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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

基本信息

批准号：
10850297
负责人：
Nidhya Navanandan
金额：
$ 7.56万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10850297
关键词：
Acceleration 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 Genes Goals Home Hospitalization Individual Infrastructure Inhalation Institution Interferons K-Series Research Career Programs Knowledge Laboratories Lead Leadership Length of Stay Measures Mentors Mentorship Methods Modeling Molecular Genetics Morbidity - disease rate Nasal Epithelium Nose Oscillometry Outcome Outpatients Parents Physicians Physiological Positioning Attribute Prediction of Response to Therapy Predictive Analytics Prospective Studies Research Research Methodology Resources Scientist Spirometry Testing Therapeutic Intervention Time Training Translational Research Validation Variant Work asthma exacerbation career career development clinical practice clinical predictive model clinical predictors diagnostic biomarker experience feasibility trial 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

项目摘要

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 clinical and historical factors, and 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.

项目总结急性哮喘加重是哮喘儿童发病和死亡的主要原因。儿科急诊科目前对哮喘急性加重的治疗遵循一种方法- 适用于所有方法，包括吸入支气管扩张剂和全身皮质类固醇。然而，治疗对最初的程序化治疗的反应是可变的和不可预测的，呈现出重要的管理急诊临床医生面临的挑战。不幸的是，驱动治疗反应的病理生物学机制仍然存在。尚不清楚，目前还不存在预测治疗反应的有效方法。因此，急诊科临床医生经常与治疗和处置决定作斗争，导致过度使用治疗，延长ED长度应答者的住院时间、住院时间和无应答者的适当治疗延误。这个护理方面的广泛差异和低效突出了对工具的迫切需要，以提供更准确和急性哮喘急性发作的有效急诊急救管理策略。鼻腔转录组与呼吸道振荡计量学(AOS)是一种新的生物学和生理学标记，具有很强的解决这一问题的潜力知识与实践的鸿沟。这项提案旨在应用一种创新的生物标记物--定向的、个性化的通过利用这些新的标记物来实现以下具体目标的ED哮喘管理方法： 1)确定AOS作为ED治疗反应性的客观衡量标准的有效性；2)识别呼吸道使用鼻部转录组分析ED治疗反应性的内型，以及3)派生和内部验证结合临床和历史因素以及生物和生理标志物的临床预测规则测定急性哮喘急性发作患儿的ED治疗反应性。为了实现这些目标，候选人Nidhya Navananda，医学博士，将利用现有的研究基础设施招收患有急诊室的急性哮喘恶化，在她的机构期间与她的导师一起发展职业发展奖。作为一名儿科急救内科医生，纳瓦南丹医生是独一无二的能够完成拟议的K23研究和培训目标。她的长期目标是成为一名临床和转化性研究方法专家，以提高急救护理的有效性儿童哮喘。纳瓦南丹博士制定了一项详细的职业发展计划，包括指导、讲授课程、动手实验室和研究指导经验，以扩大她在领导前瞻性研究、发现和应用新标记物方面的知识和技能临床实践和预测分析。纳瓦南丹博士组建了一个多学科的导师团队在上述领域拥有丰富的临床和翻译研究经验和专题专业知识确保她成功实现所述的具体目标和职业目标。这项提案将允许Dr。纳万丹过渡到一名独立的内科科学家，并为她未来的R01-资金做好准备。