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Novel biomarkers of bronchopulmonary dysplasia and bronchopulmonary dysplasia-associated pulmonary hypertension

Abstract

Objective

To quantify and compare levels of potential biomarkers in neonates with (i) Bronchopulmonary dysplasia (BPD); (ii) BPD-associated pulmonary hypertension (BPD-PH); (iii) PH without BPD; and (iv) neonates without lung disease at ~36 weeks postmenstrual age.

Study design

Multiple potential biomarkers were measured in plasma samples of 90 patients using a multi-spot enzyme-linked immunosorbent assay. Statistical tests done included one-way ANOVA to compare levels of biomarkers between different groups.

Results

Higher levels of ICAM-1 were present in infants with BPD and correlated with its severity. Infants with BPD have significantly higher levels of ANG-2 and lower levels of ANG-1. Infants with PH have higher levels of: IL-6, IL-8, IL-10, and TNF-α. Infants with BPD-PH have significantly lower levels of MCP-1 and higher levels of IL-1β than infants with PH without BPD.

Conclusion

ICAM-1 may be used as a specific biomarker for diagnosis of BPD and its severity.

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Fig. 1: Biomarkers in PC, TC, BPD, PHTN, and BPD-PH (discovery cohort).
Fig. 2: Biomarkers in PC, TC, BPD, PHTN, and BPD-PH (discovery cohort).
Fig. 3: Biomarkers in PC, TC, BPD, PHTN, and BPD-PH (discovery cohort).
Fig. 4: Biomarkers in BPD (validation cohort vs. discovery cohort).

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Funding

This work was supported by a grant from the American Heart Association Grant-in-Aid 16GRNT29430000, and National Institute of Health R01-HL133050, to HS.

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Contributions

MS designed the study, performed the experiments, carried out the statistical analysis and drafted the initial manuscript. BY did the data collection for the study. PD and DS performed the experiments, assisted with data analysis and reviewed and revised the manuscript. DP and HS performed the experiments, reviewed and revised the manuscript. LN helped design the study, coordinated sample collection, reviewed and revised the manuscript. VB conceptualized and designed the study, supervised the experiments and statistical analysis, reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Vineet Bhandari.

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The authors declare that they have no conflict of interest.

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Sahni, M., Yeboah, B., Das, P. et al. Novel biomarkers of bronchopulmonary dysplasia and bronchopulmonary dysplasia-associated pulmonary hypertension. J Perinatol 40, 1634–1643 (2020). https://doi.org/10.1038/s41372-020-00788-8

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