GLOBAL INITIATIVE FOR ● Lung inflammation is further amplified by oxidative stress and an excess of NICOBSTRUCTIVE LUNG DISEASES proteases in the lung. INFLAMMATION IN COPD Small airway disease Parenchymal destruction Airway inflammation Loss of alveolar attachments Airway remodeling Decrease of elastic recoil AIRFLOW LIMITATION
• Lung inflammation is further amplified by oxidative stress and an excess of proteases in the lung
Pathogenesis of Cigarette smoke COPD Biomass particles■T Particulates indoor air polution Host factors Amplifying mechanisms LUNG INFLAMMATION Anti-oxidants Anti-proteinases Oxidative stress Proteinases Repair mechanisms COPD PATHOLOGY Source:Peter J.Barnes,MD
Host factors Amplifying mechanisms Source: Peter J. Barnes, MD Pathogenesis of COPD
Inflammatory Cells Involved in COPD Cigarette smoke (and other irritants) Epithelial Alveolar macrophage cells Chemotactic factors CD8+ Fibroblast lymphocyte Neutrophil Monocyte PROTEASES Neutrophil elastase Cathepsins MMPs Fibrosis Alveolar wall destruction Mucus hypersecretion (Obstructive (Emphysema) bronchiolitis) Source:Peter J.Barnes,MD
Inflammatory Cells Involved in COPD Source: Peter J. Barnes, MD
Oxidative Stress in COPD Macrophage Neutrophil Anti-proteases SLPI a1-AT NF-KB ↑Proteolysis L-8一TNF- I HDAC2 O2,H202 ↓ OH,ONOO Neutrophil TInflammation recruitment Steroid resistance Isoprostanes Plasma leak Bronchoconstriction 个Mucus secretion Source:Peter J.Barnes,MD
Anti-proteases SLPI 1 -AT Proteolysis Mucus secretion Plasma leak Bronchoconstriction Oxidative Stress in COPD Macrophage Neutrophil Source: Peter J. Barnes, MD
Changes in Large Airways of COPD Patients Mucus hypersecretion Neutrophils in sputum Squamous metaplasia of epithelium No basement membrane thickening Goblet cell hyperplasia ↑Macrophages @ ○←-↑cD8*lymphocytes Mucus gland hyperplasia G Little increase in airway smooth muscle Source:Peter J.Barnes,MD
Mucus gland hyperplasia Goblet cell hyperplasia Mucus hypersecretion Neutrophils in sputum Squamous metaplasia of epithelium ↑ Macrophages No basement membrane thickening Little increase in airway smooth muscle ↑ CD8+ lymphocytes Changes in Large Airways of COPD Patients Source: Peter J. Barnes, MD