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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