Effect of omeprazole on symptoms of gastroesophageal reflux disease in children with cystic fibrosis. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The incidence of gastroesophageal reflux disease (GERD) is higher in patients with cystic fibrosis (CF) than in the general population. While the relationship between GERD and its typical symptom, heartburn, is beyond doubt, its effect on cough or abdominal pain is unclear. In CF patients, in particular, it is often difficult to confirm the causal relationship between GERD and these symptoms. The aim of this trial was to evaluate the effect of omeprazole treatment of GERD on abdominal pain and cough, in children with CF. PATIENTS AND METHODS: This was a multicentre, randomized, double-blind, placebo-controlled trial. All children aged 4-18 years underwent 24-hour multichannel intraluminal pH-impedance monitoring. The patients with diagnosed GERD were randomly assigned to receive omeprazole (20 mg twice daily for 12 weeks) or placebo. The severity of symptoms was assessed on visual analog scale. RESULTS: 22 consecutive patients (median age 11.02± 3,67, range 6.4-17.0) were enrolled. A statistically significant reduction in abdominal pain and typical GERD symptoms, but not cough, was observed in both omeprazole (N=12) and placebo (N=10) groups. However, there were no statistically significant differences between the groups in the degree of reduction. We did not observe any differences between the groups in terms of adverse reactions. CONCLUSIONS: Treatment of GERD in children with CF seems not to have a stronger effect than a placebo on the severity of cough and abdominal pain. Considering this, as well as the previously raised concerns about the impact of chronic proton pump inhibitor treatment on the course of CF, perhaps one should be more careful in intensively treating suspected atypical GERD symptoms in patients with CF.

Immunization Coverage in Children with Inflammatory Bowel Disease.

Patients suffering from inflammatory bowel diseases (IBD) are at increased risk of infections, mainly due to immunosuppressive treatment. Moreover, infections may cause flares of IBD. Vaccination is the most effective way of preventing many infections. The aim of this study was to evaluate the vaccination status of Polish children with IBD. Individual immunization cards of children with IBD and healthy controls were reviewed. Demographic data such as age, sex, and IBD history, including therapy type, were collected. We enrolled 267 children into the study, including 214 children with IBD and 53 controls. None of the children had completed the full up-to-date routine childhood immunization schedule recommended in Poland. Controls were more than 4 times more likely to be vaccinated than the IBD patients, with the vaccines that enjoy the insurance reimbursed (OR 4.1, 95% CI 2.2-7.9). In conclusion, the study demonstrates a poor vaccination status in children suffering from IBD.

Inflammatory cytokines in exhaled breath condensate in children with inflammatory bowel diseases.

BACKGROUND: Although inflammatory bowel diseases (IBD) affect mainly the gastrointestinal tract, the extra-intestinal manifestations are not uncommon. Different diagnostic methods have been applied to assess pulmonary involvement in patients with IBD, but majority of these methods show significant limitations in children. The aim of our study was to evaluate the usefulness of exhaled breath condensate (EBC) measurements of pro-inflammatory cytokines in children with IBD. MATERIAL AND METHODS: Twenty-two children with Crohn's disease (CD) (mean age 13.8 ± 3.3 years), 25 with ulcerative colitis (UC) (mean age 14.1 ± 3.3 years) and 37 healthy volunteers (mean age 13.9 ± 3.6 years) were studied. IBD activity was assessed using appropriate scoring systems. None of the patients had signs or symptoms of pulmonary disease. Exhaled breath condensate was collected and EBC concentration of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin 8 (IL-8) was measured. RESULTS: The concentrations of all the assessed cytokines were significantly higher in the study group as compared to controls. A negative correlation between IL-1ß and CD activity index was found. There were no significant relationships between TNF-α, IL-6, or IL-8 level and CD activity index as well as between IL-1ß, TNF-α, IL-6, IL-8 and UC activity index. No significant correlation between the concentration of IL-1ß, TNF-α, IL-6, IL-8, and IBD duration or treatment duration was found. CONCLUSIONS: Elevated concentration of pro-inflammatory cytokines in EBC in children with IBD may suggest the presence of asymptomatic inflammation in the lower airways.

Evaluation of laryngopharyngeal reflux in pediatric patients with asthma using a new technique of pharyngeal pH-monitoring.

There is a debate about the association between asthma and gastroesophageal and/or laryngopharyngeal reflux (LPR). Pharyngeal pH-monitoring is a new technique that allows a physician to assess whether reflux passes the upper esophageal sphincter barrier. The aim of the study was to assess the prevalence of LPR in children with difficult-to-treat asthma. The present study was an open, prospective one. A total of 21 subjects of the mean age 12.7 years were enrolled in the study. All children were asked to fill out a Reflux Symptoms Index questionnaire and a 24-h pharyngeal pH monitoring was performed, using the Dx-pH Measurement System. The LPR was diagnosed in 13 (61.9%) children. There was a positive correlation between LPR diagnosis and the degree of asthma control. The LPR was more frequent in children treated with a higher than lower doses of fluticasone (p = 0.019, OR = 17.3) and in those using montelukast compared with non-users (p = 0.008, OR = 19.0). The mean Reflux Symptoms Index score was almost twice greater in children with LPR than in those without it (13.2 vs. 6.8, respectively, p = 0.003). We conclude that the prevalence of laryngopharyngeal reflux in children with difficult-to-treat asthma is substantial.

Eosinophilic esophagitis in children: frequency, clinical manifestations, endoscopic findings, and seasonal distribution.

PURPOSE: Eosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic infiltration of the esophageal mucosa, which is associated with clinical and endoscopic manifestations. The objective of our study was to determine the frequency of EoE and to outline the clinical manifestations of EoE in Polish children. MATERIAL/METHODS: Ten large regional pediatric gastroenterology centers participated in the study. A database of endoscopy reports from January 2004 till December 2009 was reviewed. A total of 35,631 esophagogastroduodenal endoscopy studies in children, aged from 4 months to 18 years, were performed. Data pertaining to the children's age, gender, indications for endoscopy, clinical findings and histopathology diagnosis were made. RESULTS: In 84 children (20 girls and 64 boys), aged between 4 months and 18 years, EoE was diagnosed. This constituted one case per 424 endoscopic studies. In children with changes in the esophageal mucosa the frequency of EoE was higher and reached one case per 73 children. The most frequent symptoms of EoE differed between the younger (1-6 years old) and older children (aged 13-18 years old). Feeding aversion, vomiting and/or regurgitation were most frequently observed in the younger children, while in older children: abdominal pain, dysphagia and chest pain. Granular mucosa, longitudinal furrows, and mucosal rings belong to the findings most often observed in endoscopic studies. EoE was more frequently diagnosed in the spring (45.2%) and summer (28.5%). CONCLUSIONS: EoE was diagnosed in every age, with frequency of 1/424 gastrointestinal endoscopies, more frequently in boys than in girls.

Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease.

The prevalence of Clostridium difficile infection (CDI) in pediatric patients with inflammatory bowel disease (IBD) is still not sufficiently recognized. We assessed the prevalence of CDI and recurrences in outpatients with IBD. In addition, the influence of IBD therapy on CDI and antimicrobial susceptibility of the potentially causative C. difficile strains was assessed. This was a prospective, single-center, observational study. All specimens were obtained between January 2005 and January 2007 from the IBD outpatient service and screened for C. difficile and its toxins. C. difficile isolates were genotyped by PCR ribotyping. Diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was based on Porto criteria. Severity of disease was assessed using the Hyams scale (for Crohn's disease) and the Truelove-Witts scale (for ulcerative colitis). One hundred and forty-three fecal samples from 58 pediatric IBD patients (21 with Crohn's disease and 37 with ulcerative colitis) were screened. The risk of C. difficile infection was 60% and was independent of disease type (CD or UC) (χ2 = 2.5821, df = 3, p = 0.4606). About 17% of pediatric IBD patients experienced a recurrence of CDI. All C. difficile strains were susceptible to metronidazole, vancomycin and rifampin. A high prevalence of C. difficile infection and recurrences in pediatric outpatients with IBD was observed, independent of disease type. There was no significant correlation between C. difficile infection and IBD therapy. PCR ribotyping revealed C. difficile re-infection and relapses during episodes of IBD in pediatric outpatients.

Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children.

BACKGROUND: Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms. AIM: To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children. METHODS: Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat. RESULTS: Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed. CONCLUSION: Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.

Antibody response to influenza vaccination in patients suffering from asthma.

The aim of the study was to assess humoral response to influenza vaccination in 20 children with bronchial asthma vaccinated with split inactivated vaccine. Response to influenza hemagglutinin was assessed before vaccination and after 1 month by hemagglutination inhibition test. Antibody titers were significantly higher after vaccination than before vaccination. The mean fold increase of antibody levels ranged after vaccination from 12.2 to 53.7. The post-vaccination percentage of patients with protective antihemagglutinin antibody titers>or=40 ranged from 95% to 100%. The percentage of patients with at least a 4-fold increase of anthemagglutinin antibody titers ranged after vaccination from 90% to 100%. The results confirmed the immunogenicity and safety of inactivated influenza vaccine in children with asthma. The registered values of all parameters of the immunological response (mean fold increase, protection rate, response rate) fulfilled the requirements of the Committee for Proprietary Medicinal Products established for healthy people vaccinated against influenza.

Growth, bone age and nutritional status in neglected coeliac disease.

In 43 children with neglected coeliac disease (NCD) the growth and nutritional status (NS) were followed-up and analysed in the period between the age of 3 and 9 years in which prolonged exposure to gluten resulted in the persistent enteropathy. The significant "weight for age" and "height for age" deficits without concomitant "weight for height" deficits were observed at each yearly interval in the monitored period. The significant positive correlation between the percentage of children with the deficient NS and the duration of the exposure to gluten was found for the total examined period. There was also evidenced the significant bone age v. height age deficit. The linear growth retardation observed in NCD may be considered as the result of the progressive deficiency of NS.

[Activity and molecular form of intestinal gamma-glutamyltransferase (GGT) EC 2.3.2.2. in celiac disease]. / Aktywnosc i postac molekularna jelitowej gammaglutamylotransferazy (GGT) EC 2.3.2.2. w celiakii.

It has been shown that GGT activity in the duodenal biopsy homogenates of the children with coeliac disease (n-10) in remission (1 to 3 years of gluten-free diet) is lower than in those with other gastrointestinal tract diseases (n-6). In children with coeliac disease after gluten challenge (1 g of gluten) kg BW for 3 to 6 months) the GGT activity decreased fourfold (n-10). After a few months of gluten challenge there was in coeliac children (n-5) a marked predominance of GGT without sialic acid (the asialic GGT). Similarly there was a prevalence of this form (n-5) in the gut tissue of 3 month old human fetus. In the homogenates of the duodenal bioptates of the children with other gastrointestinal tract diseases (n-6) there was a predominance of the sialic form of the GGT. In the gut tissue of children older than 3 years (n-6) and adults who died of reasons other than gastrointestinal a marked predominance of the sialic form of GGT was found. It has been suggested that presence of asialic form of GGT in coeliac disease is connected with the lectin-like activity of gluten. The process of sialization or desialization takes place within or outside enterocytes. It changes the gut permeability and causes a secondary reaction to the penetrating allergens.

[Evaluation of the effect of gluten-free diet on nutritional status of children with florid celiac disease]. / Ocena wplywu diety bezglutenowej na stan odzywienia dzieci z celiakia "kwitnaca".

A dynamics of Nutritional Status of 55 children with recently diagnosed coeliac disease was assessed during the treatment with gluten free diet. No deterioration of the nutritional status was seen in 34.1% of the investigated children (time 0) whereas different degree of nutritional deficiency was noted in the remaining 75.9% of children including 10% of children with severe deficiency. After a 2-year therapy with gluten-free diet a deteriorated nutritional status was only found in 8.6% of children. In 27 children with gluten free diet for nearly 3 years, with maintenance of histological remission, the percentage of children with nutritional deficiency was 7.2%. The fact of normal Nutritional Status in more than 30% of the investigated coeliac children at the time of the initial diagnosis seems to be an effect of early and proper initial diagnosis.

[The effect of 6-month provocation with gluten on the height and weight of children with celiac disease]. / Wplyw 6-miesiecznej prowokacji glutenem na wysokosc i mase ciala u dzieci z celiakia.

Gluten challenge was performed in 22 coeliac children in the period of histological remission. Gluten in dose 0.5 g/kg was administered for 6 months. Before the Provocation Test over 60% of children have had body weight over 50 c for normal children in Warsaw. Standardized mean body weight (+ 0.13 +/- 1.1) and height (+ 0.04 +/- 1.05) of the investigated coeliac children did not differ significantly from the values of normal Warsaw population (p greater than 0.005). A 6 month provocation with gluten leading to the histological relapse did not affect body weight and height of tested children; over 50% have had body weight and height over 50 c. Mean standardized body weight (- 0.002 +/- 1.0) and height height (-0.07 +/- 0.91) did not differ significantly from the normal values (p greater than 0.05) and corresponding values before the provocation (p greater than 0.05). It seems that Provocation Test with gluten carried out in the above way does not inhibit physical development of children with coeliac disease.