The Multiple Components of COPD

Abstract

Tobacco smoking affects multiple organ systems resulting in numerous so-called tobacco-related diseases, including various chronic respiratory diseases, mainly chronic obstructive pulmonary disease (COPD). Smokers with stable COPD have a chronic inflammation of the entire tracheobronchial tree characterized by an increased number of macrophages and CD8 T lymphocytes in the airway wall and of neutrophils in the airway lumen, leading to a progressive and not fully reversible airflow limitation, as measured by the forced expiratory volume in 1 second (FEV1). The inflammatory mediators involved in COPD have not been clearly defined, but it is now apparent that many lipid mediators, inflammatory peptides, reactive oxygen and nitrogen species, chemokines, cytokines, and growth factors are involved in orchestrating the complex inflammatory process that results in small airway fibrosis and alveolar destruction. Many proteases are also involved in the inflammatory process and are responsible for the destruction of elastin fibers in the lung parenchyma, which is the hallmark of emphysema. CD8+ T lymphocytes from the bronchial mucosa of patients with COPD predominantly express the chemokine receptor CXCR3 and produce gamma interferon (IFN-γ), suggesting that these cells elaborate type I cytokines. Recent research suggests that inflammation is not confined to the lungs: inflammatory cells and mediators are detectable in the bloodstream and may have systemic effects in different areas of the body. This may account for the observation that patients with COPD also present with systemic symptoms and comorbid conditions. Long-term smoke exposure can result in systemic oxidants–antioxidants imbalance and low-grade systemic inflammatory response. Although most of the smoking-induced changes are reversible after quitting, some inflammatory mediators like C-reactive protein (CRP) are still significantly raised in ex-smokers up to 10–20 years after quitting, suggesting ongoing low-grade inflammatory response persisting in former smokers. Considering the systemic nature of the inflammatory response to cigarette smoke, there is increasing evidence that lung abnormalities may be responsible for the chronic comorbidities that develop along with COPD, particularly chronic heart failure (CHF), coronary and peripheral vascular diseases, and the metabolic syndrome. Comorbidities are highly likely to affect health outcomes in COPD, and COPD patients are more likely to die of cardiovascular complications or cancer than of respiratory failure.