Human airway branch variation and chronic obstructive pulmonary disease

• DOI: 10.1073/pnas.1715564115
• Publication Date: 2018-01-16T16:40:16Z
• Authors: Benjamin M. Smith; Hussein Traboulsi; John H. M. Austin; Ani Manichaikul; Eric A. Hoffman; Eugene R. Bleecker; Wellington V. Car...; Christopher Cooper; David J. Couper; Stephen M. Dashnaw; Jia Guo; MeiLan K. Han; Nadia N. Hansel; Emlyn W. Hughes; David R. Jacobs; Richard E. Kanner; Joel D. Kaufman; Eric Kleerup; Ching-Long Lin; Kiang Liu; Christian M. Lo C...; Fernando J. Martinez; 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
• Keywords: Aged, 80 and over; Male; 0303 health sciences; Genotype; Respiration; Smoking; Bronchi; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Phenotype; Pulmonary Emphysema; Image Processing, Computer-Assisted; Humans; Female; Disease Susceptibility; Prospective Studies; Tomography, X-Ray Computed; Fibroblast Growth Factor 10; Lung; Aged

Significance

The human airway tree is a filter of noxious particulate matter, the primary cause of chronic obstructive pulmonary disease (COPD). We demonstrate that variation in central airway tree branching occurs in over one-quarter of the general population and increases COPD susceptibility, particularly among smokers. We show that these central airway branch variants are biomarkers of altered distal lung structure, the primary site of COPD pathobiology. Finally, we demonstrate the heritability of central airway branch variants within families and identify and replicate an association with FGF 10 . These findings suggest that central airway branch variants, easily detectable by computed tomography, represent heritable biomarkers of widely altered lung structure and a COPD susceptibility factor.