Yee M, Chess PR, McGrath-Morrow SA, Wang Z, Gelein R, Zhou R, Dean DA, Notter RH, O'Reilly MA
Neonatal oxygen adversely affects lung function in adult mice without altering surfactant composition or activity. [JOURNAL ARTICLE]
Am J Physiol Lung Cell Mol Physiol 2009 Jul 17.
Supplemental oxygen is often used to treat premature infants in respiratory distress despite its potentially adverse effects on lung development and function. To understand how neonatal hyperoxia can permanently disrupt lung development, we previously reported that adult mice exposed to 100% FiO2 between postnatal days 1 - 4 have increased lung compliance, greater alveolar simplification, and disrupted epithelial development. Here, we investigate whether oxygen-induced changes in lung function are attributable to defects in surfactant composition and activity, structural changes in alveolar development, or both. Newborn mice were exposed to room air, 40%, 60%, 80%, or 100% oxygen between postnatal days 1 - 4 and recovered in room air until 8 weeks of age. Lung compliance and alveolar size increased, and airway resistance, airway elastance, tissue elastance, and tissue damping decreased in mice exposed to 60-80% oxygen with even greater changes seen at 100% oxygen. These alterations in lung function were not associated with changes in total protein content or surfactant phospholipid composition in bronchoalveolar lavage (BAL). Moreover, large surfactant aggregates centrifuged from BAL were unchanged from control in percentage content, surface activity, and total and hydrophobic protein content. Instead, the number of type II cells progressively declined in 60-100% oxygen while levels of T1alpha, a protein expressed by type I cells was comparably increased in mice exposed to 40-100% oxygen. Thickened bundles of elastin fibers were also detected in alveolar walls of mice exposed to 60% or more oxygen. These findings support the hypothesis that changes in lung development rather than surfactant activity are the primary causes of oxygen-altered lung function seen in children who were exposed to oxygen as neonates. Furthermore, the disruptive effects of oxygen on epithelial development and lung mechanics are not equivalently dose-dependent. Key words: hyperoxia, bronchopulmonary dysplasia, epithelium, type II cells.
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