Human airway branch variation and chronic obstructive pulmonary disease

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


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bronchi / anatomy & histology
  • Bronchi / physiopathology*
  • Disease Susceptibility
  • Female
  • Fibroblast Growth Factor 10 / genetics*
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Pulmonary Emphysema / physiopathology
  • Respiration
  • Smoking
  • Tomography, X-Ray Computed
  • Trachea / anatomy & histology
  • Trachea / physiopathology*


  • FGF10 protein, human
  • Fibroblast Growth Factor 10