Pathology and mechanism of airflow obstruction

Pathological changes in COPD seen in the airways, lung parenchyma and in pulmonary vasculature. These changes include:

• chronic inflammation
  • increased numbers of specific inflammatory cell types in different parts of the lung
  • results from an enhanced or abnormal inflammatory response to chronic irritants such as cigarette smoke
• structural changes due to repeated injury and repair (1)

These pathological changes in turn results in the following physiological abnormalities:

• mucous hypersecretion
  • an increase in the number of goblet cells and size of bronchial submucosal glands (caused by noxious particles and gases) is the cause
  • causes a chronic productive cough which is characteristic of chronic bronchitis
  • not necessarily associated with airflow limitation (1)
  • all COPD patients do not have symptomatic mucous hypersecretion
    
• ciliary dysfunction
  • caused by squamous metaplasia of epithelium
  • results in dysfunction of the mucociliary escalator and difficulty expectorating
    
    
• airflow obstruction and hyperinflation/air trapping
  • airflow limitations are seen mainly in the small airways (<2mm in diameter) caused by
    • inflammation, narrowing (airway remodelling) and inflammatory exudates
    • loss of lung elastic recoil (due to destruction of alveolar walls)
    • destruction of alveolar support (from alveolar attachments)
  • progressive air trapping during expiration causes hyperinflation of the lungs at rest and dynamic hyperinflation during exercise
  • hyperinflation is thought to develop early in the disease and is the main mechanism for exertional dyspnoea (1,2)
    
• gas exchange abnormalities
  • characterised by arterial hypoxaemia with or without hypercapnia
  • results from an abnormal distribution of ventilation/perfusion ratios
    
• pulmonary hypertension
  • may develop late in the course of COPD
  • contributing factors include
    • loss of pulmonary capillary bed due to emphysema and/or hypoxic vasoconstriction of the small pulmonary arteries (1)
    • endothelial dysfunction
    • remodelling of the pulmonary arteries smooth muscle (hypertrophy and hyperplasia) and intimal hyperplasia

Reference:

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2025 report. 2025 [internet publication].
2. Eapen MS, Sohal SS. Update on the pathogenesis of COPD. N Engl J Med. 2019 Dec 19;381(25):2483-4.