Prognostic Value of Serum Osteopontin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Background. Acute exacerbation (AE) is a common cause of rapid deterioration and high mortality in idiopathic pulmonary fibrosis (IPF) patients. Osteopontin (OPN) plays an important role in IPF, but the studies about serum OPN in AE-IPF are unclear. We aimed to investigate whether OPN had a potential prognostic value in acute exacerbation and mortality in IPF. Methods. Thirty-two patients with AE-IPF, 39 with S-IPF, and 20 healthy controls were included. Serum OPN and KL-6 levels were compared between AE-IPF and S-IPF. Logistic regression analysis was applied to identify the predicted value of OPN for AE. Kaplan-Meier curves were used to display survival, and Cox proportional hazards regression was used to identify risk for mortality. Results. In AE-IPF patients, serum OPN levels were significantly higher than in S-IPF subjects (p<0.001) or healthy controls (p<0.001). Immunohistochemical staining in lung transplant specimens of IPF showed strong expression of OPN in the alveolar epithelial cells lining honeycomb space and alveolar macrophages accumulating in interalveolar spaces adjacent to the fibrotic lesion. Serum OPN was correlated with higher C-reactive protein (CRP) and lactate dehydrogenase (LDH). Serum OPN, KL-6, CRP, LDH, percent forced vital capacity (FVC%), and percent diffusing capacity (DLCO%) in IPF were correlated with AE status, with respective odds ratios of 1.305 (p=0.004), 1.001 (p=0.010), 1.039 (p=0.002), 1.035 (p<0.001), 0.950 (p=0.024), and 0.929 (p=0.010). Serum OPN (above 3.24 ng/ml) was associated with an increasing risk of mortality (p=0.019). Multivariate Cox regression demonstrated an association of OPN levels with mortality risk (p=0.036). Conclusion. Elevated OPN could be a potential serum predictor for AE status and survival in IPF patients.