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Human airway branch variation and chronic obstructive pulmonary disease

2018; National Academy of Sciences; Volume: 115; Issue: 5 Linguagem: Inglês

10.1073/pnas.1715564115

1091-6490

Benjamin M. Smith, Hussein Traboulsi, John H. M. Austin, Ani Manichaikul, Eric A. Hoffman, Eugene R. Bleecker, Wellington V. Cardoso, Christopher S. Cooper, David Couper, Stephen Dashnaw, Jia Guo, MeiLan K. Han, Nadia N. Hansel, Emlyn Hughes, David R. Jacobs, Richard E. Kanner, Joel D. Kaufman, Eric Kleerup, Ching‐Long Lin, Kiang Liu, Christian M. Lo Cascio, Fernando J. Martínez, Jennifer N. Nguyen, Martin R. Prince, Stephen Rennard, Stephen S. Rich, Leora Simon, Yanping Sun, Karol E. Watson, Prescott G. Woodruff, Carolyn J. Baglole, R. Graham Barr,

Neuroscience of respiration and sleep

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.