Advancing Precision Approaches to Chronic Obstructive Pulmonary Disease.

Precision medicine aims to define subtypes of a heterogeneous disease, which can lead to more specific diagnosis, prognosis, and/or treatment. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and therefore appropriate for a precision medicine approach. The idea of COPD heterogeneity has been proposed for decades, initially with subtypes of emphysema and chronic bronchitis. Modern approaches include the use of chest computed tomography (CT) scan imaging and omics biomarkers. One path forward is to start by identifying a clinical question, then try to understand the epidemiology, to describe clinical phenotypes and disease subtypes. One can then incorporate omics biomarkers to arrive at an endotype, a subtype with a shared biologic mechanism. Eosinophilic COPD and alpha-1 antitrypsin deficiency-related emphysema are endotypes that already have specific therapies. Subtypes such as patients with frequent exacerbations can be targeted with several treatments, but multiple biological processes are likely to be important. This review will highlight these approaches, using examples such as airway-predominant COPD, frequent exacerbations, and asthma-COPD overlap. These investigations have been conducted in large observational studies, including the multi-center US Genetic Epidemiology of COPD Study (COPDGene). The analyses have leveraged the wealth of data in COPDGene, including clinical information, pulmonary function tests, chest CT scans, and multi-omics such as genetics, RNA-sequencing, and proteomics. Despite these advances, there are many challenges for COPD precision medicine, such as the requirement for large studies with longitudinal outcomes and available biospecimens. Clinical trials of targeted therapies will be needed for the ultimate application of precision medicine in COPD.