支氣管哮喘( 簡(jiǎn)稱哮喘) 作為一種異質(zhì)性疾病, 其發(fā)病機(jī)制復(fù)雜多樣, 病理生理改變和臨床表現(xiàn)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(huán)
境因素相互作用的結(jié)果[ 1] ; 它也是能將生物體分成不同獨(dú)立類群的一系列特征[ 2] 。近年來(lái), 學(xué)者們對(duì)哮喘的表現(xiàn)和治療反應(yīng)的異質(zhì)性認(rèn)識(shí)不斷增加, 從哮喘的不同角度進(jìn)行觀察
并歸納出多種臨床和炎癥表型。雖然對(duì)這些表型尚未達(dá)成共識(shí), 但它有助于深入認(rèn)識(shí)哮喘的發(fā)病機(jī)制, 有助于獲得對(duì)哮喘進(jìn)行更有針對(duì)性的治療策略。
目前現(xiàn)有的哮喘的分類主要依據(jù)是疾病病因、疾病的控制水平與嚴(yán)重程度[ 3] 。這些分類往往不能很好的反映哮喘的異質(zhì)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(dǎo)治療及判斷預(yù)后[ 3] 。雖然指南并沒(méi)有明確作出哮喘表型的分類, 但這足以顯示出學(xué)界對(duì)哮喘表型分類的關(guān)注。目前, 對(duì)哮喘的表型分類仍無(wú)統(tǒng)一的共識(shí), 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(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(5): 546-547. doi: 復(fù)制
版權(quán)信息: ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)呼吸與危重監(jiān)護(hù)雜志》版權(quán)所有,未經(jīng)授權(quán)不得轉(zhuǎn)載、改編
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(jù)支氣管哮喘患者痰嗜酸粒細(xì)胞計(jì)數(shù)調(diào)整糖皮質(zhì)激素劑量的臨床意義. 中華結(jié)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(jù)支氣管哮喘患者痰嗜酸粒細(xì)胞計(jì)數(shù)調(diào)整糖皮質(zhì)激素劑量的臨床意義. 中華結(jié)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.