山东大学耳鼻喉眼学报 ›› 2019, Vol. 33 ›› Issue (1): 42-48.doi: 10.6040/j.issn.1673-3770.1.2018.016

• 研究进展 • 上一篇    下一篇

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

朱政,王万钧,胡秋蓉,李靖*()   

  1. 呼吸疾病国家重点实验室 广州医科大学附属第一医院 广州呼吸健康研究院 变态反应科,广东 广州 510120
  • 收稿日期:2018-09-17 出版日期:2019-01-20 发布日期:2019-01-28
  • 通讯作者: 李靖 E-mail:jingli1016@vip.163.com
  • 作者简介:李靖,广州医科大学附属第一医院、呼吸疾病国家重点实验室、广州呼吸疾病健康研究院变态反应科主任,教授,博士生导师。主要学术任职:中华医学会变态反应学分会委员、中国医师协会呼吸病学分会哮喘学组成员,广东省医学会变态反应学分会副主任委员、呼吸病学分会哮喘学组副组长。承担多项国家自然基金项目和科技部重大项目,在《JACI》《Allergy》《Chest》《Clinical & Experimental Allergy》等杂志发表论著60余篇(SCI收录),参与世界卫生组织《过敏性鼻炎对哮喘的影响》指南的制订。获多项国家和广东省科技进步奖
  • 基金资助:
    国家自然科学基金面上项目(81370129);国家自然科学基金重大研究计划培育项目(91542104);国家重点研发计划“精准医学研究”(2016YFC0905800);广州市科创局科学(技术)研究专项重点项目(201607020046);广东省科技发展专项资金(前沿与关键技术创新方向-重大科技专项)(2017B020226006)

Allergen inhalation challenge in the research of allergic rhinitis and asthma

Zheng ZHU,Wanjun WANG,Qiurong HU,Jing LI*()   

  1. Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong, China
  • Received:2018-09-17 Online:2019-01-20 Published:2019-01-28
  • Contact: Jing LI E-mail:jingli1016@vip.163.com
  • Supported by:
    国家自然科学基金面上项目(81370129);国家自然科学基金重大研究计划培育项目(91542104);国家重点研发计划“精准医学研究”(2016YFC0905800);广州市科创局科学(技术)研究专项重点项目(201607020046);广东省科技发展专项资金(前沿与关键技术创新方向-重大科技专项)(2017B020226006)

摘要:

随着城市化进程,环境及生活方式的改变,我国变应性疾病发病率逐年升高。目前认为变应性鼻炎和哮喘的发病主要是在遗传基因、环境因素共同作用下导致,但具体发病机制复杂,尚未完全清楚。慢性气道炎症和气道高反应性是变应性鼻炎和哮喘的典型的病理生理特征。环境中变应原的暴露可诱发疾病症状发作,引起气道及全身炎症反应增加,并导致气道敏感性/反应性升高。人为给予变应性鼻炎或哮喘患者呼吸道变应原吸入刺激,可以模拟其变应原自然暴露所致疾病症状发作,研究其病理生理变化,尚可通过药物干预评估其对症状及炎症抑制程度评估药物治疗效果。同时变应性鼻炎和哮喘作为上下气道疾病,相互影响,通过一端变应原刺激研究气道另一端症状及炎症反应,探讨上下气道之间的联系。屋尘螨为我国,特别是南方地区最主要、最常见的变应原,与疾病关系密切。主要从屋尘螨变应原鼻激发和支气管激发方法学及其在鼻炎和哮喘的研究中的应用作一综述。

关键词: 变应原, 鼻炎, 哮喘, 激发, 气道反应性

Abstract:

The prevalence of allergic disease is increasing in China with the progress of urbanization and the environmental and lifestyle changes. The pathogenesis of allergic rhinitis and asthma is currently believed to be mainly caused by the interaction of genetic and environmental factors, but the specific mechanisms are not fully understood yet. Chronic airway inflammation and airway hyperresponsiveness are typical pathophysiological features of allergic rhinitis and asthma. Natural exposure to allergens in the environment can induce exacerbation of the symptoms, cause increases in airway and systemic inflammation, and lead to increased airway hyperresponsiveness. Stimulation by inhalation of allergens in patients with allergic rhinitis and asthma can induce the onset of symptoms induced by natural allergen exposure, which can be used as a model for studying the pathogenesis of allergic rhinitis and asthma and to evaluate the efficacy of treatment drugs for both conditions. As they occur in the same airway and as a single disease, allergic rhinitis and asthma impact each other. The relationship between the upper and lower airways can be examined by stimulating one end and observing the reaction of the other end of the airways. House dust mites are one of the most common allergens and well related to the severity of allergic rhinitis and asthma in China, especially in the southern areas. In this review, we summarized the application of allergen nasal and bronchial provocation in the research of allergic rhinitis and asthma.

Key words: Allergen, Rhinitis, Asthma, Inhalation challenge, Airway responsiveness

中图分类号: 

  • R765.22
1 GINA Report. Global Strategy for Asthma Management and Prevention, 2017. www.ginasthma.org.
2 Global burden of asthma. www.ginasthma.org.
3 Huggins KG , Brostoff J . Local production of specific IgE antibodies in allergic-rhinitis patients with negative skin tests[J]. Lancet, 1975, 2 (7926): 148- 150.
4 Rondón C , Romero JJ , López S , et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis[J]. J Allergy Clin Immunol, 2007, 119 (4): 899- 905.
doi: 10.1016/j.jaci.2007.01.006
5 López S , Rondón C , Torres MJ , et al. Immediate and dual response to nasal challenge with Dermatophagoides pteronyssinus in local allergic rhinitis[J]. Clin Exp Allergy, 2010, 40 (7): 1007- 1014.
doi: 10.1111/j.1365-2222.2010.03492.x
6 Muller B , de Groot EJ , Kortekaas IJ , et al. Nasal epithelial cells express IL-10 at levels that negatively correlate with clinical symptoms in patients with house dust mite allergy[J]. Allergy, 2007, 62 (9): 1014- 1022.
doi: 10.1111/j.1398-9995.2007.01419.x
7 Oh JH , Hur GY , Ye YM , et al. Correlation between specific IgA and eosinophil numbers in the lavage fluid of patients with perennial allergic rhinitis[J]. Allergy Asthma Proc, 2008, 29 (2): 152- 160.
doi: 10.2500/aap.2008.29.3069
8 Riechelmann H , Epple B , Gropper G . Comparison of conjunctival and nasal provocation test in allergic rhinitis to house dust mite[J]. Int Arch Allergy Immunol, 2003, 130 (1): 51- 59.
doi: 10.1159/000068369
9 Kirerleri E , Guler N , Tamay Z , et al. Evaluation of the nasal provocation test for its necessity in the diagnosis of nasal allergy to house dust mite[J]. Asian Pac J Allergy Immunol, 2006, 24 (2/3): 117- 121.
doi: 10.1016/j.polymer.2006.09.024
10 Keck T , Wiesmiller K , Lindemann J , et al. Acoustic rhinometry in nasal provocation test in perennial allergic rhinitis[J]. Eur Arch Otorhinolaryngol, 2006, 263 (10): 910- 916.
doi: 10.1007/s00405-006-0080-4
11 Kramer MF , Jordan TR , Klemens C , et al. Factors contributing to nasal allergic late phase eosinophilia[J]. Am J Otolaryngol, 2006, 27 (3): 190- 199.
doi: 10.1016/j.amjoto.2005.09.013
12 Lopuhaä CE , de Riemer MJ , Out TA , et al. Comparison of allergen-induced late inflammatory reactions in the nose and in the skin in house dust mite-allergic patients with or without asthma[J]. Int Arch Allergy Immunol, 2003, 130 (4): 266- 274.
doi: 10.1159/000070213
13 Brown JL , Behndig AF , Sekerel BE , et al. Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls[J]. Clin Exp Allergy, 2007, 37 (5): 688- 695.
doi: 10.1111/j.1365-2222.2007.02695.x
14 Andersson M , Rimmer J , Salome C , et al. Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis[J]. Acta Otolaryngol, 2001, 121 (3): 407- 413.
doi: 10.1080/000164801300102950
15 Marcucci F , Passalacqua G , Canonica GW , et al. Lower airway inflammation before and after house dust mite nasal challenge: an age and allergen exposure-related phenomenon[J]. Respir Med, 2007, 101 (7): 1600- 1608.
doi: 10.1016/j.rmed.2006.06.006
16 Tahamiler R , Saritzali G , Canakcioglu S , et al. Comparison of the long-term efficacy of subcutaneous and sublingual immunotherapies in perennial rhinitis[J]. ORL J Otorhinolaryngol Relat Spec, 2008, 70 (3): 144- 150.
doi: 10.1159/000124286
17 Tonnel AB , Scherpereel A , Douay B , et al. Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy[J]. Allergy, 2004, 59 (5): 491- 497.
doi: 10.1111/j.1398-9995.2004.00456.x
18 Krzych-Falta E , Piekarska B , Sybilski A , et al. The safety of nasal allergen challenge test assessed in lower airways[J]. Iran J Allergy Asthma Immunol, 2015, 14 (6): 581- 588.
19 Wang W , Xian M , Xie Y , et al. Aggravation of airway inflammation and hyper-responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma[J]. Allergy, 2016, 71 (3): 378- 386.
doi: 10.1111/all.12808
20 Wang DY , Goh DY , Ho AK , et al. The upper and lower airway responses to nasal challenge with house-dust mite Blomia tropicalis[J]. Allergy, 2003, 58 (1): 78- 82.
doi: 10.1034/j.1398-9995.2003.23746.x
21 Smith SG , Gugilla A , Mukherjee M , et al. Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma[J]. J Allergy Clin Immunol, 2015, 135 (6): 1594- 1602.
doi: 10.1016/j.jaci.2014.12.1918
22 Lopuhaä CE , Koopmans JG , Jansen HM , et al. Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge[J]. Allergy, 2003, 58 (4): 300- 305.
doi: 10.1034/j.1398-9995.2003.00075.x
23 Diamant Z , Gauvreau GM , Cockcroft DW , et al. Inhaled allergen bronchoprovocation tests[J]. J Allergy Clin Immunol, 2013, 132 (5): 1045- 1055.e6.
doi: 10.1016/j.jaci.2013.08.023
24 Agache I , Bilò M , Braunstahl GJ , et al. In vivodiagnosis of allergic diseases-allergen provocation tests[J]. Allergy, 2015, 70 (4): 355- 365.
doi: 10.1111/all.12586
25 Li J , Sun B , Huang Y , et al. A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China[J]. Allergy, 2009, 64 (7): 1083- 1092.
doi: 10.1111/j.1398-9995.2009.01967.x
26 Klimek L , Hoffmann HJ , Renz H , et al. Diagnostic test allergens used for in vivo diagnosis of allergic diseases are at risk: a European Perspective[J]. Allergy, 2015, 70 (10): 1329- 1331.
doi: 10.1111/all.12676
27 de Groot H GvWR. In-vivo diagnostiek: bronchiale provocative[M]. In: Bruijnzeel-Koomen CA, editor. Handboek Allergologie. Utrecht: De TIjdstroom 2008: 21-24.
28 Cockcroft DW , Ruffin RE , Frith PA , et al. Determinants of allergen-induced asthma: dose of allergen, circulating IgE antibody concentration, and bronchial responsiveness to inhaled histamine[J]. Am Rev Respir Dis, 1979, 120 (5): 1053- 1058.
doi: 10.1164/arrd.1979.120.5.1053
29 Casset A , Purohit A , Birba E , et al. Bronchial challenge test in asthmatics sensitized to mites: role of particle size in bronchial response[J]. J Aerosol Med, 2007, 20 (4): 509- 518.
doi: 10.1089/jam.2007.0591
30 Barnig C , Purohit A , Casset A , et al. Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the main determinants of the early and late asthmatic response to allergen[J]. J Invest Allergy Clin Immunol, 2013, 23 (4): 267- 274.
doi: 10.1159/000346530
31 Boulet LP , Gauvreau G , Boulay ME , et al. Allergen-induced early and late asthmatic responses to inhaled seasonal and perennial allergens[J]. Clin Exp Allergy, 2015, 45 (11): 1647- 1653.
doi: 10.1111/cea.12587
32 Fairfax AJ , Hanson JM , Morley J . The late reaction following bronchial provocation with house dust mite allergen. Dependence on arachidonic acid metabolism[J]. Clin Exp Immunol, 1983, 52 (2): 393- 398.
doi: 10.1016/0008-8749(83)90337-4
33 Asosingh K , Hanson JD , Cheng G , et al. Allergen-induced, eotaxin-rich, proangiogenic bone marrow progenitors: a blood-borne cellular envoy for lung eosinophilia[J]. J Allergy Clin Immunol, 2010, 125 (4): 918- 925.
doi: 10.1016/j.jaci.2010.01.017
34 El-Gammal A , Oliveria JP , Howie K , et al. Allergen-induced changes in bone marrow and airway dendritic cells in subjects with asthma[J]. Am J Respir Crit Care Med, 2016, 194 (2): 169- 177.
doi: 10.1164/rccm.201508-1623oc
35 Hong GH , Kwon HS , Moon KA , et al. Clusterin modulates allergic airway inflammation by attenuating CCL20-mediated dendritic cell recruitment[J]. J Immunol, 2016, 196 (5): 2021- 2030.
doi: 10.4049/jimmunol.1500747
36 Panganiban RP , Wang YL , Howrylak J , et al. Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma[J]. J Allergy Clin Immunol, 2016, 137 (5): 1423- 1432.
doi: 10.1016/j.jaci.2016.01.029
37 Lopuhaä CE , Out TA , Jansen HM , et al. Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma[J]. Clin Exp Allergy, 2002, 32 (12): 1720- 1727.
doi: 10.1046/j.1365-2222.2002.01542.x
38 Alvarez MJ , Olaguibel JM , Garcia BE , et al. Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients[J]. Allergy, 2000, 55 (6): 531- 539.
doi: 10.1034/j.1398-9995.2000.00534.x
39 Krug N , Hohlfeld JM , Kirsten AM , et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme[J]. N Engl J Med, 2015, 372 (21): 1987- 1995.
doi: 10.1056/NEJMoa1411776
40 van Rensen EL , Evertse CE , van Schadewijk WA , et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment[J]. Allergy, 2009, 64 (1): 72- 80.
doi: 10.1111/j.1398-9995.2008.01881.x
41 Singh D , Richards D , Knowles RG , et al. Selective inducible nitric oxide synthase inhibition has no effect on allergen challenge in asthma[J]. Am J Respir Crit Care Med, 2007, 176 (10): 988- 993.
doi: 10.1164/rccm.200704-588OC
42 Hesslinger C , Strub A , Boer R , et al. Inhibition of inducible nitric oxide synthase in respiratory diseases[J]. Biochem Soc Trans, 2009, 37 (Pt 4): 886- 891.
doi: 10.1042/BST0370886
43 Tworek D , Smith SG , Salter BM , et al. IL-25 receptor expression on airway dendritic cells after allergen challenge in subjects with asthma[J]. Am J Respir Crit Care Med, 2016, 193 (9): 957- 964.
doi: 10.1164/rccm.201509-1751OC
[1] 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.
[2] 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.
[3] 秦雅楠,王琳,姜彦,闫舒,陈敏,于龙刚,李娜. 2008~2017年青岛地区变应性鼻炎常见吸入性变应原分布[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 67-72.
[4] 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.
[5] 杜经纬,冯俊,马鹏,李志勇,李红光. 鼻腔冲洗联合鼻用糖皮质激素对AR患者FeNO、肺功能及生活质量的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 124-127.
[6] 洪冬冬,刘元献,邹练强,翁镌凌,邓文娴. 变应性鼻炎患者粉尘螨皮肤点刺试验阳性764例结果分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 119-123.
[7] 齐岩,刘俊其,彭舒娅,罗凯,张名霞,王振霖. 鼻内镜下选择性翼管神经切断术对伴有变应性鼻炎的慢性鼻窦炎的疗效观察[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 109-113.
[8] 关凯,王良录. 从花粉症看过敏性疾病的整体诊疗策略[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 13-19.
[9] 郭胤仕,卢慧. Ⅱ型固有淋巴细胞在变应性鼻炎发病机制中的作用[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 9-12.
[10] 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.
[11] 曹成,许昱. 变应性鼻炎患者舌下免疫治疗的临床依从性192例分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 114-118.
[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] 沙莉,刘传合. 生物制剂治疗支气管哮喘的研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 53-58.
[14] 金兴,胡大宇,朱丽,邓芙蓉,刘俊秀. PM2.5与变应性鼻炎患者上气道阻力的相关性研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 77-80.
[15] 李丽莎,关凯,王子熹,崔乐. 大气污染物对于变应性鼻炎症状严重度的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 81-87.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 林彬,王挥戈 . 功能性内镜鼻窦手术后鼻黏膜纤毛转归的研究[J]. 山东大学耳鼻喉眼学报, 2006, 20(6): 481 -487 .
[2] 杨长亮,黄治物,姚行齐,诸勇,孙艺 . 正常气骨导听性脑干反应及其应用[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 9 -13 .
[3] 栾建刚,梁传余,文艳君,李炯 . 抑制表皮生长因子受体基因表达的pSIREN-ShuttleRNAi表达载体的构建[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 4 -8 .
[4] 楼正才 . 掌拳击伤鼓膜损伤机制及临床特点分析[J]. 山东大学耳鼻喉眼学报, 2008, 22(2): 188 -188 .
[5] 万俐佳,鲁海涛,姜义道,刘 辉,李 琴,佘腊枝 . 改良腭咽成形术治疗阻塞性睡眠呼吸暂停综合征41例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 204 -205 .
[6] 汪晓锋,林 昶,程金妹 . 不同龄小鼠内耳中ABAD的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 207 -211 .
[7] 刘 艳,刘新义,王金平,李大健 . 后鼓室解剖结构测量观察及临床意义[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 218 -221 .
[8] 于青青 综述,王跃建 审校 . 硬质耳内镜的临床应用进展[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 222 -224 .
[9] 刘强和,罗香林,耿宛平,陈 晨,雷 迅,刘芳贤,邓 明 . 快速老化小鼠的听功能和耳蜗螺旋神经元的增龄性变化[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 215 -217 .
[10] 杨淑娟,袁 英,刘付星,秦海平 . 美宝湿润烧伤膏联合蛋膜贴补治疗外伤性鼓膜穿孔40例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 227 -227 .