Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with BPD severity. We analyzed profiles in tracheal aspirates (TAs) from 25 extremely preterm infants receiving invasive mechanical ventilation. Eight infants were diagnosed with mild/moderate BPD, and 17 were diagnosed with severe BPD, according to the NHLBI consensus conference classification . We found specific miRNA signatures in TAs that may serve as biomarkers for BPD severity.
Project description:Extreme preterm infants are a growing population in the neonatal intensive care unit. Multiple factors play a role in preterm birth, resulting in complications including severe bronchopulmonary dysplasia (sBPD) without or with and pulmonary hypertension (BPD-PH). The goal of this study was to identify biomarker signatures associated with sBPD and BPD-PH. We analyzed profiles in tracheal aspirates (TAs) from 46 extremely preterm infants receiving invasive mechanical ventilation (25 sBPD, 21 BPD-PH) . We found specific miRNA signatures in TAs that may serve as biomarkers for the two disease phenotypes.
Project description:Tracheal aspirate (TAs) samples were collected from intubated preterm infants with hemodynamically significant intracardiac shunt (ICS), and a diagnosis of ICS-BPD/ICS-BPD-PH. 36 TA samples were analyzed. Small RNAs were extracted and the expression miRNAs was detected with PCR arrays.
Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with prematurity and BPD. We analyzed miRNA and mRNA profiles in tracheal aspirates (TAs) from 51 infants receiving invasive mechanical ventilation. 25 infants were extremely preterm and diagnosed with BPD, and 26 were term babies receiving invasive mechanical ventilation for elective procedures. We found specific mRNA-miRNA signatures in TAs that may serve as biomarkers for BPD pathogenesis, a consequence of extreme prematurity.
Project description:Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants is associated with high morbidity and mortality within the first two years of life. In a previous unbiased study, we identified a panel 16 miRNAs in tracheal aspirates (TA) that were differentially expressed in preterm infants with BPD-PH compared to those with BPD but no PH. To endotype molecular thumbprint of BPD-PH, we used unbiased multiomics approach and identified a panel of miRNAs, mRNAs, and proteins in tracheal aspirates (TA) and found 14 differentially expressed mIRNAs. To explore to predictive potential of these miRNAs, we collected TA and extracted exosomes from extremely low gestational age infants (ELGANs) at 7 days of age and calculated the predictive AUROC of these miRNAs from TA exosomes to diagnose BPD-PH at 36 weeks PMA. AUROC of TA miRNAs was 0.89 with sensitivity and specificity of 77% and 81%, respectively. Due to challenges of obtaining TA in non-invasively ventilated infants, we collected saliva samples (SA) from ELGANs at 7 days of age and calculated the predictive AUROC of the same miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.94 with sensitivity and specificity of 93% and 78%, respectively. Of the 14 miRNAs, of particular interest is miR29-a which is highly differentially expressed in BPD-PH and has been studied in animal model for its role in modulating genes responsible for lung growth and development. We studied the effect of miR29-a on the pulmonary artery smooth muscle cells (PASMC) by transfecting them with Ago-miR29a and found low expression PDGFA which is an important key player in angiogenesis and lung development in early growth. Salivary miRNA panel is a potential non-invasive early predictor of BPD-PH in ELGANs with biological plausibility through miR29a pathway.
Project description:The search for novel biomarkers for respiratory diseases, especially those associated with extreme premature birth, has been a challenge over the past several decades. In this study, we performed a qualitative comparison of proteomic profiles derived from a novel noninvasive sampling methodology, nasopharyngeal aspiration, and an established invasive methodology, tracheal aspiration, in preterm neonates, to determine whether nasopharyngeal aspirates (NPAs) are suitable for respiratory biomarker research. Paired NPA and tracheal aspirate (TA) samples (N=5) were collected from 1-week-old neonates and analyzed via high-throughput proteomics. The shared and specific sample proteins were studied. Shared and sample-specific proteins were analyzed using state-of-the-art enrichment analyses to evaluate lung tissue specificity and proteomic similarity.
Project description:We analyzed mRNA profiles in tracheal aspirates from 53 newborns receiving invasive mechanical ventilation. Twenty-six infants were extremely preterm diagnosed with BPD and twenty-seven were term babies receiving invasive mechanical ventilation for elective procedure. Specific mRNA signatures in TAs may serve as potential biomarkers for extreme prematurity and BPD pathogenesis.