New drugs for exacerbations of chronic obstructive pulmonary disease.
Tobacco smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD), but viral and bacterial infections are the major causes of exacerbations in later stages of disease. Reactive oxygen species (ROS), pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) activate families of pattern recognition receptors (PRRs) that include the toll-like receptors (TLRs). This understanding has led to the hypothesis that COPD is an archetypal disease of innate immunity. COPD is characterised by abnormal response to injury, with altered barrier function of the respiratory tract, an acute phase reaction, and excessive activation of macrophages, neutrophils, and fibroblasts in the lung. The activated non-specific immune system then mediates the processes of inflammation and repair, fibrosis, and proteolysis. COPD is also associated with corticosteroid resistance, abnormal macrophage and T-cell populations in the airway, autoinflammation and autoimmunity, aberrant fibrosis, accelerated ageing, systemic and concomitant disease, and defective regeneration. Such concepts have been used to generate a range of molecular targets, and clinical trials are taking place to identify effective drugs for the prevention and treatment of COPD exacerbations.
Hansel
Trevor T
TT
National Heart and Lung Institute, Imperial College, London, UK. t.hansel@imperial.ac.uk
Barnes
Peter J
PJ
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D015984:Causality; D005355:Fibrosis; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D017382:Reactive Oxygen Species / Q000009:adverse effects; D051192:Receptors, Pattern Recognition / Q000502:physiology; D012008:Recurrence; D012720:Severity of Illness Index; D051193:Toll-Like Receptors / Q000502:physiology; D014777:Virus Diseases / Q000150:complications
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D001993:Bronchodilator Agents; D017382:Reactive Oxygen Species; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors