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 急性哮喘加剧是哮喘儿童发病和死亡率的主要原因。 小儿急诊室（ED）的急性哮喘患病的当前治疗 尺寸适合所有方法，包括吸入支气管扩张剂和全身性皮质类固醇。但是，治疗 对初始协议疗法的反应是可变且不可预测的，表现出重要的管理 ED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 不清楚，一种预测治疗反应的有效方法是不存在的。因此，ED临床医生经常 与治疗和处置决定斗争，导致疗法过度利用，长期长度 住院和响应者住院治疗，并延迟了对非反应者的适当疗法。这 经过广泛的差异和护理效率低下，强调了对工具的迫切需求，以便更确切地告知和 急性哮喘加重的有效管理策略。鼻记录组和气道 振荡学（AOS）是新型的生物学和生理标记物，具有强大的潜力来解决这种未经元素 知识和实践差距。该建议旨在应用创新的生物标志物指导的个性化 通过利用这些新颖的标记来追求以下特定目的，进行ED哮喘管理的方法： 1）确定AOS作为ED治疗响应的客观度量的实用性； 2）识别气道 使用鼻腔转录组学的ED治疗反应能力的内型，3）得出和内部验证A 纳入生物学和生理标记以确定ED治疗的临床预测规则 患有急性哮喘患儿童的反应能力。为了实现这些目标，候选人Nidhya 马里兰州纳瓦南丹（Navanandan），将利用现有的研究基础设施来招募急性哮喘儿童 在机构职业发展期间，与她的导师一起开发了ED的加剧 奖。作为一名儿科急诊医学医师，纳瓦南丹博士拥有独特的位置 拟议的K23研究和培训目的。她的长期目标是成为临床专家 转化研究方法是提高小儿哮喘的急诊有效性。博士 纳瓦南丹制定了一项详细的职业发展计划，包括指导，教学课程， 以及动手实验室和研究行为经验，以扩大她的知识和技能 对前瞻性研究，新颖标志物进行临床实践的领导，以及 预测分析。纳瓦南丹博士已经通过广泛的临床组成了一个多学科的导师团队 以及上述领域的翻译研究经验和局部专业知识，以确保她成功 实现既定的目的和职业目标。该建议将允许纳瓦南丹博士过渡到 独立的医师科学家，并为她准备未来的R01资金。