New approaches to COPD

Abstract

No currently available treatments reduce the progression or suppress the inflammation of chronic obstructive pulmonary disease (COPD). However, with a better understanding of the inflammatory and destructive process, several targets have been identified, and new treatments are now in clinical development. Several specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, including adhesion molecule and chemokine-directed therapy, as well as therapies to inhibit tumour necrosis factor-α. Broad spectrum anti-inflammatory drugs are also in development, and include inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase, nuclear factor-κB and phosphoinositide-3 kinase-γ. More specific approaches include antioxidants, inhibitors of inducible nitric oxide synthase, and leukotriene B 4 receptor antagonists. Inhibitors of epidermal growth factor receptor kinase and calcium-activated chloride channel inhibitors have the potential to inhibit mucus hypersecretion. Other therapies are targeted at the structural changes of COPD. Therapy to inhibit fibrosis is being developed against transforming growth factor-β 1 and protease activated receptor-2. There is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that may even reverse this process. There is the need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for chronic obstructive pulmonary disease.