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When babies are born prematurely, they're often placed promptly on a mechanical ventilator to help their immature lungs breathe. But the excess pressure on the infant's delicate lungs can lead to ventilator-induced inflammation, scarring and potentially bronchopulmonary dysplasia (BPD), a disabling chronic lung disease.
Through a quality improvement initiative, Bernadette Levesque, MD, in Children's Division of Newborn Medicine, has been able to substantially reduce the use of mechanical ventilation. She set up a simple "bubble" Continuous Positive Airway Pressure (CPAP) system, giving a warm flow of humidified oxygen that gently keeps the baby's lungs inflated, starting minutes after birth. In a study of 120 premature infants, bubble CPAP safely reduced the need for mechanical ventilation from 52 to 11 percent, lowered rates of surfactant use from 48 to 14 percent, reduced symptomatic hypotension, or low blood pressure, and lowered the incidence of death or BPD from 18 to 10 percent.
Because there have been few randomized clinical trials, other hospitals have been slow to adopt bubble CPAP. "While we have seen first hand how well this approach works, a definitive randomized study may be needed to get widespread approval," says Levesque. "I'm anxious to see other units try it."
The reasons why mechanical ventilation causes BPD haven't been fully explored, but Levesque has discovered that ventilation lowers levels of a protein involved in blood vessel growth, known as vascular endothelial growth factor (VEGF). In prior laboratory experiments, she helped show, with Donald Ingber, MD, PhD, in the Vascular Biology Program, that physical stretching of the cells lining the lungs (simulating mechanical ventilation) also led to decreased VEGF production.
In further work supported by the NIH Specialized Center of Research (SCOR) Program on Pathobiology of Lung Development (directed by Stella Kourembanas, MD, Division Chief of Newborn Medicine), and in collaboration with Linda Van Marter, MD, MPH, Levesque found that infants with low VEGF levels in their urine are the ones most likely to develop BPD, and that low VEGF levels correlated with early mechanical ventilation. These insights not only offer the possibility of urine testing to identify patients at risk, but also suggest that a VEGF stimulator in the lung might be worth exploring as a preventive therapy for BPD.
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