Foronjy Robert, Wallace Alison, D'Armiento Jeanine
Department of Medicine, Columbia University, New York, NY 10032, USA.
Pulm Pharmacol Ther. 2008;21(2):370-9. doi: 10.1016/j.pupt.2007.10.004. Epub 2007 Oct 23.
COPD is one of the leading causes of death worldwide and the age-adjusted mortality for this disease has risen significantly over the past 30 years. Current pharmacological treatments do not effectively address the inflammatory and apoptotic mechanisms that are critical in the development of this disease. Thus, despite therapy, patients typically experience a continued deterioration of their clinical status. Markers of oxidative stress are increased in the lungs of COPD patients and epidemiologic and animal studies indicate that antioxidants can protect the lungs from the damaging effects of cigarette smoke. To date, however, clinical trials of antioxidants for COPD have yielded disappointing results. This review discusses the pharmokinetic factors that limit the use of exogenous antioxidants as a treatment for this disease. In addition, it addresses strategies to overcome these limitations so that the beneficial properties of antioxidants can be translated into effective therapies for COPD patients.
慢性阻塞性肺疾病(COPD)是全球主要死因之一,在过去30年中,该疾病经年龄调整后的死亡率显著上升。目前的药物治疗无法有效解决在该疾病发展过程中起关键作用的炎症和凋亡机制。因此,尽管进行了治疗,患者的临床状况通常仍会持续恶化。COPD患者肺部的氧化应激标志物会增加,流行病学和动物研究表明,抗氧化剂可以保护肺部免受香烟烟雾的损害。然而,迄今为止,针对COPD的抗氧化剂临床试验结果令人失望。本综述讨论了限制使用外源性抗氧化剂治疗该疾病的药代动力学因素。此外,还探讨了克服这些限制的策略,以便将抗氧化剂的有益特性转化为COPD患者的有效治疗方法。