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Alan H Jobe

Publications and source records attributed to Alan H Jobe.

62 records · Page 4Linked to original sources
PubMed2002

Injury responses to different surfactants in ventilated premature lamb lungs.

The lung of the preterm infant is easily injured and an initial indication of the injury is an inflammatory response. Surfactant treatment and gentle ventilation will minimize the initiation and progression of injury. We asked if the initial lung injury response differed when preterm ventilated lambs were treated with complete natural sheep surfactant, a lipid extract of sheep surfactant, a surfactant used to treat RDS (Survanta), or a synthetic surfactant containing recombinant SP-C (Venticute). We used a gentle style of ventilation and a positive end expiratory pressure of 4 cmH(2)0 to minimize injury. The surfactants were not distinguishable based on gas exchange, compliance or lung gas volumes over the 6h ventilation period. When compared with unventilated controls the ventilated lambs had increased protein and inflammatory cells in alveolar lavages. The cells from the alveolar lavages produced more H(2)0(2), expressed more surface adhesion antigens and CD-14 receptors, and expressed more mRNA for the pro-inflammatory cytokines IL-1 beta and IL-8 than did cells from unventilated lungs. Lung tissue expressed primarily increased IL-6 mRNA relative to unventilated controls. However, there were no consistent differences in any of the inflammatory indicators between the different surfactant treated groups. Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung.

Animals↗
PubMed2002

Postnatal lung inflammation increased by ventilation of preterm lambs exposed antenatally to Escherichia coli endotoxin.

Chorioamnionitis resulting in exposure of the fetal lung to inflammation is frequent before preterm delivery. The initiation of mechanical ventilation in the preterm recruits granulocytes to the lungs and increases proinflammatory cytokine expression in the lungs. We hypothesized that when the prematurely born newborn with chorioamnionitis was ventilated, inflammation would increase. Therefore, we asked whether inflammatory exposure to the fetal lung caused by intra-amniotic endotoxin (10 mg, Escherichia coli 055:beta 5) given at 100 d gestation would alter the inflammatory responses to the mechanical ventilation in surfactant-treated preterm lambs delivered at 130 d gestation. Cells in alveolar washes, proinflammatory cytokine expression, and surfactant protein mRNA expression were not different for saline and endotoxin exposed lambs that were not ventilated. The endotoxin- and saline-exposed control animals had similar lung function for 6 h of ventilation. Bronchoalveolar lavage fluid from the ventilated and antenatal endotoxin-exposed animals contained 5.7 times more monocytes, 12 times more lymphocytes, and a nonsignificant increase in neutrophils. Cells from the bronchoalveolar lavage fluid expressed 3-fold more IL-6 and IL-8 mRNA than did cells from the saline exposed comparison animals. An antenatal exposure of the fetal lung to endotoxin enhanced the subsequent inflammatory response of the ventilated preterm lung.

Animals↗
PubMed2002

Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs.

Continuous positive airway pressure (CPAP) is being used clinically to avoid mechanical ventilation of preterm infants as a strategy to minimize lung injury. There is little experimental information about how CPAP might minimize lung injury after preterm birth. We induced preterm labor in antenatal glucocorticoid-treated sheep carrying twins at 133 d gestation with an inhibitor of progesterone synthesis. The lambs delivered spontaneously approximately 2 d later and were randomized to three groups: no ventilation (n = 4), conventional mechanical ventilation to a target PCO(2) of 40 mm Hg (n = 5), or CPAP using a bubble CPAP device set to deliver 5 cm H(2)O pressure (n = 6). The CPAP lambs breathed without distress and maintained PCO(2) values of approximately 60 mm Hg. At 2 h of age, the lungs of the CPAP lambs held 74 +/- 4 mL/kg air at 40 cm H(2)O pressure, which was more than the 60 +/- 3 mL/kg for the ventilated lambs (p < 0.05). Lymphocyte and monocyte numbers in alveolar washes were equivalent in the unventilated, ventilated, and CPAP lambs. However, no neutrophils were found in the unventilated lambs, and the ventilated lambs had 6.6 times more neutrophils in alveolar washes than did the CPAP lambs (p < 0.05). The cells in alveolar wash from CPAP lambs contained less hydrogen peroxide than did the cells from ventilated lambs (p < 0.05). In this model in preterm lambs CPAP results in lower indicators of acute lung injury than does mechanical ventilation during the first 2 h of life.

Animals↗
PubMed2002

Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia.

Because minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive (14)C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung pool sizes of saturated phosphatidylcholine were measured. Half-life of (2)H-DPPC (d 5) in tracheal aspirates was 28 +/- 4 h (mean +/- SEM). Half-life of radioactive DPPC (d 8) was 35 +/- 4 h. Saturated phosphatidylcholine pool size measured with stable isotopes on d 5 was 129 +/- 14 micro mol/kg, and 123 +/- 11 micro mol/kg on d 14 at autopsy. Half-lives were comparable to those obtained at d 0 and d 6 in our previous baboon studies. We conclude that surfactant metabolism does not change during the early development of bronchopulmonary dysplasia, more specifically, the metabolism of exogenous surfactant on d 8 is similar to that on the day of birth. Surfactant pool size is low at birth, increases after surfactant therapy, and is kept constant during the first 2 wk of life by endogenous surfactant synthesis. Measurements with stable isotopes are comparable to measurements with radioactive tracers and measurements at autopsy.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Indications for and questions about antenatal steroids.

Antenatal glucocorticoid treatment of women at risk of preterm delivery between 24 and 34 weeks' gestation has been the standard of care since 1994. Recent information supports its use with preterm prolonged rupture of membranes, in very early gestations in which neonatal survival will be attempted, and in women with preeclampsia. Many women who deliver before 30 weeks' gestation have chronic silent chorioamnionitis, which does not seem to be a contraindication to antenatal glucocorticoid therapy. The preferred antenatal treatment is a short- and long-acting betamethasone combination given as 12-mg maternal injections at the identification of preterm labor and 24 hours later. Repeated courses of antenatal glucocorticoids given at 7- to 10-day intervals if preterm delivery does not occur are not indicated. Antenatal glucocorticoid therapy is very effective, and no adverse effects of a single treatment course have been identified.

Chorioamnionitis↗
PubMedDate not supplied

Early bubble CPAP and outcomes in ELBW preterm infants.

OBJECTIVE: To test whether the introduction of early bubble continuous positive airway pressure (CPAP) results in improved respiratory outcomes in extremely low birth-weight infants. STUDY DESIGN: Outcomes of all infants between 401 and 1000 g born in a level 3 neonatal intensive care units (NICU) between July 2000 and October 2001 (period 2) were compared using historical controls (period 1). Early bubble (CPAP) was prospectively introduced in the NICU during period 1. Univariate and adjusted comparisons were made across time periods. RESULTS: Delivery room intubations, days on mechanical ventilation and use of postnatal steroids decreased (p<0.001) in period 2, while mean days on CPAP, number of babies on CPAP at 24 hours (p<0.001) and mean weight at 36 weeks corrected gestation also increased (p<0.05) after introduction of early bubble CPAP. CONCLUSIONS: Early bubble CPAP reduced delivery room intubations, days on mechanical ventilation, postnatal steroid use and was associated with increased postnatal weight gain with no increased complications.

Bronchopulmonary Dysplasia↗
PubMedDate not supplied

[Exogenous surfactant therapy--what is established and what still needs to be determined].

OBJECTIVE: To review well-known aspects of exogenous surfactant therapy, and to discuss controversial points regarding the current state of research. SOURCES: Review of the literature, using Medline and Cochrane Database Library, in association with the authors' experience in relation to exogenous surfactant replacement therapy. SUMMARY OF THE FINDINGS: The main aspects of surfactant characteristics: composition, pool, metabolism, inactivation and immediate effects after its administration are well established. However, there are some doubts related to the use of exogenous surfactants that need to be cleared up: choice of surfactant type, most appropriate length of treatment, adequate dose and number of doses, best administration route and complications associated with its use. Currently, the research about exogenous surfactant therapy focuses on two aspects: the use of surfactant in other pathologies besides the respiratory distress syndrome of the newborn, and the development of new surfactants through the addition of proteins or analogous proteins, with the aim of improving its action and reducing its inactivation. CONCLUSIONS: The use of exogenous surfactant has become a routine in neonatal intensive care units, but both clinical and experimental research is still necessary.

English Abstract↗