title: Lungs, bone marrow, and adipose tissue. A network approach to the pathobiology of chronic obstructive pulmonary disease.
abstract: Patients with chronic obstructive pulmonary disease (COPD) often suffer other concomitant disorders, such as cardiovascular diseases and metabolic disorders, that influence significantly (and independently of lung function) their health status and prognosis. Thus, COPD is not a single organ condition, and disturbances of a complex network of interorgan connected responses occur and modulate the natural history of the disease. Here, we propose a novel hypothesis that considers a vascularly connected network with (1) the lungs as the main external sensor of the system and a major source of "danger signals"; (2) the endothelium as an internal sensor of the system (also a potential target tissue); and (3) two key responding elements, bone marrow and adipose tissue, which produce both inflammatory and repair signals. According to the model, the development of COPD, and associated multimorbidities (here we focus on cardiovascular disease as an important example), depend on the manner in which the vascular connected network responds, adapts, or fails to adapt (dictated by the genetic and epigenetic background of the individual) to the inhalation of particles and gases, mainly in cigarette smoke. The caveats and limitations of the hypothesis, as well as the experimental and clinical research needed to test and explore the proposed model, are also briefly discussed.
authors.affiliation: 1 Thorax Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.forename: Victor I
authors.initials: VI
authors.lastname: Peinado
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jeffery
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers