Impact of angiopoietin-1 and -2 on clinical course of idiopathic pulmonary fibrosis.
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.



To elucidate the clinical significance of Ang-1 and -2 in patients with IPF.



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.



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).



Increases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Masahiro
M
Uehara
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.
Noriyuki
N
Enomoto
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Masashi
M
Mikamo
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshiyuki
Y
Oyama
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Masato
M
Kono
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tomoyuki
T
Fujisawa
Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Naoki
N
Inui
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yutaro
Y
Nakamura
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takafumi
T
Suda
D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D002248:Carbon Monoxide / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D012129:Respiratory Function Tests / Q000379:methods; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity / Q000502:physiology
C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D002248:Carbon Monoxide
Angiogenesis; Angiopoietin; Idiopathic pulmonary fibrosis; Usual interstitial pneumonia