Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E974-E981. doi: 10.1073/pnas.1715564115. Epub 2018 Jan 16.

Human airway branch variation and chronic obstructive pulmonary disease.

Author information

1
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032; benjamin.m.smith@mcgill.ca.
2
Translational Research in Respiratory Diseases Program, Department of Medicine, McGill University Health Centre Research Institute, Montreal, QC H4A 3J1, Canada.
3
Department of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
4
Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903.
5
Department of Radiology, University of Iowa, Iowa City, IA 52242.
6
Department of Medicine, University of Iowa, Iowa City, IA 52242.
7
Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242.
8
Department of Medicine, Wake Forest University, Winston-Salem, NC 27101.
9
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
10
Department of Medicine, University of California, Los Angeles, CA 90095.
11
Department of Biostatistics, University of North Carolina at Chapel HIll, Chapel Hill, NC 27599.
12
Department of Biomedical Engineering, Columbia University, New York, NY 10027.
13
Department of Medicine, University of Michigan, Ann Arbor, MI 48109.
14
Department of Medicine, Johns Hopkins University, Baltimore, MD 21205.
15
Department of Physics, Columbia University, New York, NY 10027.
16
Division of Epidemiology and Community Public Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454.
17
Department of Medicine, University of Utah, Salt Lake City, UT 84132.
18
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195.
19
Department of Mechanical and Industrial Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242.
20
Department of Medicine, Northwestern University, Chicago, IL 60611.
21
Department of Medicine, Weill Cornell Medical College, New York, NY 10065.
22
Department of Medicine, University of Nebraska Medical Center, Omaha, NE 68198.
23
Department of Medicine, University of California, San Francisco, CA 94110.
24
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032.

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

PMID:
29339516
PMCID:
PMC5798356
DOI:
10.1073/pnas.1715564115
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: E.A.H. is co-founder and share-holder in VIDA Diagnostics, which commercialized the software used to assess lung volumes and percent emphysema (but not airway anatomy) in this study.

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center