Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 5, Pages E974-E981Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1715564115
Keywords
airway branching; fibroblast growth factor; chronic obstructive pulmonary disease; computed tomography
Categories
Funding
- NIH/NHLBI [HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C]
- AstraZeneca
- Bellerophon Pharmaceuticals
- Boehringer-Ingelheim Pharmaceuticals, Inc.
- Chiesi Farmaceutici SpA
- Forest Research Institute, Inc.
- GlaxoSmithKline
- Grifols Therapeutics, Inc.
- Ikaria, Inc.
- Nycomed GmbH
- Takeda Pharmaceutical Company
- Novartis Pharmaceuticals Corporation
- Regeneron Pharmaceuticals, Inc.
- Sanofi
- NIH/NHLBI
- McGill University Health Center Research Institute
- Fonds de la recherche en sante Quebec (Quebec Health Research Fund)
- [HHSN268200900020C]
- [R01-HL130506]
- [R01-HL077612]
- [R01-HL093081]
- [R01-HL112986]
- [RC1HL100543]
- [RD831697]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95169]
- [N01-HC-95162]
- [N01-HC-95164]
- [U01-HL114494]
- [N01-HC95159-HC95169]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL077612, R01HL093081, R43HL095167, R44HL095169, R35HL135834, RC1HL100543, R01HL095163, R13HL095166, R43HL095161, R01HL112986, R43HL095160, R01HL121270, R21HL095165, U01HL114494, R43HL095169, R01HL130506, U01HL137880, K24HL137013] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK054759] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES009089, P30ES005605] Funding Source: NIH RePORTER
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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.
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