Project Grant K23HL189017

The National Institutes of Health National Heart, Lung, and Blood Institute awarded The Children's Hospital of Philadelphia $360,418 on August 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop integrated host-microbe classifiers for diagnosing lower respiratory tract infection in children using metagenomic next-generation sequencing applied to non-invasive samples including nasopharyngeal swabs and whole blood.

The project addresses diagnostic gaps in pediatric lower respiratory tract infection, where pathogen identification remains rare despite the condition causing more deaths annually than any other infection type and disproportionately affecting children. Current clinical microbiologic tests have significant limitations, and difficulty obtaining samples from the infection site drives inappropriate antimicrobial use and adverse outcomes. The research leverages an established prospective multicenter cohort actively enrolling critically ill children with acute respiratory failure requiring mechanical ventilation. The three project aims include developing and testing classifiers to accurately diagnose and differentiate lower respiratory tract infection from non-infectious acute respiratory failure; developing classifiers in children with clinically adjudicated lower respiratory tract infection to rule out bacterial causes; and validating performance in a prospective validation cohort. The work simultaneously profiles pathogen and host response elements from non-invasive samples, addressing the clinical diagnostic complexity created by overlap between viral lower respiratory tract infection, viral-bacterial co-infection, and non-infectious inflammatory respiratory syndromes.

Period of performance runs through July 31, 2031. Work is performed in Philadelphia, Pennsylvania.