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Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Ash SY

PROVIDER: S-EPMC5812756 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers.

Ash Samuel Y SY Harmouche Rola R Putman Rachel K RK Ross James C JC Diaz Alejandro A AA Hunninghake Gary M GM Onieva Onieva Jorge J Martinez Fernando J FJ Choi Augustine M AM Lynch David A DA Hatabu Hiroto H Rosas Ivan O IO San Jose Estepar Raul R Washko George R GR

Chest 20170512 4

<h4>Background</h4>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.<h4>Methods</h4>Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of th ...[more]

PMID: 28506611

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Project description:BackgroundQuantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.MethodsIn 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography-mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini-Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst.ResultsWe found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways.ConclusionsMetabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.

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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.

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