Masahiro Uehara1, Noriyuki Enomoto2, Masashi Mikamo1, Yoshiyuki Oyama1, Masato Kono1, Tomoyuki Fujisawa1, Naoki Inui3, Yutaro Nakamura1, Takafumi Suda1. 1. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. 2. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Health Administration Center, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: norieno@hama-med.ac.jp. 3. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract
BACKGROUND: Angiopoietin (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. OBJECTIVE: To elucidate the clinical significance of Ang-1 and -2 in patients with IPF. METHODS: Seventy-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. RESULTS: The 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). CONCLUSION: Increases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.
BACKGROUND:Angiopoietin (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. OBJECTIVE: To elucidate the clinical significance of Ang-1 and -2 in patients with IPF. METHODS: Seventy-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. RESULTS: The 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). CONCLUSION: Increases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.
Authors: Nunzia Caporarello; Jisu Lee; Tho X Pham; Dakota L Jones; Jiazhen Guan; Patrick A Link; Jeffrey A Meridew; Grace Marden; Takashi Yamashita; Collin A Osborne; Aditya V Bhagwate; Steven K Huang; Roberto F Nicosia; Daniel J Tschumperlin; Maria Trojanowska; Giovanni Ligresti Journal: Nat Commun Date: 2022-07-25 Impact factor: 17.694