Using pulmonary imaging to move chronic obstructive pulmonary disease beyond FEV1

FEV1, measured using spirometry, provides a straightforward, widely available, and inexpensive global measurement of airflow limitation and lung function. For decades, FEV1 has remained the main intermediate endpoint used in research studies and for the development of new chronic obstructive pulmonary disease (COPD) therapies. Not surprisingly, treatments that acutely improve FEV1 dominate as COPD therapies. However, in patients with COPD, the relationship of FEV1 with symptoms and outcomes such as exacerbations and mortality is weak, and, importantly, FEV1 does not take into account the heterogeneity of COPD or its different phenotypes. Thoracic imaging provides a way to quantify airway remodeling, emphysematous destruction, regional ventilation abnormalities (ventilation defects), and gas trapping in ex-smokers in whom FEV1 may be normal and in patients with COPD with very modest lung function deterioration. In individual patients and in COPD cohort studies, thoracic imaging using X-ray computed tomography, and magnetic resonance imaging (conventional (1)H as well as hyperpolarized noble gases such as (129)Xe, (3)He, and inhaled O2 and (19)F) can be used to directly visualize the structural and functional consequences of COPD and thus provide a clearer picture of COPD mechanisms, disease progression, and response to therapy. We briefly describe pulmonary imaging methods that provide a way to visualize and quantify, with high spatial and temporal resolution, regional ventilation abnormalities, gas trapping, emphysema, and airway remodeling in COPD. Finally, we discuss the implications of recent imaging findings and their impact on future biomarker and therapy research aimed at improving COPD outcomes.