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Eosinophils and childhood asthma

  • Choi, Bong Seok (Department of Pediatrics, School of Medicine, Kyungpook National University)
  • 투고 : 2020.04.22
  • 심사 : 2020.12.05
  • 발행 : 2021.02.15

초록

Eosinophils are a type of granulocyte with eosinophilic granules in the cytoplasm that play an important role in allergic and parasitic diseases. Eosinophils are important in the pathogenesis of asthma, and many studies have examined the relationship between them. In allergic eosinophilic asthma, eosinophils act not only as important effector cells but also as antigen-presenting cells in allergic inflammatory reactions. In nonallergic eosinophilic asthma, type 2 innate lymphoid cells in the airways play an important role in eosinophil activation. Direct methods, including bronchial biopsy, bronchoalveolar lavage, and the induced sputum test, are used to evaluate eosinophilic inflammatory reactions in patients with asthma, however, because of difficulty with their implementation, they are sometimes replaced by measurements of blood eosinophils, fraction of exhaled nitric oxide, and serum periostin level. However, these tests are less accurate than direct methods. For the treatment of patients with severe eosinophilic asthma, anti-interleukin-5 preparations such as mepolizumab, reslizumab, and benralizumab have recently been introduced and broadened the scope of asthma treatment. Although eosinophils are already known to play an important role in asthma, we expect that further studies will reveal more details of their action.

키워드

참고문헌

  1. Wurth M, Papantonakis CM, Nevel RJ, Thomas CS, Sokolow AG, Moore PE, et al. Risk factors associated with asthma development and control in children. Mouse infestation, antipyretics, respiratory viruses, and allergic sensitization. Am J Resp Crit Care Med 2017;196:1605. https://doi.org/10.1164/rccm.201704-0696RR
  2. Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004;59:469-78. https://doi.org/10.1111/j.1398-9995.2004.00526.x
  3. Kim BK, Kim JY, Kang MK, Yang MS, Park HW, Min KU, et al. Allergies are still on the rise? A 6-year nationwide population-based study in Korea. Allergol Int 2016;65:186-91. https://doi.org/10.1016/j.alit.2015.11.002
  4. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006;368:804-13. https://doi.org/10.1016/S0140-6736(06)69290-8
  5. Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326:298-304. https://doi.org/10.1056/NEJM199201303260504
  6. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Resp Crit Care Med 2009;180:388-95. https://doi.org/10.1164/rccm.200903-0392OC
  7. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033-9. https://doi.org/10.1056/NEJM199010113231505
  8. Holgate ST. The epidemic of allergy and asthma. Nature 1999;402:B2-4. https://doi.org/10.1038/35037000
  9. Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, et al. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy 2008;38:709-50. https://doi.org/10.1111/j.1365-2222.2008.02958.x
  10. Trivedi S, Lloyd C. Eosinophils in the pathogenesis of allergic airways disease. Cell Mol Life Sci 2007;64:1269. https://doi.org/10.1007/s00018-007-6527-y
  11. Ying S, Meng Q, Zeibecoglou K, Robinson DS, Macfarlane A, Humbert M, et al. Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP4), and CC chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. J Immunol 1999;163:6321-9. https://doi.org/10.4049/jimmunol.163.11.6321
  12. Uhm TG, Kim BS, Chung IY. Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma. Allergy Asthma Immunol Res 2012;4:68-79. https://doi.org/10.4168/aair.2012.4.2.68
  13. Young B, Woodford P, O'Dowd G. Wheater's functional histology E-Book: a text and colour atlas. 6th ed. Philadelphia (PA): Elsevier Health Sciences, 2013.
  14. Blanchard C, Rothenberg ME. Biology of the eosinophil. Adv Immunol 2009;101:81-121. https://doi.org/10.1016/S0065-2776(08)01003-1
  15. Rothenberg ME. Eosinophilia. N Engl J Med 1998;338:1592-600. https://doi.org/10.1056/NEJM199805283382206
  16. Carr TF, Zeki AA, Kraft M. Eosinophilic and noneosinophilic asthma. Am J Resp Crit Care Med 2018;197:22-37. https://doi.org/10.1164/rccm.201611-2232pp
  17. Arron JR, Choy DF, Scheerens H, Matthews JG. Noninvasive biomarkers that predict treatment benefit from biologic therapies in asthma. Ann Am Thorac Soc 2013;10:S206-13. https://doi.org/10.1513/AnnalsATS.201303-047AW
  18. Hargreave FE. Induced sputum and response to glucocorticoids. J Allergy Clin Immunol 1998;102:S102-5. https://doi.org/10.1016/S0091-6749(98)70040-5
  19. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002;109:410-8. https://doi.org/10.1067/mai.2002.122635
  20. Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol 2011;127:382-9. e13. https://doi.org/10.1016/j.jaci.2010.11.015
  21. Loza M. ADEPT and U-BIOPRED investigators. Longitudinally stable, clinically defined clusters of patient with asthma independently identified in the ADEPT and U-BIOPRED asthma studies. Ann Am Thorac Soc 2016;13:S102-3.
  22. Burks AW, Holgate ST, O'Hehir RE, Bacharier LB, Broide DH, Hershey GKK, et al. Middleton's allergy E-Book: principles and practice. Philadelphia (PA): Elsevier Health Sciences, 2019.
  23. Gleich G, Adolphson C. The eosinophil and bronchial asthma: evidence for a critical role of eosinophils in pathophysiology. Lung Biol Health Dis 1999;125:1-37.
  24. Walsh ER, August A. Eosinophils and allergic airway disease: there is more to the story. Trends Immunol 2010;31:39-44. https://doi.org/10.1016/j.it.2009.10.001
  25. Wang H-B, Ghiran I, Matthaei K, Weller PF. Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol 2007;179:7585-92. https://doi.org/10.4049/jimmunol.179.11.7585
  26. Duez C, Dakhama A, Tomkinson A, Marquillies P, Balhorn A, Tonnel AB, et al. Migration and accumulation of eosinophils toward regional lymph nodes after airway allergen challenge. J Allergy Clin Immunol 2004;114:820-5. https://doi.org/10.1016/j.jaci.2004.08.011
  27. Brusselle GG, Maes T, Bracke KR. Eosinophils in the spotlight: eosinophilic airway inflammation in nonallergic asthma. Nature med 2013;19:977-9. https://doi.org/10.1038/nm.3300
  28. Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, et al. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol 2016;137:75-86. e8. https://doi.org/10.1016/j.jaci.2015.05.037
  29. Hernnas J, Sarnstrand B, Lindroth P, Peterson C, Venge P, Malmstrom A. Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures. Eur J Cell Biol 1992;59:352-63.
  30. Zagai U, Dadfar E, Lundahl J, Venge P, Skold CM. Eosinophil cationic protein stimulates TGF-β 1 release by human lung fibroblasts in vitro. Inflammation 2007;30:153-60. https://doi.org/10.1007/s10753-007-9032-4
  31. Zagai U, Skold C, Trulson A, Venge P, Lundahl J. The effect of eosinophils on collagen gel contraction and implications for tissue remodelling. Clin Exp Allergy Immunol 2004;135:427-33. https://doi.org/10.1111/j.1365-2249.2004.02396.x
  32. Pegorier S, Wagner LA, Gleich GJ, Pretolani M. Eosinophil-derived cationic proteins activate the synthesis of remodeling factors by airway epithelial cells. J Immunol 2006;177:4861-9. https://doi.org/10.4049/jimmunol.177.7.4861
  33. Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, 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;112:1029-36. https://doi.org/10.1172/JCI17974
  34. 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 Resp Crit Care Med 1999;160:1001-8. https://doi.org/10.1164/ajrccm.160.3.9812110
  35. De Gouw H, Smits H, Sont J, Hiemstra P, Sterk P, Bel E. Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma. Eur Respir J 1996;9:2441-7. https://doi.org/10.1183/09031936.96.09122441
  36. Szefler SJ, Wenzel S, Brown R, Erzurum SC, Fahy JV, Hamilton RG, et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol 2012;129(3 Suppl):S9-23. https://doi.org/10.1016/j.jaci.2011.12.979
  37. Jayaram L, Pizzichini M, Cook R, Boulet L, Lemiere C, Pizzichini E, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006;27:483-94. https://doi.org/10.1183/09031936.06.00137704
  38. Fleming L, Wilson N, Regamey N, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax 2012;67:193-8. https://doi.org/10.1136/thx.2010.156836
  39. Berry A, Busse WW. Biomarkers in asthmatic patients: has their time come to direct treatment? J Allergy Clin Immunol 2016;137:1317-24. https://doi.org/10.1016/j.jaci.2016.03.009
  40. Hastie AT, Moore WC, Li H, Rector BM, Ortega VE, Pascual RM, et al. Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects. J Allergy Clin Immunol 2013;132:72-80. e12. https://doi.org/10.1016/j.jaci.2013.03.044
  41. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Resp Crit Care Med 2011;184:602-15. https://doi.org/10.1164/rccm.9120-11ST
  42. Korevaar DA, Westerhof GA, Wang J, Cohen JF, Spijker R, Sterk PJ, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med 2015;3:290-300. https://doi.org/10.1016/S2213-2600(15)00050-8
  43. Berry M, Shaw D, Green R, Brightling C, Wardlaw A, Pavord I. The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Clin Exp Allergy 2005;35:1175-9. https://doi.org/10.1111/j.1365-2222.2005.02314.x
  44. Mummadi SR, Hahn PY. Update on exhaled nitric oxide in clinical practice. Chest 2016;149:1340-4. https://doi.org/10.1016/j.chest.2015.11.020
  45. Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol 2012;130:647-54. e10. https://doi.org/10.1016/j.jaci.2012.06.025
  46. Simpson JL, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, et al. Periostin levels and eosinophilic inflammation in poorly-controlled asthma. BMC Pulm Med 2016;16:67. https://doi.org/10.1186/s12890-016-0230-4
  47. Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A 2007;104:15858-63. https://doi.org/10.1073/pnas.0707413104
  48. Wagener AH, de Nijs SB, Lutter R, Sousa AR, Weersink EJ, Bel EH, et al. External validation of blood eosinophils, FENO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax 2015;70:115-20. https://doi.org/10.1136/thoraxjnl-2014-205634
  49. Takatsu K, Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol 2008;20:288-94. https://doi.org/10.1016/j.coi.2008.04.001
  50. Shardonofsky FR, Venzor III J, Barrios R, Leong KP, Huston DP. Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma. J Allergy Clin Immunol 1999;104:215-21. https://doi.org/10.1016/S0091-6749(99)70138-7
  51. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93. https://doi.org/10.1056/NEJMoa0805435
  52. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84. https://doi.org/10.1056/NEJMoa0808991
  53. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207. https://doi.org/10.1056/NEJMoa1403290
  54. Gupta A, Ikeda M, Geng B, Azmi J, Price RG, Bradford ES, et al. Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype. J Allergy Clin Immunol 2019;144:1336-42. https://doi.org/10.1016/j.jaci.2019.08.005
  55. Varricchi G, Senna G, Loffredo S, Bagnasco D, Ferrando M, Canonica GW. Reslizumab and eosinophilic asthma: one step closer to precision medicine? Front Immunol 2017;8:242.
  56. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest 2016;150:799-810. https://doi.org/10.1016/j.chest.2016.03.018
  57. Mukherjee M, Aleman Paramo F, Kjarsgaard M, Salter B, Nair G, LaVigne N, et al. Weight-adjusted intravenous reslizumab in severe asthma with inadequate response to fixed-dose subcutaneous mepolizumab. Am J Resp Crit Care Med 2018;197:38-46. https://doi.org/10.1164/rccm.201707-1323OC
  58. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Resp Crit Care Med 2011;184:1125-32. https://doi.org/10.1164/rccm.201103-0396OC
  59. Nair P, Bardin P, Humbert M, Murphy KR, Hickey L, Garin M, et al. Efficacy of intravenous reslizumab in oral corticosteroid-dependent asthma. J Allergy Clin Immunol Pract 2020;8:555-64. https://doi.org/10.1016/j.jaip.2019.09.036
  60. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015;3:355-66. https://doi.org/10.1016/S2213-2600(15)00042-9
  61. Brusselle G, Germinaro M, Weiss S, Zangrilli J. Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils. Pulm Pharmacol Ther 2017;43:39-45. https://doi.org/10.1016/j.pupt.2017.01.011
  62. Murphy K, Jacobs J, Bjermer L, Fahrenholz JM, Shalit Y, Garin M, et al. Long-term safety and efficacy of reslizumab in patients with eosinophilic asthma. J Allegy Clin Immunol Pract 2017;5:1572-81.e3. https://doi.org/10.1016/j.jaip.2017.08.024
  63. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016;388:2115-27. https://doi.org/10.1016/S0140-6736(16)31324-1
  64. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016;388:2128-41. https://doi.org/10.1016/S0140-6736(16)31322-8
  65. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 2017;376:2448-58. https://doi.org/10.1056/NEJMoa1703501
  66. Ross KR, Gupta R, DeBoer MD, Zein J, Phillips BR, Mauger DT, et al. Severe asthma during childhood and adolescence: A longitudinal study. J Allergy 2020;145:140-6.e9.
  67. Teague WG. Blood eosinophilia may not adequately estimate lung fluid eosinophilia in childhood asthma. J Allergy Clin Immunol Pract 2019;7:2497-8. https://doi.org/10.1016/j.jaip.2019.05.008
  68. Wang AL, Datta S, Weiss ST, Tantisira KG. Remission of persistent childhood asthma: Early predictors of adult outcomes. J Allergy Clin Immunol 2019;143:1752-9.e6. https://doi.org/10.1016/j.jaci.2018.09.038
  69. Kansal P, Nandan D, Agarwal S, Patharia N, Arya N. Correlation of induced sputum eosinophil levels with clinical parameters in mild and moderate persistent asthma in children aged 7-18 years. J asthma 2018;55:385-90. https://doi.org/10.1080/02770903.2017.1338725
  70. Guiddir T, Saint-Pierre P, Purenne-Denis E, Lambert N, Laoudi Y, Couderc R, et al. Neutrophilic steroid-refractory recurrent wheeze and eosinophilic steroid-refractory asthma in children. J Allergy Clin Immunol Pract 2017;5:1351-61.e2. https://doi.org/10.1016/j.jaip.2017.02.003
  71. Ullmann N, Bossley C, Fleming L, Silvestri M, Bush A, Saglani S. Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma. Allergy 2013;68:402-6. https://doi.org/10.1111/all.12101
  72. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. New Engl J Med 2014;371:1189-97. https://doi.org/10.1056/NEJMoa1403291
  73. Brusselle G, Germinaro M, Weiss S, Zangrilli J. Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils. Pul Pharmacol 2017;43:39-45. https://doi.org/10.1016/j.pupt.2017.01.011
  74. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest 2016;150:789-98. https://doi.org/10.1016/j.chest.2016.03.032

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