The GOLD Study: Goal of Open Lung Ventilation in Donors
GOLD 研究:供体肺开放通气的目标
基本信息
- 批准号:9187048
- 负责人:
- 金额:$ 55.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-12-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:Acute Lung InjuryAcute respiratory failureAdult Respiratory Distress SyndromeAgonistAlbuterolAlveolarApoptosisAtelectasisBlindedBlood capillariesBody WeightBrain DeathBronchoalveolar LavageCASP3 geneCaliforniaCell CountClinicalClinical TrialsCollaborationsCritical IllnessDataDonor personElectronsEnrollmentEnvironmental air flowEpithelialEuropeanFailureFunctional disorderFundingGoalsHistologicHistologyHistopathologic GradeHumanHypoxemiaIL8 geneImmunoglobulin MIn Situ Nick-End LabelingInflammationInjuryInterleukin-6KidneyLeadLiquid substanceLiverLungLung TransplantationLung diseasesMeasuresMechanical VentilatorsMechanical ventilationMechanicsMediatingMicroscopicMolecularNebulizerOrgan DonorOutcomePARP9 genePatientsPermeabilityPeroxidasesPhysiologicalPlacebosPlasmaPositive-Pressure RespirationProteinsProtocols documentationPublishingPulmonary EdemaPulmonary Surfactant-Associated Protein DRandomized Clinical TrialsResearch DesignResearch InfrastructureResearch PersonnelResourcesRespiratory physiologyRiskSeveritiesStainsTestingThoracic RadiographyTidal VolumeTransplantationTumor Necrosis Factor Ligand Superfamily Member 6United StatesUnited States National Institutes of HealthVentilatorWait TimeWeightbaseimprovedimproved outcomeindexinglung injurymortalitynovelprospective testprotective effectpublic health relevancerandomized trialrecruittranslational study
项目摘要
DESCRIPTION (provided by applicant): Despite liver and kidney utilization rates in the 80-90% range, the donor lung utilization rate for transplantation in the United States is approximately 20%, and the demand for donor lungs far exceeds the supply. This donor lung shortage leads to long waiting times for lung transplantation and a high mortality in patients awaiting lung transplantation. The most common reason for failure to utilize donor lungs for transplantation is donor hypoxemia and pulmonary infiltrates. Although brain dead organ donors are universally mechanically ventilated, the potential contribution of the mode of mechanical ventilation to donor lung dysfunction has not been adequately studied and the choice of ventilator settings during management of the brain dead organ donor is largely empiric. In our recently completed randomized clinical trial of nebulized albuterol versus placebo in 506 organ donors, the extent of radiographic lung atelectasis was a major predictor of poor donor oxygenation and lower rates of lung utilization. An open lung protective ventilator (OLPV) that aims to reduce atelectasis by maximizing lung recruitment while minimizing lung injury has improved outcomes in other clinical settings including patients with and at risk for acute lung injury and in a small study in European organ donors. However, most U.S. organ donors are still ventilated with a conventional ventilation strategy with low levels of positive end-expiratory pressure (PEEP) and higher tidal volumes. Therefore, we propose to prospectively test the hypothesis that ventilation of organ donors with an OLPV strategy during the donor management period will improve donor lung utilization and oxygenation compared to a conventional higher tidal volume and lower PEEP strategy and to investigate the cellular and molecular mechanisms of human ventilator-associated lung injury. In Aim 1, we will test the effect of an OLPV strategy compared to a conventional ventilator strategy on donor lung utilization, donor oxygenation, atelectasis and recipient outcomes in a randomized clinical trial i 400 donors managed by the California Transplant Donor Network. In translational studies in Aim 2, we will test the effect of an OLPV strategy on lung injury in the excised human lung as measured by (1) alveolar- capillary barrier permeability to protein, (2) the extent of pulmonary edema, (3) histologic grading and (4) also determine whether the protective effects of OLPV are mediated through reductions in lung epithelial injury and apoptosis. Completion of the clinical trial in Aim 1 will have a high impact, providing significant new information that could transform donor management in the United States and lead to increased rates of donor lung utilization, decreased wait times for lung transplantation, and reduced mortality while awaiting lung transplantation. The proposed studies build on the comprehensive and unique infrastructure for donor clinical trials that our team of investigators has developed in collaboration with the California Transplant Donor Network. The proposed studies in Aim 2 will further enhance the impact of the proposed studies by studying the mechanisms of the protective effect of OLPV in large numbers of excised human lungs, a novel resource.
描述(由申请人提供):尽管肝脏和肾脏的利用率在80-90%的范围内,但在美国用于移植的供体肺利用率约为20%,对供体肺的需求远远超过供应。这种供体肺短缺导致肺移植等待时间长,等待肺移植的患者死亡率高。供肺移植失败的最常见原因是供肺低氧血症和肺浸润。尽管脑死亡器官供体普遍采用机械通气,但机械通气模式对供体肺功能障碍的潜在影响尚未得到充分研究,并且在脑死亡器官供体的管理过程中呼吸机设置的选择主要是经验性的。在我们最近完成的506例器官捐献者雾化沙丁胺醇与安慰剂的随机临床试验中,放射学肺不张的程度是供体氧合不良和肺利用率较低的主要预测因素。开放式肺保护性呼吸机(OLPV)旨在通过最大限度地增加肺复张同时最大限度地减少肺损伤来减少肺不张,在其他临床环境中(包括急性肺损伤患者和有急性肺损伤风险的患者)以及在欧洲器官捐献者中进行的一项小型研究中改善了结局。然而,大多数美国器官捐献者仍然采用传统的通气策略,低水平的呼气末正压(PEEP)和较高的潮气量。因此,我们建议前瞻性地测试这样的假设:与传统的更高潮气量和更低PEEP策略相比,在供体管理期间采用OLPV策略对器官供体进行通气将改善供体肺的利用和氧合,并研究人类呼吸机相关肺损伤的细胞和分子机制。在目标1中,我们将在加州移植供体网络管理的400名供体中进行随机临床试验,以测试OLPV策略与传统呼吸机策略相比对供体肺利用、供体氧合、肺不张和受体结局的影响。在目标2的转化研究中,我们将测试OLPV策略对离体人肺中肺损伤的影响,如通过(1)肺泡-毛细血管屏障对蛋白质的渗透性,(2)肺水肿的程度,(3)组织学分级和(4)确定OLPV的保护作用是否通过减少肺上皮损伤和细胞凋亡介导。Aim 1临床试验的完成将产生很大的影响,提供重要的新信息,可以改变美国的供体管理,提高供体肺的利用率,减少肺移植的等待时间,降低等待肺移植的死亡率。拟议的研究建立在我们的研究团队与加州移植供体网络合作开发的供体临床试验的全面和独特的基础设施上。目标2中的拟议研究将通过研究OLPV在大量离体人肺(一种新资源)中的保护作用机制,进一步增强拟议研究的影响。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Lorraine B Ware其他文献
The role of red blood cells and cell-free hemoglobin in the pathogenesis of ARDS
- DOI:
10.1186/s40560-015-0086-3 - 发表时间:
2015-06-17 - 期刊:
- 影响因子:4.700
- 作者:
David R Janz;Lorraine B Ware - 通讯作者:
Lorraine B Ware
Can nicotine treat sepsis?
尼古丁可以治疗败血症吗?
- DOI:
10.1038/nm1104-1161 - 发表时间:
2004-11-01 - 期刊:
- 影响因子:50.000
- 作者:
Michael A Matthay;Lorraine B Ware - 通讯作者:
Lorraine B Ware
Lorraine B Ware的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Lorraine B Ware', 18)}}的其他基金
The MUltidimenSional phenotyping In Critical care (MUSIC) Consortium: A pathway to precision medicine at the bedside
重症监护 (MUSIC) 多维度表型分析联盟:床边精准医疗的途径
- 批准号:
10649995 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Mechanisms of organ dysfunction and recovery in the Acetaminophen and Ascorbate Trial in Sepsis
对乙酰氨基酚和抗坏血酸脓毒症试验中器官功能障碍和恢复的机制
- 批准号:
10502613 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别:
Peri-operative factors that drive cell-free hemoglobin-mediated primary graft dysfunction
驱动无细胞血红蛋白介导的原发性移植物功能障碍的围手术期因素
- 批准号:
10677593 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别:
Mechanisms of organ dysfunction and recovery in the Acetaminophen and Ascorbate Trial in Sepsis
对乙酰氨基酚和抗坏血酸脓毒症试验中器官功能障碍和恢复的机制
- 批准号:
10644023 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别:
Peri-operative factors that drive cell-free hemoglobin-mediated primary graft dysfunction
驱动无细胞血红蛋白介导的原发性移植物功能障碍的围手术期因素
- 批准号:
10431493 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别:
Haptoglobin 2 variant and endothelial glycocalyx shedding in sepsis-induced ARDS
脓毒症诱导的 ARDS 中结合珠蛋白 2 变异和内皮糖萼脱落
- 批准号:
10473750 - 财政年份:2021
- 资助金额:
$ 55.24万 - 项目类别:
Haptoglobin 2 variant and endothelial glycocalyx shedding in sepsis-induced ARDS
脓毒症诱导的 ARDS 中结合珠蛋白 2 变异和内皮糖萼脱落
- 批准号:
10277280 - 财政年份:2021
- 资助金额:
$ 55.24万 - 项目类别:
Haptoglobin 2 variant and endothelial glycocalyx shedding in sepsis-induced ARDS
脓毒症诱导的 ARDS 中结合珠蛋白 2 变异和内皮糖萼脱落
- 批准号:
10686129 - 财政年份:2021
- 资助金额:
$ 55.24万 - 项目类别:
Inflammatory and epithelial injury markers for ARDS prognosis:A validation study
ARDS 预后的炎症和上皮损伤标志物:一项验证研究
- 批准号:
8262086 - 财政年份:2012
- 资助金额:
$ 55.24万 - 项目类别:
Inflammatory and epithelial injury markers for ARDS prognosis:A validation study
ARDS 预后的炎症和上皮损伤标志物:一项验证研究
- 批准号:
8466368 - 财政年份:2012
- 资助金额:
$ 55.24万 - 项目类别:
相似海外基金
Novel Digital Methods to Evaluate Functional and Pulmonary Outcomes following Pediatric Acute Respiratory Failure
评估小儿急性呼吸衰竭后功能和肺部结果的新型数字方法
- 批准号:
10724042 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Optimizing Time-Limited Trials of Mechanical Ventilation in Acute Respiratory Failure: A Mixed Methods Observational Study
优化急性呼吸衰竭机械通气的限时试验:混合方法观察研究
- 批准号:
10633823 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Use of Inter-Hospital Transfer Services in Critical Illness and Acute Respiratory Failure
在危重疾病和急性呼吸衰竭中使用医院间转运服务
- 批准号:
10739060 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Strengthening implementation science in Acute Respiratory Failure using multilevel analysis of existing data
利用现有数据的多级分析加强急性呼吸衰竭的实施科学
- 批准号:
10731311 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Identifying patient subgroups and processes of care that cause outcome differences following ICU vs. ward triage among patients with acute respiratory failure and sepsis
确定急性呼吸衰竭和脓毒症患者在 ICU 与病房分诊后导致结局差异的患者亚组和护理流程
- 批准号:
10734357 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Temporal trends in quality indicators of palliative care for patients with chronic illness hospitalized with acute respiratory failure
因急性呼吸衰竭住院的慢性病患者姑息治疗质量指标的时间趋势
- 批准号:
10622756 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Health expectations after acute respiratory failure in survivor-care partner dyads
幸存者护理伙伴二人组急性呼吸衰竭后的健康期望
- 批准号:
10732929 - 财政年份:2023
- 资助金额:
$ 55.24万 - 项目类别:
Association of patient characteristics and antibiotic timing with the development of acute respiratory failure in hospital-acquired sepsis
患者特征和抗生素使用时机与医院获得性脓毒症急性呼吸衰竭发展的关系
- 批准号:
10313769 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别:
Financial Hardship among Patients with Acute Respiratory Failure and their Family Member Caregivers: Understanding the Impact on Patient- and Family- Centered Outcomes
急性呼吸衰竭患者及其家庭成员护理人员的经济困难:了解对以患者和家庭为中心的结果的影响
- 批准号:
10413457 - 财政年份:2022
- 资助金额:
$ 55.24万 - 项目类别: