Alessia Marseglia

Probiotics and food allergy.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.

Omalizumab in Children

Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.

Allergic rhinitis and quality of life in children.

Allergic rhinitis is a respiratory disease caused by an inflammatory process related to IgE mediated reaction versus allergens to which the subject is sensitized. Allergic rhinitis is not an isolated disease because the nasal mucosa inflammation involves paranasal sinuses and lower airways, thus worsening the asthmatic symptoms. Recently, a new classification of allergic rhinitis based on the duration and severity of clinical symptoms has been proposed. This classification takes into consideration both the quality of life and the possible impact of the symptoms on school, work and free-time activities. Childrens quality of life is severely compromised by frequent night awakenings, easy fatigue, defects of language and irritability, which can have a negative influence on learning abilities. Allergic rhinitis has a negative impact on the quality of life of the whole family because it can cause interference on social life, and financial costs.

The discovery and development of omalizumab for the treatment of asthma

Introduction: The evolution in immunological methods used to assess human allergic diseases has led to the identification of immunoglobulin E (IgE) as a diagnostic biomarker and a potential therapeutic target. Innovative technologies in molecular biology and immunogenetics contributed to the development of a selective blocking agent, disclosing new therapeutic perspectives in the treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE monoclonal antibody that specifically binds serum-free IgE. Omalizumab also interrupts the allergic cascade by preventing binding of IgE with FcϵRI receptors on mast cells, basophils, antigen-presenting cells and other inflammatory cells. Areas covered: This review discusses the discovery strategy and preclinical development of omalizumab. Furthermore, it also provides a clinical overview of the key trials leading to its launch and a detailed analysis of safety and post-marketing data. Expert opinion: The clinical efficacy of omalizumab in allergic asthma has been well documented in clinical trials, involving adults, adolescents and children with moderate-to-severe and severe allergic asthma. To date, omalizumab has also been approved in chronic idiopathic urticaria for patients 12 years and older who remain symptomatic despite high dosages of H1 antihistamines. Omalizumab has also been investigated in many other different patient populations beyond allergic asthma and may yet have an application to other indications. While omalizumab is the only mAb available for treating allergic asthma, the authors anticipate that new mAbs will emerge in the future that overcome omalizumab’s current limitations.

Fractional exhaled nitric oxide measurements in rhinitis and asthma in children.

Exaled nitric oxide (FeNO) is considered a good noninvasive marker to assess airway inflammation in asthma and allergic rhinitis. In asthma, exhaled NO is very useful to verify adherence to therapy, and to predict upcoming asthma exacerbations. It has been also proposed that adjusting anti-inflammatory drugs guided by the monitoring of exhaled NO, could improve overall asthma control. Other studies showed increased FeNO levels in subjects with allergic rhinitis.

Passive exposure to smoke results in defective interferon-γ production by adenoids in children with recurrent respiratory infections.

There is evidence that exposure to passive smoke is associated with an increased susceptibility to respiratory infections. Indeed, cigarette smoke extracts may interfere with the immune system, even though the precise mechanism has not been fully understood yet. Recurrent respiratory infections may be sustained by a defective immune response. The aim of the present study was to evaluate whether, in a cohort of children presenting both with recurrent respiratory infections and with a history of exposure to tobacco smoke, these factors were related to a lower local production of interferon-gamma (IFN-gamma) when compared to a similar non-exposed population. The study group included 128 children undergoing adenoidectomy, presenting with more than three respiratory infections per year, independently of exposure to passive smoke at home. The intracellular cytokine profile of lymphocyte subsets in adenoids was evaluated by flow cytometry analysis. Children exposed to tobacco smoke suffered from a significantly greater number of respiratory infections and had a lower percentage of IFN-gamma-producing CD8+ cells in adenoids than non-exposed children, while other T-cell subsets were not affected. The effect of smoke exposure seems to be specific to the IFN-gamma-producing CD8+ cells in adenoids and may contribute to the increased susceptibility to the recurrence of respiratory infections.

Current recommendations and emerging options for the treatment of allergic rhinitis

Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. The aim of this review is to provide an update on AR treatment, with a focus on current therapies defined by AR and its impact on asthma guidelines and with a particular emphasis on new and future therapeutic perspectives.

The Nose and the Lung: United Airway Disease?

Epidemiologic, pathophysiologic, and clinical evidences recently revealed the link between upper and lower airways, changing the global pathogenic view of respiratory allergy. The aim of this review is to highlight the strong interaction between the upper and lower respiratory tract diseases, in particular allergic rhinitis and asthma.

Nose and lungs: one way, one disease

It’s well established that asthma, allergic rhinitis and rhinosinusitis are three closely related disease. In pediatrics, these conditions represent a common issue in daily practice. The scientific community has recently started to simply evaluate them as different manifestations of a common pathogenic phenomenon. This consideration relates to important implications in the clinical management of these diseases, which may affect the daily activity of a pediatrician. The unity of the respiratory tract is confirmed both from a morphological and from a functional point of view. When treating rhinitis, it is often necessary to assess the presence of asthma. Patients with sinusitis should be evaluated for a possible concomitant asthma. Conversely, patients with asthma should always be evaluated for possible nasal disease, especially those suffering from difficult-to-treat asthma, in which an occult sinusitis may be detected. The medications that treat nasal diseases appear to be useful in improving asthma control and in reducing bronchial hyperresponsiveness. It seems therefore important to analyze the link between asthma and sinusitis, both in terms of clinical and pathogenic features, as well the therapeutic approach of those patients presenting with these diseases.

Serum neopterin levels in spontaneous urticaria and atopic dermatitis

Serum neopterin may be considered a diagnostic marker of the degree of activation of the immune system. This preliminary study was performed to measure serum neopterin levels in patients with acute spontaneous urticaria (ASU), chronic spontaneous urticaria (CSU) and atopic dermatitis (AD). In total, 180 patients [96 men, 84 women; mean age 23.1 years; 41 with spontaneous urticaria (13 ASU and 28 CSU), 48 with AD] and 96 healthy controls were enrolled in the study. Patients with ASU had the highest neopterin levels, and all three groups of patients (ASU, CSU and AD) had higher values than normal subjects. This preliminary study demonstrates that serum neopterin could be a biomarker of immune activation in patients with SU or AD.