Pathophyisology

It results from significant exposure to noxious stimuli, increased oxidative stress (most commonly due to cigarette smoke) as well as by increased release of reactive oxygen species by inflammatory cells.

• Increased number of neutrophils, macrophages, and CD8+ T lymphocytes → release of cytokines → amplification of inflammation and induction of structural changes of lung parenchyma (e.g., via stimulation of growth factor release)

  • CD8+ T lymphocytes mediate inflammation in individuals with COPD.

  • CD4+ T lymphocytes and eosinophils mediate inflammation in individuals with bronchial asthma.

• Overproduction of growth factor → peribronchiolar fibrosis → narrowing of airway → obliteration → emphysema (airflow limitation)

• Promotion of goblet cell proliferation and hypertrophy, mucus hypersecretion, and impaired ciliary function → chronic productive cough

  • Reid index is the ratio of the thickness of the submucosal mucus-secreting glands to the thickness between the epithelium and cartilage in the bronchial tree.

  • Reid index > 0.5 is characteristic of chronic bronchitis. [13]

• Smooth muscle hyperplasia of the small airways and pulmonary vasculature (mainly due to hypoxic vasoconstriction) → pulmonary hypertension → cor pulmonale

• Bronchopulmonary inflammation → ↑ proteases

• Nicotine use (or other noxious stimuli) inactivates protease inhibitors (especially α1-antitrypsin) → imbalance of protease and antiprotease → ↑ elastase activity → loss of elastic tissue and lung parenchyma (via destruction of the alveolar walls), which causes:

  • Enlargement of airspaces → ↓ elastic recoil and ↑ compliance of the lung → ↓ tethering of small airways → expiratory airway collapse and obstruction → air trapping and hyperinflation → ↓ ventilation (due to air-trapping) and ↑ dead space → ↓ DLCOand ↑ ventilation-perfusion mismatch (V/Q) → hypoxemia and hypercapnia

  • Pulmonary shunt and ↓ blood volume in pulmonary capillaries → ↑ number of alveoli that are ventilated but not perfused (↑ dead space) → ↓ DLCO and ↑ V/Q → hypoxemia and hypercapnia

  • Imbalance of oxidants and anti-oxidants and an overabundance of free radicals → chronic inflammation and inactivation of anti-elastase → breakdown of elastic tissue.