Air Alternative? Researchers Study Liquid Ventilation for Premature Infants

Image of Dr. William Fox

For premature babies born at extremely low birth weights, severe chronic lung disease – also known as bronchopulmonary dysplasia – remains a major source of mortality and morbidity. Premature infants are born with extremely fragile lungs, and as one of the last organs to fully develop, those lungs are often unprepared to take independent breaths outside the womb. Lung tissue can then get injured, inflamed, and significantly scarred through mechanical ventilators or oxygen use, resulting in difficulty breathing and long-term respiratory problems like CLD.

Fortunately, research into caring for newborns with respiratory distress has come a long way. Within the Newborn and Infant Chronic Lung Disease Program (NeoCLD) at CHOP, a multidisciplinary team of physicians, nurses, respiratory therapists, case managers, and more have made major strides in advancing care for infants with respiratory concerns. Since its establishment in 2010, NeoCLD has treated over 300 newborns, expanding to become one of the largest specialty programs in the country. It is currently led by Huayan Zhang, MD, medical director and attending neonatologist at CHOP.

With Frontier Program designation by Children’s Hospital of Philadelphia, NeoCLD will have the support and funding that they need to advance evidence-based treatments for infants with CLD even further. A large part of the Frontier Program’s provision will focus on translational research and the continued development of one particular innovation over 25 years in the making: liquid ventilation.

William Fox, MD, medical director of the Infant Breathing Disorder Center at CHOP and a neonatologist within NeoCLD, explained that liquid ventilation delivers oxygen to an individual’s lungs through liquid rather than air – a therapeutic advance that could give infants who develop severe breathing problems a stronger chance of surviving.

Dr. Fox and his team are currently studying a substance called perfluorooctylbromide (PFOB), which is a synthetic liquid that is chemically and biologically inert, meaning that it doesn’t react easily with other chemicals. With its high capacity to carry oxygen, Dr. Fox believes PFOB has the ability to act as an artificial equivalent to surfactant – a vital substance that naturally builds inside a healthy baby’s lungs as it prepares to take its first breath of air outside the womb. Surfactant reduces surface tension in the baby’s lungs in order to prevent his or her organs from collapsing in on themselves.

Unfortunately, premature infants often emerge from the womb without the sufficient amount of surfactant that they need to develop healthy lungs and to breathe freely. PFOB can take on the role of artificial surfactant to protect the infant’s lungs and help them to breathe.

“Perfluorooctylbromide can carry nine times as much oxygen as blood, making it an ideal medium for improving lung function,” Dr. Fox said.

Over the past 25 years, Dr. Fox has treated 18 babies with PFOB therapy with good results, and in its early trials, the treatment has been shown to perform well as an artificial surfactant. Currently, Dr. Fox is leading a clinical trial that evaluates the safety and efficiency of PFOB in infants with severe CLD. These are the sickest and most expensive patients cared for by neonatologists. Similar to adult CLD, there is no specific treatment that can change the course of the disease.

Because of NeoCLD’s new Frontier designation – as well as the generous support that he has received in the lead-up to PFOB’s development – Dr. Fox said that CHOP is the perfect place for liquid ventilation research to expand. He believes the treatment can have a major impact, both medical and surgical, on CLD as well as other neonatal lung diseases. If evidence supports that it is safe and effective, liquid ventilation could be used in any neonatal intensive care unit with a ventilator. In the future, nebulized forms of the therapy could become a new alternative.

“The Frontier Program will take us to the next step, which includes multicenter trials, and it will allow us to expand several trials simultaneously,” Dr. Fox said. “I see a strong potential for CHOP to assist in commercialization, which is the best way to expand (liquid ventilation’s) use throughout the world.”

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