Amy S Labar, Bryan C Ulrich, Tyler C Lovelace, William G Bain, Faraaz A Shah, Emma B White, Elizabeth A Abe, Francesca Giacona, George A Alba, B Taylor Thompson, Eric P Schmidt, Benjamin E Zuchelkowski, John W Evankovich, Haopu Yang, Raj Ramanan, Holt Murray, Ghady Haidar, Mark E Snyder, Shulin Qin, Xiahong Wang, Yingze Zhang, Seyed M Nouraie, Charles Dela Cruz, Hēth R Turnquist, Prabir Ray, Anuradha Ray, Barbara Methé, Panayiotis V Benos, Alison Morris, Bryan J McVerry, Jehan Alladina, Georgios D Kitsios
{"title":"血浆可溶性ST2水平反映肺外器官功能障碍并预测急性呼吸衰竭的预后。","authors":"Amy S Labar, Bryan C Ulrich, Tyler C Lovelace, William G Bain, Faraaz A Shah, Emma B White, Elizabeth A Abe, Francesca Giacona, George A Alba, B Taylor Thompson, Eric P Schmidt, Benjamin E Zuchelkowski, John W Evankovich, Haopu Yang, Raj Ramanan, Holt Murray, Ghady Haidar, Mark E Snyder, Shulin Qin, Xiahong Wang, Yingze Zhang, Seyed M Nouraie, Charles Dela Cruz, Hēth R Turnquist, Prabir Ray, Anuradha Ray, Barbara Methé, Panayiotis V Benos, Alison Morris, Bryan J McVerry, Jehan Alladina, Georgios D Kitsios","doi":"10.1097/CCM.0000000000006716","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Soluble ST2 (sST2), a decoy receptor for the alarmin interleukin-33 (IL-33), has been implicated in adverse clinical outcomes in acute respiratory failure (ARF). We evaluated sST2 distribution across diverse cohorts of patients with different etiologies of ARF, compared plasma and lower respiratory tract (LRT) concentrations, and examined associations with individual organ dysfunction, biological subphenotypes, and outcomes.</p><p><strong>Design: </strong>Observational study.</p><p><strong>Setting: </strong>Multicenter cohorts of ARF patients.</p><p><strong>Patients: </strong>A total of 1432 ARF patients, including 863 non-COVID and 569 COVID-19 cases, from five cohorts.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>sST2 levels were measured in plasma and LRT specimens (when available) and analyzed for associations with ARF etiology, severity, organ dysfunction, systemic host response, subphenotypes, and 30-day mortality. Plasma sST2 levels were higher in non-COVID ARF patients compared with COVID-19 patients (p < 0.05) and were markedly elevated compared with LRT levels (> 19-fold), with weak intercompartmental correlation. Elevated plasma sST2 levels were associated with extrapulmonary organ dysfunction and a hyperinflammatory ARF subphenotype but not with respiratory indices, including hypoxemia. Plasma sST2 independently predicted 30-day mortality in pooled cohort data, adjusted for age, sex, and illness severity. In longitudinal measurements, nonsurvivors had persistently elevated plasma sST2 levels in the first 2 weeks of critical illness compared with survivors.</p><p><strong>Conclusions: </strong>Plasma sST2 levels independently predict outcomes in ARF and are strongly associated with extrapulmonary organ dysfunction. The weak correlation between plasma and LRT sST2 levels suggests a predominantly systemic source. These findings highlight the potential of the IL-33/ST2 axis as a therapeutic target and warrant further investigation into its role in multiple organ dysfunction in ARF.</p>","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":" ","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasma Levels of Soluble ST2 Reflect Extrapulmonary Organ Dysfunction and Predict Outcomes in Acute Respiratory Failure.\",\"authors\":\"Amy S Labar, Bryan C Ulrich, Tyler C Lovelace, William G Bain, Faraaz A Shah, Emma B White, Elizabeth A Abe, Francesca Giacona, George A Alba, B Taylor Thompson, Eric P Schmidt, Benjamin E Zuchelkowski, John W Evankovich, Haopu Yang, Raj Ramanan, Holt Murray, Ghady Haidar, Mark E Snyder, Shulin Qin, Xiahong Wang, Yingze Zhang, Seyed M Nouraie, Charles Dela Cruz, Hēth R Turnquist, Prabir Ray, Anuradha Ray, Barbara Methé, Panayiotis V Benos, Alison Morris, Bryan J McVerry, Jehan Alladina, Georgios D Kitsios\",\"doi\":\"10.1097/CCM.0000000000006716\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Soluble ST2 (sST2), a decoy receptor for the alarmin interleukin-33 (IL-33), has been implicated in adverse clinical outcomes in acute respiratory failure (ARF). We evaluated sST2 distribution across diverse cohorts of patients with different etiologies of ARF, compared plasma and lower respiratory tract (LRT) concentrations, and examined associations with individual organ dysfunction, biological subphenotypes, and outcomes.</p><p><strong>Design: </strong>Observational study.</p><p><strong>Setting: </strong>Multicenter cohorts of ARF patients.</p><p><strong>Patients: </strong>A total of 1432 ARF patients, including 863 non-COVID and 569 COVID-19 cases, from five cohorts.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>sST2 levels were measured in plasma and LRT specimens (when available) and analyzed for associations with ARF etiology, severity, organ dysfunction, systemic host response, subphenotypes, and 30-day mortality. Plasma sST2 levels were higher in non-COVID ARF patients compared with COVID-19 patients (p < 0.05) and were markedly elevated compared with LRT levels (> 19-fold), with weak intercompartmental correlation. Elevated plasma sST2 levels were associated with extrapulmonary organ dysfunction and a hyperinflammatory ARF subphenotype but not with respiratory indices, including hypoxemia. Plasma sST2 independently predicted 30-day mortality in pooled cohort data, adjusted for age, sex, and illness severity. In longitudinal measurements, nonsurvivors had persistently elevated plasma sST2 levels in the first 2 weeks of critical illness compared with survivors.</p><p><strong>Conclusions: </strong>Plasma sST2 levels independently predict outcomes in ARF and are strongly associated with extrapulmonary organ dysfunction. The weak correlation between plasma and LRT sST2 levels suggests a predominantly systemic source. These findings highlight the potential of the IL-33/ST2 axis as a therapeutic target and warrant further investigation into its role in multiple organ dysfunction in ARF.</p>\",\"PeriodicalId\":10765,\"journal\":{\"name\":\"Critical Care Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.7000,\"publicationDate\":\"2025-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Care Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CCM.0000000000006716\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Care Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CCM.0000000000006716","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Plasma Levels of Soluble ST2 Reflect Extrapulmonary Organ Dysfunction and Predict Outcomes in Acute Respiratory Failure.
Objectives: Soluble ST2 (sST2), a decoy receptor for the alarmin interleukin-33 (IL-33), has been implicated in adverse clinical outcomes in acute respiratory failure (ARF). We evaluated sST2 distribution across diverse cohorts of patients with different etiologies of ARF, compared plasma and lower respiratory tract (LRT) concentrations, and examined associations with individual organ dysfunction, biological subphenotypes, and outcomes.
Design: Observational study.
Setting: Multicenter cohorts of ARF patients.
Patients: A total of 1432 ARF patients, including 863 non-COVID and 569 COVID-19 cases, from five cohorts.
Interventions: None.
Measurements and main results: sST2 levels were measured in plasma and LRT specimens (when available) and analyzed for associations with ARF etiology, severity, organ dysfunction, systemic host response, subphenotypes, and 30-day mortality. Plasma sST2 levels were higher in non-COVID ARF patients compared with COVID-19 patients (p < 0.05) and were markedly elevated compared with LRT levels (> 19-fold), with weak intercompartmental correlation. Elevated plasma sST2 levels were associated with extrapulmonary organ dysfunction and a hyperinflammatory ARF subphenotype but not with respiratory indices, including hypoxemia. Plasma sST2 independently predicted 30-day mortality in pooled cohort data, adjusted for age, sex, and illness severity. In longitudinal measurements, nonsurvivors had persistently elevated plasma sST2 levels in the first 2 weeks of critical illness compared with survivors.
Conclusions: Plasma sST2 levels independently predict outcomes in ARF and are strongly associated with extrapulmonary organ dysfunction. The weak correlation between plasma and LRT sST2 levels suggests a predominantly systemic source. These findings highlight the potential of the IL-33/ST2 axis as a therapeutic target and warrant further investigation into its role in multiple organ dysfunction in ARF.
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Critical Care Medicine is the premier peer-reviewed, scientific publication in critical care medicine. Directed to those specialists who treat patients in the ICU and CCU, including chest physicians, surgeons, pediatricians, pharmacists/pharmacologists, anesthesiologists, critical care nurses, and other healthcare professionals, Critical Care Medicine covers all aspects of acute and emergency care for the critically ill or injured patient.
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