Rombout B E van Amstel, Brian Bartek, Alexander P J Vlaar, Elizabeth Gay, Lonneke A van Vught, Olaf L Cremer, Tom Van der Poll, Nathan I Shapiro, Michael A Matthay, Carolyn S Calfee, Pratik Sinha, Lieuwe D J Bos
{"title":"危重疾病中高炎性和低炎性表型的时间转变。","authors":"Rombout B E van Amstel, Brian Bartek, Alexander P J Vlaar, Elizabeth Gay, Lonneke A van Vught, Olaf L Cremer, Tom Van der Poll, Nathan I Shapiro, Michael A Matthay, Carolyn S Calfee, Pratik Sinha, Lieuwe D J Bos","doi":"10.1164/rccm.202406-1241OC","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.</p><p><strong>Objectives: </strong>To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.</p><p><strong>Methods: </strong>We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS). Critically ill patients having biomarkers available at multiple timepoints (Day 0-4) were included. We employed a validated classifier model incorporating plasma interleukin-8, protein C and serum bicarbonate to assign phenotypes on each day. We determined the association of longitudinal phenotype transition and 90-day all-cause mortality.</p><p><strong>Measurements and main results: </strong>Data from 2407, 527 and 868 patients were included in MARS, ALVEOLI and CLOVERS, respectively. In MARS, 36.0% were classified by the parsimonious model as Hyperinflammatory at day 0, decreasing to 15.6% by day 2 and 6.3% by day 4. In ALVEOLI and CLOVERS, 26.4% and 24.8% of patients were Hyperinflammatory at day 0, decreasing to 13.4% and 5.7% at day 3, respectively. In all three cohorts, switching classification from Hyperinflammatory (Day 0) to Hypoinflammatory over time was associated with significantly improved mortality compared to persistently Hyperinflammatory patients. Mediation analysis indicated that only a minor proportion of this improvement could be attributed to ameliorating organ failure.</p><p><strong>Conclusion: </strong>The prevalence of the Hyperinflammatory phenotype, as assigned by a parsimonious biomarker classifier model, decreases over the first several days of critical illness, irrespective of ARDS diagnosis. The transition from Hyperinflammatory to Hypoinflammatory mediates a trajectory towards recovery beyond the resolution of organ failure.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.3000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.\",\"authors\":\"Rombout B E van Amstel, Brian Bartek, Alexander P J Vlaar, Elizabeth Gay, Lonneke A van Vught, Olaf L Cremer, Tom Van der Poll, Nathan I Shapiro, Michael A Matthay, Carolyn S Calfee, Pratik Sinha, Lieuwe D J Bos\",\"doi\":\"10.1164/rccm.202406-1241OC\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.</p><p><strong>Objectives: </strong>To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.</p><p><strong>Methods: </strong>We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS). Critically ill patients having biomarkers available at multiple timepoints (Day 0-4) were included. We employed a validated classifier model incorporating plasma interleukin-8, protein C and serum bicarbonate to assign phenotypes on each day. We determined the association of longitudinal phenotype transition and 90-day all-cause mortality.</p><p><strong>Measurements and main results: </strong>Data from 2407, 527 and 868 patients were included in MARS, ALVEOLI and CLOVERS, respectively. In MARS, 36.0% were classified by the parsimonious model as Hyperinflammatory at day 0, decreasing to 15.6% by day 2 and 6.3% by day 4. In ALVEOLI and CLOVERS, 26.4% and 24.8% of patients were Hyperinflammatory at day 0, decreasing to 13.4% and 5.7% at day 3, respectively. In all three cohorts, switching classification from Hyperinflammatory (Day 0) to Hypoinflammatory over time was associated with significantly improved mortality compared to persistently Hyperinflammatory patients. Mediation analysis indicated that only a minor proportion of this improvement could be attributed to ameliorating organ failure.</p><p><strong>Conclusion: </strong>The prevalence of the Hyperinflammatory phenotype, as assigned by a parsimonious biomarker classifier model, decreases over the first several days of critical illness, irrespective of ARDS diagnosis. The transition from Hyperinflammatory to Hypoinflammatory mediates a trajectory towards recovery beyond the resolution of organ failure.</p>\",\"PeriodicalId\":7664,\"journal\":{\"name\":\"American journal of respiratory and critical care medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":19.3000,\"publicationDate\":\"2024-12-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of respiratory and critical care medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1164/rccm.202406-1241OC\",\"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":"American journal of respiratory and critical care medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1164/rccm.202406-1241OC","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.
Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.
Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.
Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS). Critically ill patients having biomarkers available at multiple timepoints (Day 0-4) were included. We employed a validated classifier model incorporating plasma interleukin-8, protein C and serum bicarbonate to assign phenotypes on each day. We determined the association of longitudinal phenotype transition and 90-day all-cause mortality.
Measurements and main results: Data from 2407, 527 and 868 patients were included in MARS, ALVEOLI and CLOVERS, respectively. In MARS, 36.0% were classified by the parsimonious model as Hyperinflammatory at day 0, decreasing to 15.6% by day 2 and 6.3% by day 4. In ALVEOLI and CLOVERS, 26.4% and 24.8% of patients were Hyperinflammatory at day 0, decreasing to 13.4% and 5.7% at day 3, respectively. In all three cohorts, switching classification from Hyperinflammatory (Day 0) to Hypoinflammatory over time was associated with significantly improved mortality compared to persistently Hyperinflammatory patients. Mediation analysis indicated that only a minor proportion of this improvement could be attributed to ameliorating organ failure.
Conclusion: The prevalence of the Hyperinflammatory phenotype, as assigned by a parsimonious biomarker classifier model, decreases over the first several days of critical illness, irrespective of ARDS diagnosis. The transition from Hyperinflammatory to Hypoinflammatory mediates a trajectory towards recovery beyond the resolution of organ failure.
期刊介绍：
The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences.
A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.
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