title: Systemic inflammation and comorbidity in COPD: a result of 'overspill' of inflammatory mediators from the lungs? Review of the evidence.
abstract: Chronic obstructive pulmonary disease (COPD) is characterised by an inflammatory response by the lungs to inhaled substances such as cigarette smoking and air pollutants. In addition to the pulmonary features of COPD, several systemic effects have been recognised even after controlling for common aetiological factors such as smoking or steroid use. These include skeletal muscle dysfunction, cardiovascular disease, osteoporosis and diabetes. Individuals with COPD have significantly raised levels of several circulating inflammatory markers indicating the presence of systemic inflammation. This raises the issue of cause and effect. The role of tumour necrosis factor α in COPD is thought to be central to both lung and systemic inflammation and has been implicated in skeletal muscle dysfunction, osteoporosis and type 2 diabetes. It has been hypothesised that inflammation in the lung results in 'overspill' into the circulation causing systemic inflammation. There is supportive evidence that protein movement can occur from the lung surface to the systemic circulation. Evidence from inhaled substances such as air pollutants and cigarette smoke has demonstrated a temporal link between the inflammatory process in the lung and systemic inflammation. Also, studies have shown alterations in circulating inflammatory cells in patients with COPD compared with controls which may reflect the effects of inflammatory mediators (derived from the lung) on circulating cells or the bone marrow. This paper considers the concept of 'overspill' in depth, reviews the current evidence and highlights problems in generating direct evidence to support or refute this concept.
authors.affiliation: Lung Investigation Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. rob.stockley@uhb.nhs.uk
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Sinden
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley
mesh_terms: D015897:Comorbidity; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators