Respiratory Translational Research Group, Department of Laboratory Medicine, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.
Medical Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Int J Chron Obstruct Pulmon Dis. 2019 Jul 18;14:1603-1610. doi: 10.2147/COPD.S208428. eCollection 2019.
COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates. There is an urgent need for in-depth studies of the fundamental pathogenic mechanisms that underpin COPD. This is vital, given the fact that nearly 40%-60% of the small airway and alveolar damage occurs in COPD well before the first measurable changes in lung function are detected. These individuals are also at a high risk of lung cancer. Current COPD research is mostly centered around late disease and/or innate immune activation within the airway lumen, but the actual damage to the airway wall has early onset. COPD is the end result of complex mechanisms, possibly triggered through initial epithelial activation. To change the disease trajectory, it is crucial to understand the mechanisms in the epithelium that are switched on early in smokers. One such mechanism we believe is the process of epithelial to mesenchymal transition. This article highlights the importance of this profound epithelial cell plasticity in COPD and also its regulation. We consider that understanding early changes in COPD will open new windows for therapy.
COPD 是一种常见且极具破坏性的疾病，对全球的人群和医疗服务都有着巨大的影响。它主要由吸烟引起，但环境污染也有一定影响。目前尚无影响 COPD 整体进程的治疗方法；现有药物主要针对症状缓解，并在一定程度上降低恶化率。深入研究 COPD 潜在发病机制迫在眉睫。鉴于近 40%-60%的小气道和肺泡损伤发生在肺功能首次出现可测量变化之前，这一点至关重要。这些个体也有较高的肺癌风险。目前的 COPD 研究主要集中在晚期疾病和/或气道腔内固有免疫激活，但气道壁的实际损伤很早就开始了。COPD 是复杂机制的最终结果，可能通过初始上皮细胞激活引发。为了改变疾病进程，了解吸烟者早期被激活的上皮细胞中的机制至关重要。我们认为，其中一个机制是上皮细胞向间充质转化过程。本文强调了这种深刻的上皮细胞可塑性在 COPD 中的重要性及其调控。我们认为，了解 COPD 的早期变化将为治疗开辟新的途径。
