Neonatal Chronic Lung Disease

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Premature infants are born with extremely fragile lungs, and as one of the last organs to fully develop, their lungs are often unprepared to take independent breaths outside the womb. The life sustaining therapies needed to support these fragile infants such as mechanical ventilators and high levels of oxygen can contribute to lung injury, inflammation and scarring. This can lead to difficulty breathing and long-term respiratory problems like chronic lung disease — also known as bronchopulmonary dysplasia. Premature infants with the most severe form of chronic lung disease often require six or more months on the ventilator in the neonatal intensive care unit. Since its establishment in 2010, the Newborn and Infant Chronic Lung Disease Program at Children's Hospital of Philadelphia has treated over 400 newborns, and is one of the largest programs dedicated to the care of infants with chronic lung disease in the world.

This Frontier program involves a multidisciplinary group of clinicians and researchers who are testing a broad spectrum of approaches to target prevention as well as treatment of chronic lung disease. One in particular is a novel therapy called partial liquid ventilation that involves filling the lungs of these babies with a special liquid with anti-inflammatory and unique gas exchange properties, potentially altering the course of their disease.

The Neonatal Chronic Lung Disease program received Frontier status in Fiscal Year 2018.

Here are some highlights of the Neonatal Chronic Lung Disease program's research efforts:

  • Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT): This pilot study is designed to evaluate the safety of partial liquid ventilation, which involves filling the lungs with a special liquid called Perflubron (PFOB), in infants with severe BPD. This study will allow us to take the first steps in understanding how BPD responds to PFOB-PLV.
  • Microbiome of the Airway and the Risk for Bronchopulmonary Dysplasia in the Lungs of Extreme Preterms (MARBLE Study): The CHOP CLD program is currently investigating whether imbalance in the airway microbiome in extremely preterm infants is associated with lung inflammation and the development and/or worsening of existing CLD. This research has important potential to lead to future therapies aimed at preventing CLD and reducing the burden of the disease among babies with established CLD
  • Definition and Phenotype in BPD: Chronic lung disease is unique among many conditions in medicine in that it is primarily defined by its treatment, specifically the need for supplemental oxygen and breathing assistant provided by devices such as a "CPAP machine" or from a ventilator. As neonatal care advances, new devices are introduced and the criteria used to define CLD must evolve. Moreover, the diagnostic criteria should predict meaningful long-term outcomes such as need for re-hospitalizations and home oxygen therapy as well as developmental status during childhood. Researchers for the CHOP CLD team are developing a new definition for CLD that will help achieve these goals. The group is also evaluating infants with severe CLD to determine whether particular abnormalities in the lung tissue, the large airways, or the lung blood vessels are the predominate pathology.
  • Medication exposures and polypharmacy in infants with severe bronchopulmonary dysplasia admitted to United States children's hospitals: Using administrative data from U.S. children's hospitals, our team has identified all medication exposure in infants with severe BPD (sBPD) over a decade. This comprehensive evaluation will help inform the next generation of drug trials in this vulnerable patient population in need of evidence-based practice recommendations.
  • The BPD Saturation Targeting Pilot Trial (BPD STAR Trial): Funded by the Thrasher Research Fund, this is the first study to perform continuous oxygen saturation monitoring of infants with BPD after hospital discharge and until 6 months of life. The BPD STAR Trial, which is currently enrolling infants at CHOP and HUP, will test the hypothesis that targeting higher saturations is associated with improved outcomes in infants with BPD.