Human airway branch variation and chronic obstructive pulmonary disease.

MS#: 
MS053
TitleHuman airway branch variation and chronic obstructive pulmonary disease.
Publication TypePublication
Year2018
AuthorsSmith BM, Traboulsi H, Austin JHM, Manichaikul A, Hoffman EA, Bleecker ER, Cardoso WV, Cooper C, Couper DJ, Dashnaw SM, Guo J, Han MK, Hansel NN, Hughes EW, Jacobs DR, Kanner RE, Kaufman JD, Kleerup E, Lin C-L, Liu K, Cascio CMLo, Martinez FJ, Nguyen JN, Prince MR, Rennard S, Rich SS, Simon L, Sun Y, Watson KE, Woodruff PG, Baglole CJ, R Barr G
Corporate AuthorsMESA Lung and SPIROMICS investigators
JournalProc Natl Acad Sci U S A
Volume115
Issue5
PaginationE974-E981
Date Published2018 Jan 30
ISSN1091-6490
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 ( = 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 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.

DOI10.1073/pnas.1715564115
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29339516
PubMed Central IDPMC5798356
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL112986 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL077612 / HL / NHLBI NIH HHS / United States
RC1 HL100543 / HL / NHLBI NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
R01 HL093081 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
U01 HL114494 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
R01 HL130506 / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: New York (Columbia University)
ECI: 
Manuscript Status: 
Published and Public