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Occupational exposures and longitudinal lung function decline.

ABSTRACT: Few longitudinal studies have been conducted on occupational exposure and lung function. This study investigated occupational dust exposure effects on lung function and whether genetic variants influence such effects.The study population (1,332 participants) was from the Framingham Heart Study, in which participant lung function measures were available from up to five examinations over nearly 17 years. Occupational dust exposures were classified into "more" and "less" likely dust exposure. We used linear mixed effects models for the analysis.Participants with more likely dust exposure had a mean 4.5?mL/year excess loss rate of FEV1 over time. However, occupational dust exposures alone or interactions with age or time had no significant effect on FEV1 /FVC. No statistically significant effects of genetic modifications in the different subgroups were identified for FEV1 loss.Occupational dust exposures may accelerate the rate of FEV1 loss but not FEV1 /FVC loss.

SUBMITTER: Liao SY

PROVIDER: S-EPMC4512740 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Occupational exposures and longitudinal lung function decline.

Liao Shu-Yi SY Lin Xihong X Christiani David C DC

American journal of industrial medicine 20141110 1

<h4>Background</h4>Few longitudinal studies have been conducted on occupational exposure and lung function. This study investigated occupational dust exposure effects on lung function and whether genetic variants influence such effects.<h4>Methods</h4>The study population (1,332 participants) was from the Framingham Heart Study, in which participant lung function measures were available from up to five examinations over nearly 17 years. Occupational dust exposures were classified into "more" and ...[more]

PMID: 25384732

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Project description:The Rationale: Molecular markers of disease activity that are predictive of forced vital capacity (FVC) progression in idiopathic pulmonary fibrosis are needed. Objectives: Develop a predictor using longitudinal within-patient gene expression differences (ΔGE) in peripheral blood mononuclear cells (PBMC) to predict of FVC progression. Methods: Patients in the training cohort (n=74) experiencing ≥10% relative reduction in FVC% of predicted over 12 months were categorized as progressors in contrast to the remaining stable patients. Baseline to 4-month within-patient ΔGE were correlated with FVC status. FVC-predictor genes were prioritized by two-group comparison with FDR<5%, logistic LASSO regression with p<0.05, and 10-Fold Cross-Validation with ≥50% support. Receiver operating characteristic with area under the curve (AUC) analyses were conducted in training subsets and independent validation cohorts from UChicago (n=27), UPMC (n=35), and Imperial (n=24) where different transcriptome assay platforms and varying transcriptome sampling times were used to derive ΔGE. Results: Intra-subject Compared to cross-sectional analysis of baseline GE, our longitudinal ΔGE variation approach demonstratedlargely reduced within-group sample variation and increased statistic power fin progressor and stable groups for prediction model development. A 25-gene FVC-predictor separated “progressors” from “stable” by Principal Component Analysis in the training and subsets of the training cohort. The resulting FVC-predictor consistently demonstrated high discriminatory performance independent of transcriptome assay platforms and varying sampling times in validation cohorts (AUC= 0.77-0.80). TGF beta was the highest-ranking canonical pathway by Gene Set Enrichment Analysis. Conclusions: Our novel short-term longitudinal within-patient ΔGE approach identified a FVC-predictor which may reflect disease activity and prove to be a reliable biomarker predictive of future FVC decline.

Dataset Information

Occupational exposures and longitudinal lung function decline.

Publications

Occupational exposures and longitudinal lung function decline.

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