慢性鼻窦炎的发病机制研究进展
Research Progress on the Pathogenesis of Chronic Rhinosinusitis
DOI: 10.12677/acm.2025.1551338, PDF,   
作者: 李晓露*, 何敬文:暨南大学第一临床医学院,广东 广州;李 辉#, 涂 博:暨南大学附属第一医院耳鼻咽喉头颈外科,广东 广州
关键词: 慢性鼻窦炎病因发病机制Chronic Rhinosinusitis Etiology Pathogenesis
摘要: 慢性鼻窦炎(Chronic Rhinosinusitis, CRS)是一种病程超过12周的鼻窦黏膜慢性炎症性疾病,主要表现为鼻塞、流涕、嗅觉减退及头面部闷胀感,严重影响患者生活质量,并带来沉重的社会经济负担。其确切病因至今尚未完全阐明,本文通过系统梳理国内外最新研究进展,深入探讨CRS的发病机制,以期为临床诊疗策略的优化提供理论依据。
Abstract: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinus mucosa with a duration of more than 12 weeks, which is characterized by nasal congestion, runny nose, decreased sense of smell, and stuffiness in the head and face, which seriously affects the quality of life of patients and brings a heavy socioeconomic burden. Its exact etiology has not been fully elucidated so far. In this paper, the pathogenesis of CRS is explored in depth by systematically combing the latest research progresses at home and abroad, in order to provide theoretical basis for the optimization of clinical diagnosis and treatment strategies.
文章引用:李晓露, 李辉, 涂博, 何敬文. 慢性鼻窦炎的发病机制研究进展[J]. 临床医学进展, 2025, 15(5): 23-31. https://doi.org/10.12677/acm.2025.1551338

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] Fokkens, W.J., Lund, V.J., Hopkins, C., Hellings, P.W., Kern, R., Reitsma, S., et al. (2020) European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology Journal, 58, 1-464. [Google Scholar] [CrossRef] [PubMed]
[3] Wahid, N.W., Smith, R., Clark, A., Salam, M. and Philpott, C.M. (2020) The Socioeconomic Cost of Chronic Rhinosinusitis Study. Rhinology journal, 58, 112-125. [Google Scholar] [CrossRef] [PubMed]
[4] Algahtani, S., Alhajlah, A., Abuharb, A.I., Alzarroug, A.F., Almughira, A.I., Alsywina, N., et al. (2024) Outcomes of Functional Endoscopic Sinus Surgery in Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis. Cureus, 16, e53952. [Google Scholar] [CrossRef] [PubMed]
[5] Harugop, A.S., Mudhol, R.S., Hajare, P.S., Nargund, A.I., Metgudmath, V.V. and Chakrabarti, S. (2011) Prevalence of Nasal Septal Deviation in New-Borns and Its Precipitating Factors: A Cross-Sectional Study. Indian Journal of Otolaryngology and Head & Neck Surgery, 64, 248-251. [Google Scholar] [CrossRef] [PubMed]
[6] Janovic, N., Janovic, A., Milicic, B. and Djuric, M. (2022) Relationship between Nasal Septum Morphology and Nasal Obstruction Symptom Severity: Computed Tomography Study. Brazilian Journal of Otorhinolaryngology, 88, 663-668. [Google Scholar] [CrossRef] [PubMed]
[7] Alsowey, A.M., Abdulmonaem, G., Elsammak, A. and Fouad, Y. (2018) Diagnostic Performance of Multidetector Computed Tomography (MDCT) in Diagnosis of Sinus Variations. Polish Journal of Radiology, 82, 713-725. [Google Scholar] [CrossRef] [PubMed]
[8] Kapusuz Gencer, Z., Özkırış, M., Okur, A., Karaçavuş, S. and Saydam, L. (2013) The Effect of Nasal Septal Deviation on Maxillary Sinus Volumes and Development of Maxillary Sinusitis. European Archives of Oto-Rhino-Laryngology, 270, 3069-3073. [Google Scholar] [CrossRef] [PubMed]
[9] Kennedy, D.W. (1985) Functional Endoscopic Sinus Surgery: Technique. Archives of OtolaryngologyHead and Neck Surgery, 111, 643-649. [Google Scholar] [CrossRef] [PubMed]
[10] Moorthy, P.N.S., Kolloju, S., Madhira, S. and Jowkar, A.B. (2014) Clinical Study on Deviated Nasal Septum and Its Associated Pathology. International Journal of Otolaryngology and Head & Neck Surgery, 3, 75-81. [Google Scholar] [CrossRef
[11] Rehman, A., Hamid, S., Ahmad, M. and Rashid, A.F. (2012) A Prospective Study of Nasal Septal Deformities in Kashmiri Population Attending a Tertiary Care Hospital. International Journal of Otolaryngology and Head & Neck Surgery, 1, 77-84. [Google Scholar] [CrossRef
[12] Collet, S., Bertrand, B., Cornu, S., Eloy, P. and Rombaux, P. (2001) Is Septal Deviation a Risk Factor for Chronic Sinusitis? Review of Literature. Acta Oto-Rhino-Laryngologica Belgica, 55, 299-304.
[13] Srivastava, M. and Tyagi, S. (2015) Role of Anatomic Variations of Uncinate Process in Frontal Sinusitis. Indian Journal of Otolaryngology and Head & Neck Surgery, 68, 441-444. [Google Scholar] [CrossRef] [PubMed]
[14] Netto, B., Piltcher, O.B., Meotti, C.D., Lemieszek, J. and Isolan, G.R. (2015) Computed Tomography Imaging Study of the Superior Attachment of the Uncinate Process. Rhinology Journal, 53, 187-191. [Google Scholar] [CrossRef] [PubMed]
[15] Dr. Atiur Rahman, D.A.R., Dr. Md. Sazzadul-haq, D.M.S. and Dr. Md. Raqibul Alam, D.M.R.A. (2022) The Role of Concha Bullosa in Chronic Rhinosinusitis: A Single Centre Study. South Asian Research Journal of Applied Medical Sciences, 4, 1-6. [Google Scholar] [CrossRef
[16] Jacobs, J.B., Shpizner, B.A., Brunner, E., Lebowitz, R.A. and Holliday, R.A. (1996) Role of the Agger Nasi Cell in Chronic Frontal Sinusitis. Annals of Otology, Rhinology & Laryngology, 105, 694-700. [Google Scholar] [CrossRef] [PubMed]
[17] Mendiratta, V., Baisakhiya, N., Singh, D., Datta, G., Mittal, A. and Mendiratta, P. (2015) Sinonasal Anatomical Variants: CT and Endoscopy Study and Its Correlation with Extent of Disease. Indian Journal of Otolaryngology and Head & Neck Surgery, 68, 352-358. [Google Scholar] [CrossRef] [PubMed]
[18] Mall, M.A. (2008) Role of Cilia, Mucus, and Airway Surface Liquid in Mucociliary Dysfunction: Lessons from Mouse Models. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 21, 13-24. [Google Scholar] [CrossRef] [PubMed]
[19] Zhang, J., Guan, L., Wen, W., Lu, Y., Zhu, Q., Yuan, H., et al. (2013) A Novel Mutation of DNAH5 in Chronic Rhinosinusitis and Primary Ciliary Dyskinesia in a Chinese Family. European Archives of Oto-Rhino-Laryngology, 271, 1589-1594. [Google Scholar] [CrossRef] [PubMed]
[20] Joki, S., Toskala, E., Saano, V. and Nuutinen, J. (1998) Correlation between Ciliary Beat Frequency and the Structure of Ciliated Epithelia in Pathologic Human Nasal Mucosa. The Laryngoscope, 108, 426-430. [Google Scholar] [CrossRef] [PubMed]
[21] Gudis, D., Zhao, K. and Cohen, N.A. (2012) Acquired Cilia Dysfunction in Chronic Rhinosinusitis. American Journal of Rhinology & Allergy, 26, 1-6. [Google Scholar] [CrossRef] [PubMed]
[22] Kuek, L.E. and Lee, R.J. (2020) First Contact: The Role of Respiratory Cilia in Host-Pathogen Interactions in the Airways. American Journal of Physiology-Lung Cellular and Molecular Physiology, 319, L603-L619. [Google Scholar] [CrossRef] [PubMed]
[23] Steelant, B., Farré, R., Wawrzyniak, P., Belmans, J., Dekimpe, E., Vanheel, H., et al. (2016) Impaired Barrier Function in Patients with House Dust Mite-Induced Allergic Rhinitis Is Accompanied by Decreased Occludin and Zonula Occludens-1 Expression. Journal of Allergy and Clinical Immunology, 137, 1043-1053.e5. [Google Scholar] [CrossRef] [PubMed]
[24] Tharakan, A., Halderman, A.A., Lane, A.P., Biswal, S. and Ramanathan, M. (2016) Reversal of Cigarette Smoke Extract‐induced Sinonasal Epithelial Cell Barrier Dysfunction through NRF2 Activation. International Forum of Allergy & Rhinology, 6, 1145-1150. [Google Scholar] [CrossRef] [PubMed]
[25] Xian, M., Ma, S., Wang, K., Lou, H., Wang, Y., Zhang, L., et al. (2020) Particulate Matter 2.5 Causes Deficiency in Barrier Integrity in Human Nasal Epithelial Cells. Allergy, Asthma & Immunology Research, 12, 56-71. [Google Scholar] [CrossRef] [PubMed]
[26] Zhao, R., Guo, Z., Zhang, R., Deng, C., Xu, J., Dong, W., et al. (2017) Nasal Epithelial Barrier Disruption by Particulate Matter ≤ 2.5μm via Tight Junction Protein Degradation. Journal of Applied Toxicology, 38, 678-687. [Google Scholar] [CrossRef] [PubMed]
[27] Hong, Z., Guo, Z., Zhang, R., Xu, J., Dong, W., Zhuang, G., et al. (2016) Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells. The Tohoku Journal of Experimental Medicine, 239, 117-125. [Google Scholar] [CrossRef] [PubMed]
[28] Barham, H.P., Osborn, J.L., Snidvongs, K., Mrad, N., Sacks, R. and Harvey, R.J. (2015) Remodeling Changes of the Upper Airway with Chronic Rhinosinusitis. International Forum of Allergy & Rhinology, 5, 565-572. [Google Scholar] [CrossRef] [PubMed]
[29] Tsuda, T., Maeda, Y., Nishide, M., Koyama, S., Hayama, Y., Nojima, S., et al. (2018) Eosinophil-Derived Neurotoxin Enhances Airway Remodeling in Eosinophilic Chronic Rhinosinusitis and Correlates with Disease Severity. International Immunology, 31, 33-40. [Google Scholar] [CrossRef] [PubMed]
[30] Ebenezer, J.A., Christensen, J.M., Oliver, B.G., Oliver, R.A., Tjin, G., Ho, J., et al. (2017) Periostin as a Marker of Mucosal Remodelling in Chronic Rhinosinusitis. Rhinology Journal, 55, 234-241. [Google Scholar] [CrossRef
[31] Van Bruaene, N., Derycke, L., Perez-Novo, C.A., Gevaert, P., Holtappels, G., De Ruyck, N., et al. (2009) TGF-β Signaling and Collagen Deposition in Chronic Rhinosinusitis. Journal of Allergy and Clinical Immunology, 124, 253-259.e2. [Google Scholar] [CrossRef] [PubMed]
[32] Boase, S., Foreman, A., Cleland, E., Tan, L., Melton-Kreft, R., Pant, H., et al. (2013) The Microbiome of Chronic Rhinosinusitis: Culture, Molecular Diagnostics and Biofilm Detection. BMC Infectious Diseases, 13, Article No. 210. [Google Scholar] [CrossRef] [PubMed]
[33] Armbruster, C.R. and Parsek, M.R. (2018) New Insight into the Early Stages of Biofilm Formation. Proceedings of the National Academy of Sciences of the United States of America, 115, 4317-4319. [Google Scholar] [CrossRef] [PubMed]
[34] Tajudeen, B.A., Schwartz, J.S. and Palmer, J.N. (2016) Understanding Biofilms in Chronic Sinusitis. Current Allergy and Asthma Reports, 16, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[35] You, H., Zhuge, P., Li, D., Shao, L., Shi, H. and Du, H. (2011) Factors Affecting Bacterial Biofilm Expression in Chronic Rhinosinusitis and the Influences on Prognosis. American Journal of Otolaryngology, 32, 583-590. [Google Scholar] [CrossRef] [PubMed]
[36] Lee, H.S., Volpe, S.J. and Chang, E.H. (2022) The Role of Viruses in the Inception of Chronic Rhinosinusitis. Clinical and Experimental Otorhinolaryngology, 15, 310-318. [Google Scholar] [CrossRef] [PubMed]
[37] Eloy, P., Poirrier, A.L., De Dorlodot, C., Van Zele, T., Watelet, J.B. and Bertrand, B. (2011) Actual Concepts in Rhinosinusitis: A Review of Clinical Presentations, Inflammatory Pathways, Cytokine Profiles, Remodeling, and Management. Current Allergy and Asthma Reports, 11, 146-162. [Google Scholar] [CrossRef] [PubMed]
[38] Yan, Y., Gordon, W.M. and Wang, D. (2013) Nasal Epithelial Repair and Remodeling in Physical Injury, Infection, and Inflammatory Diseases. Current Opinion in Otolaryngology & Head and Neck Surgery, 21, 263-270. [Google Scholar] [CrossRef] [PubMed]
[39] Leino, M.S., Loxham, M., Blume, C., Swindle, E.J., Jayasekera, N.P., Dennison, P.W., et al. (2013) Barrier Disrupting Effects of Alternaria Alternata Extract on Bronchial Epithelium from Asthmatic Donors. PLOS ONE, 8, e71278. [Google Scholar] [CrossRef] [PubMed]
[40] Shin, S., Ye, M., Lee, D. and Che, M. (2018) Alternaria‐Induced Barrier Dysfunction of Nasal Epithelial Cells: Role of Serine Protease and Reactive Oxygen Species. International Forum of Allergy & Rhinology, 9, 514-521. [Google Scholar] [CrossRef] [PubMed]
[41] Chotirmall, S.H., Mirkovic, B., Lavelle, G.M. and McElvaney, N.G. (2014) Immunoevasive Aspergillus Virulence Factors. Mycopathologia, 178, 363-370. [Google Scholar] [CrossRef] [PubMed]
[42] Delneste, Y., Beauvillain, C. and Jeannin, P. (2007) Immunité naturelle: Structure et Fonction des Toll-Like Receptors. Médecine/Sciences, 23, 67-74. [Google Scholar] [CrossRef] [PubMed]
[43] Williams, P.B., Barnes, C.S., Portnoy, J.M., Barnes, C., Baxi, S., Grimes, C., et al. (2016) Innate and Adaptive Immune Response to Fungal Products and Allergens. The Journal of Allergy and Clinical Immunology: In Practice, 4, 386-395. [Google Scholar] [CrossRef] [PubMed]
[44] Loures, F.V., Araújo, E.F., Feriotti, C., Bazan, S.B. and Calich, V.L.G. (2015) TLR-4 Cooperates with Dectin-1 and Mannose Receptor to Expand Th17 and Tc17 Cells Induced by Paracoccidioides Brasiliensis Stimulated Dendritic Cells. Frontiers in Microbiology, 6, Article 261. [Google Scholar] [CrossRef] [PubMed]
[45] Ebbens, F., Scadding, G., Badia, L., Hellings, P., Jorissen, M., Mullol, J., et al. (2006) Amphotericin B Nasal Lavages: Not a Solution for Patients with Chronic Rhinosinusitis. Journal of Allergy and Clinical Immunology, 118, 1149-1156. [Google Scholar] [CrossRef] [PubMed]
[46] Makary, C.A., Azar, A., Gudis, D., Crawford, A., Hannikainen, P., Kim, J., et al. (2024) Evaluation and Treatment of Rhinosinusitis with Primary Antibody Deficiency in Children: Evidence‐based Review with Recommendations. International Forum of Allergy & Rhinology, 14, 1776-1801. [Google Scholar] [CrossRef] [PubMed]
[47] Kwah, J.H., Somani, S.N., Stevens, W.W., Kern, R.C., Smith, S.S., Welch, K.C., et al. (2020) Clinical Factors Associated with Acute Exacerbations of Chronic Rhinosinusitis. Journal of Allergy and Clinical Immunology, 145, 1598-1605. [Google Scholar] [CrossRef] [PubMed]
[48] Mitchell, P.D. and O’Byrne, P.M. (2017) Epithelial-Derived Cytokines in Asthma. Chest, 151, 1338-1344. [Google Scholar] [CrossRef] [PubMed]
[49] Gauvreau, G.M., Sehmi, R., Ambrose, C.S. and Griffiths, J.M. (2020) Thymic Stromal Lymphopoietin: Its Role and Potential as a Therapeutic Target in Asthma. Expert Opinion on Therapeutic Targets, 24, 777-792. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, Y. and Zhou, B. (2012) Functions of Thymic Stromal Lymphopoietin in Immunity and Disease. Immunologic Research, 52, 211-223. [Google Scholar] [CrossRef] [PubMed]
[51] Cook, E.B., Stahl, J.L., Schwantes, E.A., Fox, K.E. and Mathur, S.K. (2012) IL-3 and TNFα Increase Thymic Stromal Lymphopoietin Receptor (TSLPR) Expression on Eosinophils and Enhance TSLP-Stimulated Degranulation. Clinical and Molecular Allergy, 10, Article No. 8. [Google Scholar] [CrossRef] [PubMed]
[52] Smith, S.G., Gugilla, A., Mukherjee, M., Merim, K., Irshad, A., Tang, W., et al. (2015) Thymic Stromal Lymphopoietin and IL-33 Modulate Migration of Hematopoietic Progenitor Cells in Patients with Allergic Asthma. Journal of Allergy and Clinical Immunology, 135, 1594-1602. [Google Scholar] [CrossRef] [PubMed]
[53] Klose, C.S.N. and Artis, D. (2016) Innate Lymphoid Cells as Regulators of Immunity, Inflammation and Tissue Homeostasis. Nature Immunology, 17, 765-774. [Google Scholar] [CrossRef] [PubMed]
[54] Lee, T., Fu, C., Wang, C., Huang, C., Huang, C., Chang, P., et al. (2017) Impact of Chronic Rhinosinusitis on Severe Asthma Patients. PLOS ONE, 12, e0171047. [Google Scholar] [CrossRef] [PubMed]
[55] Gevaert, P., Van Bruaene, N., Cattaert, T., Van Steen, K., Van Zele, T., Acke, F., et al. (2011) Mepolizumab, a Humanized Anti-Il-5 Mab, as a Treatment Option for Severe Nasal Polyposis. Journal of Allergy and Clinical Immunology, 128, 989-995.e8. [Google Scholar] [CrossRef] [PubMed]
[56] Bachert, C., Mannent, L., Naclerio, R.M., Mullol, J., Ferguson, B.J., Gevaert, P., et al. (2016) Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients with Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA, 315, 469-479. [Google Scholar] [CrossRef] [PubMed]
[57] Oakley, G.M., Curtin, K., Orb, Q., Schaefer, C., Orlandi, R.R. and Alt, J.A. (2015) Familial Risk of Chronic Rhinosinusitis with and without Nasal Polyposis: Genetics or Environment. International Forum of Allergy & Rhinology, 5, 276-282. [Google Scholar] [CrossRef] [PubMed]
[58] Pinto, J.M., Hayes, M.G., Schneider, D., Naclerio, R.M. and Ober, C. (2008) A Genomewide Screen for Chronic Rhinosinusitis Genes Identifies a Locus on Chromosome 7q. The Laryngoscope, 118, 2067-2072. [Google Scholar] [CrossRef] [PubMed]
[59] Wang, X. (2000) Mutation in the Gene Responsible for Cystic Fibrosis and Predisposition to Chronic Rhinosinusitis in the General Population. JAMA, 284, 1814-1819. [Google Scholar] [CrossRef] [PubMed]
[60] Adappa, N.D., Zhang, Z., Palmer, J.N., Kennedy, D.W., Doghramji, L., Lysenko, A., et al. (2013) The Bitter Taste Receptor T2R38 Is an Independent Risk Factor for Chronic Rhinosinusitis Requiring Sinus Surgery. International Forum of Allergy & Rhinology, 4, 3-7. [Google Scholar] [CrossRef] [PubMed]
[61] Bossé, Y., Bacot, F., Montpetit, A., Rung, J., Qu, H., Engert, J.C., et al. (2009) Identification of Susceptibility Genes for Complex Diseases Using Pooling-Based Genome-Wide Association Scans. Human Genetics, 125, 305-318. [Google Scholar] [CrossRef] [PubMed]
[62] Zhang, Y., Endam, L.M., Filali-Mouhim, A., Zhao, L., Desrosiers, M., Han, D., et al. (2012) Polymorphisms in RYBP and AOAH Genes Are Associated with Chronic Rhinosinusitis in a Chinese Population: A Replication Study. PLOS ONE, 7, e39247. [Google Scholar] [CrossRef] [PubMed]
[63] Mfuna-Endam, L., Zhang, Y. and Desrosiers, M.Y. (2011) Genetics of Rhinosinusitis. Current Allergy and Asthma Reports, 11, 236-246. [Google Scholar] [CrossRef] [PubMed]