The Host Response to Calfactant for Direct Acute Lung Injury in Critically Ill Ch

危重患者对 Calfactant 直接急性肺损伤的宿主反应

基本信息

批准号：
7648199
负责人：
DEREK S WHEELER
金额：
$ 7.5万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7648199
关键词：
Acute Acute Lung Injury Acute respiratory failure Address Adult Adult Respiratory Distress Syndrome Affect Animal Model Anti-Inflammatory Agents Anti-inflammatory Area Aspiration Pneumonia Basic Science Blinded Breathing Bronchoalveolar Lavage Fluid Child Childhood Clinical Clinical Data Clinical Investigator Clinical Research Clinical Treatment Communities Critical Care Critical Illness Critically ill children Data Databases Disease Enrollment Foundations Functional disorder Funding Future Gene Expression Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Goals Human Immune response In Vitro Infasurf Inflammatory Length of Stay Lung Mechanics Morbidity - disease rate Patients Placebo Control Play Pneumonia Pre-Clinical Model Preparation Process Proteins Pulmonary Surfactants Randomized Research Resources Respiratory physiology Risk Role Sampling Secondary to Sepsis Serum Surface Tension Testing Trauma Ventilator acute pancreatitis animal data base calfactant genetic variant improved in vivo lung injury mortality open label placebo controlled study prospective response smoke inhalation success surfactant translational study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Acute respiratory failure due to acute parenchymal lung injury (acute lung injury/acute respiratory distress syndrome or ALI/ARDS) is a common problem in both adult and pediatric critical care and is associated with significant morbidity and mortality. Human and animal data support the role of surfactant dysfunction in the disturbed lung function of ALI/ARDS and a variety of animal models have shown significant improvement with administration of exogenous surfactant. However, not all critically ill patients with ALI/ARDS respond positively to surfactant replacement. For example, post-hoc analyses suggest that patients with direct ALI/ARDS (e.g. ALI/ARDS secondary pneumonia, aspiration, smoke inhalation, etc) respond better to surfactant replacement compared to patients with indirect ALI/ARDS (e.g. ALI/ARDS secondary to sepsis, acute pancreatitis, trauma, etc). In addition, several gene polymorphisms associated with ALI/ARDS have been described which may alter the host response to surfactant administration. Surfactant functions to decrease surface tension during normal tidal breathing and is an integral part of the innate lung defense. The improvement in lung mechanics and oxygenation following surfactant administration has been associated with improved survival in critically ill children with ALI/ARDS, though other factors may play a role as well. For example, surfactant has been shown to directly inhibit pro-inflammatory gene expression in vitro and in vivo. However, clinical studies demonstrating these anti-inflammatory effects in critically ill patients are notably lacking. The goals of the current proposal therefore are to (1) further elucidate the mechanisms by which calfactant administration improves survival and (2) determine what genetic factor(s) are associated with a clinical response to calfactant administration in critically ill children with ALI/ARDS. Acute respiratory failure due to acute parenchymal lung injury (acute lung injury/acute respiratory distress syndrome or ALI/ARDS) is a common problem in both adult and pediatric critical care and is associated with significant morbidity and mortality. While there is evidence to suggest that surfactant administration improves oxygenation in critically ill children with so-called "direct" ALI/ARDS (e.g. due to pneumonia or smoke inhalation), not all critically ill patients with ALI/ARDS respond positively to surfactant replacement. Our goal is to determine the genetic factors that may alter the response to surfactant in patients with direct lung injury.

描述（由申请人提供）：由于急性实质性肺损伤（急性肺损伤/急性呼吸窘迫综合征或ALI/ARDS）引起的急性呼吸衰竭是成人和儿科重症监护的常见问题，并且与显着的发病率和死亡率有关。人类和动物数据支持表面活性剂功能障碍在ALI/ARDS受干扰的肺功能中的作用，各种动物模型已显示出外源表面活性剂的给药显着改善。但是，并非所有患有ALI/ARD的重症患者对表面活性剂的置换做出积极反应。例如，事后分析表明，与间接ALI/ARD的患者相比，直接ALI/ARD的患者（例如ALI/ARDS继发性肺炎，抽吸，烟雾吸入等）对表面活性剂的替代反应较好（例如，Ali/Ards septary to septary to septary to sepration to sepsis to sepsis sepsis，Sepsis，Sepsis，Sepsis，separe pancreatiation，trauma，trauma）。此外，已经描述了与ALI/ARD相关的几种基因多态性，这些基因可能会改变宿主对表面活性剂给药的反应。表面活性剂功能可在正常的潮汐呼吸过程中降低表面张力，并且是先天肺防御的组成部分。施用表面活性剂后的肺力学和氧合的改善与患有ALI/ARDS的重症儿童的生存率提高有关，尽管其他因素也可能起作用。例如，表面活性剂已被证明可以直接抑制体外和体内促炎基因表达。但是，明显缺乏对重症患者的这些抗炎作用的临床研究。因此，当前建议的目标是（1）进一步阐明钙活性剂施用改善生存的机制，以及（2）确定哪种遗传因素与患有ALI/ARDS的严重患病儿童的临床反应有关。急性实质性肺损伤引起的急性呼吸衰竭（急性肺损伤/急性呼吸窘迫综合征或ALI/ARDS）在成人和小儿重症监护术中都是一个常见的问题，并且与显着的发病率和死亡率有关。虽然有证据表明，表面活性剂的给药可改善患有危重儿童的“直接” ALI/ARDS（例如，由于肺炎或烟雾吸入）的氧合作用，但并非所有患有ALI/ARD的重症患者对表面活性剂替代的抗反应良好。我们的目标是确定可能改变直接肺损伤患者表面活性剂反应的遗传因素。