COPD: current therapeutic interventions and future approaches.
Although long-acting bronchodilators have been an important advance for the management of chronic obstructive pulmonary disease (COPD), these drugs do not deal with the underlying inflammatory process. No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are now in clinical development. Some therapies, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, whereas others target inflammatory cytokines such as tumour necrosis factor-alpha. Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-kappaB and phosphoinositide-3 kinase-gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase and leukotriene B(4) antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema. More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies.
Barnes
P J
PJ
National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London SW3 6LY, UK. p.j.barnes@imperial.ac.uk
Stockley
R A
RA
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D009093:Mucus / Q000187:drug effects; D044623:Nutrition Therapy / Q000379:methods; D010102:Oxygen Inhalation Therapy / Q000379:methods; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy*; D012121:Respiration, Artificial / Q000379:methods; D012138:Respiratory Therapy / Q000379:methods* / Q000639:trends*; D015398:Signal Transduction / Q000187:drug effects; D016540:Smoking Cessation / Q000379:methods; D014665:Vasodilator Agents / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001993:Bronchodilator Agents; D018836:Inflammation Mediators; D010726:Phosphodiesterase Inhibitors; D011480:Protease Inhibitors; D014665:Vasodilator Agents