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Pediatric pulmonary hypertension: insulin-like growth factor-binding protein 2 is a novel marker associated with disease severity and survival
- Source :
- Pediatric research
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background Insulin-like growth factors (IGFs), and their binding proteins (IGFBPs), play a significant role in cardiovascular function and may influence the pathobiology of PAH. We determined the diagnostic and prognostic value of IGF1 and IGFBP2 in pediatric PAH. Methods Serum was analyzed by ELISA for IGF1 and IGFBP2 in pediatric PAH subjects from the NHLBI PAH Biobank (PAHB, n = 175) and a cohort of asthmatic subjects (n = 46, age 0-21 years) as a chronic pediatric pulmonary disease control. Biomarkers were analyzed with demographic and clinical variables for PAH severity. Results Serum IGF1 was significantly lower in PAH compared to controls, while IGFBP2 was elevated in PAH subjects compared to controls. In the PAHB, IGF1 was negatively associated with mPAP and PVR, while IGFBP2 was positively associated with PVR and negatively associated with cardiac output and 6-min walk distance. Higher IGFBP2 levels were associated with use of prostacyclin therapy. IGFBP2 was associated with death, transplant, or palliative shunt with a Cox proportional hazard ratio of 8.8 (p Conclusions Circulating IGFBP2 is a novel marker for pediatric PAH, which is associated with worse functional status, and survival. IGF axis dysregulation may be an important mechanistic target in pediatric pulmonary arterial hypertension. Impact Pediatric pulmonary hypertension is a severe disease, with poorly understood pathobiology.There are few studies looking at the pathobiology of pulmonary hypertension only in children.The IGF axis is dysregulated in pediatric pulmonary arterial hypertension.IGF axis dysregulation, with increased IGFBP2, is associated with worse clinical outcomes in pediatric pulmonary artery hypertension.IGF axis dysregulation gives new insight into the disease process and may be a mechanistic or therapeutic target.Fig. 1IGF1 AND IGFBP2 CONCENTRATION (NG/ML) IN PAH BIOBANK VERSUS CONTROLS.: a IGF1 concentration (ng/mL) in PAH Biobank versus asthmatic subjects. b IGFBP2 concentration (ng/mL) in PAH Biobank versus asthmatic subjects.Fig. 2ROC CURVE OF IGF1 AND IGFBP2 IN PAH BIOBANK VERSUS CONTROLS.: a ROC curve of IGF1 in PAH Biobank subjects versus controls. AUC 0.82. Cut point for IGF1 of 177 ng/mL gives a sensitivity of 73.9% and a specificity of 78.3%. b ROC curve of IGFBP2 in PAH Biobank subjects versus controls. AUC 0.80. Cut point for IGFBP2 of 185 ng/mL gives a sensitivity of 72.2% and a specificity of 80.4%.Fig. 3IGFBP2 CONCENTRATIONS IN PAH SUBJECTS BY MEDICATION COMBINATION.: a IGFBP2 concentration in PAH subjects on a PDE5 inhibitor, a PDE5 inhibitor and an ERA, a PDE5 inhibitor and IV/SQ PCA, or a combination of PDE5 inhibitor, ERA, and IV/SQ PCA. b IGFBP2 concentrations in PAH subjects on an IV/SQ PCA and any other therapy versus subject not on IV/SQ PCA and any other therapy.Fig. 4Kaplan-Meier curve showing time to death, transplant, or palliative shunt (Pott's shunt or atrial septostomy) dichotomized by the median IGFBP2 level.
- Subjects :
- Lung Diseases
Cardiac output
medicine.medical_treatment
Prostacyclin
Walking
Severity of Illness Index
Gastroenterology
Insulin-like growth factor-binding protein
0302 clinical medicine
Medicine
Myocytes, Cardiac
Atrial septostomy
Cardiac Output
Insulin-Like Growth Factor I
Child
biology
Hazard ratio
Prognosis
Treatment Outcome
Child, Preschool
Cohort
medicine.drug
medicine.medical_specialty
Adolescent
Hypertension, Pulmonary
Enzyme-Linked Immunosorbent Assay
Article
Young Adult
03 medical and health sciences
030225 pediatrics
Internal medicine
medicine.artery
Humans
Proportional Hazards Models
business.industry
Hemodynamics
Infant, Newborn
Infant
medicine.disease
Epoprostenol
Pulmonary hypertension
Asthma
Insulin-Like Growth Factor Binding Protein 2
Cross-Sectional Studies
Pediatrics, Perinatology and Child Health
Pulmonary artery
biology.protein
business
Biomarkers
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15300447 and 00313998
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Pediatric Research
- Accession number :
- edsair.doi.dedup.....5548db750fc3cc7377fa4f3dc97011fd