• Masahiro Uehara, Noriyuki Enomoto, Masashi Mikamo, Yoshiyuki Oyama, Masato Kono, Tomoyuki Fujisawa, Naoki Inui, Yutaro Nakamura, and Takafumi Suda.
• Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
• Respir Med. 2016 May 1; 114: 18-26.

BackgroundAngiopoietin (Ang) -1 and -2 are glycoproteins that play roles in vascular development, angiogenesis, and lung vascular permeability. Although the serum concentrations of Ang-1 and -2 have been evaluated in patients with sepsis, those in patients with idiopathic pulmonary fibrosis (IPF) have received less attention.ObjectiveTo elucidate the clinical significance of Ang-1 and -2 in patients with IPF.MethodsSeventy-five patients with IPF were retrospectively studied. Serum concentrations of Ang-1 and -2 at diagnosis of IPF were measured by enzyme-linked immunosorbent assay. The relationships of the Ang-1 and -2 concentrations with pulmonary function test results, high-resolution computed tomography findings, histologic findings, occurrence of acute exacerbation of IPF (AE-IPF), and prognosis were evaluated.ResultsThe median patient age was 68 year-old and the median observation period was 44 months. IPF patients with high Ang-2 concentrations showed a significantly lower forced vital capacity (FVC) (2.28 vs. 2.69 L, respectively; p = 0.047) and lower percent diffusion lung capacity for carbon monoxide (%DLCO) (61.4 vs. 81.4%, respectively; p = 0.015) than patients with low Ang-2 concentrations. Serum Ang-2 concentrations were negatively correlated with %DLCO (r = -0.375, p = 0.021) and the change in %FVC in 12 months (r = -0.348, p = 0.043). The Ang-2 concentration was significantly higher in several patients with AE-IPF than in patients in stable condition (p = 0.011). Finally, patients with high Ang-2 concentrations showed a significantly worse prognosis than those with low Ang-2 concentrations (log-rank p = 0.039). Multivariate analysis showed that the serum Ang-2 concentration, but not the Ang-1 concentration, was a significant prognostic factor in patients with IPF (hazard ratio 1.439, p = 0.028).ConclusionIncreases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.Copyright © 2016 Elsevier Ltd. All rights reserved.

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