The Korean Journal of Medicine

  • 제83권2호
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  • Pages.190-196
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  • 2012
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  • 1738-9364(pISSN)
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  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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천식의 새로운 치료제들

Novel Drugs for Asthma Treatment: Immunomodulatory Therapy

  • 이준혁 (순천향대학교 의과대학 부천병원 호흡기-알레르기내과)
  • Lee, June-Hyuk (Division of Respiratory and Allergy, Internal Medicine, Soonchunhyang University School of Medicine)
  • 발행 : 2012.08.01
⟨ 이전 논문 다음 논문 ⟩

초록

The management of asthma focuses on the reduction of airway inflammation accompany with symptomatic care after recognition. Glucocorticosteroid is the most important drug to reduce airway inflammation, and it has been used inhaled, orally and systemically. New knowledge about the pathogenesis of allergy and asthma has made the development and clinical trial of target or immunomodulator therapy. It includes cytokine, cytokine blockers, specific cytokine receptor blocker, and immunostimulatory oligodeoxynucleotides. These agents are thought to hold the promise for more beneficial outcomes in the future, although it showed limited therapeutic benefits only for patients, especially intractable or severe asthma, until now.

키워드

참고문헌

  1. Casale TB, Stokes JR. Immunomodulators for allergic respiratory disorders.J Allergy Clin Immunol 2008;121:288-296. https://doi.org/10.1016/j.jaci.2007.11.040
  2. Dimov VV, Casale TB. Immunomodulators for asthma. Allergy Asthma Immunol Res 2010;2:228-234. https://doi.org/10.4168/aair.2010.2.4.228
  3. Nguyen TH, Casale TB. Immune modulation for treatment of allergic disease. Immunol Rev 2011;242:258-271. https://doi.org/10.1111/j.1600-065X.2011.01034.x
  4. Casale TB, Kessler J, Romero FA. Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. Ann Allergy Asthma Immunol 2006;97:454-456. https://doi.org/10.1016/S1081-1206(10)60934-9
  5. Rosewich M, Schulze J, Eickmeier O, et al. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children. Clin Exp Immunol 2010;160:403-410. https://doi.org/10.1111/j.1365-2249.2010.04106.x
  6. Creticos PS, Schroeder JT, Hamilton RG, et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006;355:1445-1455. https://doi.org/10.1056/NEJMoa052916
  7. Gauvreau GM, Hessel EM, Boulet LP, Coffman RL, O'Byrne PM. Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am J Respir Crit Care Med 2006;174:15-20 https://doi.org/10.1164/rccm.200601-057OC
  8. Busse WW, Israel E, Nelson HS, et al. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am J Respir Crit Care Med 2008;178:1002-1008. https://doi.org/10.1164/rccm.200708-1200OC
  9. Borish LC, Nelson HS, Corren J, et al. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001;107:963-970. https://doi.org/10.1067/mai.2001.115624
  10. Corren J, Busse W, Meltzer EO, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med 2010;181: 788-796. https://doi.org/10.1164/rccm.200909-1448OC
  11. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 2007;370:1422-1431. https://doi.org/10.1016/S0140-6736(07)61600-6
  12. Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebocontrolled study. Am J Respir Crit Care Med 2011;184: 1125-1132. https://doi.org/10.1164/rccm.201103-0396OC
  13. Flood-Page P, Menzies-Gow A, Phipps S, et al. Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003;112:1029-1036.
  14. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003;167:199-204. https://doi.org/10.1164/rccm.200208-789OC
  15. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-984. Erratum in: N Engl J Med 2011; 364:588. https://doi.org/10.1056/NEJMoa0808991
  16. Oldhoff JM, Darsow U, Werfel T, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 2005;60:693-696. https://doi.org/10.1111/j.1398-9995.2005.00791.x
  17. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-2148. https://doi.org/10.1016/S0140-6736(00)03496-6
  18. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-993. https://doi.org/10.1056/NEJMoa0805435
  19. Oh CK, Raible D, Geba GP, Molfino NA. Biology of the interleukin-9 pathway and its therapeutic potential for the treatment of asthma. Inflamm Allergy Drug Targets 2011;10: 180-186. https://doi.org/10.2174/187152811795564073
  20. Antoniu SA. MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma. Curr Opin Mol Ther 2010;12:233-239.
  21. Singh D, Kane B, Molfino NA, Faggioni R, Roskos L, Woodcock A. A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. BMC Pulm Med 2010;10:3.
  22. Gauvreau GM, Boulet LP, Cockcroft DW, et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med 2011; 183:1007-1014. https://doi.org/10.1164/rccm.201008-1210OC
  23. Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708. https://doi.org/10.1056/NEJMoa050580
  24. Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-1018. https://doi.org/10.1136/thx.2005.045260
  25. Rouhani FN, Meitin CA, Kaler M, Miskinis-Hilligoss D, Stylianou M, Levine SJ. Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation. Respir Med 2005;99:1175-1182. https://doi.org/10.1016/j.rmed.2005.02.031
  26. Erin EM, Leaker BR, Nicholson GC, et al. The effects of a monoclonal antibody directed against tumor necrosis factoralpha in asthma. Am J Respir Crit Care Med 2006;174:753-762. https://doi.org/10.1164/rccm.200601-072OC
  27. Morjaria JB, Chauhan AJ, Babu KS, Polosa R, Davies DE, Holgate ST. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008;63:584-591. https://doi.org/10.1136/thx.2007.086314
  28. Meltzer EO, Berkowitz RB, Grossbard EB. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol 2005;115:791-796. https://doi.org/10.1016/j.jaci.2005.01.040
  29. Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care 2002;25:401.
  30. Spears M, Donnelly I, Jolly L, et al. Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther 2009;86:49-53. https://doi.org/10.1038/clpt.2009.41
  31. Lin H, Boesel KM, Griffith DT, et al. Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol 2004;113:297-302. https://doi.org/10.1016/j.jaci.2003.11.044
  32. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001;108: 184-190. https://doi.org/10.1067/mai.2001.117880
  33. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthmarelated emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003;111: 87-90 https://doi.org/10.1067/mai.2003.49
  34. Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001;18:254-261. https://doi.org/10.1183/09031936.01.00092101
  35. Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001;108:E36. https://doi.org/10.1542/peds.108.2.e36
  36. Holgate S, Buhl R, Bousquet J, Smith N, Panahloo Z, Jimenez P. The use of omalizumab in the treatment of severe allergic asthma: aclinical experience update. Respir Med 2009;103: 1098-1113. https://doi.org/10.1016/j.rmed.2009.03.008
  37. Adelroth E, Rak S, Haahtela T, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2000;106:253-259. https://doi.org/10.1067/mai.2000.108310
  38. Casale TB, Busse WW, Kline JN, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006;117:134-140. https://doi.org/10.1016/j.jaci.2005.09.036
  39. Massanari M, Nelson H, Casale T, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol 2010;125: 383-389. https://doi.org/10.1016/j.jaci.2009.11.022
  40. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol 2007;120:1378-1381. https://doi.org/10.1016/j.jaci.2007.09.022