Poster Presentation ESA-SRB-APEG-NZSE 2022

Progression of experimental asthma during ovine pregnancy  (#404)

Andrea J Roff 1 , Joshua L Robinson 1 , David J Sharkey 1 , Andrew N Davies 2 , Vicki L Clifton 3 , Megan J Wallace 4 5 , Tim JM Moss 5 , Sarah J Hammond 1 6 , Jack RT Darby 6 , Andrew Tai 1 7 , Michael J Stark 1 7 , Beverly S Muhlhausler 8 9 , Robert J Bischof 10 , Janna L Morrison 6 , Kathryn L Gatford 1
  1. Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia
  2. Biomedicine Discovery Institute, Monash University, Frankston, VIC, Australia
  3. Mater Medical Research Institute, , University of Queensland, Brisbane, QLD, Australia
  4. The Ritchie Centre, Hudson Institute for Medical Research, Clayton, VIC, Australia
  5. Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
  6. Early Origins of Adult Health Research Group, Health and Biomedical Innovation and Health Sciences, University of South Australia, Adelaide, SA, Australia
  7. Women’s & Children’s Hospital, Adelaide, SA, Australia
  8. Health & Biosecurity, CSIRO, Adelaide, SA, Australia
  9. School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, South Australia, Australia
  10. Institute for Innovation, Science and Sustainability, Federation University Australia, Berwick, VIC, Australia

Asthma affects >40,000 Australian pregnancies each year and increases the risk of adverse pregnancy outcomes. Good asthma control normalises risks of most adverse pregnancy outcomes, but ~50% of women with asthma experience a loss of asthma control during pregnancy. It is not clear from human studies whether pregnancy itself worsens asthma.

We explored this question using an experimental sheep model of allergic asthma, induced by sensitisation and repeated airway challenge with house dust mite (HDM); controls received saline. Circulating cytokines were measured in age-matched non-pregnant ewes (8 control, 9 asthmatic), singleton-bearing ewes (5 control, 8 asthmatic) and twin-bearing ewes (6 control, 9 asthmatic) before sensitisation, and before and 48 hours after airway challenge, pre-mating and in late pregnancy (gestational day (GD)132, term = GD150). Pre-challenge airway function was studied in the same animals before mating, in early-mid (GD62) and late pregnancy, and in age-matched non-pregnant ewes.

In late pregnancy, plasma IL-4 (P=0.026) and IL-6 (P=0.010), but not IL-10 (P>0.9), increased post airway challenge, and did not differ between control and asthmatic ewes overall. Plasma IL-6 (P<0.001) levels were higher in late pregnant ewes than age-matched non-pregnant ewes. The decrease in dynamic compliance from pre-mating to GD132 was greater in asthmatic than control ewes (P=0.040), irrespective of litter size. Transpulmonary pressure, a measure of breathing effort, increased similarly across pregnancy in control and asthmatic ewes (P=0.123) and more in twin-bearing than non-pregnant ewes (P=0.020). At GD132, transpulmonary pressure was higher in asthmatic than control non-pregnant (P=0.031), but not pregnant, ewes.

Asthma had no effect on circulating IL-4, IL-6 or IL-10 concentrations. Lung function in experimental asthma worsened similarly in non-pregnant and pregnant ewes. This suggests that variable changes in asthma phenotype during human pregnancy may reflect behaviours such as reducing medication use rather than effects of pregnancy itself.