The imbalance between increased oxidative agents and antioxidant defence mechanisms is central in the pathogenesis of obstructive lung diseases such as asthma and COPD. In these patients, there are increased levels of reactive oxygen species. Superoxide anions (O₂ -), Hydrogen Peroxide (H₂O₂) and hydroxyl radicals (•OH) are critical for the formation of further cytotoxic radicals in the bronchi and lung parenchyma. Chronic inflammation, partly induced by oxidative stress, can further increase the oxidant burden through activated phagocytic cells (neutrophils, eosinophils, macrophages), particularly in severer disease states. Antioxidants and anti-inflammatory genes are, in fact, frequently downregulated in diseased patients. Nrf2, which activates the Antioxidant Response Element (ARE) leading to upregulation of GPx, thiol metabolism-associated detoxifying enzymes (GSTs) and stressresponse genes (HO-1) are all downregulated in animal models and patients with asthma and COPD. An exaggerated production of Nitric Oxide (NO) in the presence of oxidative stress can promote the formation of oxidizing reactive nitrogen species, such as peroxynitrite (ONO₂ -), leading to nitration and DNA damage, inhibition of mitochondrial respiration, protein dysfunction, and cell damage in the biological systems. Protein nitration also occurs by activation of myeloperoxidase and H₂O₂, promoting oxidation of nitrite (NO₂ -). There is increased nitrotyrosine and myeloperoxidase in the bronchi of COPD patients, particularly in severe disease. The decreased peroxynitrite inhibitory activity found in induced sputum of COPD patients correlates with pulmonary function. Markers of protein nitration - 3- nitrotyrosine, 3-bromotyrosine, and 3-chlorotyrosine - are increased in the bronchoalveolar lavage of severe asthmatics. Targeting the oxidative, nitrosative stress and associated lung inflammation through the use of either denitration mechanisms or new drug delivery strategies for antioxidant administration could improve the treatment of these chronic disabling obstructive lung diseases.

氧化剂增加和抗氧化剂防御机制之间的不平衡是阻塞性肺疾病（如哮喘和COPD）的发病机理的中心。在这些患者中，活性氧水平升高。超氧阴离子（O _2-），过氧化氢（H ₂ O ₂和羟基自由基（•OH）对于在支气管和肺实质中进一步形成细胞毒性自由基至关重要。慢性炎症（部分由氧化应激引起）可通过活化的吞噬细胞（嗜中性粒细胞，嗜酸性粒细胞，巨噬细胞）进一步增加氧化剂负担，尤其是在严重的疾病状态下。实际上，在患病的患者中抗氧化剂和抗炎基因经常被下调。Nrf2激活抗氧化剂反应元件（ARE），导致GPx上调，硫醇代谢相关的解毒酶（GSTs）和应激反应基因（HO-1）在动物模型以及哮喘和COPD患者中均被下调。在存在氧化应激的情况下，一氧化氮（NO）的过量产生会促进氧化性反应性氮的形成，_2-），导致生物系统中的硝化作用和DNA损伤，线粒体呼吸抑制，蛋白质功能障碍和细胞损伤。蛋白的硝化作用还通过激活髓过氧化物酶和H ₂ O _2发生，从而促进亚硝酸盐（NO ₂-）。在COPD患者的支气管中，硝基酪氨酸和髓过氧化物酶增加，特别是在严重疾病中。在COPD患者的诱导痰中发现的过氧亚硝酸盐抑制活性降低与肺功能相关。在严重哮喘患者的支气管肺泡灌洗中，蛋白质硝化的标记物-3-硝基酪氨酸，3-溴酪氨酸和3-氯酪氨酸增加。通过使用反硝化机制或抗氧化剂给药的新药物递送策略来针对氧化，亚硝化应激和相关的肺部炎症，可以改善对这些慢性致残性阻塞性肺疾病的治疗。