RS L17 Obstructive lung disease
Def: A decrease in the exhaled air flow caused by acute or chronic narrowing or blockage of the airways causing increased resistance to airflow. This obstruction is usually progressive, not fully reversible and does not change markedly over several months. The most common group of COPD include chronic bronchitis, emphysema and small airway disease. COPD is predominantly caused by smoking.
Airflow obstruction is defined as a reduced FEV (volume of air that can be expelled from maximum inspiration in 1st second) and a reduced FEV1/FVC ratio (Tifferean-Pinelli index) such that FEV1 is less than 80% predicted and the ratio is less than 0.7. FVC: Volume of air that can be forcibly expelled from the lung from max inspiration o max expiration. Airflow obstruction is due to major pathological changes in following 4 compartments of the lung.
1. Central airways (cartilaginous >2mm diam)
2. Peripheral airways (noncartilaginous <2mm diam)
3. Lung parenchyma (respiratory bronchioles, alveoli, capillaries)
4. Pulmonary vasculature
The damage is a result of chronic inflammation and significant obstruction may occur before the individual is aware of it.
1. Central airways
Bronchial gland hyper trophy and goblet cell metaplasia- results in excessive mucus production (chronic bronchitis). Squamous metaplasia of airway epithelium, loss of cilia and cilia dysfunction, increased smooth muscle and connective tissue.
2. Peripheral airways
Bronchiolitis at an early stage. Pathological extension of goblet cells and squamous metaplasia in the peripheral airways. As the disease progresses there is fibrosis and increased deposition of collagen. Presence of inflammatory exudate in the wall and lumen of airway. Reduced lumen due to increased smooth muscle.
3. Lung parenchyma
Emphysema defined as abnormal enlargement of air spaces distal to terminal bronchioles. Loss of alveolar walls
4. Pulmonary vasculature
It changes begin early in disease. Initially characterised by thickening of the vessel wall and endothelial cell dysfunction. Followed by increased smooth muscle, infiltration of inflammatory cells and in advanced disease there is collagen deposition and destruction of the capillary bed.
Molecular Level
COPD is characterized by an increase in neutrophils, macrophages and T lymphocytes (CD8+) in various parts of the lung. There may also be increase in eosinophils in some patients, particularly during exacerbations. These increases are brought about by increases in inflammatory cell recruitment, survival and activation. Many studies reveal a correlation between the number of inflammatory cells of various types in the lung and the severity of COPD.
Large airways: Macrophages, T cell (CD8+), neutrophils (severe only), eosinophils

Small airways: Macrophages, T cells, eosinophils
Parenchyma: Macrophages, T cells, neutrophils
Pulmonary arteries: T cells and neutrophils
Cigarette smoke activates macrophages and epithelial cells to produce tumour necrosis factor α (TNF α) and IFNγ. These bind to receptors on macrophages (TNFR and TFNGR). TNF α causes the transcription of interleukin 8 (CXCL8) through the NF-kB pathway and IFNγ causes the up-regulation of IP10 (CXCL10)- interferon gamma induced protein 10.
Injury is caused either directly by inhaled toxic particles and