Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

Adel Boueiz, Yale Chang, Michael H. Cho, George R. Washko, Raul San José Estépar, Russell P. Bowler, James D. Crapo, Dawn L. DeMeo, Jennifer G. Dy, Edwin K. Silverman, Peter J. Castaldi, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael H. Cho, Stephanie SantoricoJohn Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Robert Busch, Adel Boueiz, Peter Castaldi, Megan Hardin, Dandi Qiao, Elizabeth Regan, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Sharon Lutz, David A. Lynch, Harvey O. Coxson, Mei Lan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Joanne Billings, Tadashi Allen, for the, COPDGene Investigators, COPDGene Investigators

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)65-76
Number of pages12
Issue number1
StatePublished - Jan 2018

Bibliographical note

Publisher Copyright:
© 2017 American College of Chest Physicians


  • COPD
  • COPD disease progression
  • clustering
  • emphysema distribution
  • machine learning


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