Browsing by Subject "bronchopulmonary dysplasia"
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Item Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice(MDPI, 2021-08-09) Das, Pragnya; Acharya, Suchismita; Prahaladan, Varsha M.; Kumova, Ogan K.; Malaeb, Shadi; Behera, Sumita; Agarwal, Beamon; Christensen, Dale J.; Carey, Alison J.; Bhandari, VineetBronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton's Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton's Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.Item Evaluation of respiratory outcomes in pre-term infants receiving nCPAP versus surfactant and mechanical ventilation during transport.(2012-12-01) Jacobs, Linda M.; Sumihiro SuzukiThe initial respiratory treatment for premature infants is trending toward nCPAP but this therapy sometimes fails requiring surfactant plus mechanical ventilation. This retrospective review of respiratory interventions by referral hospitals and a neonatal transport team evaluated predictors of respiratory support at 72 hours. A unique variable of time between birth and transport arrival was added to the multivariate regression model. This study confirmed that gestational age and high levels of respiratory support in the first hours of life are strong predictors for higher levels of respiratory support at 72 hours. Time to transport arrival was not a factor. The transport team has trended toward utilizing nCPAP more often over the past two years.Item Predictors of Chronic Kidney Disease During Childhood in Neonates with Bronchopulmonary Dysplasia(2022-08) Wallace, Samantha W.; Mathew, Stephen O.; Ortega, Sterling; Fudala, Rafal; Starr, MichellePremature infants are more likely to survive at earlier gestational ages today than ever before. However, many of these infants face long-term complications associated with their prematurity, as their organs have not had sufficient time to develop. This is particularly notable in the kidney and the lung. Due to physiological similarities, injury of one of these systems can lead to the injury of another, a phenomenon known as kidneylung crosstalk. Furthermore, infants who experience acute kidney injury are also at increased risk of experiencing chronic kidney disease in the future. Therefore, early identification and management of kidney and lung injuries is key for effective prevention of future chronic disease. This study addresses the frequency of kidney disease in a population of neonates with bronchopulmonary dysplasia, a chronic lung disease which is common in premature neonates.