Understanding COPD Etiology, Pathophysiology, and Definition.

COPD, one of the leading worldwide health problems, currently lacks truly disease-modifying medical therapies applicable to most patients. Developing such novel therapies has been hampered by the marked heterogeneity of phenotypes between individuals with COPD. Such heterogeneity suggests that, rather than a single cause (particularly just direct inhalation of tobacco products), development and progression of COPD likely involve both complex gene-by-environment interactions to multiple inhalational exposures and a variety of molecular pathways. However, there has been considerable recent progress toward understanding how specific pathological processes can lead to discrete COPD phenotypes, particularly that of small airways disease. Advances in imaging techniques that correlate to specific types of histological damage, and in the immunological mechanisms of lung damage in COPD, hold promise for development of personalized therapies. At the same time, there is growing recognition that the current diagnostic criteria for COPD, based solely on spirometry, exclude large numbers of individuals with very similar disease manifestations. This concise review summarizes current understanding of the etiology and pathophysiology of COPD and provides background explaining the increasing calls to expand the diagnostic criteria used to diagnose COPD and some challenges in doing so.