Abstract
Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.
Highlights
Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development [1].BPD is associated with significant human and public health burdens, with reported cases varying significantly among centers worldwide [2]
The current recommendations include optimizing ventilator settings while focusing on nutrition and addressing comorbidities [38]. This mostly stems from the fact that the exact underlying mechanisms of severe BPD are uncertain
We sought to identify the molecular signatures associated with BPD severity to uncover regulatory pathways and new biomarkers for severe BPD
Summary
Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development [1]. BPD is associated with significant human and public health burdens, with reported cases varying significantly among centers worldwide [2]. The disease was first described by Northway and colleagues in 1967 in preterm infants receiving invasive mechanical ventilation with characteristic clinical, chest radiological, and pathologic findings [4]. The contributing factors include genetic predisposition, epigenetic factors, arrest of lung development, chronic inflammation, mechanical ventilation, and oxygen toxicity [1,5]. Several maternal health factors such as pre-eclampsia, obesity, gestational diabetes, and inflammation can predispose to preterm birth and BPD development [6,7,8].
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