Markers of autoreactivity, coagulation and angiogenesis in patients with nonallergic asthma

Background: Patients with nonallergic asthma frequently show autoreactivity as do subjects with chronic urticaria (CU). Activation of the coagulation cascade and hyper-expression of vascular endothelial growth factor (VEGF) were recently found in CU, and there is sparse evidence that the same may occur in asthma. Objective: To investigate autoreactivity, activation of the coagulation cascade, and expression of VEGF in patients with nonallergic asthma. Methods: Twenty-one adults with nonallergic asthma underwent autologous plasma skin test (APST) and the measurement of plasma levels of the prothrombin fragment F1 + 2, D-dimer, VEGF, and the inflammatory marker C-reactive protein (CRP). Twenty-one healthy sex-and age-matched subjects served as normal controls. Results: The APST scored positive in 19 of 21 (90%) patients vs 0 controls. Mean fragment F1 + 2 plasma levels were significantly higher in patients with asthma (267 +/- 243 pM) than in controls (150 +/- 51 pM; P = 0.0001). Similarly, plasma levels of both D-dimer and VEGF were significantly higher in patients than in controls (D-dimer: 2364 +/- 1467 vs 1301 +/- 525 pM; P = 0.0001; VEGF: 1721 +/- 2566 vs 76 +/- 375 fM; P = 0.0001). A trend toward increased levels of F1 + 2, D-dimer, VEGF, and CRP was found in patients with a more severe disease according to GINA classification. Conclusion: Nonallergic asthma is characterized by autoreactivity as well as increased coagulation and angiogenesis markers, which are known to enhance vascular permeability. The presence of circulating vasoactive factors may be relevant to understand the disease pathophysiology and to detect novel therapeutic strategies in nonallergic asthma.