Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension

Chen, Jenny Y.; Griffiths, Megan; Yang, Jun; Nies, Melanie; Damico, Rachel; Simpson, Carol; Vaidya, Dhananjay; Brandal, Stephanie; Ivy, D. Dunbar; Austin, Eric D.; Nichols, William C.; Pauciulo, Michael W.; Lutz, Katie A.; Rosenzweig, Erika B.; Hirsch, Russel; Yung, Delphine

doi:10.1016/j.jpeds.2020.04.041

Cited by 11 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported findings are against those of Chen [ 18 ]. The latter reported that each log-unit higher IL-6 is significantly associated with higher mPAP over time [ 18 ].…”

Section: Discussioncontrasting

confidence: 61%

“…The reported findings are against those of Chen [ 18 ]. The latter reported that each log-unit higher IL-6 is significantly associated with higher mPAP over time [ 18 ]. The difference between their findings and ours could be attributed to the difference in time between hemodynamic measures and serum samples.…”

Section: Discussioncontrasting

confidence: 61%

“…PAH is characterized by endothelial dysfunction and subsequent remodeling of the pulmonary vasculature, which has been linked to the pro-inflammatory cytokine IL-6 [ 14 ]. More research has been done on IL-6 in adults as a potential therapeutic target and an early pathobiological biomarker of disease development [ 18 ]. Although IL-6 has not been extensively researched in children, a study of pediatric PAH incorporating a broad cytokine panel and univariate analysis found that IL-6 was linked to unfavorable outcomes, indicating that IL-6 may have some use as a prognostic marker in pediatric patients [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic and diagnostic utility of interleukin-6 in pediatric pulmonary arterial hypertension — a case-control study

Megied,

Abouelhassan,

Hadwa

2024

Eur J Pediatr

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) in pediatrics is a progressive disease with significant vascular remodeling, right sided heart failure, and death if left untreated. Elevated interleukin-6 (IL-6) level in PAH patients is taken as an independent predictor of adverse outcome including mortality. The aim of this study was to investigate and compare serum levels of IL-6 in children with PAH and healthy matched controls, and correlate between IL-6 and degree of PAH, as well as mortality. IL-6 was measured by ELISA in serum samples in 40 children with PAH (age 1–12 years) and 40 age and sex-matched healthy controls. There was a statistically significant increase in IL-6 level among PAH cases compared with the controls (1.85 ng/L vs 1.30 ng/L, p-value = 0.004). IL-6 at cut off point 1.45 ng/L significantly predict pulmonary hypertension in children (AUC = 0.685, 75% sensitivity, and 65% specificity with p = 0.002). There was no statistically significant association between IL-6 level and degree of PAH (p = 0.218). There was no statistically significant association between IL-6 level and mortality (p = 0.662). Conclusion: IL-6 significantly predict PAH in pediatrics but there is no association between IL-6 level and degree of PAH or mortality. IL-6 may provide a less costly and less invasive method for disease detection. What is Known:• Definitive diagnosis of PAH is made by right heart catheterization, while echocardiography is the gold standard for tracking the course of the disease. What is New:• It was assumed that children with a diagnosis of PAH would have higher serum IL-6 levels than controls. Furthermore, an adverse relationship between the blood IL-6 level and PPAH was predicted.

show abstract

“…The reported findings are against those of Chen [ 18 ]. The latter reported that each log-unit higher IL-6 is significantly associated with higher mPAP over time [ 18 ].…”

Section: Discussioncontrasting

confidence: 61%

Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic and diagnostic utility of interleukin-6 in pediatric pulmonary arterial hypertension — a case-control study

Megied,

Abouelhassan,

Hadwa

2024

Eur J Pediatr

View full text Add to dashboard Cite

show abstract

“…While our transcriptomic analysis identified multiple pseudogenes, and noncoding RNAs as the top differentially expressed transcripts between BPD‐PH and sBPD, it also revealed IL6 as a highly expressed gene in TAs from infants with BPD‐PH. Previously, a multicenter study identified IL6 as a clinical marker to predict severe phenotype in pediatric pulmonary arterial hypertension 54 . This cytokine has been found to modulate expression of BMPR2 55 similar to miRNA 29a which plays a role in vascular remodeling 56 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…While our transcriptomic analysis identified multiple pseudogenes, and non-coding RNAs as the top differentially expressed transcripts between BPD-PH and sBPD, it also revealed IL6 as a highly expressed gene in TAs from infants with BPD-PH. Previously, a multicenter study identified IL6 as a clinical marker to predict severe phenotype in pediatric pulmonary arterial hypertension (54). This cytokine has been found to modulate expression of BMPR2 (55) similar to miRNA 29a which plays a role in vascular remodeling (56).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics endotype of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension

Siddaiah

Oji-Mmuo

Aluquin

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Rationale: 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. Objectives: To identify markers to help understand biological processes and endotype characterization of infants with pulmonary hypertension associated with bronchopulmonary dysplasia in tracheal aspirates. Methods: We conducted multi-omic analysis of tracheal aspirates via miRNA PCR arrays, RNA sequencing and mass spectrometry proteomics in preterm infants with severe bronchopulmonary dysplasia with (n=21) and without (n=25) pulmonary hypertension. Results: Our 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 to infants with severe lung disease but no pulmonary hypertension. Pathway analysis of the integrated multi-omic expression signatures revealed NFkB, VEGF, SERPINA1, IL6 and ERK12 as target molecules for miRNAs, and angiogenesis and hyperoxia stress as recurrent pathways of individual markers. Conclusion: Our multi-omic 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.

show abstract

Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension

Cited by 11 publications

References 28 publications

Prognostic and diagnostic utility of interleukin-6 in pediatric pulmonary arterial hypertension — a case-control study

Prognostic and diagnostic utility of interleukin-6 in pediatric pulmonary arterial hypertension — a case-control study

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

Multi-omics endotype of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension

Contact Info

Product

Resources

About