Proteomics-Based Mapping of Bronchopulmonary Dysplasia-Associated Changes in Noninvasively Accessible Oral Secretions

Abstract

ObjectiveTo determine if oral secretions (OS) can be used as a non-invasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. Study DesignThis 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). ResultsIn 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 (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. ConclusionOS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization of at-risk infants for timely clinical trial enrollment with novel therapies.