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Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study

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  • ASTHMA
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Abstract

Background

Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients.

Objective

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.

Methods

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.

Results

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.

Conclusion

These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endoty** asthma.

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Abbreviations

ACT:

Asthma control test

BEC:

Blood eosinophil count

Bude_eq:

Budesonide equivalent dose

COREA:

Cohort for Reality and Evolution of Adult Asthma in Korea

FeNO:

Fractional exhaled nitric oxide

FEV:

Forced expiratory volume in the first second

ICS:

Inhaled corticosteroids

IL:

Interleukin

MSEA:

Moderate-to-severe eosinophilic asthma

OCS:

Oral systemic steroids

PBMC:

Peripheral blood mononuclear cells

Pred_eq:

Prednisolone equivalent dose

TSLP:

Thymic stromal lymphopoietin

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Funding

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2019M3E5D3073365).

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Authors and Affiliations

  1. Division of Allergy and Clinical Immunology, Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea

    Duong Duc Pham, Ji-Hyang Lee, Woo-Jung Song, Hyouk-Soo Kwon, You Sook Cho & Tae-Bum Kim

  2. DNA Link, Seoul, South Korea

    Eunsoon Shin & Jong Eun Lee

  3. Department of Public Health Sciences, Graduate School of Public Health, Interdisciplinary Program of Bioinformatics, College of Natural Science, Institute of Health and Environment, Seoul National University, Seoul, South Korea

    Sungho Won

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  1. Duong Duc Pham
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  2. Eunsoon Shin
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  3. Jong Eun Lee
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  4. Ji-Hyang Lee
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  7. You Sook Cho
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  9. Tae-Bum Kim
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Contributions

TBK designed the study, applied for the project, and supervised the whole process. DDP analyzed the data and drafted the manuscript. ES and JEL collected the gene expression data, while JHL, WJS, HSK, and YSK collected clinical data. SHW designed and supervised the analysis of the gene expression data

Corresponding author

Correspondence to Tae-Bum Kim.

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The authors declare no competing interests.

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Pham, D.D., Shin, E., Lee, J.E. et al. Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study. Lung (2024). https://doi.org/10.1007/s00408-024-00728-9

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