Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD. However, it has proven difficult to develop selective kinase inhibitors that are both effective and safe after oral administration and this has led to a search for inhaled kinase inhibitors, which would reduce systemic exposure. Although many kinases have been implicated in inflammation and remodeling of airway disease, very few classes of drug have reached the stage of clinical studies in these diseases. The most promising drugs are p38 MAP kinases, isoenzyme-selective PI3-kinases, Janus-activated kinases, and Syk-kinases, and inhaled formulations of these drugs are now in development. There has also been interest in developing inhibitors that block more than one kinase, because these drugs may be more effective and with less risk of losing efficacy with time. No kinase inhibitors are yet on the market for the treatment of airway diseases, but as kinase inhibitors are improved from other therapeutic areas there is hope that these drugs may eventually prove useful in treating refractory asthma and COPD.

中文翻译：

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激酶作为哮喘和慢性阻塞性肺疾病的新型治疗靶标。

多种激酶在协调哮喘和慢性阻塞性肺疾病（COPD）患者的慢性炎症和呼吸道结构变化中起关键作用。激酶激活信号通路，导致气道平滑肌收缩并释放炎性介质（例如细胞因子，趋化因子，生长因子）以及细胞迁移，激活和增殖。由于这个原因，人们对开发激酶抑制剂作为抗炎疗法非常感兴趣，尤其是在严重的哮喘和COPD患者中，皮质类固醇激素疗效较差的地方。然而，已经证明很难开发出口服给药后既有效又安全的选择性激酶抑制剂，这导致人们寻找可减少全身暴露的吸入激酶抑制剂。尽管许多激酶与气道疾病的炎症和重塑有关，但是很少有几类药物进入这些疾病的临床研究阶段。最有前途的药物是p38 MAP激酶，同工酶选择性PI3激酶，Janus活化激酶和Syk激酶，这些药物的吸入制剂正在开发中。还存在开发阻断一种以上激酶的抑制剂的兴趣，因为这些药物可能更有效，并且随着时间的流逝失去功效的风险较小。市场上尚无激酶抑制剂可用于治疗气道疾病，但随着激酶抑制剂在其他治疗领域的发展，人们希望这些药物最终可证明可用于治疗难治性哮喘和COPD。