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We hypothesized that <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> disrupts airway development leading to postnatal structural abnormalities of the airway that predispose to disease. This study therefore examined structural changes to the airway and lung in a rat model of maternal hypoxia\u2010induced <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant rats were housed under hypoxic conditions (11.5% <jats:styled-content style=\"fixed-case\">O<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>) from gestational days (<jats:styled-content style=\"fixed-case\">GDs<\/jats:styled-content>) 13 to <jats:styled-content style=\"fixed-case\">20<\/jats:styled-content> (pseudoglandular\u2013canalicular stages, i.e. period of airway development) and then returned to normoxic conditions (21% <jats:styled-content style=\"fixed-case\">O<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>). A control group of pregnant rats was housed under normoxic conditions throughout pregnancy. Weights of male offspring were recorded at birth and 7\u2009weeks of age (adulthood), at which point lungs were fixed for morphometry and stereology (<jats:italic>n<\/jats:italic>\u2009=\u20096\/group), or bronchoalveolar lavage fluid (<jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content>) was collected for cell counts (<jats:italic>n<\/jats:italic>\u2009=\u20096\/group).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\n<jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> offspring were lighter at birth compared with control, but not at 7\u2009weeks. While there was no difference in mean airway dimensions or lung volume, there was greater anatomical variation in airway lumen area in the <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> group. A mathematical model of the human lung was used to show that greater heterogeneity in lumen area in <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content>\u2010affected individuals increases bronchoconstriction during simulated bronchial challenge. More macrophages were identified in the <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The rat model demonstrates that <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> leads to a more heterogeneous distribution of airway lumen calibre in adulthood with potential implications for bronchoconstriction in human subjects. Together with increased lung macrophages, these findings support a phenotypic shift after <jats:styled-content style=\"fixed-case\">IUGR<\/jats:styled-content> that may impact disease susceptibility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.13071","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T01:32:48Z","timestamp":1495071168000},"page":"1329-1335","source":"Crossref","is-referenced-by-count":16,"title":["Increased heterogeneity of airway calibre in adult rats after hypoxia\u2010induced intrauterine growth restriction"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-5909","authenticated-orcid":false,"given":"Kimberley C.W.","family":"Wang","sequence":"first","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jude 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