Dysanapsis is differentially related to lung function trajectories with distinct structural and functional patterns in COPD and variable risk for adverse outcomes.

Background: Abnormal lung function trajectories are associated with increased risk of chronic obstructive pulmonary disease (COPD) and premature mortality; several risk factors for following these trajectories have been identified. Airway under-sizing dysanapsis (small airway lumens relative to lung size), is associated with an increased risk for COPD. The relationship between dysanapsis and lung function trajectories at risk for adverse outcomes of COPD is largely unexplored. We test the hypothesis that dysanapsis differentially affects distinct lung function trajectories associated with adverse outcomes of COPD. Methods: To identify lung function trajectories, we applied Bayesian trajectory analysis to longitudinal FEV1 and FVC Z-scores in the COPDGene Study, an ongoing longitudinal study that collected baseline data from 2007 to 2012. To ensure clinical relevance, we selected trajectories based on risk stratification for all-cause mortality and prospective exacerbations of COPD (ECOPD). Dysanapsis was measured in baseline COPDGene CT scans as the airway lumen-to-lung volume (a/l) ratio. We compared a/l ratios between trajectories and evaluated their association with trajectory assignment, controlling for previously identified risk factors. We also assigned COPDGene participants for whom only baseline data is available to their most likely trajectory and repeated our analysis to further evaluate the relationship between trajectory assignment and a/l ratio measures. Findings: We identified seven trajectories: supranormal, reference, and five trajectories at increased risk for mortality and exacerbations. Three at-risk trajectories are characterized by varying degrees of concomitant FEV1 and FVC impairments and exhibit airway predominant COPD patterns as assessed by quantitative CT imaging. These trajectories have lower a/l ratio values and increased risk for mortality and ECOPD compared to the reference trajectory. Two at-risk trajectories are characterized by disparate levels of FEV1 and FVC impairment and exhibit mixed airway and emphysema COPD patterns on quantitative CT imaging. These trajectories have markedly lower a/l ratio values compared to both the reference trajectory and airway-predominant trajectories and are at greater risk for mortality and ECOPD compared to the airway-predominant trajectories. These findings were observed among the participants with baseline-only data as well. Interpretation: The degree of dysanapsis appears to portend patterns of progression leading to COPD. Assignment of individuals-including those without spirometric obstruction-to distinct trajectories is possible in a clinical setting and may influence management strategies. Strategies that combine CT-assessed dysanapsis together with spirometric measures of lung function and smoke exposure assessment are likely to further improve trajectory assignment accuracy, thereby improving early detection of those most at risk for adverse outcomes. Funding: United States National Institute of Health, COPD Foundation, and Brigham and Women's Hospital.