慢性鼻窦炎伴鼻息肉的内型研究及其指导下的精准控制与治疗

doi:10.6040/j.issn.1673-3770.1.2022.005

摘要/Abstract

摘要： 慢性鼻窦炎伴鼻息肉(CRSwNP)是指病程超过12周、伴息肉形成的鼻腔鼻窦慢性炎症,是一组表型相似但内在机制存在显著差异的复杂疾病。基于其中参与的炎症因子及其病理机制的不同可将其分为1、2、3型炎症,其中2型炎症对应于嗜酸粒细胞浸润为主的CRSwNP。不同内型(endotype)的临床表现、人口学特征、治疗反应性、预后均存在差异。因此,在深入了解不同内型病理机制的基础上,可根据其临床特点建立多种间接预测模型,以优化诊断;还可在内型指导下实现症状的精准控制与治疗,以改善预后。本文就CRSwNP内型的研究进展及其指导下的精准控制与治疗作一综述。

关键词: 慢性鼻窦炎, 鼻息肉, 内型, 2型炎症, 生物制剂

Abstract: Chronic rhinosinusitis with nasal polyps(CRSwNP)refers to chronic inflammation of the nasal cavity and paranasal sinuses with polyp formation over a course of more than 12 weeks. CRSwNP covers a group of complex diseases with similar phenotypes, but significantly different underlying mechanisms. Based on the inflammatory factors involved and the pathological mechanisms, CRSwNP can be divided into type 1, 2, and 3 inflammation, among which type 2 inflammation corresponds to CRSwNP dominated by eosinophil infiltration. There are many differences in the clinical manifestations, demographic characteristics, treatment responses, and prognosis of the different endotypes. Therefore, to optimize diagnosis, it is necessary to establish indirect predictive models that are based on the clinical characteristics and an in-depth of the different pathological mechanisms. Furthermore, the accurate control and treatment of symptoms can also be achieved to improve prognosis, under the guidance of endotypes. This article reviews the current progresses in the field of CRSwNP endotypes and their precise control and treatment under clinical guidance.

Key words: Chronic rhinosinusitis, Nasal polyps, Endotype, Type 2 inflammation, Biologics

中图分类号:

R765.41

敖天, 程雷. 慢性鼻窦炎伴鼻息肉的内型研究及其指导下的精准控制与治疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 7-14.

AO Tian,CHENG Lei. An endotype study of chronic rhinosinusitis with nasal polyps and precise control and treatment under the guidance[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 7-14.

参考文献

[1] Shi JB, Fu QL, Zhang H, et al. Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities[J]. Allergy, 2015, 70(5): 533-539. doi:10.1111/all.12577.
[2] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国慢性鼻窦炎诊断和治疗指南(2018)[J]. 中华耳鼻咽喉头颈外科杂志, 2019, 54(2): 81-100. doi:10.3760/cma.j.issn.1673-0860.2019.02.001.
[3] Benjamin MR, Stevens WW, Li N, et al. Clinical characteristics of patients with chronic rhinosinusitis without nasal polyps in an academic setting[J]. J Allergy Clin Immunol Pract, 2019, 7(3): 1010-1016. doi:10.1016/j.jaip.2018.10.014.
[4] Kong IG, Kim DW. Pathogenesis of recalcitrant chronic rhinosinusitis: the emerging role of innate immune cells[J]. Immune Netw, 2018, 18(2): e6. doi:10.4110/in.2018.18.e6.
[5] Khan A, Vandeplas G, Huynh TMT, et al. The Global Allergy and Asthma European Network(GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps[J]. Rhinology, 2019, 57(1): 32-42. doi:10.4193/Rhin17.255.
[6] Shay AD, Tajudeen BA. Histopathologic analysis in the diagnosis and management of chronic rhinosinusitis[J]. Curr Opin Otolaryngol Head Neck Surg, 2019, 27(1): 20-24. doi:10.1097/MOO.0000000000000510.
[7] Brescia G, Zanotti C, Parrino D, et al. Nasal polyposis pathophysiology: Endotype and phenotype open issues[J]. Am J Otolaryngol, 2018, 39(4): 441-444. doi:10.1016/j.amjoto.2018.03.020.
[8] Wang XD, Zhang N, Bo MY, et al. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania[J]. J Allergy Clin Immunol, 2016, 138(5): 1344-1353. doi:10.1016/j.jaci.2016.05.041.
[9] Kim DW, Cho SH. Emerging endotypes of chronic rhinosinusitis and its application to precision medicine[J]. Allergy Asthma Immunol Res, 2017, 9(4): 299-306. doi:10.4168/aair.2017.9.4.299.
[10] Cao PP, Wang ZC, Schleimer RP, et al. Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes[J]. Ann Allergy Asthma Immunol, 2019, 122(1): 33-40. doi:10.1016/j.anai.2018.10.014.
[11] Delemarre T, Holtappels G, de Ruyck N, et al. Type 2 inflammation in chronic rhinosinusitis without nasal polyps: another relevant endotype[J]. J Allergy Clin Immunol, 2020, 146(2): 337-343.e6. doi:10.1016/j.jaci.2020.04.040.
[12] Grayson JW, Hopkins C, Mori ER, et al. Contemporary classification of chronic rhinosinusitis beyond polyps vs no polyps: a review[J]. JAMA Otolaryngol Head Neck Surg, 2020, 146(9): 831-838. doi:10.1001/jamaoto.2020.1453.
[13] Dogan M, Sahin M, Yenisey C. Increased TSLP, IL-33, IL-25, IL-19, IL-21 and amphiregulin(AREG)levels in chronic rhinosinusitis with nasal polyp[J]. Eur Arch Otorhinolaryngol, 2019, 276(6): 1685-1691. doi:10.1007/s00405-019-05379-8.
[14] Divekar R, Kita H. Recent advances in epithelium-derived cytokines(IL-33, IL-25, and thymic stromal lymphopoietin)and allergic inflammation[J]. Curr Opin Allergy Clin Immunol, 2015, 15(1): 98-103. doi:10.1097/ACI.0000000000000133.
[15] Ahern S, Cervin A. Inflammation and endotyping in chronic rhinosinusitis-A paradigm shift[J]. Medicina(Kaunas), 2019, 55(4): 95. doi:10.3390/medicina55040095.
[16] Ryu G, Kim DW. Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis[J]. Curr Opin Allergy Clin Immunol, 2020, 20(1): 1-8. doi:10.1097/ACI.0000000000000588.
[17] Bachert C, Zhang N, Hellings PW, et al. Endotype-driven care pathways in patients with chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2018, 141(5): 1543-1551. doi:10.1016/j.jaci.2018.03.004.
[18] Klingler AI, Stevens WW, Tan BK, et al. Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps[J]. J Allergy Clin Immunol, 2021, 147(4): 1306-1317. doi:10.1016/j.jaci.2020.11.037.
[19] Ryu G, Kim DK, Dhong HJ, et al. Immunological characteristics in refractory chronic rhinosinusitis with nasal polyps undergoing revision surgeries[J]. Allergy Asthma Immunol Res, 2019, 11(5): 664-676. doi:10.4168/aair.2019.11.5.664.
[20] 陈杰, 毛弈友, 陈卓, 等. Ⅱ型炎症在慢性鼻窦炎伴鼻息肉中的作用机制和治疗进展[J]. 中华耳鼻咽喉头颈外科杂志, 2020, 55(10): 993-997. doi:10.3760/cma.j.cn115330-20200813-00671. CHEN Jie, MAO Yiyou, CHEN Zhuo, et al. Research progress on the role of type Ⅱ inflammation in chronic rhinosinusitis with polyps[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2020, 55(10): 993-997. doi:10.3760/cma.j.cn115330-20200813-00671.
[21] Patel NN, Kohanski MA, Maina IW, et al. Solitary chemosensory cells producing interleukin-25 and group-2 innate lymphoid cells are enriched in chronic rhinosinusitis with nasal polyps[J]. Int Forum Allergy Rhinol, 2018,(8):900-906. doi:10.1002/alr.22142.
[22] Hong HY, Chen FH, Sun YQ, et al. Nasal IL-25 predicts the response to oral corticosteroids in chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2018, 141(5): 1890-1892. doi:10.1016/j.jaci.2017.10.050.
[23] Yamada T, Miyabe Y, Ueki S, et al. Eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration in chronic rhinosinusitis[J]. Front Immunol, 2019, 10: 74. doi:10.3389/fimmu.2019.00074.
[24] Hwang CS, Park SC, Cho HJ, et al. Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status[J]. Sci Rep, 2019, 9(1): 8061. doi:10.1038/s41598-019-44627-z.
[25] Ueki S, Tokunaga T, Melo RCN, et al. Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death[J]. Blood, 2018, 132(20): 2183-2187. doi:10.1182/blood-2018-04-842260.
[26] Persson EK, Verstraete K, Heyndrickx I, et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment[J]. Science, 2019, 364(6442): eaaw4295. doi:10.1126/science.aaw4295.
[27] Wu D, Yan B, Wang Y, et al. Charcot-Leyden crystal concentration in nasal secretions predicts clinical response to glucocorticoids in patients with chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2019, 144(1): 345-348.e8. doi:10.1016/j.jaci.2019.03.029.
[28] 杜崑, 郑铭, 王向东, 等. 白细胞介素-21与复发性鼻息肉组织中IgE的相关性分析[J]. 首都医科大学学报, 2020, 41(2): 194-199. doi:10.3969/j.issn.1006-7795.2020.02.009. DU Kun, ZHENG Ming, WANG Xiangdong, et al. Analysis for the relationship between interleukin-21 and tissue IgE in recurrent nasal polyps[J]. Journal of Capital Medical University, 2020, 41(2): 194-199. doi:10.3969/j.issn.1006-7795.2020.02.009.
[29] Gong F, Zheng T, Zhou PC. T follicular helper cell subsets and the associated cytokine IL-21 in the pathogenesis and therapy of asthma[J]. Front Immunol, 2019, 10: 2918. doi:10.3389/fimmu.2019.02918.
[30] Oakley GM, Christensen JM, Sacks R, et al. Characteristics of macrolide responders in persistent post-surgical rhinosinusitis[J]. Rhinology, 2018, 56(2): 111-117. doi:10.4193/Rhin17.049.
[31] Besnard AG, Sabat R, Dumoutier L, et al. Dual Role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A[J]. Am J Respir Crit Care Med, 2011, 183(9): 1153-1163. doi:10.1164/rccm.201008-1383OC.
[32] Choy DF, Hart KM, Borthwick LA, et al. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma[J]. Sci Transl Med, 2015, 19(7): 301ra129. doi:10.1126/scitranslmed.aab3142.
[33] Yang X, Shen S, Deng Y, et al. Air pollution exposure affects severity and cellular endotype of chronic rhinosinusitis with nasal polyps[J]. Laryngoscope, 2021:6. doi:10.1002/lary.29974.
[34] Stevens WW, Peters AT, Tan BK, et al. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis[J]. J Allergy Clin Immunol Pract, 2019, 7(8): 2812-2820.e3. doi:10.1016/j.jaip.2019.05.009.
[35] Ryu G, Dhong HJ, Park M, et al. Age-associated changes in chronic rhinosinusitis endotypes[J]. Clin Exp Allergy, 2020, 50(5): 585-596. doi:10.1111/cea.13586.
[36] Wang M, Bu XT, Fang GL, et al. Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps[J]. Allergy, 2021, 76(3): 789-803. doi:10.1111/all.14665.
[37] 胡万玉, 敖天, 殷敏, 等. 慢性鼻-鼻窦炎伴与不伴鼻息肉患者临床特征的比较[J]. 国际耳鼻咽喉头颈外科杂志, 2020, 44(2): 63-68. doi:10.3760/cma.j.issn.1673-4106.2020.02.006. HU Wanyu, AO Tian, YIN Min, et al. Comparison of clinical characteristics of chronic rhinosinusitis with and without nasal polyps[J]. International Journal of Otolaryngology-Head and Neck Surgery, 2020, 44(2): 63-68. doi:10.3760/cma.j.issn.1673-4106.2020.02.006.
[38] 陶丹丹, 董红军, 褚云锋, 等. 慢性鼻-鼻窦炎伴鼻息肉患者组织嗜酸性粒细胞与嗅觉功能障碍的相关性研究[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 16-20. doi:10.6040/j.issn.1673-3770.0.2019.388. TAO Dandan, DONG Hongjun, CHU Yunfeng, et al. Correlation between eosinophils and olfactory dysfunction in patients with CRSwNP after nasal operation[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(6): 16-20. doi:10.6040/j.issn.1673-3770.0.2019.388.
[39] Lou HF, Meng YF, Piao YS, et al. Cellular phenotyping of chronic rhinosinusitis with nasal polyps[J]. Rhinology, 2016, 54(2): 150-159. doi:10.4193/Rhino15.271.
[40] Wei B, Liu F, Zhang J, et al. Multivariate analysis of inflammatory endotypes in recurrent nasal polyposis in a Chinese population[J]. Rhinology, 2018, 56(3): 216-226. doi:10.4193/Rhin17.240.
[41] Lin L, Lan J, Dai F, et al. Efficacy of budesonide nasal spray on neutrophilic chronic rhinosinusitis with nasal polyps: a combined clinical and experimental study[J]. Int Arch Allergy Immunol, 2020, 181(7): 551-562. doi:10.1159/000507395.
[42] Cao PP, Li HB, Wang BF, et al. Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese[J]. J Allergy Clin Immunol, 2009, 124(3): 478-484, 484.e1-2. doi:10.1016/j.jaci.2009.05.017.
[43] Lou HF, Zhang N, Bachert C, et al. Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement[J]. Int Forum Allergy Rhinol, 2018, 8(11): 1218-1225. doi:10.1002/alr.22214.
[44] Tokunaga T, Sakashita M, Haruna T, et al. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study[J]. Allergy, 2015, 70(8): 995-1003. doi:10.1111/all.12644.
[45] Lou HF, Meng YF, Piao YS, et al. Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population[J]. Am J Rhinol Allergy, 2015, 29(5): 350-356. doi:10.2500/ajra.2015.29.4231.
[46] Meng YF, Lou HF, Wang CS, et al. Predictive significance of computed tomography in eosinophilic chronic rhinosinusitis with nasal polyps[J]. Int Forum Allergy Rhinol, 2016, 6(8): 812-819. doi:10.1002/alr.21749.
[47] Hu Y, Cao PP, Liang GT, et al. Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults[J]. Laryngoscope, 2012, 122(3): 498-503. doi:10.1002/lary.22507.
[48] 李静, 施心怡, 杨瑶, 等. 慢性鼻窦炎的临床病理与预后关系的探讨[J]. 临床耳鼻咽喉头颈外科杂志, 2021, 35(10): 914-919. doi:10.13201/j.issn.2096-7993.2021.10.011. LI Jing, SHI Xinyi, YANG Yao, et al. The relationship between clinical pathology and prognosis of chronic rhinosinusitis[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2021, 35(10): 914-919. doi:10.13201/j.issn.2096-7993.2021.10.011.
[49] 张志存, 李佩忠, 唐海燕, 等. 慢性鼻-鼻窦炎伴鼻息肉患者外周血和息肉组织中嗜酸粒细胞相关性分析[J]. 临床耳鼻咽喉头颈外科杂志, 2019, 33(1): 14-16, 22. doi:10.13201/j.issn.1001-1781.2019.01.004. ZHANG Zhicun, LI Peizhong, TANG Haiyan, et al. Correlation analysis of eosinophils in peripheral blood and polyp tissues of patients with chronic rhinosinusitis with nasal polyps[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2019, 33(1): 14-16, 22. doi:10.13201/j.issn.1001-1781.2019.01.004.
[50] Ba L, Zhang N, Meng J, et al. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps[J]. Allergy, 2011, 66(10): 1296-1303. doi:10.1111/j.1398-9995.2011.02637.x.
[51] Zhu MD, Gao XH, Zhu Z, et al. The roles of nasal nitric oxide in diagnosis and endotypes of chronic rhinosinusitis with nasal polyps[J]. J Otolaryngol Head Neck Surg, 2020, 49(1): 68. doi:10.1186/s40463-020-00465-y.
[52] Pundir V, Pundir J, Lancaster G, et al. Role of corticosteroids in Functional Endoscopic Sinus Surgery: a systematic review and meta-analysis[J]. Rhinology, 2016, 54(1): 3-19. doi:10.4193/Rhino15.079.
[53] Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma[J]. Allergy, 2019, 74(12): 2312-2319. doi:10.1111/all.13875.
[54] Fokkens WJ, Lund VJ, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020[J]. Rhinology, 2020, 58(Suppl S29): 1-464. doi:10.4193/Rhin20.600.
[55] 王成硕, 张罗. 慢性鼻窦炎伴鼻息肉进入生物制剂治疗时代[J]. 中华耳鼻咽喉头颈外科杂志, 2021, 56(10): 1023-1027. doi:10.3760/cma.j.cn115330-20210509-00260. WANG Chengshuo, ZHANG Luo. Biologics: a new option in treatment of chronic rhinosinusitis with nasal polyps[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2021, 56(10): 1023-1027. doi:10.3760/cma.j.cn115330-20210509-00260.
[56] 奥马珠单抗治疗过敏性哮喘专家组, 中华医学会呼吸病学分会哮喘学组. 奥马珠单抗治疗过敏性哮喘的中国专家共识[J]. 中华结核和呼吸杂志, 2018, 41(3): 179-185. doi:10.3760/cma.j.issn.1001-0939.2018.03.007.
[57] 国家呼吸系统疾病临床医学研究中心, 中华医学会儿科学分会呼吸学组哮喘协作组, 中国医药教育协会儿科专业委员会, 等. 奥马珠单抗在儿童过敏性哮喘临床应用专家共识[J]. 中华实用儿科临床杂志, 2021, 36(12): 881-890. doi:10.3760/cma.j.cn101070-20210531-00621.
[58] Gevaert P, Calus L, van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma[J]. J Allergy Clin Immunol, 2013, 131(1): 110-116.e1. doi:10.1016/j.jaci.2012.07.047.
[59] Bachert C, Nan Z, Cavaliere C, et al. Biologics for chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2020, 145(3): 725-739. doi:10.1016/j.jaci.2020.01.020.
[60] Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study[J]. Am J Respir Crit Care Med, 2011, 184(10): 1125-1132. doi:10.1164/rccm.201103-0396OC.
[61] Busse W, Chupp G, Nagase H, et al. Anti-IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: indirect treatment comparison[J]. J Allergy Clin Immunol, 2019, 143(1): 190-200.e20. doi:10.1016/j.jaci.2018.08.031.
[62] Bleecker ER, FitzGerald JM, Chanez 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[J]. Lancet, 2016, 388(10056): 2115-2127. doi:10.1016/S0140-6736(16)31324-1.
[63] Patel GB, Peters AT. The role of biologics in chronic rhinosinusitis with nasal polyps[J]. Ear Nose Throat J, 2021, 100(1): 44-47. doi:10.1177/0145561320964653.
[64] Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial[J]. JAMA, 2016, 315(5): 469-479. doi:10.1001/jama.2015.19330.
[65] Sawangjit R, Dilokthornsakul P, Lloyd-Lavery A, et al. Systemic treatments for eczema: a network meta-analysis[J]. Cochrane Database Syst Rev, 2020, 9(9): CD013206. doi:10.1002/14651858.CD013206.pub2.
[66] Osinka K, Dumycz K, Kwiek B, et al. Novel therapeutic approaches to atopic dermatitis[J]. Arch Immunol Ther Exp(Warsz), 2018, 66(3): 171-181. doi:10.1007/s00005-017-0487-1.
[67] Pelaia C, Pelaia G, Longhini F, et al. Monoclonal antibodies targeting alarmins: a new perspective for biological therapies of severe asthma[J]. Biomedicines, 2021, 9(9): 1108. doi:10.3390/biomedicines9091108.
[68] Schleimer RP, Schnaar RL, Bochner BS. Regulation of airway inflammation by Siglec-8 and Siglec-9 sialoglycan ligand expression[J]. Curr Opin Allergy Clin Immunol, 2016, 16(1): 24-30. doi:10.1097/ACI.0000000000000234.
[69] Lavigne P, Lee SE. Immunomodulators in chronic rhinosinusitis[J]. World J Otorhinolaryngol Head Neck Surg, 2018, 4(3): 186-192. doi:10.1016/j.wjorl.2018.09.002.
[70] Ghafouri-Fard S, Shoorei H, Taheri M, et al. Emerging role of non-coding RNAs in allergic disorders[J]. Biomed Pharmacother, 2020, 130: 110615. doi: 10.1016/j.biopha.2020.110615.
[71] Tubita V, Callejas-Díaz B, Roca-Ferrer J, et al. Role of microRNAs in inflammatory upper airway diseases[J]. Allergy, 2021, 76(7):1967-1980. doi: 10.1111/all.14706.
[72] Qiu CY, Cui XY, Lu MP, et al. CircRNA expression profiles and circRNA-miRNA-mRNA crosstalk in allergic rhinitis[J]. World Allergy Organ J, 2021,14(6):100548. doi: 10.1016/j.waojou.2021.100548.

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