Translating the COPD transcriptome: insights into pathogenesis and tools for clinical management

While the role cigarette smoke plays in chronic obstructive pulmonary disease (COPD) is undisputed, the molecular mechanisms by which inhaled smoke contributes to disease pathogenesis remains unclear. One of the major barriers to effective approaches to diagnose and manage COPD is the remarkable heterogeneity displayed by patients with the disease. Whole-genome gene-expression studies of airway and lung tissue from patients with COPD provide an opportunity to gain insights into disease pathogenesis, allowing for both a molecular understanding of the pathogenic processes that contribute to this heterogeneity, and the ability to target therapies to these processes. This review focuses on synthesizing and integrating the limited numbers of high-throughput gene expression studies that have been conducted on lung tissue and airway samples from smokers with COPD. Comparing several lung tissue studies using computational approaches, we find that the results suggest fundamental similarities and identify common biological processes underlying COPD, despite each study having identified largely nonoverlapping lists of differentially expressed genes. Given these similarities, we argue that additional lung tissue and airway gene-expression studies are warranted, and present a roadmap for how such studies could lead to clinically relevant tools that would impact COPD management.