Elevated Vascular Endothelial Growth Factor is Correlated With Elevated Erythropoietin in Stable, Young Cystic Fibrosis Patients
The Division of Pulmonary Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA. Pediatric Pulmonology
(Impact Factor: 2.7).
07/2011; 46(7):683-7. DOI: 10.1002/ppul.21428
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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Available from: Doris Staab
- "Some authors ,  have even observed an increase in red cell volume in CF probably stimulated by erythropoietin which might be explained as a typical hypoxia reaction. However, only in a fraction of the corresponding studies , , , http://www.ncbi.nlm.nih.gov/ pubmed?term = McColley%20SA%5BAuthor%5D&cauthor = true&cauthor_uid = 21365780 erythropoietin concentration was increased. "
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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 06/2014; 9(6):e97932. DOI:10.1371/journal.pone.0097932 · 3.23 Impact Factor
Available from: Minoru Satoh
- "However, few reports describe the ectopic production of Epo in benign diseases. Patients with a benign cystic lesion have been shown to have increased Epo production [9,10], but Epo has not been reported as produced ectopically in a lymph node. Here, we describe a dialysis patient who presented with a fever of unknown etiology that was caused by a caseating tubercle granuloma. "
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We describe a case of a fever of unknown etiology that was caused by a caseating tubercle granuloma which produced erythropoietin. To our knowledge, this is the first report of an erythropoietin- producing granuloma.
A 48-year-old Japanese man with a 5-year history of maintenance hemodialysis for diabetic nephropathy presented with an intermittent fever over a few months. During febrile periods he developed erythema nodosum on his legs. Computed tomography showed axillary lymph node enlargement and this was further corroborated by a gallium scan that revealed high gallium uptake in these nodes. A Mantoux test was positive and an interferongamma release assay for tuberculosis diagnosis was also positive. Lymph node tuberculosis was suspected and the patient underwent lymphadenectomy. Histological analysis of the lymph nodes revealed a caseating granuloma that showed positive results on an acid-fast bacteria stain and a Mycobacterium tuberculosis polymerase chain reaction test. After lymphadenectomy, however, the patient’s hemoglobin levels rapidly decreased from 144 to 105 g/L, and this was further compounded by a decrease in serum erythropoietin from 223 mIU/mL to 10.7 mIU/mL by postoperative day 21. We suspected the tubercle to be a source of the erythropoietin and this was further confirmed by in situ hybridization.
We report for the first time ectopic erythropoietin production by a tuberculous lymph node. Our observations are substantiated by a postoperative decline in his erythropoietin level and a clinical requirement for erythropoietin treatment.
BMC Nephrology 04/2013; 14(1):91. DOI:10.1186/1471-2369-14-91 · 1.69 Impact Factor
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ABSTRACT: The chronic infection and inflammation of cystic fibrosis (CF) lung disease causes a progressive decline of lung function resulting in daily symptoms such as cough and sputum production. There are intermittent episodes of acute worsening of symptoms, more commonly referred to as pulmonary exacerbations. Despite this being a common event, there is still no standardized definition of an exacerbation. A recent set of guidelines from the CF Foundation Pulmonary Therapies Committee on the treatment of exacerbations noted the paucity of data supporting commonly used therapies. This review describes our current understanding of pulmonary exacerbations and the therapies used to treat them.
The treatment of an exacerbation is intended to resolve the worsened symptoms and to restore the lung function that is commonly lost in the acute presentation. A most striking finding is the observation that for many patients there is no restoration of lung function, suggesting we either need better therapies to prevent exacerbations or better treatment of exacerbations.
We have established recommendations on specific treatment of a pulmonary exacerbation and have outlined the areas where we need better information on appropriate therapies. Once we have a standardized definition of an exacerbation, we can proceed with clinical trials of therapies specific for its treatment.
Current opinion in pulmonary medicine 08/2011; 17(6):442-7. DOI:10.1097/MCP.0b013e32834b8c04 · 2.76 Impact Factor
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