Biomarker Discovery for Bronchopulmonary Dysplasia Using Mass Spectrometry Based Urine Proteomics

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disorder that primarily affects premature infants. BPD commonly begins as respiratory distress syndrome (RDS) and progresses to BPD when respiratory complications persist past the original due date of the infant. BPD can last for years depending on the severity, with respiratory complications seen into adulthood for a subset of cases. To ensure the best possible health outcome, it is imperative to identify the premature infants at risk for BPD as early as possible. Given the fragility of these premature infants and the limited availability and invasive extraction of blood, I investigated the use of urine for the discovery of biomarker candidates for BPD. These samples were uniquely collected by inserting cotton balls into the diapers of these premature infants. Using less than 150 ul of urine per sample, I employed data dependent and data independent acquisition LC/MS methods to perform high throughput urine proteomics on premature infants with and without BPD. I identified several urinary proteins that show altered abundance levels in the severe BPD population. Interestingly, many of these proteins have been described before in the context of BPD, though not as urinary proteins. The identified proteins potentially point to prognostic markers to identify infants at risk of BPD and ultimately to develop novel targeted therapeutics for prevention and treatment of BPD.