Respiratory Medicine
Volume 103, Issue 7 , Pages 995-1003 , July 2009

Montelukast and bronchial inflammation in asthma: A randomised, double-blind placebo-controlled trial

  • C.F. Ramsay

      Affiliations

    • Department of Respiratory Medicine, Royal London Hospital, London, UK
    • ,
  • P. Sullivan

      Affiliations

    • Department of Gene Therapy, Imperial College London, Royal Brompton Hospital, London, UK
    • ,
  • M. Gizycki

      Affiliations

    • Department of Gene Therapy, Imperial College London, Royal Brompton Hospital, London, UK
    • ,
  • D. Wang

      Affiliations

    • Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK
    • ,
  • A.S. Swern

      Affiliations

    • Merck Research Laboratories, Rahway, NJ, USA
    • ,
  • N.C. Barnes

      Affiliations

    • Department of Respiratory Medicine, Royal London Hospital, London, UK
    • ,
  • T.F. Reiss

      Affiliations

    • Merck Research Laboratories, Rahway, NJ, USA
    • ,
  • P.K. Jeffery

      Affiliations

    • Department of Gene Therapy, Imperial College London, Royal Brompton Hospital, London, UK
    • Corresponding Author InformationCorresponding author. Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel.: +44 0 207 351 8422; fax: +44 0 207 351 8435.

Received 6 November 2008 ,Accepted 19 January 2009.

References 

  1. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161:1720–1745
  2. Jeffery PK. Remodeling in asthma and chronic obstructive lung disease. Am J Respir Crit Care Med. 2001;164:S28–S38
  3. Jeffery PK, Godfrey RWA, Adelroth E, Nelson F, Rogers A. Johansson S-A. Effects of treatment on airway inflammation and thickening of reticular collagen in asthma: a quantitative light and electron microscopic study. Am Rev Respir Dis. 1992;145:890–899
  4. Bentley AM, Hamid Q, Robinson DS, Schotman E, Meng Q, Assoufi B, et al. Prednisolone treatment in asthma: reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med. 1996;153:551–556
  5. Ward C, Reid DW, Orsida BE, Feltis B, Ryan VA, Johns DP, et al. Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis. Clin Exp Allergy. 2005;35:1565–1571
  6. Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med. 1999;159:1043–1051
  7. Laitinen LA, Laitinen A, Haahtela T, Vilkka V, Spur BW, Lee TH. Leukotriene E4 and granulocytic infiltration into asthmatic airways. Lancet. 1993;341:989–990
  8. Currie GP, McLaughlin K. The expanding role of leukotriene receptor antagonists in chronic asthma. Ann Allergy Asthma Immunol. 2006;97:731–741
  9. Jeffery PK. The roles of leukotrienes and the effects of leukotriene receptor antagonists in the inflammatory response and remodelling of allergic asthma. Clin Exp Allergy Rev. 2001;1:148–153
  10. Holgate ST, Peters-Golden M, Panettieri RA. Henderson WR Jr. Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling. J Allergy Clin Immunol. 2003;111:S18–S34
  11. Wenzel SE. The role of leukotrienes in asthma. Prostaglandins Leukot Essent Fatty Acids. 2003;69:145–155
  12. Henderson WR, Lewis DB, Albert RK, Zhang Y, Lamm WJ, Chiang GK, et al. The importance of leukotrienes in airway inflammation in a mouse model of asthma. J Exp Med. 1996;184:1483–1494
  13. Drazen JM. Anti-leukotrienes as novel anti-inflammatory treatments in asthma. Adv Exp Med Biol. 2002;507:217–221
  14. Figueroa DJ, Breyer RM, Defoe SK, Kargman S, Daugherty BL, Waldburger K, et al. Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am J Resp Crit Care Med. 2001;163:226–233
  15. Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, et al. Nature. 1999;399:789–793
  16. Zhu J, Qiu YS, Figueroa DJ, Bandi V, Galczenski H, Hamada K, et al. Localization and upregulation of cysteinyl leukotriene-1 receptor in asthmatic bronchial mucosa. Am J Respir Cell Mol Biol. 2005;33:531–540
  17. Reiss TF, Chervinsky P, Dockhorn RJ, Shingo S, Seidenberg B, Edwards TB. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Arch Intern Med. 1998;158:1213–1220
  18. Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast Study Group. JAMA. 1998;279:1181–1186
  19. Wenzel SE, Trudeau JB, Kaminsky DA, Cohn J, Martin RJ, Westcott JY. Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. Am J Respir Crit Care Med. 1995;152:897–905
  20. Calhoun WJ, Lavins BJ, Minkwitz MC, Evans R, Gleich GJ, 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
  21. Pizzichini E, Leff JA, Reiss TF, Hendeles L, Boulet L-P, Wei LX, et al. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. Eur Respir J. 1999;14:12–18
  22. Laviolette M, Malmstrom K, Lu S, Chervinsky P, Pujet JC, Peszek I, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Am J Respir Crit Care Med. 1999;160:1862–1868
  23. Krawiec ME, Wenzel SE. Leukotriene inhibitors and non-steroidal therapies in the treatment of asthma. Expert Opin Pharmacother. 2001;2:47–65
  24. Volovitz B, Tabachnik E, Nussinovitch M, Shtaif B, Blau H, Gil-Ad I, et al. 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
  25. Nakamura Y, Hoshino M, Sim JJ, Ishii K, Hosaka 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
  26. Sullivan P, Stephens D, Ansari T, Costello J, Jeffery P. Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies. Eur Respir J. 1998;12:811–815
  27. Lambert D. Zero-inflated Poisson regression, with an application to defects in manufacturing. Technometrics. 1992;34:1–14
  28. Böhning D, Dietz E, Schlattmann P, Mendonca L, Kirchner U. The zero-inflated Poisson model and the decayed, missing and filled teeth index in dental epidemiology. J R Stat Soc Ser A. 1999;162:195–209
  29. Dietz E, Böhning D. On estimation of the Poisson parameter in zero-modified Poisson models. Computl Stat Data Anal. 2000;34:441–459
  30. Trigg CJ, Manolitsas ND, Wang J, Calderón MA, McAulay A, Jordan SE, et al Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med. 1994;150:17–22
  31. Manolitsas ND, Wang J, Devalia JL, Trigg CJ, McAulay AE, Davies RJ. Regular albuterol, nedocromil sodium, and bronchial inflammation in asthma. Am J Respir Crit Care Med. 1995;151:1925–1930
  32. Biernacki WA, Kharitonov SA, Biernacka HM, Barnes PJ. Effect of montelukast on exhaled leukotrienes and quality of life in asthmatic patients. Chest. 2005;128:1958–1963
  33. Diamant Z, Grootendorst DC, Veselic-Charvat M, Timmers M, de Smet M, Leff JA, et al. 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. 1999;29:1–3
  34. Panettieri RA, Tan EM, Ciocca V, Luttmann MA, Leonard TB, Hay DW. Effects of LTD4 on human airway smooth muscle cell proliferation, matrix expression, and contraction in vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists. Am J Respir Cell Mol Biol. 1998;19:453–461
  35. Parameswaran K, Cox G, Radford K, Janssen LJ, Sehmi R. O'Byrne PM. Cysteinyl leukotrienes promote human airway smooth muscle migration. Am J Respir Crit Care Med. 2002;166:738–742
  36. Gizycki MJ, Adelroth E, Rogers AV, O'Byrne PM, Jeffery PK. Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. Am J Respir Cell Mol Biol. 1997;16:664–673
  37. Kelly MM, Chakir J, Vethanayagam D, Boulet LP, Laviolette M, Gauldie J, et al. Montelukast treatment attenuates the increase in myofibroblasts following low-dose allergen challenge. Chest. 2006;130:741–753
  38. Overbeek SE, O'Sullivan S, Leman K, Mulder PGH, Hoogsteden HC, Prins J-B. Effect of montelukast compared with inhaled fluticasone on airway inflammation. Clin Exp Allergy. 2004;34:1388–1394
  39. Henderson WR, Chiang GK, Tien YT, Chi EY. Reversal of allergen-induced airway remodeling by cysLT1 receptor blockade. Am J Respir Crit Care Med. 2006;173:718–728
  40. Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, et al. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med. 1999;160:1001–1008
  41. Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007;62:1043–1049
  42. Richmond I, Booth H, Ward C, Walters EH. Intrasubject variability in the airway inflammation in biopsies in mild to moderate stable asthma. Am J Respir Crit Care Med. 1996;153:899–903
  43. Bentley AM, Menz G, Storz C, Robinson DS, Bradley B, Jeffery PK, et al. Identification of T-lymphocytes, macrophages and activated eosinophils in the bronchial mucosa in intrinsic asthma: relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992;146:500–506
  44. Gamble E, Qiu Y, Wang D, Zhu J, Vignola AM, Kroegel C, et al. Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design. Eur Respir J. 2006;27:293–299
  45. Gamble E, Burns W, Zhu J, Ansari T, De Rose V, Kips J, et al. Variation of CD8+ T-lymphocytes around the bronchial internal perimeter in chronic bronchitis. Eur Respir J. 2003;22:992–995
  46. O'Byrne PM. The demise of anti-IL-5 for asthma or not. Am J Respir Crit Care Med. 2007;176:1059–1060
  47. Jeffery PK, Wenzel SE, Holgate S. Methods for the assessment of endobronchial biopsies in clinical research. Am J Respir Crit Care Med. 2003;168(Suppl. 6P2):S1–17

PII: S0954-6111(09)00035-3

doi: 10.1016/j.rmed.2009.01.019

Respiratory Medicine
Volume 103, Issue 7 , Pages 995-1003 , July 2009

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