Thrombin in the airways of asthmatic patients

The mechanism of airway remodeling in asthmatic patients is poorly understo od. Thrombin is a multifunctional protease that, in addition to its critica l role in thrombotic processes, has also been described as inducing cellula r and molecular events relevant to tissue remodeling. The present investiga tion was undertaken to evaluate the activity of thrombin in the sputum of a sthmatic patients and its potential role in airway remodeling. The study po pulation comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT ), and tissue factor were measured in the sputum of all subjects. The conce ntrations of thrombin (p = 0.007), TAT (p = 0.01), and tissue factor (p = 0 .02) in sputum were significantly higher in asthmatic patients than in heal thy controls. The proliferative effects that sputum from asthmatic patients (p = 0.01) and thrombin (p = 0.03) have on cultured human smooth muscle ce lls was inhibited significantly in the presence of recombinant hirudin, a s pecific thrombin inhibitor. Significant statistical correlation was observe d between the degree of branchial responsiveness and the sputum concentrati ons of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The resu lts of this study showed that increased thrombin generation occurs in the a irway of patients with asthma and that it may play a role in the pathogenes is of airway remodeling. Further studies should be carried out to assess wh ether these findings are also observed in other airway diseases.