Autoimmune mechanisms contributing to chronic obstructive pulmonary disease

The pathophysiology of smoking-related chronic obstructive pulmonary disease (COPD) and lung parenchymal destruction (emphysema) has evolved over time from simplistic concepts involving only neutrophils and macrophages to more comprehensive models that further include adaptive immune cells such as T cells and B cells in addition to antigen presenting cells (APC). Evidence from human studies specifically point to a role for the recruitment and activation of pathogenic lymphocytes and lung APC in emphysema; similarly, animal models have confirmed a complex role for the immune response in progressive smoke-induced emphysema. Increased numbers of activated APCs, T helper 1 (Th1), and Th17 cells are now clearly associated with smoke induced lung inflammation and the canonical cytokines produced by these cells, including IFN-γ and IL-17A, constitute critical effectors of disease through their ability to promulgate the pro-elastolytic lung environment that leads to emphysema. T and B cells with autoimmune specificity directed toward lung matrix proteins, especially elastin and potentially vascular endothelium and airway epithelium, specifically appear to distinguish COPD patients with emphysema from those without this devastating complication. These and further discoveries will permit the development of improved diagnostic, prognostic and therapeutic strategies in COPD.