10-year experience with umbilical cord blood IgE and microbiome therapy.

BACKGROUND: The benefit of probiotics in newborn children in relation to allergy and general morbidity later in life appears to be controversial. Allergic diseases represent an increasingly important health problem worldwide in recent years. This is evident in all age groups. The occurrence of allergic illnesses also continues to rise exponentially, and thus the use of preventive and prognostic methods, particularly in children with an inherently higher risk of allergy, is gaining increased importance. Since the advent of probiotics the effect of probiosis on immunity through alterations of composition and function of the human gut microbiome has been increasingly studied. The exact mechanisms have not yet been clearly defined. The Academy of Sciences of the Czech Republic (The Czech Academy of Sciences has suggested that the expression of TH1 and TH2 cytokines in umbilical blood is associated with an increased risk of allergies. The counter -balance of Th1 and Th2 affect Immunoglobulin E (IgE) production and maturation of the gastrointestinal tract epithelium. CASE PRESENTATION: We examined IgE levels in 3000 samples of umbilical blood taken from children born into families with a positive history of allergy in one or both parents from 2007 to 2017. At the age of ten days, those with high IgE were given Colinfant Newborn (a lyophilized non-pathogenic strain of Escherichia.coli) for one month, three times weekly. At 15 months and three years we investigated the levels of Immunoglobulins E,A and G, and the incidence of illness and allergy. The results revealed that allergy and high umbilical IgE is strongly linked with family history (p ≤ 0.001). We also detected differences in seasonality, especially with regards to pollen allergies. Eighty percent of children treated with Colinfant Newborn had significantly reduced IgE and morbidity at 13-15 months and 3 years, and furthermore without any clinical signs of allergy. Normalization of Immunoglobulins A and G was seen in 90% of treated subjects (p ≤ 0.001). These levels significantly correlated with an almost negligible morbidity up to 4 years of life. Colinfant Newborn, a lyophilized strain of Esherichia coli (E. coli), and a normal component of intestinal flora, readily colonizes the intestinal tract. It's long term presence significantly stimulates the production of specific and non-specific intestinal antibodies. and optimalizes immune development through tolerance. In our study Colinfant Newborn reduced the incidence of infections later in life by safely and effectively normalizing immunoglobulin levels in the majority of treated patients. CONCLUSION: Our study strongly suggests as positive effect of physiological Escherichia coli on the microbiome of newborn children as evidenced by a significantly reduced incidence of allergy and morbidity when applied early in life. These benefits appear to be strongly strain specific.

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

OBJECTIVES: Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. METHODS: Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. RESULTS: A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 µg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 µg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). CONCLUSIONS: H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis.

AIM: The aim of the study is to evaluate faecal calprotectin (f-CP) in children ≤3 years of age with acute gastroenteritis (AG) as an early predictor of bacterial inflammation. METHODS: We prospectively analysed f-CP levels and diagnostic workup in 107 consecutive children (66 AG, 41 controls). RESULTS: Children with bacterial AG (BAG) was found to have higher diarrheal frequency (p < 0.01), fever (p < 0.01), erythrocyte sedimentation rate (p < 0.001), white blood count (p < 0.01) and C-reactive protein (CRP) (p < 0.001) compared with viral AG (VAG). Vomiting was frequent in VAG (p < 0.001). f-CP negatively correlated with age in controls (r = -0.5998). BAG demonstrated significantly higher f-CP levels [median, 219 µg/g, interquartile range (IQR): 119-350.2] compared with VAG (49.3 µg/g, IQR: 8.8-131.1) as well as controls (26.5 µg/g, IQR: 14.9-55.1) (p < 0.001). VAG and control f-CP levels were similar. f-CP was the best-rated marker of BAG with a diagnostic accuracy of 92%. Receiver-operator characteristic analysis revealed an area under curve of 0.95 for identifying BAG; sensitivity and specificity of f-CP were 93% and 88%, respectively, at an adjusted cut-off point of 103.9 µg/g faeces. Combined f-CP and CRP yield improved diagnostic accuracy of 94% for BAG. CONCLUSION: f-CP facilitates early discrimination between bacterial and viral causes of AG in young children. Combining f-CP with CRP increases the diagnostic power of diagnosing BAG.

Treatment of encapsulated pleural effusions in children: a prospective trial.

BACKGROUND: The aim of this study was to improve the efficacy of treatment of complicated pleural effusions. METHODS: In this prospective study, 76 consecutive children (average age 5.0 +/- 4.14 years) fulfilling the required classification criteria were duly treated with chest tube placement and divided into two groups depending on the presence of encapsulated or non-encapsulated effusions. Treatment of the former group was supplemented by intrapleural fibrinolysis. The effectiveness of treatment was assessed in terms of chest tube dwell-time and total length of hospitalization. Regression analysis was performed using independent factors that were associated with these dependent factors. Value differences for P < 0.05 were considered significant. RESULTS: The ultrasound pleural distance and lactic-dehydrogenase content in the pleural fluid was significantly associated with the length of treatment (P < 0.01). Improved response to treatment, reduced duration of hospitalization (9.2 +/- 1.9 vs 11.5 +/- 0.9; P < 0.01) and tube dwell-time (7.6 +/- 1.3 vs 9.5 +/- 0.9; P < 0.01) was achieved in the intrapleural-fibrinolysis-treated group (n= 38) compared with controls (n= 38), with virtually the same total tube output (606.1 +/- 257.5 vs 673.1 +/- 347.4; P= 0.175). All patients were completely cured. Following 104 applications of the fibrinolytic agent there was one change in coagulation parameters: hypofibrinogenemia (in 1%). CONCLUSIONS: The authors recommend intrapleural fibrinolysis as an effective and safe alternative treatment strategy in treating encapsulated pleural effusions in children.

Epidemiology of Helicobacter pylori infection in asymptomatic children: a prospective population-based study from the Czech Republic. Application of a monoclonal-based antigen-in-stool enzyme immunoassay.

BACKGROUND: Acquisition of Helicobacter pylori occurs mainly in childhood and is significantly influenced by geographical variations. The aim of this study is to evaluate the prevalence of H. pylori infection in a population-based sample of asymptomatic children in the Czech Republic. Furthermore, this study aims to identify potential risk factors associated with this infection. MATERIALS AND METHODS: A prospective, cross-sectional, population-based study was undertaken in 1545 asymptomatic Czech children (aged 0-15 years; male 49.3%). Active H. pylori infection was diagnosed by monoclonal antibody-based antigen-in-stool enzyme immunoassay. Socio-demographic details of each subject were analyzed using a self-administered standardized questionnaire. Multiple regression analysis was performed. RESULTS: Overall, 7.1% of asymptomatic children were diagnosed with H. pylori infection. Of the infected children, 5.8% lived in the general population. A positive association was found with increasing age, although not with gender. Independent risk factors associated with H. pylori infection in our pediatric population were: the number of children in a household (odds ratio [OR] 4.26; confidence interval [CI] 1.91-9.80); lack of formal education of fathers (OR 0.23; CI 0.18-0.64) and institutionalized children (OR 6.33; CI 2.25-26.50). CONCLUSIONS: This study of a large cohort of children demonstrated that, independent of gender, H. pylori infection in the Czech Republic is among the lowest reported in Europe. Socioeconomically disadvantaged children, unfortunately, are still at risk of harboring this potentially preventable infection in this low-prevalence region.

Cytokine tumor necrosis factor-alpha A promoter gene polymorphism at position -308 G-->A and pediatric inflammatory bowel disease: implications in ulcerative colitis and Crohn's disease.

OBJECTIVES: Our pilot study aimed to determine the effect of tumor necrosis factor-alpha (TNF-alpha) 308 G-->A promoter single-nucleotide polymorphism in pediatric inflammatory bowel disease (IBD), its influence on inflammatory activity and the clinical manifestations. METHODS: We obtained genomic DNA from 164 subjects, 82 with long-standing IBD aged 8 to 18 years: 46 with Crohn disease (CD) and 36 with ulcerative colitis (UC). Eighty-two healthy children served as the control population. Genotyping was determined by using a restriction enzyme-based assay. TNF-alpha 308 G-->A polymorphism was assessed in terms of inflammatory (C-reactive protein [CRP]) and disease activity. The latter was assessed by the Pediatric Crohn's Disease Activity Index (PCDAI) and the Truelove index for CD and UC, respectively. RESULTS: Significant differences in TNF-alpha 308 A polymorphism were found between the IBD group and controls (P < 0.05) and the UC group and controls (P < 0.001). No differences were noted between TNF-alpha 308 A polymorphism and clinical characteristics in UC. The frequency of the -308 A allele of TNF was not different in CD compared with that in the control group. The frequency of TNF-alpha 308 A genotype was significantly higher in CD patients with predominantly stenosing/penetrating disease compared with patients without complications (P < 0.001) and healthy controls (P < 0.01). In CD patients, those carrying TNF -308 A had a significant increase in CRP (P < 0.05) and the PCDAI (P < 0.05). In CD, CRP levels strongly correlated with the PCDAI (r = 0.6150, P < 0.001). In UC, significant differences among the mean levels of CRP (P < 0.05) and disease activity (P < 0.001) related to TNF-alpha 308 A polymorphism were found. Allele distribution (odds ratio, 12.9; CI, 1.18-140.81, P < 0.001) and CRP serum levels (odds ratio, 1.020; CI, 1.00-1.04, P < 0.001) were independently associated with CD complications. CONCLUSIONS: Although not necessarily dictating IBD initiation, the TNF-alpha 308 A polymorphism may play a role in modifying the CD phenotype. The polymorphism may influence disease activity as well as more intense inflammatory activity in both forms of IBD and may modify the progression of chronic digestive tract inflammation.

Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study.

GOALS: To determine the efficacy of triple therapy supplemented with a specially designed fermented milk product containing specific probiotic Lactobacillus casei (L. casei) DN-114 001 strain on Helicobacter pylori eradication in children. BACKGROUND: Lactobacillus species possess in vitro activity against H. pylori. There are no consistent data on the impact of eradication therapy supplemented with probiotics on H. pylori cure rates in childhood in vivo. STUDY: Multicenter, prospective, randomized, double-blind controlled study. Eighty-six symptomatic H. pylori-positive children were randomized either to receive the control treatment of omeprazole, amoxicillin, and clarithromycin (OAC) for 7 days or the test treatment of omeprazole, amoxicillin, and clarithromycin for 7 days supplemented with fermented milk (Actimel) containing L. casei DN-114 001 (OAC-LC), for 14 days. H. pylori status was assessed at 4 weeks following therapy using two noninvasive tests. RESULTS: Intention-to-treat (ITT) based eradication rates for the OAC-LC group were 84.6% (95% CI, 71.2%-95.5%), and 91.6% (95% CI, 76.9%-98.2%) by per-protocol (PP) analysis. Eradication in the OAC group was 57.5% (95% CI, 42.2%-72.3%) in the ITT set and 61.3% (95% CI, 44.4%-75.0%) in the PP group. Eradication success was higher in the OAC-LC group compared with the OAC group in both ITT (P=0.0045) and PP analysis (P=0.0019). Primary resistance for clarithromycin could be determined in 21.2%. Side effects were infrequent. Drug compliance was good throughout the study. CONCLUSION: Supplementation with fermented milk, containing live special probiotic L. casei DN-114 001, confers an enhanced therapeutic benefit on H. pylori eradication in children with gastritis on triple therapy.

Aspects of oxidative stress in children with type 1 diabetes mellitus.

Diabetes mellitus is considered to be one of a rank of free radical diseases. The existence of hyperglycemia produces increased oxidative stress (OS) via non-enzymatic glycation, glucose autoxidation, and alterations in polyol pathway activity with subsequent influences on the whole organism. In childhood, Type 1 diabetes prevails and is characterized by its autoimmune character with progressive destruction of beta cells and lack of insulin in genetically predisposed patients. Our study focused on diabetic children and their 1st degree relatives and confirmed increased oxidative stress in diabetic children as well as a similar tendency in their siblings. Following this, we carried out a one-year study comprising diabetic children supplemented with vitamins E and C. The vitamin treatment improved diabetes control and reduced markers of oxidative stress substantially when compared with non-supplemented diabetic children. As oxidative stress impairs not only lipids and proteins, but also DNA, we attempted to examine the level of DNA strand breaks as well as DNA repair processes using comet assay modifications. Though children with Type 1 diabetes demonstrated increased oxidative stress (lower SOD and GSH when compared with healthy children), their oxidative DNA damage (measured as DNA strand breaks) were not substantially altered compared with normals. On the other hand, their DNA repair capacity was significantly increased. This demonstrates a stimulated DNA repair process that is most certainly a response to the permanently elevated state of oxidative stress. Owing to the presented results, it is appropriate to ponder the increased influence of oxidative stress on children with Type 1 diabetes and to take into account this fact when considering their treatment.

Gastric emptying of solids in children with H. pylori-positive and H. pylori-negative non-ulcer dyspepsia.

OBJECTIVE: There is currently no data available in children on possible relationships among Helicobacter pylori, gastric motility and gastric inflammation. This is a prospective study of gastric emptying (GE) in symptomatic children with and without H. pylori who met symptom-based criteria for non-ulcer dyspepsia (NUD). METHODS: 47 consecutive dyspeptic patients (23 males; age range, 7 to 18 years) were enrolled. All patients had extensive negative diagnostic investigations. Scintigraphic solid-phase gastric emptying was assessed. RESULTS: 21 H. pylori-positive and 26 H. pylori-negative patients were identified with non-ulcer dyspepsia. The groups were not different in clinical symptoms except that pain related to feeding was more frequent in infected children (P < 0.03). Nodular antral gastritis was found more frequently in the H. pylori positive group (P < 0.0001). The gastritis score was more severe in H. pylori infected than H. pylori negative patients in both fundic and body mucosa (P < 0.001). Within the H. pylori-positive NUD group, the mean half-time GE of a solid meal was significantly accelerated compared to the non-infected group (P < 0.05). There was no difference in the intragastric food distribution and curves of gastric emptying of both groups. A significant relationship was found between the degree of gastric body inflammation gastric emptying, but not antral inflammation. Gastric emptying rate did not differ by sex or age of the subjects in either group. CONCLUSIONS: In dyspeptic children with H. pylori, gastric emptying of a solid was significantly accelerated compared with symptomatic H. pylori uninfected patients. This suggests that H. pylori is able to induce gastric emptying acceleration. Our findings add more information on H. pylori infection and gastroduodenal disease.