Pulmonary hypertension in bronchopulmonary dysplasia

Hansmann, Georg; Sallmon, Hannes; Roehr, Charles C; Kourembanas, Stella; Austin, Eric D.; Köestenberger, Martin

doi:10.1038/s41390-020-0993-4

Cited by 113 publications

(116 citation statements)

References 78 publications

(128 reference statements)

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“…Approximately one-fourth of infants with moderate to severe BPD developed pulmonary hypertension later in their life (30). In our cohort, 22 infants developed moderate to severe BPD (13 in group A, nine in group B).…”

Section: Limitationsmentioning

confidence: 71%

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern

Yang

Liu

et al. 2020

Front. Pediatr.

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Background: Patent ductus arteriosus (PDA) with a bidirectional shunt reflects critical clinical conditions. The operability of PDA with a bidirectional shunt in pre-term infants is still not clearly clarified. This study aimed to investigate the feasibility and the outcomes of PDA ligation in pre-term infants with a bidirectional shunt PDA. Methods: All pre-term infants receiving PDA ligation between 2013 and 2019 were enrolled in this prospective study. Patients were allocated into two groups based on the shunting direction of PDA, which were the left-to-right group (group A) and the bidirectional group (group B). Clinical characteristics and pre-op comorbidities were analyzed. Intraoperative complications, post-op neurological sequelae, necrotizing enterocolitis, survival, and mortality were compared between these two groups. Results: Thirty-seven pre-term infants were enrolled (18 in group A, 19 in group B). The mean post-menstrual age at PDA surgery was 32.0 ± 1.3 and 32.8 ± 1.5 weeks, respectively. Before surgery, 44.4 and 89.5% (group A vs. B) of the patients were using invasive mechanical ventilator (p < 0.01). The requirement of high-frequency oscillatory ventilatory support was significantly higher in group B. PDA rupture-related bleeding during exposing PDA or ligating PDA occurred in four infants, and all were all in group B, including one with delayed hemothorax. Early surgical mortality within 30 days of surgery was higher in group B (0 vs. 21.1%, p < 0.05), but only one death could be attributed to the surgery, which was caused by a pain-induced pulmonary hypertension crisis. The 5-year survival was 100% in group A, and 73.7% in group B (p < 0.05). Conclusion: We did not recommend routine PDA ligation in pre-term infants with a bidirectional shunt. However, a bidirectional shunt should not be an absolute contraindication if they fulfill indications of PDA closure. Unexpected intraoperative PDA rupture and delayed hemothorax in a bidirectional shunt PDA should be carefully monitored. Aggressive post-op pain control is also warranted to avoid pulmonary Yang et al. PDA Ligation in Pre-term Infants hypertension crisis. The post-op early mortality rate was higher in the bidirectional group, which could be inherent to their poor pre-operative lung condition. Only one death was directly related to the surgery.

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Section: Limitationsmentioning

confidence: 71%

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern

Yang

Liu

et al. 2020

Front. Pediatr.

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“…Through murine studies PFKFB3 has been identified as potential therapeutic target for the treatment of Pulmonary Hypertension (PH) (53). Increased expression PFKFB3 in BPD is consistent with PH associated with BPD which is characterized by abnormal vascular remodeling, and vascular growth arrest, which are well documented pathophysiology associated with BPD (54). In vitro studies have reported that PFKFB3-kinase activity attenuates the activation of T cells, and demonstrated the effectiveness of PFKFB3 antagonists, even in small amounts, as T cell immunosuppressive agents (55).…”

Section: Discussionmentioning

confidence: 93%

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

et al. 2021

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Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at <29 weeks gestational age (GA); n=72), 501 genes were associated with oxygen utilization. In the same set of subjects, 571 genes were differentially expressed in subjects with a diagnosis of BPD and 105 genes were different in BPD subjects as defined by physiologic challenge. A set of 92 genes could predict BPD with a moderately high degree of accuracy. We consistently observed dysregulation of TGFB, NRF2, HIPPO, and CD40-associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy, which also were involved in TGFB signaling. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers of inflammation associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.

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“…Among the differentially expressed genes associated with BPD, PFKFB3 gene was not only consistently identified as differentially expressed in BPD subjects irrespective of the approach used, but was also identified as a BPD marker in an independent transcriptomic analysis of PBMCs derived from BPD subjects (9). Through murine studies PFKFB3 has been identified as potential therapeutic target for the treatment of Pulmonary Hypertension (PH) (36) Increased expression PFKFB3 in BPD is consistent with PH associated with BPD which is characterized by abnormal vascular remodeling, and vascular growth arrest, which are well documented pathophysiology associated with BPD (37). One of the differentially expressed genes, KLF9 , has been previously identified as differentially expressed in T cells from patients with autoimmune rheumatoid arthritis (38), while another, DLG5, is involved in the HIPPO pathway.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte-Specific Biomarkers Associated with Preterm Birth and Bronchopulmonary Dysplasia

Bhattacharya

Mereness

Baran

et al. 2020

Preprint

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Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at <29 weeks gestational age (GA); n=72), 501 genes were associated with oxygen utilization. In the same set of subjects, 571 genes were differentially expressed in subjects with a diagnosis of BPD and 105 genes were different in BPD subjects as defined by physiologic challenge. A set of 92 genes could predict BPD with a moderately high degree of accuracy. We consistently observed dysregulation of NRF2, HIPPO and CD40-associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.

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Pulmonary hypertension in bronchopulmonary dysplasia

Cited by 113 publications

References 78 publications

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

Lymphocyte-Specific Biomarkers Associated with Preterm Birth and Bronchopulmonary Dysplasia

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