L. Cosenza

Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease

BACKGROUND An accurate monitoring of mucosal inflammation is important for an effective management of patients with inflammatory bowel disease. Intestinal inflammation can be detected by faecal calprotectin level determination. AIM To comparatively evaluate the accuracy of faecal calprotectin, clinical scores, common serum markers and endoscopy in the assessment of the severity of intestinal mucosa inflammation in children with inflammatory bowel disease. METHODS Fifty-eight paediatric patients (mean age 13.9 years, 95% CI 2.9-14.8; male 28) with confirmed inflammatory bowel disease (26 Crohns disease, 32 ulcerative colitis) were enrolled. Before endoscopy, all patients underwent a complete evaluation including: clinical scores, erythrocyte sedimentation rate, C-reactive protein and faecal calprotectin determination. The severity of mucosal inflammation was assessed using specific endoscopic and histologic scores. RESULTS Faecal calprotectin showed a high correlation (r=0.655) with the histologic grade of mucosal inflammation, similar to that observed for endoscopy (r=0.699), and it resulted the most accurate tool (sensitivity 94%, specificity 64%, positive predictive value 81%, negative predictive value 87%) to detect the presence of active mucosal inflammation when compared to clinical scores and common serum markers. In patients with apparent clinical and laboratory remission the accuracy of faecal calprotectin resulted further improved (sensitivity 100%, specificity 80%, positive predictive value 67%, negative predictive value 100%). CONCLUSIONS A more accurate assessment of the severity of mucosal inflammation can be achieved by the determination of faecal calprotectin levels compared to other common clinical and laboratory indices. This non-invasive and objective method could be particular useful in patients with apparent clinical and laboratory remission.

Efficacy of a New Hypotonic Oral Rehydration Solution Containing Zinc and Prebiotics in the Treatment of Childhood Acute Diarrhea: A Randomized Controlled Trial

OBJECTIVE To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children. STUDY DESIGN We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours. RESULTS A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups. CONCLUSION The addition of zinc and prebiotics to ORS limits diarrhea duration in children.

The Effects of Dietary Counseling on Children with Food Allergy: A Prospective, Multicenter Intervention Study

Although dietary counseling is generally recommended in children with food allergy (FA), its effect on the nutritional status of these patients has not yet been evaluated. Our nonrandomized multicenter prospective intervention study was undertaken to investigate the effects of dietary counseling on children with FA. Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional status were evaluated in children with FA (aged 6 to 36 months) before and after dietary counseling, by multidisciplinary teams composed of pediatricians, dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41 boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls providing baseline values only. At enrollment, energy and protein intakes were lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1, minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7, respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6, maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively; P<0.001). A weight to length ratio <2 standard deviations was more frequent in children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months following dietary counseling, the total energy intake of children with FA was similar to the baseline values of control children. Dietary counseling also resulted in a significant improvement of their anthropometric and laboratory biomarkers of nutritional status. The results of our study support the crucial role of dietary counseling in the clinical management of children with FA.

Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea

Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society.

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial

Background Children with cows milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). Objective We performed a parallel‐arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. Methods Children with IgE‐mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double‐blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. Results A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0‐8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was −0.23 (95% CI, −0.36 to −0.10; P < .001), and the absolute risk difference for the acquisition of cows milk tolerance was 0.20 (95% CI, 0.05‐0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08‐0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11‐0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. Conclusions EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE‐mediated CMA.

The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System

The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network.

Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy prevention and treatment in children

Food allergy (FA) is a major health issue for children living in Western countries. At this time the only proven treatment for FA is elimination of offender antigen from the diet. It is becoming clear that the development of gut microbiota exerts a profound influence on immune system maturation and tolerance acquisition. Increasing evidence suggests that perturbations in gut microbiota composition of infants are implicated in the pathogenesis of FA. These findings have unveiled new strategies to prevent and treat FA using probiotics bacteria or bacterial substance to limit T-helper (Th)/Th2 bias, which changes during the disease course. Selected probiotics administered during infancy may have a role in the prevention and treatment of FA. Lactobacillus rhamnosus GG (LGG) is the most studied probiotic in this field. Administration of LGG in early life have a role in FA prevention. Preliminary evidence shows that LGG accelerates oral tolerance acquisition in cows milk allergic infants. We are understanding the mechanisms elicited by LGG and metabolites in influencing food allergen sensitization. A deeper definition of these mechanisms is opening the way to new immunotherapeutics for children affected by FA that can efficiently limit the disease burden.

The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management

Food allergies (FAs) are an increasing problem in Western countries, affecting up to 10% of young children. FAs are frequently associated with gastrointestinal manifestations. The role of FAs as a potential causative factor for infantile colic (IC) is still controversial. We report the most recent evidence on the pathogenesis, clinical and diagnostic aspects of FA-induced infantile colic (IC) and suggest a stepwise diagnostic approach. We selected articles on clinical and immunologic features, pathogenesis and management of FAs and IC from of 1981 to 2015. Original and review articles were identified through selective searches performed on PubMed, using the following terms: colic, infantile colic, food allergy and infantile colic, infantile colic treatment. The possible relationship between FAs and IC derives from the presence of dysmotility with visceral hypersensitivity and dysbiosis, demonstrated in both conditions, and the clinical response to dietary interventions. Unfortunately, the design of the studies, poor characterization of atopy and different dietary approaches limit the understanding of the importance of FAs in subjects with IC. The role of FAs in IC subjects without other symptoms of atopy remains controversial. However, where there is a suspicion of FAs, a short trial with an extensively hydrolyzed cow’s proteins formula or, if breast fed, with maternal elimination diet may be considered a reasonable option.

Toward a standardized reading of the atopy patch test in children with suspected cow’s milk allergy-related gastrointestinal symptoms

Patients with non-IgE-mediated cow’s milk allergy (CMA) often present with gastrointestinal symptoms (1). Atopy patch tests (APTs) have been proposed for the diagnosis of non-IgEmediated food allergy (2) and are recommended for the diagnosis of eosinophilic esophagitis in adults and children (2). We previously found them to be a useful diagnostic tool in children with gastrointestinal symptoms and suspected CMA (1). These tests have also been proposed for the early diagnosis of CMA-related gastrointestinal symptoms in preterm infants (3). However, the use of APTs in the clinical practice of pediatric gastroenterology is still limited by the subjective interpretation and intraobserver variation. Moreover, the diagnostic accuracy of the test varies between studies, and data about the effect of the severity of skin signs on APTs are scarce. A standardized interpretation of APTs in children with atopic dermatitis has been proposed (4), whereas the issue of APT reading in children with suspected CMA-related gastrointestinal symptoms has yet to be addressed. Consequently, we evaluated whether the diagnostic accuracy of APTs in children with suspected CMA-related gastrointestinal symptoms could be influenced by the severity of skin signs. From October 2008 to September 2010, 119 consecutive children (77 boys, median age 26.7 months, range 3–48 months) with suspected CMA-related gastrointestinal symptoms were evaluated in our tertiary Pediatric Gastroenterology and Allergology Center. Gastrointestinal symptoms at presentation were vomiting (73/ 119, 61.3%), chronic diarrhea (34/119, 28.5%), and hematochezia (17/119, 14.2%). The APTs were performed in all enrolled subjects using previously reported method in which a drop (20 ll) of fresh cow’s milk containing 3.5% fat is placed on filter paper and applied with adhesive tape to the unaffected skin of the child’s back using a 12-mm aluminum cup (1). Isotonic saline solution was used as negative control to exclude false positive reactions. The occlusion time was 48 h, and the results were read 20 min and 24 h after removal of the cups. Antihistamines and anti-inflammatory agents were discontinued at least 7 days before the test. All tests were performed by the same nursing staff, and the results were read by two expert pediatric allergists blind to the outcome of the double-blind, placebo-controlled food challenges (DBPCFC). Skin findings were recorded on a standardized form. Reactions were judged to be either negative or positive. Positive skin reactions on the APT site were classified mild (erythema and slight infiltration, +), moderate (erythema plus papules, ++), or severe (erythema plus vesicles, +++), as previously suggested (1, 5). All children enrolled in the study also underwent skin prick tests (SPT) with fresh cow’s milk containing 3.5% fat and evaluation of specific serum IgE with a commercial kit (CAP-RAST; Pharmacia Diagnostic AB, Uppsala, Sweden), as reported previously (1). The children subsequently underwent DBPCFC as previously described (5, 6). Briefly, successive doses (0.1, 0.3, 1.0, 3.0, 10.0, 30.0, and 100.0 ml) of fresh cow’s milk containing 3.5% fat or placebo (Neocate , Nutricia, Italy) were administered at 20-min intervals. Data were analyzed with the Stats Direct statistical software (Altrincham, Cheshire, UK, release 2.5.6, 15 April 2006). Regarding DBPCFC outcomes, we calculated sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratio (LR) for single and several combinations of skin signs at 72 h. The Ethics Committee of our Institution approved the study, and written informed consent was obtained from the parents of each child. Erythema plus papules at APT has high diagnostic accuracy in children with CMA-related gastrointestinal symptoms.

Tolerance to a new free amino acid-based formula in children with IgE or non-IgE-mediated cow's milk allergy: a randomized controlled clinical trial

BackgroundAmino acid-based formulas (Aaf) are increasingly used in children with cow’s milk allergy (CMA). To be labeled hypoallergenic these formulas must demonstrate in clinical studies that they don’t provoke reactions in 90% of subjects with confirmed CMA with 95% confidence when given in prospective randomized, double-blind, placebo-controlled challenge (DBPCFC) trials. The majority of available safety data on Aaf derived from patients with IgE-mediated CMA. Considering substantial differences in the immunologic mechanism and clinical presentation of non-IgE-mediated CMA it’s important to investigate the hypoallergenicity of these formulas also in these patients. We prospectively assessed the tolerance to a new commercially available Aaf in children affected by IgE- or non-IgE-mediated CMA.MethodsConsecutive patients affected by IgE- or non-IgE-mediated CMA, aged ≤ 4 years, were enrolled. DBPCFC was carried out with increasing doses of the new Aaf (Sineall, Humana, Milan, Italy), using validated Aaf as placebo. Faecal concentrations of calprotectin (FC) and eosinophilic cationic protein (ECP) were monitored.ResultsSixty patients (44 male, 73.3%, median age 37, 95%CI 34.5–39.6 months, IgE-mediated CMA 29, 48.3%) were enrolled. At the diagnosis clinical symptoms were gastrointestinal (46.6%), cutaneous (36.6%), respiratory (23.3%), and systemic (10.0%). After DBPCFC with the new Aaf, no patient presented early or delayed clinical reactions. Faecal concentration of calprotectin and of ECP remained stable after the exposure to the new Aaf.ConclusionsThe new Aaf is well tolerated in children with IgE- or non-IgE-mediated CMA, and it could be used as a safe dietotherapy regimen for children with this condition.Trial registrationThe trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT01622426).