Dataset Information

Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities.

ABSTRACT: Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening, including healthy subjects, subjects with ILAs, and subjects who were healthy initially and with ILAs one year later (Healthy?ILAs), were recruited for this study. The metabolic profiles of all of the subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolic characteristics of the ILAs subjects were discovered, and the corresponding biomarkers were predicted. The metabolomic data from the Healthy?ILAs subjects were collected for further verification. The results indicated that five serum metabolite alterations (up-regulated phosphatidylcholine, phosphatidic acid, betaine aldehyde and phosphatidylethanolamine, as well as down-regulated 1-acylglycerophosphocholine) were sensitive and reliable biomarkers for identifying ILAs. Perturbation of the corresponding biological pathways (RhoA signaling, mTOR/P70S6K signaling and phospholipase C signaling) might be at least partially responsible for the pathogenesis of ILAs. This study may provide a good template for determining the early diagnostic markers of subclinical disease status and for obtaining a better understanding of their pathogenesis.

SUBMITTER: Tan Y

PROVIDER: S-EPMC4964521 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities.

Tan Yong Y Jia Dongmei D Lin Zhang Z Guo Baosheng B He Bing B Lu Cheng C Xiao Cheng C Liu Zhongdi Z Zhao Ning N Bian Zhaoxiang Z Zhang Ge G Zhang Weidong W Liu Xinru X Lu Aiping A

International journal of molecular sciences 20160716 7

Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening, including healthy subjects, subjects with ILAs, and subjects who were healthy initially and with ILAs one year later (Healthy→ILAs), were recruited for this study. The metabolic profil ...[more]

PMID: 27438829

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Project description:Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.

Project description:Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known.We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema.Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking.In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Project description:Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.To investigate whether interstitial lung abnormalities are associated with increased mortality.Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).Interstitial lung abnormality status as determined by chest CT evaluation.All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P?=?.03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P?<?.001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P?=?.01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P?=?.02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

Dataset Information

Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities.

Publications

Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities.

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