Drugs

, Volume 59, Supplement 1, pp 29–34 | Cite as

Clinical Evidence with Montelukast in the Management of Chronic Childhood Asthma

  • Allan Becker
Original Research Article

Abstract

Objective: The aim of this article is to review data on the efficacy and safety of montelukast in the treatment of children with asthma.

Methodology: Available published literature, including published abstracts, is reviewed.

Results: In patients aged 6 to 14 years with asthma (n = 27), montelukast 5mg demonstrated a significant decrease in exercise-induced bronchoconstriction 20 to 24 hours postdose after 2 days of treatment. For children with chronic asthma, only one study of the regular use of a leukotriene receptor antagonist has been published. The efficacy and safety of montelukast in children aged 6 to 14 years with asthma (n = 336) were studied during an 8-week, double-blind, placebo-controlled trial. There was a significantly greater improvement in forced expiratory volume in 1 second (FEV1) from baseline for the montelukast group (8.23%) compared with the placebo group (3.58%). There was a significant decrease in the use of a β-agonist for symptom relief, as well as in the percentage of days and percentage of patients with asthma exacerbations. An asthma specific quality-of-life (QOL) questionnaire revealed a significant overall improvement in QOL and a significant improvement in the QOL domains for symptoms, activity and emotions in montelukast recipients. There was no significant difference between montelukast and placebo recipients in the frequency of adverse events, with the exception of allergic rhinitis, which was more prevalent in the placebo group. An open label follow-up of patients from the above study was undertaken. The effect of montelukast on FEV1 was consistent for up to 1.4 years, with the increase in FEV1 being not significantly different from that in a small control group treated with inhaled beclomethasone dipropionate. QOL remained significantly improved during the open treatment period.

Conclusions: Montelukast appears effective and safe for the treatment of children with asthma.

Keywords

Asthma Salmeterol Allergy Clin Immunol Montelukast Sodium Cromoglycate 

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References

  1. 1.
    Kellaway CH, Trethewie ER. The liberation of a slow-reacting smooth muscle-stimulating substance in anaphylaxis. Q J Exp Physiol 1940; 30: 121–45Google Scholar
  2. 2.
    Brocklehurst W. The release of histamine and formation of a slow reacting substance (SRS-A) during anaphylactic shock. J Physiol 1960; 151: 416–35PubMedGoogle Scholar
  3. 3.
    Kaiser E, Chiba P, Zaky K. Phospholipases in biology and medicine. Clin Biochem 1990; 20: 217–23Google Scholar
  4. 4.
    Griffin M, Weiss JW, Leitch AG, et al. Effects of leukotriene D on the airways in asthma. N Engl J Med 1983; 308: 436–9PubMedCrossRefGoogle Scholar
  5. 5.
    Marom Z, Shekhamer JH, Bach MK, et al. Slow-reacting substances leukotrienes C4 and D4 increase the release of mucus from human airways in vitro. Am Rev Respir Dis 1982; 126: 449–51PubMedGoogle Scholar
  6. 6.
    Peck MJ, Piper PJ, Williams TJ. The effect of leukotrienes C4 and D4 on the microvasculation of guinea pig skin. Prostaglandins 1981; 21: 315–21PubMedCrossRefGoogle Scholar
  7. 7.
    Rajah R, Nunn SE, Herrick DJ, et al. Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells. Am J Physiol 271 (Lung Cell Mol Physiol 15): L1014-22Google Scholar
  8. 8.
    Taylor GM, Taylor I, Black P, et al. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet 1989; 1: 584–8PubMedCrossRefGoogle Scholar
  9. 9.
    Manning PJ, Rokach J, Malo JL, et al. Urinary leukotriene E4 levels during early and late asthmatic responses. J Allergy Clin Immunol 1990; 86: 211–20PubMedCrossRefGoogle Scholar
  10. 10.
    Manning PJ, Watson RM, Margolskee DJ, et al. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med 1990; 323: 1736–9PubMedCrossRefGoogle Scholar
  11. 11.
    Kikawa Y, Miyanomae T, Inoue Y, et al. Urinary leukotriene E4 after exercise challenge in children with asthma. J Allergy Clin Immunol 1992; 89: 1111–9PubMedCrossRefGoogle Scholar
  12. 12.
    Sampson AP, Castling DP, Green CP, et al. Persistent increase in plasma and urinary leukotrienes after acute asthma. Arch Dis Child 1995; 73: 221–5PubMedCrossRefGoogle Scholar
  13. 13.
    Smith LJ, Geller J, Elbright L, et al. Inhibition of leukotriene D4-induced bronchoconstriction in normal subjects by the oral./D4 receptor antagonists ICI 204, 219. Am Rev Respir Dis 1990; 141: 988–92PubMedCrossRefGoogle Scholar
  14. 14.
    Wahedna I, Wisniewski AS, Tattersfield AE. 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 1991; 32: 512PubMedCrossRefGoogle Scholar
  15. 15.
    Dahlén B, Kumlin M, Margolskee DJ, et al. The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. Eur Respir J 1993; 6: 1018–26PubMedGoogle Scholar
  16. 16.
    Dahlén B, Zetterström O, Björck T, et al. The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics. Eur Respir J 1994; 7: 324–31PubMedCrossRefGoogle Scholar
  17. 17.
    Diamant Z, Timmers MC, van der Veen H, et al. The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergen-induced airway responses in asthmatic subjects in vivo. J Allergy Clin Immunol 1995; 95 (1 Pt 1): 42–51PubMedCrossRefGoogle Scholar
  18. 18.
    Anderson SD. Is there a unifying hypothesis for exercise-induced asthma? J Allergy Clin Immunol 1984; 73: 660–5PubMedCrossRefGoogle Scholar
  19. 19.
    McFadden Jr ER. Exercise-induced airway obstruction. Clin Chest Med 1995; 16: 671–82PubMedGoogle Scholar
  20. 20.
    Randolph C. Exercise-induced asthma: update on pathophysiology, clinical diagnosis and treatment. Curr Probl Pediatr 1997; 27: 53–77PubMedGoogle Scholar
  21. 21.
    Manning PJ, Watson RM, Margolskee DJ, et al. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med 1990; 232: 1736–9CrossRefGoogle Scholar
  22. 22.
    Makker HK, Lau LC, Thomson HW, et al. The protective effect of inhaled leukotriene D4 receptor antagonist ICI 204,219 against exercise-induced asthma. Am Rev Respir Dis 1993; 147: 1413–8PubMedGoogle Scholar
  23. 23.
    Kemp JP, Dockhorn RJ, Shapiro GG, et al. Montelukast, once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr 1998; 133(3): 424–8PubMedCrossRefGoogle Scholar
  24. 24.
    de Benedictis FM, Tuteri G, Pazzelli P, et al. Cromolyn versus nedocromil: duration of action in exercise-induced asthma in children. J Allergy Clin Immunol 1995; 96: 510–4PubMedCrossRefGoogle Scholar
  25. 25.
    Berkowitz R, Schwartz E, Bukstein MD, et al. Albuterol protects against exercise-induced asthma longer than metaproterenol sulfate. Pediatrics 1986; 77(2): 173–8PubMedGoogle Scholar
  26. 26.
    Green CP, Price JF. Prevention of exercise induced asthma by inhaled salmeterol xinafoate. Arch Dis Child 1992; 67: 1014–7PubMedCrossRefGoogle Scholar
  27. 27.
    Simons FER, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 1997; 99(5): 655–9PubMedCrossRefGoogle Scholar
  28. 28.
    Leff JA, Busse WW, Pearlman D, et al. Montelukast, a leukotriene receptor antagonist, for treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med 1998; 339: 147–52PubMedCrossRefGoogle Scholar
  29. 29.
    Turpin JA, Edelman JM, DeLucca PT, et al. Chronic administration of montelukast (MK-476) is superior to inhaled salmeterol in the prevention of exercise-induced bronchoconstriction (EIB) Am J Respir Crit Care Med 1998; 157: A456Google Scholar
  30. 30.
    Villaran C, O'Neill S, Helbling A, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. J Allergy Clin Immunol 1999; 104 (3 Pt 1): 547–53PubMedCrossRefGoogle Scholar
  31. 31.
    Edelman JM, Turpin JA, DeLucca PT. The Exercise Study Group; Merck & Co., Inc., Horsham, PA, United States. Comparison of oral montelukast, a leukotriene antagonist and inhaled salmeterol in exercise induced asthma (EIA). Eur Respir J 1998; 12: 18sGoogle Scholar
  32. 32.
    Knorr B, Matz J, Bernstein J, et al. Montelukast for chronic asthma in 6- to 14-year-old children. JAMA 1998; 279(15); 1181–6PubMedCrossRefGoogle Scholar
  33. 33.
    Juniper EF, Guyatt GH, Feeny D, et al. Measuring the quality of life in children with asthma. Qual Life Res 1996; 5: 35–46PubMedCrossRefGoogle Scholar
  34. 34.
    Pizzichini E, Leff JA, Reiss TF, et al. Montelukast reduces airway inflammation in asthma: a randomized controlled trial. Eur Resp J 1999; 14: 12–8CrossRefGoogle Scholar
  35. 35.
    Seidenberg BC, Reiss TF. Montelukast — an antileukotriene treatment for asthma. In: Drazen JM, Dahlèn SE, Lee TH, editors. Five-lipoxygenase products in asthma. New York, NY: Marcel Dekker Inc., 1998: 327–46Google Scholar
  36. 36.
    Noonan G, Reiss TF, Shingo S, et al. Montelukast (MK-0476) maintains long-term asthma control in adults and pediatric patients (aged ≥6 years). Am J Respir Crit Care Med 1999; 159: A640Google Scholar
  37. 37.
    Knorr BA, Matz J, Sveum RJ, et al. Montelukast (MK-0476) improves asthma over 6 months of treatment in 6- to 14-year-old patients. Eur Respir J 1997; 10: 219SCrossRefGoogle Scholar
  38. 38.
    Edelman JM, Preston SR, Turpin JA, et al. Parent and child preference for montelukast, a leukotriene receptor antagonist, compared to inhaled cromolyn in asthmatic children ages 6 to 11. Eur Respir J 1998; 12: 18sGoogle Scholar
  39. 39.
    Edelman JM, Milewski KA, Turpin JA, et al. Effectiveness and safety of montelukast, a leukotriene receptor antagonist, compared to inhaled cromolyn in moderate asthmatic children ages 6 to 11. J Allergy Clin Immunol 1999; 103: S134Google Scholar
  40. 40.
    Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. Ann Intern Med 1999; 130(6); 487–95PubMedGoogle Scholar
  41. 41.
    Tamaoki J, Kondo M, Sakai N, et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. Am J Crit Care Med 1997; 155: 1235–40Google Scholar
  42. 42.
    Lofdahl GG, Reiss TF, Leff JA, et al. Randomised, placebo-controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ 1999; 319: 87–90PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Allan Becker
    • 1
  1. 1.Department of Pediatrics and Child Health Section of Allergy & Clinical Immunology, Department of Pediatrics and Child HealthUniversity of ManitobaWinnipegCanada

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