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.
Lab Invest. 2019 Feb;99(2):150-157. doi: 10.1038/s41374-018-0146-0. Epub 2018 Nov 19.
Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation. Small airway fibrosis and obliteration are known to cause fixed airflow obstruction in COPD, and the consequential damage to the lung has an early onset. So far, there is little evidence of the mechanisms that underlie this aspect of pathology. However, emerging research confirms that airway epithelial reprogramming or epithelial to mesenchymal transition (EMT) is a key mechanism that drives fibrotic remodelling changes in smokers and patients with COPD. A recent study by Lai et al. further highlights the importance of EMT in smoking-related COPD pathology. The authors identify HB-EGF, an EGFR ligand, as a key driver of EMT and a potential new therapeutic target for the amelioration of EMT and airway remodelling. There are also wider implications in lung cancer prophylaxis, which is another major comorbidity associated with COPD. We consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications.
慢性阻塞性肺疾病（COPD）是一种进行性和破坏性的慢性肺部疾病，在医学和经济方面都有重大的全球负担。目前尚无药物可以改变疾病进程。在临床实践中，药物最多只能通过缓解急性加重来为受苦的患者提供症状缓解。大多数当前的临床研究活动都集中在晚期严重疾病上，对早期疾病表现的关注较少。目前，人们对疾病进展的潜在机制以及涉及疾病表现的分子开关还缺乏了解。小气道纤维化和闭塞被认为会导致 COPD 中的固定气流阻塞，而对肺部的后续损害则很早就出现了。到目前为止，对于这种病理学方面的机制，证据很少。然而，新兴的研究证实，气道上皮细胞重编程或上皮细胞向间充质转化（EMT）是驱动吸烟者和 COPD 患者纤维化重塑改变的关键机制。最近 Lai 等人的一项研究进一步强调了 EMT 在与吸烟相关的 COPD 病理学中的重要性。作者确定 HB-EGF，一种 EGFR 配体，是 EMT 的关键驱动因素，也是改善 EMT 和气道重塑的潜在新治疗靶点。这对肺癌预防也有更广泛的影响，这是另一种与 COPD 相关的主要合并症。我们认为，对与吸烟者和 COPD 患者上皮细胞可塑性相关的复杂途径的分子理解的提高将具有重大的治疗意义。
