Novel Markers of Treatment Responsiveness for Pediatric Acute Asthma Exacerbations

小儿哮喘急性加重治疗反应性的新标志物

• 批准号: 10348963
• 负责人: Nidhya Navanandan
• 金额: $ 18.88万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348963
• 关键词: Accident and Emergency department; Accounting; Acute; Acute Respiratory Distress Syndrome; Address; Adrenal Cortex Hormones; Airway Resistance; Asthma; Automobile Driving; Biological; Biological Markers; Biological Response Modifier Therapy; Bronchodilator Agents; Caring; Child; Childhood; Childhood Asthma; Chronic; Clinical; Clinical Research; Development Plans; Effectiveness; Emergency Care; Emergency Medicine; Emergency department visit; Enrollment; Ensure; Epithelial Cells; Funding; Future; Goals; Home; Hospitalization; Individual; Infrastructure; Inhalation; Interferons; K-Series Research Career Programs; Knowledge; Laboratories; Laboratory Research; Lead; Leadership; Length of Stay; Measures; Mentors; Mentorship; Methods; Modeling; Molecular Genetics; Morbidity - disease rate; Nasal Epithelium; Nose; Oscillometry; Outcome; Outpatients; Physicians; Physiological; Positioning Attribute; Prediction of Response to Therapy; Predictive Analytics; Prospective Studies; Protocols documentation; Research; Research Methodology; Research Training; Resources; Scientist; Spirometry; Testing; Therapeutic Intervention; Time; Translational Research; Validation; Variant; Work; asthma exacerbation; career; career development; clinical practice; diagnostic biomarker; experience; feasibility trial; gene network; hospital readmission; improved; improved outcome; individualized medicine; innovation; mortality; multidisciplinary; novel; novel diagnostics; novel marker; pediatric emergency; personalized approach; predictive modeling; prospective; pulmonary function; response; skills; success; targeted treatment; therapy development; tool; transcriptome; transcriptome sequencing; transcriptomics; treatment response; treatment strategy; unnecessary treatment

PROJECT SUMMARY Acute asthma exacerbations are the primary cause of morbidity and mortality in children with asthma. Current treatment for acute asthma exacerbations in the pediatric Emergency Department (ED) follows an one- size-fits all approach including inhaled bronchodilators and systemic corticosteroids. However, treatment response to initial protocolized therapies is variable and unpredictable presenting a significant management challenge for ED clinicians. Unfortunately, the pathobiologic mechanisms driving treatment response remain unclear, and an effective method to predict treatment response does not exist. Thus, ED clinicians frequently struggle with treatment and disposition decisions leading to over-utilization of therapies, prolonged ED length of stay, and hospitalizations in responders, and delays in appropriate therapy for non-responders. The extensive variation and inefficiency in care highlights the critical need for tools to inform more precise and effective ED management strategies for acute asthma exacerbations. The nasal transcriptome and airway oscillometry (AOS) are novel biologic and physiologic markers with strong potential to address this unmet knowledge and practice gap. This proposal aims to apply an innovative biomarker-directed, individualized approach to ED asthma management by leveraging these novel markers to pursue the following specific aims: 1) determine the utility of AOS as an objective measure of ED treatment responsiveness; 2) identify airway endotypes of ED treatment responsiveness using nasal transcriptomics, and 3) derive and internally validate a clinical prediction rule incorporating biologic and physiologic markers to determine ED treatment responsiveness in children with acute asthma exacerbations. To achieve these aims, the candidate, Nidhya Navanandan, MD, will leverage an existing study infrastructure for enrolling children with acute asthma exacerbations in the ED, developed in conjunction with her mentors during her institutional career development award. As a pediatric emergency medicine physician, Dr. Navanandan is uniquely positioned to accomplish the proposed K23 research and training aims. Her long-term goal is to become an expert in clinical and translational research methods to improve the effectiveness of emergency care for pediatric asthma. Dr. Navanandan has developed a detailed career development plan consisting of mentorship, didactic coursework, and hands-on laboratory and research conduct experience in order to expand her knowledge and skills in leadership of prospective studies, discovery and application of novel markers for clinical practice, and predictive analytics. Dr. Navanandan has assembled a multidisciplinary team of mentors with extensive clinical and translational research experience and topical expertise in the above realms to ensure her success in achieving the stated specific aims and career goals. This proposal will allow Dr. Navanandan to transition to an independent physician-scientist and prepare her for future R01-funding.

项目摘要 哮喘急性加重是哮喘儿童发病和死亡的主要原因。 目前儿科急诊科（艾德）对哮喘急性加重的治疗遵循一种单一的方法， 适合所有方法，包括吸入性支气管扩张剂和全身性皮质类固醇。然而，治疗 对初始方案治疗的反应是可变的和不可预测的，这是一个重要的管理方法。 对艾德临床医生的挑战。不幸的是，驱动治疗反应的病理生物学机制仍然存在， 不清楚，并且不存在预测治疗反应的有效方法。因此，艾德临床医生经常 难以做出治疗和处置决定，导致过度使用治疗，延长艾德持续时间 治疗有效者的住院时间和住院时间，以及治疗无效者的适当治疗延迟。的 护理中的广泛变化和低效率突出了对工具的迫切需要， 哮喘急性加重的有效艾德管理策略。鼻转录组和气道 骨密度测量（AOS）是一种新型的生物和生理标志物，具有很强的潜力来解决这一问题。 知识和实践差距。该提案旨在应用创新的生物标记指导，个性化 通过利用这些新的标志物来实现以下特定目标的艾德哮喘管理方法： 1)确定AOS作为艾德治疗反应性的客观指标的效用; 2）识别气道 使用鼻转录组学的艾德治疗反应性的内型，以及3）导出并内部验证 结合生物学和生理学标志物的临床预测规则以确定艾德治疗 哮喘急性发作儿童的反应性。为了实现这些目标， Navanandan博士将利用现有的研究基础设施招募急性哮喘儿童 艾德的病情恶化，在她的机构职业发展期间与她的导师一起发展 奖作为一名儿科急诊医生，Navanandan博士处于独特的地位，可以完成 提出了K23研究和培训目标。她的长期目标是成为一名临床专家， 转化研究方法，以提高儿童哮喘急诊护理的有效性。博士 Navanandan制定了一个详细的职业发展计划，包括指导，教学课程， 以及实践实验室和研究进行经验，以扩展她的知识和技能， 领导前瞻性研究，发现和应用新的标记物用于临床实践， 预测分析Navanandan博士组建了一个多学科的导师团队， 以及在上述领域的翻译研究经验和专题知识，以确保她在 实现既定的具体目标和职业目标。这一提议将使纳瓦南丹博士能够过渡到一个 独立的物理学家，科学家和准备她未来的R 01-资金。