Multiomics endotyping of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension-A pilot study

Roopa Siddaiah; Christiana Oji-Mmuo; Vincent P R Aluquin; Yuka Imamura Kawasawa; Ann Donnelly; Dustin Rousselle; Nathalie Fuentes; Eric D Austin; Patricia Silveyra

doi:10.1002/pul2.12232

Multiomics endotyping of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension-A pilot study

Pulm Circ. 2023 Apr 1;13(2):e12232. doi: 10.1002/pul2.12232. eCollection 2023 Apr.

Authors

Roopa Siddaiah¹, Christiana Oji-Mmuo¹, Vincent P R Aluquin¹, Yuka Imamura Kawasawa², Ann Donnelly³, Dustin Rousselle⁴, Nathalie Fuentes¹, Eric D Austin⁵, Patricia Silveyra^{1

4}

Affiliations

¹ Department of Pediatrics Penn State Health Children's Hospital Hershey Pennsylvania USA.
² Department of Pharmacology Penn State Health Children's Hospital Hershey Pennsylvania USA.
³ Department of Respiratory Therapy Penn State Health Children's Hospital Hershey Pennsylvania USA.
⁴ Department of Environmental and Occupational Health Indiana University School of Public Health Bloomington Indiana USA.
⁵ Department of Pediatrics Vanderbilt University Nashville Tennessee USA.

Abstract

Pulmonary hypertension associated with bronchopulmonary dysplasia is a severe complication of preterm birth resulting in high mortality of up to 50% within the first 2 years of life. There is a direct relationship between bronchopulmonary dysplasia severity and incidence of associated pulmonary hypertension. However, it is challenging to clinically characterize severe bronchopulmonary dysplasia with and without pulmonary hypertension and there is need for better understanding of the two entities. Our main objective is to identify markers to help understand biological processes and characterize infants with pulmonary hypertension associated with bronchopulmonary dysplasia using tracheal aspirates. We conducted an unbiased multiomic analysis of tracheal aspirates via microRNA (miRNA) polymerase chain reaction arrays, RNA sequencing, and mass spectrometry proteomics in preterm infants with severe bronchopulmonary dysplasia with and without pulmonary hypertension (n = 46). Our pilot study analysis revealed 12 miRNAs (hsa-miR-29a, has-miR-542-3p, has-miR-624, has-miR-183, hsa-miR-501-3p, hsa-miR-101, hsa-miR-3131, hsa-miR-3683, hsa-miR-3193, hsa-miR-3672, hsa-miR-3128, and hsa-miR-1287), 6 transcripts (IL6, RPL35P5, HSD3B7, RNA5SP215, OR2A1-AS1, and RNVU1-19), and 5 proteins (CAPS, AAT, KRT5, SFTPB, and LGALS3BP) with significant differential expression in preterm infants with severe lung disease with pulmonary hypertension when compared with infants with severe lung disease but no pulmonary hypertension. Pathway analysis of the integrated multiomic expression signatures revealed NFkB, VEGF, SERPINA1, IL6, and ERK1/2 as target molecules and cellular development, cellular growth and proliferation, and cellular movement as key affected molecular functions. Our multiomic analysis of tracheal aspirates revealed a comprehensive thumbprint of miRNAs, mRNAs, and proteins that could help endotype infants with severe lung disease and pulmonary hypertension.

Keywords: bronchopulmonary dysplasia; multiomics; preterm infants; pulmonary hypertension; tracheal aspirate.