Duong Duc Pham, Eunsoon Shin, Jong Eun Lee, Ji-Hyang Lee, Woo-Jung Song, Hyouk-Soo Kwon, You Sook Cho, Sungho Won, Tae-Bum Kim
{"title":"外周血单核细胞中 T2 炎症基因的转录组表达与哮喘的纵向临床结果:来自 COREA 研究的启示","authors":"Duong Duc Pham, Eunsoon Shin, Jong Eun Lee, Ji-Hyang Lee, Woo-Jung Song, Hyouk-Soo Kwon, You Sook Cho, Sungho Won, Tae-Bum Kim","doi":"10.1007/s00408-024-00728-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.\",\"authors\":\"Duong Duc Pham, Eunsoon Shin, Jong Eun Lee, Ji-Hyang Lee, Woo-Jung Song, Hyouk-Soo Kwon, You Sook Cho, Sungho Won, Tae-Bum Kim\",\"doi\":\"10.1007/s00408-024-00728-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":18163,\"journal\":{\"name\":\"Lung\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lung\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00408-024-00728-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00408-024-00728-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.
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 endotyping asthma.
期刊介绍:
Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.