Barnes Peter J
National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St., London SW3 6LY, UK.
Proc Am Thorac Soc. 2008 Dec 1;5(8):857-64. doi: 10.1513/pats.200807-069TH.
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.
认识到慢性阻塞性肺疾病（COPD）患者可能有全身表现且常伴有合并症，这对需要进一步研究的治疗具有重要意义。COPD与肺外效应之间最可能的联系是肺周边的炎症“溢出”到体循环中，并对其他可能也受吸烟全身效应影响的器官产生作用。COPD的外周肺炎症和全身炎症效应可以通过全身抗炎治疗来处理，但这可能有较高的全身副作用风险，或者通过吸入抗炎治疗来抑制肺部炎症并防止炎症介质溢入体循环。目前用于COPD的治疗方法，包括吸入性糖皮质激素、长效β2受体激动剂和茶碱，有可能减轻COPD的全身特征和合并症。针对合并症的治疗，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受体激动剂，也可能对COPD炎症有有益作用。新型抗炎治疗，如磷酸二酯酶-4、核因子-κB和p38丝裂原活化蛋白激酶抑制剂，可能对COPD和合并症都有益，但全身给药时不良反应风险较高，可能需要通过吸入给药。氧化应激增加可能是连接COPD炎症、全身效应和合并症的重要机制，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。加速衰老可能是COPD和几种合并症共有的特征，这促使人们开发抗衰老分子，如沉默调节蛋白1激动剂，其也可能有效降低肺癌风险。
