Nutritional Aspects of Pediatric Gastrointestinal Diseases.

In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively "harmless" nature. Apart from a diet's therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical "side effects", however, it should be emphasized that any dietary modification might have negative consequences on children's growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.

Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorders (EGID) are a group of disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms (J Pediatr Gastroenterol Nutr; Spergel et al., 52: 300-306, 2011). These disorders include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic enteritis (EE), and eosinophilic colitis (EC). Symptoms are dependent not only on the location (organ) as well as extent (layer invasion of the bowel wall). Common symptoms of EoE include dysphagia and food impaction in adults and heartburn, abdominal pain, and vomiting in children. Common symptoms of the other EGIDs include abdominal pain, nausea, vomiting, early satiety, diarrhea, and weight loss. These disorders are considered immune-mediated chronic inflammatory disorders with strong links to food allergen triggers. Treatment strategies focus on either medical or dietary therapy. These options include not only controlling symptoms and bowel inflammation but also on identifying potential food triggers. This chapter will focus on the clinical presentation, pathophysiology, and treatment of these increasingly recognized disorders.

Treatment of chronic obstructive pulmonary disease in patients with different fractional exhaled nitric oxide levels.

Some patients with chronic obstructive pulmonary disease (COPD) have eosinophilic inflammation which may be evaluated via the measurement of fractional exhaled nitric oxide (FeNO) like asthma. The aim of this prospective study was to assess whether FeNO levels can be used to identify patients with COPD with eosinophilic inflammation who may respond to inhaled corticosteroid (ICS) therapy.This study included patients (N = 112) with COPD (age >18 years) who were divided into 4 groups depending upon whether they had high (≥25 parts per billion [ppb]) or low (<25 ppb) pretreatment (baseline) FeNO and if they were treated with either ICS plus long-acting ß-agonist (ICS + LABA) or a long-acting muscarinic antagonist (LAMA). The 4 groups were: high FeNO/ICS + LABA, high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA. Outcomes assessed included FeNO, COPD assessment test (CAT), and pulmonary function.The high FeNO/ICS + LABA group had the greatest reduction from baseline in FeNO levels (-25.80 ppb ±â€Š27.14) compared with the high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA groups (range, -4.45 to 1.31 ppb; P < .001). The high FeNO/ICS + LABA group also showed the greatest improvement in CAT (-7.20), which was statistically larger than the low FeNO/ICS + LABA and low FeNO/LAMA groups (-1.72 and -2.03, respectively). No difference in pulmonary function following treatment was observed across the 4 groups.This study found that patients with high FeNO showed the greatest reduction in FeNO and improvement in CAT with ICS + LABA therapy, supporting the use of FeNO to identify patients who would benefit from ICS use.

A bispecific antibody strategy to target multiple type 2 cytokines in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease in which innate and adaptive immune cells act together to cause eosinophilic inflammation, goblet cell metaplasia (GCM), and bronchial hyperreactivity (BHR). In clinical trials using biologicals against IL-4 receptor (IL-4R) α or IL-5, only a subset of patients with moderate-to-severe asthma responded favorably, suggesting that distinct pathophysiologic mechanisms are at play in subgroups of patients called endotypes. However, the effect of multiple cytokine blockade using bispecific antibodies has not been tested. OBJECTIVE: We sought to target simultaneously the IL-4, IL-13, and IL-5 signaling pathways with a novel IL-4Rα/IL-5-bispecific antibody in a murine house dust mite (HDM) model of asthma. METHODS: Two mAbs neutralizing IL-4Rα and IL-5 were generated by using a llama-based antibody platform. Their heavy and light chains were then cotransfected in mammalian cells, resulting in a heterogeneous antibody mixture from which the bispecific antibody was isolated by using a dual anti-idiotypic purification process. C57BL/6J mice were finally sensitized and challenged to HDM extracts and treated during challenge with the antibodies. RESULTS: We successfully generated and characterized the monospecific and bispecific antibodies targeting IL-4Rα and IL-5. The monospecific antibodies could suppress eosinophilia, IgE synthesis, or both, whereas only the IL-4Rα/IL-5-bispecific antibody and the combination of monospecific antibodies additionally inhibited GCM and BHR. CONCLUSION: Type 2 cytokines act synergistically to cause GCM and BHR in HDM-exposed mice. These preclinical results show the feasibility of generating bispecific antibodies that target multiple cytokine signaling pathways as superior inhibitors of asthma features, including the difficult-to-treat GCM.

Enfoque diagnóstico y terapéutico de la eosinofilia. A propósito de un caso / Diagnosis and treatment of eosinophilia. A case report

La eosinofilia es el aumento del número total de eosinófilos por encima de 500/μl. En la edad pediátrica la causa más frecuente es la parasitosis por helmintos; otras causas frecuentes son la ingesta de algunos fármacos y las enfermedades alérgicas. Presentamos el caso de una niña de cinco años con dolor abdominal y analítica con eosinofilia moderada en repetidas ocasiones, sin causa secundaria aparente y con normalidad en el resto de las pruebas complementarias realizadas en el centro de salud y en el hospital de referencia. Ante una eosinofilia persistente sin causa secundaria que la explique y con normalidad de las pruebas complementarias indicadas, se recomienda tratamiento empírico con antiparasitarios (AU)

Eosinophilia is the increased number of eosinophils above 500/μl. The most common cause in pediatric patients is parasitic worm disease; other common causes are ingestion of some drugs and allergic diseases. We present the case of a five year old girl with abdominal pain and moderate eosinophilia in repeated ocasions, without apparent secondary cause, and with normality in other complementary tests in the health center and in the reference hospital. In case of persistent eosinophilia without secondary causes and normal complementary tests, empiric antiparasitic therapy is recommended (AU)

Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice.

Limonene is one of the main flavonoids which is reported to inhibit the inflammatory response by suppressing the production of reactive oxygen species. The aim of this study was to evaluate whether limonene can inhibit Dermatophagoides farinae-induced airway hyperresponsiveness (AHR), eosinophilic infiltration and other histological changes in the lung, T helper (Th) 2 cytokine production and airway remodeling in a mice model of asthma. Treatment with limonene significantly reduced the levels of IL-5, IL-13, eotaxin, MCP-1, and TGF-ß1 in bronchoalveolar lavage fluid. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were markedly decreased in limonene-treated mice. Furthermore, AHR to acetylcholine was significantly abrogated in limonene-treated mice. These results indicate that limonene has a potential to reduce airway remodeling and AHR in asthma model.

Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals.

INTRODUCTION: Goblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice. METHODS: Male BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale. RESULTS: Inflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57±1.30% for low dose; 1.50±0.93% for high dose versus 12.93±7.55%, P<0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45±0.30 for low dose; 0.81±1.00 for high dose versus 2.85±0.86 in the sensitized control group, P<0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1±0.43 versus 4.7±0.96, P<0.05 and 91.8±47.7 versus 14.8±4.6, P<0.01, respectively). CONCLUSION: Verapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.

Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia.

The similarity of eosinophilia-myalgia syndrome (EMS) and toxic-oil syndrome (TOS) to systemic sclerosis and diffuse fasciitis with eosinophilia (DFE) highlights the potential for environmental agents to induce autoimmune disease. Further, a candidate etiologic agent for EMS, 3-(phenylamino)alanine, is chemically similar to the aniline derivative identified in samples of oil implicated in TOS, 3-(N-phenylamino)-1,2-propanediol, suggesting pathogenic overlap. The late-stage manifestations of EMS and TOS are muscle cramping, arthralgia, severe fatigue, and cognitive impairment. This review focuses on the divergent and parallel findings in EMS, TOS, and DFE. The formation of the Environmentally Associated Connective Tissue Disease Study Group within the American College of Rheumatology will provide a forum for the development of registries to study suspected toxin-induced disorders.

[Hypereosinophilia in premature newborn infants]. / L'hyperéosinophilie du nouveau-né prématuré.

Eosinophilia is a common finding in premature babies during the neonatal period (75%). It has a variable correlation with several factors that may influence it: gestational age, birth weight, time required to regain birthweight, neonatal stress, caesarean birth, formula feeding, endotracheal intubation, positive pressure ventilation, parenteral nutrition, umbilical catheterization, blood transfusions, antibiotics, phototherapy, sex, neutropenia and sepsis. The possible mechanisms are discussed: resolution of a stress, anabolic state, reaction to antigens, normal granulopoietic maturation, transplacental transfer of a factor stimulating the eosinophil synthesis.

Experimental monoarthritis. Modulatory effect of injected eosinophils on influx of various types of inflammatory cells.

Bovine serum albumin (BSA) in complete Freund's adjuvant (CFA) was injected into the knee joints of previously BSA-sensitized guinea pigs and rabbits. The primary immune reaction to BSA prevented secondary immune response to Trichinella larvae infection. We were unable to produce either eosinophilia in the peripheral blood or antibodies against Trichinella antigen (shown by complement fixation test). The additional injection of mediators of the inflammatory reaction or their precursors, e.g., complement component C5 and arachidonic acid, caused different histological pictures. C5 produced a prolonged acute inflammatory phase with abundant neutrophils, whereas arachidonic acid did not significantly change the inflammatory response as compared to controls. The additional application of eosinophil-enriched preparation (EEP) caused a conspicuously reduced influx of monocytes/macrophages, a reduction of lymphocyte numbers, a prolonged influx of neutrophils, increased arylsulfatase activity, earlier reduction of the inflammatory process, and earlier onset of synoviocyte regeneration as compared to controls.