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 language | English (US) |
|---|---|
| Pages (from-to) | E974-E981 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 115 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 30 2018 |
Bibliographical note
Funding Information:We thank the other investigators, the staff, and the participants of the MESA Lung Study and SPIROMICS for their valuable contributions (a full list of participating MESA investigators and institutions can be found at https://www.mesa-nhlbi.org; more information about the study and how to access SPIROMICS data is available at www.spiromics.org) and acknowledge the following current and former investigators of the SPIROMICS sites and reading centers: Neil E. Alexis, PhD; Wayne H. Anderson, PhD; Richard C. Boucher, MD; Russell P. Bowler, MD, PhD; Elizabeth E. Carretta, MPH; Stephanie A. Christenson, MD; Alejandro P. Comellas, MD; Gerard J. Criner, MD; Ronald G. Crystal, MD; Jeffrey L. Curtis, MD; Claire M. Doerschuk, MD; Mark T. Dransfield, MD; Christine M. Freeman, PhD; Annette T. Hastie, PhD; Jerry A. Krishnan, MD, PhD; Lisa M. LaVange, PhD; Stephen C. Lazarus, MD; Deborah A. Meyers, PhD; John D. Newell, Jr, MD; Elizabeth C. Oelsner, MD, MPH; Wanda K. O’Neal, PhD; Robert Paine, III, MD; Nirupama Putcha, MD, MHS; Donald P. Tashkin, MD; Mary Beth Scholand, MD; J. Michael Wells, MD; and Robert A. Wise, MD. The project officers from the Lung Division of the National Heart, Lung, and Blood Institute (NHLBI) were Lisa Postow, PhD, Thomas Croxton, PhD, MD, and Antonello Punturieri, MD, PhD. SPIROMICS was supported by NIH/NHLBI Contracts HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C HHSN268200900019C, and HHSN268200900020C, which were supplemented by contributions made through the Foundation for the NIH and COPD Foundation from 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., and Sanofi. Financial support was provided by NIH/NHLBI Grants 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, the NIH/NHLBI contracts named above, the McGill University Health Center Research Institute, and the Fonds de la recherche en santé Québec (Quebec Health Research Fund).
Funding Information:
ACKNOWLEDGMENTS. We thank the other investigators, the staff, and the participants of the MESA Lung Study and SPIROMICS for their valuable contributions (a full list of participating MESA investigators and institutions can be found at https://www.mesa-nhlbi.org; more information about the study and how to access SPIROMICS data is available at www.spiromics.org) and acknowledge the following current and former investigators of the SPIROMICS sites and reading centers: Neil E. Alexis, PhD; Wayne H. Anderson, PhD; Richard C. Boucher, MD; Russell P. Bowler, MD, PhD; Elizabeth E. Carretta, MPH; Stephanie A. Christenson, MD; Alejandro P. Comellas, MD; Gerard J. Criner, MD; Ronald G. Crystal, MD; Jeffrey L. Curtis, MD; Claire M. Doerschuk, MD; Mark T. Dransfield, MD; Christine M. Freeman, PhD; Annette T. Hastie, PhD; Jerry A. Krishnan, MD, PhD; Lisa M. LaVange, PhD; Stephen C. Lazarus, MD; Deborah A. Meyers, PhD; John D. Newell, Jr, MD; Elizabeth C. Oelsner, MD, MPH; Wanda K. O’Neal, PhD; Robert Paine, III, MD; Nirupama Putcha, MD, MHS; Donald P. Tashkin, MD; Mary Beth Scholand, MD; J. Michael Wells, MD; and Robert A. Wise, MD. The project officers from the Lung Division of the National Heart, Lung, and Blood Institute (NHLBI) were Lisa Postow, PhD, Thomas Croxton, PhD, MD, and Antonello Punturieri, MD, PhD. SPIROMICS was supported by NIH/NHLBI Contracts HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C HHSN268200900019C, and HHSN268200900020C, which were supplemented by contributions made through the Foundation for the NIH and COPD Foundation from 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., and Sanofi. Financial support was provided by NIH/NHLBI Grants 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, the NIH/NHLBI contracts named above, the McGill University Health Center Research Institute, and the Fonds de la recherche en santé Québec (Quebec Health Research Fund).
Keywords
- Airway branching
- Chronic obstructive pulmonary disease
- Computed tomography
- Fibroblast growth factor
