Pulmonary function in bronchopulmonary dysplasia

Robin, Beverley; Kim, Young Jee; Huth, Jaimee; Klocksieben, Jim; Torres, Margaret; Tepper, Robert S.; Castile, Robert G.; Solway, Julian; Hershenson, Marc B.; Goldstein-Filbrun, Amy

doi:10.1002/ppul.10424

Cited by 140 publications

(139 citation statements)

References 23 publications

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“…20,21 Abnormalities in airflow obstruction and air trapping persist into adolescence. [22][23][24][25][26] Similarly, newborn animals exposed to Ն65% oxygen and recovered in room air develop long-term changes in airway responsiveness and increased lung volumes. [27][28][29][30][31] We previously reported that 8-week-old adult mice exposed to Ն60% oxygen for the first 4 days of life have simplified alveoli attributed to changes in elastin expression and an imbalance in alveolar epithelial type I and II cells.…”

mentioning

confidence: 99%

Neonatal Hyperoxia Causes Pulmonary Vascular Disease and Shortens Life Span in Aging Mice

Yee

White

Awad

et al. 2011

The American Journal of Pathology

113

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Bronchopulmonary dysplasia is a chronic lung disease observed in premature infants requiring oxygen supplementation and ventilation. Although the use of exogenous surfactant and protective ventilation strategies has improved survival, the long-term pulmonary consequences of neonatal hyperoxia are unknown. Here, we investigate whether neonatal hyperoxia alters pulmonary function in aging mice. By 67 weeks of age, mice exposed to 100% oxygen between postnatal days 1 to 4 showed significantly a shortened life span (56.6% survival, n ‫؍‬ 53) compared to siblings exposed to room air as neonates (100% survival, n ‫؍‬ 47). Survivors had increased lung compliance and decreased elastance. There was also right ventricular hypertrophy and pathological evidence for pulmonary hypertension, defined by reduction of the distal microvasculature and the presence of numerous dilated arterioles expressing von Willebrand factor and ␣-smooth muscle actin. Consistent with recent literature implicating bone morphogenetic protein (BMP) signaling in pulmonary vascular disease, BMP receptors and downstream phospho-Smad1/ 5/8 were reduced in lungs of aging mice exposed to neonatal oxygen. BMP signaling alterations were not observed in 8-week-old mice. These data suggest that loss of BMP signaling in aged mice exposed to neonatal oxygen is associated with a shortened life span, pulmonary vascular disease, and associated cardiac failure. People exposed to hyperoxia as neonates may be at increased risk for pulmonary hypertension.

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confidence: 99%

Neonatal Hyperoxia Causes Pulmonary Vascular Disease and Shortens Life Span in Aging Mice

Yee

White

Awad

et al. 2011

The American Journal of Pathology

113

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“…Although advances in the care of neonates have markedly reduced infant mortality, survivors often exhibit nonatopic airway wheezing (9,10), and many are rehospitalized when infected with respiratory syncytial virus (11,12). High blood pressure has also been observed in young adolescents who were born preterm (13).…”

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confidence: 99%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

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Supplemental oxygen used to treat infants born prematurely disrupts angiogenesis and is a risk factor for persistent pulmonary disease later in life. Although it is unclear how neonatal oxygen affects development of the respiratory epithelium, alveolar simplification and depletion of type II cells has been observed in adult mice exposed to hyperoxia between postnatal Days 0 and 4. Because hyperoxia inhibits cell proliferation, we hypothesized that it depleted the adult lung of type II cells by inhibiting their proliferation at birth. Newborn mice were exposed to room air (RA) or hyperoxia, and the oxygenexposed mice were recovered in RA. Hyperoxia stimulated mRNA expressed by type II (Sftpc, Abca3) and type I (T1a, Aquaporin 5) cells and inhibited Pecam expressed by endothelial cells. 5-Bromo-2'-deoxyuridine labeling and fate mapping with enhanced green fluorescence protein controlled statically by the Sftpc promoter or conditionally by the Scgb1a1 promoter revealed increased Sftpc and Abca3 mRNA seen on Day 4 reflected an increase in expansion of type II cells shortly after birth. When mice were returned to RA, this expanded population of type II cells was slowly depleted until few were detected by 8 weeks. These findings reveal that hyperoxia stimulates alveolar epithelial cell expansion when it disrupts angiogenesis. The loss of type II cells during recovery in RA may contribute to persistent pulmonary diseases such as those reported in children born preterm who were exposed to supplemental oxygen.

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“…Fortunately, antenatal steroid administrations to mothers in preterm labor, and the application of exogenous surfactant and mild ventilation strategies to premature babies, have markedly reduced their mortality. Unfortunately, survivors continue to show decreased lung capacity at 5-10 years of age and even as young adolescents (2)(3)(4). Moreover, these children are at increased risk for asthma, infection, and other respiratory diseases, and are often rehospitalized after respiratory infection (5,6).…”

mentioning

confidence: 99%

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

O’Reilly

Marr

Yee

et al. 2008

Am J Respir Crit Care Med

112

124

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Rationale: Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection. Objectives: To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. Methods: Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus. Measurements and Main Results: The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infectionassociated changes in IFN-g, IL-1b, IL-6, tumor necrosis factor-a, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1a, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis. Conclusions: These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.

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Pulmonary function in bronchopulmonary dysplasia

Cited by 140 publications

References 23 publications

Neonatal Hyperoxia Causes Pulmonary Vascular Disease and Shortens Life Span in Aging Mice

Neonatal Hyperoxia Causes Pulmonary Vascular Disease and Shortens Life Span in Aging Mice

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

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