Barnes Peter J, Hansel Trevor T
National Heart and Lung Institute, Imperial College School of Medicine, London SW3 6LY, UK.
Lancet. 2004;364(9438):985-96. doi: 10.1016/S0140-6736(04)17025-6.
No currently available treatments have been shown to slow the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments are in clinical development; some target the inflammatory process and others are directed against structural cells. A group of specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD; these include agents directed against adhesion molecules and chemokines, as well as therapies to oppose tumour necrosis factor alpha and increase interleukin 10. Broad-range anti-inflammatory drugs are now in phase III development for COPD; they include inhibitors of phosphodiesterase 4. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor kappaB, and phosphoinositide-3-kinase gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase, and antagonists of leukotriene B4 receptor. Inhibitors of epidermal-growth-factor-receptor kinase and calcium-activated chloride channels have the potential to prevent overproduction of mucus. Therapy to inhibit fibrosis is being developed against transforming growth factor beta1 and protease-activated receptor 2. There is also a search for inhibitors of serine proteinases and matrix metalloproteinases to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that might even reverse this process. Effective delivery of drugs to the sites of disease in the peripheral lung is an important consideration, and there is a need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for COPD.
目前尚无已证实能减缓慢性阻塞性肺疾病（COPD）进展或抑制小气道及肺实质炎症的治疗方法。然而，有几种新疗法正在进行临床开发；一些针对炎症过程，另一些则针对结构细胞。一组特定疗法针对COPD中发生的炎症细胞流入气道和肺实质的情况；这些疗法包括针对黏附分子和趋化因子的药物，以及对抗肿瘤坏死因子α和增加白细胞介素10的疗法。广谱抗炎药物目前正处于COPD的III期开发阶段；它们包括磷酸二酯酶4抑制剂。其他抑制细胞信号传导的药物包括p38丝裂原活化蛋白激酶、核因子κB和磷酸肌醇-3-激酶γ的抑制剂。更具针对性的方法是给予抗氧化剂、诱导型一氧化氮合酶抑制剂和白三烯B4受体拮抗剂。表皮生长因子受体激酶和钙激活氯离子通道的抑制剂有可能防止黏液过度产生。针对转化生长因子β1和蛋白酶激活受体2正在开发抑制纤维化的疗法。此外，正在寻找丝氨酸蛋白酶和基质金属蛋白酶的抑制剂，以防止肺组织破坏和肺气肿的发展，以及可能逆转这一过程的药物，如类视黄醇。将药物有效递送至外周肺的疾病部位是一个重要考虑因素，并且在COPD新疗法的早期临床研究中需要经过验证的生物标志物和监测技术。
