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 and occupational exposure are other common etiologies. Oxidative stress and an imbalance in proteinases and antiproteinases are also important factors in the pathogenesis of COPD, especially in patients with alpha-1 antitrypsin deficiency, who have panacinar emphysema that usually presents at an early age.[1]


The hallmark of COPD is chronic inflammation that affects central airways, peripheral airways, lung parenchyma and alveoli, and pulmonary vasculature. The main components of these changes are narrowing and remodeling of airways, increased number of goblet cells, enlargement of mucus-secreting glands of the central airways, and, finally, subsequent vascular bed changes leading to pulmonary hypertension. This is thought to lead to the pathologic changes that define the clinical presentation.

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. In contrast to asthma, eosinophils play no role in COPD, except for occasional acute exacerbations. However, a patient-level meta-analysis found that patients with COPD with lower blood eosinophil counts have more pneumonia events than do those with higher counts.[7]

In emphysema, which is a subtype of COPD, the final outcome of the inflammatory responses is elastin breakdown and subsequent loss of alveolar integrity.[8] In chronic bronchitis, another phenotype of COPD, these inflammatory changes lead to ciliary dysfunction and increased goblet cell size and number, which leads to the excessive mucus secretion. These changes are responsible for decreased airflow, hypersecretion, and chronic cough. In both conditions, changes are progressive and usually not reversible.

Increased airway resistance is the physiologic 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. This finding, in addition to destruction of lung parenchyma, predisposes COPD patients 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.[9][10]

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