Emerging pharmacotherapies for COPD

Chest. 2008 Dec;134(6):1278-1286. doi: 10.1378/chest.08-1385.


The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments have so far been shown to reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive processes in the pathophysiology of COPD, several new targets have been identified. Several mediator antagonists tested in COPD patients have so far been disappointing, but CXC receptor 2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad-spectrum antiinflammatory drugs, including inhibitors of the enzymes phosphodiesterase 4, p38 mitogen-activated protein kinase, nuclear factor-kappaB, and phosphoinositide-3-kinase-gamma, may be more effective, but the side effects will be a major limitation so that inhaled delivery may be necessary. Perhaps the most promising approach is the reversal of corticosteroid resistance through increasing histone deacetylase-2 activity. This might be achieved by theophylline-like drugs, more effective antioxidants, and nonantibiotic macrolide agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Bronchodilator Agents / therapeutic use
  • Cytokines / antagonists & inhibitors
  • Drug Discovery
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Protease Inhibitors / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Transcription Factors / antagonists & inhibitors


  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Cytokines
  • Enzyme Inhibitors
  • Protease Inhibitors
  • Transcription Factors