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Am J Respir Cell Mol Biol. 2019 Mar 15. doi: 10.1165/rcmb.2018-0245PS. [Epub ahead of print]

Omics and the Search for Blood Biomarkers in COPD: Insights from COPDGene.

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National Jewish Health, 2930, Department of Medicine, Denver, Colorado, United States ;
Brigham and Women's Hospital, Channing Laboratory, Boston, Massachusetts, United States.
Brigham and Women's Hospital Department of Medicine, 370908, Boston, Massachusetts, United States.
Brigham and Women's Hospital, Department of Medicine, Boston, Massachusetts, United States.
National Jewish Health, 2930, Department of Medicine, Denver, Colorado, United States.


There is an unmet need for blood biomarkers in diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). The search for these biomarkers has been revolutionized by high throughput sequencing techniques and multiplex platforms which can measure thousands of gene transcripts, proteins, or metabolites. We review COPDGene publications which include DNA methylation, transcriptomics, proteomics, and metabolomic blood biomarkers and discuss their impact on COPD. Key contributions from COPDGene include: identification of DNA methylation effects from smoking and genetic variation; new transcriptomic signatures in the blood; identification of protein biomarkers associated with severity and progression (e.g. sRAGE (soluble receptor for advanced glycosylation end products), inflammatory cytokines IL-6 and IL-8); and identification of small molecules (ceramides and sphingomyelin) which may be pathogenic. COPDGene studies have revealed that some of the COPD GWAS polymorphisms are strongly associated with blood biomarkers (e.g. rs2070600 in AGER is a pQTL for sRAGE) underscoring the importance of combining omics results. Investigators have developed molecular networks identifying lower CD4+ resting memory cells associated with COPD. Genes, proteins, and metabolite networks are particularly important because the explanatory value of any single molecule is small (1-10% ) compared to panels of multiple markers. COPDGene has been a useful resource in the identification and validation of multiple biomarkers for COPD. These biomarkers, either combined in multiple biomarker panels or integrated with other omics data types, will hopefully one day lead to novel diagnostic and prognostic tests for COPD phenotypes and may be relevant for assessing novel therapies.


COPD; biomarkers; emphysema; epigenetics; smoking


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