scholarly journals Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Author(s):  
Roopa Siddaiah ◽  
Christiana Oji-Mmuo ◽  
Deborah Montes ◽  
Nathalie Fuentes ◽  
Ann Donnelly ◽  
...  

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. 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 severe BPD. We collected tracheal aspirates (TA) 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, FDR < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD vs. the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extreme premature infants contain miRNA signatures associated with severe BPD. These signatures may serve as biomarkers of disease severity in infants with BPD.

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 257
Author(s):  
Roopa Siddaiah ◽  
Christiana N. Oji-Mmuo ◽  
Deborah T. Montes ◽  
Nathalie Fuentes ◽  
Debra Spear ◽  
...  

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.


2018 ◽  
Vol 315 (5) ◽  
pp. L810-L815 ◽  
Author(s):  
Charitharth Vivek Lal ◽  
Jegen Kandasamy ◽  
Kalsang Dolma ◽  
Manimaran Ramani ◽  
Ranjit Kumar ◽  
...  

The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.


Author(s):  
Yousuke Imanishi ◽  
Katsuya Hirata ◽  
Masatoshi Nozaki ◽  
Narutaka Mochizuki ◽  
Shinya Hirano ◽  
...  

Objective: To evaluate the association between bronchopulmonary dysplasia (BPD) development at 36 weeks postmenstrual age (PMA) and Gram-negative bacteria in tracheal aspirate cultures among extremely preterm infants. Study Design: Retrospective cohort study. Patients were 155 infants aged less than or equal to 26 gestational weeks who were admitted to the neonatal intensive care unit of Osaka Women’s and Children’s Hospital from 2009 to 2018. Primary outcome was respiratory outcomes expressed as BPD development. Multivariable logistic regression analysis was used to identify neonatal and bacterial factors associated with BPD. Results: After adjusting for gestational age, birth weight, sex, chorioamnionitis, Gram-positive cocci (GPC) and Gram-negative rods (GNRs) in tracheal aspirate cultures within 28 days after birth, GNRs were significantly associated with BPD development (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.68–8.94). In contrast, GPC were not associated with BPD development (OR: 0.47, 95% CI: 0.05–1.61). Conclusion: Gram-negative bacteria in tracheal cultures within 28 days of birth are associated with BPD development in infants aged less than or equal to 26 gestational weeks.


2019 ◽  
Vol 109 (4) ◽  
pp. 711-719
Author(s):  
Hirokazu Arai ◽  
Masato Ito ◽  
Tomoo Ito ◽  
Syozo Ota ◽  
Tsutomu Takahashi ◽  
...  

2019 ◽  
Vol 39 (12) ◽  
pp. 1648-1655 ◽  
Author(s):  
Hussnain Mirza ◽  
Jorge Garcia ◽  
Genevieve McKinley ◽  
Laura Hubbard ◽  
Wendla Sensing ◽  
...  

2021 ◽  
Author(s):  
Kentaro Tamura ◽  
Mitsuhide Nagaoka ◽  
Satomi Inomata ◽  
Yukako Kawasaki ◽  
Masami Makimoto ◽  
...  

Abstract Systemic hydrocortisone administration has been widely used in preterm infants who are at a risk of bronchopulmonary dysplasia (BPD). However, the effects of hydrocortisone on cytokine profiles have not been examined. We aimed to investigate the effects of postnatal hydrocortisone treatment on serum cytokine levels in extremely preterm infants at risk for BPD. In 29 extremely preterm infants (born at less than 28 weeks of gestational age), we obtained serum from blood samples collected during an early phase (5–20 days) and a late phase (28‒60 days) after birth. We measured the levels of proinflammatory cytokines (tumor necrosis factors α and β, interleukin [IL]-1β, and IL-6), T-helper (Th) 1 cytokines (interferon-γ, IL-2, and IL-12p70), Th2 cytokines (IL-4, IL-5, and IL-10), Th17 cytokine IL-17A, and chemokine IL-8. We found that serum IL-6 and IL-8 levels were significantly higher during the early phase than during the late phase (both P = 0.03). Other cytokines concentrations did not change between the phases. Thirteen infants (45%) received systemic hydrocortisone treatment at a median age of 15 days (IQR 10.0–21.5) after birth due to respiratory deterioration, after which the serum IL-6 levels significantly decreased (P = 0.04). Median duration of treatment was 16.0 (IQR 8.0–34.5) days. Conclusion: Extremely preterm infants show high serum IL-6 and IL-8 levels in the early phase of life. Moreover, postnatal systemic hydrocortisone treatment might suppress IL-6 overproduction.


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