Association of plasma cortisol and chronic lung disease in preterm infants.

BACKGROUND: It has been suggested that preterm infants may have developmental immaturity of the hypothalamic-pituitary-adrenal axis, and that decreased cortisol response to stress increases risk of chronic lung disease (CLD) secondary to inflammatory lung injury. METHODS: To investigate the relationship between endogenous corticosteroid and CLD, we measured plasma cortisol during the first 28 days of life in a subset of neonates in the North American Thyrotropin-Releasing Hormone (TRH) Collaborative Trial. Analyses were performed on 314 infants, 24 to 32 weeks' gestation, whose mothers received 1 or 2 courses of antenatal corticosteroids plus TRH or placebo. RESULTS: Mean cortisol was 3.1 microg/dL (range: 0.1-17.9) at birth, reached maximal levels at 24 hours (19.4 microg/dL, range: 0.8-124.6), and decreased to 5.9 microg/dL (range: 0.2-24.7) at 14 to 28 days of age; levels during the first week were not associated with gestational age. The Clinical Risk Index for Babies (CRIB), a neonatal assessment tool that is correlated with risk of mortality, was positively associated with cortisol level on days 1 and 3 through 7. TRH versus placebo treatment did not influence cortisol levels at any time point. To examine the relationship between cortisol and adverse outcome of death or CLD at 36 weeks' postmenstrual age (CLD36), logistic regression models adjusting for known contributing clinical factors (gestational age and CRIB score) were fit. There was a statistically borderline negative association between median cortisol level at 3 to 7 days and CLD36. After adjusting for gestational age and CRIB score, the predicted probability of CLD36 was only minimally influenced by the cortisol concentration. CONCLUSION: In preterm infants, basal plasma cortisol concentration during the first week is a weak predictor for CLD36. Possible benefits as well as risks of supplemental, low-dose cortisol treatment of high-risk preterm infants remain to be determined.

Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyrotropin-Releasing Hormone Study Group.

OBJECTIVES: We sought to examine outcome for premature neonates after multiple courses of antenatal corticosteroids compared with a single course. STUDY DESIGN: We performed a post hoc nonrandomized analysis on 710 neonates of 25-32 weeks' gestation who were born to mothers enrolled in the North American Thyrotropin-Releasing Hormone Trial and who received 1, 2, or >/=3 courses of antenatal corticosteroids. RESULTS: There was no detectable clinical difference in incidence of respiratory distress syndrome, chronic lung disease, and intraventricular hemorrhage related to courses of antenatal corticosteroids, and outcome was similar for infants delivered at 7-13 days compared with those delivered at 1-6 days after receiving antenatal corticosteroids. Compared with those who received a single course, neonates who received >/=2 courses had lower birth weights (-39 g, P =.02), and those receiving >/=3 courses had increased risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P =.01) and lower levels of plasma cortisol at age 2 hours. CONCLUSION: In this retrospective analysis multiple courses of antenatal corticosteroids did not improve outcome and were associated with increased mortality, decreased fetal growth, and prolonged adrenal suppression.

Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia.

BACKGROUND: Severe bronchopulmonary dysplasia (BPD), which is associated with high mortality and morbidity, is thought to be the result of mechanical, inflammatory, and oxidant injury to the immature lung, and includes the development of pulmonary hypertension with vascular remodeling. METHODS: A phase II pilot study was conducted to determine the effect of inhaled nitric oxide (iNO) on oxygenation in severe BPD. This was an open-labeled, noncontrolled trial to evaluate safety and determine appropriate dosing for a future randomized controlled trial. Infants were eligible for enrollment if they were >/=4 weeks of age and ventilator dependent with a mean airway pressure of >/=10 cm H2O and an FIO2 of >/=0.45. Study infants received iNO (20 ppm) for 72 hours, and FIO2 was adjusted to maintain oxygen saturations of >92%. Infants who had a >/=15% reduction in FIO2 after 72 hours received prolonged treatment with low-dose iNO, weaning by 20% every 3 days as tolerated. FINDINGS: Sixteen preterm infants (23-29 weeks of gestation), age 1 to 7 months, were enrolled. Eleven of 16 infants had a significant increase in PaO2 after 1 hour of iNO (median change, 24 mm Hg; range, -15 to 59 mm Hg; P <.01), but there was no significant change in PaCO2. After 72 hours of iNO, 11 infants had >/=15% reduction in FIO2, and 7 of the 11 had >/=35% reduction (P <. 01). Among the 11 infants who responded to iNO after 72 hours, 10 had a sustained improvement in oxygenation throughout their course of treatment (duration, 8-90 days), and ventilator support could also be decreased. No adverse effects from iNO (increased methemoglobin, bleeding, or increased plasma 3-nitrotyrosine) were observed. Four of the 11 infants (36%) who responded to iNO ultimately weaned off mechanical ventilation and 4 died, whereas all the infants who failed to respond to iNO either died or continue to require mechanical ventilation. INTERPRETATION: We conclude that the use of low-dose iNO may improve oxygenation in some infants with severe BPD, allowing decreased FIO2 and ventilator support without evidence of adverse effects. Randomized clinical trials of low-dose iNO for BPD are warranted.

Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia.

OBJECTIVE: Premature infants are susceptible to bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy that appears to be caused in part by oxidative stress from hyperoxia. To investigate the possible role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins. PATIENTS AND METHODS: Ten premature infants who developed BPD, defined as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were identified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected on these infants during the first month of life as part of the trial. Sixteen comparison premature infants were identified from the same population: 5 had no lung disease, 6 had respiratory distress syndrome that resolved, and 5 had residual lung disease at 28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels were measured using a solid phase immunoradiochemical method. RESULTS: All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg protein, and levels did not change with postnatal age. Plasma 3-nitrotyrosine concentrations were significantly higher in infants with BPD, increasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxygen that the infant was receiving (r = 0.7). CONCLUSION: Plasma 3-nitrotyrosine content is increased during the first month of life in infants who develop BPD. This suggests that peroxynitrite-mediated oxidant stress may contribute to the development of this disease in premature infants and that 3-nitrotyrosine may be useful as an early plasma indicator of infants at risk for developing BPD.

Attitudes of teenagers toward sun exposure and sunscreen use.

A survey of 220 adolescents attending a multiphysician pediatric office in Virginia was conducted to determine the frequency with which they used sunscreens. Eighty-one percent of the teenagers in the study stated that they spent most weekends in the sun; however, only 9% always used sunscreen, while 33% never did. Factors found to be associated with increased sunscreen use included female sex (odds ratio = 4.5, P less than .0001), having a best friend who routinely used sunscreen (odds ratio = 3.0, P less than .001), having parents who insisted on sunscreen use when the teenagers were children (odds ratio = 3.0, P = .006), and knowing that the maximum time for safe exposure to the sun is short (odds ratio = 6.2, P less than .0001). Adolescents with a history of skin cancer in the family were not more likely to use sunscreens than other teenagers. Thirty-three percent of the girls and 16% of the boys older than 15 years of age reported that they had visited a tanning salon at least once. This survey substantiates poor compliance with sunscreen use by teenagers despite increasing evidence of the dangers of excessive sun exposure.

Cardiac allograft prolongation in mice treated with combined posttransplantation total-lymphoid irradiation and anti-L3T4 antibody therapy.

Neonatal cardiac allograft survival was examined in mice treated with anti-L3T4 antibody, posttransplantation total lymphoid irradiation (TLI) or a combination of both therapies. Independently, both posttransplantation TLI and short-course antibody treatment allowed minimal prolongation. However, synergistic prolongation in graft survival was observed with the combination (synergistic) therapy. Fluorescence-activated cell sorter analysis of peripheral blood lymphocytes from animals treated with combined anti-L3T4 and posttransplantation TLI additionally revealed "synergy" with respect to the degree of peripheral lymphocyte depletion.

Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes.

Spontaneous diabetes mellitus was blocked in nonobese diabetic mice by treatment with a monoclonal antibody against the L3T4 determinant present on the surface of T-helper lymphocytes. Sustained treatment with the monoclonal antibody led to cessation of the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Moreover, the mice remained normoglycemic after the antibody therapy was stopped. These studies indicate that immunotherapy with monoclonal antibodies to the lymphocyte subset may not only halt the progression of diabetes, but may lead to long-term reversal of the disease after therapy has ended.