TY - JOUR
T1 - Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression
AU - for the
AU - COPDGene Investigators
AU - COPDGene Investigators
AU - Boueiz, Adel
AU - Chang, Yale
AU - Cho, Michael H.
AU - Washko, George R.
AU - San José Estépar, Raul
AU - Bowler, Russell P.
AU - Crapo, James D.
AU - DeMeo, Dawn L.
AU - Dy, Jennifer G.
AU - Silverman, Edwin K.
AU - Castaldi, Peter J.
AU - Crapo, James
AU - Silverman, Edwin
AU - Make, Barry
AU - Regan, Elizabeth
AU - Beaty, Terri
AU - Laird, Nan
AU - Lange, Christoph
AU - Cho, Michael H.
AU - Santorico, Stephanie
AU - Hokanson, John
AU - DeMeo, Dawn
AU - Hansel, Nadia
AU - Hersh, Craig
AU - Castaldi, Peter
AU - McDonald, Merry Lynn
AU - Wan, Emily
AU - Hardin, Megan
AU - Hetmanski, Jacqueline
AU - Parker, Margaret
AU - Foreman, Marilyn
AU - Hobbs, Brian
AU - Busch, Robert
AU - Boueiz, Adel
AU - Castaldi, Peter
AU - Hardin, Megan
AU - Qiao, Dandi
AU - Regan, Elizabeth
AU - Halper-Stromberg, Eitan
AU - Begum, Ferdouse
AU - Won, Sungho
AU - Lutz, Sharon
AU - Lynch, David A.
AU - Coxson, Harvey O.
AU - Han, Mei Lan K.
AU - Hoffman, Eric A.
AU - Humphries, Stephen
AU - Anzueto, Antonio
AU - Adams, Sandra
AU - Maselli-Caceres, Diego
N1 - Publisher Copyright:
© 2017 American College of Chest Physicians
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - COPD
KW - COPD disease progression
KW - clustering
KW - emphysema distribution
KW - machine learning
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U2 - 10.1016/j.chest.2017.09.022
DO - 10.1016/j.chest.2017.09.022
M3 - Article
C2 - 28943279
AN - SCOPUS:85040161197
SN - 0012-3692
VL - 153
SP - 65
EP - 76
JO - Chest
JF - Chest
IS - 1
ER -