title: Progression of chronic obstructive pulmonary disease: impact of inflammation, comorbidities and therapeutic intervention.
abstract: OBJECTIVE
  Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, and through under-diagnosis, is often inappropriately treated. This multicomponent disease involves both airway and systemic inflammation at all stages and may influence the progression of disease and the pathophysiology of comorbidities. This review examines evidence linking inflammation, disease progression and comorbidities in COPD, and the potential role of anti-inflammatory therapies.
  
  
  METHODS
  Systematic searches of Medline and Cochrane Reviews databases from 1976 to March 2008 using the terms: chronic obstructive pulmonary disease, disease progression, inflammation, inflammatory, comorbid condition, comorbidity, treatment, therapy, bronchodilator, inhaled corticosteroid.
  
  
  RESULTS
  Increased levels of interleukin-8, tumour necrosis factor-alpha and systemic C-reactive protein correlate with worse disease severity, exacerbation rates and lung function decline. Increased systemic C-reactive protein is also associated with poorer health status and comorbidities (e.g. cardiovascular disease, cancer and skeletal muscle dysfunction). The pivotal role of inflammation in the pathogenesis of COPD and its comorbidities suggests anti-inflammatory therapies will be important in the overall management of COPD. Long-term studies indicate that combination therapies consisting of a long-acting beta-agonist plus an inhaled corticosteroid in one inhaler have the potential to modify disease progression through positive effects on lung function, exacerbations, symptoms and health status. The TOwards a Revolution in COPD Health (TORCH) study is the first to demonstrate that a COPD pharmacotherapy (combination salmeterol plus fluticasone propionate) significantly decreased the rate of lung function decline versus placebo.
  
  
  CONCLUSIONS
  Better understanding of the specific inflammatory mechanisms underlying COPD disease progression and associated comorbidities will likely lead to more effective management of the disease.
authors.affiliation: University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. r.a.stockley@bham.ac.uk
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley