Systemic manifestations of COPD and comorbidities Professor William MacNee E.L.E.G.I.

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4. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs

5. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs Oxidative stress Activated inflammatory cells Neutrophils Monocytes Lymphocytes

7. Superoxide anion release fromcirculating neutrophils in COPD

17. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs Weight loss Systemic Inflammation Increased resting energy expenditure Abnormal amino acid metabolism

19. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs Exercise limitation Inflammation/oxidative stress Abnormal mass & structure Abnormal enzyme activities & bioenergetics

22. Quadriceps strength predicts mortality in patients with moderate to severe COPD

26. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs Systemic inflammation and oxidative stress Vascular dysfunction

30. Inflammation and atherothrombosis Atherosclerosis is a chronic inflammatory disease. Atherosclerotic plaque formation is mediated by inflammation and oxidative stress Inflammation can also be linked to atherosclerosis formation. Traditionally, inflammatory markers such as CRP have been considered risk markers rather than risk factors, although this viewpoint is changing. Picture is of atheroma formation at the intima of a coronary artery, showing CRP (light brown) deep to macrophages (red, CD68 marker). Sequential sections suggest that CRP uptake occurs early, acting as a driver of macrophage entry into the atheromatous lesion.Inflammation can also be linked to atherosclerosis formation. Traditionally, inflammatory markers such as CRP have been considered risk markers rather than risk factors, although this viewpoint is changing. Picture is of atheroma formation at the intima of a coronary artery, showing CRP (light brown) deep to macrophages (red, CD68 marker). Sequential sections suggest that CRP uptake occurs early, acting as a driver of macrophage entry into the atheromatous lesion.

34. Circulating monocytes and alveolar macrophages from COPD patients show enhanced release of MMP-9

35. Systemic effects of COPD Systemic inflammation Abnormal nutrition & metabolism Skeletal muscle dysfunction Cardiovascular disease Other organs Osteoskeletal effects Nervous system Diabetes Peptic Ulceration Cancer

37. Systemic effects of COPD Osteoskeletal system

42. Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD

44. Meta-analysis: Conclusions COPD associated with an excess risk of developing lung cancer, after adjusting for confounders including smoking FEV1 < 70% predicted Men: 2.23 x increased risk lung cancer Women: 3.94 x increased risk lung cancer

50. Metabolic syndrome has similar mechanisms as other systemic diseases

51. Systemic effects of COPDTypes Nervous system

54. Accelerated aging (Telomere shortening) in COPD

56. Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD

61. Potential therapeutic role for statins in respiratory disease

64. Prevalence of heart failure in stable �COPD� (aged 65 years or over) Rutten FH et al, Eur Heart J 2005;26:1887-94

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