The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Erik A. Jensen, MD, MSCE, Instructor of Pediatrics at the University of Pennsylvania and the Children's Hospital of Philadelphia with the mentorship, training, and research experience needed to become an independent clinician scientist and leader in neonatal lung disease research. His long-term career goal is to reduce the burden of bronchopulmonary dysplasia (BPD) through novel translational studies and large scale, multi-center clinical trials of promising new therapies. His immediate goal is to acquire the skills needed to direct a research program studying the airway microbiome in extremely preterm infants. To achieve these goals and transition to independence, Dr. Jensen and his mentors developed a comprehensive career development plan based on: (1) intensive mentorship from a team with whom he has a proven track record of collaboration; (2) in-depth hands on and didactic training in microbiome research methods; and (3) an innovative research plan to describe the role of the airway microbiome in the development of BPD. BPD is among the most devastating complications of preterm birth. It affects half of surviving extremely preterm infants, is associated with enduring deficits in health and cognition, and carries an enormous societal burden and cost. Unfortunately, BPD rates are not improving and few safe, preventative therapies exist. Novel research paradigms in BPD are needed to enable discovery of new, evidence based approaches to BPD prevention. The neonatal airway microbiome holds significant promise as a potential therapeutic target. Modern molecular assays demonstrate that pathologic alterations (dysbiosis) in the microbial communities in the airway are associated with chronic inflammation and lung injury in older children and adults. Gastro- esophageal reflux (GER) related microaspiration is one potential contributor to airway dysbiosis in chronic respiratory disease. Moreover, recent evidence suggests that amelioration of GER related microaspiration may improve lung function by restoring normal airway flora. Whether airway microbial dysbiosis contributes to the development of BPD is a pressing, unanswered question. Dr. Jensen's research proposal will address this knowledge gap by (1) identifying patterns in the upper and lower respiratory tract microbiota associated with increased lung inflammation and the development of BPD in extremely preterm infants and (2) characterizing the potential association between microbial dysbiosis in the preterm lung and GER related microaspiration. Dr. Jensen's K23 studies will produce novel insights into the pathophysiology of BPD that will directly inform his future R01 proposals aimed at preventing neonatal lung injury. His career development plan outlines a clear path to gain the knowledge, skills, and experience needed to become an independent clinician scientist, leader, and innovator in neonatal lung disease research.
Infant chronic lung disease, or bronchopulmonary dysplasia (BPD), affects 50% of surviving extremely preterm infants and results in enduring cardiorespiratory and neurodevelopmental disability. Pathologic alteration in the airway microbiome mediates chronic lung injury in older children and adults but has been inadequately studied as a potential contributor to BPD. This proposal seeks to (1) determine whether imbalance in the airway microbiome in extremely preterm infants is associated with lung inflammation and the development of BPD and (2) characterize patterns in the airway microbiome associated with greater severity of gastroesophageal reflux related microaspiration (a risk factor for BPD in infants and lung microbial dysbiosis in older children and adults).