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

Abstract

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. We sought to examine the roles of angiopoietin-2 in EIB in asthmatic patients with inhaled corticosteroid therapy. 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. 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. 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.