A very brief outline of our understanding of the mechanisms of COPD is provided for context. Alveolar macrophages and airway epithelial cells appears to initiate the inflammatory process in the lungs (Fig 1).7 Following repeated noxious stimuli such as cigarette smoke, they are activated and release a variety of chemokines, chemoattractants, and growth factors. Macrophages, neutrophils, and thymic helper cell 1 lymphocytes enter the tissue and become abundant. The chemokines activate neutrophils, monocytes, and lymphocytes, and the chemoattractants (eg, leukotriene B4) bring more inflammatory cells into the lungs. Activated macrophages also release reactive oxygen species and a variety of serine- and metalloproteases, all of which can damage lung tissues, destroy alveolar walls, increase mucus secretion, and promote hyperplasia of mucus-secreting cells. Activated inflammatory cells, in turn, also release reactive oxygen species and other proinflammatory agents and tend to inactivate defensive agents such as α1-antitrypsin (AAT) and secretory leukocyte peptidase inhibitor. Growth factors such as epidermal growth factor, granulocyte-macrophage colony-stimulating factor and transforming growth factor-β (TGF-β), promote fibrosis, angiogenesis, and other structural changes.7 Also abundant are markers of inflammation such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (CRP), and fibrinogen. The sequence of inflammatory events is not well understood, nor are the factors that drive pathology toward one COPD phenotype rather than another, nor the reasons why inflammation may persist long after smoking ceases.