Diagnostic utility of high-mobility group box 1 for acute exacerbations of idiopathic pulmonary fibrosis

There are no established biomarkers for acute exacerbations in idiopathic pulmonary fibrosis (AE-IPF). The bronchoalveolar lavage fluid of patients with IPF notably has elevations in high-mobility group box 1 protein (HMGB1), a nuclear non-histone chromosomal protein that functions as an alarmin that perpetuates the inflammatory process. This study investigated the potential of serum HMGB1 levels as a diagnostic marker for AE-IPF. This prospective, multicenter, observational cohort study included 779 HMGB1 readings from 269 Japanese patients with IPF. Diagnostic performance was assessed using four different methods of recording serial HMGB1 measurements rather than relying on a simple comparison between stable IPF and AE-IPF. Additionally, KL-6 was measured in cases of stable IPF and AE-IPF. A comparative analysis for the usefulness of HMGB1 and KL-6 as biomarkers for AE-IPF was performed. The cohort accounted for 505.6 person-years, with a mean follow-up duration of 1.88 years. A total of 46 cases with AE were recorded with their corresponding HMGB1 levels. All four diagnostic methods examined had high diagnostic accuracy (area under the curve > 0.75). HMGB1 had significantly better diagnostic performance than KL-6. HMGB1 demonstrated high diagnostic utility in AE-IPF, which can be used to facilitate earlier diagnosis and treatment.