Projects per year
Abstract
Abnormalities of the airway smooth muscle (ASM) layer in asthma may develop before birth. We hypothesize that antenatal inflammation causes physiological abnormalities of the ASM that predisposes asthma. This study determined the short-term effects of antenatal inflammation on the developing ASM. Fourteen pregnant ewes were randomly assigned to one of three groups. Fetal lambs were exposed to intra-amniotic injections of lipopolysaccharide (LPS, n = 4) or saline (controls; n = 5) at 127 days' gestational age (GA). Preterm lambs were surgically delivered at 129 days' GA and received intensive care for 7 days before euthanasia. Naïve fetal controls (n = 5) were delivered and euthanized at 136 days' GA. ASM force to acetylcholine was measured in bronchial rings and normalized to ring length (tension) and ASM cross-sectional area (stress). Airway narrowing (% volume) to acetylcholine was assessed in bronchial segments. Fetal controls were structurally and functionally similar to saline-exposed lambs. Compared with saline, LPS-exposed lambs had increased macrophages in lung tissue (P = 0.0002) and interleukin-8 in alveolar wash (P = 0.003). LPS exposure increased ASM thickness (P = 0.005), airway narrowing (P = 0.003), ASM tension (P = 0.0002), and contractile stress (P < 0.0001). Notably, LPS-exposed lambs were more dependent on mechanical ventilation, and both LPS (P < 0.001) and ventilation (P = 0.012) were independent factors in increasing ASM stress. Only LPS independently increased ASM thickness (P = 0.045). Results indicate that antenatal exposure to LPS and subsequent mechanical ventilation promotes intrinsic changes to the ASM that enhances bronchoconstriction. If persistent into postnatal life, these developmental abnormalities may contribute to the known association between chorioamnionitis and asthma.NEW & NOTEWORTHY Abnormalities of the airway smooth muscle (ASM) layer in asthma may develop before birth. Using an ovine model of antenatal inflammation, we demonstrate thickening and increased contraction of the premature ASM layer. If such physiological abnormalities persist throughout postnatal life, this represents a predisposition to an asthma diagnosis.
Original language | English |
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Pages (from-to) | 959-969 |
Number of pages | 11 |
Journal | Journal of applied physiology (Bethesda, Md. : 1985) |
Volume | 133 |
Issue number | 4 |
DOIs | |
Publication status | Published - 1 Oct 2022 |
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Dive into the research topics of 'Airway smooth muscle thickness and contraction are enhanced by intra-amniotic lipopolysaccharide in an ovine model of premature birth'. Together they form a unique fingerprint.Projects
- 3 Finished
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Ontogeny of the airway smooth muscle layer
Noble, P. (Investigator 01), Pillow, J. (Investigator 02), James, A. (Investigator 03) & Elliot, J. (Investigator 04)
NHMRC National Health and Medical Research Council
1/01/15 → 31/12/19
Project: Research
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Separating the adverse neurodevelopmental consequences of mechanical ventilation and postnatal steroids in preterm lambs
Pillow, J. (Investigator 01), Blache, D. (Investigator 02), Albertine, K. (Investigator 03), Noble, P. (Investigator 04), Gill, A. (Investigator 05), Black, M. (Investigator 06) & Rubenson, J. (Investigator 07)
NHMRC National Health and Medical Research Council
1/01/14 → 31/12/18
Project: Research
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Improving the Immediate and Longer-Term Health Outcomes of Preterm Infants
Pillow, J. (Investigator 01), Simmer, K. (Investigator 02), Patole, S. (Investigator 03), Strunk, T. (Investigator 04), Moss, T. (Investigator 05), Burgner, D. (Investigator 06), Whitehouse, A. (Investigator 07), Prescott, S. (Investigator 08), Tingay, D. (Investigator 09) & Gill, A. (Investigator 10)
NHMRC National Health and Medical Research Council
1/01/13 → 30/09/21
Project: Research