Autor: |
Robinson, Joshua L., Roff, Andrea J., Hammond, Sarah J., Darby, Jack R. T., Meakin, Ashley S., Holman, Stacey L., Tai, Andrew, Moss, Tim J. M., Dimasi, Catherine G., Jesse, Sarah M., Wiese, Michael D., Davies, Andrew N., Muhlhausler, Beverly S., Bischof, Robert J., Wallace, Megan J., Clifton, Vicki L., Morrison, Janna L., Stark, Michael J., Gatford, Kathryn L. |
Předmět: |
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Zdroj: |
Experimental Physiology; Nov2024, Vol. 109 Issue 11, p1967-1979, 13p |
Abstrakt: |
Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant‐producing cells and lower surfactant‐protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P < 0.001), but not SFTPC (P = 0.177) or SFTPD (P = 0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P = 0.007), dynamic lung compliance (P < 0.001), and SFTPA (P = 0.037) and SFTPB gene expression (P = 0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near‐term neonates, even in the absence of impairment by maternal asthma. What is the central question of this study?Does antenatal betamethasone before near‐term delivery mitigate the increased risk of neonatal lung disease in a sheep model of maternal asthma?What is the main finding and its importance?Maternal asthma did not impair neonatal lung function or reduce surfactant gene expression, likely reflecting a mild maternal and fetal phenotype in this cohort. Nevertheless, antenatal maternal betamethasone treatment in asthmatic pregnancies increased dynamic lung compliance and surfactant protein A and B mRNA expression in newborn lambs. These data suggest potential benefits of betamethasone on lung maturation when mothers have asthma. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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