Pediatric Drugs

, Volume 14, Issue 5, pp 317–330 | Cite as

Role of Leukotriene Receptor Antagonists in the Management of Pediatric Asthma

An Update
  • Catalina Dumitru
  • Susan M. H. Chan
  • Victor Turcanu
Review Article

Abstract

At present, the main indications for leukotriene receptor antagonists (LTRA) in pediatric asthma are as add-on therapy to inhaled corticosteroids (ICS) and as initial controller therapy in children with mild asthma, especially those who cannot or will not use ICS.

LTRA are also useful for patients who have concomitant rhinitis, and patients with viral-induced wheeze and exercise-induced asthma. It should be noted that the benefits of LTRA therapy have been demonstrated in children as young as 6 months of age and recent clinical trials have further proven the benefits of LTRA in acute asthma exacerbations.

However, considering the important pro-inflammatory effects that leukotrienes (LT) have in experimental models of asthma, it may seem surprising that LTRA treatment outcomes are not better and that in some clinical trials only a minority of patients could be classified as full responders. This could be explained by potential additional LT receptors that are not affected by LTRA. Such receptors could represent new therapeutic targets in asthma.

Furthermore, progress in differentiating between asthma phenotypes that result from different pathogenic mechanisms, some of which may involve LT to a lesser degree, should lead to an improved, personalized use of LTRA for treating asthma.

References

  1. 1.
    National Institutes of Health, National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Institute. Expert panel report 3: guidelines for the diagnosis and management of asthma. No. 07–4051 [online]. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm [Accessed 2012 Jul 24]
  2. 2.
    Van den Akker-van Marle ME, Bruil J, Detmar SB. Evaluation of cost of disease: assessing the burden to society of asthma in children in the European Union. Allergy 2005; 60: 140–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Szefler SJ, Apter A. Advances in pediatric and adult asthma. J Allergy Clin Immunol 2005; 115:470–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Peters-Golden M, Henderson Jr WR, Leukotrienes. N Engl J Med 2007; 357: 1841–54.PubMedCrossRefGoogle Scholar
  5. 5.
    Dahlen SE. Treatment of asthma with antileukotrienes: first line or last resort therapy? Eur J Pharmacol 2006; 533: 40–56.Google Scholar
  6. 6.
    Salvi SS, Krishna MT, Sampson AP, et al. The anti-inflammatory effects of leukotriene-modifying drugs and their use in asthma. Chest 2001; 119: 1533–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Schwab JM, Serhan CN. Lipoxins and new lipid mediators in the resolution of inflammation. Curr Opin Pharmacol 2006; 6: 414–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Kanoaka Y, Boyce JA. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol 2004; 173: 1503–10.Google Scholar
  9. 9.
    Barnes PJ, Chung KF, Page CP. Inflammatory mediators in asthma: an update. Pharmacol Rev 1998; 50: 515–96.PubMedGoogle Scholar
  10. 10.
    Hay DWP, Torphy TJ, Undem RJ. Cysteinyl leukotrienes in asthma: old mediators up to new tricks. Trends Pharmacol Sci 1995; 16: 304–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Dahlen SE, Hedqvist P, Hammarstrom S, et al. Leukotrienes are potent constrictors of human bronchi. Nature 1980; 288: 484–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Weiss JW, Drazen JM, Coles N, et al. Bronchoconstrictor effects of leukotriene C in humans. Science 1982; 216: 196–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Wenzel SE, Szefler SJ, Leung DY, et al. Bronchoscopic evaluation of severe asthma: persistent inflammation associated with high dose glucocorticoids. Am J Resp Crit Care Med 1997; 156: 737–43.PubMedCrossRefGoogle Scholar
  14. 14.
    Capra V. Molecular and functional aspects of human cystenil leukotriene receptors. Pharmacol Res 2004; 50: 1–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Elias J, Lee CG, Zheng T, et al. New insights into the pathogenesis of asthma. J Clin Invest 2003; 111: 291–7.PubMedGoogle Scholar
  16. 16.
    Brightling CE, Bradding P, Symon FA, et al. Mast cell infiltration of airway smooth muscle in asthma. N Engl J Med 2003; 346: 1699–705.CrossRefGoogle Scholar
  17. 17.
    Jeffrey PK, Laitnen A, Venge P. Biopsy markers of airway inflammation and remodelling. Respir Med 2000; 94: S9–15.CrossRefGoogle Scholar
  18. 18.
    Dworsky R, Fitzgerald GA, Oates JA, et al. Effects of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med 1994; 194: 953–9.CrossRefGoogle Scholar
  19. 19.
    Henderson Jr WR, Chiang GK, Tien YT, et al. Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade. Am J Resp Crit Care Med 2006; 173: 718–28.PubMedCrossRefGoogle Scholar
  20. 20.
    Kelly MM, Chakir J, Vethanayagam D, et al. Montelukast treatment attenuates the increase in myofibroblasts following low-dose allergen challenge. Chest 2006; 130: 741–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Zyflo consumer information [online]. Available from URL: http://www.drugs.com/pro/zyflo-cr.html [Accessed 2011 Aug 21]
  22. 22.
    Montuschi P, Sala A, Dahlén S-E, et al. Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug Discov Today 2007; 12:404–12.PubMedCrossRefGoogle Scholar
  23. 23.
    Singulair® paediatric 4mg chewable tablets: summary of product characteristics. Merck Sharp & Dohme Ltd, 2001 Jan [online]. Available from URL: http://www.medicines.org.uk/emc/medicine/21560 [Accessed 2012 Jul 26]
  24. 24.
    US FDA. Follow-up to the March 27, 2008 communication about the ongoing safety review of montelukast (Singulair). 2009 Jan 13 [online]. Available from URL: http://www.fda.gov [Accessed 2011 Nov 11]
  25. 25.
    Busse W, Kraft M. Cysteinyl leukotrienes in allergic inflammation. Chest 2005; 127: 1312–26.PubMedCrossRefGoogle Scholar
  26. 26.
    Storms W. Update on montelukast and its role in the treatment of asthma, allergic rhinitis and exercise-induced bronchoconstrinction. Expert Opinion Pharmacother 2007; 8: 2173–3287.CrossRefGoogle Scholar
  27. 27.
    Knorr B, Nguyen HH, Kearins G, et al. Montelukast dose selection in children ages 2-to 5- years: comparison of population pharmacokinetics between children and adults. J Clin Pharmacol 2001; 41: 612–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Brocks DR, Upward JW, Georgiou P, et al. The single and multiple pharmacokinetics of pranlukast in healthy volunteers. Eur J Clin Pharmacol 1996; 51: 303–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Merck & Co., Inc. Singulair (montelukast sodium): package insert. White house Station (NJ): Merck & Co., Inc., May 2010.Google Scholar
  30. 30.
    Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest 1998; 114: 332–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Montuschi P, Sala A, Dahlén S-E, et al. Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug Discov Today 2007; 12: 404–12.PubMedCrossRefGoogle Scholar
  32. 32.
    Green RH, Pavord ID. Leukotriene antagonists and symptom control in chronic persistent asthma. Lancet 2001; 357: 1991–2.PubMedCrossRefGoogle Scholar
  33. 33.
    Leff JA, Busse WW, Pearlman D, et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med 1998; 339: 147–52.PubMedCrossRefGoogle Scholar
  34. 34.
    Straub DA, Moeller A, Minocchieri S, et al. The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma. Eur Respir J 2005; 25: 289–94.PubMedCrossRefGoogle Scholar
  35. 35.
    Global Initiative for Asthma (GINA) [online]. Available from URL: http://www.ginasthma.org/ [Accessed 2011 Sep 5]
  36. 36.
    Bacharier LB, Boner A, Carlsen KH, et al. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy 2008; 63: 5–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Del Giudice MM, Pezzulo A, Capristo C, et al. Leukotriene modifiers in the treatment of asthma in children. Ther Adv Respir Dis 2009; 3 (5): 245–51.PubMedCrossRefGoogle Scholar
  38. 38.
    The British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: quick reference guide. May 2008, revised May 2011 [online]. Available from URL: http://www.sign.ac.uk/pdf/qrg101.pdf [Accessed 2012 Jul 26]
  39. 39.
    Spahn JD, Covar RA, Jain N, et al. Effect of montelukast on peripheral airflow obstruction in children with asthma. Ann Allergy Asthma Immunol 2006; 96: 541–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Bisgaard H, Zielen S, Garcia-Garcia L, et al. Montelukast reduces asthma exacerbations in 2- to 5-years old children with intermittent asthma. Am J Respir Crit Care Med 2005; 171: 315–22.PubMedCrossRefGoogle Scholar
  41. 41.
    Van Adelsberg J, Moy J, Wei LX, et al. Safety, tolerability, and exploratory efficacy of montelukast in 6- to 24-month-old patients with asthma. Curr Med Res Opin 2005; 21: 971–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001; 108: E48.PubMedCrossRefGoogle Scholar
  43. 43.
    Knorr B, Matz J, Bernstein JA, et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, doubleblind trial. Pediatric Montelukast Study Group. JAMA 1998; 279: 1181–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Wahn U, Dass SB. Review of recent results of montelukast use as a monotherapy in children with mild asthma. Clin Ther 2008; 30: 1026–35.PubMedCrossRefGoogle Scholar
  45. 45.
    Dempsey OJ. Leukotrienes receptor antagonist therapy. Postgrad Med J 2000; 76: 767–73.PubMedCrossRefGoogle Scholar
  46. 46.
    Knorr B, Maganti L, Ramakrishnan R, et al. Pharmacokinetics and safety of montelukast in children aged 3 to 6 months. J Clin Pharmacol 2006; 46:620–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Kearns GL, Lu S, Maganti L, et al. Pharmacokinetics and safety of montelukast oral granules in children 1 to 3 months of age with bronchiolitis. J Clin Pharmacol 2008; 48: 502–11.PubMedCrossRefGoogle Scholar
  48. 48.
    Ducharme FM. Inhaled glucocorticoids versus leukotriene receptor antagonists as single agent asthma treatment: systematic review of current evidence. BMJ 2003; 326: 621.PubMedCrossRefGoogle Scholar
  49. 49.
    Sorkness CA, Lemanske Jr RF, Mauger DT, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol 2007; 119: 64–72.PubMedCrossRefGoogle Scholar
  50. 50.
    Zeiger RS, Szefler SJ, Phillips BR, et al. Response profiles to fluticasone and montelukast in mild-tomoderate persistent childhood asthma. J Allergy Clin Immunol 2006; 117:45–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Szefler SJ, Phillips BR, Martinez FD, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol 2005; 115: 233–42.PubMedCrossRefGoogle Scholar
  52. 52.
    Ostrom NK, Decotiis BA, Lincourt WR, et al. Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma. J Pediatr 2005; 147 (2): 213–20.PubMedCrossRefGoogle Scholar
  53. 53.
    Garcia ML, Wahn U, Gilles L, et al. Montelukast compared with fluticasone, control of asthma among 6 to 14 year old patients with mild asthma: The MOSAIC Study. Pediatrics 2005; 116: 360–9.CrossRefGoogle Scholar
  54. 54.
    Jartti T. Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for pediatric asthma? Eur J Pediatr 2008; 167: 731–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Becker AB, Kuznetsova O, Vermeulen J, et al. Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Ann Allergy Asthma Immunol 2006; 96: 800–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Pedersen S, Agertoft L, Williams-Herman D, et al. Placebo-controlled study of montelukast and budesonide on short-term growth in prepubertal asthmatic children. Pediatr Pulmonol 2007; 42: 838–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Wang L, Hollenbeak CS, Mauger DT, et al. Cost-effectiveness analysis of fluticasone versus montelukast in children with mild-to-moderate persistent asthma in the Pediatric Asthma Controller Trial. J Allergy Clin Immunol 2011; 127(1): 161–6, 166.e1PubMedCrossRefGoogle Scholar
  58. 58.
    Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med 2011; 364 (18): 1695–707.PubMedCrossRefGoogle Scholar
  59. 59.
    Bukstein DA, Luskin AT, Bernstein A. “Real-world” effectiveness of daily controller medicine in children with mild persistent asthma. Ann Allergy Asthma Immunol 2003; 90: 543–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Ducharme FM, Lasserson TJ, Cates CJ. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev 2011; (5): CD003137.Google Scholar
  61. 61.
    Lemanske Jr RF, Mauger DT, Sorkness CA, et al. Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med 2010; 362: 975–85.PubMedCrossRefGoogle Scholar
  62. 62.
    Miraglia del Giudice M, Piacentini GL, Capasso M, et al. Formoterol, montelukast and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide. Respir Med 2007; 101: 1809–13.PubMedCrossRefGoogle Scholar
  63. 63.
    Buchvald F, Bisgaard H. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol vs montelukast in asthmatic children taking regular inhaled budesonide. Ann Allergy Asthma Immunol 2003; 91: 309–13.PubMedCrossRefGoogle Scholar
  64. 64.
    Ducharme FM, Lasserson TJ, Cates CJ. Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev 2006; (4): CD003137.Google Scholar
  65. 65.
    Ringdal N, Eliraz A, Prunizec R, et al. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respir Med 2003; 97: 234–41.PubMedCrossRefGoogle Scholar
  66. 66.
    Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma, exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ 2008; 327: 891–7.CrossRefGoogle Scholar
  67. 67.
    Van den Burgt JA, Busse WW, Martin RJ, et al. Efficacy and safety overview of a new inhaled corticosteroid in asthma. J Allergy Clin Immunol 2000; 106: 1209–26.CrossRefGoogle Scholar
  68. 68.
    Laviolette M, Malmstrom K, Lu S, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Am J Respir Crit Care Med 1999; 160: 1862–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Currie GP, Bates CE, Lee DK, et al. Effects of montelukast on surrogate inflammatory markers in corticosteroid treated patients with asthma. Am J Respir Crit Care Med 2003; 167: 1232–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Strunk RC, Bacharier LB, Phillips BR, et al. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J Allergy Clin Immunol 2008; 122: 1138–44.PubMedCrossRefGoogle Scholar
  71. 71.
    Reiss TF, Hill JB, Harman E, et al. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cystenil leukotriene receptor antagonist. Thorax 1997; 52: 1030–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Sandrini A, Ferreira IM, Gutierrez C, et al. Effects of montelukast on exaled nitric oxide and non-volatile markers of inflammation in mild asthma. Chest 2003; 124: 1334–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Kopriva F, Janostakova A, Jarmila S, et al. Montelukast decreases plasma endothelin-1 and serum eosinophil cationic protein levels in paediatric atopic asthma. Clin Drug Investig 2006; 26: 351–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Strauch E, Moske O, Thomas S. A randomised controlled trial on the effect of montelukast on sputum eosinophil cationic protein in children with corticosteroid-dependent asthma. Pediatr Res 2003; 54: 198–203.PubMedCrossRefGoogle Scholar
  75. 75.
    Borker R, Emmett A, Jhingran P, et al. Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Ann Allergy Asthma Immunol 2005 Aug; 95 (2): 181–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Navarro RP, Parasuraman B. Cost effectiveness of asthma controller therapies: influence of disease severity and other variables. Manag Care Interface 2005; 18 (6): 31–40.PubMedGoogle Scholar
  77. 77.
    Peroni DG, Piacentini GL, Ress M, et al. Time efficacy of a single dose of montelukast on exercise-induced asthma in children. Pediatr Allergy Immunol 2002; 13:434–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Pajaron-Fernandez M, Garcia-Rubia S, Sanchez- Solis M, et al. Montelukast administred in the morning or evening to prevent exercise-induced bron-choconstiction in children. Ped Pulmonol 2006; 41: 222–7.CrossRefGoogle Scholar
  79. 79.
    De Benedictis FM, Miraglia del Giudice M, Forenza N, et al. Lack of tolerance to the protective effect of montelukast in exercise-induced broncho-constriction in children. Eur Respir 2006; J28: 291–5.CrossRefGoogle Scholar
  80. 80.
    Villaran C, O’Neill SJ, Helbling A, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group. J Allergy Clin Immunol 1999; 104: 547–53.PubMedCrossRefGoogle Scholar
  81. 81.
    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: 424–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994; 88: 363–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Melo RE, Sole D, Naspitz CK. Exercise-inducedbronchoconstriction in children: montelukast attenuates the immediate phase and late phase responses. J Allergy Clin Immunol 2003; 111: 301–17.PubMedCrossRefGoogle Scholar
  84. 84.
    Robertson C, Price D, Henry R, et al. Short-course montelukast for intermittent asthma in children. Am J Respir Crit Care Med 2007; 175: 323–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Harmanci K, Bakirtas A, Turktas I, et al. Oral montelukast treatment of preschool-aged children with acute asthma. Ann Allergy Asthma Immunol 2006; 96: 731–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Nelson KA, Smith SR, Trinkaus K, et al. Pilot study of oral montelukast added to standard therapy for acute asthma exacerbations in children aged 6 to 14 years. Pediatr Emerg Care 2008; 24: 21–7.PubMedGoogle Scholar
  87. 87.
    Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol 2008; 122: 1127–35.PubMedCrossRefGoogle Scholar
  88. 88.
    Johnston NW, Mandhane P, Duncan J, et al. Attenuation of the September epidemic of asthma exacerbations in children: a randomised, controlled trial of montelukast added to usual therapy. Pediatrics 2007; 120: 702–12.CrossRefGoogle Scholar
  89. 89.
    Brand P, Baraldi E, Bisgaard H, et al. Definition, assessment ant treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J 2008; 32: 1096–110.PubMedCrossRefGoogle Scholar
  90. 90.
    Heymann PW, Carper HT, Murphy DD, et al. Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 2004; 114: 239–47.PubMedCrossRefGoogle Scholar
  91. 91.
    Montuschi P, Mondino C, Koch P, et al. Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma. Chest 2007; 132: 1876–81.PubMedCrossRefGoogle Scholar
  92. 92.
    Lee TH, Woszczek G, Farooque SP. Leukotriene E4: perspective on the forgotten mediator. J Allergy Clin Immunol 2009; 124 (3): 417–21.PubMedCrossRefGoogle Scholar
  93. 93.
    Christie PE, Tagari P, Ford-Hutchinson AW, et al. Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects. Am Rev Respir Dis 1991 May; 143 (5 Pt 1): 1025–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Schäper C, Noga O, Koch B, et al. Anti-inflammatory properties of monte lukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis. J Investig Allergol Clin Immunol 2011; 21 (1): 51–8.PubMedGoogle Scholar
  95. 95.
    Park JS, Jang AS, Park SW, et al. Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics. Allergy Asthma Immunol Res 2010 Jan; 2 (1): 48–54.PubMedCrossRefGoogle Scholar
  96. 96.
    White A, Ludington E, Mehra P, et al. Effect of leukotriene modifier drugs on the safety of oral aspirin challenges. Ann Allergy Asthma Immunol 2006 Nov; 97 (5): 688–93.PubMedCrossRefGoogle Scholar
  97. 97.
    Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network. Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010 Sep; 126 (3): 466–76.PubMedCrossRefGoogle Scholar
  98. 98.
    Keskin O, Alyamac E, Tuncer A, et al. Do the LTRA work in children with grass pollen-induced allergic rhinitis? Pediatr Allergy Immunol 2006; 17: 259–68.PubMedCrossRefGoogle Scholar
  99. 99.
    Razi C, Bakirtas A, Harmanci K, et al. Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to 14-year-old children with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2006; 97:767–74.PubMedCrossRefGoogle Scholar
  100. 100.
    Chen ST, Lu KH, Sun HL, et al. Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr. Pediatr Allergy Immunol 2006; 17: 49–54.PubMedCrossRefGoogle Scholar
  101. 101.
    Sazonov-Kocevar V, Laforest L, Travier N, et al. Asthma and allergy medication use and costs among pediatric primary care patients on asthma controller therapy. Pediatr Allergy Immunol 2006 Dec; 17 (8): 620–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Szefler SJ, Martin RJ. Lessons learned from variation in response to therapy in clinical trials. J. Allergy Clin Immunol 2010; 125: 285–92.CrossRefGoogle Scholar
  103. 103.
    Montuschi P, Mondino C, Koch P, et al. Effect of a leukotriene receptor antagonist on exhaled leukotriene E4 and prostanoids in asthmatic children. J Allergy Clin Immunol 2006; 118: 347–53.PubMedCrossRefGoogle Scholar
  104. 104.
    Rabinovitch N, Graber NJ, Chinchilli VM, et al. Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in childhood asthma [published erratum appears in J Allergy Clin Immunol 2010; 126: 959–60]. J Allergy Clin Immunol 2010; 126: 545–51.PubMedCrossRefGoogle Scholar
  105. 105.
    Ward C, Pais M, Bish R, et al. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002; 57: 309–16.PubMedCrossRefGoogle Scholar
  106. 106.
    Hoshino M, Takahashi M, Takai Y, et al. ICS decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. J Allergy Clin Immunol 1999; 103: 1054–61.PubMedCrossRefGoogle Scholar
  107. 107.
    Bisgaard H, Hermansen MN, Loland L, et al. Intermittent ICS in infants with episodic wheezing. N Engl J Med 2006; 354: 1998–2005.PubMedCrossRefGoogle Scholar
  108. 108.
    Woszczek G, Chen LY, Alsaaty S, et al. Concentration-dependent non-cysteinyl leukotriene type 1 receptor-mediated inhibitory activity of leukotriene receptor antagonists. J Immunol 2010; 184 (4): 2219–25.PubMedCrossRefGoogle Scholar
  109. 109.
    Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma [published erratum appears in Am J Respir Crit Care Med 2009; 180 (8): 796]. Am J Respir Crit Care Med 2009; 180 (5): 388–95.PubMedCrossRefGoogle Scholar
  110. 110.
    Choy DF, Modrek B, Abbas AR, et al. Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways. J Immunol 2011; 186(3): 1861–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365 (12): 1088–98.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Catalina Dumitru
    • 1
    • 2
  • Susan M. H. Chan
    • 1
    • 2
  • Victor Turcanu
    • 1
    • 2
  1. 1.Department of Asthma, Allergy and Respiratory Science, Guy’s HospitalKing’s College London, King’s Health Partners, Asthma-UK Centre in Allergic Mechanisms of AsthmaLondonUK
  2. 2.Guy’s and St Thomas’ NHS Foundation TrustNational Institute for Health Research (NIHR), Biomedical Research CentreLondonUK

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