B. Kordys-Darmolinska

Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data

D-Lactate is produced by the intestinal biota and later absorbed into circulation. Some patients with cystic fibrosis (CF) develop exocrine pancreatic insufficiency that may disturb the gut microbiome and enhance the production of D-lactate. However, this concept has not been studied yet. The aim of the study was to assess D-lactate concentration in relation to the occurrence of clinical features, activity of CF, and diet composition in paediatric patients. Patients and Method. Serum concentrations of D-lactate were measured in 38 CF patients (19 girls and 19 boys) from 6 months to 18 years of age. The analysis included age, sex, clinical symptoms, diet (the variety and calorie needs), the laboratory tests for pancreatic efficiency (serum levels of albumin and glucose, faecal elastase activity, and faecal fat index) and faecal calprotectin (the marker of intestinal inflammation), and parameters of liver damage and of cholestasis (the activity of aminotransferases, γ-glutamyltransferase, level of bilirubin, and international normalized ratio). Results. The median level of D-lactate was 0.86 μg/ml (1Q–3Q: 0.48–2.03) and correlated with the CF severity in the Schwachman-Kulczycki score, parameters of pancreatic insufficiency, and the presence of intestinal inflammation. An increased level of D-lactate was observed in the subgroup with pancreas insufficiency (1.05 versus 0.73; p < 0.05), parallel with an elevated level of calprotectin (0.948 versus 0.755; p = 0.08). There was no relationship between energy consumption and diet composition and serum D-lactates. Conclusion. Serum D-lactate concentration in CF patients is a promising new marker of exocrine pancreatic insufficiency probably related to intestinal flora dysbiosis/overgrowth.

The concentration of calprotectin in the stools of children with diagnosed cystic fibrosis

Introduction Calprotectin is a protein that plays a regulatory role in inflammatory reactions as an antibacterial and antiproliferative factor. Aim To assess the concentration of calprotectin in the stools of patients with diagnosed cystic fibrosis. Material and methods Forty-one patients were included in the study, 24 boys and 17 girls, aged from 7 weeks to 18 years. The concentration of calprotectin in stools was assessed with the ELISA method. The analysis included clinical symptoms and the results of laboratory tests and the type of mutation. Results An elevated level of calprotectin in the stool was observed in 4/41 (9.7%) patients, mainly in older children, and mainly delta F508/deltaF508 mutation. The correlation between the concentration of calprotectin and clinical symptoms, age, increased indicators of an inflammatory process, levels of protein and aminotransferases in blood serum and the values of acid steatocrit of the stool was not proven. Conclusions High concentrations of calprotectin in the stools of children with diagnosed cystic fibrosis do not correlate with the level of advancement of lesions within the gastrointestinal tract. Elevated concentrations of calprotectin in the stools of patients with cystic fibrosis may indicate inflammation of intestine and should be further scrutinised.

180 Evaluation of leptin and ghrelin levels in the blood serum of patients diagnosed with cystic fibrosis

Objectives Leptin and ghrelin are peptide hormones which, working antagonistically, regulate the energy balance of the body. The aim of the study was to evaluate the levels of leptin and ghrelin in the blood serum of patients diagnosed with cystic fibrosis (CF), in relation to their nutritional status and function of liver cells. Methods The study group consisted of 34 patients, aged from 3 months to 18 years (mean age 4.5 years) who were diagnosed with CF on the basis of screening and/or diagnostic tests. The analysis included the nutritional status, CFTR gene mutation, assessment of the exocrine pancreas function, abnormal lipid metabolism, as well as liver cell function parameters. In all children, serum leptin and ghrelin levels were measured by means of an immunoenzymatic test, using reagents from DRG Instruments. The results were statistically analyzed. Results Serum ghrelin levels were significantly lower in the youngest patients ( Conclusion Ghrelin and leptin levels in children with cystic fibrosis correlate with the nutritional status and can be an early marker of exocrine pancreatic insufficiency.

Concentrations of Ghrelin and Leptin in Children with Cystic Fibrosis

Ghrelin and leptin are peptide hormones which, working antagonistically, regulate the energy balance of the body. Abnormal concentrations of these hormones are observed in the course of gastrointestinal diseases, where the clinical picture is characterized by nutritional disorders. Approximately 70% of patients with cystic fibrosis have body weight deficiency due to exocrine pancreatic insufficiency, respiratory failure, and secondary circulatory disorders as well as eating disorders. The aim of the study was to evaluate the levels of ghrelin and leptin in the blood serum of patients diagnosed with cystic fibrosis, in relation to their nutritional status and function of liver cells. Patients and methods: The study group consisted of 34 patients, 17 girls (50%) and 17 boys (50%), aged from 3 months to 18 years (mean age 4.5 years) who were diagnosed with cystic fibrosis on the basis of screening and/ or diagnostic tests. The analysis included the nutritional status (body weight and height, BMI), CFTR gene mutation, assessment of the exocrine pancreas function (albumin and glucose concentration in the blood serum, acid steatocrit in stool), abnormal lipid metabolism (cholesterol and triglyceride levels in blood serum), as well as liver cell function parameters and cholestasis (serum activity amino-transpherase, gamma-glutamyl transpeptidase, concentration of bile acids, coagulation parameters). In all children, serum ghrelin and leptin levels were measured by means of an immunoenzymatic test, using reagents from DRG Instruments. The results were statistically analyzed. Results: Serum ghrelin levels were significantly lower in the youngest patients (<1 year of age) compared with older age groups. Ghrelin concentration was significantly lower in patients with salt wasting syndrome (p<0.05). The statistically lower serum leptin levels were observed in patients with growth deficiency and increased parameters of cholestasis, particularly in the youngest age group. Conclusion: Ghrelin and leptin levels in children with cystic fibrosis correlate with the nutritional status and can be an early marker of exocrine pancreatic insufficiency.

184 Evaluation of the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis

SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in approximately 5% of patients with cystic fibrosis (CF) and concomitant changes in the liver. Aim: The aim of this study was to assess the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis. Patients and Methods: The analysis included 30 children, 13 girls (43.3%) and 17 boys (56.6%), aged from 6 months to 18 years, with diagnosed CF. All patients underwent genetic testing for SERPINA gene mutation. The analysis included age, sex, clinical symptoms, type of mutation of the CFTR protein, laboratory abnormalities (levels of transaminases, GGTP, FA, protein, acid steatocrit) and ultrasound examination of the abdomen. Results: Elevated transaminases were found in 9/30 (30%), whereas elevated levels of gamma-glutamyl transferase in 6/30 (20%) children. In 5/30 patients the ultrasound examination demonstrated liver enlargement with increased echogenicity. The mutation in SERPINA gene was found in 1/30 (3.3%) patient with cystic fibrosis. Currently, this patient has normal values of transaminases, GGTP and FA, whereas, a significant worsening of respiratory symptoms is observed. There was no correlation between the occurrence of SERPINA gene mutation and clinical symptoms, type of CFTR protein mutation, results of laboratory tests of liver function and hepatocyte damage, and ultrasound examination of the abdomen. Conclusions: There was no correlation between the occurrence of SERPINA gene mutation and the presence of features of liver damage and cholestasis in children diagnosed with cystic fibrosis.

193 Concentration of calprotectin in the stool of children with cystic fibrosis

Objectives: Investigation of the diagnostic process and treatment of Distal Intestinal Obstructive Syndrome (DIOS) in Norwegian Cystic Fibrosis patients in comparison with ECFS guidelines. Methods: Retrospective review of electronic patient files from 50 CF patients. 19 of these patients experienced at least one suspected episode of DIOS within the previous 5 years. The 19 patient records were systematically reviewed for information about symptoms of DIOS, clinical work-up and treatment. Results: The included patients had an equal gender distribution and were born in 1977–2007. 18 patients had a serious genetic mutation. 17 had pancreatic insufficiency. 18 patients reported two or more symptoms of DIOS. 7 patients were examined with an abdominal x-ray. 3 patients got a diatrizoinic acid lavage as a part of the diagnostic and treatment regimen. 8 patients were hospitalized and received 7 different treatment regimens. 18 patients got N-acetylcystein as prophylactic treatment after an episode of DIOS. None of the patients was treated with laxatives containing polyethylene glycol. Conclusion: Significant divergence from ECFS guidelines (2011) was identified on the hospitals performance on diagnostic work up and treatment for DIOS. Our opinion was that the attending physicians and the patients would benefit from specific guidelines in how they approach CF patients with possible DIOS. Clinical impact: Guidelines on diagnosis and management of DIOS, based mainly on the ECFS guidelines, were constructed and implemented in April 2013.

359 DIOS syndrome in 11-month-old infant with cystic fibrosis

Introduction: DIOS syndrome in patients with CF occurs with a frequency of 6.2/ 1000 patients/year, mainly in adolescents and young adults. It is extremely rare in younger children. Known risk factors for DIOS include: meconium obstructions in the neonatal period, abnormal enzyme supplementation, dietary errors, dehydration and others. Objective: Analysis of the clinical assessment of risk factors for DIOS syndrome in an 11-month-old infant suffering from cystic fibrosis. Material and Methods: We present a case of DIOS in an 11-month-old female infant diagnosed with CF by newborn screening test. The baby was referred to the district hospital because of febrile conditions, reduction in fluid consumption and eating, and ion disorders. On admission the child had features of dehydration and bloated belly with lazy motility. Additional examination revealed high rates of inflammation, electrolyte disturbances, hypoproteinaemia, and high rates of acidic steatocrit. Despite the persistence of observed treatment of infections parameters, growth of abdominal circumference, disposable vomiting. The diagnostic imaging studies, including the intestinal passage, showed retention of contrast around the ileocaecal bowel. Child consulted surgery. Oral feeding was stopped, starting rectal infusions of N-acetylcysteine, irrigation, included metronidazole, standard realimentation with enzyme supplementation. Improvement in clinical status was obtained. Conclusions: 1. Avoidance and effective treatment of states of dehydration and the proper enzyme supplementation may reduce the risk for DIOS syndrome in infants. 2. Coexistence of several risk factors in the same child greatly increases the risk of developing ovarian DIOS. 360 A case series of thrombotic and thromboembolic complications of central venous access in cystic fibrosis patients N. Kandamany1, M. Tariq1, B. Elnazir1, P. Greally1. 1Adelaide & Meath Hospital inc the National Children’s Hospital, Tallaght, Respiratory, Dublin, Ireland

173 Upper respiratory tract colonization in infants with cystic fibrosis diagnosed by newborn screening

Cystic fibrosis, is characterised by production of abnormally thick and viscous mucus. It results in disturbances of mucociliary clearance, a basic defensive mechanism of the respiratory system, leading to increased susceptibility to recurrent and chronic respiratory infections in over 90% of patients. The aim of this study is to evaluate nasopharyngeal cavity colonization in infants with cystic fibrosis diagnosed by newborn screening. Material and Methods: Nasal and pharyngeal swabs were obtained from 26 infants aged 10−20 weeks, without any signs of infections, who were examined in the Cystic Fibrosis Outpatient Clinic. Isolates were identified by means of routine diagnostic methods. Results: Negative nasal swabs were obtained in 10 (40%) infants, negative pharyngeal swabs − in 6 (23%), and in 4 patients both nasal and pharyngeal swabs were negative. In the nasal swabs the most frequently observed growths were: Staphylococcus aureus MSSA(+) in 9 (34.5%), Corynebacterium sp. in 6 (23.5%), and b-lactamase(+) Moraxella catarrhalis in 2 (8%). Pharyngeal swabs revealed a-hemolytic Streptococcus in 20 (80%), Staphylococcus aureus MRSA(+) in 7 (27%), Neisseria sp. in 4 (15%), Escherichia coli ESBL(−) and Candida albicans in 3 (11.5%) examined infants. Conclusion: Nasopharyngeal cavity colonization by pathogenic bacteria in infants suffering from cystic fibrosis occurs during the first months of life, in the absence of noticeable signs of upper respiratory infection.

The diagnostic and therapeutic difficulties of the recurrent lower respiratory tract infections in children with neurological disorders

Abstract Background and aims Severe clinical course of the respiratory tract infections is very frequent in children with neurological disorders. The aim of this study was to establish the diagnostic and therapeutic procedures giving the best results in this group of children. Methods The symptoms, clinical picture, diagnostics, treatment an outcome of lower respiratory system infections in children with neurological disorders were analyzed. The patients, according to the type of neurological dysfunction, were divided into 5 groups: progressive encephalophaties, cerebral palsy, developmental delay, chromosomal anomalies and other dysmorphic syndromes, neuromuscular diseases. The patients were analyzed according to: lower respiratory tract infections risk factors, diagnostic signs of acute lower respiratory tract infections, outcome and treatment. Results In the study group the most numerous were children with cerebral palsy and with progressive encephalopaties. Those patients required target, broad-spectrum antibiotic therapy, intensive chest physiotherapy, energetic and metabolic deficits supplementation, using prokinetics and careful administration of mucolitics. Conclusions In the treatment of the respiratory tract diseases in children with neurological disorders cooperation of pneumologist, neurologist, gastrologist and physioterapeutist is necessary.