Human airway branch variation and chronic obstructive pulmonary disease

the MESA Lung and SPIROMICS investigators

Research output: Contribution to journalArticle

Abstract

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

Original languageEnglish (US)
Pages (from-to)E974-E981
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number5
DOIs
StatePublished - Jan 30 2018

Fingerprint

Chronic Obstructive Pulmonary Disease
Lung
Disease Susceptibility
Emphysema
Genetic Polymorphisms
Biomarkers
Smoking
Tomography
Population
Genes

Keywords

  • Airway branching
  • Chronic obstructive pulmonary disease
  • Computed tomography
  • Fibroblast growth factor

ASJC Scopus subject areas

  • General

Cite this

Human airway branch variation and chronic obstructive pulmonary disease. / the MESA Lung and SPIROMICS investigators.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 5, 30.01.2018, p. E974-E981.

Research output: Contribution to journalArticle

@article{029b349f2bd7493eace00afa47203a50,
title = "Human airway branch variation and chronic obstructive pulmonary disease",
abstract = "Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5{\%} of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.",
keywords = "Airway branching, Chronic obstructive pulmonary disease, Computed tomography, Fibroblast growth factor",
author = "{the MESA Lung and SPIROMICS investigators} and Smith, {Benjamin M.} and Hussein Traboulsi and Austin, {John H.M.} and Ani Manichaikul and Hoffman, {Eric A.} and Bleecker, {Eugene R.} and Cardoso, {Wellington V.} and Christopher Cooper and Couper, {David J.} and Dashnaw, {Stephen M.} and Jia Guo and Han, {Mei Lan K.} and Nadia Hansel and Hughes, {Emlyn W.} and Jacobs, {David R.} and Kanner, {Richard E.} and Kaufman, {Joel D.} and Eric Kleerup and Lin, {Ching Long} and Kiang Liu and {Lo Cascio}, {Christian M.} and Martinez, {Fernando J.} and Nguyen, {Jennifer N.} and Prince, {Martin R.} and Stephen Rennard and Rich, {Stephen S.} and Leora Simon and Yanping Sun and Watson, {Karol E.} and Woodruff, {Prescott G.} and Baglole, {Carolyn J.} and Barr, {R. Graham}",
year = "2018",
month = "1",
day = "30",
doi = "10.1073/pnas.1715564115",
language = "English (US)",
volume = "115",
pages = "E974--E981",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Human airway branch variation and chronic obstructive pulmonary disease

AU - the MESA Lung and SPIROMICS investigators

AU - Smith, Benjamin M.

AU - Traboulsi, Hussein

AU - Austin, John H.M.

AU - Manichaikul, Ani

AU - Hoffman, Eric A.

AU - Bleecker, Eugene R.

AU - Cardoso, Wellington V.

AU - Cooper, Christopher

AU - Couper, David J.

AU - Dashnaw, Stephen M.

AU - Guo, Jia

AU - Han, Mei Lan K.

AU - Hansel, Nadia

AU - Hughes, Emlyn W.

AU - Jacobs, David R.

AU - Kanner, Richard E.

AU - Kaufman, Joel D.

AU - Kleerup, Eric

AU - Lin, Ching Long

AU - Liu, Kiang

AU - Lo Cascio, Christian M.

AU - Martinez, Fernando J.

AU - Nguyen, Jennifer N.

AU - Prince, Martin R.

AU - Rennard, Stephen

AU - Rich, Stephen S.

AU - Simon, Leora

AU - Sun, Yanping

AU - Watson, Karol E.

AU - Woodruff, Prescott G.

AU - Baglole, Carolyn J.

AU - Barr, R. Graham

PY - 2018/1/30

Y1 - 2018/1/30

N2 - Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

AB - Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

KW - Airway branching

KW - Chronic obstructive pulmonary disease

KW - Computed tomography

KW - Fibroblast growth factor

UR - http://www.scopus.com/inward/record.url?scp=85041228991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041228991&partnerID=8YFLogxK

U2 - 10.1073/pnas.1715564115

DO - 10.1073/pnas.1715564115

M3 - Article

VL - 115

SP - E974-E981

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -