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Neonatal inhalation of hyperoxic gas and altered postnatal growth: effects on the pulmonary airways in adulthood

Richard Harding, Megan O’Reilly, Foula Sozo

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Abstract

Our objective was to determine the long‐term effects of neonatal hyperoxia alone on the bronchioles, in the absence of growth restriction. Newborn mice (C57Bl/6J) were raised in hyperoxic gas (65% O 2 ) until postnatal day 7 (P7d), after which they lived in room air until adulthood (P56d). During hyperoxia, dams remained in 65% O 2 (H‐E group), or were alternated every 24h between hyperoxia and room air (H‐E/air group) to prevent weight loss and growth restriction of offspring. Controls breathed room air. At P56d, the structure of the bronchioles and lung parenchyma was morphometrically analysed. H‐E dams were lighter 4–13d after delivery whereas weights of H‐E/air dams were not different from controls. During hyperoxia, H‐E pups had reduced growth; H‐E/air pups grew at the same rate as controls. At P56d, lungs of H‐E (n=26) and H‐E/air (n=21) mice had larger alveoli, less parenchymal tissue and thicker airway epithelium than controls (n=27). The airway epithelium of H‐E/air mice had a greater proportion of proliferating and ciliated cells and a lower proportion of Clara cells. H‐E mice had more airway smooth muscle and collagen, whereas collagen was reduced in H‐E/air mice. Neonatal hyperoxia with or without growth restriction induces persistent alterations in the bronchioles and lung parenchyma, which may contribute to lung dysfunction. Research support: National Health and Medical Research Council of Australia.

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What this paper is about

Our objective was to determine the long‐term effects of neonatal hyperoxia alone on the bronchioles, in the absence of growth restriction. Newborn mice (C57Bl/6J) were raised in hyperoxic gas (65% O 2 ) until postnatal day 7 (P7d), after which they lived in room air until adulthood (P56d). During hyperoxia, dams remained in 65% O 2 (H‐E group), or were alternated every 24h between hyperoxia and room air (H‐E/air group) to prevent weight loss and growth restriction of offspring. Controls breathed room air. At P56d, the structure of the bronchioles and lung parenchyma was morphometrically analysed. H‐E dams were lighter 4–13d after delivery whereas weights of H‐E/air dams were not different from controls. During hyperoxia, H‐E pups had reduced growth; H‐E/air pups grew at the same rate as controls. At P56d, lungs of H‐E (n=26) and H‐E/air (n=21) mice had larger alveoli, less parenchymal tissue and thicker airway epithelium than controls (n=27). The airway epithelium of H‐E/air mice had a greater proportion of proliferating and ciliated cells and a lower proportion of Clara cells. H‐E mice had more airway smooth muscle and collagen, whereas collagen was reduced in H‐E/air mice. Neonatal hyperoxia with or without growth restriction induces persistent alterations in the bronchioles and lung parenchyma, which may contribute to lung dysfunction. Research support: National Health and Medical Research Council of Australia.

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Available abstract

Our objective was to determine the long‐term effects of neonatal hyperoxia alone on the bronchioles, in the absence of growth restriction. Newborn mice (C57Bl/6J) were raised in hyperoxic gas (65% O 2 ) until postnatal day 7 (P7d), after which they lived in room air until adulthood (P56d). During hyperoxia, dams remained in 65% O 2 (H‐E group), or were alternated every 24h between hyperoxia and room air (H‐E/air group) to prevent weight loss and growth restriction of offspring. Controls breathed room air. At P56d, the structure of the bronchioles and lung parenchyma was morphometrically analysed. H‐E dams were lighter 4–13d after delivery whereas weights of H‐E/air dams were not different from controls. During hyperoxia, H‐E pups had reduced growth; H‐E/air pups grew at the same rate as controls. At P56d, lungs of H‐E (n=26) and H‐E/air (n=21) mice had larger alveoli, less parenchymal tissue and thicker airway epithelium than controls (n=27). The airway epithelium of H‐E/air mice had a greater proportion of proliferating and ciliated cells and a lower proportion of Clara cells. H‐E mice had more airway smooth muscle and collagen, whereas collagen was reduced in H‐E/air mice. Neonatal hyperoxia with or without growth restriction induces persistent alterations in the bronchioles and lung parenchyma, which may contribute to lung dysfunction. Research support: National Health and Medical Research Council of Australia.

Key concepts: Hyperoxia, Parenchyma, Room air distribution, Lung, Inhalation, Andrology, Respiratory epithelium, Respiratory system

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