Angiopoietin-2 concentration in serum is associated with severe asthma phenotype

Background: Several proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling. The aim of the study was to compare the concentration of proangiogenic factors in the sera of asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity. Methods: Serum was collected from 45 patients with severe/refractory asthma (SRA) and 51 patients with non-severe asthma (nSA). The control group included 30 HS. Serum concentrations of Angiopoietin-1, Angiopoietin-2, vascular endothelial growth factor (VEGF) and osteopontin were assessed by the enzyme-linked immunosorbent assay. Results: The levels of Angiopoietin-1 (68.8 +/- 2.7 vs 56.4 +/- 9.3 ng/ml; p < 0.05), Angiopoietin-2 (4.9 +/- 0.35 vs 1.38 +/- 0.14 ng/ml; p < 0.0001) and VEGF were significantly higher in asthmatic patients (n = 94) as compared to HS (255 +/- 45.4 vs 424.5 +/- 27.8 pg/ml; p < 0.01). The mean serum level of Angiopoietin-2 was found to be significantly higher in patients with SRA as compared to nSA patients (6.04 +/- 0.46 vs 3.84 +/- 0.43; p < 0.001). Angiopoietin-2 serum level correlated with respiratory function and with parameters of asthma severity: the mean number of asthma exacerbations in the preceding 12 months (R = 0.21; p < 0.05), mean number of emergency visits due to severe asthma exacerbation (R = 0.24; p < 0.04) and mean number of hospitalizations (R = 0.21; p < 0.05) or dose of inhaled gluco-corticosteroids taken by the patients (R = 0.36; p < 0.001). Conclusion: Angiopoietin-2 seems to be a crucial proangiogenic cytokine overproduced in patients with SRA characterized by repeated exacerbations and Angiopoietin-2 serum levels can serve as a biomarker of severe asthma.