A case–control study of bronchial asthma associated with ulcerative colitis: role of airway microvascular permeability

Abstract

Recent attention has been devoted to the respiratory manifestations that may be associated with diseases of distant organs. The most prevalent and distinctive pattern of respiratory involvement in ulcerative colitis (UC) is airway inflammation. This study was designed to examine the contribution of airway microvascular permeability to the pathophysiological association of asthma with UC. Sputum induction and methacholine provocation test were performed in 27 asthmatic patients (15 without UC and 12 with UC), nine patients with UC and 15 normal controls. Inflammatory indexes, vascular endothelial growth factor (VEGF) levels in induced sputum, airway vascular permeability index and exhaled nitric oxide (NO) levels were examined in all subjects. The percentage of eosinophils and concentration of eosinophil cationic protein in induced sputum were similar in all four groups. Though exhaled NO levels were significantly higher in asthmatics with or without UC than in normal controls or UC patients, these levels were comparable in asthmatics with and without UC. VEGF levels in induced sputum and airway vascular permeability index were significantly higher in asthmatics without UC (VEGF: 1920 (990) pg/mL; airway vascular permeability index: 0.018 (0.008)) and asthmatics with UC (6570 (1000) pg/mL; 0.040 (0.006)) than in normal controls (950 (700) pg/mL; 0.009 (0.003)), whose levels were comparable to those of UC patients (900 (600) pg/mL; 0.011 (0.003)). In particular, these parameters were markedly increased in asthmatics with UC than in asthmatics without UC. VEGF level was significantly correlated with airway vascular permeability index in asthmatics with UC. Moreover, VEGF level and airway vascular permeability index was inversely correlated with degree of airway obstruction and airway hyper-reactivity to methacholine in these asthmatics. Airway microvascular hyper-permeability induced by VEGF may have a profound effect on airway function and can explain the heightened airway hyper-responsiveness characteristic of asthma associated with UC.