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

for the

Research output: Contribution to journalArticle

Abstract

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
JournalChest
Volume153
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Emphysema
Disease Progression
Chronic Obstructive Pulmonary Disease
alpha 1-Antitrypsin Deficiency
Molecular Epidemiology
Pneumonectomy
Dyspnea
Cluster Analysis

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression. / for the.

In: Chest, Vol. 153, No. 1, 01.01.2018, p. 65-76.

Research output: Contribution to journalArticle

@article{e420649d426b4c7f86820bac5183c9e8,
title = "Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression",
abstract = "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.",
keywords = "clustering, COPD, COPD disease progression, emphysema distribution, machine learning",
author = "{for the} and Adel Boueiz and Yale Chang and Cho, {Michael H.} and Washko, {George R.} and {San Jos{\'e} Est{\'e}par}, Raul and Bowler, {Russell P.} and Crapo, {James D.} and DeMeo, {Dawn L.} and Dy, {Jennifer G.} and Silverman, {Edwin K.} and Castaldi, {Peter J.} and James Crapo and Edwin Silverman and Barry Make and Elizabeth Regan and Beaty, {Terri L} and Nan Laird and Christoph Lange and Cho, {Michael H.} and Stephanie Santorico and John Hokanson and Dawn DeMeo and Nadia Hansel and Craig Hersh and Peter Castaldi and McDonald, {Merry Lynn} and Emily Wan and Megan Hardin and Jacqueline Hetmanski and Margaret Parker and Marilyn Foreman and Brian Hobbs and Robert Busch and Adel Boueiz and Peter Castaldi and Megan Hardin and Dandi Qiao and Elizabeth Regan and Eitan Halper-Stromberg and Ferdouse Begum and Sungho Won and Sharon Lutz and Lynch, {David A.} and Coxson, {Harvey O.} and Han, {Mei Lan K.} and Hoffman, {Eric A.} and Stephen Humphries and Wise, {Robert A} and Horton, {Karen M} and Nirupama Putcha",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.chest.2017.09.022",
language = "English (US)",
volume = "153",
pages = "65--76",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "1",

}

TY - JOUR

T1 - Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

AU - for the

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 L

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 - Wise, Robert A

AU - Horton, Karen M

AU - Putcha, Nirupama

PY - 2018/1/1

Y1 - 2018/1/1

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 - clustering

KW - COPD

KW - COPD disease progression

KW - emphysema distribution

KW - machine learning

UR - http://www.scopus.com/inward/record.url?scp=85040161197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040161197&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2017.09.022

DO - 10.1016/j.chest.2017.09.022

M3 - Article

VL - 153

SP - 65

EP - 76

JO - Chest

JF - Chest

SN - 0012-3692

IS - 1

ER -