Sturton Graham, Persson Carl, Barnes Peter J
National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK.
Trends Pharmacol Sci. 2008 Jul;29(7):340-5. doi: 10.1016/j.tips.2008.04.003.
Changes in the structure and function of the small airways (<2mm diameter) are now recognized to play a major role in airflow limitation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Increased thickness of the small airway wall causes lumenal narrowing, which can be further occluded by mucus and/or inflammatory cell exudate. This leads to increased peripheral resistance, air trapping and shortness of breath on exertion. Studies in animal models and in subjects with COPD have suggested that oxidant-driven transforming growth factor (TGF)-beta1 activation and subsequent increased airway wall collagen synthesis might be central to the changes in small airway structure. However, it remains difficult to measure small airway function in patients, and delivery of inhaled drugs to peripheral airways has not yet been optimised. The increased understanding of the processes underlying the development of small airways disease should facilitate pharmacological intervention targeted at this hitherto neglected compartment.
现在人们认识到，小气道（直径<2mm）的结构和功能变化在慢性阻塞性肺疾病（COPD）和重度哮喘的气流受限中起主要作用。小气道壁厚度增加会导致管腔狭窄，黏液和/或炎性细胞渗出物会使其进一步阻塞。这会导致外周阻力增加、气体潴留和运动时呼吸急促。动物模型和COPD患者的研究表明，氧化剂驱动的转化生长因子（TGF）-β1激活以及随后气道壁胶原蛋白合成增加可能是小气道结构变化的核心。然而，在患者中测量小气道功能仍然困难，吸入药物向周边气道的递送尚未得到优化。对小气道疾病发病过程的深入了解应有助于针对这一迄今被忽视的部位进行药物干预。
