title: Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.
abstract: BACKGROUND
  Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease.
  
  
  METHODS
  93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels.
  
  
  RESULTS
  At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024).
  
  
  CONCLUSIONS
  Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.
authors.affiliation: Department of Academic Respiratory Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK. J.A.Wedzicha@mds.qmw.ac.uk
authors.forename: J A
authors.initials: JA
authors.lastname: Wedzicha
authors.forename: T A
authors.initials: TA
authors.lastname: Seemungal
authors.forename: P K
authors.initials: PK
authors.lastname: MacCallum
authors.forename: E A
authors.initials: EA
authors.lastname: Paul
authors.forename: G C
authors.initials: GC
authors.lastname: Donaldson
authors.forename: A
authors.initials: A
authors.lastname: Bhowmik
authors.forename: D J
authors.initials: DJ
authors.lastname: Jeffries
authors.forename: T W
authors.initials: TW
authors.lastname: Meade
mesh_terms: D000368:Aged; D001784:Blood Gas Analysis; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000097:blood; D012307:Risk Factors; D014797:Vital Capacity
chemical_list: D015850:Interleukin-6; D005340:Fibrinogen