Inflammatory Mechanisms in Chronic Obstructive Pulmonary Disease

COPD is associated with chronic inflammation affecting predominantly lung parenchyma and peripheral airways, which results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increasing numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly Tc1, Th1, and Th17 cells), and innate lymphoid cells (ILC) that are recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines chemokines, growth factors, and lipid mediators. Although most COPD patients have a predominantly neutrophilic inflammation, some have an increase in eosinophils, which may be orchestrated by Th2 and ILC2 cells through the release of IL-33 from epithelial cells. These patients may be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD inflammation, even in ex-smokers, and may result in activation of the proinflammatory transcription factor NF-κB, impaired antiprotease defenses, DNA damage, cellular senescence, generation of autoantibodies, and corticosteroid resistance through inactivation of histone deacetylase-2. Systemic inflammation is also found in COPD patients and may worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in COPD lungs may also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients that show optimal responses to more specific therapies and the development of biomarkers that identify the therapeutic phenotypes will be important.