Chapter

Pathology and molecular features of COPD

Andrew J. Tan

Edited by Trevor T. Hansel and Onn Min Kon

in Chronic Obstructive Pulmonary Disease (COPD)

Published on behalf of Oxford University Press

ISBN: 9780199549146
Published online May 2011 | e-ISBN: 9780199607273 | DOI: http://dx.doi.org/10.1093/med/9780199549146.003.0002

Series: Oxford Respiratory Medicine Library

Pathology and molecular features of COPD

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• Cigarette smoke is estimated to contain 1017 reactive oxidant species (ROS) and chronic smoking in genetically susceptible individuals is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). • COPD involves a spectrum of diseases: chronic bronchitis, obstructive bronchiolitis, emphysema, pulmonary vascular disease, cor pulmonale, and a systemic syndrome of cachexia and muscle weakness. • ROS trigger an exaggerated host inflammatory, mucosecretory, proteolytic, and fibrotic response. Epithelial cell injury and macrophage activation causes release of chemotactic factors and cytokines such as CXCL1, CXCL8, CCL2, and TNF-α. • Macrophages and neutrophils then release proteases, with involvement of matrix metalloproteases (MMPs) and neutrophil elastase (NE) that may break down extracellular matrix (ECM). T cells of various subtypes (Th1, Th2, Tc1, Tc2, Treg, Th17) as well as B cells may also be involved in this inflammatory cascade. • Transforming growth factor-β1 (TGF-β1) is produced by epithelial cells and causes fibrosis. Inhibition of fibrosis is caused by interferon-γ (IFN-γ), while profibrotic factors include interleukin-13 (IL-13), platelet-derived growth factor (PDGF), CCL2 (MCP-1) and CXCL12 (ligand for CXCR4), and protease activated receptor 2 (PAR-2). • Many years of injury from cigarette smoke causes cycles of inflammation and repair. These cycles may result in resolution, but are commonly associated with mucus hypersecretion, fibrosis, proteolysis, and both airway and parenchymal remodelling.

Chapter.  3082 words.  Illustrated.

Subjects: Respiratory Medicine and Pulmonology

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