Miniature Device to Promote Lung Development

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DESCRIPTION (provided by applicant): Congenital diaphragmatic hernia (CDH) affects 1 in 2000 newborns. CDH is a disorder in which part of the diaphragm fails to form, allowing abdominal organs to migrate into the chest, resulting in lung hypoplasia (underdevelopment) in affected infants. Although great strides have been made in the management of this disease, significant morbidity and mortality persist. Pooled results from over 50 centers worldwide indicate overall survival to be 68% with standard, postnatal therapy. Specific morbidities in survivors include neurodevelopmental, nutritional, sensorineural hearing, and pulmonary function deficiencies. The public health impact of this disease is also significant, in that CDH has been identified as the third-most-costly of birth defects in a recent study. The severe consequences of this congenital anomaly have led others to pursue methods of correcting CDH or its main consequence, lung hypoplasia, prior to birth, allowing for more normal postnatal function. The most promising in utero therapy developed thus far consists of complete occlusion of the fetal trachea, which has been shown to encourage lung growth. However, this procedure impairs the phasic mechanical forces that are known to critically regulate proper lung development. To overcome this, we propose the use of a miniature valve to provide dynamic tracheal occlusion (dTO) to promote lung growth. In preliminary experiments, a custom-designed, modified ventriculoperitoneal shunt valve was used to maintain a tracheal pressure of 6-8 mmHg, yet allow for efflux of lung fluid, in a fetal lamb CDH model. Compared to complete occlusion, dTO resulted in improved (near-normal) lung morphometrics and function. Here, we propose to further define the pressure characteristics for optimal lung growth and to create a miniature device that will allow for minimally invasive deployment. To create the device, a microvalve will be made using MEMS (micro electro mechanical systems) microfabrication techniques that allow for precise control of device geometry and performance specifications. The Phase I Specific Aims are to: (1) Establish microvalve designs with opening pressures in the range of 2-10 mmHg and (2) Determine valve pressure setting for optimal lung development. PUBLIC HEALTH RELEVANCE: Congenital diaphragmatic hernia (CDH) afflicts approximately 1 in 2000 newborns. As common as cystic fibrosis and spina bifida, CDH incurs significant long-term morbidity, mortality, and socioeconomic costs due to poor fetal lung development. The ultimate goal of the proposed STTR project is to apply novel technologies to develop a miniature device for treatment of CDH.