AIMS: The hypothesis of this study is that BPD is the result of injury and abnormal repair to an immature lung. We hypothesize that factors involved in the pathogenesis of BPD include abnormalities (congenital or acquired) of the surfactant proteins, oxidative stress, inflammation and cell migration, changes in insulin-like growth factors (IGF's) and elastin components of connective tissue, and pulmonary hypertension with vascular remodeling.
AIM 1 : To create a Clinical Sample Bank of neonates with lung disease, some of whom will progress to the development of BPD, with a broad clinical database and biostatistical support, to allow basic science investigators in the SCOR project to test hypotheses regarding the pathogenesis of BPD.
AIM 2 : To determine whether a developmental deficiency of surfactant protein-B (SP-B) contributes to the occurrence of respiratory distress and BPD, and to study metabolic abnormalities associated with inherited deficiency of SP-B.
AIM 3 : To determine whether plasma nitrotyrosine levels, a marker of peroxynitrite mediated oxidant stress, are elevated in premature infants who develop BPD.
AIM 4 : To measure the temporal changes in critical components of the inflammatory process (cell composition, inducible nitric oxide synthase (iNOS), hyaluronan (HA), and Receptor for HA-mediated mobility (RHAMM), and selected cytokines) in bronchoalveolar lavage (BAL), blood, and urine samples obtained from intubated infants with lung disease, and to correlate these changes with their clinical course.
AIM 5 : To examine changes in the IGF axis that occurs in lungs of infants with RDS and BPD.
AIM 6 : To determine whether there is a relationship between degradation of elastin, as determined by assay of elastin-derived peptides in BAL samples, and the clinical course of BPD.
AIM 7 : To determine whether the normal fall in plasma endothelin-1 concentrations after birth are delayed in infants with RDS and BPD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
3M01RR000240-35S1
Application #
6264758
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
35
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L et al. (2017) Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nat Commun 8:121
Agopian, A J; Goldmuntz, Elizabeth; Hakonarson, Hakon et al. (2017) Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects. Circ Cardiovasc Genet 10:e001449
Ruan, Alexandra; Tobin, Nicole H; Mulligan, Kathleen et al. (2016) Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021. J Acquir Immune Defic Syndr 72:372-5
Medoff-Cooper, Barbara; Irving, Sharon Y; Hanlon, Alexandra L et al. (2016) The Association among Feeding Mode, Growth, and Developmental Outcomes in Infants with Complex Congenital Heart Disease at 6 and 12 Months of Age. J Pediatr 169:154-9.e1
Ollberding, Nicholas J; Gilsanz, Vicente; Lappe, Joan M et al. (2015) Reproducibility and intermethod reliability of a calcium food frequency questionnaire for use in Hispanic, non-Hispanic Black, and non-Hispanic White youth. J Acad Nutr Diet 115:519-27.e2
Medina-Gómez, Carolina; Chesi, Alessandra; Heppe, Denise H M et al. (2015) BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures. Mol Biol Evol 32:2961-72
Avitabile, Catherine M; Goldberg, David J; Zemel, Babette S et al. (2015) Deficits in bone density and structure in children and young adults following Fontan palliation. Bone 77:12-6
Rutstein, Richard M; Samson, Pearl; Fenton, Terry et al. (2015) Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: the Pediatric AIDS Clinical Trials Group Protocol 1020A. Pediatr Infect Dis J 34:162-7
Trabulsi, Jillian C; Irving, S Y; Papas, M A et al. (2015) Total Energy Expenditure of Infants with Congenital Heart Disease Who Have Undergone Surgical Intervention. Pediatr Cardiol 36:1670-9
Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente et al. (2015) The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res 30:156-64

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