{Reference Type}: Journal Article
{Title}: Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.
{Author}: Pham DD;Shin E;Lee JE;Lee JH;Song WJ;Kwon HS;Cho YS;Won S;Kim TB;
{Journal}: Lung
{Volume}: 202
{Issue}: 4
{Year}: 2024 Aug 12
{Factor}: 3.777
{DOI}: 10.1007/s00408-024-00728-9
{Abstract}: <B>BACKGROUND: </B>Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients.<BR><B>OBJECTIVE: </B>This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use.<BR><B>METHODS: </B>Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines.<BR><B>RESULTS: </B>In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients.<BR><B>CONCLUSIONS: </B>These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma.