Cyclic AMP-dependent protein kinase (PKA) gene expression is developmentally regulated in fetal lung

AbstractWe characterized the ontogeny of cAMP-dependent protein kinase (PKA) enzymatic activity and PKA subunit mRNA expression in developing lung. The lungs of fetal Sprague–Dawley rat pups were removed after 16, 18, or 20 days of gestation and at term. PKA activity was greatest in the 18- and 20-day gestation lungs. Tissue cAMP levels were lowest in the 16-day lungs and increased with lung maturity. We were able to detect only low levels of mRNA for the Cβ subunit of PKA by northern blot analysis of total lung RNA and we were able to detect mRNA for the RIβ and RIIβ subunits only by RT-PCR. Therefore, we limited our analysis of PKA subunit mRNA levels to those for Cα, RIα and RIIα. The mRNA levels for Cα, were highest in the 16-day lung, decreased at 18 and 20 days, were lower in the newborn and lowest in the adult lung. RIα mRNA levels were also highest at 16 days and lowest in the adult lung. However, RIIα mRNA levels were similar in the 18-day, 20-day and newborn lungs. Dexamethasone treatment of fetal lung explants resulted in a small decrease in RIα mRNA levels but was not associated with a change in PKA activity. We conclude that PKA activity and PKA subunit mRNA expression are developmentally regulated in fetal lung. Such regulation results in optimal PKA activity at the time of type II alveolar cell differentiation, presumably in preparation for air breathing. The absence of an effect of glucocorticoid on PKA activity suggests that glucocorticoids are not responsible for the increase in PKA activity which accompanies this critical time in lung maturation

Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT)

To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant. The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention. One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P<.05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P<.05) by 18-22 months CA. Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates