Using Experimental Models to Identify Pathogenic Pathways and Putative Disease Management Targets in Bronchopulmonary Dysplasia

Morty, Rory E.

doi:10.1159/000506989

Cited by 20 publications

(12 citation statements)

References 48 publications

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“…Despite this, prenatal hypoxia, especially in preterm infants, and hyperoxia risk factors are far less significant clinical frameworks in animal BPD models. In addition, There there are limited utility for examining breathing dynamics, gas exchange, and pulmonary hemodynamics [159]. There seems to be an urgent need to adapt current models to more accurately reflect the pathological mechanisms at work in affected fetus and newborn infant, and conduct more rigorous evaluations of possible eligible pharmacological and nonpharmacological therapies for the treatment of BPD.…”

Section: Perspectives For Treatment and Prevention Of Neonatal Chronic Lung Diseasementioning

confidence: 99%

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

et al. 2021

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Clinically, intrauterine hypoxia is the foremost cause of perinatal morbidity and developmental plasticity in the fetus and newborn infant. Under hypoxia, deviations occur in the lung cell epigenome. Epigenetic mechanisms (e.g., DNA methylation, histone modification, and miRNA expression) control phenotypic programming and are associated with physiological responses and the risk of developmental disorders, such as bronchopulmonary dysplasia. This developmental disorder is the most frequent chronic pulmonary complication in preterm labor. The pathogenesis of this disease involves many factors, including aberrant oxygen conditions and mechanical ventilation-mediated lung injury, infection/inflammation, and epigenetic/genetic risk factors. This review is focused on various aspects related to intrauterine hypoxia and epigenetic programming in lung development and disease, summarizes our current knowledge of hypoxia-induced epigenetic programming and discusses potential therapeutic interventions for lung disease.

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Section: Perspectives For Treatment and Prevention Of Neonatal Chronic Lung Diseasementioning

confidence: 99%

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

et al. 2021

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“…Refining the existing models to recapitulate the pathology at play in the infants is an urgent matter in order to better evaluate new interventions for BPD [ 54 ]. Most animal experiments are carried out to gather information about health in humans and aim to investigate new interventions that are intended for future use in humans.…”

Section: Discussionmentioning

confidence: 99%

Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns: a systematic review

et al. 2021

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Background Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation plays an important role in pathogenesis, antileukotrienes have been explored in both clinical and animal studies. We aimed to assess the benefits and harms of antileukotrienes for the prevention and treatment of respiratory morbidity and mortality in very preterm newborns. Methods In this systematic review, we included randomized trials and non-randomized studies in humans and animals reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. Our pre-specified primary outcomes were all-cause mortality and any harm, and, for the clinical studies, incidence of chronic lung disease. Included studies underwent risk of bias-assessment and data extraction performed by two authors independently. There were no language restrictions. Results Fifteen studies totally met our inclusion criteria: one randomized trial and four non-randomized studies in humans and 10 animal studies (five in rodents, two in lambs and one in either guinea pigs, rabbits or caprinae). All five clinical studies used montelukast and had a small sample size, ranging from 4 to 77 infants. The randomized trial (n = 60) found no difference in the incidence of chronic lung disease between the groups. Only one clinical study, which enrolled four very preterm infants and had a critical overall risk of bias, reported long-term outcomes. All other studies had unclear or greater overall risk of bias and meta-analyses were therefore deemed unfeasible. Eight of ten animal studies used leukotriene receptor antagonists as antileukotriene (montelukast in three of ten studies) and seven had an experimental study design (i.e. some animals were not exposed to antileukotrienes but no randomization). Three of the ten animal studies assessed different doses. Animal studies found no effect on the outcomes mortality, growth, or lung function related surrogate outcomes. Conclusions Use of antileukotrienes in very preterm infants to prevent or treat chronic lung disease is not supported by the available evidence. Large randomized trials focusing on outcomes relevant to patients, including long-term outcomes, are needed. Studies should also minimize risk of bias.

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“…What is the internal validity of these studies, and consequently, how reliable and applicable are these findings? As the volume of research reports continues to grow, this is an important consideration in systematic reviews that aim to synthesize evidence from studies using animal models [9][10][11]. Animal models are used to study a range of neonatal morbidities with the aim of informing selection of the most promising treatment strategies for clinical trials.…”

Section: Reducing Research Wastementioning

confidence: 99%