This Mentored-Patient Oriented Research Career proposal will provide decisive clinical research experience in a supportive and mentored environment. The candidate is fully committed to neonatal clinical research and will benefit both from superior senior mentorship and the outstanding research resources at Duke University. Approximately 80% of infants weighing less than 1000 grams at birth require intubation and about 30% of the survivors develop bronchopulmonary dysplasia (BPD). Although lifesaving, neonatal mechanical ventilation is associated with severe morbidities including BPD, nosocomial infection, subglottic injury, tracheomalacia, multi-organ failure, altered immune response, respiratory muscle atrophy, and poor growth in extremely premature infants. Mechanical ventilation is also an important determinant of NICU resource use, accounting for 29% of the variance in neonatal intensive care ancillary costs. Neonatal extubation is usually decided based on a poorly defined combination of clinical criteria, radiological findings, and blood gases. This approach has not been particularly successful. Prior analyses reveal that approximately 66% of infants less than 800 grams fail extubation. Extubation failure has a significant independent association with increased risk of death and nosocomial infection. In older children, mortality was significantly higher among patients who required reintubation when compared with successfully extubated patients. There is lack of equivalent data available in neonates. The current proposal focuses on the weaning from mechanical ventilation and extubation of very low birth weight (VLBW) premature infants. First, it will identify and validate physiologic weaning parameters associated with successful extubation of VLBW infants. Subsequently, we will determine the effect of identifying VLBW infants capable of breathing spontaneously on the duration of mechanical ventilation and associated morbidities. This work is a natural extension of the candidate's prior research experience in neonatal pulmonary failure and mechanical ventilation, now focused on weaning, and will provide essential clinical information for the successful and safe discontinuation of mechanical ventilation in premature newborns. Furthermore, this career development proposal will be crucial to promote the candidate's clinical research career development leading to complete independence as an outstanding clinical investigator.
