Noninvasive Biomarker Discovery for Bronchopulmonary Dysplasia (BPD)

Objective: To determine if oral secretions (OS) can be used in lieu of tracheal aspirates (TA), as a non-invasively collected body fluid, to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. Study Design: This was a retrospective, single-center cohort study that included data and convenience samples from week-of-life (WoL) 3 from two independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatology Intensive Care Unit (NICU) (Cohort 1; N=23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; N=17 infants including 8 with BPD). Results: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (e.g., SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. Conclusion: OS is a noninvasive, easily accessible alternative to TA, that is amenable to high-throughput proteomic analysis in preterm newborns. Additionally, OS samples can yield actionable biomarkers of BPD development and allow for timely, individualized treatment of at-risk infants.