Pulmonary phenotypes of bronchopulmonary dysplasia in the preterm infant.

Bronchopulmonary dysplasia (BPD) remains the most common complication of premature birth, imposing a significant and potentially life-long burden on patients and their families. Despite advances in our understanding of the mechanisms that contribute to patterns of lung injury and dysfunctional repair, current therapeutic strategies remain non-specific with limited success. Contemporary definitions of BPD continue to rely on clinician prescribed respiratory support requirements at specific time points. While these criteria may be helpful in broadly identifying infants at higher risk of adverse outcomes, they do not offer any precise information regarding the degree to which each compartment of the lung is affected. In this review we will outline the different pulmonary phenotypes of BPD and discuss important features in the pathogenesis, clinical presentation, and management of these frequently overlapping scenarios.

Reduction of unnecessary antibiotic days in a level IV neonatal intensive care unit.

Objective: Antibiotics are widely prescribed in the neonatal intensive care unit (NICU) and duration of prescription is varied. We sought to decrease unnecessary antibiotic days for the most common indications in our outborn level IV NICU by 20% within 1 year. Design and interventions: A retrospective chart review was completed to determine the most common indications and treatment duration for antibiotic therapy in our 39-bed level IV NICU. A multidisciplinary team was convened to develop an antibiotic stewardship quality improvement initiative with new consensus guidelines for antibiotic duration for these common indications. To optimize compliance, prospective audit was completed to ensure antibiotic stop dates were utilized and provider justification for treatment duration was documented. Multiple rounds of educational sessions were conducted with neonatology providers. Results: In total, 262 patients were prescribed antibiotics (139 in baseline period and 123 after the intervention). The percentage of unnecessary antibiotic days (UAD) was defined as days beyond the consensus guidelines. As a balancing measure, reinitiation of antibiotics within 2 weeks was tracked. After sequential interventions, the percentage of UAD decreased from 42% to 12%, which exceeded our goal of a 20% decrease. Compliance with antibiotic stop dates increased from 32% to 76%, and no antibiotics were reinitiated within 2 weeks. Conclusions: A multidisciplinary antibiotic stewardship team coupled with a consensus for antibiotic therapy duration, prescriber justification of antibiotic necessity and use of antibiotic stop dates can effectively reduce unnecessary antibiotic exposure in the NICU.

Moving bronchopulmonary dysplasia research from the bedside to the bench.

Although advances in the respiratory management of extremely preterm infants have led to improvements in survival, this progress has not yet extended to a reduction in the incidence of bronchopulmonary dysplasia (BPD). BPD is a complex multifactorial condition that primarily occurs due to disturbances in the regulation of normal pulmonary airspace and vascular development. Preterm birth and exposure to invasive mechanical ventilation also compromises large airway development, leading to significant morbidity and mortality. Although both predisposing and protective genetic and environmental factors have been frequently described in the clinical literature, these findings have had limited impact on the development of effective therapeutic strategies. This gap is likely because the molecular pathways that underlie these observations are yet not fully understood, limiting the ability of researchers to identify novel treatments that can preserve normal lung development and/or enhance cellular repair mechanisms. In this review article, we will outline various well-established clinical observations while identifying key knowledge gaps that need to be filled with carefully designed preclinical experiments. We will address these issues by discussing controversial topics in the pathophysiology, the pathology, and the treatment of BPD, including an evaluation of existing animal models that have been used to answer important questions.

Diagnosis and management of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infants and is associated with increased mortality, respiratory morbidity, neurodevelopmental impairment, and increased healthcare costs. In parallel with advances made in the field of neonatal intensive care, the phenotype of BPD has evolved from a fibrocystic disease affecting late preterm infants to one of impaired parenchymal development and dysregulated vascular growth predominantly affecting infants born before 29 weeks' gestational age. BPD has been shown to have significant lifelong consequences. Adults with BPD have been found to have abnormal lung function tests, reduced exercise tolerance, and may be at increased risk for developing chronic obstructive pulmonary disease. Evidence shows that BPD occurs secondary to genetic-environmental interactions in an immature lung. In this review, we evaluate the various clinical definitions, imaging modalities, and biomarker data that are helpful in making an early diagnosis of BPD. In addition, we evaluate recent evidence about the prevention and treatment of BPD. We discuss the invasive and non-invasive ventilation strategies and pharmacological agents used in the early, evolving, and established phases of BPD.

Correction to: Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitigation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia.

An amendment to this paper has been published and can be accessed via the original article.

Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitgation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia.

BACKGROUND: Macrophage migration inhibitory factor (MIF) has been implicated as a protective factor in the development of bronchopulmonary dysplasia (BPD) and is known to be regulated by MicroRNA-451 (miR-451). The aim of this study was to evaluate the role of miR-451 and the MIF signaling pathway in in vitro and in vivo models of BPD. METHODS: Studies were conducted in mouse lung endothelial cells (MLECs) exposed to hyperoxia and in a newborn mouse model of hyperoxia-induced BPD. Lung and cardiac morphometry as well as vascular markers were evaluated. RESULTS: Increased expression of miR-451 was noted in MLECs exposed to hyperoxia and in lungs of BPD mice. Administration of a miR-451 inhibitor to MLECs exposed to hyperoxia was associated with increased expression of MIF and decreased expression of angiopoietin (Ang) 2. Treatment with the miR-451 inhibitor was associated with improved lung morphometry indices, significant reduction in right ventricular hypertrophy, decreased mean arterial wall thickness and improvement in vascular density in BPD mice. Western blot analysis demonstrated preservation of MIF expression in BPD animals treated with a miR-451 inhibitor and increased expression of vascular endothelial growth factor-A (VEGF-A), Ang1, Ang2 and the Ang receptor, Tie2. CONCLUSION: We demonstrated that inhibition of miR-451 is associated with mitigation of the cardio-pulmonary phenotype, preservation of MIF expression and increased expression of several vascular growth factors.

Biomarkers for the diagnosis of neonatal sepsis and necrotizing enterocolitis: Clinical practice guidelines.

Sepsis and necrotizing enterocolitis are major contributors to morbidity and mortality in neonates, especially in those born preterm. While therapeutic interventions are available for both (for e.g. antibiotics), a major dilemma is early diagnosis so that these interventions can be done in a timely manner. As clinical evaluation alone is unreliable in identifying infants in the early stages of neonatal sepsis or necrotizing enterocolitis, there is a need to find specific biomarkers associated with these conditions to improve diagnostic capabilities. Optimal use of biomarkers in the identification and management of affected neonates requires an understanding of the properties of each marker within the timeline of the inflammatory response. We propose that early- and mid-phase markers such as neutrophil CD64 and procalcitonin should be combined with the late-phase biomarker C-reactive protein for maximal diagnostic benefit. Appropriately powered trials evaluating the serial measurements of these markers in decisions related to antibiotic stewardship in the neonatal population are indicated, in addition to more studies investigating other potentially useful biomarkers.