Tobacco smoking is by far the main risk factor for COPD. It is responsible for 40% to 70% of COPD cases and exerts its effect by causing an inflammatory response, cilia dysfunction, and oxidative injury. Air pollution, indoor burning of biomass fuels, and occupational exposure to dusts, chemical agents, and fumes are other aetiologies. Oxidative stress and an imbalance in proteases and antiproteases are also important factors in the pathogenesis of COPD, especially in patients with alpha-1 antitrypsin deficiency.
The hallmark of COPD is chronic inflammation that affects central and peripheral airways, lung parenchyma and alveoli, and pulmonary vasculature. Repeated injury and repair leads to structural and physiological changes. The inflammatory and structural changes in the lung increase with disease severity and persist after smoking cessation.
The main components of these changes are narrowing and remodelling of airways, increased number of goblet cells, enlargement of mucus-secreting glands of the central airways, alveolar loss, and, finally, vascular bed changes leading to pulmonary hypertension.
Evidence suggests that the host response to inhaled stimuli generates the inflammatory reaction responsible for the changes in the airways, alveoli, and pulmonary blood vessels. Activated macrophages, neutrophils, and leukocytes are the core cells in this process. Oxidative stress and an excess of proteases amplify the effects of chronic inflammation. Airway remodelling thickens the epithelium, lamina propria, smooth muscle, and adventitia of airways less than 2 mm in diameter, leading to progressive loss of patent terminal and transitional bronchioles.
Elastin breakdown and subsequent loss of alveolar integrity causes emphysema. Ciliary dysfunction and increased goblet cell size and number lead to excessive mucus secretion.
Increased airway resistance is the physiological definition of COPD. Decreased elastic recoil, fibrotic changes in lung parenchyma, and luminal obstruction of airways by secretions all contribute to increased airways resistance. Expiratory flow limitation promotes hyperinflation. Hyperinflation and destruction of lung parenchyma predispose patients with COPD to hypoxia, particularly during activity. Progressive hypoxia causes vascular smooth muscle thickening with subsequent pulmonary hypertension, which is a late development conveying a poor prognosis. Reduced gas transfer may also lead to hypercapnia as the disease progresses.
Systemic inflammatory mediators may contribute to skeletal muscle wasting or cachexia, and initiate or worsen cardiac, metabolic, and skeletal comorbidities.
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