Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (3): 30-35.doi: 10.6040/j.issn.1673-3770.1.2022.572

Previous Articles     Next Articles

Research progress in biologic targeted drug therapy for chronic sinusitis

LIANG XuOverview,SHI Li   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2022-06-15

PDF (PC)

417

Abstract: Chronic sinusitis(CRS)is a chronic inflammatory disease of the nasal cavity and sinuses. Based on its pathogenesis, CRS can be divided into type 1, type 2, and type 3 inflammatory intrinsic type. At present, the drug therapy and surgical treatment of CRS have the risk of various adverse reactions and complications; among these cases of refractory sinusitis, some cannot achieve satisfactory results and are prone to recurrence despite appropriate drug and surgical treatment, thus seriously affecting the quality of life of patients. The application and development of biologic targeted drugs provide an effective and safe alternative to the treatment of CRS. This review focuses on the research progress of biologic targeted drug therapy targeting the cytokines associated with the three intrinsic types of CRS inflammation, including TNF-α, IL-4, IL-5, IL-13, IgE, and IL-17.

Key words: Sinusitis, Nasal polyps, Eosinophils, Inflammatory factor, Biologic targeted drug, Treatment

CLC Number: 

  • R765.41
[1] 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.
[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(2):81-100. doi: 10.3760/cma.j.issn.1673-0860.2019.02.001.
[3] van der Veen J, Seys SF, Timmermans M, et al. Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre[J]. Allergy, 2017, 72(2):282-290. doi:10.1111/all.12983.
[4] Deconde AS, Mace JC, Levy J M, et al. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis[J]. Laryngoscope, 2017, 127(3):550-555. doi:10.1002/lary.26391.
[5] Lou H, Meng Y, Piao Y, 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.
[6] Hox V, Lourijsen E, Jordens A, et al. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper[J]. Clin Transl Allergy, 2020, 3(10):1. doi:10.1186/s13601-019-0303-6.
[7] 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.
[8] Zhang N, Van Zele T, Perez-Novo C, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease[J]. J Allergy Clin Immunol, 2008, 122(5):961-968. doi:10.1016/j.jaci.2008.07.008.
[9] Michel O, Dinh PH, Doyen V, et al. Anti-TNF inhibits the airways neutrophilic inflammation induced by inhaled endotoxin in human[J]. BMC Pharmacol Toxicol, 2014,3(15):60. doi:10.1186/2050-6511-15-60.
[10] Malaviya R, Laskin JD, Laskin DL. Anti-TNFalpha therapy in inflammatory lung diseases[J]. Pharmacol Ther, 2017, 180:90-98. doi:10.1016/j.pharmthera.2017.06.008.
[11] Winthrop KL. Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor[J]. Nat Clin Pract Rheumatol, 2006, 2(11):602-610. doi:10.1038/ncprheum0336.
[12] Van Crombruggen K, Zhang N, Gevaert P, et al. Pathogenesis of chronic rhinosinusitis: inflammation[J]. J Allergy Clin Immunol, 2011, 128(4):728-732. doi:10.1016/j.jaci.2011.07.049.
[13] Lan F, Zhang N, Holtappels G, et al. Staphylococcus aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines[J]. Am J Respir Crit Care Med, 2018, 198(4):452-463. doi:10.1164/rccm.201710-2112OC.
[14] Kohanski MA, Workman AD, Patel NN, et al. Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2018, 142(2):460-469. doi:10.1016/j.jaci.2018.03.019.
[15] Nagarkar DR, Poposki JA, Tan BK, et al. Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2013, 132(3):593-600. doi:10.1016/j.jaci.2013.04.005.
[16] Shaw JL, Fakhri S, Citardi MJ, et al. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps[J]. Am J Respir Crit Care Med, 2013, 188(4):432-439. doi:10.1164/rccm.201212-2227OC.
[17] Poposki JA, Klingler AI, Tan BK, et al. Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps[J]. Immun Inflamm Dis, 2017, 5(3):233-243. doi:10.1002/iid3.161.
[18] Nagarkar DR, Poposki JA, Comeau MR, et al. Airway epithelial cells activate TH2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin[J]. J Allergy Clin Immunol, 2012,130(1):225-232. doi:10.1016/j.jaci.2012.04.019.
[19] Cao PP, Zhang YN, Liao B, et al. Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps[J]. Clin Exp Allergy, 2014, 44(5):690-700. doi:10.1111/cea.12304.
[20] Bachert C, Han JK, Wagenmann M, et al. EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps(CRSwNP)and biologics: Definitions and management[J]. J Allergy Clin Immunol, 2021,147(1):29-36. doi:10.1016/j.jaci.2020.11.013.
[21] Kim H, Ellis AK, Fischer D, et al. Asthma biomarkers in the age of biologics[J]. Allergy Asthma Clin Immunol, 2017, 17(13):48. doi:10.1186/s13223-017-0219-4.
[22] Bachert C, Wagenmann M, Hauser U, et al. IL-5 synthesis is upregulated in human nasal polyp tissue[J]. J Allergy Clin Immunol, 1997, 99(6 Pt 1):837-842. doi:10.1016/s0091-6749(97)80019-x.
[23] Bachert C, Sousa AR, Lund VJ, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial[J]. J Allergy Clin Immunol, 2017, 140(4):1024-1031. doi:10.1016/j.jaci.2017.05.044.
[24] Gevaert P, Van Bruaene N, Cattaert T, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis[J]. J Allergy Clin Immunol, 2011, 128(5):989-995. doi:10.1016/j.jaci.2011.07.056.
[25] Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps[J]. J Allergy Clin Immunol, 2006,118(5):1133-1141. doi:10.1016/j.jaci.2006.05.031.
[26] Mitchell P, Leigh R. A drug safety review of treating eosinophilic asthma with monoclonal antibodies[J]. Expert Opin Drug Saf, 2019, 18(12):1161-1170. doi:10.1080/14740338.2019.1675634.
[27] Tamechika SY, Isogai S, Maeda S, et al. Improvement of Chronic Rhinosinusitis and Reduction of the Myeloperoxidase-Antineutrophil Cytoplasmic Antibody Titer in a Patient with Eosinophilic Granulomatosis with Polyangiitis by Additional Mepolizumab[J]. Case Rep Rheumatol, 2021, 29:5561762. doi:10.1155/2021/5561762.
[28] 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.
[29] Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps(LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials[J]. Lancet, 2019, 394(10209):1638-1650. doi:10.1016/S0140-6736(19)31881-1.
[30] Desrosiers M, Mannent LP, Amin N, et al. Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP[J]. Rhinology, 2021, 59(3):301-311. doi:10.4193/Rhin20.415.
[31] 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. doi:10.1016/j.jaci.2012.07.047.
[32] Pinto JM, Mehta N, Ditineo M, et al. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis[J]. Rhinology, 2010, 48(3):318-324. doi:10.4193/Rhino09.144.
[33] Wu Q, Yuan L, Qiu H, et al. Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials[J]. BMJ Open, 2021, 11(9):e47344. doi:10.1136/bmjopen-2020-047344.
[34] Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis[J]. J Allergy Clin Immunol, 2015, 136(6):1431-1440. doi:10.1016/j.jaci.2015.10.010.
[35] Sel S, Wegmann M, Dicke T, et al. Effective prevention and therapy of experimental allergic asthma using a GATA-3-specific DNAzyme[J]. J Allergy Clin Immunol, 2008, 121(4):910-916. doi:10.1016/j.jaci.2007.12.1175.
[36] Garn H, Renz H. GATA-3-specific DNAzyme - A novel approach for stratified asthma therapy[J]. Eur J Immunol, 2017, 47(1):22-30. doi:10.1002/eji.201646450.
[37] Gauvreau GM, O'Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses[J]. N Engl J Med, 2014, 370(22):2102-2110. doi:10.1056/NEJMoa1402895.
[38] Shin HW, Kim DK, Park MH, et al. IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2015, 135(6):1476-1485. doi:10.1016/j.jaci.2015.01.003.
[39] Teufelberger AR, Nordengrun M, Braun H, et al. The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D[J]. J Allergy Clin Immunol, 2018, 141(2):549-559. doi:10.1016/j.jaci.2017.05.004.
[40] Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps[J]. J Allergy Clin Immunol, 2006, 118(5):1133-1141. doi:10.1016/j.jaci.2006.05.031.
[41] Eidenschenk C, Rutz S, Liesenfeld O, et al. Role of IL-22 in microbial host defense[J]. Curr Top Microbiol Immunol, 2014, 380:213-236. doi:10.1007/978-3-662-43492-5_10.
[42] Nirula A, Nilsen J, Klekotka P, et al. Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases[J]. Rheumatology(Oxford), 2016, 55(suppl 2):i43-i55.doi:10.1093/rheumatology/kew346.
[43] 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.
[44] Catley MC, Coote J, Bari M, et al. Monoclonal antibodies for the treatment of asthma[J]. Pharmacol Ther, 2011, 132(3):333-351.doi:10.1016/j.pharmthera.2011.09.005.
[45] Legrand F, Cao Y, Wechsler JB, et al. Sialic acid-binding immunoglobulin-like lectin(Siglec)8 in patients with eosinophilic disorders: Receptor expression and targeting using chimeric antibodies[J]. J Allergy Clin Immunol, 2019, 143(6):2227-2237. doi:10.1016/j.jaci.2018.10.066.
[1] FENG Sicong, YU Xiaolan, LOU Dan. Evaluation of the effect of Messerklinger middle turbinate plasty on chronic rhinosinusitis with nasal polyps based on the expression of Ki67 and GM-CSF in vesicular tissue [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 31-39.
[2] LI Kai, LUO Dan. Runmu ling formula ameliorates ocular surface damage in dry eye rats by activating the LC3-ATG5 autophagy pathway and inhibiting inflammatory factor expression [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 92-101.
[3] ZHAI Xuechun, BIAN Xin, CHEN Jingcai, DENG Jiayu, YE Zi, YANG Pingli. Characteristics and influencing factors of anxiety and depression in patients with chronic frontal sinusitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 35-43.
[4] ZHU Mingqiong, LI Zheng, LIU Ru, TIAN Tao, PENG Jingli, LYU Qianyi, TAN Huaxia. The application of AI screening system based on OCT/OCTA in the evaluation of the effect of anti VEGF treatment in patients with diabetes macular edema [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 68-73.
[5] LU Zhaoyang, ZHAI Zhaoxue, WANG Huikang, SHAO Liting, ZHANG Yu. COVID-19 treatment-induced diabetic ketoacidosis combined with rhino-orbital cerebral mucormycosis: a case report and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 90-94.
[6] LIU Yijie, LU Xiuzhen, WU Qiuxin. Research rogress of exosomes in the pathogenesis, diagnosis and treatment in ophthalmic diseases [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 135-141.
[7] LI Zan, LU Qi, SHEN Weidong, HOU Zhaohui, WU Nan. Clinical diagnosis and treatment features of 18 cases of necrotizing otitis externa [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 17-22.
[8] LI Yangsong, YUAN Fayang, YANG Yan, ZHANG Tian, YU Guodong. Bibliometric analysis of biologic agents for the treatment of chronic rhinosinusitis based on the Web of Science database [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 54-64.
[9] DU Kangli, ZHENG Zhenyu, XU Zhanjiang, ZHANG Yu, CHEN Lu, LU Mengyao. Construction and validation of risk prediction model for nasal septal deviation complicated with chronic sinusitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 78-86.
[10] LIU Yuzhu, CHEN Yao, YUAN Tiejun, LI Chunsen, LI Bo. Larynx fibrosarcoma: a case report and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 133-137.
[11] XIONG Qin, ZHANG Yan, WU Rina, LI Feng, TANG Lixing. Application of intranasal corticosteroids in pediatrics [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 160-167.
[12] HUANG Huan, HUA Hongli, DENG Yuqin, JIANG Chengyang, WANG Yuwei, YANG Xinghai. Correlation of allergic rhinitis, tonsil adenoid hypertrophy, and sinusitis in children and analysis of its clinical guiding value [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(5): 34-41.
[13] ZHANG Jiaqi, YUAN Ye, HONG Chen, GU Min, CHENG Lei, LU Meiping. Mendelian randomization study of gut microbiota, chronic sinusitis, and nasal polyps: Causal relationships and metabolite-mediated effects [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(5): 49-60.
[14] ZHANG Ting, WANG Meilan, GAO Yingqin. Research progress of IL-35 in allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(5): 139-147.
[15] GU Zhanxin, ZHAO Zhouyang, ZHANG Xiaobin, YANG Yimei, HUANG Lijin, HUANG Yan. Syndrome differentiation treatment and understanding of traditional Chinese medicine in carotid blowout syndrome [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(4): 100-107.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd