Bronchopulmonary dysplasia (BPD) results from disrupted lung development after premature birth and results in life long pulmonary morbidity. Intrauterine and postnatal lung inflammation contribute to structural airway simplification and increased pulmonary vascular resistance, critical components of BPD. The Human Microbiome Project is designed to understand the interactions between microbial communities that inhabit a host and the host itself. Emerging data suggest that imbalances between components of commensal organisms in the gastrointestinal tract are associated with atopy, allergic rhinitis, or recurrent wheezing. These data prompt consideration of the role for gut microbiota-mediated lung inflammation as a trigger for BPD. In this single center project, limited polysomnography and echocardiography will be used to non- invasively and longitudinally assess airspace and pulmonary vascular development in premature newborns <30 weeks'gestation who are at risk for developing BPD to test the hypothesis that signatures of the neonatal enteric microbiome are associated with BPD-related adverse pulmonary outcomes, including death, technology dependence, and need for bronchodilators or corticosteroids at 36 weeks and 1 year of age. Ongoing, parallel initiatives at Washington University that are characterizing the enteric microbiome of premature newborns will be leveraged to explore associations between this biomass and the development of BPD-related adverse pulmonary outcomes.
The Specific Aims are: 1) utilize existing data to determine differences in the composition of the microbiota between groups of linked mothers and premature newborns with and without BPD, and 2) utilize existing data to determine differences in the metagenomic and/or transcriptional repertoire of the enteric microbiota between linked mothers and premature newborns with and without BPD. The metagenomic and transcriptional differences identified in Specific Aim II that are associated with adverse pulmonary outcomes will permit identification of factors that are amenable to early intervention and prevention of BPD, and furthermore, will inform selection of candidate gene networks that can be interrogated for the multicenter component of this proposal in which next generation sequencing will be used to identify the interactions between and among alleles of the infant and microbiota that are associated with BPD-related adverse pulmonary outcomes.

Public Health Relevance

The proposed studies will evaluate whether bacteria in the intestinal tract of premature newborns play a role in the development of bronchopulmonary dysplasia, the most significant chronic lung problem of prematurity. Identifying the role that these bacteria play will permit early treatment in an effort to prevent the development of these lung problems.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL101465-04
Application #
8464209
Study Section
Special Emphasis Panel (ZHL1-CSR-D (F1))
Program Officer
Blaisdell, Carol J
Project Start
2010-05-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2013
Total Cost
$469,426
Indirect Cost
$136,226
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Levy, Philip T; Patel, Meghna D; Choudhry, Swati et al. (2018) Evidence of Echocardiographic Markers of Pulmonary Vascular Disease in Asymptomatic Infants Born Preterm at One Year of Age. J Pediatr 197:48-56.e2
Blaisdell, Carol J; Troendle, James; Zajicek, Anne et al. (2018) Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study. J Pediatr 197:42-47.e1
Rusconi, B; Jiang, X; Sidhu, R et al. (2018) Gut Sphingolipid Composition as a Prelude to Necrotizing Enterocolitis. Sci Rep 8:10984
Hamvas, Aaron; Feng, Rui; Bi, Yingtao et al. (2018) Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth. BMC Genet 19:94
Choudhry, Swati; Salter, Amber; Cunningham, Tyler W et al. (2017) Normative Left Ventricular M-Mode Echocardiographic Values in Preterm Infants up to 2 kg. J Am Soc Echocardiogr 30:781-789.e4
Levy, Philip T; El-Khuffash, Afif; Patel, Meghna D et al. (2017) Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two-Dimensional Speckle-Tracking Echocardiography in Preterm Infants over the First Year of Age. J Am Soc Echocardiogr 30:685-698.e1
Rusconi, Brigida; Good, Misty; Warner, Barbara B (2017) The Microbiome and Biomarkers for Necrotizing Enterocolitis: Are We Any Closer to Prediction? J Pediatr 189:40-47.e2
Brennan, Colleen; Ulm, Lara; Julian, Samuel et al. (2017) Thoracoabdominal Asynchrony Is Not Associated with Oxyhemoglobin Saturation in Recovering Premature Infants. Neonatology 111:297-302
Keller, Roberta L; Feng, Rui; DeMauro, Sara B et al. (2017) Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study. J Pediatr 187:89-97.e3
Horani, Amjad; Ferkol, Thomas W (2016) Primary ciliary dyskinesia and associated sensory ciliopathies. Expert Rev Respir Med 10:569-76

Showing the most recent 10 out of 25 publications