Domej Wolfgang, Oettl Karl, Renner Wilfried
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria.
Int J Chron Obstruct Pulmon Dis. 2014 Oct 17;9:1207-24. doi: 10.2147/COPD.S51226. eCollection 2014.
Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.
当自由基和其他活性物质超过抗氧化剂的供应时,就会发生氧化应激。活性氧(ROS)、活性氮及其对应的抗氧化剂对于生理信号传导、宿主防御以及炎症的发生和持续至关重要。当它们的正常稳态受到干扰时,氧化剂和抗氧化剂之间的失衡可能引发病理反应,导致一系列非呼吸道和呼吸道疾病,尤其是慢性阻塞性肺疾病(COPD)。在呼吸系统中,ROS可能来自或多或少可吸入的气态或颗粒物质,如空气污染物、香烟烟雾、环境高海拔缺氧和一些职业粉尘,这些为外源性;或者在针对细菌、病毒或真菌等传染性病原体的防御机制中内源性产生。ROS也可能根据接触的量和持续时间损害身体组织,并可能进一步触发从呼吸道、免疫和炎症细胞释放的酶促产生的ROS。本文重点关注自由基与COPD和肺气肿的发生发展的一般相关性以及治疗选择的新观点。不幸的是,目前的治疗选择不足以预防慢性气道炎症,也无法实质性改变COPD的病程。迫切需要有效的治疗性抗氧化措施来控制和减轻COPD和其他呼吸道疾病中的局部和全身氧爆发。除了当前的治疗前景和基因组医学的各个方面,还介绍了COPD的热门研究课题。