一氧化氮在哮喘患者气道微血管通透性中的作用。

Tohyama Yoshiki, Kanazawa Hiroshi, Fujiwara Hiroshi, Hirata Kazuto, Fujimoto Shigeo, Yoshikawa Junichi

Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Japan.

Osaka City Med J. 2005 Jun;51(1):1-9.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

背景

我们最近强调气道微循环可能参与哮喘的病理生理过程。因此，我们推测气道一氧化氮（NO）生成增加通过微血管高通透性在哮喘发病机制中起重要作用。为验证我们的假设，我们比较了正常受试者和哮喘患者的呼出气NO水平，并研究气道微血管通透性对哮喘病理生理的影响。

方法

检测了11名正常对照者、19名接受丙酸倍氯米松（BDP）治疗的哮喘患者和20名未接受BDP治疗的哮喘患者诱导痰中的炎症指标、呼出气NO水平和气道血管通透性指数。

结果

未接受BDP治疗的哮喘患者诱导痰中嗜酸性粒细胞百分比（%Eos）和嗜酸性粒细胞阳离子蛋白（ECP）浓度（%Eos：16.4（6.5）%，p<0.0001；ECP：674.5（294.2）ng/mL，p<0.0001）显著高于正常对照者（0.6（0.3）%；112.7（65.5）ng/mL）和接受BDP治疗的哮喘患者（0.7（0.6）%；116.3（72.6）ng/mL）。然而，未接受BDP治疗（16.4（6.9）ppb，p<0.0001）和接受BDP治疗（11.2（3.5）ppb，p=0.007）的哮喘患者呼出气NO水平显著高于正常对照者（5.9（1.8）ppb）。同样，未接受BDP治疗（0.028（0.009），p<0.0001）和接受BDP治疗（0.016（0.006），p=0.005）的哮喘患者气道血管通透性指数显著高于正常对照者（0.008（0.003））。我们发现未接受BDP治疗的哮喘患者（r=0.85，p<0.0001）和接受BDP治疗的哮喘患者（r=0.64，p=0.0023）呼出气NO水平与气道血管通透性指数之间存在显著相关性。此外，未接受BDP治疗（r=-0.68，p=0.003）和接受BDP治疗（r=-0.49，p=0.037）的哮喘患者对乙酰甲胆碱的气道高反应性也与呼出气NO水平显著相关。