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Nephrotic syndrome is a condition of massive proteinuria that leads to hypoalbuminaemia and oedema. In the pediatric age, the most common form of nephrotic syndrome is childhood idiopathic nephrotic syndrome (CINS). Although the etiological mechanisms underlying CINS are still unclear, the disease is considered to be immune-mediated. Several studies have previously reported a possible association between CINS and atopy, with the latter defined as abnormal immunoglobulin-E response on the background of a T-helper 2 (Th2)-driven immune system. In fact, both experimental and clinical studies have suggested that idiopathic nephrotic syndrome can be associated and/or triggered by a wide array of atopic diseases, though this remains a highly controversial topic. Exposure to inhalant-allergens (and/or introduction of food-allergens) has been previously correlated with the onset and/or the relapse of CINS in some children and a significant worse response to steroid therapy has been also described in reports of CINS associated to concomitant atopic diseases. In this review, we analyzed previous studies with the aim to clarify, basing on the existent literature, the association between atopy and idiopathic nephrotic syndrome. Additionally, we also speculated on the underlying immunological pathways that could potentially make some children prone to both CINS and atopic diseases.

β2-agonists reduce airflow limitation by improving airway diameter as a consequence of a direct action on airway smooth muscle. β;2-agonists can be broadly classified according to their duration of action: short-acting β2-agonists (SABAs), including albuterol, terbutaline and fenoterol, have pharmacodynamics half–lives between 2 and 6 h and long-acting β2-agonists (LABAs), including salmeterol and formoterol, require twice daily treatment. SABAs are often used “as needed” for asthma exacerbations and before exercise in the presence of exercise-induced bronchospasm. LABAs provide longer symptom control, which is a particularly useful feature for preventing night-time symptoms. There are two main LABAs, salmeterol and formoterol. This review focused on the recent data published on this topic.

Bronchial asthma is a chronic inflammatory disease characterized by bronchial obstruction, usually reversible spontaneously or after therapy, bronchial hyperreactivity and accelerated decrease of lung function that may possibly evolve into irreversible obstruction of the respiratory tract. Bronchial provocation tests can be used in order to assess the presence and degree of bronchial hyper reactivity. The recently introduced mannitol powder inhalation indirect test seems to have an interesting and promising role, especially in childhood, because of its high diagnostic specificity, easiness of execution and best standardization. In this study the authors focused on the significance and clinical use of mannitol bronchial challenge test in asthmatic children.

The role of the vitamin D in calcium homeostasis and bone metabolism is well known. In recent years it has been recognized that in addition to the traditional functions, vitamin D modulates a variety of processes such as host defense, inflammation and immunity. Epidemiological data indicate that low levels of vitamin D in serum are associated with impaired lung function and increased incidence of inflammatory diseases, infectious diseases and cancer. The authors studied the correlation among vitamin D levels, allergic inflammation, lung function and control of asthma and found a significant decrease of FeNO values (p= 0.0018) in children with vitamin D levels>30 ng/ml. These findings confirm that vitamin D plays a major role in bronchial inflammation.

The aim of this randomized open study was to evaluate the safety and efficacy of different dosages (2000 UI vs 4000 UI) of sublingual immunotherapy (SLIT) in patients with allergic diseases such as asthma associated to rhinitis and rhinoconjunctivitis sensitized to house dust mites. We enrolled 61 patients with a history of allergic asthma, and a positive skin prick test for Dermatophagoides (D.) pteronyssinus/farinae. Patients were randomly assigned to receiving SLIT at dosage of 2000 UI (Group A) or 4000 UI (Group B) maintenance dose. We evaluated: subjective symptoms using a Visual Analogic Scale (VAS), the amount of prescribed symptomatic drugs, bronchial reactivity to methacoline and side effects using a specific questionnaire. A significant improvement in symptoms, assessed by VAS, was observed with both SLIT doses with no significant differences between groups. The provocation dose of methacoline inducing a 20% fall of FEV1 significantly increased after 12 months only in the 4000 UI dose group. In conclusion, both monomeric allergoid dosages of SLIT (2000 UI and 4000 UI) are a safe and efficacy option to reduce symptoms in patients with allergic asthma caused by house dust mites. Moreover, both dosages are efficacious even to protect against airway reactivity but it seems that monomeric allergoid of SLIT at higher dosage (4000 UI) is better than at the lower dosage (2000 UI).

Atopic dermatitis is a chronic relapsing-remitting inflammatory skin condition, characterized by a skin barrier dysfunction resulting in epidermal damage and altered permeability to allergens and microbes. Although pathogenesis of atopic dermatitis is complex and still not fully understood, it has been hypothesized that genetic predisposition, environmental factors, and skin barrier dysfunction are involved. Innate and adaptive immune system has also a pivotal role in the development, maintenance and flare-up of atopic dermatitis. The immune-pathogenesis of atopic dermatitis is determined by the impairment of different T helper cells, of their cytokine secretion profiles as well as of their specific receptor. In this review, we focus on the current knowledge of the etiopathogenetic pathways of atopic dermatitis in relationship to the critical role of the innate and adaptive immune system, providing a unifying view.

Allergic immunotherapy (AIT) today represents a therapeutic practice for the treatment of allergic diseases such as rhinitis or asthma and is recognized as the only treatment able to modify the natural history of the disease. Administering gradually increasing doses of the causative allergen, AIT, has the objective of achieving immune tolerance against allergens. One of the administration routes most used in clinical practice is represented by the sublingual route. Current research on sublingual immunotherapy (SLIT) is focused on confirming the efficacy for all the different relevant allergens, on a better definition of allergen extracts and the improvement of their immunological properties and safety, on the identification of best treatment regimens, and on the possibility of extending the clinical indications. The aim of this review is to describe the most recent step in the field of SLIT development.

Probiotics are able to restore microbiome and the normal intestinal permeability, improve the immunological function of gut barrier and reduce the intestinal inflammatory response and the production of pro-inflammatory cytokine characteristics of local and systemic allergic inflammation. Clinical studies have demonstrated the efficacy of probiotics in the treatment of various clinical conditions such as atopic dermatitis and food allergies and in the primary prevention of atopy. Recent studies have shown that oral administration of certain probiotic exerts therapeutic effects in the treatment of allergic respiratory diseases such as asthma and rhinitis.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common in children and are often associated with each other. Recent studies have shown improvement of respiratory symptoms and reduction in the adenoid volume after anti-allergic medical therapy (intranasal corticosteroids, antihistamines). The aim of our retrospective study is to evaluate the effectiveness of adenoidectomy on respiratory symptoms in pediatric patients with AR. We recruited 404 pediatric patients with AR, and we divided them into 4 groups (1. intermittent-mild rhinitis; 2. intermittent-moderate/severe rhinitis; 3. persistent-mild rhinitis; 4. persistent-moderate/severe rhinitis), using ARIA classification. For each patient we evaluated: age at onset of AR; family history of allergy; the presence of other allergic diseases; serum total IgE values; skin prick test (SPT) results; presence of AH evaluated by rhino-laringeal fibroscopy; adenoidectomy and its efficacy on respiratory symptoms. Our data show an association between AR and AH: 90 of 404 (22%) children with AR had AH of a degree greater than 2nd. A significant percentage (80%) of children suffering from AR did not present satisfactory benefits from adenoidectomy. They reported persistence or recurrence of rhinitic symptoms after surgery or only partial benefits, especially of recurrent respiratory tract infections and nasal obstruction. The local allergic persistent inflammation on nasal mucosa and adenoid tissue is probably the cause of the unsatisfactory results of adenoidectomy, therefore surgery cannot be the first therapeutic step for these children. It is important to extinguish the local inflammation by medical anti-allergic therapy to obtain improvements of nasal symptoms and to prevent adenoid regrowth.

The aim of the study was to evaluate fasting levels of glucose, insulin, leptin, total ghrelin, and obestatin in a group of prepubescent obese children before and after weight loss. We enrolled 64 prepubescent obese children, but only 35 completed the study (mean age 7.6 +- 0.9 years, 19 females) and 20 normal-weight prepubescent children as controls. Fasting plasma concentration of glucose, insulin, Homeostasis Model assessment for insulin resistance (HOMA-IR), and leptin, total ghrelin, and obestatin levels were measured at baseline and after a 6-month lifestyle intervention (i.e. improved nutrition and increased physical activity). At baseline, obese children showed significantly (p less than 0.001) higher leptin and obestatin levels, and lower total ghrelin concentrations than control subjects. Weight loss significantly (p less than 0.001) diminished plasma leptin and insulin levels and increased ghrelin and obestatin concentrations. Weight loss in prepubescent children is associated with a significant change in leptin, ghrelin and obestatin concentrations. These results confirm the hypothesis that levels of these hormones are closely associated with obesity in childhood and might take part, as consequence but not as a cause, in glucose, fat, and energy metabolism.

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

Patients with pollen allergy may frequently present an additional food-related allergy (Oral Allergic Syndrome, OAS), as consequence of cross-reactivity between pollen allergens (mainly birch, hazelnut, alder, mugwort) and vegetable allergens. The aim of this study was to evaluate the effect on Bet v 1-induced T cell proliferation exerted by the presence of OAS in birch patients. Fourteen allergic patients were evaluated (6 males, mean age 35.8 years). All of them were monosensitized to birch and suffered from allergic rhinitis: 4 had also OAS to apple. Proliferation of peripheral mononuclear cells was evaluated using Bet v 1 and non-specific stimuli. OAS had higher proliferation than non-OAS patients. In addition, there were significant relationships between immunological and clinical parameters in OAS patients. This study evidences that OAS characterizes a more severe form of birch allergy: as OAS patients had higher SI, circulating eosinophils, and IgE levels. Thus, this study confirms the previous report and underlines the relevance of measuring recombinant birch allergen as higher values may suggest a reliable prediction of OAS.

Approximately 50 percent of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30 percent. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seem to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

Recently, there has been considerable interest in the relationship between allergic and autoimmune diseases. We evaluated the prevalence of thyroid autoimmunity in 566 children affected by atopic dermatitis (AD), urticaria, rhinitis, chronic cough, and asthma. Our results suggest that allergy and autoimmunity can be two potential outcomes of dysregulated immunity. It is tempting to speculate that NK Th2 cells can favour asthma onset and at the same time improve thyroid autoimmunity.

PTX3 behaves as an acute-phase response protein as its blood levels rapidly and dramatically increase during endotoxic shock, sepsis, and other inflammatory and infectious conditions. Therefore, this study was designed to investigate a possible role of PTX3 in children with Atopic Dermatitis (AD). One-hundred-and-thirty-six patients (37 females, 99 males, mean age 10.4 years) were enrolled in the study. One hundred patients (74%) had only respiratory symptoms (allergic rhinitis and/or bronchial asthma); thirty-six patients (26%) showed dermatitis associated with respiratory allergy (allergic rhinitis and/or bronchial asthma). PTX3 levels were higher in children with AD and there was a significant correlation between serum PTX3 levels and SCORAD index (p-value=0.0001, rho=0.658). Therefore, this study may show that PTX3 might be a reliable marker for the severity of AD in children with respiratory allergy.

FEV1 is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that FEF25-75 could be more sensitive than FEV1 to detect slight airways obstruction. Bronchial reversibility defined by positive response to bronchodilation test. The aim of the present study was to define whether an impaired FEF25-75 value (less than 65 percent of predicted) may be predictive for reversibility in a large cohort of allergic children with rhinitis or asthma. Six hundred allergic children were recruited: 300 with controlled asthma and 300 with allergic rhinitis. All of them were evaluated by performing spirometry, bronchodilation test, and skin prick test. Two predictors were significantly associated with bronchial reversibility: i) an impaired FEF25-75 value (less than 65 percent of predicted), and ii) sensitization to perennial allergens. It was more relevant in children with rhinitis (ORAdj:8.9 and 2.2 respectively). In conclusion, this study, conducted in real life, could suggest that an impaired FEF25-75 value (less than 65 percent of predicted) may be considered a reliable marker of bronchial reversibility, mainly in children with allergic rhinitis.

Recently, it has been hypothesized that the oral administration of specific live probiotic strains may have therapeutic potential in the treatment of allergic inflammation. The aim of this study was to evaluate the effect of the oral L. reuteri DSM 17938 administration (1X108CFU), in airways allergic inflammation in mild persistent asthmatic children. In this DBPC randomized study we selected 50 children (6-14 years old), affected by mild persistent asthma (GINA step 2) and allergic to HDM. At the run-in period (T-2), the children were submitted to medical examination, prick tests for the main respiratory allergens, spirometry and children asthma control test (C-ACT). We selected only the children with well controlled asthma (C-ACT >19 and FEV1> 80%). After two weeks (T0) the children were allocated into two groups, the FeNO was measured and the breath condensate was collected. Group A children were treated with the placebo (5 drops per day) and Group B children with L. reuteri (108CFU =5 drops per day) for 60 days. After the treatment period (T1), all patients were evaluated by medical examination, C-ACT, spirometry, FeNO measurement and exaled breath condensate analysis. The FeNO values showed a significant reduction (p=0,045) in L. reuteri group but not in the placebo group at the end of the treatment (T1). Furthermore, the cytokines exam showed an increase in IL-10 levels (p less than 0.05) and a significant reduction in IL-2 levels (p less than 0.05) only in L. reuteri group at T1. No significant differences in FEV1 values and C-ACT score were found in both groups. In conclusion, these data showed that L. reuteri (108 CFU) was effective in reducing bronchial inflammation in asthmatic children. No significant effect was found on FEV1 values and C-ACT score, probably because we selected children with well controlled asthma.

The increasing prevalence of allergy and its impact on individual quality of life underline the need of an improvement of the treatment options in order to modify the natural course of allergic diseases. In this context, specific sublingual immunotherapy (SLIT) represents an approach currently available to redirect inappropriate immune response in atopic patients. The immunological mechanism that underlies SLIT has only started to be investigated. Oral mucosal tissue displays high permeability for allergens. It is conceivable that the sublingual administration route might induce immunological tolerance towards allergens involving cells and mediators specific of oral and intestinal mucosa. Recent literature data stated the presence in oral mucosa of dendritic cells (DCs) which express the high-affinity receptor for immunoglobulin (Ig)E (FcERI). Moreover some studies indicated that the mechanism of immunotherapy might be based on the increase of number and activity of regulatory T cells. Accumulating evidences suggest that the generation of T regulatory cells in periphery is orchestrated by a particular subset of DCs. It seems that repeated stimulation of naive CD4 T cells with allogenic immature DCs induce Tr1 cells maturation. Nevertheless other cells are involved in this process, such as TLR, MHC of I and II class and costimolatory molecules such as CD40, CD 80/B7.1 and CD 86/B7.2. An increase of serum IgG4 and IgA, a reduced number of inflammatory cells infiltrating target organs, as well as a reduction of eosinophilic cationic protein and a very heterogenous influence on T cells in the peripheral blood in terms of T cell suppression also occur with SLIT. All these molecules orchestrate the immune response within the regional immune system, recreating a favourite environment for the induction of tolerance operated by SLIT.

Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. High IgE levels in infancy may predict subsequent allergy. The aims of this study were: i) to evaluate the role of specific IgE to tetanus toxoid in children in response to tetanus immunization and the possible factors associated with specific IgE levels, and ii) to investigate the correlation between specific IgE levels to tetanus toxoid and the late development of allergy (up to 12 years). Initially, 278 healthy infants (152 males and 126 females, aged 12 months) living in an urban city were screened for serum total IgE and specific IgE to tetanus toxoid, after having obtained informed consent from parents. After 12 years, 151 children could be evaluated. Total IgE summed with tetanus specific IgE were significantly associated with allergy at 12 years. In conclusion, this study demonstrates that serum total IgE and tetanus specific IgE may be predictive of subsequent allergy onset.

Asthma is characterized by airway inflammation that is controlled by a complex cytokine network. The Th1/Th2 imbalance has been well documented in the pathogenesis of allergic asthma. Recently, Th17 cells and regulatory T (Treg) cells have been found to participate in the pathogenesis of allergic asthma. This study aimed at verifying whether anti-inflammatory treatment could change serum IL-4, IL-10 and IL-23 in asthmatic children. Globally, 78 children (40 males and 38 females, median age 9.3 +- 3.7 years), with asthma and monosensitized to house dust mites, were evaluated. Lung function (such as FEV1) and serum IL-4, IL-10 and IL-23 levels were measured at baseline (T0), after 4 weeks (T1) and after 12 weeks (T2) of inhaled corticosteroid (ICS) treatment. The control group consisted of 40 healthy children (22 males and 18 females) age matched. At baseline, IL-4 and IL-23 levels were higher in severe asthmatics than in control group (p less than 0.001), while serum IL-10 levels were significantly lower in group of asthmatic children as compared to healthy control group (p less than 0.001). At T2, IL-4 and IL-23 significantly diminished (p less than 0.001), while IL-10 significantly increased. There was significant relationship between FEV1 and IL-4, IL-10 and IL-23 at T0 (r=-0.784; r=-0.735 and r=-0.787, respectively). Moreover, there were correlations between FEV1 and IL-4, IL-10 and IL-23 in patients at T1 (r=-0.563; r=-0.539 and r=-0.583, respectively) and at T2 (r=-0.549; r=-0.428 and r=-0.393, respectively). The present study provided evidence that: i) serum IL-23 was up-regulated also in asthmatic children, ii) ICS treatment was able of reducing IL-23, and iii) IL-23 change well related with lung function improvement. Thus, it is presumable that IL-23 could be a suitable marker of allergic inflammation in asthma.

A potential role of Helicobater Pylori (HP) infection in several extra-intestinal pathologies has been recently suggested. The aim of our study was to assess the role of serology positive for HP in atopic and non atopic infants and children affected by atopic dermatitis, urticaria, rhinitis and asthma. We included 615 children affected by atopic diseases. According to prick test positivity and age, we divided the patients into two groups: atopic or non-atopic patients and infants (0-2 years) or children (2-12 years). The serum levels of antibodies for H. pylori immunoglobulin G were measured by using an ELISA test. We found a not significant difference between group 1 and group 2 about atopy. There was a significant higher frequency of HP positive serology in older children. As for infants, a higher significant prevalence of HP positive serology was found in non-atopic patients. HP positive serology was significantly higher only in non-atopic infants affected by atopic dermatitis and urticaria than in atopic. In group 2, non atopic children shown a significant increase in the prevalence of HP serum positivity than atopic children. As for asthma, there was an higher prevalence of HP serology positive in non atopic asthmatic children group than in atopic asthmatics. On the contrary, the prevalence of positive HP serology was not significantly different between atopic and non atopic children affected by dermatitis, urticaria, and rhinitis. The present data confirm an inverse association between HP positive serology and atopy in both groups. However, the higher prevalence of positive HP serology was observed in non atopic asthmatics children than in atopic asthmatics. We could speculate that HP infection can favour non-atopic asthma onset.

The present study confirms that sensitization is very frequent in the general population and suggests that impaired FEF25-75 may be a marker of sensitization. Therefore, when spirometry is abnormal, mainly concerning FEF25-75, sensitization should be suspected.

Sinusitis is frequently associated with asthma. The diagnosis and management of patients with asthma associated with sinusitis are often challenging, though sometimes unsatisfactory. Detection and treatment of sinusitis in asthmatics may lead to a better control of asthma symptoms. Most of the studies regarding the relationship between sinusitis and asthma have been conducted in adults. The aim of the present study was to evaluate the presence of sinusal comorbidity in children with un-controlled asthma both clinically and through nasal endoscopy after the first 6 months of treatment. The present study included 294 consecutive asthmatic children (97 males, mean age 7.3 years). Asthma diagnosis, severity assessment and treatment were performed according to GINA guidelines. Twenty-one patients with non-controlled asthma presented with endoscopic features of sinusitis, but without any clinical sign or symptom. We defined such condition occult sinusitis. Not only overt sinusitis, but also occult sinusitis could be a significant comorbidity in asthmatic patients. For this reason, it may be beneficial to determine the presence of sinus inflammation in children with non-controlled asthma, even when they do not present clinical signs or symptoms of upper airways involvement.

Asthma is traditionally defined as a chronic disease characterized by bronchial hyper-responsiveness and lung inflammation. The airway inflammation and remodelling together likely explain the clinical manifestations of asthma. The mechanisms by which the external environmental cues, together with the complex genetic actions, propagate the inflammatory process that characterizes asthma are beginning to be understood. There is also an evolving awareness of the active participation of structural elements, such as the airway epithelium, airway smooth muscle, and endothelium, in this process; these structural elements within the lung and the bone marrow serve as reservoirs for and the source of inflammatory cells and their precursors. Although often viewed as separate mechanistic entities, so-called innate and acquired immunity often overlap in the propagation of the asthmatic response. This review examines the newer information on the pathophysiologic characteristics of asthma and focuses on the role of airway epithelium in the exacerbation of the disease.

Allergic disorders are typically characterized by an inflammatory response to allergen exposure. PTX3 behaves as an acute-phase response protein as there is a relationship between PTX3 plasma levels and disease severity. Therefore, this study was designed to investigate a possible role of PTX3 in children with allergic rhinitis. One hundred patients (28 females, 72 males, median age 11 years) were enrolled in the study. All patients were monosensitized: 43 (43%) to seasonal allergens (Graminaceae), 57 (57%) to perennial allergens (house dust mites, cat and dog epithelium, alternaria tenuis). Patients' blood samples for assessing serum PTX3 levels were performed during the spring. Children with rhinitis had higher PTX3 levels and there was a significant relationship between symptom severity and serum levels. Therefore, this study shows that PTX3 serum levels could be a reliable marker for symptom severity in children with allergic rhinitis.

Allergic rhinitis and asthma are closely associated. Inflammation is a common pathological characteristic shared by both disorders. The measure of the fractional concentration of exhaled nitric oxide (FeNO) may be considered a surrogate marker for airway inflammation. Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) has been previously demonstrated to be able to predict BHR and bronchial reversibility. The aim of this study was to evaluate whether impaired FEF25-75 values may be related to FeNO values in a pediatric cohort of allergic subjects. 850 children with allergic rhinitis, allergic asthma, or both, were evaluated. Bronchial function (FEV1, FVC, and FEF25-75), FeNO, and sensitizations were assessed. Bronchial function and FeNO were significantly different in the 3 groups (p less than 0.001). A strong inverse correlation between FeNO and FEV1was found in patients with rhinitis, asthma and asthma with rhinitis (r= -0.72, r=-0.70 and r= -0.70, respectively). Impaired FEF25-75 values (such as less than 65 percent of predicted) were significantly associated with high FeNO levels (such as =34 ppb). In conclusion, this study provided evidence that FEF25-75 is strongly and inversely related with FeNO and FEF25-75 may predict high FeNO levels in children with allergic rhinitis, asthma or both.