Background Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. Methods We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. Results Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. Conclusions Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.
Bibliographical noteFunding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. H. C. reports grants from GSK and National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute during the conduct of the study. G. R. W. reports grants from Beohringer Ingelheim, Genentech, GlaxoSmithKline, PulmonX, and Janssen Pharmaceuticals outside the submitted work. D. L. D. reports grants from NIH and personal fees from Novartis outside the submitted work. E. K. S. reports grants from NIH during the conduct of the study, personal fees from Novartis, and grant and travel support from GlaxoSmithKline outside the submitted work. P. J. C. reports grants and advisory board membership from GSK outside the submitted work. None declared (A. B., Y. C., R. S. J. E., R. P. B., J. D. D., J. G. D.).
© 2017 American College of Chest Physicians
- COPD disease progression
- emphysema distribution
- machine learning