title: Persistent endothelial dysfunction turns the frequent exacerbator COPD from respiratory disorder into a progressive pulmonary and systemic vascular disease.
abstract: 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.
authors.affiliation: University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Vukic Dugac
authors.affiliation: University Hospital Centre Rijeka, Rijeka, Croatia; School of Medicine, University of Rijeka, Rijeka, Croatia. Electronic address: alen.ruzic1@ri.t-com.hr.
authors.forename: A
authors.initials: A
authors.lastname: Ruzic
authors.affiliation: University Hospital Centre Zagreb, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Samarzija
authors.affiliation: University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Badovinac
authors.affiliation: Hospital Thalassotherapia Opatija, Opatija, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Kehler
authors.affiliation: University Hospital Centre Zagreb, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Jakopovic
mesh_terms: D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D014652:Vascular Diseases / Q000503:physiopathology*