Kanazawa H, Shiraishi S, Hirata K, Yoshikawa J
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Abenoku, Osaka, Japan.
Thorax. 2003 Feb;58(2):106-9. doi: 10.1136/thorax.58.2.106.
The prevalent theory concerning the pathogenesis of chronic obstructive pulmonary disease (COPD) is of an imbalance between oxidants and antioxidants in the lung. It has recently been reported that the production of peroxynitrite, an extremely potent oxidant, is increased in the airways of patients with COPD. A study was undertaken of the imbalance between the levels of nitrogen oxides and antioxidant activity against peroxynitrite in the airways of patients with COPD.
Sputum induction was performed in 30 patients with COPD and 15 normal control subjects. Levels of nitrogen oxides, percentage of neutrophils, and interleukin 8 (IL-8) levels were measured in sputum samples, and peroxynitrite inhibitory activity was assayed by monitoring rhodamine formation.
Nitrite and nitrate levels in induced sputum were significantly higher in patients with COPD than in normal controls (949 (133) microM v 621 (89) microM, p<0.001). In contrast, peroxynitrite inhibitory activity in induced sputum was significantly lower in patients with COPD than in normal controls (47.4 (12.7)% v 92.9 (3.9)%, p<0.001). There was a negative correlation between nitrite and nitrate levels and peroxynitrite inhibitory activity in induced sputum (r=-0.775, p<0.001). Peroxynitrite inhibitory activity was also significantly correlated with forced expiratory volume in 1 second (FEV(1)) % predicted (r=0.539, p=0.004), FEV(1)/FVC (r=0.512, p=0.006), and carbon monoxide transfer factor (TLCO) (r=0.486, p=0.009). Moreover, there was a significant negative correlation between peroxynitrite inhibitory activity and the degree of neutrophilic inflammation (percentage of neutrophils: r=-0.754, p<0.001; IL-8 levels: r=-0.497, p=0.007).
Reduced peroxynitrite inhibitory activity and increased levels of nitrogen oxides are found in induced sputum from patients with COPD. An imbalance in nitrogen oxides and antioxidant defence may contribute to the pathogenesis of COPD.
关于慢性阻塞性肺疾病（COPD）发病机制的普遍理论是肺部氧化剂与抗氧化剂之间失衡。最近有报道称，过氧亚硝酸盐（一种极强的氧化剂）在COPD患者气道中的生成增加。本研究对COPD患者气道中氮氧化物水平与针对过氧亚硝酸盐的抗氧化活性之间的失衡情况进行了研究。
对30例COPD患者和15名正常对照者进行痰液诱导。检测痰液样本中氮氧化物水平、中性粒细胞百分比和白细胞介素8（IL-8）水平，并通过监测罗丹明生成来测定过氧亚硝酸盐抑制活性。
COPD患者诱导痰液中的亚硝酸盐和硝酸盐水平显著高于正常对照者（949（133）μM对621（89）μM，p<0.001）。相比之下，COPD患者诱导痰液中的过氧亚硝酸盐抑制活性显著低于正常对照者（47.4（12.7）%对92.9（3.9）%，p<0.001）。诱导痰液中的亚硝酸盐和硝酸盐水平与过氧亚硝酸盐抑制活性之间呈负相关（r=-0.775，p<0.001）。过氧亚硝酸盐抑制活性还与预测的第1秒用力呼气量（FEV(1)）%（r=0.539，p=0.004）、FEV(1)/FVC（r=0.512，p=0.006）以及一氧化碳转运因子（TLCO）（r=0.486，p=0.009）显著相关。此外，过氧亚硝酸盐抑制活性与中性粒细胞炎症程度之间存在显著负相关（中性粒细胞百分比：r=-0.754，p<0.001；IL-8水平：r=-0.497，p=0.007）。
在COPD患者的诱导痰液中发现过氧亚硝酸盐抑制活性降低以及氮氧化物水平升高。氮氧化物与抗氧化防御之间的失衡可能导致COPD的发病机制。
