Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease
Introduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-05-01
|
Series: | Frontiers in Medicine |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.674324/full |
id |
doaj-fa42c31b72fc4b46aad88959c39597a3 |
---|---|
record_format |
Article |
spelling |
doaj-fa42c31b72fc4b46aad88959c39597a32021-05-31T05:43:12ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-05-01810.3389/fmed.2021.674324674324Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic DiseaseJack O. Kalotas0Carolyn J. Wang1Peter B. Noble2Kimberley C. W. Wang3Kimberley C. W. Wang4School of Human Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Human Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Human Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Human Sciences, The University of Western Australia, Crawley, WA, AustraliaTelethon Kids Institute, The University of Western Australia, Nedlands, WA, AustraliaIntroduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness.Methods: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control – normoxic and saline challenge; IUGR – hypoxic and saline challenge; Allergy – normoxic and OVA challenge; and IUGR + Allergy – hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry.Results: IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome.Conclusion: IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen.https://www.frontiersin.org/articles/10.3389/fmed.2021.674324/fullairway hyperresponsivenessallergyintrauterine growth restrictionasthmalung function |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jack O. Kalotas Carolyn J. Wang Peter B. Noble Kimberley C. W. Wang Kimberley C. W. Wang |
spellingShingle |
Jack O. Kalotas Carolyn J. Wang Peter B. Noble Kimberley C. W. Wang Kimberley C. W. Wang Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease Frontiers in Medicine airway hyperresponsiveness allergy intrauterine growth restriction asthma lung function |
author_facet |
Jack O. Kalotas Carolyn J. Wang Peter B. Noble Kimberley C. W. Wang Kimberley C. W. Wang |
author_sort |
Jack O. Kalotas |
title |
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease |
title_short |
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease |
title_full |
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease |
title_fullStr |
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease |
title_full_unstemmed |
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease |
title_sort |
intrauterine growth restriction promotes postnatal airway hyperresponsiveness independent of allergic disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2021-05-01 |
description |
Introduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness.Methods: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control – normoxic and saline challenge; IUGR – hypoxic and saline challenge; Allergy – normoxic and OVA challenge; and IUGR + Allergy – hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry.Results: IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome.Conclusion: IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen. |
topic |
airway hyperresponsiveness allergy intrauterine growth restriction asthma lung function |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2021.674324/full |
work_keys_str_mv |
AT jackokalotas intrauterinegrowthrestrictionpromotespostnatalairwayhyperresponsivenessindependentofallergicdisease AT carolynjwang intrauterinegrowthrestrictionpromotespostnatalairwayhyperresponsivenessindependentofallergicdisease AT peterbnoble intrauterinegrowthrestrictionpromotespostnatalairwayhyperresponsivenessindependentofallergicdisease AT kimberleycwwang intrauterinegrowthrestrictionpromotespostnatalairwayhyperresponsivenessindependentofallergicdisease AT kimberleycwwang intrauterinegrowthrestrictionpromotespostnatalairwayhyperresponsivenessindependentofallergicdisease |
_version_ |
1721419552971030528 |