What is chronic obstructive pulmonary disease (COPD)?

Chronic Obstructive Pulmonary Disease (COPD), also known as chronic lung disease, is a progressive lung disease characterized by chronic inflammation of the airways and irreversible airflow obstruction, making it difficult to breathe. COPD encompasses several conditions, including chronic bronchitis and emphysema, which often coexist and contribute to the overall disease presentation. Here’s a breakdown of the key components of COPD:

  • Chronic Bronchitis: Chronic bronchitis is defined by persistent inflammation and irritation of the bronchial tubes (airways) in the lungs. This inflammation leads to increased production of mucus (sputum) and narrowing of the airways, which makes it difficult for air to flow in and out of the lungs. Symptoms of chronic bronchitis include a persistent cough that produces mucus, shortness of breath, wheezing, and chest tightness.
  • Emphysema: Emphysema is characterized by damage to the alveoli (air sacs) in the lungs, causing them to lose their elasticity and become stretched out. This damage reduces the surface area available for gas exchange, leading to impaired oxygen uptake and carbon dioxide removal. Symptoms of emphysema include shortness of breath, especially with exertion, chronic cough, wheezing, and fatigue.
  • Airflow Obstruction: In COPD, chronic inflammation and structural changes in the airways and lung tissue lead to airflow limitation, making it difficult for air to flow in and out of the lungs. This airflow obstruction is typically irreversible and worsens over time, resulting in progressive lung function decline. Airflow limitation contributes to symptoms such as shortness of breath, cough, and reduced exercise tolerance.

What is the relationship between COPD and oxidative stress?

Oxidative stress is integral to the pathogenesis and progression of COPD. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants. In COPD, oxidative stress plays a significant role in causing inflammation, tissue damage, and progressive lung function decline. Here’s how COPD and oxidative stress are interrelated:

  • Inflammatory Response: Chronic inflammation of the airways and lung tissue is a hallmark feature of COPD. In response to inhaled irritants, such as cigarette smoke, pollutants, and occupational dust, immune cells in the lungs release ROS as part of the inflammatory response. These ROS promote the activation of inflammatory pathways, recruit inflammatory cells (such as neutrophils and macrophages), and perpetuate the inflammatory cascade. Chronic inflammation in COPD leads to tissue damage, airway remodeling, and worsening of airflow limitation.
  • Oxidative Damage: ROS generated during inflammation can directly damage cellular components, including lipids, proteins, and DNA, leading to oxidative stress-induced cellular injury. Oxidative damage to lung cells impairs their function, disrupts cellular signaling pathways, and promotes apoptosis (cell death). In COPD, oxidative damage contributes to airway epithelial cell dysfunction, mucus hypersecretion, and impairment of mucociliary clearance mechanisms, leading to airway obstruction and increased susceptibility to respiratory infections.
  • Antioxidant Defenses: COPD is associated with dysregulation of antioxidant defense mechanisms, which further exacerbates oxidative stress. Antioxidants, such as superoxide dismutase (SOD), catalase, glutathione, and vitamin E, play a crucial role in neutralizing ROS and protecting lung cells from oxidative damage. However, in COPD, the antioxidant capacity of the lungs may be compromised due to depletion of antioxidants, decreased activity of antioxidant enzymes, or oxidative inactivation of antioxidants by cigarette smoke and other environmental pollutants.
  • Mitochondrial Dysfunction: Mitochondria are major sources of ROS production within cells, and mitochondrial dysfunction is implicated in the pathogenesis of COPD. Oxidative stress-induced damage to mitochondrial DNA, proteins, and membranes impairs mitochondrial function and bioenergetics, leading to increased ROS production and cellular dysfunction. Mitochondrial dysfunction further exacerbates oxidative stress and inflammation in the lungs, contributing to lung injury and disease progression in COPD.
  • Structural Changes: Oxidative stress contributes to structural changes in the airways and lung tissue in COPD, such as airway remodeling, fibrosis, and emphysematous destruction. ROS promote the activation of pro-fibrotic and pro-inflammatory signaling pathways, leading to collagen deposition, fibrosis, and airway wall thickening. Oxidative stress-induced lung tissue damage and emphysema are characterized by loss of alveolar integrity, airspace enlargement, and destruction of lung parenchyma.

Overall, oxidative stress plays a central role in mediating inflammation, tissue damage, and progressive lung function decline in COPD.