Future treatments for chronic obstructive pulmonary disease and its comorbidities.
Future treatments for chronic obstructive pulmonary disease and its comorbidities.
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DOI：
10.1513/pats.200807-069th
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发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Barnes, Peter J
中科院分区：
文献类型：
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作者：
Barnes, Peter J
认识到慢性阻塞性肺疾病（COPD）患者可能有全身性表现，并经常患有共病，这对需要进一步研究的治疗具有重要意义。COPD和肺外效应之间最可能的联系是肺部外周炎症“溢出”进入体循环，并对其他器官产生影响，这些器官也可能受到吸烟全身效应的影响。COPD的外周肺部炎症和全身炎症效应可以通过全身性COPD治疗来治疗，但这可能具有全身性副作用的高风险，或者通过吸入施用抑制肺部炎症并防止炎症介质溢出到体循环中的COPD治疗来治疗。目前COPD的治疗方法，包括吸入性皮质类固醇、长效β 2受体激动剂和茶碱，有可能减少COPD和共病的全身特征。对共病的治疗，如他汀类药物、血管紧张素转换酶抑制剂和过氧化物酶体增殖物激活激动剂激动剂，也可能对COPD炎症有有益作用。新型COPD治疗，如磷酸二酯酶-4、核因子-κ B和p38丝裂原活化蛋白激酶抑制剂，可能对COPD和合并症均有益处，但全身给药时不良反应风险高，可能需要吸入给药。增加的氧化应激可能是连接COPD炎症、全身效应和共病的重要机制，因此开发抗氧化剂，包括核因子红细胞-2相关因子2激活剂，是当务之急。加速老化可能与COPD和几种合并症共同相关，促进了抗衰老分子的开发，如sirtuin 1激动剂，这也可能有效降低肺癌的风险。
The recognition that patients with chronic obstructive pulmonary disease (COPD) may have systemic manifestations and often suffer from comorbid conditions has important implications for therapy that require further research. The most likely link between COPD and extrapulmonary effects is that inflammation in the lung periphery "spills over" into the systemic circulation and effects on other organs that may also be affected by the systemic effects of cigarette smoking. The peripheral lung inflammation of COPD and systemic inflammatory effects could be treated by systemic antiinflammatory treatments, but this may have a high risk of systemic side effects, or by inhaled administration of antiinflammatory treatments that suppress inflammation in the lung and prevent the spillover of inflammatory mediators into the systemic circulation. Current therapies for COPD, including inhaled corticosteroids, long-acting beta(2)-agonists, and theophylline, have the potential to reduce systemic features of COPD and comorbid diseases. Treatments for comorbid diseases, such as statins, angiotensin-converting enzyme inhibitors, and peroxisome proliferator-activated agonist agonists, may also have beneficial effects on COPD inflammation. Novel antiinflammatory treatments, such as phosphodiesterase-4, nuclear factor-kappaB, and p38 mitogen-activated protein kinase inhibitors, may provide benefits in both COPD and comorbidities, but have a high risk of adverse effects when given systemically, and may need to be given by inhalation. Increased oxidative stress may be an important mechanism linking COPD inflammation, systemic effects, and comorbid disease, so the development of antioxidants, including nuclear factor erythroid-2-related factor 2 activators, is a priority. Accelerated aging may be associates in common to COPD and several comorbidities, prompting the development of antiaging molecules, such as sirtuin 1 agonists, which may also be effective in reducing the risk of lung cancer.