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摘要: 慢性鼻窦炎(chronic rhinosinusitis，CRS)是累及鼻窦黏膜超过12周的炎性疾病，根据临床表型是否合并鼻息肉(nasal polyp，NP)，可以分为CRSwNP和CRSsNP 2种。临床发现，相似临床表型患者的疾病预后和生活质量改善存在明显差异。炎症细胞浸润和免疫炎症介质是CRS内型驱动的重要因素，其中，尤以嗜酸性粒细胞浸润的2型CRS的疾病严重程度、并发症、治疗高复发率和较低生活质量成为CRS治疗的难点。以CRS内型为导向的治疗方法可能更有助于患者的预后和生活质量的提高。本文总结目前CRS内型研究的进展和以内型为导向的治疗选择展开综述。Abstract: Chronic rhinosinusitis(CRS) is an inflammatory disease involving the mucosa of the nasal and paranasal sinuses for more than 12 weeks and can be classified as CRS with nasal polyp(CRSwNP) and CRS without nasal polyp(CRSsNP) depending on the phenotype. Clinical treatments reveal significant differences in disease prognosis and improvement in quality of life in patients with the same clinical phenotype. Inflammatory cells infiltration and inflammatory mediators are important factors driving CRS endotypes. In particular, CRS with predominantly eosinophilic infiltration and type 2 CRS present severe clinical symptoms, comorbidities, and high recurrence rates. CRS endotype-oriented treatment methods may better contribute to improving patient prognosis and quality of life. This article summarizes the current progress of CRS endotype research and reviews the endotype-oriented treatment options.
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Key words:
- chronic rhinosinusitis /
- endotype /
- eosinophil /
- type 2 inflammation /
- biologics
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[1] Bachert C, Marple B, Schlosser RJ, et al. Adult chronic rhinosinusitis[J]. Nat Rev Dis Primers, 2020, 6(1): 86. doi: 10.1038/s41572-020-00218-1
[2] 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
[3] 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
[4] 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
[5] Cho SH, Kim DW, Gevaert P. Chronic Rhinosinusitis without Nasal Polyps[J]. J Allergy Clin Immunol Pract, 2016, 4(4): 575-582. doi: 10.1016/j.jaip.2016.04.015
[6] Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers[J]. J Allergy Clin Immunol, 2016, 137(5): 1449-1456. doi: 10.1016/j.jaci.2015.12.1324
[7] Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2022, 149(5): 1491-1503. doi: 10.1016/j.jaci.2022.02.016
[8] Wang X, Sima Y, Zhao Y, et al. Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors[J]. J Allergy Clin Immunol, 2023, 151(2): 458-468. doi: 10.1016/j.jaci.2022.10.010
[9] Gevaert E, Zhang N, Krysko O, et al. Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation[J]. J Allergy Clin Immunol, 2017, 139(6): 1849-1860. doi: 10.1016/j.jaci.2017.01.019
[10] 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.
[11] 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
[12] McHugh T, Snidvongs K, Xie M, et al. High tissue eosinophilia as a marker to predict recurrence for eosinophilic chronic rhinosinusitis: a systematic review and meta-analysis[J]. Int Forum Allergy Rhinol, 2018, 8(12): 1421-1429. doi: 10.1002/alr.22194
[13] Wei Y, Zhang J, Wu X, et al. Activated pyrin domain containing 3(NLRP3) inflammasome in neutrophilic chronic rhinosinusitis with nasal polyps(CRSwNP)[J]. J Allergy Clin Immunol, 2020, 145(3): 1002-1005. doi: 10.1016/j.jaci.2020.01.009
[14] Ruan JW, Zhao JF, Li XL, et al. Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps[J]. Front Cell Dev Biol, 2021, 9: 793073. doi: 10.3389/fcell.2021.793073
[15] Jiang WX, Cao PP, Li ZY, et al. A retrospective study of changes of histopathology of nasal polyps in adult Chinese in central China[J]. Rhinology, 2019, 57(4): 261-267.
[16] Wang W, Gao Y, Zhu Z, et al. Changes in the clinical and histological characteristics of Chinese chronic rhinosinusitis with nasal polyps over 11 years[J]. Int Forum Allergy Rhinol, 2019, 9(2): 149-157. doi: 10.1002/alr.22234
[17] Yu J, Xian M, Piao Y, et al. Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades[J]. Int Arch Allergy Immunol, 2021, 182(7): 615-624. doi: 10.1159/000513312
[18] 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. doi: 10.1016/j.jaci.2020.04.040
[19] Ueki S, Tokunaga T, Melo R, 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
[20] Shin SH, Ye MK, Park J, et al. Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis[J]. Int J Mol Sci, 2022, 23(21): 13313. doi: 10.3390/ijms232113313
[21] Cha H, Lim HS, Park JA, et al. Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps[J]. Allergy Asthma Immunol Res, 2023, 15(1): 94-108. doi: 10.4168/aair.2023.15.1.94
[22] 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
[23] Gevaert E, Delemarre T, De Volder J, et al. Charcot-Leyden crystals promote neutrophilic inflammation in patients with nasal polyposis[J]. J Allergy Clin Immunol, 2020, 145(1): 427-430. doi: 10.1016/j.jaci.2019.08.027
[24] Watelet JB, Demetter P, Claeys C, et al. Wound healing after paranasal sinus surgery: neutrophilic inflammation influences the outcome[J]. Histopathology, 2006, 48(2): 174-181. doi: 10.1111/j.1365-2559.2005.02310.x
[25] Delemarre T, Holtappels G, De Ruyck N, et al. A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2021, 147(1): 179-188. doi: 10.1016/j.jaci.2020.08.036
[26] Poposki JA, Klingler AI, Stevens WW, et al. Elevation of activated neutrophils in chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2022, 149(5): 1666-1674. doi: 10.1016/j.jaci.2021.11.023
[27] Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J]. Immunity, 2005, 23(5): 479-490. doi: 10.1016/j.immuni.2005.09.015
[28] Hwang JW, Kim JH, Kim HJ, et al. Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier[J]. Clin Exp Allergy, 2019, 49(10): 1306-1320. doi: 10.1111/cea.13448
[29] Thammavongsa V, Missiakas DM, Schneewind O. Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death[J]. Science, 2013, 342(6160): 863-866. doi: 10.1126/science.1242255
[30] Ueki S, Melo RC, Ghiran I, et al. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans[J]. Blood, 2013, 121(11): 2074-2083. doi: 10.1182/blood-2012-05-432088
[31] Rodríguez-Alcázar JF, Ataide MA, Engels G, et al. Charcot-Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1β Inflammation in Human Macrophages[J]. J Immunol, 2019, 202(2): 550-558. doi: 10.4049/jimmunol.1800107
[32] Zhao Y, Mo S, Yu L, et al. Crystalline State Determines the Potency of Galectin-10 Protein Assembly to Induce Inflammation[J]. Nano Lett, 2022, 22(6): 2350-2357. doi: 10.1021/acs.nanolett.1c04817
[33] Pothoven KL, Norton JE, Suh LA, et al. Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease[J]. J Allergy Clin Immunol, 2017, 139(6): 1966-1978. doi: 10.1016/j.jaci.2016.10.039
[34] Wang BF, Cao PP, Norton JE, et al. Evidence that oncostatin M synergizes with IL-4 signaling to induce TSLP expression in chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2023, 151(5): 1379-1390. doi: 10.1016/j.jaci.2022.11.029
[35] Xue L, Fergusson J, Salimi M, et al. Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk[J]. J Allergy Clin Immunol, 2015, 135(5): 1358-1366. doi: 10.1016/j.jaci.2014.09.006
[36] 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
[37] Karin J, Tim D, Gabriele H, et al. Type 2 Inflammatory Shift in Chronic Rhinosinusitis During 2007-2018 in Belgium[J]. Laryngoscope, 2021, 131(5): E1408-E1414.
[38] 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. doi: 10.1016/j.jaip.2019.05.009
[39] DeConde AS, Mace JC, Levy JM, 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
[40] Calus L, Van Bruaene N, Bosteels C, et al. Twelve-year follow-up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis[J]. Clin Transl Allergy, 2019, 9: 30. doi: 10.1186/s13601-019-0269-4
[41] Zhang Y, Gevaert E, Lou H, et al. Chronic rhinosinusitis in Asia[J]. J Allergy Clin Immunol, 2017, 140(5): 1230-1239. doi: 10.1016/j.jaci.2017.09.009
[42] Patel GB, Kern RC, Bernstein JA, et al. Current and Future Treatments of Rhinitis and Sinusitis[J]. J Allergy Clin Immunol Pract, 2020, 8(5): 1522-1531. doi: 10.1016/j.jaip.2020.01.031
[43] Harvey RJ, Snidvongs K, Kalish LH, et al. Corticosteroid nasal irrigations are more effective than simple sprays in a randomized double-blinded placebo-controlled trial for chronic rhinosinusitis after sinus surgery[J]. Int Forum Allergy Rhinol, 2018, 8(4): 461-470. doi: 10.1002/alr.22093
[44] Goshtasbi K, Abouzari M, Abiri A, et al. Efficacy of steroid-eluting stents in management of chronic rhinosinusitis after endoscopic sinus surgery: updated meta-analysis[J]. Int Forum Allergy Rhinol, 2019, 9(12): 1443-1450. doi: 10.1002/alr.22443
[45] Kern RC, Stolovitzky JP, Silvers SL, et al. A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps[J]. Int Forum Allergy Rhinol, 2018, 8(4): 471-481. doi: 10.1002/alr.22084
[46] Wang C, Yu L, Chu X, et al. Short-term postoperative efficacy of steroid-eluting stents for eosinophilic chronic rhinosinusitis with nasal polyps: A randomized clinical trial[J]. Int Forum Allergy Rhinol, 2023, 13(5): 899-909. doi: 10.1002/alr.23085
[47] Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE Ⅱ: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis[J]. J Allergy Clin Immunol, 2019, 143(1): 126-134. doi: 10.1016/j.jaci.2018.06.010
[48] Hopkins C. Surgery and uncontrolled chronic rhinosinusitis[J]. Lancet Respir Med, 2022, 10(4): 315-317. doi: 10.1016/S2213-2600(21)00490-2
[49] Gurrola J 2nd, Borish L. Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response[J]. J Allergy Clin Immunol, 2017, 140(6): 1499-1508. doi: 10.1016/j.jaci.2017.10.006
[50] Wen W, Liu W, Zhang L, et al. Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy[J]. J Allergy Clin Immunol, 2012, 129(6): 1522-1528. doi: 10.1016/j.jaci.2012.01.079
[51] Milara J, Morell A, Ballester B, et al. MUC4 impairs the anti-inflammatory effects of corticosteroids in patients with chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2017, 139(3): 855-862. doi: 10.1016/j.jaci.2016.06.064
[52] Milara J, Peiró T, Armengot M, et al. Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2015, 135(2): 470-476. doi: 10.1016/j.jaci.2014.07.011
[53] Li Y, Chang LH, Huang WQ, et al. IL-17A mediates pyroptosis via the ERK pathway and contributes to steroid resistance in CRSwNP[J]. J Allergy Clin Immunol, 2022, 150(2): 337-351. doi: 10.1016/j.jaci.2022.02.031
[54] Delemarre T, Bochner BS, Simon HU, et al. Rethinking neutrophils and eosinophils in chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2021, 148(2): 327-335. doi: 10.1016/j.jaci.2021.03.024
[55] Smith KA, Gill AS, Beswick DM, et al. Cystic Fibrosis Increases Long-Term Revision Rates of Endoscopic Sinus Surgery in Patients With Comorbid Chronic Rhinosinusitis[J]. Am J Rhinol Allergy, 2022, 36(2): 222-228. doi: 10.1177/19458924211046719
[56] Huang Y, Zhang N, Xu Z, et al. The Development of the Mucosal Concept in Chronic Rhinosinusitis and Its Clinical Implications[J]. J Allergy Clin Immunol Pract, 2022, 10(3): 707-715. doi: 10.1016/j.jaip.2021.10.054
[57] Alsharif S, Jonstam K, van Zele T, et al. Endoscopic Sinus Surgery for Type-2 CRS wNP: An Endotype-Based Retrospective Study[J]. Laryngoscope, 2019, 129(6): 1286-1292. doi: 10.1002/lary.27815
[58] 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
[59] Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials[J]. J Allergy Clin Immunol, 2020, 146(3): 595-605. doi: 10.1016/j.jaci.2020.05.032
[60] Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps(SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Respir Med, 2021, 9(10): 1141-1153. doi: 10.1016/S2213-2600(21)00097-7
[61] Bachert C, Han JK, Desrosiers MY, et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial[J]. J Allergy Clin Immunol, 2022, 149(4): 1309-1317. doi: 10.1016/j.jaci.2021.08.030
[62] 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
[63] Gevaert P, Saenz R, Corren J, et al. Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study[J]. J Allergy Clin Immunol, 2022, 149(3): 957-965. doi: 10.1016/j.jaci.2021.07.045
[64] Bachert C, Peters AT, Heffler E, et al. Responder analysis to demonstrate the effect of targeting type 2 inflammatory mechanisms with dupilumab across objective and patient-reported endpoints for patients with severe chronic rhinosinusitis with nasal polyps in the SINUS-24 and SINUS-52 studies[J]. Clin Exp Allergy, 2022, 52(2): 244-249. doi: 10.1111/cea.14051
[65] Cai S, Xu S, Lou H, et al. Comparison of Different Biologics for Treating Chronic Rhinosinusitis With Nasal Polyps: A Network Analysis[J]. J Allergy Clin Immunol Pract, 2022, 10(7): 1876-1886. doi: 10.1016/j.jaip.2022.02.034
[66] Bachert C, Sousa AR, Han JK, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count[J]. J Allergy Clin Immunol, 2022, 149(5): 1711-1721. doi: 10.1016/j.jaci.2021.10.040
[67] Lou H, Zhang L. Knowledge gaps in using type 2 biologics for real-world treatment of chronic rhinosinusitis with nasal polyps[J]. Allergy, 2022, 77(7): 1952-1954. doi: 10.1111/all.15307
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