Attilio L. Boner

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 × 10−14, 5.4 × 10−10, 8.6 × 10−17, 1.2 × 10−10 and 6.5 × 10−19, respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 × 10−12) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 × 10−6, 2.2 × 10−5 and 2.4 × 10−4, respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 × 10−8) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative ** , which is endorsed by both academies.

Early identification of atopy in the prediction of persistent asthma in children

The long-term solution to the asthma epidemic is thought to be prevention, and not treatment of established disease. Atopic asthma arises from gene-environment interactions, which mainly take place during a short period in prenatal and postnatal development. These interactions are not completely understood, and hence primary prevention remains an elusive goal. We argue that primary-care physicians, paediatricians, and specialists lack knowledge of the role of atopy in early life in the development of persistent asthma in children. In this review, we discuss how early identification of children at high risk is feasible on the basis of available technology and important for potential benefits to the children. Identification of an asthmatic childs atopic status in early life has practical clinical and prognostic implications, and sets the basis for future preventative strategies.

TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity.

ABSTRACT The natural history and pathogenic potential of the recently identified TT virus (TTV) are currently a matter of intensive investigation. In an attempt to shed some light on these issues, nasal and blood specimens of 1- to 24-month-old children hospitalized with a clinical diagnosis of acute respiratory disease (ARD) were examined for the presence, load, and genetic characteristics of TTV. The results have indicated that at least in young children, the respiratory tract not only represents a route by which abundant TTV can be shed into the environment but also may be a site of primary infection and continual replication. Although we found no compelling evidence that TTV was the direct cause of ARD in some of the children studied, the average loads of TTV were considerably higher in patients with bronchopneumonia (BP) than in those with milder ARD, raising interesting questions about the pathophysiological significance of TTV at this site. Furthermore, group 4 TTV was detected almost exclusively in children with BP.

Vitamin D Serum Levels and Markers of Asthma Control in Italian Children

OBJECTIVE To establish the relationship between vitamin D serum levels, pulmonary function, and asthma control in children. STUDY DESIGN We studied the relationship between 25-hydroxy cholecalciferol [25(OH)D] concentrations and baseline spirometry and levels of asthma control, assessed according to Global Initiative for Asthma guidelines and the Childhood Asthma Control Test, in 75 children with asthma (age range 5-11 years; 43 males) in a cross-sectional study carried out during the winter and early spring. RESULTS Only 9.4% of our children had a sufficient serum 25(OH)D (at least 30 to 40 ng/mL). A significant positive correlation was found between forced vital capacity percent predicted and serum 25(OH)D (r = 0.25, P = .040). This was true also for forced expiratory volume in 1 second, even though it was not statistically significant (r = 0.16, P = .157). Subjects with well-controlled asthma had higher serum levels of 25(OH)D than children with partially controlled or non-controlled asthma, with values of (median [Q1; Q3]) 22.2 (16.3; 25.4), 17.8 (11.8; 22.1) and 18.1 (15.0; 18.5), respectively (P = .023). Furthermore, a positive correlation was found between 25(OH)D and the Childhood Asthma Control Test (r = 0.28; P = .011). CONCLUSIONS Our results indicate that hypovitaminosis D is frequent in children with asthma living in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced asthma control.

Asthma, allergy and respiratory infections: the vitamin D hypothesis

To cite this article: Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy, and respiratory infections: the vitamin D hypothesis. Allergy 2012; 67: 10–17.

Antigen avoidance in a mountain environment: Influence on basophil releasability in children with allergic asthma

BACKGROUND The influence of natural antigen avoidance in an environment free of relevant allergens (Istituto Pio XII, Misurina, Italian Alps, 1756 m) and of antigen exposure (sea level) on basophil releasability, as well as on bronchial hyperreactivity (BHR) and specific IgE serum level, were investigated in a group of children with asthma who were allergic to Dermatophagoides pteronyssinus. METHODS Twenty allergic children with asthma participated in the study. Spontaneous and antigen-induced histamine release, BHR, and serum IgE were investigated at the time of admission, after 40 and 80 days of antigen avoidance, and after 15 days of exposure at sea level. RESULTS Significant drops in antigen-induced basophil histamine release, BHR, and specific IgE serum level but not in spontaneous basophil histamine release were observed after 40 days of antigen avoidance and were confirmed at a further evaluation after 40 more days. After 15 days of antigen exposure at sea level, specific antigen-induced basophil histamine release, BHR, and serum IgE but not spontaneous basophil histamine release increased promptly, even if not significantly. CONCLUSION In children with allergic asthma, antigen-induced basophil releasability, BHR, and specific IgE serum levels appear to be modifiable by periods of antigen avoidance or exposure.

A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay.

BACKGROUND Peanut allergy is relatively common, typically permanent, and often severe. Double-blind, placebo-controlled food challenge is considered the gold standard for the diagnosis of food allergy-related disorders. However, the complexity and potential of double-blind, placebo-controlled food challenge to cause life-threatening allergic reactions affects its clinical application. A laboratory test that could accurately diagnose symptomatic peanut allergy would greatly facilitate clinical practice. OBJECTIVE We sought to develop an allergy diagnostic method that could correctly predict symptomatic peanut allergy by using peptide microarray immunoassays and bioinformatic methods. METHODS Microarray immunoassays were performed by using the sera from 62 patients (31 with symptomatic peanut allergy and 31 who had outgrown their peanut allergy or were sensitized but were clinically tolerant to peanut). Specific IgE and IgG(4) binding to 419 overlapping peptides (15 mers, 3 offset) covering the amino acid sequences of Ara h 1, Ara h 2, and Ara h 3 were measured by using a peptide microarray immunoassay. Bioinformatic methods were applied for data analysis. RESULTS Individuals with peanut allergy showed significantly greater IgE binding and broader epitope diversity than did peanut-tolerant individuals. No significant difference in IgG(4) binding was found between groups. By using machine learning methods, 4 peptide biomarkers were identified and prediction models that can predict the outcome of double-blind, placebo-controlled food challenges with high accuracy were developed by using a combination of the biomarkers. CONCLUSIONS In this study, we developed a novel diagnostic approach that can predict peanut allergy with high accuracy by combining the results of a peptide microarray immunoassay and bioinformatic methods. Further studies are needed to validate the efficacy of this assay in clinical practice.

Safety of Sublingual Immunotherapy in Children with Asthma

AbstractIntroduction: Two previously published studies on sublingual immunotherapy (SLIT) did not report any serious adverse event associated with the local therapy; however, adverse events were observed in greatly variable percentages. The aim of the study was to evaluate the tolerability profile of sublingual swallow and spit immunotherapy in a large number of children treated for allergic asthma. Methods: Adverse effects related to sublingual administration of allergen vaccines were evaluated in 354 children with allergic asthma. Each patient was followed for at least 37 months and received a monthly dose of major allergens (extract) in the range of 1.5–14.8μg, equivalent to 3–20 times the amount contained in the usual monthly maintenance injections via the subcutaneous routes. Results: No adverse event was observed in 90.4% of the children. We observed 0.155 mild to moderate reactions per 1000 administrations. Dosage adjustment was required in 15 patients. In five children, immunotherapy was stopped as a precaution – one patient developed rhino-conjunctivitis, two patients developed urticaria, and two children developed wheezing. None of the reactions were due to dosage errors. No anaphylactic reaction or multiple-organ life-threatening events occurred. Conclusions: The results of our study showed an incidence of mild to moderate unwanted effects of 9.6%, lower than that previously reported, and no life-threatening adverse effects. Nevertheless, asthma, urticaria, and rhinoconjunctivitis can occur. SLIT is quite a safe therapy for the treatment of allergic children with asthma; however, careful evaluation of the single patient is necessary since SLIT is self-administered and a cumulative monthly dose higher than that normally administered as an injection is usually attainable.

Influence of allergen avoidance on the eosinophil phase of airway inflammation in children with allergic asthma

BACKGROUND Exposure to relevant allergens causes an increase in bronchial hyperresponsiveness, as well as an inflammatory reaction at the site of the bronchial mucosa in patients with asthma. OBJECTIVE The purpose of this study was to determine whether antigen avoidance can exert an antiinflammatory effect on the eosinophil phase of airway inflammation in children with asthma. METHODS The level of bronchial hyperreactivity and the percentage of eosinophils in sputum samples obtained by inhalation of hypertonic saline solution, were evaluated in a group of asthmatic children allergic to house dust mite before and after a period of antigen avoidance in an Alpine environment (1756 m). RESULTS At the end of the avoidance period PC20 increased from a median value (lower and upper quartile: Q1, Q3) of 1.17 (0.74, 4.75) to 3.5 (1.18, 8.87) mg/ml (p = 0.02), and eosinophil percentage in the sputum decreased from a median value (Q1, Q3) of 14.02 (3.34, 28.24) to 2.08 (0, 7.4) (p less than 0.01). CONCLUSION A 3-month period of antigen avoidance can significantly reduce the eosinophil phase of airway inflammation, along with bronchial hyperresponsiveness, in patients with asthma.