Michele Miraglia del Giudice

The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever

BACKGROUND Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. OBJECTIVES We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. METHODS Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA(2)LEN-European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. RESULTS No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 [69%]), Betulaceae (146/252 [60%]), pellitory (78/257 [30%]), olive (111/390 [28%]), cypress (28/184 [15%]), and grass (56/568 [10%]). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. CONCLUSIONS In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested.

Fractional Exhaled Nitric Oxide (FENO), Lung Function and Airway Hyperresponsiveness in Naïve Atopic Asthmatic Children

Background. Measurement of fractional exhaled nitric oxide (FENO) is a noninvasive, simple, well‐tolerated, and reproducible marker of airway inflammation. Asthmatic children with normal respiratory function could be affected by airway inflammation. The aim of this study was to assess the correlation between FENO and bronchial hyperesponsiveness (BHR) to methacholine, and between FENO and lung function in atopic children with intermittent asthma. Methods. Thirty‐seven children (21 male), aged 7.2–14.4 years (median: 10.9 years), suffering from mild intermittent atopic asthma with a physician‐diagnosed history of wheezing and/or chest tightness were studied. None had taken anti‐asthmatic therapy for at least three months before the study. No child had symptoms of respiratory tract infection in the month before the study. All subjects underwent FENO measurement, pulmonary function testing and the methacholine provocation tests. Results. The mean percentages of FEV1 and FEF25–27 were 91.9 ± 10.5 and 88.3 ± 11.8, respectively. The mean FENO was 62.2 ± 39.2 ppb and PC20 methacholine was 0.93 mg/ml ± 0.54. Significant correlations were identified between FENO and FEV1 (p < 0.0059, r = 0.468) and between FENO and FEF25–75 (p < 0.0098, r = 0.439). There was no correlation between FENO and logPC20 (p = 0.14). Conclusions. A single FENO measurement is probably of scarce prognostic and predictive value and it is not surprising to find discordance with BHR. We suggest that FENO measurement could represent a good marker of airway inflammation also in naïve atopic children with intermittent asthma. Repeated measurements over time are probably necessary to understand better the clinical implications of the data obtained in this study.

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

Pollen‐induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked.

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.

Food allergy and probiotics in childhood.

Food allergy is a frequent problem in childhood and its prevalence is increasing. In most cases food allergy is an IgE-mediated hypersensitivity response that cause skin reactions as urticaria. Subacute or chronic disorders have generally a not IgE mediated mechanism. Milk is the most common food allergen in USA and UK followed by egg, peanut and walnuts. Sensitization to milk or egg in infancy is associated with an increased risk to develop house dust mite sensitization and asthma later in childhood. Commensal gut flora play a role in induction of oral tolerance and the importance of the intestinal microbiota in the development of food allergy is essential in early ages, when the mucosal barrier and immune system are still immature. Probiotics interact with the mucosal immune system by the same pathways as commensal bacteria. Recent study show that probiotic bacteria induced in vivo increased plasma levels IL-10 and total IgA in children with allergic predisposition. Many clinical studies reporting significant benefits by probiotics supplementation in food allergy prevention and management but not everyone agree on their effectiveness. These differences are probably related to differences in selected populations and in probiotic strains used.

Allergic reactions to foods by inhalation in children.

This article focuses on hypersensitivity reactions after inhalation of food particles as primary cause for food allergy. This is an increasingly recognized problem in children. Reactions are commonly diagnosed in children who develop symptoms when the food is ingested. Some children tolerate the food when it is eaten but they experience reactions to airborne food particles such as peanut, cows milk, and fish. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. Usually, respiratory manifestations include rhinoconjunctivitis, coughing, wheezing, and asthma, but in some cases even anaphylaxis has been observed. Practical approaches concerning diagnosing clinical reactivity including skin tests, serum IgE antibodies, specific provocation tests, and management have been identified. Studies are warranted to establish the accuracy of diagnostic tests as well as incidence, prevalence, and natural history of food allergy through inhalation route.

Serum IL-23 strongly and inversely correlates with FEV1 in asthmatic children.

Background: Recently, Th17 cells have been found to participate in the pathogenesis of allergic asthma. IL-23 is a cytokine that may be implicated in modulating Th17 response. This study aimed at evaluating IL-23 and relating it to lung function in asthmatic children. Methods: Seventy-eight asthmatic children and 40 healthy children were evaluated. Spirometry and serum IL-23 measurement (ELISA kit) were performed in all asthmatic children. Results: IL-23 levels were higher in asthmatic than in healthy children (p < 0.001). There was a strong inverse relationship between FEV1 and IL-23 (r = –0.787). Conclusions: This preliminary study suggests that serum IL-23 could be a suitable marker of bronchial function impairment in allergic asthmatic children.

Prevalence and Clinical Relevance of IgE Sensitization to Profilin in Childhood: A Multicenter Study

Background: Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children. Objectives: The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas. Methods: Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA. Results: IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber. Conclusions: Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age.

Leukotriene modifiers in the treatment of asthma in children

Asthma is one of the most common respiratory disorders in clinical practice, affecting up to 13% of people worldwide. Inflammation is the most important component of asthma and inhaled corticosteroids (ICS) are recommended as the first line controller treatment for patients of all ages. Treatment with corticosteroids is often unable to fully control asthma symptoms and progression. Recently, leukotrienes have come to the forefront of research as they have been found play a pivotal role in the airway inflammatory process, and specific drugs have been developed to target them. Cysteiny leukotriene antagonists (LTRAs) have recently emerged as important therapeutic options that show a large potential clinical utility. Three specific LTRAs are licensed for clinical use: montelukast, zafirlukast and pranlukast, although montelukast is the only drug approved in the paediatric age range. It is well tolerated (although adverse effects such as headaches, abdominal pain, rashes, angioedema, pulmonary eosinophilia and arthralgia have been reported) and shows many positive effects in asthmatic patients. Current Global Initiative for Asthma guidelines recommend LTRAs as: (1) a second choice treatment to ICS for patients with mild persistent asthma, (2) an add-on therapy to reduce the dose of ICS in patients with moderate or severe asthma, due to the different and complementary mechanisms of action of these agents. LTRAs may be particularly appropriate choices in a number of clinical situations, including the following: patients with concomitant rhinitis; patients with viral-induced wheeze; patients with exercise-induced bronchoconstriction (EIB) and, in children aged 2-5 years, to reduce the frequency of asthma exacerbations.

Hepatitis B vaccination failure in children with diabetes mellitus? The debate continues

Background The aim of our study was to evaluate the presence of specific antibodies against HBsAg in diabetic children (IDDM) previously vaccinated against hepatitis B virus. Patients and methods 110 diabetic children were retrospectively studied and 100 healthy controls were recruited. In all patients surface antigen, HBV core IgG, antibodies against HBV “e” antigen and quantitative HBV surface antibodies were detected. In 45 patients molecular typing of HLA alleles was performed. Metabolic control was evaluated as mean glycated hemoglobin (HbA1c) and all patients were compliant to insulin therapy Results 46 of 110 diabetic children (41.8%) and 16 of 100 healthy controls (16%) were found to have not anti-HBs antibodies (p < 0.0001). The mean antibody titer was found significantly-lower (p < 0.0001) in IDDM children than healthy controls. No correlation was found between antibody titer, age, duration of disease and HbA1c. We did not find any difference of gender, age, years of onset of the disease and metabolic control, between diabetics with anti-HBs antibodies and those without. Conclusions Our data confirm the reduced seroprotection rate for HBV vaccination in diabetics. However it remains poorly clarify the real clinical significance of this result. In our study no diabetic children showed markers of HBV infection.