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.