Blood gene expression risk profiles and interstitial lung abnormalities: COPDGene and ECLIPSE cohort studies

Area of Science:

• Pulmonary Medicine
• Genomics
• Radiology

Background:

• Interstitial lung abnormalities (ILA) are radiological findings that can progress to idiopathic pulmonary fibrosis (IPF).
• Blood gene expression profiles are known predictors of IPF mortality.
• The association between IPF mortality genes and ILA outcomes was previously unknown.

Purpose of the Study:

• To evaluate if a previously identified blood gene expression profile associated with IPF mortality is also associated with ILA and all-cause mortality.
• To develop and validate a novel gene expression score for ILA using genes from the IPF mortality profile.

Main Methods:

• Utilized data from the COPDGene and ECLIPSE studies, including visual scoring of ILA and gene expression data.
• Evaluated the association of a previously described IPF mortality score with ILA and mortality.
• Trained and tested a new ILA gene expression score derived from IPF score genes in COPDGene and ECLIPSE participants.

Main Results:

• The original IPF mortality score was not associated with ILA or mortality.
• A novel ILA score, derived from IPF score genes, was significantly associated with ILA (OR 1.4) and mortality (HR 1.25).
• Six of the 11 genes in the ILA score showed discordant effects compared to the IPF score; the ILA score partially mediated age-related mortality.

Conclusions:

• A gene expression score for ILA, developed using genes linked to IPF mortality, identified both shared and unique biological pathways.
• These findings suggest complex biological relationships between ILA, IPF, aging, and mortality.
• The developed ILA score offers potential for predicting disease progression and outcomes.