Predicting and Preventing Acute Respiratory Distress Syndrome after Hematopoietic Stem Cell Transplantation

预测和预防造血干细胞移植后急性呼吸窘迫综合征

• 批准号: 10685406
• 负责人: Hemang Yadav
• 金额: $ 16.28万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685406
• 关键词: Acute Disease; Acute Respiratory Distress Syndrome; Address; Area; Biological; Biological Markers; Caring; Clinical; Complex; Complication; Computing Methodologies; Critical Care; Data; Development; Development Plans; Electronic Health Record; Environment; Exclusion; Functional disorder; Funding; Future; Goals; Heart Diseases; Hematologic Neoplasms; Hematological Disease; Hematopoietic Stem Cell Transplantation; Hospitals; Informatics; Infrastructure; Interdisciplinary Study; Investigation; Knowledge; Lung; Lung Transplantation; Lung diseases; Machine Learning; Medical; Mentors; Mentorship; Mission; Modeling; Nature; Operative Surgical Procedures; Pathway interactions; Patient Recruitments; Patient-Focused Outcomes; Patients; Phenotype; Physiological; Plasma; Population; Prevention strategy; Reproducibility; Research; Research Methodology; Research Personnel; Respiratory Failure; Risk; Risk Factors; Role; Scientist; Stem cell transplant; Syndrome; System; Systems Biology; Techniques; Time; Training; Translational Research; Transplant Recipients; Transplantation; United States National Institutes of Health; Work; analytical tool; career development; clinical predictors; computer studies; effective therapy; endophenotype; experience; health care service utilization; high risk; improved; improved outcome; innovation; metabolomics; mortality; novel; patient subsets; personalized approach; post-transplant; precision medicine; predictive modeling; predictive tools; prevent; preventive intervention; prognostic; programs; prospective; respiratory; risk prediction; risk prediction model; skills; statistics; success; translational physician; translational scientist; translational study; transplant centers

PROJECT SUMMARY/ABSTRACT Hematopoietic stem cell transplantation (HSCT) offers an advanced treatment option for conditions that are otherwise incurable. Pulmonary complications are common following HSCT and severely compromise its overall success rate. The most severe end of this spectrum is acute respiratory distress syndrome (ARDS), which occurs in 5% of patients following HSCT, with a mortality >60%. As effective treatments for ARDS are lacking, developing new ways to prevent ARDS is likely to be more successful in improving patient outcomes. Two critical knowledge gaps make developing successful prevention strategies difficult: 1) an inability to reliably identify high-risk patients before ARDS has developed and; 2) an incomplete understanding of the mechanisms and subtypes of post-HSCT ARDS. The scientific objectives of this application are to address these critical knowledge gaps through the following Specific Aims: 1) Develop and validate a risk-prediction model incorporating pre-transplant, post-transplant and in- hospital risk factors that can help identify which patients are most likely to develop post-HSCT ARDS. 2) Prospectively evaluate metabolomics in patients at high-risk of developing post-HSCT ARDS and utilize clinical, biomarker and metabolomics data to explore endophenotypes of post-HSCT ARDS. Aim 1 leverages highly innovative data extraction techniques to develop a real-time continuous ARDS risk surveillance system for patients who undergo HSCT. Aim 2 evaluates the role of metabolomics, an emerging analytic tool, in advancing mechanistic understanding of why patients develop post-HSCT ARDS, as well as whether recently described ARDS endophenotypes can be identified post-HSCT ARDS. The applicant’s long-term goals are to: 1) become an independent translational clinician-scientist leading a multidisciplinary research team focused on improving outcomes of patients who develop respiratory complications after HSCT, and 2) develop effective strategies to prevent post-HSCT ARDS, one of the most significant post-transplant complications today. The training goals of the applicant are to develop advanced skills in statistics, biomedical modeling, machine learning, and metabolomics to facilitate these long-term goals. To address these training needs, the applicant has constructed a comprehensive career development plan that includes targeted didactic opportunities in the areas of training need above, with additional “hands-on” experience in all of these areas. The mentorship team and research environment is uniquely well suited to the applicant’s needs, combining expertise in critical care informatics and metabolomics at a high-volume academic transplant center. The proposal supports the NIH mission by striving to improve outcomes of patients who develop respiratory failure after transplantation, while training a junior investigator in the essential skills necessary for his transition to research independence.

项目摘要/摘要 造血干细胞移植(HSCT)为以下疾病提供了先进的治疗选择 否则就无法治愈。HSCT后肺部并发症是常见的，并严重损害其 总体成功率。最严重的是急性呼吸窘迫综合征(ARDS)， HSCT后5%的患者会发生这种情况，死亡率为60%。因为ARDS的有效治疗方法是 缺乏预防ARDS的新方法可能会更成功地改善患者的预后。 两个关键的知识差距使制定成功的预防战略变得困难：1)无法 在ARDS发生之前可靠地识别高危患者；2)对 HSCT后ARDS的机制和亚型。本申请的科学目标是解决 这些关键知识差距体现在以下具体目标上： 1)开发和验证风险预测模型，包括移植前、移植后和移植后- 医院风险因素，可帮助确定哪些患者最有可能发生HSCT后ARDS。 2)前瞻性评估HSCT后ARDS高危患者的代谢组学，并利用 临床、生物标记物和代谢组学数据，以探索HSCT后ARDS的内表型。 AIM 1利用高度创新的数据提取技术开发实时连续ARDS风险 对接受造血干细胞移植患者的监测系统。AIM 2评估代谢组学的作用，这是一种新兴的 分析工具，促进对患者为什么会发生HSCT后ARDS的机制理解，以及 最近描述的ARDS内表型是否可以在HSCT后ARDS中确定。 申请者的长期目标是：1)成为一名独立的翻译临床医生-科学家，领导 多学科研究团队专注于改善患有呼吸系统疾病的患者的预后 HSCT后的并发症，以及2)制定有效的策略来预防HSCT后ARDS，最 今天移植后的严重并发症。申请者的培训目标是发展先进的 统计学、生物医学建模、机器学习和代谢组学方面的技能，以促进这些长期目标。 为了满足这些培训需求，申请人构建了一个全面的职业发展计划， 在上述培训需求领域包括有针对性的授课机会，并提供额外的“实践” 在所有这些领域的经验。导师团队和研究环境非常适合 申请人的需求，大量结合重症监护信息学和代谢组学的专业知识 学术移植中心。该提案通过努力改善患者的预后来支持NIH的使命 他们在移植后出现呼吸衰竭，同时培训初级研究人员基本技能 对于他向研究独立的过渡来说是必要的。

项目成果

Characterization of Platelet Biologic Markers in the Early Pathogenesis of Postoperative Acute Respiratory Distress Syndrome.

• DOI: 10.1097/cce.0000000000000728
• 发表时间: 2022-07
• 期刊: Critical care explorations
• 作者: Yadav, Hemang;Meade, Laurie A.;Carter, Rickey E.;Knutson, Keith;Gajic, Ognjen;Kor, Daryl J.
• 通讯作者: Kor, Daryl J.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

造血干细胞移植后发生 ARDS 的移植后和院内危险因素。

• DOI: 10.4187/respcare.10224
• 发表时间: 2023
• 期刊: Respiratory care
• 影响因子: 2.5
• 作者: Herasevich,Svetlana;Frank,RyanD;Hogan,WilliamJ;Alkhateeb,Hassan;Limper,AndrewH;Gajic,Ognjen;Yadav,Hemang
• 通讯作者: Yadav,Hemang

Pulmonary function and long-term survival in patients with PERDS after autologous hematopoietic stem cell transplantation.

自体造血干细胞移植后 PERDS 患者的肺功能和长期生存。

• DOI: 10.1038/s41409-023-02101-5
• 发表时间: 2023
• 期刊: Bone marrow transplantation
• 影响因子: 4.8
• 作者: Zhang,Zhenmei;Wieruszewski,PatrickM;HefaziTorghabeh,Mehrdad;Hogan,WilliamJ;Yadav,Hemang
• 通讯作者: Yadav,Hemang

Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

全球肺功能倡议全球肺量测定参考方程在大型、多中心肺功能实验室人群中的应用。

• DOI: 10.1164/rccm.202303-0613oc
• 发表时间: 2024
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Kanj,AmjadN;Scanlon,PaulD;Yadav,Hemang;Smith,WilliamT;Herzog,TylerL;Bungum,Aaron;Poliszuk,Daniel;Fick,Edward;Lee,AugustineS;Niven,AlexanderS
• 通讯作者: Niven,AlexanderS

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

骨髓移植中的肺损伤预测模型：多中心队列研究。

• DOI: 10.1164/rccm.202308-1524oc
• 发表时间: 2024
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Herasevich,Svetlana;Schulte,PhillipJ;Hogan,WilliamJ;Alkhateeb,Hassan;Zhang,Zhenmei;White,BradleyA;Khera,Nandita;Roy,Vivek;Gajic,Ognjen;Yadav,Hemang
• 通讯作者: Yadav,Hemang