以肥大细胞为靶细胞探索慢性鼻窦炎伴鼻息肉内在型的初步研究
A Preliminary Exploration of Chronic Rhinosinusitis with Nasal Polyps Endotypes Based on Mast Cells as Target Cells
DOI: 10.12677/acm.2026.1672495, PDF,   
作者: 包笑萌:青岛大学医学部,山东 青岛;姜 彦*:青岛大学附属医院耳鼻咽喉头颈外科,山东 青岛
关键词: 慢性鼻窦炎伴鼻息肉肥大细胞嗜酸性粒细胞内在型Chronic Rhinosinusitis with Nasal Polyps Mast Cells Eosinophils Endotype
摘要: 目的:通过高倍镜下计数鼻息肉组织中的肥大细胞数目,分析其与患者临床特征的相关性,评估肥大细胞能否作为CRSwNP内在型分型的靶细胞。方法:回顾性纳入2021年3月至2024年6月于青岛大学附属医院就诊的361例CRSwNP患者,收集人口学、合并症及检验检查资料。鼻息肉组织行HE和CD117染色,计数肥大细胞与嗜酸性粒细胞。以肥大细胞计数中位数为界,分为肥大细胞型与非肥大细胞型组;依据JESREC标准,分为嗜酸性组与非嗜酸性组。采用t检验、χ2检验比较组间基线差异,分析两种细胞计数与临床指标的相关性,并通过单因素及多因素Logistic回归分析筛选肥大细胞型及嗜酸性鼻息肉分型的独立预测因素。结果:肥大细胞型与嗜酸性型CRSwNP均与外周血嗜酸性粒细胞百分比、Lund-Mackay评分及过敏状态呈正相关。多因素分析显示,组织嗜酸性粒细胞计数和Lund-Mackay评分是肥大细胞型的独立危险因素,外周血嗜酸性粒细胞百分比和Lund-Mackay评分是嗜酸性型的独立危险因素。结论:肥大细胞型与嗜酸性粒细胞型CRSwNP对疾病严重程度和临床特征的指示作用相近。但肥大细胞分型更依赖于局部组织2型炎症的严重程度,能识别出外周血嗜酸性粒细胞正常而组织嗜酸性粒细胞增高的隐匿性2型炎症,弥补JESREC标准对局部病理重视不足的局限。对肥大细胞增多的患者,可考虑靶向肥大细胞的治疗策略(如奥马珠单抗),为临床提供更全面的治疗选择。
Abstract: Objective: To quantify mast cells in nasal polyp tissue under high-power field, analyze their correlation with clinical characteristics, and evaluate whether mast cells can serve as target cells for the endotyping of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: A total of 361 patients with CRSwNP treated at the Affiliated Hospital of Qingdao University from March 2021 to June 2024 were retrospectively enrolled. Demographic data, comorbidities, and laboratory and imaging findings were collected. Nasal polyp tissues were stained with hematoxylin and eosin (HE) and CD117 for mast cell and eosinophil counting. Patients were classified into mast cell-high and mast cell-low groups based on the median mast cell count, and into eosinophilic and non-eosinophilic groups according to the JESREC criteria. Intergroup differences in baseline characteristics were compared using the t-test or χ2 test. Correlations between the two cell counts and clinical parameters were analyzed, and univariate and multivariate logistic regression analyses were performed to identify independent predictors for the mast cell-high and eosinophilic endotypes. Results: Both mast cell-high and eosinophilic CRSwNP were positively associated with blood eosinophil percentage, Lund-Mackay score, and atopic status. Multivariate analysis revealed that tissue eosinophil count and Lund-Mackay score were independent risk factors for the mast cell-high endotype, while blood eosinophil percentage and Lund-Mackay score were independent risk factors for the eosinophilic endotype. Conclusion: The mast cell-high and eosinophilic endotypes of CRSwNP exhibit comparable indicative value for disease severity and clinical features. However, mast cell-based endotyping is more dependent on the severity of local type 2 inflammation and may identify occult type 2 inflammation in patients with normal blood eosinophil percentages but high tissue eosinophil counts, thereby compensating for the insufficient emphasis on local histopathology in the JESREC criteria. In patients with elevated mast cell counts, mast cell-targeted therapies, such as omalizumab, may be considered, offering a more comprehensive treatment approach.
文章引用:包笑萌, 姜彦. 以肥大细胞为靶细胞探索慢性鼻窦炎伴鼻息肉内在型的初步研究[J]. 临床医学进展, 2026, 16(7): 35-49. https://doi.org/10.12677/acm.2026.1672495

参考文献

[1] 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. 慢性鼻窦炎诊断和治疗指南(2024) [J]. 中华耳鼻咽喉头颈外科杂志, 2025, 60(3): 221-249.
[2] Fujieda, S., Imoto, Y., Kato, Y., Ninomiya, T., Tokunaga, T., Tsutsumiuchi, T., et al. (2019) Eosinophilic Chronic Rhinosinusitis. Allergology International, 68, 403-412. [Google Scholar] [CrossRef] [PubMed]
[3] Perić, A., Mirković, C.Š. and Vojvodić, D. (2018) Clara Cell Protein 16 Release from the Nasal Mucosa in Allergic Rhinitis, Chronic Rhinosinusitis, and Exposure to Air Pollutants. Archives of Industrial Hygiene and Toxicology, 69, 215-219. [Google Scholar] [CrossRef] [PubMed]
[4] Kawakita, K., Kouzaki, H., Murao, T., Kubo, Y., Nishiguchi, T., Nakamura, K., et al. (2024) Role of Basal Cells in Nasal Polyp Epithelium in the Pathophysiology of Eosinophilic Chronic Rhinosinusitis (eCRS). Allergology International, 73, 563-572. [Google Scholar] [CrossRef] [PubMed]
[5] Sit, A., Alvarado, R., Earls, P., Rimmer, J., Kalish, L., Campbell, R., et al. (2023) CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis. American Journal of Rhinology & Allergy, 37, 402-409. [Google Scholar] [CrossRef] [PubMed]
[6] Shijubo, N., Itoh, Y., Yamaguchi, T., Imada, A., Hirasawa, M., Yamada, T., et al. (1999) Clara Cell Protein-Positive Epithelial Cells Are Reduced in Small Airways of Asthmatics. American Journal of Respiratory and Critical Care Medicine, 160, 930-933. [Google Scholar] [CrossRef] [PubMed]
[7] Hermans, C. and Bernard, A. (1999) Lung Epithelium-Specific Proteins: Characteristics and Potential Applications as Markers. American Journal of Respiratory and Critical Care Medicine, 159, 646-678. [Google Scholar] [CrossRef] [PubMed]
[8] Snidvongs, K., Earls, P., Dalgorf, D., Sacks, R., Pratt, E. and Harvey, R.J. (2015) Osteitis Is a Misnomer: A Histopathology Study in Primary Chronic Rhinosinusitis. International Forum of Allergy & Rhinology, 4, 390-396. [Google Scholar] [CrossRef] [PubMed]
[9] Tokunaga, T., Sakashita, M., Haruna, T., Asaka, D., Takeno, S., Ikeda, H., et al. (2015) Novel Scoring System and Algorithm for Classifying Chronic Rhinosinusitis: The JESREC Study. Allergy, 70, 995-1003. [Google Scholar] [CrossRef] [PubMed]
[10] Lou, H., Meng, Y., Piao, Y., Wang, C., Zhang, L. and Bachert, C. (2015) Predictive Significance of Tissue Eosinophilia for Nasal Polyp Recurrence in the Chinese Population. American Journal of Rhinology & Allergy, 29, 350-356. [Google Scholar] [CrossRef] [PubMed]
[11] Bachert, C., Han, J.K., Desrosiers, M., Hellings, P.W., Amin, N., Lee, S.E., et al. (2019) 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. The Lancet, 394, 1638-1650. [Google Scholar] [CrossRef] [PubMed]
[12] 杨秀云. 血清特异性IgE和总IgE测定在过敏性疾病诊断中的应用价值[J]. 现代诊断与治疗, 2020, 31(4): 597-599.
[13] Almuntashiri, S., Zhu, Y., Han, Y., Wang, X., Somanath, P.R. and Zhang, D. (2020) Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases. Journal of Clinical Medicine, 9, Article 4039. [Google Scholar] [CrossRef] [PubMed]
[14] Johansson, S., Keen, C., Ståhl, A., Wennergren, G. and Benson, M. (2005) Low Levels of CC16 in Nasal Fluid of Children with Birch Pollen-Induced Rhinitis. Allergy, 60, 638-642. [Google Scholar] [CrossRef] [PubMed]
[15] Benson, M., Jansson, L., Adner, M., Luts, A., Uddman, R. and Cardell, L.O. (2005) Gene Profiling Reveals Decreased Expression of Uteroglobin and Other Anti-Inflammatory Genes in Nasal Fluid Cells from Patients with Intermittent Allergic Rhinitis. Clinical & Experimental Allergy, 35, 473-478. [Google Scholar] [CrossRef] [PubMed]
[16] Benson, M., Fransson, M., Martinsson, T., Naluai, Å.T., Uddman, R. and Cardell, L.O. (2007) Inverse Relation between Nasal Fluid Clara Cell Protein 16 Levels and Symptoms and Signs of Rhinitis in Allergen-Challenged Patients with Intermittent Allergic Rhinitis. Allergy, 62, 178-183. [Google Scholar] [CrossRef] [PubMed]
[17] Biaoxue, R., Tian, F., Wenlong, G., Min, L., Congxue, R., Wen, L., et al. (2020) Reduced Serum Concentration of CC16 Is Associated with Severity of Chronic Obstructive Pulmonary Disease and Contributes to the Diagnosis and Assessment of the Disease. International Journal of Chronic Obstructive Pulmonary Disease, 15, 461-470. [Google Scholar] [CrossRef] [PubMed]
[18] Špadijer-Mirković, C., Perić, A., Belić, B. and Vojvodić, D. (2016) Clara Cell Protein 16 and Eosinophil Cationic Protein Production in Chronically Inflamed Sinonasal Mucosa. International Forum of Allergy & Rhinology, 6, 529-536. [Google Scholar] [CrossRef] [PubMed]
[19] Lund, V.J. and Kennedy, D.W. (1997) Staging for Rhinosinusitis. OtolaryngologyHead and Neck Surgery, 117, S35-S40. [Google Scholar] [CrossRef
[20] Phillips, K.M., Singerman, K.W. and Sedaghat, A.R. (2022) Individual Symptom Visual Analogue Scale Severity Scores for Determining EPOS Guideline-Based Chronic Rhinosinusitis Disease Control. Rhinology, 60, 229-235. [Google Scholar] [CrossRef] [PubMed]
[21] Tepeš, I., Košak Soklič, T. and Urbančič, J. (2022) The Agreement of the Endoscopic Modified Lund-Kennedy Scoring in a Clinical Research Group: An Observational Study. European Annals of Otorhinolaryngology, Head and Neck Diseases, 139, 185-188. [Google Scholar] [CrossRef] [PubMed]
[22] Watelet, J., Gevaert, P., Holtappels, G., Van Cauwenberge, P. and Bachert, C. (2004) Collection of Nasal Secretions for Immunological Analysis. European Archives of Oto-Rhino-Laryngology, 261, 242-246. [Google Scholar] [CrossRef] [PubMed]
[23] Shijubo, N., Kawabata, I., Sato, N. and Itoh, Y. (2003) Clinical Aspects of Clara Cell 10-kDa Protein/Uteroglobin (Secretoglobin 1A1). Current Pharmaceutical Design, 9, 1139-1149. [Google Scholar] [CrossRef] [PubMed]
[24] Van Vyve, T., Chanez, P., Bernard, A., Bousquet, J., Godard, P., Lauwerijs, R., et al. (1995) Protein Content in Bronchoalveolar Lavage Fluid of Patients with Asthma and Control Subjects. Journal of Allergy and Clinical Immunology, 95, 60-68. [Google Scholar] [CrossRef] [PubMed]
[25] Modena, B.D., Dazy, K. and White, A.A. (2016) Emerging Concepts: Mast Cell Involvement in Allergic Diseases. Translational Research, 174, 98-121. [Google Scholar] [CrossRef] [PubMed]
[26] Kudo, M., Ishigatsubo, Y. and Aoki, I. (2013) Pathology of Asthma. Frontiers in Microbiology, 4, Article 263. [Google Scholar] [CrossRef] [PubMed]
[27] Lensmar, C., Nord, M., Gudmundsson, G.H., Roquet, A., Andersson, O., Jörnvall, H., et al. (2000) Decreased Pulmonary Levels of the Anti-Inflammatory Clara Cell 16 kDa Protein after Induction of Airway Inflammation in Asthmatics. Cellular and Molecular Life Sciences, 57, 976-981. [Google Scholar] [CrossRef] [PubMed]
[28] Liu, Z., Lu, X., Zhang, X.H., Bochner, B.S., Long, X.B., Zhang, F., et al. (2009) Clara Cell 10-kDa Protein Expression in Chronic Rhinosinusitis and Its Cytokine-Driven Regulation in Sinonasal Mucosa. Allergy, 64, 149-157. [Google Scholar] [CrossRef] [PubMed]
[29] Gion, Y., Okano, M., Koyama, T., Oura, T., Nishikori, A., Orita, Y., et al. (2020) Clinical Significance of Cytoplasmic Ige-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis. International Journal of Molecular Sciences, 21, Article 1843. [Google Scholar] [CrossRef] [PubMed]
[30] Locatello, L.G., Tonon, S., Mele, V., Santini, S., Miani, C. and Pucillo, C.E.M. (2024) Update on the Biological and Clinical Relevance of Mast Cells in Chronic Rhinosinusitis with Nasal Polyps. Biomedicines, 12, Article 2647. [Google Scholar] [CrossRef] [PubMed]
[31] Gelardi, M., Giancaspro, R., Duda, L., Quaranta, V.N., Pizzulli, C., Maiorano, E., et al. (2023) Eosinophil-Mast Cell Pattern of Intraepithelial Infiltration as a Marker of Severity in CRSwNP. Scientific Reports, 13, Article No. 12101. [Google Scholar] [CrossRef] [PubMed]
[32] Belsky, M.A., Corredera, E., Banerjee, H., Moore, J., Wang, L., Kane, L.P., et al. (2021) Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps. Annals of Otology, Rhinology & Laryngology, 130, 1069-1077. [Google Scholar] [CrossRef] [PubMed]
[33] 杨婷, 罗章雨. 慢性鼻窦炎伴鼻息肉复发患者血清MMP-2和IL-25表达与组织中肥大细胞浸润的相关性研究[J]. 中国耳鼻咽喉头颈外科, 2025, 32(3): 169-174.
[34] 郑晓静, 陈冰, 熊国锋. 奥马珠单抗在嗜酸性粒细胞性慢性鼻窦炎伴鼻息肉患者鼻内窥镜术后的应用价值[J]. 临床药物治疗杂志, 2025, 23(9): 58-63.
[35] 刘承耀, 王向东, 司马宇彤, 等. 嗜酸粒细胞性鼻窦炎伴鼻息肉患者术后症状及体征变化在预测复发中的作用[J]. 临床耳鼻咽喉头颈外科杂志, 2023, 37(11): 864-870.
[36] Barroso, B., Valverde-Monge, M., Alobid, I., et al. (2023) Improvement in Olfaction in Patients with CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study. Journal of Investigational Allergology and Clinical Immunology, 33, 37-44.
[37] 张韵秋, 任秀敏, 徐鸥, 等. 奥马珠单抗靶向治疗慢性鼻窦炎伴鼻息肉的研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 136-140.
[38] 石帅, 郑泉, 程雷. 度普利尤单抗在慢性鼻窦炎伴鼻息肉治疗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 36-42.