Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

Samuel Y Ash; Rola Harmouche; Rachel K Putman; James C Ross; Alejandro A Diaz; Gary M Hunninghake; Jorge Onieva Onieva; Fernando J Martinez; Augustine M Choi; David A Lynch; Hiroto Hatabu; Ivan O Rosas; Raul San Jose Estepar; George R Washko; COPDGene Investigators

doi:10.1016/j.chest.2017.04.185

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Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

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Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

Samuel Y Ash, Rola Harmouche, Rachel K Putman, James C Ross, Alejandro A Diaz, Gary M Hunninghake, Jorge Onieva Onieva, Fernando J Martinez, Augustine M Choi, David A Lynch, …

Chest, Vol.152(4), pp.780-791

10/2017

DOI: 10.1016/j.chest.2017.04.185

PMCID: PMC5812756

PMID: 28506611

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Abstract

Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. A total of 8,345 participants had clinical and CT scanning data available. A 5% absolute increase in interstitial changes was associated with an absolute decrease in FVC % predicted of 2.47% (P < .001) and a 1.36-point higher St. George’s Respiratory Questionnaire score (P < .001). Among the 6,827 participants with mortality data, a 5% increase in interstitial changes was associated with a 29% increased risk of death (P < .001). These associations were present in a subgroup without visually defined interstitial lung abnormalities, as well as in those with normal spirometric test results, and in those without chronic respiratory symptoms. In non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter polymorphism, there was a 0.64% (P < .001) absolute increase in the percentage of lung with interstitial changes. Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures.

mortality

CT scanning

interstitial lung abnormalities

pulmonary fibrosis

emphysema

Details

Title: Subtitle: Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers
Creators: Samuel Y Ash - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
Rola Harmouche - Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Boston, MA
Rachel K Putman - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
James C Ross - Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Boston, MA
Alejandro A Diaz - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
Gary M Hunninghake - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
Jorge Onieva Onieva - Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Boston, MA
Fernando J Martinez - Department of Medicine, Weil Cornell Medical College, New York, NY
Augustine M Choi - Department of Medicine, Weil Cornell Medical College, New York, NY
David A Lynch - Department of Radiology, National Jewish Health, Denver, CO
Hiroto Hatabu - Department of Radiology, Brigham and Women’s Hospital, Boston, MA
Ivan O Rosas - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
Raul San Jose Estepar - Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Boston, MA
George R Washko - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, MA
COPDGene Investigators
Contributors: Eric A Hoffman (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Chest, Vol.152(4), pp.780-791
DOI: 10.1016/j.chest.2017.04.185
PMID: 28506611
PMCID: PMC5812756
NLM abbreviation: Chest
ISSN: 0012-3692
eISSN: 1931-3543
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: 5-T32-HL007633-30, P01-HL114501, R01-HL089856, R01-HL107246, R01-HL111024, R01-HL116933; DOI: 10.13039/100001003, name: Boehringer Ingelheim
Language: English
Date published: 10/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051590302771

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