Amelia Licari

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.

Adenoids during childhood: the facts.

Adenoids are constantly exposed to viral and bacterial agents as well as to allergens. They play a major role in the upper airways immunity, being effector organs in both mucosal-type and systemic-type adaptive immunity. Because of both their immunological function and their specific location, adenoids are considered to be as reservoirs of viruses and bacteria. Reiterative infections may therefore contribute both to Eustachian tube dysfunction and to tissue hypertrophy. Nasal endoscopy is a key diagnostic tool to detect both adenoid hypertrophy and adenoiditis. Moreover, such a procedure may be very helpful in detecting bacterial biofilms that could justify the concomitant presence of recurrent episodes of otitis media, chronic and occult sinusitis in children. Even though the connection between allergies and adenoidal diseases is not completely clear, allergic diseases cause an inflammatory state that influences adenoidal tissue as well, configuring the picture of allergic adenoiditis, a condition in which adenoid tissue exhibit numerous IgE positive mast cells. Several studies are still needed to better understand the relationship between allergies and infections and the influence they play on adenoids during childhood.

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.

Adenoids in children: Advances in immunology, diagnosis, and surgery.

Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options. Clin. Anat. 27:346–352, 2014.

From IgE to clinical trials of allergic rhinitis.

The current scientific research is continuously aiming at identifying new therapeutic targets with the purpose of modifying the immune response to allergens. The evolution in immunological methods has led to the identification of immunoglobulin E (IgE) as both a diagnostic biomarker and potential therapeutic target in allergic diseases, such as allergic rhinitis. Allergen immunotherapy has been used for more than 100 years to treat allergic diseases and it is today considered the only disease-modifying treatment capable of inducing a long-lasting immunological and clinical tolerance toward the causal allergen. During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. Moreover, there has been considerable progress in allergen extract modifications and additions to standard extracts. The recognition that IgE plays a pivotal role in basic regulatory mechanisms of allergic inflammation has recently stimulated research into the therapeutic potential of directly targeting this antibody. Omalizumab, the most advanced humanized anti-IgE monoclonal antibody, is currently approved for the treatment of uncontrolled allergic asthma and chronic spontaneous urticaria. Interesting results also arise from studies in which omalizumab was administered in patients with allergic rhinitis. The aim of this review is to provide an update on current findings on immunological and clinical effects of allergen immunotherapy and anti-IgE therapy, which have been shown to have synergistic modes of action for the treatment of allergic rhinitis.

Nasal cytology in children: recent advances

Nasal cytology is a very useful diagnostic tool in nasal disorders, being able to detect both the cellular modifications of the nasal epithelium caused by either allergen exposure or irritative stimuli (that may be physical or chemical, acute or chronic), or inflammation. Over these past few years, nasal cytology has allowed to identify new disorders, such as the non-allergic rhinitis with eosinophils (NARES), the non-allergic rhinitis with mast cells (NARMA), the non-allergic rhinitis with neutrophils (NARNE), and the non-allergic rhinitis with eosinophils and mast cells (NARESMA). The rhinocytogram is actually able to distinguish the different forms of allergic rhinitis and to suggest the appropriate treatment, such as antinflammatory drugs or allergen immunotherapy. The technique is easy to perform and nasal cytology is therefore particularly suitable even for children. Such a consideration suggests the utility of a systematic use of nasal cytology in the diagnostic work-up of nasal disorders in children, in order to reach a proper defined diagnosis and to set a rational therapeutic approach: in facts, these two elements are fundamental in order to prevent from complications and to improve the patient’s quality of life.

Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Congenital vascular rings: A clinical challenge for the pediatrician

Vascular rings are congenital anomalies that lead to variable degrees of respiratory problems or feeding difficulties by forming a complete or partial ring compressing the trachea, the bronchi, and the esophagus. The clinical diagnosis of vascular rings is often challenging for the pediatrician because the clinical manifestations are heterogeneous and nonspecific. Symptoms can vary from wheezing, stridor, dyspnea, and/or dysphagia to life‐threatening conditions; however, they may not be present. The aim of this study is to review the recent literature on this subject and describe new developments in diagnostics and imaging. Pediatr Pulmonol. 2015; 50:511–524.

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.