Dataset Information

Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study.

ABSTRACT: RATIONALE:The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated. OBJECTIVES:To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study. METHODS:ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality). MEASUREMENTS AND MAIN RESULTS:During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, ±6 ml; P?=?0.0005) and with those with ILA without progression (25 ml; SE, ±11 ml; P?=?0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P?=?0.01) when compared with those without ILA. CONCLUSIONS:These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.

SUBMITTER: Araki T

PROVIDER: S-EPMC5215030 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study.

Araki Tetsuro T Putman Rachel K RK Hatabu Hiroto H Gao Wei W Dupuis Josée J Latourelle Jeanne C JC Nishino Mizuki M Zazueta Oscar E OE Kurugol Sila S Ross James C JC San José Estépar Raúl R Schwartz David A DA Rosas Ivan O IO Washko George R GR O'Connor George T GT Hunninghake Gary M GM

American journal of respiratory and critical care medicine 20161201 12

<h4>Rationale</h4>The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated.<h4>Objectives</h4>To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study.<h4>Methods</h4>ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (a ...[more]

PMID: 27314401

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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.

Dataset Information

Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study.

Publications

Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study.

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