Giuseppe Di Cara

Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

BackgroundGrass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses) are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE) production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized.MethodsWe investigated in 30 children (19 males and 11 females, mean age 11.3 years), 19 treated with sublingual immunotherapy (SLIT) by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components.ResultsSignificant increases (p < 0.001) were detected for Phl p 1, Phl p 2, Phl p 5, and Phl p 6, while sIgE levels induced in response to Phl p 7 and Phl p 12 were low or absent at baseline and unchanged following SLIT treatment; no new sensitisation was detected. As to IgG4, significant increases were found for Phl p2 and Phl p 5, while the increase for Phl p 12 was not significant. In the control group, no significant increase in sIgE for any single allergen component was found.ConclusionsThese findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

Exhaled nitric oxide in children with allergic rhinitis: A potential biomarker of asthma development

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Effects of Sublingual Immunotherapy on Allergic Inflammation: An Update

The most common allergic diseases, and especially the respiratory disorders such as rhinitis and asthma, are closely related to the allergic inflammation elicited by the causative allergen. This makes inflammation the main target of anti-allergic therapies. Among the available treatments, allergen specific immunotherapy (AIT) has a patent effect on allergic inflammation, which persists also after its discontinuation, and is the only therapy able to modify the natural history of allergy. The traditional, subcutaneous route of administration was demonstrated to modify the allergen presentation by dendritic cells (DCs) that in turn correct the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation and characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy of Th2 or to tolerance, the latter being related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual AIT with high allergen doses proved to be similar to subcutaneous immunotherapy. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa, with particular importance for mucosal DCs, plays a crucial role in inducing tolerance to the administered allergen.

Anti-inflammatory activity and clinical efficacy of a 3-month levocetirizine therapy in mite-allergic children.

The non-sedating third generation antihistamine levocetirizine has ample evidence of efficacy in allergic rhinitis. In vitro studies suggested that levocetirizine has anti-inflammatory properties not simply related to the antihistamine activity but also to regulation of eosinophils. We performed a double-blind placebo-controlled study in 40 children allergic to house dust mites with persistent rhinitis with the primary aim to evaluate the anti-inflammatory efficacy of levocetirizine measuring eosinophil-related parameters and exhaled nitric oxide (eNO). After one month of treatment, a significant improvement in nasal symptom-medication scores was observed in actively but not in placebo treated patients. After 3 months of treatment, a significant effect was detected on eosinophilic cationic protein (ECP) in nasal mucosa and on nasal eNO in active treated patients. This suggests that during treatment of mite-allergic children with levocetirizine the early improvement in nasal symptoms is due to the antihistamine activity, while more time is needed to achieve an effect on allergic inflammation.

Echocardiographic alterations in a child with cow’s milk allergy: a case report

IntroductionCow’s milk allergy is the most frequent food allergy in Europe and western countries and shows a wide spectrum of clinical features, including atopic dermatitis and gastrointestinal disease. To the best of our knowledge, this report is the first to describe Kawasaki disease-like clinical features and echocardiographic alterations which resolved after a cow’s milk-free diet.Case presentationWe report a case of a 9-month-old Caucasian girl with atopic dermatitis who developed clinical features commonly present in Kawasaki disease (erythematous skin rash, non-exudative conjunctivitis, fissured lips and neck lymph nodes), together with mild echocardiographic alterations (perivascular brightness, pericardial effusion) in the absence of fever. These features resolved within 2 weeks after the beginning of a cow’s milk-free diet.ConclusionKawasaki disease has recently been considered a possible risk factor for subsequent allergic disease secondary to immune dysfunction. This case report suggests that the immune-related alterations which are commonly present in allergic patients could be similar to the antigen-related immune response in Kawasaki disease and thus could lead to similar clinical features.

Prevention of Invasive Pneumococcal Disease: Problems Emerged After Some Years of the 13-Valent Pneumococcal Conjugate Vaccine Use

Starting from 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in several countries. This paper discusses some of the problems recently emerged after PCV13 use and their clinical impact. The impact of PCV13 has been relevant and has saved millions of children and adults by severe infectious diseases. However, it seems likely that in the future, effectiveness of the vaccine might be even higher than that presently evidenced. This is because long-term administration of PCV13 to the pediatric population can favor a more extensive reduction of nasopharyngeal colonization with vaccine serotypes of both vaccinated and unvaccinated subjects and further reduce invasive pneumococcal disease in all the individuals (herd immunity). While waiting for new vaccines to be able to overcome the problem of a limited number of pneumococcal strains included in PCV13, it is recommended to increase pneumococcal vaccination coverage in the entire pediatric population.

Severity of allergic rhinitis and asthma development in children.

Allergic rhinitis (AR) is a relevant risk factor for the development of asthma in children. We recruited a cohort of 104 children with AR and re-evaluated them after 5 years. We considered the ARIA classification. All patients, who had moderate to severe persistent AR at baseline, developed asthma symptoms. These results strongly indicate that the severity of AR may be an important factor that increases the risk of asthma development in children.

Secondary involvement of Meckel’s diverticulum by group A β-hemolytic streptococcus in a child with upper airways infection treated by laparoscopic-assisted resection

We report a case of a 5-year-old boy with acute abdomen following an upper airways infection who developed Meckel’s diverticulum perforation secondary to group A &bgr;-hemolytic streptococcus and its successful treatment by a laparoscopic-assisted intervention. To the best of our knowledge, such an event has never been reported previously.

Association between a low IgE response to Phl p 5 and absence of asthma in patients with grass pollen allergy

BackgroundThe introduction of component-resolved diagnosis was a great advance in diagnosis of allergy. In particular, molecular allergy techniques allowed investigation of the association between given molecular profiles and clinical expression of allergy. We evaluated the possible correlation between the level of specific IgE (sIgE) to single components of Phleum pratense and clinical issues such as the severity of allergic rhinitis (AR) and the presence or absence of asthma.MethodsThe study included 140 patients with rhinitis and/or asthma caused by sensitization to grass pollen. sIgE to Phl p 1, Phl p 5, Phl p 7, and Phl p 12 from Phleum pratense were measured, and the correlation between the stage of AR according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and the presence of asthma was studied by multivariate logistic regression in terms of sIgE and ARIA stage, while univariate logistic regression was used for IgE and a dichotomic classification of asthma as present or absent.ResultsTen patients had intermittent AR, 48 had mild persistent AR, and 82 had severe persistent AR. Asthma was present in 86 patients and absent in 54. A significant correlation was found between severe persistent AR and presence of asthma (p < 0.01). The only significant correlation between clinical data and sIgE values was that of low values of sIgE to Phl p 5 and absence of asthma (p < 0.01).ConclusionsThis preliminary finding suggests that low values of sIgE to Phl p 5 are correlated with the absence of asthma in patients with grass-pollen induced allergy. The data, provided they are confirmed by further studies, could be useful when selecting patients who are candidates for allergen immunotherapy, since a higher risk of asthma could be used as a selection criterion for using this approach.

Omalizumab in children with severe allergic asthma: The Italian real- life experience

Background Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. To date, omalizumab is the only biological drug currently licensed as add-on therapy in children aged > 6 years with moderate-to-severe and severe allergic asthma uncontrolled after treatment with high dose of inhaled corticosteroids plus long-acting inhaled beta2-agonist. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. Our aim is to describe the impact of omalizumab on asthma management, by reporting the results of the first Italian multicenter observational study conducted in children and adolescents with severe allergic asthma. Methods The study was a 1-year real-life multicenter survey conducted in 13 pediatric allergy and pulmonology tertiary centers in Italy. All patients with confirmed severe allergic asthma from whom Omalizumab add-on treatment was initiated between 2007 and 2015 were included in the study. Results Forty-seven patients with severe allergic asthma were included in the study. A significant reduction in the number of asthma exacerbations was observed during treatment with omalizumab, when compared with the previous year (1.03 vs 7.2 after 6 months (p<0.001) and 0.8 after 12 months (p<0.001), respectively). Hospital admissions were reduced by 96%. At 12 months, forced expiratory volume in 1 s improved and a corticosteroid sparing effect was observed.No serious adverse events were reported during the follow-up period of 12 months. Conclusion The results of the first Italian multicenter observational study confirmed that omalizumab is an effective and safe add-on therapy in uncontrolled severe allergic asthma in children.