Karen E. Willet

Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs.

In utero inflammation may accelerate fetal lung maturation but may also play a role in the pathogenesis of chronic lung disease. We examined the impact of endotoxin, a potent proinflammatory stimulus, on structural and functional maturation of preterm sheep lungs. Date bred ewes received 20 mg Escherichia coli endotoxin or saline by ultrasound guided intra-amniotic injection at 119 d gestation. A comparison group of animals received 0.5 mg/kg betamethasone, a known maturational agent, at 118 d gestation. Lambs were delivered by cesarean section at 125 d (term = 150 d) and ventilated for 40 min. Lung function data are reported elsewhere. Total and differential white cell counts were performed on amniotic fluid and fetal lung fluid samples. Morphometric analyses were performed on inflation fixed right upper lobes. Total cell count increased slightly but not significantly in both amniotic fluid and fetal lung fluid. Both endotoxin and betamethasone had similar effects on alveolarization: average alveolar volume increased by approximately 20% and total alveolar number decreased by almost 30%. Both treatments led to thinning of alveolar walls, although this was statistically significant in the betamethasone-treated group only. Although antenatal endotoxin leads to striking improvements in postnatal lung function, this may be at the expense of normal alveolar development.

Accuracy of mini peak flow meters in indicating changes in lung function in children with asthma

Abstract Objective: To assess whether mini flow meters used to measure peak expiratory flow can track changes in lung function and indicate clinically important changes. Design: Comparison of measurements with a spirometer and different brands of mini flow meter;the meters were allocated to subjects haphazardly. Subjects: 12 boys with asthma aged 11 to 17 attending boarding school. Main outcome measures - Peak expiratory flow measured twice daily for three months with a spirometer and at least one of four brands of mini flow meter. Results: The relation between changes in lung function measured with the spirometer and those measured with the mini flow meters was generally poor. In all, 26 episodes (range 1-3 in an individual child) of clinically important deterioration in lung function were detected from the records obtained with the spirometer. ONe mini flow meter detected six of 19 episodes, one detected six of 15, one detected six of 18, and one detected three of 21. Conclusions: Not only are the absolute values of peak expiratory flow obtained with mini flow meters inaccurate but the clinical message may also be incorrect. These findings do not imply that home monitoring of peak expiratory flow has no place in the management of childhood asthma but that the values obtained should be interpreted cautiously.

Postnatal Lung Function after Prenatal Steroid Treatment in Sheep: Effect of Gender

The effect of fetal gender on postnatal lung function and response to prenatal steroid exposure were examined retrospectively in a group of 115 preterm lambs. Fetuses received a single intramuscular injection of 0.5 mg/kg betamethasone alone or in conjunction with l-thyroxine 48 h before delivery at 128-d gestational age. Control animals received an equivalent volume of saline. After delivery, respiratory mechanics and blood gas parameters were recorded for 40 min. Deflation pressure volume curves were constructed in excised lungs. Right upper lobes from a randomly selected subgroup of control animals were examined morphometrically. Control (saline-treated) females were able to be ventilated at lower ventilatory pressures with equivalent tidal volumes and more efficient gas exchange. There were no gender differences in compliance, conductance, or excised lung volumes for saline-treated animals. More efficient gas exchange in females could not be explained by thinner alveolar septa or greater alveolar surface area. After hormone treatment, both males and females exhibited significant improvements in respiratory mechanics, gas exchange, and an increase in alveolar surfactant concentration. However, females exhibited a significantly greater improvement than males for compliance, conductance, excised lung volume, and arterial oxygen partial pressure. These data provide a comprehensive description of gender differences in postnatal lung function and response to steroid treatment in preterm animals, and support clinical findings of sexual dimorphism.

Differing patterns of mechanical response to direct fetal hormone treatment

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Influence of duration of occlusion time on respiratory mechanics measured with the single-breath technique in infants

To determine the effect of the length of end‐inspiratory occlusion on the values of respiratory system compliance (Crs and resistance (Rrs) calculated from the single‐breath technique, 6 infants with cystic fibrosis were studied. End‐inspiratory occlusions lasted between 0.3 and 1.2 seconds, and between 8 and 32 separate occlusions were made in each infant. Examination of the individual data showed a systematic tendency for C, to decrease as the length of the airway occlusion increased, with statistical significance reached in two subjects. Using a random effects model, it was demonstrated that there was a decrease of 0.1 5 Ml/cmH2O in Crs for each 0.1 s increase in occlusion time. The influence of length of plateau time for C, was similar to that of total occlusion time. No such tendency was seen for Rrs. These data reinforce the current emphasis on greater standardization in the methodologies used for infant lung function testing and for more fully reporting methodological details. Pediatr Pulmonol. 1994; 17:250–257.

Environmental effects on pulmonary mechanics and the response to inhaled methacholine

To investigate the role of environmental exposure from birth on airway and lung parenchymal responsiveness to inhaled methacholine (Mch), three litters of puppies (n = 14) were studied when 8–10 weeks of age. Two litters, one mongrel (n = 7) and one foxhound‐beagle cross (n = 3), were born and raised in a clean animal house environment (clean mongrels and clean cross, respectively). Another litter of mongrels was born (n = 4) and raised in an external environment (external mongrels), exposed to normal rural environmental contaminants. Animals were studied open‐chested with alveolar capsules used to partition mechanics into airway and parenchymal components. Lung mechanics were measured after abrupt flow interruptions.

Effect of elastase instilled into the trachea on airways mechanics in guinea pigs

Instilled elastase caused an inflammatory response in the lungs of guinea pigs which was observed at 6 h, 24 h, and 48 h post-treatment. The inflammation was most marked at 24 h and was characterised by a loss of epithelial cilia and detachment of epithelial cells from the basement membrane, a marked increase in polymorphonuclear leukocytes (PMNs) in blood vessels of the tracheal submucosa and an infiltration of macrophages into the parenchyma. Compared with controls, isolated tracheal preparations from 24 h and 48 h elastase pretreated animals were hyperreactive (Emax) to histamine and carbachol. This hyperreactivity persisted in tracheas from 48 h elastase pretreated animals after removal of the epithelial layer. Parenchymal strips were hyperreactive to histamine only. Tissue sensitivity (EC50) was little affected by elastase. Tracheal preparations incubated in 0.01% elastase for 3 h responded normally. In vivo responses of Raw and Cdyn to histamine were unaffected by elastase at 24 h and 48 h. However, the slope of the dose-response curve to acetylcholine was steepened 24 h after elastase instillation, but not at 48 h. In contrast to other models of inflammation elastase evokes in vitro but not in vivo hyperresponsiveness.

Single and Repetitive Doses of Maternal Antenatal Betamethasome (Beta) are more potent than fetal Beta † 1034

Single and Repetitive Doses of Maternal Antenatal Betamethasome (Beta) are more potent than fetal Beta † 1034

Repetitive Prenatal Glucocorticoids Affect Lung Function and Growth in Preterm Lambs. † 911

Repetitive Prenatal Glucocorticoids Affect Lung Function and Growth in Preterm Lambs. † 911