Vukic Dugac A, Ruzic A, Samarzija M, Badovinac S, Kehler T, Jakopovic M
University Hospital Centre Zagreb, Zagreb, Croatia.
University Hospital Centre Rijeka, Rijeka, Croatia; School of Medicine, University of Rijeka, Rijeka, Croatia.
Med Hypotheses. 2015 Feb;84(2):155-8. doi: 10.1016/j.mehy.2014.11.017. Epub 2014 Dec 10.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in developed countries of the world, while the main cause of mortality and morbidity in COPD patients are acute exacerbations and cardiovascular diseases. With regard to the frequency of exacerbations the phenotype "frequent exacerbators" has been defined, which, besides a more severe clinical course and a significantly higher total mortality, is also characterised by an elevated risk of cardiovascular mortality, as some indicators show us. It is notable that during the exacerbation of COPD, next to other changes, a significant aggravation of endothelial function occurs while the ED and COPD relationship seems very complex and is still in greater part unknown. Making the pathophysiological link between the frequency of exacerbations of COPD and ED could change our understanding of the character of this type of pulmonary disease. We hypothesize that frequent exacerbator COPD is a progressive and generalised vascular disease, not only an isolated respiratory disorder with ancillary systemic effects. Our opinion is that differences in COPD phenotype do not only determine the clinical picture but could also be of key importance in defining the progressivity of the disease. ED, which in these patients persists between frequent exacerbations, could be the main cause of the progression of pulmonary disease, and not only of the high cardiovascular risk of these patients. Such a persistent ED in FE COPD, with its pro-inflammatory, vasoconstrictory and prothrombotic mechanisms, could contemporaneously induce new exacerbations of COPD, the progression of pulmonary changes and the development of systemic atherosclerosis as a main extrapulmonary manifestation in these patients. Such a model defines endothelium as a common soil of progressive pulmonary and cardiovascular changes in FE COPD. It can fully explain all the elements of the clinical course and co-morbidity in FE COPD, for which we still do not have adequate explanation.
慢性阻塞性肺疾病（COPD）是世界发达国家主要的死亡原因之一，而COPD患者死亡和发病的主要原因是急性加重和心血管疾病。关于加重频率，已定义了“频繁加重者”这一表型，正如一些指标所示，除了临床病程更严重和总死亡率显著更高外，其心血管死亡率风险也升高。值得注意的是，在COPD加重期间，除其他变化外，内皮功能会显著恶化，而内皮功能障碍（ED）与COPD的关系似乎非常复杂，在很大程度上仍不为人知。建立COPD加重频率与ED之间的病理生理联系可能会改变我们对这种类型肺部疾病特征的理解。我们假设频繁加重型COPD是一种进行性全身性血管疾病，而不仅仅是一种伴有附属全身效应的孤立性呼吸系统疾病。我们认为，COPD表型的差异不仅决定临床症状，在定义疾病的进展性方面也可能至关重要。在这些患者中，频繁加重之间持续存在的ED可能是肺部疾病进展的主要原因，而不仅仅是这些患者心血管高风险的原因。在频繁加重型COPD中这种持续存在的ED，凭借其促炎、血管收缩和促血栓形成机制，可能同时诱发COPD的新的加重、肺部病变的进展以及全身性动脉粥样硬化的发展，而全身性动脉粥样硬化是这些患者主要的肺外表现。这样一种模型将内皮定义为频繁加重型COPD中进行性肺部和心血管变化的共同根源。它可以充分解释频繁加重型COPD临床病程和合并症的所有要素，而对于这些要素我们目前仍没有充分的解释。
