Abstract
The review performs a systems medicine analysis of underlying biological mechanisms of non-pulmonary phenomena: skeletal muscle dysfunction and co-morbidity clustering, seen in patients suffering from chronic obstructive pulmonary disease (COPD). The overarching hypothesis is that non-pulmonary manifestations play a major role and they cannot solely be explained by the activity of the pulmonary disease. The manuscript articulates the outcomes of several research and deployment initiatives carried out to foster convergence between systems medicine and integrated care in the region of Catalonia (ES) aiming at generating healthcare efficiencies in the management of chronic patients. The analyses identified abnormalities in co-regulation of bioenergetics, inflammation and tissue remodelling processes, operating as central players in non-pulmonary manifestations. The findings showed significant associations of non-pulmonary phenomena with aerobic capacity, but not with lung function, with a relevant role of oxidative stress as a key characteristic mechanism in these patients. The review points out the need for novel health risk assessment strategies to enhance service selection. The findings strongly indicate that current standards for clinical management should be complemented by a patient-oriented approach prioritizing enhanced comorbidity prevention and management.