V. Mancini

Evolution of Gastric Electrical Features and Gastric Emptying in Children with Duchenne and Becker Muscular Dystrophy

OBJECTIVES:Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course.METHODS:Twenty children with MD (median age: 4.6 yr; range age: 3–7 yr) were investigated by means of ultrasonography, for measuring GET, and by electrogastrography (EGG); 70 children served as controls.RESULTS:Ten patients had Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD). GET was significantly more delayed in MD patients (DMD, median: 195 min; range 150–260 min; BMD, median: 197 min; range: 150–250 min) than in controls (median: 150 min; 110–180 min; p < 0.05); it markedly worsened at the follow-up in DMD (median: 270 min; range 170–310 min; p < 0.001 vs controls) but not in BMD patients (median: 205 min; 155–275 min; p < 0.05 vs DMD). Baseline EGG showed a significantly lower prevalence of normal rhythm and significantly higher prevalence of dysrhythmias in both groups of patients as compared to controls (% of normal rhythm: DMD 66.7 ± 8.2, BMB 67.2 ± 11.5, controls 85.3 ± 7.2, p < 0.001; % of tachygastria: DMD 28.4 ± 8.0, BMB 29.8 ± 12.3, controls 10.6 ± 5.1, p < 0.001; % of dominant frequency instability coefficient: DMD 36.1 ± 6.0, BMB 33.2 ± 2.9, controls 17.9 ± 7.1, p < 0.001); furthermore, no difference in fed-to-fasting ratio of the dominant EGG power was found between the two groups and controls (DMD 2.84 ± 1.27, BMB 2.82 ± 0.98, controls 3.04 ± 0.85, ns). However, at the follow-up no significant change in the prevalence of normal rhythm and dysrhythmias occurred in both groups (ns vs baseline values), whereas only DMD patients showed a marked reduction in fed-to-fasting power ratio (0.78 ± 0.59; p < 0.001 vs controls and BMD; p < 0.05 vs baseline), which correlated with the progressive neuromuscular weakness occurring in DMD subjects (r, 0.75; p < 0.001).CONCLUSIONS:In children with MD, there is an early abnormality in gastric motility that is due to deranged regulatory mechanisms, whereas contractile activity of smooth muscle cells seems to be preserved. At the follow-up, DMD patients exhibited a progressive failure in neuromuscular function, which was accompanied by a gastric motility derangement with worsening in GET and in EGG features suggesting an altered function of gastric smooth muscle cells.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non‐erosive reflux disease

Background  Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro‐esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease.

Activation of NOD2-mediated Intestinal Pathway in a Pediatric Population with Crohn's Disease

Background: NOD2 is an intracellular protein involved in host recognition of specific bacterial molecules and is genetically associated with several inflammatory diseases, including Crohns disease (CD). NOD2 stimulation activates the transcription factor, NF‐κB, through RIP2, a caspase‐recruitment domain‐containing kinase. NOD2/RIP2 signaling also mediates the activation of antimicrobial peptides such as human α‐defensin 5 (HD‐5) and human α‐defensin 6 (HD‐6), both produced by Paneth cells. The present study is aimed at describing the downstream events triggered specifically by NOD2 induction in order to demonstrate that the protein, other than overexpressed, is also physiologically associated with RIP2 and Erbin in the bioptic intestinal inflamed specimens of children affected by CD. Methods: Fifteen children with CD and 10 children used as controls were entered in the study. Mucosal biopsy specimens were taken during endoscopy and mRNA and protein expressions were detected by using real‐time polymerase chain reaction and Western blot. Results: NOD2 is able to form an immunocomplex with the kinase RIP2. As compared to controls, in the inflamed mucosa of patients both mRNA and protein expression levels of RIP2 are increased, and its active phosphorylated form is overexpressed. Conclusions: In this study we provide for the first time ex vivo evidence of physiologically relevant protein interactions with NOD2, which are able to trigger the innate immune response in intestinal mucosal specimens of children with CD. (Inflamm Bowel Dis 2009)

Role of gastroesophageal reflux in children with unexplained chronic cough

Objective: The relation between respiratory symptoms and gastroesophageal reflux (GER) is a matter of contention and debate, with limited data in children to substantiate or refute cause and effect. Moreover, there are few data on the relation between nonacid reflux and chronic cough in childhood. We aimed to describe the type and physical characteristics of reflux episodes in children with unexplained chronic cough. Patients and Methods: Forty-five children with chronic cough underwent 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH monitoring). Symptom association probability (SAP) characterized the reflux-cough association. Twenty children with erosive reflux disease (ERD) served as controls. Results: Twenty-four children had cough-related reflux (CRR), with 19 having no gastrointestinal symptoms. Twenty-one had cough-unrelated reflux (CUR). CRR and ERD had increased acid (AR), weakly acidic (WAc), and weakly alkaline (WAlk) reflux. Esophageal acid exposure time and acid clearance time were higher in ERD than in CRR and CUR. In the CRR group, of 158 cough episodes related to reflux episodes, 66% involved AR, 18% WAc, and 16% WAlk. Seventeen children had positive SAP, 7 for AR, 5 for both AR and WAc, 4 for both WAc and WAlk, and 1 for WAlk. Conclusions: In children with unexplained chronic cough, asymptomatic acid and nonacid GER is a potential etiologic factor. The increased acid exposure time and delayed acid clearance characteristic of ERD are absent in cough-related GER. MII-pH monitoring increases the likelihood of demonstrating a temporal association between the cough and all types of reflux.

Non-acid gastro-oesophageal reflux in children with suspected pulmonary aspiration.

BACKGROUND & AIMS In a group of children with suspected pulmonary aspiration, we aimed to describe the type and physical characteristics of gastro-oesophageal reflux (GOR) episodes, and to determine their correlation with the lipid-laden macrophage (LLM) content in bronchoalveolar lavage (BAL). PATIENTS AND METHODS Twenty-one children with a diagnosis of bronchial asthma, recurrent lung consolidations and recurrent laryngotracheitis underwent 24-h multichannel intraluminal impedance and pH (MII-pH) monitoring, fibreoptic bronchoscopy and BAL. The following parameters were evaluated: total number of reflux episodes, number of acid reflux [AR; pH<4] and non-acid reflux [NAR] episodes [pH>4], height of reflux episodes, LLM content and percentage of neutrophils in the BAL. RESULTS The number of NAR episodes and the number of those reaching the proximal oesophagus were significantly higher in patients with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01 and p<0.01). BAL studies showed a significantly higher LLM content in children with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01). The LLM content correlated significantly with the total number of reflux episodes (r=0.73; p<0.001) and with those reaching the proximal oesophagus (r=0.67; p<0.001). Finally, the LLM content correlated with the number of NAR episodes (r=0.61; p<0.01), with those reaching the proximal oesophagus (r=0.64; p<0.01) and with the percentage of BAL neutrophils (r=0.7; p<0.01). CONCLUSION NAR episodes reaching the proximal oesophagus correlate with diagnostic marker for pulmonary micro-aspiration. MII-pH monitoring increases the yield in identifying types and proximal extension of reflux episodes, that discriminate between patients with and without pulmonary aspiration.

Inflammation of the gastric cardia in children with symptoms of acid peptic disease

OBJECTIVES To assess the severity and causes of inflammation of the gastric cardia in children undergoing endoscopy for symptoms of acid peptic disease. STUDY DESIGN Patients undergoing upper gastrointestinal endoscopy for symptoms of acid peptic disease had biopsies from gastric cardia, gastric, and esophageal sites, and 24-hour intraesophageal pH monitoring. Gastric cardia was defined at endoscopy as the anatomic zone from the squamocolumnar junction to 0.5 cm below it. Severity of gastric cardia inflammation was scored 0 to 9 according to densities of inflammatory cells and epithelial abnormalities in surface and pit epithelium. A score > or =2 was considered positive. RESULTS Forty-seven children (median age, 6.5 years; range, 3-15) had Helicobacter pylori infection, gastroesophageal reflux disease (GERD), or both. In 22 patients, H pylori was detected in cardiac biopsies by rapid urease test and histology; it was detected also in the corpus and antrum in only seven of the 22. No patient had H pylori in gastric corpus/antrum without having the organism at the cardia as well. In 12 H pylori-positive patients, GERD was also diagnosed. Twenty-five patients had GERD and no H. pylori infection. Severity score was 3.8+/-0.8 in the H pylori group and 2.08+/-0.9 in the GERD alone group (P<.001); however, there was no difference in reflux index (24-hour % of gastroesophageal reflux) between the two groups. In neither group was correlation found between reflux index and severity score (H pylori, r=0.22; GERD alone, r=0.31; NS) nor between cardia inflammation and esophagitis grade (H pylori, r=0.37; GERD alone, r=0.22; NS). CONCLUSIONS In children with symptoms of acid peptic disease, inflammation of the gastric cardia does occur. It is more severe when the cardiac zone is infected with H pylori than in its absence. Of major practical significance is the finding that the gastric cardia is a highly sensitive site for the detection of H pylori infection.

Oesophageal mucosal intercellular space diameter and reflux pattern in childhood erosive and non-erosive reflux disease

BACKGROUND AND AIMS We sought to compare intercellular space diameter in children with non-erosive and erosive reflux disease, and a control group. We also aimed to characterize the reflux pattern in erosive and non-erosive reflux disease patients, and to explore the relationship between intercellular space diameter values and reflux parameters. METHODS Twenty-four children with non-erosive reflux disease, 20 with erosive reflux disease, and 10 controls were prospectively studied. All patients and controls underwent upper endoscopy. Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter was measured using transmission electron microscopy. Non-erosive and erosive reflux disease patients underwent impedance-pH monitoring. RESULTS Mean intercellular space diameter values were significantly higher in both non-erosive (0.9 ± 0.2 μm) and erosive reflux disease (1 ± 0.2 μm) compared to controls (0.5 ± 0.2 μm, p<0.01). No difference was found between the two patient groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline reflux events did not differ between the two patient groups. No difference was found in the mean intercellular space diameter between non-erosive reflux disease children with and without abnormal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 μm). No correlation was found between any reflux parameter and intercellular space diameter values. CONCLUSIONS Dilated intercellular space diameter seems to be a useful and objective marker of oesophageal damage in paediatric gastro-oesophageal reflux disease, regardless of acid exposure. In childhood, different gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis of reflux pattern.

CO15 OESOPHAGEAL MUCOSAL DILATED INTERCELLULAR SPACES (DIS): IS IT A REAL ULTRASTRUCTURAL MARKER OF GERD PHENOTYPE? A CHILDREN POPULATION STUDY

Results: All patients under 2 years of age were normal for weight. Between 2 and 20 years, 18/143 (12.6%) were underweight and 48/143 (33.6%) were “at risk”. Over 20 years 6/12 (50.0%) “at risk” and no one was underweight. We confirm the positive relationship between FEV1% and nutritional status (FEV1% M±DS 98.03±24.11 in normal weight vs 67.05±25.67 in underweight; p 20 yrs BMI “at risk” M±DS T0 18.50±9.57 vs T1 20.11±10.52). In patients between 2 and 20 years the percentage of patients less than the 10th BMI percentile and between 10th and 50th BMI percentile decreased from 18/143 to 4/143 (12.6% vs 2.7% p<0.001) and from 48/143 to 34/143 (33.6% vs 23.7%, p<0.001) respectively. Conclusion: Our study confirms the crucial role of an early diagnosis of CF in order to prevent nutritional failure. Individual management with an aggressive nutritional treatment in CF patients in or at highest risk for malnutrition can increase rates of adherence to nutrition recommendation for improving clinical outcomes. References [1] Lai HJ, Shoff SM. Classification of malnutrition in cystic fibrosis: implications for evaluating and benchmarking clinical practice performance. Am J Clin Nutr 2008;88:161–6.