New drugs for exacerbations of chronic obstructive pulmonary disease.

Full Abstract

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.

Author information

Author/s: Hansel, Trevor T (TT); Barnes, Peter J (PJ);

Affiliation: National Heart and Lung Institute, Imperial College, London, UK. t.hansel(-atsign-)imperial.ac.uk

Journal and publication information

Publication Type: Journal Article; Review

Journal: Lancet (Lancet), published in England. (Language: eng)

Reference: 2009-Aug; vol 374 (issue 9691) : pp 744-55

Dates: Created 2009/08/31; Completed 2009/09/11;

PMID: 19716967, status: MEDLINE (last retrieval date: 9/11/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Anti-Bacterial Agents - therapeutic use
Anti-Inflammatory Agents - therapeutic use
Antioxidants - therapeutic use
Bacterial Infections - complications
Biological Markers - analysis; metabolism
Bronchodilator Agents - therapeutic use
Causality
Fibrosis
Humans

Associated Chemicals: Anti-Bacterial Agents (0) ; Anti-Inflammatory Agents (0) ; Antioxidants (0) ; Biological Markers (0) ; Bronchodilator Agents (0) ; Reactive Oxygen Species (0) ; Receptors, Pattern Recognition (0) ; Toll-Like Receptors (0)

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