Improving Outcomes for Infants with Severe Chronic Lung Disease Through Individualized Patient Care and Research

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Neonatology Update

Contributed by Erik Jensen, MD, MSCE, Assistant Professor of Pediatrics and Attending Neonatologist in the Division of Neonatology.

Infant in ICU Infant chronic lung disease, also known as bronchopulmonary dysplasia (BPD), is among the most common and consequential complications associated with prematurity. Roughly half of all extremely preterm infants develop BPD during their newborn hospitalization and most of those with the disease go on to suffer significant deficits in lung and cardiovascular health, growth, and neurodevelopment throughout childhood and even into adulthood. While considerable research has focused on the prevention of BPD, there is comparatively minimal available data on the best strategies to care for and improve outcomes among infants with established BPD.

In 2010, clinicians and investigators at Children’s Hospital of Philadelphia (CHOP) created the CHOP Newborn/Infant Chronic Lung Disease (NeoCLD) Program to address this gap. One of the first of its kind in the world, the CHOP NeoCLD Program was designed to be a clinical and research home for infants with BPD receiving neonatal intensive care throughout the surrounding region and nation at large.

Our team recognized early in the course of the NeoCLD Program that BPD is not one uniform disease. Rather, each infant with BPD is unique and requires an individualized care plan. Much of our research focuses on developing new strategies to understand each infant’s pathophysiology and tailor appropriate therapies.   

We are currently using next-generation sequencing techniques to characterize the lung microbiome in infants with established BPD and have been approved by the U.S. Food and Drug Administration to conduct a novel phase-1 trial of inhaled antibiotic therapy among infants with harmful bacterial pathogens identified in the airways. In addition to the injurious invasion of micro-organisms into the lungs, gastroesophageal reflux (GER) with pulmonary aspiration is an often cited but poorly understood potential contributor to ongoing respiratory disease in infants with BPD.

Our research team is actively recruiting patients into a multifaceted study that will provide valuable new data on GER in BPD titled “Gastroesophageal reflUx in and the association with Lung disease in Preterms (GULP): A prospective cohort study.” The GULP study employs 24-hour esophageal pH and multichannel intraluminal impedance (pH/MII) testing to diagnose and quantify GER in infants with BPD. This gold-standard technique is coupled with concurrent cardiac echocardiography, continuous cardiorespiratory physiologic monitoring, and videography. These diagnostic studies are then combined with the results from computed tomography (CT) imaging of the lungs and bronchoscopy of the airways to develop a detailed and individualized picture of each patient’s disease. Our neonatal clinicians, in conjunction with a wide-range of pediatric subspecialists, use this information to select appropriate respiratory support strategies, medications, feeding regimens, and when needed to recommend surgical interventions to families.

Additional recently completed and ongoing studies conducted by the NeoCLD team include:

  • Single and multicenter cohort studies proposing new, evidence-based diagnostic criteria for BPD and BPD sub-types.
  • Randomized clinical trial comparing two different goal oxygen saturation target ranges in infants with established BPD to help determine the optimal level and duration of oxygen therapy in this population.
  • Placebo-controlled randomized trial of aerosolized albuterol in ventilator dependent infants with BPD.
  • Novel N-of-1 multiple crossover trial comparing cardiorespiratory stability during gastric and transpyloric feedings.
  • Optimization of positive end expiratory pressure (PEEP) level selection.
  • Development of dosage and duration informed treatment strategies for diuretic therapy in severe BPD.
  • Development of novel techniques to characterize and improve early motor development in infants with severe BPD.

Investigators in the NeoCLD Program receive funding to conduct this research from the National Institutes of Health, the American Lung Association, the Thrasher Research Fund, CHOP, and other national organizations. 

Our ability to perform state-of-the-art research and combine it in real-time with ongoing clinical care allows us to positively influence the health of our current patients and to design our next studies aimed at improving outcomes for our future patients. We take extreme pride in being able to offer our patients and their families the opportunity to participate in this exciting research, and we are hopeful that this work will continue to yield important insights into the optimal care of infants and young children with BPD.

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