{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:07:46Z","timestamp":1789834066443,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002701","name":"ministry of Education of the Republic of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2025S1A5C3A03022311"],"award-info":[{"award-number":["NRF-2025S1A5C3A03022311"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2018R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2022R1A2C1091779"],"award-info":[{"award-number":["NRF-2022R1A2C1091779"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NRF-2025S1A5C3A03022311"],"award-info":[{"award-number":["NRF-2025S1A5C3A03022311"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NRF-2018R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018R1A6A1A03025124"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NRF-2022R1A2C1091779"],"award-info":[{"award-number":["NRF-2022R1A2C1091779"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Bio Bigdata Project","award":["RS-2024-00509118"],"award-info":[{"award-number":["RS-2024-00509118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa whose pathogenesis is characterized by complex interactions of immunological and environmental factors. The maintenance of normal sinonasal function requires a balance of sinus ostial patency, mucociliary clearance, and mucus secretion, and disruption of this balance can lead to CRS. Although many studies have examined the pathophysiology of CRS, the role of reactive oxygen species (ROS) remains incompletely understood. In this review, we analyzed 22 studies of CRS that examined the effects of ROS on epithelial barrier function, local immune responses, and tissue remodeling. The results from in vitro studies, animal models, and human tissue analyses suggest that ROS are not merely by-products of inflammation, but appear to function as key mediators in the pathophysiology of CRS, particularly in the formation and persistence of the CRS phenotype with nasal polyps (CRSwNP). In particular, CRSwNP is characterized by increased activity of enzymes in the dual oxidase (DUOX) and NADPH oxidase (NOX) families, mitochondrial dysfunction, and decreased activity of superoxide dismutase (SOD) and peroxiredoxin 2 (PRDX2). At the molecular level, these alterations increase the generation of ROS and impair antioxidant defense. At the cellular level, these alterations disrupt the epithelial barrier, activate inflammasomes, increase pyroptosis, and induce the formation of neutrophilic and eosinophilic extracellular traps. These changes culminate in the epithelial\u2013mesenchymal transition (EMT), with the formation of nasal polyps and tissue remodeling. Increased oxidative stress can also occur in CRS without nasal polyps (CRSsNP), but this phenotype appears to have relatively preserved antioxidant defense systems, which may partly explain the more limited structural remodeling. External stimuli, such as fungal proteases, bacterial toxins, and certain antibiotics, can also increase the production of ROS and may contribute to disease chronicity. Taken together, the level and pathophysiological roles of ROS differ in the two primary phenotypes of CRS. Further mechanistic studies are needed to clarify the specific alterations of redox pathways in these two phenotypes and to develop novel therapeutic strategies that target ROS.<\/jats:p>","DOI":"10.3390\/cimb48070709","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:51:09Z","timestamp":1783936269000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Reactive Oxygen Species in Chronic Rhinosinusitis: A Narrative Review"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3551-0257","authenticated-orcid":false,"given":"Jeongmin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-1297","authenticated-orcid":false,"given":"Su Young","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Myongji Hospital, Hanyang University College of Medicine, Goyang 10475, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Clinical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-9765","authenticated-orcid":false,"given":"Jae Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, 23 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-0350","authenticated-orcid":false,"given":"Manish Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7668","authenticated-orcid":false,"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3820-0107","authenticated-orcid":false,"given":"Tong In","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-4987","authenticated-orcid":false,"given":"Dong Choon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-1024","authenticated-orcid":false,"given":"Seung Geun","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Clinical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, 23 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinol. Off. Organ Int. Rhinol. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jaci.2022.02.016","article-title":"Mechanisms and pathogenesis of chronic rhinosinusitis","volume":"149","author":"Kato","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/wjo2.91","article-title":"Enhanced Oxidative Stress Is Associated with Tissue Neutrophilia and Poor Steroid Response in Chronic Rhinosinusitis with Nasal Polyps","volume":"9","author":"Hu","year":"2024","journal-title":"World J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative Stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Albano, G.D., Gagliardo, R.P., Montalbano, A.M., and Profita, M. (2022). Overview of the Mechanisms of Oxidative Stress: Impact in Inflammation of the Airway Diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11112237"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2458942","DOI":"10.1080\/13510002.2025.2458942","article-title":"Oxidative Stress and Reactive Oxygen Species in Otorhinolaryngological Diseases: Insights from Pathophysiology to Targeted Antioxidant Therapies","volume":"30","author":"Meng","year":"2025","journal-title":"Redox Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1001\/archotol.128.9.1055","article-title":"The Role of Free Radicals in Chronic Rhinosinusitis","volume":"128","author":"Friedman","year":"2002","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/alr.21133","article-title":"Expression of Dual Oxidases and Secreted Cytokines in Chronic Rhinosinusitis","volume":"3","author":"Cho","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/alr.21114","article-title":"Gene Expression Differences in Nitric Oxide and Reactive Oxygen Species Regulation Point to an Altered Innate Immune Response in Chronic Rhinosinusitis","volume":"3","author":"Jardeleza","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13020-024-00897-y","article-title":"Platycodon D Protects Human Nasal Epithelial Cells from Pyroptosis through the Nrf2\/HO-1\/ROS Signaling Cascade in Chronic Rhinosinusitis","volume":"19","author":"Wang","year":"2024","journal-title":"Chin. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1177\/1945892420982411","article-title":"Increased Expression of TXNIP Facilitates Oxidative Stress in Nasal Epithelial Cells of Patients with Chronic Rhinosinusitis with Nasal Polyps","volume":"35","author":"Lin","year":"2021","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tsai, Y.-J., Hsu, Y.-T., Ma, M.-C., Wu, C.-K., Luo, S.-D., and Wu, W.-B. (2022). Transcriptomic Analysis of Genes Associated with Oxidative Stress in Chronic Rhinosinusitis Patients with Nasal Polyps: Identifying Novel Genes Involved in Nasal Polyposis. Antioxidants, 11.","DOI":"10.3390\/antiox11101899"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhou, J., Zhou, J., Liu, R., Liu, Y., Meng, J., Wen, Q., Luo, Y., Liu, S., Li, H., and Ba, L. (2024). The Oxidant-Antioxidant Imbalance Was Involved in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1380846"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nishida, M., Takeno, S., Takemoto, K., Takahara, D., Hamamoto, T., Ishino, T., and Kawasumi, T. (2020). Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps. Diagnostics, 10.","DOI":"10.3390\/diagnostics10040246"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e38029","DOI":"10.1016\/j.heliyon.2024.e38029","article-title":"NOX2 Mediates NLRP3\/ROS Facilitating Nasal Mucosal Epithelial Inflammation in Chronic Rhinosinusitis with Nasal Polyps","volume":"10","author":"Jiang","year":"2024","journal-title":"Heliyon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/alr.22530","article-title":"Expression of Nicotinamide Adenine Dinucleotide Phosphate Oxidase in Chronic Rhinosinusitis with Nasal Polyps","volume":"10","author":"Zheng","year":"2020","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"653","DOI":"10.4168\/aair.2020.12.4.653","article-title":"Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated with Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps","volume":"12","author":"Yoon","year":"2020","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Han, M.S., Lee, T.H., Lee, D.B., Park, J.H., Lee, S.H., and Kim, T.H. (2023). Hydrogen Peroxide Attenuates Rhinovirus-Induced Anti-Viral Interferon Secretion in Sinonasal Epithelial Cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1086381"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/alr.22266","article-title":"Alternaria-Induced Barrier Dysfunction of Nasal Epithelial Cells: Role of Serine Protease and Reactive Oxygen Species","volume":"9","author":"Shin","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jaci.2025.07.004","article-title":"Role of APE1 Redox Function in Chronic Rhinosinusitis Pathogenesis: Implications for Targeted Therapy","volume":"156","author":"Zhang","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/19458924251386929","article-title":"Peroxiredoxin 2 Alleviates Oxidative Stress-Induced Epithelial Remodeling in Chronic Rhinosinusitis with Nasal Polyps","volume":"40","author":"Gao","year":"2026","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/0003489418812905","article-title":"Reactive Oxygen Species Are Necessary for Bleomycin A5-Induced Apoptosis and Extracellular Matrix Elimination of Nasal Polyp-Derived Fibroblasts","volume":"128","author":"Wu","year":"2019","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1177\/0194599813496377","article-title":"Reactive Oxygen Species in Chronic Rhinosinusitis and Secondhand Smoke Exposure","volume":"149","author":"Fordham","year":"2013","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tsai, Y.-J., Shieh, J.-M., Ma, M.-C., and Wu, W.-B. (2025). Differential Expression of Antioxidant and Oxidant Pathways in Chronic Rhinosinusitis without Nasal Polyps. Antioxidants, 14.","DOI":"10.3390\/antiox14111292"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2500\/ajra.2015.29.4155","article-title":"Superoxide Dismutase Reduces the Inflammatory Response to Aspergillus and Alternaria in Human Sinonasal Epithelial Cells Derived from Patients with Chronic Rhinosinusitis","volume":"29","author":"Lawrence","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/alr.21646","article-title":"Bactericidal Antibiotics Promote Reactive Oxygen Species Formation and Inflammation in Human Sinonasal Epithelial Cells","volume":"6","author":"Kohanski","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/alr.21914","article-title":"Bactericidal Antibiotics Promote Oxidative Damage and Programmed Cell Death in Sinonasal Epithelial Cells","volume":"7","author":"Kohanski","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shin, S.-H., Ye, M.-K., Lee, D.-W., Choi, M.-H., and Geum, S.-Y. (2023). Aspergillus Enhances Eosinophil and Neutrophil Extracellular DNA Trap Formation in Chronic Rhinosinusitis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417264"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tai, J., Shin, J.M., Park, J., Han, M., and Kim, T.H. (2023). Oxidative Stress and Antioxidants in Chronic Rhinosinusitis with Nasal Polyps. Antioxidants, 12.","DOI":"10.3390\/antiox12010195"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"C68","DOI":"10.1152\/ajpcell.00043.2017","article-title":"Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: Role of oxidative stress","volume":"313","author":"Zaidman","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Baaske, R., Richter, M., M\u00f6ller, N., Ziesemer, S., Eiffler, I., M\u00fcller, C., and Hildebrandt, J.P. (2016). ATP release from human airway epithelial cells exposed to Staphylococcus aureus alpha-toxin. Toxins, 8.","DOI":"10.3390\/toxins8120365"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e202421424","DOI":"10.1002\/anie.202421424","article-title":"Chemical proteomics reveals human off-targets of fluoroquinolone induced mitochondrial toxicity","volume":"64","author":"Reinhardt","year":"2025","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9625","DOI":"10.1093\/nar\/gky793","article-title":"Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of topoisomerase 2","volume":"46","author":"Hangas","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/709\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:13:29Z","timestamp":1784002409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070709"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070709","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]}}}