After 12 weeks of inhaled fluticasone therapy, airway obstruction and hyperreactivity to methacholine were markedly improved. Moreover, eosinophilic airway inflammation and exhaled NO levels had decreased to the same levels as in normal control subjects. VEGF and angiopoietin-1 levels were significantly decreased in the fluticasone group (VEGF: before, 4,310 ± 770 pg/mL; after, 2,300 ± 720 pg/mL, p < 0.001; angiopoietin-1: before, 8.7 ± 3.9 ng/mL; after, 5.7 ± 2.7 ng/mL, p = 0.02) [Fig 2
, top left, A, and top right, B]. In contrast, the angiopoietin-2 level did not differ from before to after fluticasone therapy (before, 650 ± 260 pg/mL; after, 630 ± 220 pg/mL) [Fig 2, bottom left, C]. In the montelukast group, airway obstruction did not change, but airway hyperreactivity to methacholine was significantly improved. In addition, eosinophilic airway inflammation and exhaled NO level had also decreased but were still higher compared with normal control levels. VEGF and angiopoietin-2 levels in the montelukast group were significantly decreased (VEGF: before, 4,320 ± 960 pg/mL; after, 3,720 ± 790 pg/mL, p = 0.04; angiopoietin-2: before, 670 ± 230 pg/mL; after, 480 ± 170 pg/mL, p = 0.01), but the angiopoietin-1 level was not (before, 8.3 ± 3.9 ng/mL; after, 9.1 ± 4.0 ng/mL). In addition, the VEGF level in the montelukast group was significantly higher than that in the fluticasone group (p < 0.001). Nevertheless, airway vascular permeability index in the montelukast group was significantly decreased, to the same level as that in the fluticasone group (montelukast group: before, 0.035 ± 0.009; after, 0.024 ± 0.005; fluticasone group: before, 0.034 ± 0.010; after, 0.028 ± 0.007) [Fig 2, bottom right, D]. Moreover, decrease in angiopoietin-1 level after fluticasone therapy was inversely correlated with improvement in airway vascular permeability index (r = − 0.53, p = 0.04) [Fig 3
, left, A]. In contrast, decrease in angiopoietin-2 level after montelukast therapy was positively correlated with improvement in airway vascular permeability index (r = 0.59, p = 0.03) [Fig 3, right, B].