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.

项目总结