Angiopoietin-2 as a contributing factor of exercise-induced bronchoconstriction in asthmatic patients receiving inhaled corticosteroid therapy

Background: Airway microcirculation has the potential to contribute to the pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma. Recently, angiopoietin-1 has been found to stabilize microvessels and make them leak resistant, whereas angiopoietin-2 is an antagonist of angiopoietin-1 and enhances microvascular permeability. Objective: We sought to examine the roles of angiopoietin-2 in EIB in asthmatic patients with inhaled corticosteroid therapy. Methods: Levels of angiopoietin-1 and angiopoietin-2 in induced sputum were examined in 32 asthmatic patients who were receiving inhaled corticosteroid therapy for more than 6 months at the entry of this study and 14 healthy control subjects. All asthmatic patients performed an exercise test. Results: The degree of eosinophilic airway inflammation did not differ significantly between asthmatic patients and healthy control subjects. Angiopoietin-1 levels were also similar in the 2 groups (asthmatic patients: median, 6.0 ng/mL [range, 2.0-10.7 ng/mL]; healthy control subjects: median, 4.2 ng/mL [range, 1.5-10.7 ng/mL]). In contrast, angiopoietin-2 levels were significantly higher in asthmatic patients than in healthy control subjects (asthmatic patients: median, 0.74 ng/mL [range, 0.3-1.2 ng/mL]; healthy control subjects: median, 0.26 ng/mL [range, 0.05-0.47 ng/mL]; P < .001). There was no significant correlation between angiopoietin-1 levels and the severity of EIB in asthmatic patients. However, angiopoietin-2 levels were significantly correlated with the severity of EIB and airway microvascular permeability index. Conclusion: Angiopoietin-2 levels were increased in the airways of asthmatic patients with inhaled corticosteroid therapy, and its levels were associated with the severity of EIB.