Temporal Exploration of COPD Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts.

Background: Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships.

Methods: Cross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features.

Lung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations.

Rationale: While many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort.

Objectives: Our goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell types in which these emphysema-associated pathways are altered, and to detect unique and overlapping transcriptomic signatures in blood and lung samples.

Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema.

Emphysema is a chronic obstructive pulmonary disease phenotype with important prognostic implications. Identifying blood-based biomarkers of emphysema will facilitate early diagnosis and development of targeted therapies. To discover blood omics biomarkers for chest computed tomography-quantified emphysema and develop predictive biomarker panels.

Cigarette smoking-associated isoform switching and 3' UTR lengthening via alternative polyadenylation.

Cigarette smoking induces a profound transcriptomic and systemic inflammatory response. Previous studies have focused on gene level differential expression of smoking, but the genome-wide effects of smoking on alternative isoform regulation have not yet been described. We conducted RNA sequencing in whole-blood samples of 454 current and 767 former smokers in the COPDGene Study, and we analyzed the effects of smoking on differential usage of isoforms and exons.