Recent advances in antenatal factors predisposing to bronchopulmonary dysplasia

Taglauer, Elizabeth; Abman, Steven H.; Keller, Roberta L.

doi:10.1053/j.semperi.2018.09.002

Cited by 64 publications

(55 citation statements)

References 76 publications

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“…Similarly, decreased placental villous vascularity was seen in BPD-associated PH 14 , 15 . These studies show that placental disturbances play a vital role in lung alveolarization and represent a novel and important area in lung developmental pathobiology 16 , 17 .…”

Section: Epidemiology and Pathophysiologymentioning

confidence: 79%

Recent advances in understanding and management of bronchopulmonary dysplasia

Sahni

Bhandari

2020

F1000Res

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In the current era, the survival of extremely low-birth-weight infants has increased considerably because of new advances in technology; however, these infants often develop chronic dysfunction of the lung, which is called bronchopulmonary dysplasia (BPD). BPD remains an important cause of neonatal mortality and morbidity despite newer and gentler modes of ventilation. BPD results from the exposure of immature lungs to various antenatal and postnatal factors that lead to an impairment in lung development and aberrant growth of lung parenchyma and vasculature. However, we still struggle with a uniform definition for BPD that can help predict various short- and long-term pulmonary outcomes. With new research, our understanding of the pathobiology of this disease has evolved, and many new mechanisms of lung injury and repair are now known. By utilizing the novel ‘omic’ approaches in BPD, we have now identified various factors in the disease process that may act as novel therapeutic targets in the future. New investigational agents being explored for the management and prevention of BPD include mesenchymal stem cell therapy and insulin-like growth factor 1. Despite this, many questions remain unanswered and require further research to improve the outcomes of premature infants with BPD.

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Section: Epidemiology and Pathophysiologymentioning

confidence: 79%

Recent advances in understanding and management of bronchopulmonary dysplasia

Sahni

Bhandari

2020

F1000Res

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“…Analysis of placental tissues also allows a critical viewpoint of SARS CoV-2 physiology in primary human tissue, which may be informative for other organ systems. The placenta shares many developmental and physiological similarities with the lung [ 44 ] and as mucosal immune interface, placental leukocyte populations have many well-recognized parallels with the immune repertoire of the small and large intestine [ 45 ]. Thus ongoing study of COVID-19 physiology within the placenta can significantly inform management and surveillance of pregnant women and infants during this pandemic, while providing a key source of primary tissue for development of ongoing diagnostic and therapeutic targets critical in the effort to reduce the global burden of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads

et al. 2020

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Introduction While the COVID-19 pandemic continues to have a significant global health impact, rates of maternal to infant vertical transmission remain low (<5%). Parenchymal changes of placentas from COVID-19 infected mothers have been reported by several groups, but the localization and relative abundance of SARS-CoV-2 viral proteins and cellular entry machinery has not been fully characterized within larger placental tissue cohorts. Methods An extended placental tissue cohort including samples from 15 COVID-19 positive maternal-fetal dyads (with n = 5 cases with evidence of fetal transmission) in comparison with 10 contemporary COVID-19 negative controls. Using comparative immunofluorescence, we examined the localization and relative tissue abundance of SARS-CoV2 spike glycoprotein (CoV2 SP) along with the co-localization of two SARS-CoV2 viral entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Results/conclusions CoV2 SP was present within the villous placenta in COVID-19 positive pregnancies with and without evidence of fetal transmission. We further identified the predominance of ACE2 expression in comparison with TMPRSS2. Importantly, both CoV2 SP and ACE2 expression consistently localized primarily within the outer syncytiotrophoblast layer placental villi, a key physiologic interface between mother and fetus. Overall this study provides an important basis for the ongoing evaluation of SARS-CoV-2 physiology in pregnancy and highlights the importance of the placenta as a key source of primary human tissue for ongoing diagnostic and therapeutic research efforts to reduce the global burden of COVID-19.

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“…The risk factors for PH, which overlap with those for BPD, include low gestational age, fetal growth restriction, oligohydramnios, prolonged mechanical ventilation, and oxygen dependency (9, 10). In normal lung development, alveolarization, and vascularization of the distal lung saccules run in parallel (11).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension

et al. 2019

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Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously shown that IL-1 receptor antagonist (IL-1Ra) protects against murine BPD; therefore, we hypothesized that IL-1Ra may also be effective against BPD-PH. We employed daily injections of IL-1Ra in a murine model in which BPD/BPD-PH was induced by antenatal LPS and postnatal hyperoxia of 65% O 2 . Pups reared in hyperoxia for 28 days exhibited a BPD-PH-like disease accompanied by significant changes in pulmonary vascular morphology: micro-CT revealed an 84% reduction in small vessels (4–5 μm diameter) compared to room air controls; this change was prevented by IL-1Ra. Pulmonary vascular resistance, assessed at day 28 of life by echocardiography using the inversely-related surrogate marker time-to-peak-velocity/right ventricular ejection time (TPV/RVET), increased in hyperoxic mice (0.27 compared to 0.32 in air controls), and fell significantly with daily IL-1Ra treatment (0.31). Importantly, in vivo cine-angiography revealed that this protection afforded by IL-1Ra treatment for 28 days is maintained at day 60 of life. Despite an increased abundance of mediators of pulmonary angiogenesis in day 5 lung lysates, namely vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1), no difference was detected in ex vivo pulmonary vascular reactivity between air and hyperoxia mice as measured in precision cut lung slices, or by immunohistochemistry in alpha-smooth muscle actin (α-SMA) and endothelin receptor type-A (ET A ) at day 28. Further, on day 28 of life we observed cardiac fibrosis by Sirius Red staining, which was accompanied by an increase in mRNA expression of galectin-3 and CCL2 (chemokine (C-C motif) ligand 2) in whole hearts of hyperoxic pups, which improved with IL-1Ra. In summary, our findings suggest that daily administration of the anti-inflammatory IL-1Ra prevents the increase in pulmonary vascular resistance and the pulmonary dysangiogenesis of murine BPD-PH, thus pointing to IL-1Ra as a promising candidate for the treatment of both BPD and BPD-PH.

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Recent advances in antenatal factors predisposing to bronchopulmonary dysplasia

Cited by 64 publications

References 76 publications

Recent advances in understanding and management of bronchopulmonary dysplasia

Recent advances in understanding and management of bronchopulmonary dysplasia

Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension

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