Infants born prematurely are at risk for bronchopulmonary dysplasia, which is defined as a requirement for ventilatory support at 36 wk post-menstrual age, and for later respiratory disorders including asthma. Chronic lung disease remains the major cause of morbidity among premature infants despite current approaches to both prevention and intensive care support. This proposal responds to RFA-HL-15-025 and the request to leverage longitudinal cohorts to generate clinical, physiologic, biological, and/or genomic data that can define chronic lung disease(s). We will use 2 recent discovery/validation cohorts of well- phenotyped, extremely premature infants with biospecimen repositories of tracheal aspirate, urine and DNA to examine associations of proteomic findings with longitudinal measures of pulmonary outcome. The Trial Of Late SURFactant (TOLSURF) study was an interventional trial conducted in 25 US hospitals with follow- up of 511 infants through 24 months. The Prematurity and Respiratory Outcomes Project (PROP) enrolled 835 premature infants at 13 centers to investigate molecular mechanisms that contribute to risk for continuing respiratory disease. The overall hypothesis of this project is that altered amounts of specific proteins in lung lining fluid and/or urine of premature infants, reflecting both the developmental stage and response to lung injury, are associated with adverse pulmonary outcome.
The first aim uses a global proteomic approach plus immunoassays to identify and validate proteins in neonatal lung fluid that are biomarkers for adverse pulmonary outcome.
The second aim will Identify and validate urinary proteins associated with first-year respiratory morbidity. Statistica power is increased by the use of an extreme phenotype approach---infants with no lung disease in the first year versus those with disease in each quarter. The post-discharge assessment provides a more clinically meaningful outcome measure compared to 36 wk (preterm) pulmonary status. The studies will provide the first proteomic profile of lung fluid and urine in well-phenotyped infants and identify biomarkers for persistent lung disease of infants, with the potential to enhance understanding of mechanisms and to develop preventative strategies.
This project uses high resolution studies of lung proteins to investigate causes of breathing disorders in infants who were born prematurely. The results will identify new markers of disease susceptibility and provide insights for development of new treatments to prevent lung disease in infants and children.
| Ballard, Philip L (2017) Commentary on the identity of fibroblast pneumocyte factor: rat vs. human. Pediatr Res 82:4-5 |
| Barrette, Anne Marie; Roberts, Jessica K; Chapin, Cheryl et al. (2016) Antiinflammatory Effects of Budesonide in Human Fetal Lung. Am J Respir Cell Mol Biol 55:623-632 |
