Association between oxidative stress index and lung cancer risk in idiopathic pulmonary fibrosis: an exploratory retrospective analysis

Background: Idiopathic pulmonary fibrosis (IPF) is a significant risk factor for lung cancer. However, early detection is often hindered by background fibrotic changes. This study assessed whether the oxidative stress index (OSI), which reflects the balance between systemic oxidative stress and antioxidant capacity, is associated with lung cancer development in patients with IPF.

Methods: We retrospectively analyzed 90 patients with newly diagnosed IPF. Serum levels of derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured at diagnosis to calculate the OSI (100 × d-ROMs/BAP). Using a 1-year landmark approach (n=83), the primary endpoint was lung cancer development during the follow-up period.

Results: Fifteen patients (18.1%) developed lung cancer. Although individual d-ROMs showed no significant differences between cohorts, the baseline OSI was significantly higher in the lung cancer group than in the non-lung cancer group (P<0.001). Receiver operating characteristic analysis demonstrated high discriminative capacity of the OSI (area under the curve: 0.857), with an optimal cut-off of 14.39. Multivariate Cox regression analysis indicated an independent association between the OSI and lung cancer development, even after adjusting for antifibrotic use and macrophage proportion in bronchoalveolar lavage fluid (BALF). Notably, the OSI did not significantly predict all-cause mortality, suggesting its relative specificity for carcinogenesis in this population.

Conclusions: Baseline OSI may serve as a potential biomarker associated with future lung cancer development in patients with IPF, independent of antifibrotic agent use and BALF macrophage proportion. Further large-scale prospective studies are needed to validate whether OSI-guided risk stratification can help optimize surveillance strategies for this high-risk population.