Pathophysiology of COPD

COPD is a complex syndrome comprised of airway inflammation, mucociliary dysfunction and consequent airway structural changes.1

Airway inflammation

COPD is characterized by chronic inflammation of the airways, lung tissue and pulmonary blood vessels as a result of exposure to inhaled irritants such as tobacco smoke.

The inhaled irritants cause inflammatory cells such as neutrophils, CD8+ T-lymphocytes, B cells and macrophages to accumulate.2 When activated, these cells initiate an inflammatory cascade that triggers the release of inflammatory mediators such as tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), matrix-metalloproteinases (MMP-6, MMP-9), C-reactive protein (CRP), interleukins (IL-1, IL-6, IL-8) and fibrinogen. These inflammatory mediators sustain the inflammatory process and lead to tissue damage as well as a range of systemic effects. The chronic inflammation is present from the outset of the disease and leads to various structural changes in the lung which further perpetuate airflow limitation. The chronic inflammatory cascade for COPD is illustrated in Figure 1.

Structural changes

Airway remodeling in COPD is a direct result of the inflammatory response associated with COPD and leads to narrowing of the airways. Three main factors contribute to this: peribronchial fibrosis, build-up of scar tissue from damage to the airways and over-multiplication of the epithelial cells lining the airways.3,4

Parenchymal destruction is associated with loss of lung tissue elasticity, which occurs as a result of destruction of the structures supporting and feeding the alveoli (emphysema). This means that the small airways collapse during exhalation, impeding airflow, trapping air in the lungs and reducing lung capacity (Figure 2).

Inflammatory cells__2 
Figure 1: Inflammatory and immune cells involved in COPD.2
Adapted from Barnes, PJ. Nat Rev Immunol 2008;8:183-92



Figure 2: Airflow limitation in COPD.


Mucociliary dysfunction

Smoking and inflammation enlarge the mucous glands that line airway walls in the lungs, causing goblet cell metaplasia and leading to healthy cells being replaced by more mucus-secreting cells.5 Additionally, inflammation associated with COPD causes damage to the mucociliary transport system which is responsible for clearing mucus from the airways. Both these factors contribute to excess mucus in the airways which eventually accumulates, blocking them and worsening airflow (Figure 3).


 Figure 3: Mucociliary effects in the COPD airway. 



  1. Agusti A. COPD, a multicomponent disease: implications for management. Respir Med 2005;99:670-82.
  2. Barnes, PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008;8:183-92. 
  3. Chung KF. The role of airway smooth muscle in the pathogenesis of airway remodelling in COPD. Proc Am Thorac Soc 2005;2:347-54.
  4. Laperre TS, Sont JK, van Schadewijk A, et al. Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respir Res 2007;8:85-93.
  5. Danahay H & Jackson AD. Epithelial mucus-hypersecretion and respiratory disease. Curr Drug Targets Inflamm Allergy 2005;4:651-64.

Risk factors for COPD

Find out which risk factors are associated with COPD.Go

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