Surfactant disaturated phosphatidylcholine kinetics in infants with bronchopulmonary dysplasia measured with stable isotopes and a two-compartment model.
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We previously found a shorter surfactant disaturated phosphatidylcholine palmitate (DSPC-PA) half-life in infants with bronchopulmonary dysplasia (BPD) by using a single stable isotope tracer and simple formulas based on a one-exponential fit of the final portion of the enrichment decay curve. The aim of this study was to apply noncompartmental and compartmental analysis on the entire enrichment decay curve of DSPC-PA and to compare the kinetic data with our previous results. We analyzed 10 preterm newborns with BPD (gestational age 26 +/- 0.6 wk, weight 777 +/- 199 g) and 6 controls (gestational age 26 +/- 1.4 wk, weight 787 +/- 259 g). All took part in our previous study. Endotracheal 13C-labeled dipalmitoyl phosphatidylcholine was administered, and the 13C-enrichment of surfactant DSPC-PA was measured from serial tracheal aspirates by gas chromatography-mass spectrometry. Noncompartmental and compartmental models were numerically identified from the tracer-to-tracee ratio and kinetic parameters related to the accessible (pool accessible to sampling, likely to be the lung alveolar pool) and to the nonaccessible pools (pools not accessible to samplings, likely to be the intracellular storage pool) were estimated in the two study groups. Comparison was performed by Mann-Whitney test. A two-compartment model provided the most reliable assessment of DSPC-PA kinetics. In BPD vs. controls, mean +/- SE residence time of DSPC-PA in the accessible was 17.5 +/- 2.6 vs. 32.2 +/- 6.4 h (P < 0.05), whereas it was 49.7 +/- 3.5 vs. 54.4 +/- 3.9 h (NS, not significant) in the nonaccessible pool; DSPC-PA recycling was 0.26 +/- 0.05 vs. 0.43 +/- 0.04% (NS), respectively. A two-compartment model of surfactant DSPC-PA kinetics allowed a thorough assessment of DSPC-PA kinetics, including masses, synthesis, and fluxes between pools. The most important findings of this study are that in BPD infants DSPC-PA loss from the alveolar pool was higher and recycling through the intracellular pool lower than in controls. (+info)
Developmental regulation of p66Shc is altered by bronchopulmonary dysplasia in baboons and humans.
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RATIONALE: The p66(Shc) adapter protein antagonizes mitogen-activated protein, or MAP, kinase, mediates oxidative stress, and is developmentally regulated in fetal mouse lungs. OBJECTIVES: To determine if p66(Shc) is similarly regulated in primates and in bronchopulmonary dysplasia (BPD), which results from oxidative injury to immature lungs. METHODS: Normal and injured lungs from humans and baboons were evaluated by Western analysis and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: In baboons, p66(Shc) decreased 80% between 125 and 175 days' gestation (p = 0.025), then doubled after term delivery at 185 days (p = 0.0013). In the hyperoxic 140-day fetal baboon BPD model, p66(Shc) expression persisted, and its localization shifted from the epithelium of gestational controls to the mesenchyme of diseased lungs, coincident with expression of proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase, a marker of apoptosis. Treatment with the antibombesin antibody 2A11 attenuated BPD, reduced cell proliferation, increased p66(Shc) expression 10.5-fold, and preserved epithelial p66(Shc) localization. p66(Shc) also decreased during normal human lung development, falling 87% between 18 and 24 weeks' gestation (p = 0.02). p66(Shc) was expressed throughout 18-week human lungs, became restricted to scattered epithelial cells by 24 weeks, and localized to isolated mesenchymal cells after term delivery. In contrast, p66(Shc) remained prominent in the epithelium of lungs with acute injury or mild BPD, and in the mesenchyme of lungs with severe disease. p66(Shc) localized to tissues expressing proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase. CONCLUSIONS: p66(Shc) expression, cell proliferation, and apoptosis are concomitantly altered during lung development and in BPD. (+info)
Does sustained lung inflation at resuscitation reduce lung injury in the preterm infant?
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BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common outcome of preterm birth. Experimental animal work has shown that initial ventilation strategies injure the immature lung and may lead to BPD. Studies with asphyxiated babies have shown that, if tidal ventilation at birth is preceded by sustained lung inflation, larger inflation volumes can be achieved, which is thought to lead to clearance of lung fluid and formation of the functional residual capacity (FRC). OBJECTIVE: To see if sustained lung inflation at initial resuscitation of preterm babies would facilitate the removal of lung fluid, establish the FRC, and allow an even distribution of alveolar opening, permitting less aggressive ventilation, leading to a reduction in pulmonary inflammation and subsequent BPD. METHOD: The outcomes of 52 babies of less than 31 weeks gestation, resuscitated at birth using either a sustained lung inflation of five seconds or a conventional lung inflation of two seconds for the first assisted breath of resuscitation, were examined. Evidence of pulmonary inflammation was determined by quantification of interleukins 6, 10, and 1beta and tumour necrosis factor alpha in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. RESULTS: There were no significant differences in any of the cytokines. Death occurred in 3/26 babies in the conventional group and 6/26 babies in the sustained lung inflation group. Survival without BPD occurred in 13/26 and 14/26 respectively. CONCLUSION: The use of sustained lung inflation at resuscitation did not reduce lung injury, as measured by inflammatory markers. (+info)
Does the use of 50% oxygen at birth in preterm infants reduce lung injury?
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BACKGROUND: Bronchopulmonary dysplasia is an inflammatory fibrotic condition produced as a consequence of injurious influences in the neonatal lung. Exposing the premature lung to high concentrations of oxygen is thought to play an important part in lung injury pathogenesis. OBJECTIVE: To see if the amount of oxygen used during resuscitation at birth triggers events that lead to the subsequent lung injury and if a reduction in oxygen used leads to a reduction in lung injury. METHOD: The outcomes of newborn babies less than 31 weeks gestation who were resuscitated using either 50% or 100% oxygen were examined. Eight of the babies receiving 50% oxygen required an increase in their oxygen concentration. Evidence of pulmonary inflammation was determined by quantifying interleukin 6, 1beta, and 10 and tumour necrosis factor alpha in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. RESULTS: There were no significant differences in any of the cytokines studied in either of the groups. Death occurred in 5/26 (19%) babies who received 100% oxygen and 4/26 (15%) babies who received 50% oxygen. Survival without bronchopulmonary dysplasia at 36 weeks postmenstrual age occurred in 14/26 (54%) and 13/26 (50%). CONCLUSION: Reducing the oxygen to 50% at resuscitation did not influence either short or long term outcomes, but a small benefit could not be excluded. There was no increase in adverse clinical outcomes in babies who received 100% oxygen. (+info)
Effects of corticosteroids in very low birth weight newborns dependent on mechanical ventilation.
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Corticosteroids have been used in bronchopulmonary dysplasia prevention because of their antiinflammatory effects. Among their effects is a decrease in the incidence of bronchopulmonary dysplasia. However, short- and long-term side effects have been detected in preterm newborns. PURPOSE: To analyze the effects of corticosteroids on bronchopulmonary dysplasia, length of stay, mortality, growth, as well as the adverse effects in very low birth weight newborns between 10 and 14 days of life and dependent on mechanical ventilation. METHODS: Cohort study. All newborns with a birth weight under 1500 g, mechanical ventilation-dependent between 10 and 14 days of life, during the period January 2000 and June 2001 were included (n = 38). They were divided into 2 groups: Group I with corticosteroids (n = 16) and Group II without corticosteroids (n = 22). Dexamethasone administration: from the 10th day of life, d1-d3, 0.3 mg/kg/d; d4-d6, 0.2 mg/kg/d; d7-d9, 0.1 mg/kg/d. Respiratory evolution, bronchopulmonary dysplasia (oxygen dependence at 28 days of life), growth pattern and the presence of adverse effects were analyzed. RESULTS: The incidence of bronchopulmonary dysplasia was 6.5% (Group I) and 30% (Group II), P = .07. A decrease in growth was detected in Group I compared with Group II (change in weight: Group I--47 g/week, Group II--85.5 g/week, P = .06; change in head circumference: Group I--0.75 cm/week, Group II--1 cm/week, P = .05). CONCLUSION: Use of corticosteroids in very low birth weight infants dependent on mechanical ventilation during the first 10 to 14 days of life did not affect the respiratory evolution and occurrence of bronchopulmonary dysplasia, but the velocity of growth was reduced. (+info)
Recombinant human VEGF treatment enhances alveolarization after hyperoxic lung injury in neonatal rats.
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VEGF signaling inhibition decreases alveolar and vessel growth in the developing lung, suggesting that impaired VEGF signaling may contribute to decreased lung growth in bronchopulmonary dysplasia (BPD). Whether VEGF treatment improves lung structure in experimental models of BPD is unknown. The objective was to determine whether VEGF treatment enhances alveolarization in infant rats after hyperoxia. Two-day-old Sprague-Dawley rats were placed into hyperoxia or room air (RA) for 12 days. At 14 days, rats received daily treatment with rhVEGF-165 or saline. On day 22, rats were killed. Tissue was collected. Morphometrics was assessed by radial alveolar counts (RAC), mean linear intercepts (MLI), and skeletonization. Compared with RA controls, hyperoxia decreased RAC (6.1 +/- 0.4 vs. 11.3 +/- 0.4, P < 0.0001), increased MLI (59.2 +/- 1.8 vs. 44.0 +/- 0.8, P < 0.0001), decreased nodal point density (447 +/- 14 vs. 503 +/- 12, P < 0.0004), and decreased vessel density (11.7 +/- 0.3 vs. 18.9 +/- 0.3, P < 0.001), which persisted despite RA recovery. Compared with hyperoxic controls, rhVEGF treatment after hyperoxia increased RAC (11.8 +/- 0.5, P < 0.0001), decreased MLI (42.2 +/- 1.2, P < 0.0001), increased nodal point density (502 +/- 7, P < 0.0005), and increased vessel density (23.2 +/- 0.4, P < 0.001). Exposure of neonatal rats to hyperoxia impairs alveolarization and vessel density, which persists despite RA recovery. rhVEGF treatment during recovery enhanced vessel growth and alveolarization. We speculate that lung structure abnormalities after hyperoxia may be partly due to impaired VEGF signaling. (+info)
The radiology of chronic lung disease in children.
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Chronic lung disease (CLD) in children represents a heterogeneous group of many distinct clinicopathological entities. The prevalence of CLD has increased in the past decade because of the more advanced and intensive respiratory support provided for compromised children and additionally the overall improved survival of preterm babies. The disorders which constitute CLD generally have a slow tempo of progression over many months or even years. The most common causes of CLD in children are cystic fibrosis (CF), and other causes of bronchiectasis (such as immunodeficiency, and in the third world, post-infective bronchiectasis, for example, measles), bronchopulmonary dysplasia (BPD) (or lung disease of prematurity), asthma, chronic gastro-oesophageal reflux/aspiration pneumonitis, and constrictive obliterative bronchiolitis. (+info)
Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants.
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OBJECTIVE: Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. DESIGN, SETTING, AND PATIENTS: We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. INTERVENTION: The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. MAIN OUTCOME MEASURES: We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. RESULTS: Infants in the liberal-transfusion group received more RBC transfusions (5.2 +/- 4.5 [mean +/- SD] vs 3.3 +/- 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 +/- 2.5 vs 2.2 +/- 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. CONCLUSIONS: Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants. (+info)