airway levels of mast cell-derived mediators in exercise-induced asthma. Am Rev Respir Dis 141: 563–568PubMedCrossRefGoogle Scholar
  68. 68.
    Pliss LB, Ingenito EP, Ingram RH, Pichurko B (1990) Assessment of bronchoalveolar cell and mediator response to isocapnic hyperpnea in asthma. Am Rev Respir Dis 142: 73–78PubMedGoogle Scholar
  69. 69.
    Kikawa Y, Miyanomae T, Inoue Y, Saito M, Nakai A, Shigematsu Y, Hosoi S, Sudo M (1992) Urinary leukotriene E4 after exercise challenge in children with asthma. J Allergy Clin Immunol 89: 1111–1119.PubMedCrossRefGoogle Scholar
  70. 70.
    Smith CM, Christie PE, Hawksworth RJ, Thien F, Lee TH (1991) Urinary leukotriene E4 levels after allergen and exercise challenge in bronchial asthma. Am Rev Respir Dis 144: 1411–1413PubMedGoogle Scholar
  71. 71.
    Taylor IK, Wellings R, Taylor GW, Fuller RW (1992) Urinary leukotriene E4 excretion in exercise-induced asthma. J Appl Physiol 73: 743–748PubMedGoogle Scholar
  72. 72.
    Hejal RB, Walenga RW, Lenner KA, Nelson JA, McLane ML, Gilbert IA (1995) Urinary leukotriene E4 levels following isocapnic hyperventilation in asthmatics. Am J Respir Crit Care Med 151: A678 (Abstract)Google Scholar
  73. 73.
    Diamant Z (1996) Experimental interventions in leukotriene-and allergen-induced airway responses in asthma in vivo. PhD thesis, Pasmans Publishers, The Hague, The NetherlandsGoogle Scholar
  74. 74.
    Chafee FH, Settipane GA (1974) Aspirin intolerance. 1. Frequency in an allergic population. J Allergy Clin Immunol 3: 193–199CrossRefGoogle Scholar
  75. 75.
    Smith CM, Hawksworth RJ, Thien FCK, Christie PE, Lee TH (1992) Urinary leukotriene E4 in bronchial asthma. Eur Respir J 5: 693–699PubMedGoogle Scholar
  76. 76.
    Christie PE, Tagari P, Ford-Hutchinson AW, Black C, Markendorf A, Schmitz-Schumann M, Lee TH (1992) Urinary leukotriene E4 after lysine-aspirin inhalation in asthmatic subjects. Am Rev Respir Dis 146: 1531–1534PubMedGoogle Scholar
  77. 77.
    Sladek K, Dworski R, Soja J, Sheller JR, Nizankowska E, Oates JA, Szczeklik A (1994) Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. Am J Respir Crit Care Med 149: 940–946PubMedGoogle Scholar
  78. 78.
    Sestini P, Armetti L, Gambaro G, Pieroni MG, Refini RM, Sala A, Vaghi A, Folco GC, Bianco S, Robuschi M (1996) Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med 153: 572–575PubMedGoogle Scholar
  79. 79.
    Sampson AP, Cowburn AS, Sladek K, Adamek L, Nizankowska E, Szczeklik A, Penrose J, Austen KF, Holgate ST (1997) Profound over-expression of leukotriene C4 synthase in the bronchial biopsies of aspirin-intolerant asthmatics. Int Arch Allergy Immunol 113: 355–357PubMedCrossRefGoogle Scholar
  80. 80.
    Nasser SMS, Pfister R, Christie PE, Sousa AR, Barker J, Schmitz-Schumann M, Lee TH (1996) Inflammatory cell populations in bronchial biopsies from aspirin-sensitive asthmatic subjects. Am J Respir Crit Care Med 153: 90–96PubMedGoogle Scholar
  81. 81.
    Arm JP, O’Hickey SP, Spur BW, Lee TH (1989) Airway responsiveness to histamine and leukotriene E4 in subjects with aspirin-induced asthma. Am Rev Respir Dis 140: 148–153PubMedCrossRefGoogle Scholar
  82. 82.
    Adelroth E, Morris MM, Hargreave FE, O’Byrne PM (1986) Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N Engl J Med 315: 480–484.PubMedCrossRefGoogle Scholar
  83. 83.
    Smith LJ, Greenberger PA, Patterson R, Krell RD, Bernstein PR (1985) The effect of inhaled leukotriene D4 in humans. Am Rev Respir Dis 131: 368–372PubMedGoogle Scholar
  84. 84.
    Kern R, Smith LJ, Patterson R, Krell RD, Bernstein PR (1986) Characterization of the airway response to inhaled leukotriene D4 in normal subjects. Am Rev Respir Dis 133: 1127–1132PubMedGoogle Scholar
  85. 85.
    O’Hickey SP, Hawksworth RJ, Fong CY, Arm JP, Spur BW, Lee TH (1991) Leukotrienes C4, D4 and E4 enhance histamine responsiveness in asthmatic airways. Am Rev Respir Dis 144: 1053–1057PubMedCrossRefGoogle Scholar
  86. 86.
    Arm JP, O’Hickey SP, Hawksworth RJ, Fong CY, Crea AEG, Spur BW, Lee TH (1990) Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. Am Rev Respir Dis 142: 1112–1118PubMedGoogle Scholar
  87. 87.
    Bel EH, van der Veen H, Kramps JA, Dijkman JH, Sterk PJ (1987) Maximal airway narrowing to inhaled leukotriene D4 in normal subjects: comparison and interaction with methacholine. Am Rev Respir Dis 136: 979–984PubMedCrossRefGoogle Scholar
  88. 88.
    Higgins DA, O’Byrne PM (1987) Inhaled leukotriene D4 does not cause a late response in atopic subjects. J Allergy Clin Immunol 79: 141 (Abstract)Google Scholar
  89. 89.
    Wang CG, Du T, Xu LJ, Martin JG (1993) Role of leukotriene D4 in allergen-induced increases in airway smooth muscle in the rat. Am Rev Respir Dis 148: 413–417PubMedCrossRefGoogle Scholar
  90. 90.
    Kurosawa M, Yodonawa S, Tsukagoshi H, Miyachi Y (1994) Inhibition by a novel peptide leukotriene receptor antagonist ONO-1078 of airway wall thickening and airway hyperresponsiveness to histamine induced by leukotriene C4 or leukotriene D4 in guinea-pigs. Clin Exp Allergy 24: 960–968PubMedCrossRefGoogle Scholar
  91. 91.
    Cohen P, Noveral JP, Bhala A, Nunn SE, Herrick DJ, Grunstein MM (1995) Leukotriene D4 facilitates airway smooth muscle cell proliferation via modulation of the IGF axis. Am J Physiol 269: L151–L157PubMedGoogle Scholar
  92. 92.
    Laitinen LA, Laitinen A (1994) Structural and cellular changes in asthma. Eur Respir Rev 4: 348–351Google Scholar
  93. 93.
    Lambert RK, Wiggs BR, Kuwano K, Hogg JC, Pare PD (1993) Functional significance of increased airway smooth muscle in asthma and COPD. J Appl Physiol 74: 2771–2781PubMedCrossRefGoogle Scholar
  94. 94.
    Sampson SE, Costello JF, Sampson AP (1997) The effect of inhaled leukotriene B4 in normal and in asthmatic subjects. Am J Respir Crit Care Med 155: 1789–1792PubMedGoogle Scholar
  95. 95.
    Kuitert L, Barnes NC (1995) PAF and asthma — time for an appraisal? Clin Exp Allergy 25: 1159–1162PubMedCrossRefGoogle Scholar
  96. 96.
    Koh YY, Dupuis R, Pollice M, Albertine KH, Fish JE, Peters SP (1993) Neutrophils recruited to the lungs of humans by segmental antigen challenge display a reduced chemotactic response to leukotriene B4. Am J Respir Cell Mol Biol 8: 493–499PubMedGoogle Scholar
  97. 97.
    Kim CJ, Kane GC, Zangrilli JG, Cho SK, Koh YY, Peters SP (1994) Eosinophils recruited to the lung by segmental antigen challenge show a reduced chemotactic response to leukotriene B4. Prostaglandins 47: 393–403PubMedCrossRefGoogle Scholar
  98. 98.
    Powell WS (1982) Rapid extraction of arachidonic acid metabolites from biological samples using octadecylsilyl silica. Methods Enzymol 86: 467–477PubMedCrossRefGoogle Scholar
  99. 99.
    Sehmi R, Wardlaw AJ, Cromwell O, Kurihara K, Waltmann P, Kay AB (1992) Interleukin-5 selectively enhances the chemotactic response of eosinophils obtained from normal but not eosinophilic subjects. Blood 79: 2952–2959PubMedGoogle Scholar
  100. 100.
    Richards IM, Griffin RL, Oostveen JA, Morris J, Whishka DG, Dunn CJ (1989) Effect of the selective leukotriene B4 antagonist U-75302 on antigen-induced bronchopulmonary eosinophilia in sensitized guinea pigs. Am Rev Respir Dis 140: 1712–1716PubMedCrossRefGoogle Scholar
  101. 101.
    Evans DJ, Barnes PJ, Spaethe SM, van Alstyne EL, Mitchell MI, O’Connor BJ (1996) Effect of a leukotriene B4 receptor antagonist, LY-293, 111, on allergen induced responses in asthma. Thorax 51: 1178–1184PubMedCrossRefGoogle Scholar
  102. 102.
    Rossi GA, Crimi E, Lantero S, Gianiorio P, Oddera S, Crimi P, Brusasco V (1991) Late-phase asthmatic reaction to inhaled allergen is associated with early recruitment of eosinophils in the airways. Am Rev Respir Dis 144: 379–383PubMedCrossRefGoogle Scholar
  103. 103.
    Christie PE, Barnes NC (1996) Leukotriene B4 and asthma. Thorax 51: 1171–1173PubMedCrossRefGoogle Scholar
  104. 104.
    Sur S, Crotty TB, Kephart GM, Hyma BA, Colby TV, Reed CE, Hunt LW, Gleich GJ (1993) Sudden-onset fatal asthma: a distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis 148: 713–719PubMedCrossRefGoogle Scholar
  105. 105.
    Wenzel SE, Trudeau JB, Westcott JY, Beam WR, Martin RJ (1994) Single oral dose of prednisone decreases leukotriene B4 production by alveolar macrophages from patients with nocturnal asthma but not control subjects: relationship to changes in cellular influx and FEV1. J Allergy Clin Immunol 94: 870–881PubMedCrossRefGoogle Scholar
  106. 106.
    Holroyde MC, Altounyan RE, Cole M, Dixon M, Elliott EV (1982) Selective inhibition of bronchoconstriction induced by leukotrienes C and D in man. Adv Prostaglandin Thromhoxane Leukot Res 9: 237–242Google Scholar
  107. 107.
    Jones TR, Guindon Y, Young R, Champion E, Charette L, Denis D, Ethier D, Hamel R, Ford-Hutchinson AW, Fortin R et al (1986) L-648, 051, sodium 4-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-propylsylfonyl]-τ-oxo-benzenebutanoate: a leukotriene D4 receptor antagonist. Can J Physiol Pharmacol 64: 1535–1542PubMedCrossRefGoogle Scholar
  108. 108.
    Barnes NC, Piper PJ, Costello J (1987) The effect of an oral leukotriene antagonist L-649,923 on histamine and leukotriene D4-induced bronchoconstriction in normal man. J Allergy Clin Immunol 79: 816–821PubMedCrossRefGoogle Scholar
  109. 109.
    Phillips GD, Rafferty P, Robinson C, Holgate ST (1988) Dose-related antagonism of leukotriene D4-induced bronchoconstriction by p.o. administration of LY-171883 in nonasthmatic subjects. J Pharmacol Exp Ther 246: 732–738PubMedGoogle Scholar
  110. 110.
    Wood-Baker R, Phillips GD, Lucas RA, Turner GA, Holgate ST (1991) The effect of inhaled LY-170680 on leukotriene D4-induced bronchoconstriction in healthy volunteers. Drug Invest 3: 239–247CrossRefGoogle Scholar
  111. 111.
    Wahedna I, Wisniewski AS, Tattersfield AE (1991) Effect of RG 12525, an oral leukotriene D4 antagonist, on the airway response to inhaled leukotriene D4 in subjects with mild asthma. Br J Clin Pharmacol 32: 512–515PubMedCrossRefGoogle Scholar
  112. 112.
    Joos GF, Kips J C, Pauwels RA, Van der Straeten ME (1991) The effect of aerosolized SK&F 104353-Z2 on the bronchoconstrictor effect of leukotriene D4 in asthmatics. Pulmon Pharmacol 4: 37–42CrossRefGoogle Scholar
  113. 113.
    Gaddy JN, Margolskee DJ, Bush RK, Williams VC, Busse WW (1992) Bronchodilation with a potent and selective leukotriene D4 (LTD4) receptor antagonist (MK-571) in patients with asthma. Am Rev Respir Dis 146: 358–363PubMedGoogle Scholar
  114. 114.
    Lammers J-WJ, Van Daele P, Van den Elshout FMJ, Decramer M, Buntinx A, De Lepeleire I, Friedman B (1992) Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast, MK-0679) in asthmatic patients. Pulmon Pharmacol 5: 121–125CrossRefGoogle Scholar
  115. 115.
    Dahlen B, Kumlin M, Margolskee DJ, Larsson C, Blomqvist H, Williams VC, Zetterstrom O, Dahlen SE (1993) The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. Eur Respir J 6: 1018–1026PubMedGoogle Scholar
  116. 116.
    Adelroth E, Inman MD, Summers E, Pace D, Modi M, O’Byrne PM (1997) Prolonged protection against excercise-induced bronchoconstriction by the leukotriene D4 receptor antagonist cinalukast. J Allergy Clin Immunol 99: 210–215PubMedCrossRefGoogle Scholar
  117. 117.
    Calhoun WJ, Williams KL, Simonson SG, Lavins BJ (1997) Effect of zafirlukast (Accolate) on airway inflammation after segmental allergen challenge in patients with mild asthma. Am J Respir Crit Care Med 155: A662Google Scholar
  118. 118.
    Tamaoki J, Kondo M, Tagaya E, Takemura H, Nagai A, Takizawa T, Konno K (1997) Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. Am J Respir Crit Care Med 155: 1235–1240PubMedGoogle Scholar
  119. 119.
    Micheletto C, Turco P, Dal Negro R (1997) Accolate 20 mg works as steroid sparing in moderate asthma. Am J Respir Crit Care Med 155: A664 (Abstract)Google Scholar
  120. 120.
    Leff JA, Israel E, Noonan MJ, Finn AF, Godard P, Lofdahl CG, Friedman BS, Connors L, Weinland DE, Reiss TF et al (1997) Montelukast (MK-0476) allows tapering of inhaled corticosteroids (ICS) in asthmatic patients while maintaining clinical stability. Am J Respir Crit Care Med 155: A976Google Scholar
  121. 121.
    Fujimura M, Sakamoto S, Kamio Y, Matsuda T (1993) Effect of a leukotriene antagonist, ONO-1078, on bronchial hyperresponsiveness in patients with asthma. Respir Med 87: 133–138PubMedCrossRefGoogle Scholar
  122. 122.
    Margolskee DJ (1991) Clinical experience with MK-571, a potent and specific LTD4 receptor antagonist. Ann NY Acad Sci 629: 148–156PubMedCrossRefGoogle Scholar
  123. 123.
    Spector SL, Smith LJ, Glass M (1994) Effects of 6 weeks of therapy with oral doses of ICI204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J Respir Crit Care Med 150: 618–623PubMedGoogle Scholar
  124. 124.
    Reiss TF, Altman LC, Chervinsky P, Bewtra A, Stricker WE, Noonan GP, Kundu S, Zhang J (1996) Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma. J Allergy Clin Immunol 98: 528–534PubMedCrossRefGoogle Scholar
  125. 125.
    Barnes NC, Pujet J-C (1997) Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo-controlled, multicentre clinical study in asthma. Thorax 52: 523–527PubMedCrossRefGoogle Scholar
  126. 126.
    Grootendorst DC, Diamant Z, Veselic M, Hiemstra PS, DeSmet M, Leff JA, Peszek I, Sterk PJ (1997) Effect of oral montelukast, a cysLT1-receptor antagonist, on eosinophil counts and ECP in induced sputum before and after allergen challenge in asthmatics. Am J Respir Crit Care Med 155: A976Google Scholar
  127. 127.
    Leff JA, Pizzichini E, Efthimiadis A, Boulet LP, Wei LX, Weinland DE, Hendeles L, Hargreave FE (1997) Effect of montelukast (MK-0476) on airway eosinophilic inflammation in mildly uncontrolled asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med 155: A977Google Scholar
  128. 128.
    Taki F, Suzuki R, Torii K, Matsumoto S, Taniguchi H, Takagi K (1994) Reduction of the severity of bronchial hyperresponsiveness by the novel leukotriene antagonist 4-oxo-8-[4-(4-phenyl-butoxy)benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate. Arzneimittelforschung 44: 330–333PubMedGoogle Scholar
  129. 129.
    Rosenthal RR, Lavins BJ, Hanby LA (1996) Effect of treatment with zafirlukast (‘Accolate’) on bronchial hyperresponsiveness in patients with mild-to-moderate asthma. J Allergy Clin Immunol 97: 250Google Scholar
  130. 130.
    McGill KA, Busse WW (1996) Zileuton. Lancet 348: 519–524PubMedCrossRefGoogle Scholar
  131. 131.
    Storms W, Friedman BS, Zhang J, Santanello N, Allegar N, Appel D, Beaucher W, Bronsky F, Busse W, Chervinsky P et al (1995) Treating asthma by blocking the lipoxygenase pathway. Am J Respir Crit Care Med 151: A377Google Scholar
  132. 132.
    Virchow JC, Noller PS, Wiessmann KJ, Buhl R, Thalhofer S, Dorow G, Kunkel G, Ukena D, Ulbrich E, Sybrecht G, Matthys H (1995) Multicenter trial of BAY-x1005, a new 5-lipoxygenase activating protein (FLAP) inhibitor in the treatment of chronic asthma. Am J Respir Crit Care Med 151: A377Google Scholar
  133. 133.
    Liu MC, Dubé LM, Lancaster J, Zileuton Study Group (1996) Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. J Allergy Clin Immunol 98: 859–871PubMedCrossRefGoogle Scholar
  134. 134.
    Israel E, Cohn J, Dube L, Drazen J (1996) Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma: a randomized controlled trial. JAMA 275: 931–936PubMedCrossRefGoogle Scholar
  135. 135.
    Dahlén S-E, Nizankowska E, Dahlén B, Bochenek G, Kumlin M, Mastalerz L, Blomqvist H, Pinis G, Rasberg B, Swanson LJ et al (1995) The Swedish-Polish treatment study with the 5-lipoxygenase inhibitor zileuton in aspirin-intolerant asthmatics. Am J Respir Crit Care Med 151: A376Google Scholar
  136. 136.
    Fischer AR, McFadden CA, Frantz R, Awni WM, Cohn J, Drazen JM, Israel E (1995) Effect of chronic 5-lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects. Am J Respir Crit Care Med 152: 1203–1207PubMedGoogle Scholar
  137. 137.
    Dekhuijzen PNR, Bootsma GP, Wielders PLML, Van den Berg LRM, Festen J, Van Meerwaarden CLA (1997) Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids. Eur Respir J 10: 2749–2753PubMedCrossRefGoogle Scholar
  138. 138.
    Kane GC, Pollice M, Kim C-J, Cohn J, Dworski RT, Murray JJ, Sheller JR, Fish JE, Peters SP (1996) A controlled trial of the effect of the 5-lipoxygenase inhibitor, zileuton, on lung inflammation produced by segmental antigen challenge in human beings. J Allergy Clin Immunol 97: 646–654PubMedCrossRefGoogle Scholar
  139. 139.
    Wenzel SE, Trudeau JB, Kaminsky DA, Cohn J, Martin RJ, Westcott JY (1995) Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. Am J Respir Crit Care Med 152: 897–905PubMedGoogle Scholar
  140. 140.
    Spector SL (1996) Management of asthma with zafirlukast: clinical experience and tolerability profile. Drugs 52 Suppl 6: 36–46PubMedCrossRefGoogle Scholar
  141. 141.
    British Thoracic Society, Research Unit of the Royal College of Physicians of London, King’s Fund Centre and National Asthma Campaign (1990) Guidelines for the management of asthma in adults — I. Chronic persistent asthma. Br Med J 301: 651–653CrossRefGoogle Scholar
  142. 142.
    Drazen JM, Israel E (1991) Asthma: a solution of half the puzzle? Am Rev Respir Dis 144: 743–744PubMedCrossRefGoogle Scholar
  143. 143.
    Ikeda K, Hyashi M, Obata H, Fujita H, Nakanishi T, Izumi T (1997) Two weeks’ observation of pranlukast (ONO-1078, leukotriene receptor antagonist) by peak expiratory flow rate (PEFR) was enough to evaluate clinical efficacies in severe chronic adult asthmatics. Am J Respir Crit Care Med 155: A664Google Scholar
  144. 144.
    In K, Asano K, Beler D, Grobholz J, Finn PW, Solverman EK, Silverman ES, Collins T, Fischer AR, Keith TP et al (1997) Naturally-ocurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest 99: 1130–1137PubMedCrossRefGoogle Scholar
  145. 145.
    Sampson AP, Corne J, Holgate ST (1997) Will the advent of anti-leukotriene therapy lead to changes in asthma treatment guidelines? BioDrugs 7: 167–173PubMedCrossRefGoogle Scholar
  146. 146.
    Israel E, Fischer AR, Rosenberg MA, Lilly CM, Callery JC, Shapiro J, Cohn J, Rubin P, Drazen JM (1993) The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin. Am Rev Respir Dis 148: 1447–1451PubMedCrossRefGoogle Scholar
  147. 147.
    O’Byrne PM, Israel E, Drazen JM (1997) Antileukotrienes in the treatment of asthma. Ann Intern Med 127: 472–480PubMedGoogle Scholar
  148. 148.
    Robuschi M, Riva E, Fuccella LM, Vida E, Barnabe R, Rossi M, Gambaro G, Spagnotto S, Bianco S (1992) Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104,353). Am Rev Respir Dis 145: 1285–1288PubMedGoogle Scholar
  149. 149.
    Hofstra WB, Sterk PJ, Neijens HJ, Van der Weij AM, Van Zoest JGCM, Duiverman EJ (1997) Two weeks treatment with zafirlukast (Accolate™), sodium cromoglycate or placebo on exercise-induced bronchoconstriction in asthmatic adolescents. Am J Respir Crit Care Med 155: A665Google Scholar
  150. 150.
    Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, Becker A (1998) Montelukast for chronic asthma in 6-to 14-year-old children: a randomized, double-blind trial. JAMA 279: 1181–1186PubMedCrossRefGoogle Scholar
  151. 151.
    Taylor IK, O’Shaughnessy KM, Fuller RW, Dollery CT (1991) Effect of cysteinyl-leukotriene receptor antagonist ICI 204,219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects. Lancet 337: 690–694PubMedCrossRefGoogle Scholar
  152. 152.
    Makker HK, Lau LC, Thomson FIW, Binks SM, Holgate ST (1993) The protective effect of inhaled leukotriene D4 receptor antagonist ICI 204,219 against exercise-induced asthma. Am Rev Respir Dis 147: 1413–1418PubMedGoogle Scholar
  153. 153.
    Finnerty JP, Wood-Baker R, Thomson H, Holgate ST (1992) Role of leukotrienes in exercise-induced asthma. Am Rev Respir Dis 145: 746–749PubMedGoogle Scholar
  154. 154.
    Rasmussen JB, Eriksson L-O, Margolskee DJ, Tagari P, Williams VC, Andersson K-E (1992) Leukotriene D4 receptor blockade inhibits the immediate and late bronchoconstrictor responses to inhaled antigen in patients with asthma. J Allergy Clin Immunol 90: 193–201PubMedCrossRefGoogle Scholar
  155. 155.
    Manning PJ, Watson RM, Margolskee DJ, Williams VC, Schwartz JI, O’Byrne PM (1990) Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med 323: 1736–1739PubMedCrossRefGoogle Scholar
  156. 156.
    Diamant Z, Grootendorst DC, Veselic-Charvat M, Timmers MC, De Smet M, Leff JA, Seidenberg BC, Zwinderman AM, Peszek I, Sterk PJ (1999) The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy 29: 42–51PubMedCrossRefGoogle Scholar
  157. 157.
    Reiss TF, Bronsky E, Hendeles L, Hill J, Harman E, Guerreiro D, Zhang J (1995) MK-0476, a potent leukotriene (LT)D4 receptor antagonist, inhibits exercise induced bronchocontriction in asthmatics at the end of a once daily dosing interval. Am J Respir Crit Care Med 151: A377Google Scholar
  158. 158.
    Christie PE, Smith CM, Lee TH (1991) The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma. Am Rev Respir Dis 144: 957–958PubMedCrossRefGoogle Scholar
  159. 159.
    Yamamoto H, Nagata M, Kuramitsu K, Tabe K, Kiuchi H, Sakamoto Y, Yamamoto K, Dohi Y (1994) Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078. Am J Respir Crit Care Med 150: 254–257PubMedGoogle Scholar
  160. 160.
    Suguro H, Majima T, Ichimura K, Hashimoto N, Koyama S, Horie T (1997) Effect of a leukotriene antagonist, pranlukast hydrate, on exercise-induced bronchoconstriction. Am J Respir Crit Care Med 155: A662Google Scholar
  161. 161.
    Israel E, Dermarkarian R, Rosenberg M, Sperling R, Taylor G, Rubin P, Drazen J (1990) The effects of 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med 323: 1740–1744PubMedCrossRefGoogle Scholar
  162. 162.
    Meltzer SS, Hasday JD, Cohn J, Bleecker ER (1996) Inhibition of exercise-induced bronchospasm by zileuton: a 5-lipoxygenase inhibitor. Am J Respir Crit Care Med 153: 931–935PubMedGoogle Scholar
  163. 163.
    Nasser SMS, Bell GS, Foster S, Spruce KE, MacMillan R, Williams AJ, Lee TH, Arm JP (1994) Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma. Thorax 49: 749–756PubMedCrossRefGoogle Scholar
  164. 164.
    Friedman BS, Bel EH, Buntinx A, Tanaka W, Han Y-HR, Shingo S, Spector R, Sterk P (1993) Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses. Am Rev Respir Dis 147: 839–844PubMedGoogle Scholar
  165. 165.
    Diamant Z, Timmers MC, Van der Veen H, Friedman BS, De Smet M, Depre M, Hilliard D, Bel EH, Sterk PJ (1995) The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergen-induced subjects in vivo. J Allergy Clin Immunol 95: 42–51PubMedCrossRefGoogle Scholar
  166. 166.
    Hamilton AL, Watson RM, Wyile G, O’Byrne PM (1997) Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating protein antagonist, BAYx1005. Thorax 52: 348–354PubMedCrossRefGoogle Scholar
  167. 167.
    Margolskee D, Bodman S, Dockhorn R, Israel E, Kemp J, Mansmann H, Minotti DA, Spector S, Stricker W, Tinkelman D, Townley R, Winder J, Williams V (1991) The therapeutic effects of MK-571, a potent and selective leukotriene (LT) D4 receptor antagonist, in patients with chronic asthma. J Allergy Clin Immunol 87: 309CrossRefGoogle Scholar
  168. 168.
    Suzuki N, Kudo K, Sano Y, Adachi M, Kanazawa M, Kudo S, Horie T, Kobayashi H, Konno K, Itoh K, Miyamoto T (1997) Efficacy of oral pranlukast, a leukotriene receptor antagonist, in the treatment of asthma: an open study in Tokyo. Am J Respir Crit Care Med 155: A664Google Scholar
  169. 169.
    Sahn S, Galant S, Murray J, Bronsky E, Spector S, Faiferman I, Stober P et al (1997) Pranlukast (UltairTM) improves FEV1 in patients with asthma: results of a 12-week multicenter study vs nedocromil. Am J Respir Crit Care Med 155: A665Google Scholar
  170. 170.
    Reiss TF, Altman LC, Chervinsky P, Bewtra A, Stricker WE, Noonan GP et al (1996) Effects of montelukast (MK-0476), a new potent leukotriene (LTD4) receptor antagonist, in patients with chronic asthma. J Allergy Clin Immunol 98: 528–534PubMedCrossRefGoogle Scholar
  171. 171.
    Reiss TF, Chervinsky P, Edwards T, Dockhorn R, Nayak A, Hess J, Zhang J, Shingo S et al (1997) Montelukast (MK-0476), a CysLY1 receptor antagonist, improves asthma outcomes over a 3-month treatment period. Am J Respir Crit Care Med 155: A662Google Scholar
  172. 172.
    Israel E, Cohn J, Dube L, Drazen JM (1996) Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. JAMA 275: 931–936PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 1999

Authors and Affiliations

  • Zuzana Diamant
    • 1
  • Anthony P. Sampson
    • 2
  1. 1.Department of Respiratory DiseasesErasmus University Medical Centre RotterdamRotterdamThe Netherlands
  2. 2.Immunopharmacology Group, Level F, Centre Block (825)Southampton General HospitalSouthamptonUK

Personalised recommendations