Elevated vascular endothelial growth factor is correlated with elevated erythropoietin in stable, young cystic fibrosis patients.
ABSTRACT Angiogenesis is an important mechanism of airway remodeling in lung disease. We previously demonstrated that serum vascular endothelial growth factor (VEGF) is elevated in cystic fibrosis (CF) patients and declines with therapy for pulmonary exacerbation. We hypothesized that VEGF is elevated early in the course of CF and is associated with markers of tissue hypoxia. A prospective, single-visit evaluation of thirty stable infants and children with CF was performed. Serum was analyzed for VEGF and for other markers of tissue hypoxia (erythropoietin (EPO), insulin-like growth factor binding protein-1 (IGFBP-1)) and for inflammatory mediators (IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNFα)) using Meso Scale multi-spot serum immunoassays. Measurements were correlated between assay groups; and with age in months and pulmonary function (FEV0.5 or FEV1). VEGF, EPO, TNFα and IL-8 were elevated compared to published normative values. VEGF levels were not significantly correlated with any inflammatory mediators. However, VEGF correlated with EPO (r=0.505; P<0.05). There was no correlation between lung function and markers of inflammation or tissue hypoxia. VEGF is elevated in young, stable infants and children suggesting angiogenesis as a contributing mechanism for early lung disease in CF. VEGF elevation does not show significant correlation with inflammatory mediators known to be increased in CF, but is significantly correlated with EPO levels. We propose that VEGF elevation and angiogenesis contribute to early lung disease and may result from a direct tissue hypoxia pathway in CF.
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ABSTRACT: The value of ferritin in the diagnosis of iron deficiency is limited in patients with CF since it increases in the presence of inflammation. We hypothesized that the soluble transferrin receptor (sTfR) and hepcidin may provide more information than ferritin in assessing iron status in children with CF. We analyzed sTfR and hepcidin in relation to conventional iron status indicators in 49 children with CF. We found no differences in sTfR concentration between children with and those without ID. sTfR concentrations were within the normal range in all children. Hepcidin concentrations were low, and concentrations below the limit of detection were observed in 25% of the clinically stable children. The sTfR is not useful to determine the iron status in this population, whereas hepcidin might serve as an early indicator of deficient iron stores in children with CF.Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 04/2014; · 3.19 Impact Factor
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ABSTRACT: In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st) and slope (Hill's n) of the O2 dissociation curve as well as the Bohr coefficients (BC) for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females) and 14 healthy controls (6 males, 8 females). While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1mmHg in both patient groups (controls male 26.7±0.2, controls female 27.0±0.1, patients male 27.7±0.5, patients female 28.0±0.3 mmHg; mean and standard error, overall p<0.01). Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg) and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin). There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity.PLoS ONE 01/2014; 9(6):e97932. · 3.53 Impact Factor
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ABSTRACT: BACKGROUND: Cystic fibrosis (CF) is a common genetic disease in Caucasians. Chronic pulmonary disease with progressive destruction of the pulmonary parenchyma is two of the major morbidities, but the relationship between clinical severity of CF and aortopulmonary collateral blood flow has not been assessed. OBJECTIVE: The purpose of this study is to measure changes in aortopulmonary collateral blood flow by phase-contrast magnetic resonance imaging (MRI) in children with CF across the spectrum of disease severity as measured by the forced expiratory volume in one second as percent predicted value (FEV1% predicted). MATERIALS AND METHODS: Sixteen patients with CF were prospectively evaluated. Eight were classified as having mild CF lung disease (FEV1 ≥80% predicted) and eight were classified as having moderate to severe CF lung disease (FEV1 <80% predicted). Seventeen age- and gender-matched non-CF subjects without cardiac or lung disease served as controls. Phase-contrast flow was measured at the ascending aorta, main pulmonary artery and both pulmonary arteries. Aortopulmonary collateral blood flow was calculated for each subject. The relationship between collateral flow and FEV1% predicted was modeled using nonparametric regression. Group differences were assessed by analysis of variance. RESULTS: Aortopulmonary collateral blood flow began to increase as FEV1% predicted in subjects with CF fell below 101.5% with significant further increase in the aortopulmonary collateral blood flow in the subjects with CF with moderate to severe lung disease compared to controls (0.89 vs. 0.20 L/min, P < 0.0001). Aortopulmonary collateral blood flow correlated negatively with FEV1% predicted (r=0.70, P = 0.0050) confirming its relationship to this established marker of disease severity. There was no statistically significant difference in results obtained from two independent observers. CONCLUSION: These preliminary findings suggest that phase-contrast MRI can be performed reliably with consistent results and without interobserver variability. While the aortopulmonary collateral blood flow is within the normal range in subjects with mild CF disease, it begins to increase even when lung function is still in the normal range. A significant increase in the aortopulmonary collateral blood flow compared to controls is measured in patients with moderate to severe CF lung disease. The studies support the notion that aortopulmonary collateral blood flow may serve as a novel and sensitive biomarker of early pulmonary disease in cystic fibrosis.Pediatric Radiology 05/2013; · 1.57 Impact Factor