Altered miR-193a-5p expression in children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. METHODS: Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. RESULTS: Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. CONCLUSIONS: Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.

Atopy patch tests are useful to predict oral tolerance in children with gastrointestinal symptoms related to non-IgE-mediated cow's milk allergy.

Atopy patch tests (APTs) have been proposed for the diagnostic approach in children with non-IgE-mediated cow's milk allergy and gastrointestinal symptoms. We aimed to investigate the benefit of APTs in predicting oral tolerance in these patients. We prospectively evaluated 172 subjects with a sure diagnosis of non-IgE-mediated CMA and gastrointestinal symptoms (97 boys, 56.4%; age, 6.37 m; range, 2-12 m). At diagnosis, 113/172 (65.7%) children had positive APTs to cow's milk proteins (CMP). After 12 months of exclusion, diet APTs were repeated immediately before OFC. APTs significantly correlated (P < 0.001) with the OFC outcome (r 0.579). Diagnostic accuracy was sensitivity of 67.95%, specificity of 88.3%, PPV of 82.81%, NPV of 76.85%, and a +LR of 5.80. APTs are a valuable tool in the follow-up of children with non-IgE-mediated CMA-related gastrointestinal symptoms by contributing in determining whether an OFC can safely be undertaken.

Effect of intrauterine growth retardation on liver and long-term metabolic risk.

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.

Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children.

Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed.

Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn's disease.

BACKGROUND: Comparative data on the therapeutic efficacy of different enteral nutrition formulas and corticosteroids to obtain clinical remission and to induce mucosal healing influencing long-term disease course in paediatric Crohn's disease are still scarce. AIMS: To investigate the efficacy of nutritional therapy using three different formulas versus corticosteroids to achieve clinical remission as well as to induce intestinal mucosal healing in active Crohn's disease children. Duration of remission and effect on growth recovery were also assessed. PATIENTS AND METHODS: Clinical, laboratory, endoscopic and histological data of all new diagnosed active Crohn's disease paediatric cases were retrospectively recorded and reviewed. Thirty-seven children (median age 12.1 years) received nutritional therapy (12 polymeric; 13 semi-elemental; 12 elemental diet) and 10 subjects (median age 12.4 years) received corticosteroids. RESULTS: Similar clinical remission rate were observed after 8 weeks of treatment: 86.5% children receiving nutritional therapy versus 90% treated with corticosteroids. Improvement in mucosal inflammation occurred in 26 out of 37 (64.8%) patients on nutritional therapy and in 4 out of 10 (40%) children on steroids (p < 0.05). Finally, seven subjects on nutritional therapy and none on corticosteroids achieved complete mucosal healing (p < 0.005) at the end of the treatment. Nutritional therapy was more effective than corticosteroids in improving nutritional status and linear growth recovery. Compared to corticosteroids, the duration of clinical remission was longer in the nutritional therapy groups without differences among the three different formulas. CONCLUSIONS: In children with active Crohn's disease, nutritional therapy is more effective than corticosteroids to improve intestinal inflammation and to maintain a more sustained clinical remission.

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 cow's 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.

Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients.

BACKGROUND: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. AIMS: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. PATIENTS AND METHODS: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. RESULTS: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05). CONCLUSIONS: This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

Costs associated with outpatient diarrhoea in infants and toddlers: a nationwide study of the Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP).

BACKGROUND: As diarrhoea mortality is negligible in Italy, other costs should be considered when planning health strategies. Little is known about the costs associated with diarrhoea in Italian children. AIMS: To assess the costs associated with outpatient infantile diarrhoea in Italy. METHODS: Primary care paediatricians from five regions filled in a questionnaire for the first 10 children (1-47 months) they visited for acute diarrhoea during a 3-month period. RESULTS: We analysed 473 questionnaires. Mean age (standard deviation) of children was 21 (11) months; mean duration of diarrhoea (standard deviation) was 4.3 (2.6) days. An overall cost of 110 (137) euro per episode was estimated, with significant difference between children younger and older than 36 months (116 euro versus 72 euro). Missed work by relatives accounts for 75% of the cost. The parents of children attending a day-care centre had an increased risk to miss work (relative risk = 2.15). A weak relationship was found between days of diarrhoea and missed work (r = 0.30); it could be estimated that the diarrhoea should be shortened by about 4 days in order to save I day of missed work. CONCLUSIONS: Acute outpatient diarrhoea is associated with a significant financial burden in Italy. Simply shortening the diarrhoea does not seem to be the most expeditious way to reduce the cost of diarrhoea itself.

Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice.

BACKGROUND: Faecal calprotectin (FC) is a new marker of intestinal inflammation. Data on FC in paediatric gastroenterology clinical practice are still scarce. AIMS: To assess FC values in different paediatric gastrointestinal diseases comparing them with those obtained in healthy children. PATIENTS: Two hundred and eighty-one children (age range 13-216 months) consecutively referred for gastrointestinal symptoms. Seventy-six healthy controls (age range 13-209 months). The exclusion criteria in healthy children were the following: any known underlying chronic disease or a history of abdominal pain, diarrhoea, acute respiratory tract infection, intake of non-steroidal anti-inflammatory drugs, gastric acidity inhibitors, antibiotics, drugs influencing gut motility, and menstrual or nasal bleeding in the last 3 weeks. METHODS: Stool samples stored, prepared and analyzed by an ELISA assay. RESULTS: In healthy children the median FC value was 28.0 microg/g (15-57 interquartile range) with a 95th percentile value of 95.3 microg/g. An increase in FC concentration was observed in all diseases characterized by gastrointestinal mucosa inflammation, and the active inflammatory bowel disease patients showed the higher FC values. All children affected by functional bowel disorders or by non-inflammatory diseases showed normal values. We calculated an optimized FC cut off value of 102.9266 microg/g (revealed by the receiver operating characteristic curve) to distinguish patients with active organic/inflammatory disorders from healthy subjects and from patients with functional bowel disorders. CONCLUSIONS: Calprotectin is a sensitive, but not disease specific, marker to easily detect inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal mucosa inflammation and in the differential diagnosis of functional bowel disorders.

[Acute infectious diarrhea in children]. / La diarrea acuta infettiva in età pediatrica.

Infantile acute gastroenteritis is still a frequent problem particularly in younger children, with high mortality rate in developing countries and high impact on health costs in industrialized countries. The increased knowledge on its pathophysiology has led to the definition of two distinct mechanisms of diarrhea: the secretory and the osmotic pathway. Investigation on the host-microorganism interaction revealed a complex scenario with sophisticated mechanisms developed by microorganisms during evolution to overcome the host defense system. The latter includes immune and non immune coordinated components, with a major role played by the GALT (gut associated lymphoreticular tissue). Knowledge of epidemiology and of the natural history of intestinal infections has led to rational diagnostic approach with substantial cut of medical costs. Novel therapeutic strategies have been made available with the use of probiotics and of passive immunotherapy together with a dramatic reduction of antibiotic treatment. HIV pandemy raises major problems which need rapid responses.

["Silent" gastroesophageal reflux and upper airway pathologies in childhood]. / Reflusso gastroesofageo "silente" e patologia delle alte vie respiratorie in età pediatrica.

In children, gastroesophageal reflux (GER) plays an important role in both acute and chronic upper airway disorders including stridor, chronic cough, recurrent upper respiratory infections, obstructive apnea, laryngospasm, and wheezing. Diagnosis may prove difficult unless there is reason to suspect GER and one is aware of the concept of "silent" GER. This paper presents our experience with chronic and/or recurrent respiratory disorders of uncertain origin and without gastrointestinal symptoms in children. Thirty-two pediatric patients with upper respiratory symptoms were evaluated. Out-patient 24-hour intraesophageal pH was monitored and 56% of the patients underwent pharyngo-laryngeal fibroscopy. The patients were divided into two subgroups: Group A (18 patients < 6 months of age) and Group B (14 patients > 6 months). All the patients tested positive for GER with a mean Reflux Index of 21.5. The most common symptoms in Group A were apnea-cianosis and stridor while they were chronic cough for group B. The present study confirms the association between GER and respiratory disease and between GER respiratory-related symptoms and patient age. Emphasis is placed on the importance of otolaryngological diagnostic procedures and 24-hour pH-gastroesophageal monitoring in evaluating patients with respiratory disorders related to silent GER.

[Study of the activity of ambroxol in children with aspecific bronchial hyperreactivity]. / Studio sull'attività dell'Ambroxol in bambini con iperreattività bronchiale aspecifica.

The authors examined the action of non-specific bronchial reactivity to methacholine (IBA) before and after treatment with ambroxol in a group of a children with clinic symptomatology of recurrent cough and/or rhinitis. The little patients are selected from a pediatric population that, besides the clinical data mentioned above, had a high probability to manifest nonspecific bronchial reactivity for which clinical and anamnestic data predisposed. In all patients were carried out an allergologic examination with the execution of Prick test and determination of total IgE. The results obtained and discussed suggest a favorable employ of the drug that is able to normalize the functional condition of the bronchial mucous membrane and of the ciliary apparatus which alteration are frequently present in subjects with high non-specific bronchial reactivity.

[Cardiac involvement in food allergy. Study of cardiac activity by Holter monitoring in 12 allergic children during food challenge]. / Coinvolgimento cardiaco nell'allergia alimentare. Studio dell'attività cardiaca mediante Holter in 12 ragazzi allergici durante challenge alimentare.

The authors have based their study on recent research of cardiac anaphylaxis in vitro and studied the cardiac involvement in vivo, by Holter trace in a group of 12 children with food allergy in basal period (food allergens exclusion) and during food allergens reintroduction. In the same time the involvement of respiratory apparatus was followed by RAW's insp.esp. study. The results showed contemporaneously at the RAW's rise a mean increase of cardiac frequency of slight moment when the frequency was computed during 24 h, but evident in challenge phase. The cardiac frequency study in "late" phase of reply at the food allergens challenge showed a heavy and significant increase of cardiac frequency and extrasystole.

[Immunological and trace element study in 50 children with various diseases caused by food allergens and aeroallergens]. / Studio immunologico e degli oligoelementi in 50 bambini affetti da varia patologia indotta da allergeni alimentari e da aeroallergeni.

The authors executed a study on the levels of T lymphocytes and of serum Fe, Zn and Cu in 50 atopic children. The boys showed a various pathology who included the eczema, the laryngotracheobronchostenosis, the choanal obstruction and/or the adenoid's obstruction, abdominal pains, stomatitis, relapsing herpes, shock, neurosis. The T4/T8 relationship resulted lower in the 34.5% of subjects, higher in the 30.5% normal in the 35.5%. In the patients with hyper-IgE the 28.2% of children showed this relationship in the normality, but in the children with a heavy atopic syndrome and normal IgE only the 7.3% of subjects showed the T4/T8 relationship in the normality. The authors dwell on the heavy iron deficiency (72%) and of the Zn (52%) and of the Cu (33%) in the serum present in these subjects. The authors suppose that these changes come from a short absorption of these ions coming from the epithelial gut's damage caused by the daily ingestion of food allergens.

[Results of nasal brushing in the study of ciliary conformation and function in chronic bronchopneumopathies in childhood]. / Risultati dell'aplicazione del brushing nasale per lo studio della conformazione e funzione ciliare nelle broncopneumopatie croniche infantili.

UNLABELLED: For the frequent remark in childhood of relapsing bronchitis and/or broncho-pneumonic sickness we resolved to use for the differential diagnosis the nasal brushing method according to Rutland (for samples of ciliated epithelium from the deep surface of the inferior nasal turbinate using a 2 mm diameter nasal brush. The samples were used for ultrastructural study of cilia. RESULTS: Children studied 22:14 (6-14) y.old with relapsing bronchitis, 4 with relapsing broncho-pneumonitis, 1 Nemaline myopathy (n.m.) with heavy respiratory insufficiency; 3 Werdnig Hoffmann syndromes (W.H.). Control group of 4 normal children. In the control group and 14 relapsing bronchitis normal tubular pattern (9 + 2) and ciliary conformation were present; in the relapsing broncho-pneumonic syndrome group, 2 children presented deficiency of some brace dynein arms = chronic inflammation; in the Nemaline myopathy we noted total lack of interior dynein arms with random cilia orientation; in the 3 W.H. = normal cilia conformation. The authors noted for the heavy respiratory insufficiency of the Nemaline myopathy the presence of immotile cilia and discuss possibility that in all Nemaline myopathy syndromes this association may be present (a new syndrome?). The W.H. myopathy is characterized by normal cilia aspects and the respiratory insufficiency is caused by muscular respiratory insufficiency secondary to anterior spinal corn horn. In the Nemaline myopathy the same genetic defect can act in muscular fibres and on dynain arms (cytoskeleton). The technique described is suitable for processing epithelial brushings from other parts of the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gastric mucosa changes caused by anti-inflammatory agents in childhood]. / Alterazioni mucosali gastriche da assunzione di farmaci antinfiammatori in età pediatrica.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids are very commonly prescribed. Morbidity and mortality from nonsteroidal anti-inflammatory drugs (NSAID) and steroids continue to be a significant health problem. In this paper are reported: 1) the biological insights into injurious effects of NSAIDs and steroids on mucosal protection and repair; 2) our clinical experience in the diagnosis and the management of children affected by secondary ulcer disease induced by therapeutic doses of NSAIDs and steroids; 3) the guidelines in the prevention of the NSAIDs and steroids-induced gastric damage.

[Clinico-epidemiological considerations of 30 cases of pulmonitis and pleuropulmonitis in childhood]. / Considerazioni clinico-epidemiologiche su 30 casi di polmonite e pleuropolmonite in età pediatrica.

The authors studied 30 children affected with pneumonia or pleuropneumonia. They point out some clinical and epidemiological features pertinent to the pathology examined.

[The correlation between psittacosis-ornithosis and the immune status in childhood: apropos 5 cases]. / Correlazione fra psittacosi-ornitosi ed assetto immunitario in età infantile: a proposito di 5 casi.

The authors studied 5 children affected with a pneumopathy by Chlamydia psittaci. They discuss the effects of a transitory immunodeficiency relative to NK cells in predisposing little patients to the infective disease.

[Changes in the motor apparatus of the bronchial cilia. Comparative study of two types of myopathies: nemaline myopathy and the Werdnig-Hoffmann syndrome]. / L'alterazione dell'apparato motore delle ciglia bronchiali. Studio in rapporto a due diversi tipi di miopatia: la nemaline myopathy e la sindrome di Werdnig-Hoffmann.

The Authors during an extensive applications of nasal brushing in infancy according to Rutland and Cole, remarked--first time in literature--the contemporary presence in a child of the nemaline myopathy syndrome and immotile cilia syndrome. Supposing the possibility that in other myopathy may be present the same ciliary immotile syndrome, they studied with nasal brushing three cases of Werdnig-Hoffman syndromes: but they presented normal ciliary conformation. The Authors suppose that in case in future it should be found in other cases of nemaline myopathy the contemporary presence of dinein arms lack, it should be demonstrated that this syndrome takes derivation from a genetic alteration both of the muscular apparatus and the ciliary mobility system of bronchial epithelius.

The potential role of fatty liver in paediatric metabolic syndrome: a distinct phenotype with high metabolic risk?

BACKGROUND: The prevalence of obesity and its metabolic consequences has dramatically increased in the last two decades urging physicians to find a reliable definition for early detection, treatment and possibly prevention of metabolic syndrome (MS). MS could be diagnosed in adult patients in the presence of a large waist circumference and ≥2 of the following features: high serum triglycerides, low serum high-density lipoprotein cholesterol, high blood pressure and high fasting glucose. The definition of MS in children is more problematic, and the potential role of its single components on metabolic risk remains largely undefined. Recent evidence strongly suggests not only a relationship between non-alcoholic fatty liver disease (NAFLD) and MS in obese children, adolescents and adults, but also the key role exerted by liver fat deposition in the pathogenesis of MS. CONCLUSION: We propose that NAFLD should be routinely checked in obese subjects because early lifestyle changes may be effective in reducing the overall risk of MS.