Pathophysiology

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition involving the airways, lung parenchyma, and pulmonary vasculature.¹

This condition is characterized by persistent and poorly reversible airflow limitation, as well as significant respiratory symptoms, including cough, shortness of breath, and sputum production.^1,2 The pathogenesis of COPD is related to increased oxidative stress and protease-antiprotease imbalance. In particular, cigarette smoke produces oxidative stress (Figure), which activates macrophages and epithelial cells to release chemotactic factors that recruit neutrophils and CD8 cells from the circulation to the lungs.¹

In general, the extent of inflammation correlates with the degree of airflow obstruction. These inflammatory cells release factors that activate fibroblasts, resulting in abnormal repair processes and bronchiolar fibrosis. Furthermore, an imbalance between proteases released from neutrophils, macrophages, and antiproteases leads to alveolar wall destruction (emphysema) and obstructive physiology. Proteases also cause mucus release. An increased oxidant burden, resulting from smoke inhalation or the release of oxidants from inflammatory leukocytes, causes epithelial and other cells to release chemotactic factors, inactivates antiproteases, and directly injures alveolar walls, causing mucus secretion. The protease-mediated destruction of elastin leads to the loss of elastic recoil and results in airway collapse during exhalation.¹

The inflammatory response causes airway obstruction, reflected by a decrease in forced expiratory volume (FEV₁) and tissue destruction, leading to further airflow limitation and impaired gas exchange. This results in gas-trapping and hyperinflation of the lungs, which is often seen on imaging studies. As the disease progresses, impairment of gas exchange is often seen. The reduction in ventilation or increase in physiologic dead space leads to CO₂ retention. Pulmonary hypertension may occur due to diffuse vasoconstriction from hypoxemia.⁴

Acute exacerbations of COPD are common and usually occur due to a trigger (eg, bacterial or viral pneumonia, environmental irritants). The presentation of COPD is often one of multiple comorbidities that share risk factors, such as age, smoking, inflammation, and physical inactivity, which can predispose the individual to COPD. Alternately, the presence of COPD may further increase risk for other chronic diseases via shared pathways that include inflammation and physical inactivity. The complex interplay of other chronic comorbidities may worsen COPD morbidity and mortality.⁵ For instance, patients with comorbidities such as pulmonary hypertension, cardiovascular disease, and lung cancer tend to have a poorer prognosis.⁶ Comorbid conditions should be routinely monitored and appropriately treated utilizing a multidisciplinary approach.^7-10

References

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