Paediatric origins of adult lung disease bullet 8: Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy)

Eber, Ernst; Zach, M

doi:10.1136/thorax.56.4.317

Cited by 174 publications

(149 citation statements)

References 106 publications

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“…The consensus from these histologic studies is that there is delay in acinar and alveolar development in preterm survivors up to 3 years of age. Taken together with the theory that human alveolarization is complete at 3 years, it was assumed that deranged alveolar structure would be a lifelong feature in preterm survivors (9,15).…”

Section: Discussionmentioning

confidence: 99%

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Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance

Narayanan

Beardsmore

Owers‐Bradley

et al. 2013

Am J Respir Crit Care Med

133

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Rationale: Histologic data from fatal cases suggest that extreme prematurity results in persisting alveolar damage. However, there is new evidence that human alveolarization might continue throughout childhood and could contribute to alveolar repair. Objectives: To examine whether alveolar damage in extreme-preterm survivors persists into late childhood, we compared alveolar dimensions between schoolchildren born term and preterm, using hyperpolarized helium-3 magnetic resonance. Methods: We recruited schoolchildren aged 10-14 years stratified by gestational age at birth (weeks) to four groups: (1) term-born (37-42 wk; n ¼ 61); (2) mild preterm (32-36 wk; n ¼ 21); (3) extreme preterm (,32 wk, not oxygen dependent at 4 wk; n ¼ 19); and (4) extreme preterm with chronic lung disease (,32 wk and oxygen dependent beyond 4 wk; n ¼ 18). We measured lung function using spirometry and plethysmography. Apparent diffusion coefficient, a surrogate for average alveolar dimensions, was measured by helium-3 magnetic resonance. Measurements and Main Results: The two extreme preterm groups had a lower FEV 1 (P ¼ 0.017) compared with term-born and mild preterm children. Apparent diffusion coefficient was 0.092 cm 2 /second (95% confidence interval, 0.089-0.095) in the term group. Corresponding values were 0.096 (0.091-0.101), 0.090 (0085-0.095), and 0.089 (0.083-0.094) in the mild preterm and two extreme preterm groups, respectively, implying comparable alveolar dimensions across all groups. Results did not change after controlling for anthropometric variables and potential confounders. Conclusions: Alveolar size at school age was similar in survivors of extreme prematurity and term-born children. Because extreme preterm birth is associated with deranged alveolar structure in infancy, the most likely explanation for our finding is catch-up alveolarization.Keywords: alveolar structure; lung acinus; bronchopulmonary dysplasia; neonatal chronic lung disease Advances in preterm care have led to increased survival of extremely premature babies, with increasing numbers reaching adulthood. This has shifted the focus of research from survival toward long-term sequelae of prematurity (1, 2). Infants born extremely preterm are known to have arrested alveolar development, manifesting as fewer and larger alveoli (3, 4). Schoolage and adult survivors of extreme preterm birth are known to have long-term respiratory problems, particularly decreased forced expiratory volumes and increased residual lung volumes, suggesting airway damage (5, 6). There are insufficient data regarding structure and development of the periphery of the lung in long-term survivors of preterm birth because studies on this cohort have relied on traditional lung function tests that only provide an overall estimate of function.The short-and long-term outcomes described previously correlate with gestational age (GA) at birth and the presence of chronic lung disease of prematurity (CLD), one of the early pulmonary sequelae of extreme preterm birth (6-8). Most evidence regard...

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Section: Discussionmentioning

confidence: 99%

“…Animal studies have not assessed preterm survivors beyond a human equivalent of 3 years of age (9). Because human alveolarization was thought to be complete by 3 years of age (13,14), the histologic data were extrapolated to postulate persistence of acinar damage in preterm and CLD survivors (9,15).…”

mentioning

confidence: 99%

Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance

Narayanan

Beardsmore

Owers‐Bradley

et al. 2013

Am J Respir Crit Care Med

133

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“…1 Infants born prematurely also have reduced antioxidant defenses and are sensitive to oxidant injury that can be exacerbated by therapeutic oxygen. [2][3][4][5] Although improved clinical treatments have reduced the incidence of airway injury, inflammation, and fibrosis typically seen in the pre-surfactant era, infants dying from BPD today have simplified alveoli that are less vascularized.…”

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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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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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“…Supplemental oxygen used to treat preterm infants in respiratory distress is a major risk factor for bronchopulmonary dysplasia (BPD), a chronic lung disease seen in infants needing oxygen therapy beyond 36 weeks postconceptual age (1). Although the use of milder ventilation strategies, exogenous surfactant, and antenatal steroids has reduced the incidence of airway inflammation and fibrosis, infants dying from BPD have simplified alveoli that are less vascularized (2).…”

mentioning

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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Paediatric origins of adult lung disease bullet 8: Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy)

Cited by 174 publications

References 106 publications

Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance

Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance

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

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

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Paediatric origins of adult lung disease bullet 8: Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy)

Cited by 174 publications

References 106 publications

Catch-up Alveolarization in Ex-Preterm Children. Evidence from 3He Magnetic Resonance

Catch-up Alveolarization in Ex-Preterm Children. Evidence from 3He Magnetic Resonance

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

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

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Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance

Catch-up Alveolarization in Ex-Preterm Children. Evidence from ³He Magnetic Resonance