title: Chronic obstructive pulmonary disease: effects beyond the lungs.
abstract: OBJECTIVE
  This article reviews the systemic effects of chronic obstructive pulmonary disease in general and the musculoskeletal effects and cachexia in particular.
  
  
  RESULTS
  Shift in muscle fiber type from I to II, reduction of capillary/mitochondria ratio, reduction of oxidative enzymes and oxidative capacity, alteration in amino acid profile, changes in respiratory muscle dynamics, activation of the ubiquitin-proteosome pathway with loss of contractile proteins are some of the factors found to cause muscle dysfunction in chronic obstructive pulmonary disease. Chemotaxis and capability to produce more reactive oxygen species and to cause extracellular proteolysis are enhanced in neutrophils of chronic obstructive pulmonary disease patients. Tumor necrosis factor-alpha is shown to cause loss of myosin chains in a time and dose-dependent fashion and to induce production of reactive oxygen species through activation of the cyclooxygenase pathway. Inflammation and oxidative stress caused by reactive oxygen species fuel each other. Weight loss due to muscle wasting (cachexia) in chronic obstructive pulmonary disease is not solely related to malnutrition and is an independent predictor of mortality. Causative factors for cachexia include cytokine effects, protein degradation enhanced by increased ubiquination, upregulation of mRNA for key enzymes, increased energy expenditure and neurohormonal effects such as leptin production and an imbalance in anabolic and catabolic hormone homeostasis.
  
  
  CONCLUSIONS
  The findings noted above may well have the common link of inflammation in and beyond the lungs.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee 53226, USA. bvarkey@mcw.edu
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Balasubramanian
authors.forename: Basil
authors.initials: B
authors.lastname: Varkey
mesh_terms: D002100:Cachexia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012132:Respiratory Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018377:Neurotransmitter Agents