Oxidative Stress in Chronic Rhinosinusitis with Nasal Polyps: Pathophysiological Mechanisms, Biomarkers, and Therapeutic Implications

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the sinonasal mucosa characterized by persistent symptoms, high recurrence rates, and a significant impact on quality of life. Increasing evidence suggests that oxidative stress plays a role in its pathophysiology, although its precise contribution remains incompletely defined. Materials and Methods: A narrative review was conducted following SANRA recommendations. A structured literature search was performed using PubMed, Scopus, and Google Scholar to identify studies investigating oxidative stress, antioxidant systems, and molecular pathways in CRSwNP. Relevant articles published between January 2000 and March 2026 were included and critically appraised, distinguishing clinical from ex vivo, in vitro, and animal evidence.

Results

Available evidence, derived mainly from small cross-sectional case-control studies, consistently associates CRSwNP with increased oxidative stress, characterized by elevated levels of reactive oxygen and nitrogen species, lipid peroxidation products, and DNA damage. Impaired antioxidant defenses accompany this imbalance, although findings for individual enzymes such as superoxide dismutase, catalase, and glutathione peroxidase are inconsistent across sample types and assays. At the molecular level, oxidative stress activates pro-inflammatory signalling pathways, including NF-κB and the NLRP3 inflammasome, and is linked to epithelial barrier dysfunction and type 2 immune responses. Oxidative signatures appear to differ between eosinophilic and non-eosinophilic endotypes. Furthermore, oxidative stress represents a plausible mechanistic link between CRSwNP, asthma, and allergic rhinitis, supporting the concept of united airways disease. Antioxidant strategies are supported almost exclusively by preclinical data.