Title | Human airway branch variation and chronic obstructive pulmonary disease. |
Publication Type | Publication |
Year | 2018 |
Authors | Smith BM, Traboulsi H, Austin JHM, Manichaikul A, Hoffman EA, Bleecker ER, Cardoso WV, Cooper C, Couper DJ, Dashnaw SM, Guo J, Han MK, Hansel NN, Hughes EW, Jacobs DR, Kanner RE, Kaufman JD, Kleerup E, Lin C-L, Liu K, Cascio CMLo, Martinez FJ, Nguyen JN, Prince MR, Rennard S, Rich SS, Simon L, Sun Y, Watson KE, Woodruff PG, Baglole CJ, R Barr G |
Corporate Authors | MESA Lung and SPIROMICS investigators |
Journal | Proc Natl Acad Sci U S A |
Volume | 115 |
Issue | 5 |
Pagination | E974-E981 |
Date Published | 2018 Jan 30 |
ISSN | 1091-6490 |
Keywords | Aged, Aged, 80 and over, Bronchi, Disease Susceptibility, Female, Fibroblast Growth Factor 10, Genotype, Humans, Image Processing, Computer-Assisted, Lung, Male, Middle Aged, phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Respiration, smoking, Tomography, X-Ray Computed, Trachea |
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 ( = 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 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. |
DOI | 10.1073/pnas.1715564115 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 29339516 |
PubMed Central ID | PMC5798356 |
Grant List | HHSN268200900019C / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States R01 HL112986 / HL / NHLBI NIH HHS / United States P30 ES005605 / ES / NIEHS NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States R01 HL077612 / HL / NHLBI NIH HHS / United States RC1 HL100543 / HL / NHLBI NIH HHS / United States K24 HL137013 / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States R01 HL093081 / HL / NHLBI NIH HHS / United States HHSN268200900015C / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States HHSN268200900016C / HL / NHLBI NIH HHS / United States U01 HL114494 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States HHSN268200900018C / HL / NHLBI NIH HHS / United States R01 HL121270 / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL137880 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States P30 DK054759 / DK / NIDDK NIH HHS / United States R01 HL130506 / HL / NHLBI NIH HHS / United States HHSN268200900017C / HL / NHLBI NIH HHS / United States HHSN268200900020C / HL / NHLBI NIH HHS / United States HHSN268200900013C / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States HHSN268200900014C / HL / NHLBI NIH HHS / United States R35 HL135834 / HL / NHLBI NIH HHS / United States P30 ES009089 / ES / NIEHS NIH HHS / United States |
Human airway branch variation and chronic obstructive pulmonary disease.
MS#:
MS053
Manuscript Full Title:
Human airway branch variation and chronic obstructive pulmonary disease.
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Published and Public