山东大学耳鼻喉眼学报 ›› 2019, Vol. 33 ›› Issue (1): 53-58.doi: 10.6040/j.issn.1673-3770.1.2018.040

• 研究进展 • 上一篇    下一篇

生物制剂治疗支气管哮喘的研究进展

沙莉,刘传合*()   

  1. 首都儿科研究所附属儿童医院变态反应科，北京 100020
  • 收稿日期:2018-11-15 出版日期:2019-01-20 发布日期:2019-01-28
  • 通讯作者: 刘传合 E-mail:liuchcip@126.com
  • 作者简介:沙莉，主任医师，医学博士。主要学术任职：中华医学会变态反应学分会儿童过敏学组(筹)委员，中国医师协会变态反应医师分会青年委员，中国中西医结合学会儿科专业委员会青年委员会副主任委员，北京市儿科哮喘协作组秘书。参与多项哮喘、慢性咳嗽的课题研究，参与翻译《儿童哮喘管理和预防的指南袖珍本》《过敏性鼻炎的处理及其对哮喘的影响》，编写《哮喘儿童百问》《儿童支气管哮喘的诊断及治疗》等。擅长治疗反复喘息、儿童哮喘、慢性咳嗽、反复呼吸道感染等

Research progress in the treatment of bronchial asthma with biological agents

Li SHA,Chuanhe LIU*()   

  1. Department of Allergy, Children′s Hospital, Capital Institute of Pediatrics, Beijing 100020, China
  • Received:2018-11-15 Online:2019-01-20 Published:2019-01-28
  • Contact: Chuanhe LIU E-mail:liuchcip@126.com

RichHTML

159

PDF (PC)

1451

摘要：

支气管哮喘是呼吸系统常见的气道慢性炎症性疾病，吸入皮质激素是其主要治疗策略。随着哮喘发病机制的深入研究，发现气道炎症类型不同，吸入激素治疗的反应不同。针对气道炎症反应过程中的炎性介质，已经开发了多种生物制剂。临床随机对照研究中，严重嗜酸粒细胞性哮喘患者从中获益，部分临床疗效存在争议。儿童用药的疗效和安全性及药物对疾病产生的长期影响还需进一步研究证实。

关键词: 哮喘, 气道炎症, 生物制剂治疗

Abstract:

Bronchial asthma is a common chronic airway inflammatory disease of the respiratory system. Inhaled corticosteroids are the primary treatment strategy. Studies have shown that the clinical response to inhaled corticosteroids varies due to different types of airway inflammation. A variety of biological agents aimed at inflammatory mediators in airway inflammation have been developed. Randomized controlled trials of these agents have shown that patients with severe eosinophilic asthma benefit from therapy, but controversy remains regarding some aspects of their clinical effects. Their efficacy and safety in children, as well as their long-term effects on disease course and progression need further study and confirmation.

Key words: Asthma, Airway inflammation, Biologic therapy

中图分类号: 

  • R562.2
1 Paul WE , Zhu JF . How are T(H)2-type immune responses initiated and amplified?[J]. Nat Rev Immunol, 2010, 10 (4): 225- 235.
doi: 10.1038/nri2735
2 Harper RW , Zeki AA . Immunobiology of the critical asthma syndrome[J]. Clin Rev Allergy Immunol, 2015, 48 (1): 54- 65.
doi: 10.1007/s12016-013-8407-6
3 Dunn RM , Wechsler ME . Anti-interleukin therapy in asthma[J]. Clin Pharmacol Ther, 2015, 97 (1): 55- 65.
doi: 10.1002/cpt.11
4 Kearley J , Erjefalt JS , Andersson C , et al. IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways[J]. Am J Respir Crit Care Med, 2011, 183 (7): 865- 875.
doi: 10.1164/rccm.200909-1462OC
5 Moro K , Yamada T , Tanabe M , et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells[J]. Nature, 2010, 463 (7280): 540- 544.
doi: 10.1038/nature08636
6 Christianson CA , Goplen NP , Zafar I , et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33[J]. J Allergy Clin Immunol, 2015, 136 (1): 59- 68.e14.
doi: 10.1016/j.jaci.2014.11.037
7 Normansell R , Walker S , Milan SJ , et al. Omalizumab for asthma in adults and children[J]. Cochrane Database Syst Rev, 2014, (1): CD003559.
doi: 10.1002/14651858.CD003559.pub4
8 Storms W , Bowdish MS , Farrar JR . Omalizumab and asthma control in patients with moderate-to-severe allergic asthma: a 6-year pragmatic data review[J]. Allergy Asthma Proc, 2012, 33 (2): 172- 177.
doi: 10.2500/aap.2012.33.3527
9 Long AD , Rahmaoui A , Rothman KJ , et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab[J]. J Allergy Clin Immunol, 2014, 134 (3): 560- 567.e4.
doi: 10.1016/j.jaci.2014.02.007
10 Gauvreau GM , Arm JP , Boulet LP , et al. Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses[J]. J Allergy Clin Immunol, 2016, 138 (4): 1051- 1059.
doi: 10.1016/j.jaci.2016.02.027
11 Bel EH , Wenzel SE , Thompsen PJ , et al. Oral glucocorticoidsparing effect of mepolizumab in eosinophilic asthma[J]. N Ensl Jmed, 2014, 371 (13): 1189- 1197.
doi: 10.1056/NEJMoa1403291
12 Castro M , Zangrilli J , Wechsler ME , 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[J]. The Lancet Respiratory Medicine, 2015, 3 (5): 355- 366.
doi: 10.1016/S2213-2600(15)00042-9
13 Fitzgerald JM , Bleecker ER , Nair P , 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[J]. The Lancet, 2016, 388 (10056): 2128- 2141.
doi: 10.1016/S0140-6736(16)31322-8
14 Antoniu SA , Cojocaru I . Pitrakinra for asthma[J]. Expert Opin Biol Ther, 2010, 10 (11): 1609- 1615.
doi: 10.1517/14712598.2010.524203
15 Wenzel S , Wilbraham D , Fuller R , et al. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies[J]. Lancet, 2007, 370 (9596): 1422- 1431.
doi: 10.1016/S0140-6736(07)61600-6
16 Slager RE , Otulana BA , Hawkins GA , et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist[J]. J Allergy Clin Immunol, 2012, 130 (2): 516- 522.e4.
doi: 10.1016/j.jaci.2012.03.030
17 Vatrella A , Fabozzi I , Calabrese C , et al. Dupilumab: a novel treatment for asthma[J]. J Asthma Allergy, 2014, 7: 123- 130.
doi: 10.2147/JAA.S52387
18 Castro M , Corren J , Pavord ID , et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma[J]. N Engl J Med, 2018, 378 (26): 2486- 2496.
doi: 10.1056/NEJMoa1804092
19 Zayed Y , Kheiri B , Banifadel M , et al. Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials[J]. J Asthma, 2018, 1- 10.
doi: 10.1080/02770903.2018.1520865
20 Corren J , Lemanske RF , Hanania NA , et al. Lebrikizumab treatment in adults with asthma[J]. N Engl J Med, 2011, 365 (12): 1088- 1098.
doi: 10.1056/NEJMoa1106469
21 Piper E , Brightling C , Niven R , et al. A phase Ⅱ placebo-controlled study of tralokinumab in moderate-to-severe asthma[J]. Eur Respir J, 2013, 41 (2): 330- 338.
doi: 10.1183/09031936.00223411
22 Brightling CE , Chanez P , Leigh R , et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial[J]. Lancet Respir Med, 2015, 3 (9): 692- 701.
doi: 10.1016/S2213-2600(15)00197-6
23 Corren J , Parnes JR , Wang LW , et al. Tezepelumab in adults with uncontrolled asthma[J]. N Engl J Med, 2017, 377 (10): 936- 946.
doi: 10.1056/NEJMoa1704064
24 Kirsten A , Watz H , Pedersen F , et al. The anti-IL-17A antibody secukinumab does not attenuate ozone-induced airway neutrophilia in healthy volunteers[J]. Eur Respir J, 2013, 41 (1): 239- 241.
doi: 10.1183/09031936.00123612
25 Busse WW , Holgate S , Kerwin E , et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma[J]. Am J Respir Crit Care Med, 2013, 188 (11): 1294- 1302.
doi: 10.1164/rccm.201212-2318OC
26 O′Byrne PM , Metev H , Puu M , et al. Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial[J]. Lancet Respir Med, 2016, 4 (10): 797- 806.
doi: 10.1016/S2213-2600(16)30227-2
27 Watz H , Uddin M , Pedersen F , et al. Effects of the CXCR2 antagonist AZD5069 on lung neutrophil recruitment in asthma[J]. Pulm Pharmacol Ther, 2017, 45: 121- 123.
doi: 10.1016/j.pupt.2017.05.012
28 Berry MA , Hargadon B , Shelley M , et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma[J]. N Engl J Med, 2006, 354 (7): 697- 708.
doi: 10.1056/NEJMoa050580
29 Howarth PH , Babu KS , Arshad HS , et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma[J]. Thorax, 2005, 60 (12): 1012- 1018.
doi: 10.1136/thx.2005.045260
30 Erin EM , Leaker BR , Nicholson GC , et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma[J]. Am J Respir Crit Care Med, 2006, 174 (7): 753- 762.
doi: 10.1164/rccm.200601-072OC
31 Taille C . Monoclonal anti-TNF-α antibodies for severe steroid-dependent asthma: a case series[J]. TORMJ, 2013, 7 (1): 21- 25.
doi: 10.2174/1874306401307010021
32 Rouhani FN , Meitin CA , Kaler M , et al. Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation[J]. Respir Med, 2005, 99 (9): 1175- 1182.
doi: 10.1016/j.rmed.2005.02.031
33 Morjaria JB , Chauhan AJ , Babu KS , et al. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial[J]. Thorax, 2008, 63 (7): 584- 591.
doi: 10.1136/thx.2007.086314
[1] 段思妤,薛金梅. 组蛋白去乙酰化酶2在慢性气道炎症性疾病糖皮质激素抵抗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2026, 40(1): 120-126.
[2] 曹正勇,李小波. 慢性鼻-鼻窦炎合并哮喘术后短程局部使用糖皮质激素辅助治疗的安全性和有效性[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 43-50.
[3] 崇维琨,王娟. 联合应用奥马珠单抗在儿童中重度变应性哮喘合并慢性鼻窦炎中的疗效观察[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 21-26.
[4] 孙汐文,骆春雨,李志鹏,张维天. 铁死亡在呼吸道炎症性疾病中的作用及研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(6): 24-32.
[5] 卢淦,邓玉琴,陶泽璋. 过敏性疾病与糖尿病的相关性及潜在关联机制[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 215-222.
[6] 袁玥,付圣尧,姜彦,陈敏. 细胞焦亡在慢性气道炎症性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 166-171.
[7] 王娜,柴向斌. 前列腺源性ETS因子在哮喘及鼻黏膜炎性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 136-141.
[8] 李孟辉,郅莉莉,戚凯文,王珊珊,高倩,步美玲,姜荷云,冯绛楠,王金荣. 皮下免疫治疗对单一尘螨和合并霉菌过敏儿童哮喘的临床研究[J]. 山东大学耳鼻喉眼学报, 2022, 36(1): 75-80.
[9] 杨一帆, 程雷. 儿童鼻窦炎与哮喘:统一气道疾病[J]. 山东大学耳鼻喉眼学报, 2019, 33(6): 10-15.
[10] 邵洁. 探讨儿童过敏性哮喘的若干问题[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 25-27.
[11] 刘传合. 我国儿童哮喘患病与诊治现状[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 28-32.
[12] 邱前辉,高俊潇. 特异性免疫治疗对过敏性鼻炎和哮喘的同步控制和远期疗效[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 33-37.
[13] 余洪猛,刘琢扶,戴琪. 合并哮喘的慢性鼻-鼻窦炎的鼻内镜手术治疗[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 38-41.
[14] 朱政,王万钧,胡秋蓉,李靖. 变应原气道激发在变应性鼻炎和哮喘研究中的作用研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 42-48.
[15] 张宇,宋西成. 慢性鼻窦炎伴鼻息肉与哮喘的相关性机制及治疗策略研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 49-52.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
网站版权所有 © 2018 《山东大学耳鼻喉眼学报》编辑部　
地址：山东省济南市山大南路27号（250100）电话：+86-0531-88366912 E-mail: ebhxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发