Bronchopulmonary Dysplasia (BPD)

Babies who are born prematurely or who experience respiratory problems shortly after birth are at risk for bronchopulmonary dysplasia (BPD), sometimes called chronic lung disease. Although most infants fully recover from BPD and have few long-term health problems as a result, BPD can be a serious condition requiring intensive medical care.

Investigators are identifying biomarkers associated with BPD in order to develop personalized therapies to prevent the disease and improve patient outcome. Collaboration within Nationwide Children’s Hospital and a unique relationship with the Antipartum Unit and the Labor and Delivery Unit at The Ohio State University Medical Center allows researchers to more easily identify eligible study participants and merge clinical and laboratory data.

Faculty and Staff Focused on BPD Research

Basic Science/Translational:

• Trent E. Tipple, MD
• Leif D. Nelin, MD
• Lynette K. Rogers, PhD
• Bernadette Chen, MD
• Fred Long, MD

Clinical/Translational Research:

• George Mandy, MD
• Edward Shepherd, MD
• Robert Castille, MD
• Kelly Susey, PT
• Melissa Hanin, OT

Latest Findings in BPD Research

Variations Discovered: Study Reveals Need to Establish Best Practices for Diuretic Use in Preterm Infants with Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia, or BPD, is a multifaceted disease that affects low birth weight, preterm infants who spend longer periods of time on oxygen and mechanical ventilation. BPD encompasses all of the medical problems associated with impaired lung function, as well as the growth and development of the infant.

While use of diuretic medications for preterm infants with BPD has been a common regimen for more than 30 years, researchers at Nationwide Children’s Hospital have found significant variation in how infants receive these medications at hospitals across the nation.

The study, published in the March 11, 2013 issue of Pediatrics, was led by Jonathan Slaughter, MD, MPH, principal investigator in the Center for Perinatal Research and a neonatologist at Nationwide Children’s Hospital. He is also an assistant professor of Pediatrics at The Ohio State University.

He and his colleagues evaluated data during a 54-month period (January 2007 to June 2011) from 35 U.S. children’s hospitals involving 1429 infants with BPD.

Overall, 86 percent of the infants in the study received a diuretic, with 84 percent of those infants receiving at least one course of the drug for five days or less, and 40 percent receiving courses of medication for longer than five consecutive days.

Study findings reveal that among hospitals with at least 15 BPD patients during the study period, the percentage of infants receiving a diuretic course of longer than five days ranged from 4 percent to 86 percent.

“We found that the length of time infants required mechanical ventilation was the greatest predictor of diuretic medication use,” explains Dr. Slaughter. “On average, among infants that develop BPD, courses of diuretic use of five days or less predominate in the first month of life, with more than five days of diuretic use more common thereafter.”

Very little evidence exists to support long-term diuretic use and minimal data can be found on long-term side effects of extended use. However, long-term use is routine among the nation’s neonatal intensive care units.

A separate study of 400 neonatologists examining their clinical decisions to use diuretics showed that 66 percent of the respondents expected decreased ventilator days and 59 percent expected decreased length of stay for the patient.

“Our baseline findings can serve as the foundation for a prospective comparative effectiveness study to determine whether long-term use of diuretics in BPD patients is truly beneficial,” says Dr. Slaughter. “We have a critical need for a better understanding of the benefits and side effects in diuretic-exposed patients. If long-term diuretic use is shown to be advantageous for BPD patients, more research will be needed to determine which type of diuretics provide the most benefit and the lowest long-term risks.”

This research was funded by the National Center for Advancing Translational Science (NCATS) at the National Institutes of Health via the Ohio State University Center for Clinical and Translational Sciences (CCTS) KL2 Career Development Program, and also by the Agency for Healthcare Research and Quality (AHRQ).

Plasma Lipid Metabolites are Associated with Gestational Age but Not Bronchopulmonary Dysplasia
This study tested the idea that plasma lipid metabolite levels in premature infants are associated with the development of bronchopulmonary dysplasia. Data suggest that immature lipid metabolism pathways in premature infants may contribute to BPD and other diseases.

Access an abstract of this study: Plasma Lipid Metabolites are Associated with Gestational Age but Not Bronchopulmonary Dysplasia. Acta Paediatr. 2012 Apr 12. doi: 10.1111/j.1651-2227.2012.02694.x. [Epub ahead of print]

Inhibiting TrxR1 May Serve as Therapy for Oxidant-Mediated Lung Injury
This study finds that inhibiting TrxR1 production may represent a new therapeutic strategy that reduces the severity of oxidant-mediated lung injury.  

Access an abstract of this study: Thioredoxin Reductase Inhibition Elicits Nrf2-mediated Responses in Clara Cells: Implications for Oxidant-induced Lung Injury. Antioxid Redox Signal. 2012 May 18. [Epub ahead of print]

Animal Models Suggest Maternal Inflammation and Oxygen Treatment Contribute to Long-Term Consequence for Offspring
Maternally-derived inflammatory-mediators such as IL-6 and IL-8 contribute to preterm delivery, low birth weight, and respiratory insufficiency, which are routinely treated with oxygen. This study examines the impacts perinatal inflammation and oxygen treatment have on lung structure and function of animal model offspring.   

Access an abstract of this study: Prenatal Inflammation Exacerbates Hyperoxia Induced Functional and Structural Changes in Adult Mice. Am J Physiol Regul Integr Comp Physiol. 2012 Jun 20. [Epub ahead of print]

Tracheostomy Placement in Infants with Bronchopulmonary Dysplasia: Safety and Outcomes
This study describes data from a single institution about the efficacy and safety of tracheostomy placement in infants with BPD needing long-term respiratory support.

Access an abstract of this study: Tracheostomy placement in infants with bronchopulmonary dysplasia: Safety and outcomes. Pediatr Pulmonol. 2012 May 8. doi: 10.1002/ppul.22572. [Epub ahead of print]

Current BPD Research Grants

Lipoxin-Mediated Inflammatory Resolution in Newborn Hyperoxic Lung Injury, National Institutes of Health (Rodney Britt)

DHA Attenuates Inflammatory Responses through Altering RAGE Signaling, National Institutes of Health (Lynette Rogers)

Cationic Amino Acid Transporters and Lung NO Production, National Heart, Lung and Blood Institute, National Institutes of Health (Leif D. Nelin)

Lipoxin Receptor and Inflammatory Resolution in the Development of Bronchopulmonary Dysplasia, American Thoracic Society (Lynette K. Rogers)

Regulation of Lung Growth and Development by Thioredoxin Interacting Protein, National Institutes of Health, National Hearth, Lung, and Blood Institute (Trent E. Tipple)

miR-17~92 Cluster Expression in Bronchopulmonary Dysplasia, Richard P. & Marie R. Bremer Medical Research Fund and William H. Davis Endowment for Basic Medical Research and The Ohio State University Center for Clinical & Translational Science Pilot Program (Trent E. Tipple, MD)