Preterm infants are at increased risk for symptomatic airway dysfunction, manifested by wheezing or cough, in early childhood. This K23 award invesigates the neonatal antecedents of airway dysfunction in early childhood among pretern infants. The proposal provides Dr. Stevens with a rigorous didactic and mentored training program in clinical research, focusing on causes of airway dysfunction that require ongoing pulmonary care in childhood. The didactic curriculum includes targeted training in 10 courses and seminars, providing background and experience that bridge basic and clinical research. Essential clinical research experience will be obtained by conducting 2 interlocking projects under the guidance of an experienced, multi-disciplinary mentoring team. The overarching hypothesis of the 2 projects is that preterm infants exposed to supplemental oxygen in the immediate newborn period experience oxidant stress in the lung that results in impaired airway growth and development. These airway changes predispose them to greater airway dysfunction and respiratory symptoms when challenged with subsequent environmental or infectious exposures. Project 1 is The NICHD SUPPORT Trial Follow On Study of Pulmonary Outcomes In Infants <28 Weeks'. The SUPPORT Trial is a randomzied clincal trial of management with high vs. low targeted oxygen saturations on the incidence of death or BPD. The Pulmonary Outcome Study will add 6, 12 and 18-22 month pulmonary outcome assessments of randomized infants, measuring the incidence of symptomatic airway dysfunction in infants managed with high vs. low oxygen saturation targets. In Project 1, we hypothesize that management with lower oxygen saturation targets reduces oxygen exposure, oxidant stress and incidence of symptomatic airway dysfunction in infants <28 weeks'. Project 2, Oxygen Exposure, Oxidant Stress and Pulmonary Outcomes, is a Rochester-based prospective cohort study that evaluates the relationship between level of supplemental oxygen exposure, burden of oxidant stress and incidence of airway dysfunction in older infants, those 28-32 weeks'. From Project 2, we expect to find an association between less oxygen exposure, less oxidant stress and reduced symptomatic airway dysfunction in early childhood. If so, then a definitive, randomized trial of high vs. low targeted oxygen saturation to reduce symptomatic airway dysfunction will be indicated in infants 28-32 weeks', a population in.whom the incidence of BPD is low. The dramatic rise in childhood airway dysfunction over the last ten years has been a major public health concern. By evaluating the effect of oxygen exposure on oxidant stress and airway dysfunction this award will identify new therapeutic approaches to improve respiratory health of preterm infants in early childhood.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Pediatrics Subcommittee (CHHD)
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Raju, Tonse N
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University of Rochester
Schools of Dentistry
United States
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Stevens, Timothy P; Finer, Neil N; Carlo, Waldemar A et al. (2014) Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT). J Pediatr 165:240-249.e4
Halterman, J S; Lynch, K A; Conn, K M et al. (2009) Environmental exposures and respiratory morbidity among very low birth weight infants at 1 year of life. Arch Dis Child 94:28-32
Stevens, Timothy P; van Wijngaarden, Edwin; Ackerman, Kate G et al. (2009) Timing of delivery and survival rates for infants with prenatal diagnoses of congenital diaphragmatic hernia. Pediatrics 123:494-502
Narang, Shalu; Roy, Jason; Stevens, Timothy P et al. (2009) Risk factors for umbilical venous catheter-associated thrombosis in very low birth weight infants. Pediatr Blood Cancer 52:75-9
Stevens, Timothy P; Sinkin, Robert A (2007) Surfactant replacement therapy. Chest 131:1577-82