哮喘的臨床與炎癥表型_《中國呼吸與危重監護雜志》

作者：

梁振宇 , 蔡紹曦 , 趙海金

南方醫科大學南方醫院呼吸科( 廣東廣州 510515) 通訊作者: 蔡紹曦, E-mail: hxkcai@ 126. com;

關鍵詞：

哮喘炎癥表型

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支氣管哮喘( 簡稱哮喘) 作為一種異質性疾病, 其發病機制復雜多樣, 病理生理改變和臨床表現同樣具有多樣性。表型( Phenotypes) 是指生物體的可觀察特征, 是基因型和環
境因素相互作用的結果[ 1] ; 它也是能將生物體分成不同獨立類群的一系列特征[ 2] 。近年來, 學者們對哮喘的表現和治療反應的異質性認識不斷增加, 從哮喘的不同角度進行觀察
并歸納出多種臨床和炎癥表型。雖然對這些表型尚未達成共識, 但它有助于深入認識哮喘的發病機制, 有助于獲得對哮喘進行更有針對性的治療策略。
目前現有的哮喘的分類主要依據是疾病病因、疾病的控制水平與嚴重程度[ 3] 。這些分類往往不能很好的反映哮喘的異質性。2009 版的哮喘防治指南( GINA) 首次將“表型”的定義引入, 并提出基于表型的分類有助于指導治療及判斷預后[ 3] 。雖然指南并沒有明確作出哮喘表型的分類, 但這足以顯示出學界對哮喘表型分類的關注。目前, 對哮喘的表型分類仍無統一的共識, 以不同的方法和分類原則可有不同的分類。

引用本文： 梁振宇,蔡紹曦,趙海金. 哮喘的臨床與炎癥表型. 中國呼吸與危重監護雜志, 2010, 9(5): 546-547. doi: 復制

1.	Wenzel SE. Asthma: defining of the persistent adult phenotypes.Lancet, 2006, 368: 804-813 .
2.	Henderson J, Granell R, Sterne J. The search for new asthma phenotypes. Arch Dis Child, 2009, 94: 333-336 .
3.	Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention 2009 ( update) .
4.	Martinez FD. Development of wheezing disorders and asthma in preschool children. Pediatrics, 2002 , 109: 362-367 .
5.	Taussig LM, Wright AL, Holberg CJ, et al. Tucson Children’s Respiratory Study: 1980 to present. J Allergy Clin Immunol, 2003 ,111 : 661-675.
6.	De Marco R, Locatelli F, Cerveri I, et al. Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J Allergy Clin Immunol, 2002, 110: 228-235.
7.	Bel EH. Clinical phenotypes of asthma. Curr Opin PulmMed, 2004 ,10: 44-50 .
8.	Wardlaw AJ, Silverman M, Siva R, et al. Multi-dimensional phenotyping: towards a new taxonomy for airway disease. Clin Exp Allergy, 2005, 35 : 1254 -1262 .
9.	Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med, 2008 , 178 : 218 -224 .
10.	Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med, 2010, 181: 315 -323.
11.	Fahy JV. Identifying clinical phenotypes of asthma: steps in the right direction. Am J Respir Crit Care Med, 2010 , 181: 296-297.
12.	Strek ME. Difficult asthma. Proc Am Thorac Soc , 2006 , 3: 116-123 .
13.	Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med, 2000 , 162: 2341-2351.
14.	Alves Rde S, Vianna Fde A, Pereira CA. Clinical phenotypes of severe asthma. J Bras Pneumol, 2008, 34: 646 -653.
15.	Miranda C, Busacker A, Balzar S, et al. Distinguishing severe asthma phenotypes: role of age at onset and eosinophillic inflammation. J Allergy Clin Immunol, 2004, 113: 101-108 .
16.	Gibson PG. Inflammatory phenotypes in adult asthma: clinical applications. Clin Respir J, 2009, 3: 198-206 .
17.	Pavord ID, Shaw DE, Gibson PG, et al. Inflammometry to assess airway diseases. Lancet, 2008, 372 : 1017-1019.
18.	Simpson JL, Scott R, Boyle MJ, et al. Inflammatory subtypes in asthma: assessment and identification using induced sputum.Respirology, 2006, 11: 54 -61 .
19.	Nadif R, Siroux V, Oryszczyn MP. et al. Heterogeneity of asthma according to blood inflammatory patterns. Thorax, 2009, 64: 374 -380.
20.	Meijer RJ, Postma DS, Kauffman HF, et al. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma. Clin Exp Allergy, 2002, 32 : 1096-1103. 21 Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2 -driven inflammationdefines major subphenotypes of asthma. Am J Respir Crit Care Med, 2009, 180: 388-395.
21.	Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest, 2001, 119 :1329-1336.
22.	Simpson JL, Grissell TV, Douwes J, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax, 2007,62:211-218.
23.	ML Fajt, SE Wenzel. Asthma phenotypes in adults and clinical implications. Expert Rev Resp Med, 2009, 3: 607 -625.
24.	Haldar P, Pavord ID. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol, 2007, 119: 1043 -1052.
25.	Parameswaran K, Leigh R, Hargreave FE. Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma. J Allergy Clin Immunol, 1999, 104: 502 -503.
26.	Green R, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.Lancet, 2002, 360 : 1715 -1721 .
27.	Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J, 2006, 27 : 483 -494.
28.	曹文利, 孫永昌, 姚婉貞. 根據支氣管哮喘患者痰嗜酸粒細胞計數調整糖皮質激素劑量的臨床意義. 中華結核和呼吸雜志,2009, 30: 334-338 .
29.	Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med,2009, 360: 973-984.
30.	Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med, 2009, 360: 985-993.
31.	Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet, 2000, 356 :2144-2148.
32.	Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med, 2007 , 176: 1062 -1071.

1. Wenzel SE. Asthma: defining of the persistent adult phenotypes.Lancet, 2006, 368: 804-813 .
2. Henderson J, Granell R, Sterne J. The search for new asthma phenotypes. Arch Dis Child, 2009, 94: 333-336 .
3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention 2009 ( update) .
4. Martinez FD. Development of wheezing disorders and asthma in preschool children. Pediatrics, 2002 , 109: 362-367 .
5. Taussig LM, Wright AL, Holberg CJ, et al. Tucson Children’s Respiratory Study: 1980 to present. J Allergy Clin Immunol, 2003 ,111 : 661-675.
6. De Marco R, Locatelli F, Cerveri I, et al. Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J Allergy Clin Immunol, 2002, 110: 228-235.
7. Bel EH. Clinical phenotypes of asthma. Curr Opin PulmMed, 2004 ,10: 44-50 .
8. Wardlaw AJ, Silverman M, Siva R, et al. Multi-dimensional phenotyping: towards a new taxonomy for airway disease. Clin Exp Allergy, 2005, 35 : 1254 -1262 .
9. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med, 2008 , 178 : 218 -224 .
10. Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med, 2010, 181: 315 -323.
11. Fahy JV. Identifying clinical phenotypes of asthma: steps in the right direction. Am J Respir Crit Care Med, 2010 , 181: 296-297.
12. Strek ME. Difficult asthma. Proc Am Thorac Soc , 2006 , 3: 116-123 .
13. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med, 2000 , 162: 2341-2351.
14. Alves Rde S, Vianna Fde A, Pereira CA. Clinical phenotypes of severe asthma. J Bras Pneumol, 2008, 34: 646 -653.
15. Miranda C, Busacker A, Balzar S, et al. Distinguishing severe asthma phenotypes: role of age at onset and eosinophillic inflammation. J Allergy Clin Immunol, 2004, 113: 101-108 .
16. Gibson PG. Inflammatory phenotypes in adult asthma: clinical applications. Clin Respir J, 2009, 3: 198-206 .
17. Pavord ID, Shaw DE, Gibson PG, et al. Inflammometry to assess airway diseases. Lancet, 2008, 372 : 1017-1019.
18. Simpson JL, Scott R, Boyle MJ, et al. Inflammatory subtypes in asthma: assessment and identification using induced sputum.Respirology, 2006, 11: 54 -61 .
19. Nadif R, Siroux V, Oryszczyn MP. et al. Heterogeneity of asthma according to blood inflammatory patterns. Thorax, 2009, 64: 374 -380.
20. Meijer RJ, Postma DS, Kauffman HF, et al. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma. Clin Exp Allergy, 2002, 32 : 1096-1103. 21 Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2 -driven inflammationdefines major subphenotypes of asthma. Am J Respir Crit Care Med, 2009, 180: 388-395.
21. Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest, 2001, 119 :1329-1336.
22. Simpson JL, Grissell TV, Douwes J, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax, 2007,62:211-218.
23. ML Fajt, SE Wenzel. Asthma phenotypes in adults and clinical implications. Expert Rev Resp Med, 2009, 3: 607 -625.
24. Haldar P, Pavord ID. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol, 2007, 119: 1043 -1052.
25. Parameswaran K, Leigh R, Hargreave FE. Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma. J Allergy Clin Immunol, 1999, 104: 502 -503.
26. Green R, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.Lancet, 2002, 360 : 1715 -1721 .
27. Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J, 2006, 27 : 483 -494.
28. 曹文利, 孫永昌, 姚婉貞. 根據支氣管哮喘患者痰嗜酸粒細胞計數調整糖皮質激素劑量的臨床意義. 中華結核和呼吸雜志,2009, 30: 334-338 .
29. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med,2009, 360: 973-984.
30. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med, 2009, 360: 985-993.
31. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet, 2000, 356 :2144-2148.
32. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med, 2007 , 176: 1062 -1071.

《中國呼吸與危重監護雜志》

哮喘的臨床與炎癥表型

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《中國呼吸與危重監護雜志》

哮喘的臨床與炎癥表型

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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Content

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