Serum high mobility group box 1 is associated with the onset and severity of acute exacerbation of idiopathic pulmonary fibrosis

Abstract

Background and Objective: High mobility group box 1 (HMGB1) is known as a mediator of acute lung injury through the acceleration of pro-inflammatory signaling. Previous studies showed that HMGB1 is increased in the lung and circulation of patients with acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF). This study investigated the predictive value of circulatory HMGB1 for disease progression and prognosis of IPF in the stable phase and AE phase. Methods: Seventy-six patients with stable IPF, 17 patients with AE-IPF, and 74 healthy controls were included. Serum HMGB1 levels were compared among the three groups, and the associations of HMGB1 levels with lung function variables, the onset of AE, and prognosis were evaluated in patients with stable IPF. The prognostic value of HMGB1 was determined in AE-IPF. Results: Serum HMGB1 levels in patients with stable IPF were significantly higher than those in healthy controls; those in patients with AE-IPF were even higher when compared with levels in the other two groups (6.26 ± 16.77 ng/mL, 3.42 ± 2.69 ng/mL, and 19.20 ± 16.76 ng/mL, respectively). In patients with stable IPF, higher HMGB1 levels were associated with lower diffusion capacity for carbon monoxide (r= -0.248, p = 0.039) and earlier onset of AE (p = 0.030). In patients with AE-IPF, increased HMGB1 levels were associated with shorter survival (p= 0.001). Conclusions: Higher levels of serum HMGB1 predict earlier onset of AE in stable IPF and shorter survival in AE-IPF, indicating that HMGB1 is associated with acute deterioration of the disease.