Role of nitric oxide on airway microvascular permeability in patients with asthma

We have recently emphasized that airway microcirculation has the potential to contribute to the pathophysiology of asthma. We therefore hypothesized that increased production of airway nitric oxide (NO) plays an important role in the pathogenesis of asthma through microvascular hyperpermeability. To test our hypothesis, we compared exhaled NO levels in normal subjects and asthmatic patients, and examined the contribution of airway microvascular permeability to the pathophysiology of asthma.

Inflammatory indexes in induced sputum, exhaled NO levels, and airway vascular permeability index were examined in 11 normal controls, 19 beclomethasone dipropionate (BDP)-treated asthmatics, and 20 BDP-untreated asthmatics.

The percentage of eosinophils (% Eos) and concentration of eosinophil cationic protein (ECP) in induced sputum were significantly higher in BDP-untreated asthmatics (% Eos: 16.4 (6.5)%, p < 0.0001; ECP: 674.5 (294.2) ng/mL, p < 0.0001) than in normal controls (0.6 (0.3)%; 112.7 (65.5) ng/mL) and BDP-treated asthmatics (0.7 (0.6)%; 116.3 (72.6) ng/mL). However, exhaled NO levels were significantly higher in BDP-untreated (16.4 (6.9) ppb, p < 0.0001) and -treated (11.2 (3.5) ppb, p = 0.007) asthmatics than in normal controls (5.9 (1.8) ppb). Similarly, airway vascular permeability index was significantly higher in BDP-untreated (0.028 (0.009), p < 0.0001) and -treated (0.016 (0.006), p = 0.005) asthmatics than in normal controls (0.008 (0.003)). We found a significant correlation between exhaled NO level and airway vascular permeability index in both BDP-untreated asthmatics (r = 0.85, p < 0.0001) and -treated asthmatics (r = 0.64, p = 0.0023). Moreover, airway hyperreactivity to methacholine was also significantly correlated with exhaled NO level in BDP-untreated (r = -0.68, p = 0.003) and -treated (r = -0.49, p = 0.037) asthmatics.

Increased production of airway NO is a key factor in the development of airway hyperresponsiveness. Interaction between airway microcirculation and NO may be a key element in disordered airway function in asthma.