Targeting Lung Inflammation: Novel Therapies for the Treatment of COPD

Irfan      Rahman; Hongwei      Yao; Willem   I.   de Boer

Abstract

Chronic obstructive pulmonary disease (COPD) is a global health problem. COPD is associated with the progressive pulmonary inflammation and destruction of lung parenchyma (emphysema) that relate to disease severity. Therefore, it is anticipated that drugs that reduce pulmonary inflammation will provide effective, disease modifying therapy for COPD. Several specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD; these include agents directed against cytokines and chemokines. Broad-range antiinflammatory drugs are now in phase III development for COPD; they include inhibitors of phosphodiesterase 4 (PDE4). Other drugs that inhibit cell signaling include inhibitors of p38 mitogen-activated protein kinase (MAPK), nuclear factor- κB (NF-κB), HDAC2 modifiers and phosphoinositide-3-kinase (PI3K). There is also a search for inhibitors of proteinases and matrix metalloproteinases (MMPs) to prevent lung destruction and the development of emphysema. This review highlights the studies on novel or potential anti-inflammatory agents that might be considered in the development of new future therapies for COPD.

Keywords: NF-κB, MAP kinase, MMPs, cigarette smoke, cytokines, antagonists

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