Retrospective definition of reaction risk in Italian children with peanut, hazelnut and walnut allergy through component-resolved diagnosis.

BACKGROUND: Serum IgE evaluation of peanut, hazelnut and walnut allergens through the use of component-resolved diagnosis (CRD) can be more accurate than IgE against whole food to associate with severe or mild reactions. OBJECTIVES: The aim of the study was to retrospectively define the level of reaction risk in children with peanut, hazelnut and walnut sensitization through the use of CRD. METHODS: 34 patients [n=22 males, 65%; median age eight years, interquartile range (IQR) 5.0-11.0 years] with a reported history of reactions to peanut and/or hazelnut and/or walnut had their serum analyzed for specific IgE (s-IgE) by ImmunoCAP® and ISAC® microarray technique. RESULTS: In children with previous reactions to peanut, the positivity of Arah1 and Arah2 s-IgE was associated with a history of anaphylaxis to such food, while the positivity of Arah8 s-IgE were associated with mild reactions. Regarding hazelnut, the presence of positive Cora9 and, particularly, Cora14 s-IgE was associated with a history of anaphylaxis, while positive Cora1.0401 s-IgE were associated with mild reactions. Concerning walnut, the presence of positive Jug r 1, Jug r 2, Jug r 3 s-IgE was associated with a history of anaphylaxis to such food. ImmmunoCAP® proved to be more useful in retrospectively defining the risk of hazelnut anaphylaxis, because of the possibility of measuring Cor a14 s-IgE. CONCLUSIONS: Our data show that the use of CRD in patients with allergy to peanut, hazelnut and walnut could allow for greater accuracy in retrospectively defining the risk of anaphylactic reaction to such foods.

Awareness of allergic enterocolitis among primary-care paediatricians: A web-based pilot survey.

BACKGROUND: Allergic enterocolitis, also known as food protein-induced enterocolitis syndrome (FPIES), is an increasingly reported and potentially severe non-IgE mediated food allergy of the first years of life, which is often misdiagnosed due to its non-specific presenting symptoms and lack of diagnostic guidelines. OBJECTIVE: We sought to determine the knowledge of clinical, diagnostic and therapeutic features of FPIES among Italian primary-care paediatricians. METHODS: A 16-question anonymous web-based survey was sent via email to randomly selected primary care paediatricians working in the north of Italy. RESULTS: There were 194 completed surveys (48.5% response rate). Among respondents, 12.4% declared full understanding of FPIES, 49% limited knowledge, 31.4% had simply heard about FPIES and 7.2% had never heard about it. When presented with clinical anecdotes, 54.1% recognised acute FPIES and 12.9% recognised all chronic FPIES, whereas 10.3% misdiagnosed FPIES as allergic proctocolitis or infantile colic. To diagnose FPIES 55.7% declared to need negative skin prick test or specific-IgE to the trigger food, whereas 56.7% considered necessary a confirmatory oral challenge. Epinephrine was considered the mainstay in treating acute FPIES by 25.8% of respondents. Only 59.8% referred out to an allergist for the long-term reintroduction of the culprit food. Overall, 20.1% reported to care children with FPIES in their practice, with cow's milk formula and fish being the most common triggers; the diagnosis was self-made by the participant in 38.5% of these cases and by an allergist in 48.7%. CONCLUSION: There is a need for promoting awareness of FPIES to minimise delay in diagnosis and unnecessary diagnostic and therapeutic interventions.

Ambroxol inhibits neutrophil respiratory burst activated by alpha chain integrin adhesion.

The purpose of the present study was to investigate the possible anti-oxidant effect(s) of Ambroxol on neutrophils activated by ligand-binding of the drug with membrane-associated adhesion integrin CD11a and to estimate dose-response changes in oxygen free radical production. The amount of free radical production by anti-CD11a- and anti-CD4-coated neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and challenged with increasing concentration of Ambroxol, was evaluated within a time frame of 90 minutes. A significant dose-dependent effect response of Ambroxol on O2‾ production by cells coated with anti-CD11a antibody was observed. This preliminary study opens a new perspective on the therapeutic role of Ambroxol as an antioxidant drug and for its potential use in controlling oxidative stress, particularly in leukocyte-dependent inflammation.

Timing of introduction of solid food and risk of allergic disease development: understanding the evidence.

Strategies to prevent or reduce the risk of allergic diseases are needed. The time of exclusive breastfeeding and introduction of solid foods is a key factor that may influence the development of allergy. For this reason, the aim of this review was to examine the association between exposure to solid foods in the infant's diet and the development of allergic diseases in children. Classical prophylactic feeding guidelines recommended a delayed introduction of solids for the prevention of atopic diseases. Is it really true that a delayed introduction of solids (after the 4th or 6th month) is protective against the development of eczema, asthma, allergic rhinitis and food or inhalant sensitisation? In recent years, many authors have found that there is no statistically significant association between delayed introduction of solids and protection for the development of allergic diseases. Furthermore, late introduction of solid foods could be associated with increased risk of allergic sensitisation to foods, inhalant allergens and celiac disease in children. Tolerance may be driven by the contact of the mucosal immune system with the allergen at the right time of life; the protective effects seem to be enhanced by the practice of the breastfeeding at the same time when weaning is started. Therefore, recent guidelines propose a "window" approach for weaning practice starting at the 17th week and introducing almost all foods within the 27th week of life to reduce the risk of chronic diseases such as allergic ones and the celiac disease. Guidelines emphasize the role of breastfeeding during the weaning practice.

Unusual shift from IgE-mediated milk allergy to food protein-induced enterocolitis syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy usually caused by cow's milk or soy, and more rarely by solid foods such as rice, oats, barley, chicken, turkey, egg white, green peas and peanuts. In children with FPIES, the presence of specific IgE antibodies to the causative food, either at presentation or during follow-up, defines an "atypical form" of FPIES characterized by a lesser probability of developing tolerance and a potential progression to typical IgE-mediated hypersensitivity. Although it is uncommon, the shift from non-IgE-mediated milk-protein induced enterocolitis syndrome to IgE-mediated milk allergy has recently been described. We report the first case, to our knowledge, of a shift from IgE-mediated cow's milk allergy to pure non-IgE-mediated FPIES, in a 4-month-old male infant.

Exhaled nitric oxide in pediatrics: what is new for practice purposes and clinical research in children?

Fractional exhaled NO (FeNO) is universally considered an indirect marker of eosinophilic airways inflammation, playing an important role in the physiopathology of childhood asthma. Advances in technology and standardization have allowed a wider use of FeNO in clinical practice in children from the age of four years. FeNO measurements add a new dimension to the traditional clinical tools (symptoms scores, lung function tests) in the assessment of asthma. To date a number of studies have suggested a possible use of FeNO in early identification of exacerbation risk and in inhaled corticosteroids titration. The aim of this paper is to address practical issues of interest to paediatric clinicians who are attempting to use FeNO measurements as an adjunctive tool in the diagnosis and management of childhood airway diseases.

Markers of oxidative stress are increased in exhaled breath condensates of children with atopic dermatitis.

BACKGROUND: Airway inflammation may be present in subjects affected by atopic dermatitis (AD) but still without asthma symptoms. Exhaled breath condensate (EBC) reflects the composition of bronchoalveolar extracellular lining fluid that contains a large number of mediators of airway inflammation and oxidative damage. OBJECTIVES: We assessed inflammatory markers in the EBC of patients with AD. Fifty-six children (34 girls and 22 boys) were enrolled: 33 affected by AD and 23 healthy controls. METHODS: EBC was collected using a condenser device. We measured EBC pH and concentrations of leukotriene B4 (LTB4), 8-isoprostane, H(2) O(2) , malondialdehyde and 4-hydroxynoneal. Respiratory resistance was also evaluated. RESULTS: EBC pH in patients with AD was significantly lower than in healthy children, median (range) being 8·02 (7·94-8·12) in AD vs. 8·11 (8·05-8·16) (P = 0·02). The values of exhaled 8-isoprostane and LTB4 were significantly increased in subjects with AD compared with normal controls (P < 0·01 and P < 0·001, respectively). There was increased 4-hydroxynoneal in patients with AD but this did not reach statistical significance. Evaluating respiratory resistance, no bronchoreversibility was demonstrated in the children with AD. CONCLUSIONS: pH, LTB4 and 8-isoprostane in EBC could be sensitive markers of airway inflammation in children with AD. Prospective studies would be of interest to evaluate if airway inflammation, not yet clinically evident, could predict the development of asthma later in life in children with AD.

Assessment of problematic severe asthma in children.

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.

Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children.

BACKGROUND: Vitamin D deficiency could be associated with the prevalence of atopic dermatitis (AD). OBJECTIVES: We carried out a study to see whether deficient/insufficient levels of vitamin D correlate with the severity of atopic skin disease. METHODS: Using the SCORAD index, we evaluated the severity of disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years with AD, consecutively enrolled in the study. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by the ImmunoCAP system. anova and the Pearson correlation test were used for statistical evaluation. RESULTS: We found severe, moderate and mild AD in nine (24%), 13 (35%) and 15 (41%) children, respectively. Mean ± SD serum levels of 25(OH)D were significantly higher (P < 0·05) in patients with mild disease (36·9 ± 15·7 ng mL(-1)) compared with those with moderate (27·5 ± 8·3 ng mL(-1)) or severe AD (20·5 ± 5·9 ng mL(-1)). The prevalence of patients with sIgE to microbial antigens increased in relation to vitamin D deficiency and AD severity. CONCLUSIONS: These data suggest that vitamin D deficiency may be related to the severity of AD and advocate the need for studies evaluating the use of vitamin D as a potential treatment in patients with this disease.

Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma.

Epidemiological studies have established a relationship between low levels of serum vitamin D and reduced lung function in healthy adults, and asthma onset and severity in children. However, no study has examined the relationship between vitamin D levels and exercise-induced bronchoconstriction in asthmatic children. We evaluated the relationship between 25-hydroxyvitamin D concentrations and baseline forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and change in FEV1 (ΔFEV1) after a standardised exercise challenge in 45 children with intermittent asthma. Only 11% of the children had desirable serum vitamin D levels (at least 30-40 ng·mL(-1)). A positive correlation was found between serum 25-hydroxyvitamin D and both FVC (r=0.34; p=0.037) and FEV1 (r=0.32; p=0.037). Subjects with a positive response to the exercise challenge (ΔFEV1≥10%) presented lower serum levels of 25-hydroxyvitamin D than children with a negative challenge (mean±sd 16.2±5.2 versus 23.4±7.0 ng·mL(-1), respectively; p=0.001). Our results indicate that hypovitaminosis D is frequent in asthmatic children who live in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced lung function and increased reactivity to exercise.

A comparison between IgE and IgG4 as markers of allergy in children: an experimental trial in a model of natural antigen avoidance.

IgG4 have been hypothesized to act as blocking antibodies capable of preventing IgE-mediated effector cell triggering. This study aims to evaluate the changes in IgG4 in children during a period of natural antigen avoidance. Serum IgE and IgG4 were evaluated in a group of asthmatic children, aged between 7 and 17 years, admitted to the residential house Istituto Pio XII (Misurina, BL, Italy), located at 1,756 m, in a natural model of antigen avoidance. All the patients were skin prick test positive to at least two of the following allergens: Dermatophagoides pteronissynus, Dermatophagoides farinae, cat epithelium, timothy grass pollen and Parietaria pollen. During the 180 days of hospitalization, serum specific IgE and IgG4 were measured six times. A significant decrease (p≤0.05) in serum specific IgE to house dust mite and pollen allergens was observed; by contrast, no significant variations were shown by IgG4 and IgG4/IgE ratio. No significant relationship was found between serum specific IgE, IgG4 and IgG4/IgE ratio variations and the re-exposure to house dust mite allergens during the Christmas holidays. A positive correlation between specific IgE and specific IgG4 was observed at each considered time (T0: r=0.57, p=0.08; T1: r=0.85, p=0.001; T3: r=0.76, p=0.01). The positive correlation between specific IgE and specific IgG4, enduring throughout the entire time of study, suggests a relationship between these classes of immunoglobulins.

Nasal nitric oxide levels in healthy pre-school children.

The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool in children with clinically suspectable primary ciliary dyskinesia. Nevertheless, normal values have been reported for school-aged children. This study was designed to identify normal nNO levels in pre-school children. nNO was assessed in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them were unable to fulfill the guideline requirements for nNO measurement and were assessed by sampling the nasal air continuously with a constant trans-nasal aspiration flow for 30 s during tidal breathing. For those children who were able to cooperate, the average nNO concentration was calculated according to guidelines. A statistically significant relationship between nNO level and age was demonstrated in this study group of pre-school children (p < 0.001). An increase in nNO of about 100 ppb was observed in children older than 6 yr vs. those aged < 3. This study presents a description of normal nNO values in pre-school children. The effect of the age and the eventual presence of rhinitis and snoring need to be considered whenever nNO is evaluated in the clinical practice, in particular in non-cooperative children.

Neonatal sepsis and later development of atopy.

BACKGROUND: The role of infections on the development of atopy is still widely debated. We aimed to evaluate the effects of neonatal severe sepsis and consequent antibiotic treatment on the development of atopy and allergic diseases. MATERIAL AND METHODS: A retrospective enrollment at school age of children with a clear history of neonatal sepsis (NS) was performed from registers of neonatal intensive care units. A normal control was assigned to each patient with sepsis. Thirty six cases with sepsis (18 males, 18 females) and 36 controls (21 males, 15 females) were selected (8.5+/-3.6 yrs). Physical examination and lung function evaluation were performed. Atopic status was verified by blood eosinophil count, total IgE serum level and skin prick tests (SPT). RESULTS: SPT positivity for at least one allergen was present in 30% of subjects in both groups. No difference for all investigated parameters between groups and no influence by other factors such as familiarity or gender was observed. No correlation was associated to NS history. CONCLUSIONS: Neonatal sepsis, even if clinically severe and dramatic, could represent an event too limited and really precocious in life to influence the development of immune response. Furthermore, other factors, besides infections, may influence the atopic future of newborns.

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C-ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function. METHODS: A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma ('New') and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow-up visit ('Follow-up'). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated. RESULTS: In New vs Follow-up participants, C-ACT score (P < 0.001), FVC (P < 0.005) and FEV1 (P < 0.05) were significantly lower, and FeNO (P = 0.011) were significantly higher. In New, but not in Follow-up participants, significant correlations were observed between C-ACT score and FeNO (r = -0.51; P < 0.001), FEV1 (r = 0.34; P = 0.022) and FEV1/FVC (r = 0.32; P = 0.03). This lack of correlation in Follow-up visits seemed attributable to dissociation between inadequately controlled asthma by C-ACT ratings with normalization of other measures such as FeNO levels. CONCLUSIONS: This study confirms and expands the concept that C-ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow-up visits.

Bioimpedance monitoring of airway inflammation in asthmatic allergic children.

BACKGROUND: Asthma in childhood is characterized by chronic inflammation. Measurement of bioimpedance (BI) is a non-invasive way of detecting airway inflammation. The aim was to compare BI with exhaled nitric oxide (eNO) and lung function evaluations in asthmatic allergic children while not exposed to offending allergens. METHODS: 22 asthmatic children allergic to house dust mites have been enrolled while residents at high altitude in an environment free of house dust mites. They were evaluated at T0 after allergen exposure at home, at T1 and at T2 after 1 and 4 months of allergen avoidance, respectively. RESULTS: eNO decreased from 32.21 +/- 5.70 ppb at T0 to 21.92 +/- 4.36 ppb at T1, after one month at high altitude (p = 0.038), without a further decrease at T2. Data in electrical activity showed a significant decrease in conductivity of lower airways between T0 (48.53 +/- 3.53 microA) and T1 (42.08 +/- 3.47 microA) (p = 0.023). deltaB parameter (difference between conductivity of lower respiratory tract and average yield) showed significant decrease from T0 (20.75 +/- 2.64 microA), and T1 (12.84 +/- 2.52 microA) (p < 0.01), but no further decrease at T2. No difference in lung function parameters was observed. CONCLUSION: Allergen avoidance regimen modifies inflammatory parameters in allergic asthmatics. Evaluation of extracellular bioelectrical conductivity seems to represent a promising non-invasive method to assess airway inflammation.

Prevalence and risk factors for atopic dermatitis in preschool children.

BACKGROUND: Atopic dermatitis (AD) is a common condition in infancy which usually disappears by 3 years of age in a significant proportion of children. The prognosis is mostly determined by severity and presence of atopic sensitization. OBJECTIVES: To investigate prevalence of AD, comorbidities and risk factors in a population of preschool children aged 3-5 years. METHODS: Children in kindergartens were evaluated. The International Study of Asthma and Allergies in Childhood written questionnaire (WQ) was used, with additional questions on risk factors. Atopy was investigated by skin prick tests. RESULTS: One thousand, four hundred and two valid WQs (92% response rate) were returned for evaluation. The prevalence of AD symptoms in the last 12 months in the whole population was 18.1% (254 cases). Seventy-two per cent of these children presented AD-specific localizations. The prevalence of eczema as a doctor's diagnosis in the total population was 15.4%. Positive atopic sensitization was present in 18.6% of the total and in 32.2% of the AD study population, respectively. Multiple sensitivities were observed in 58.2% of sensitized children. The prevalence of sensitization demonstrated that the most common sensitizing allergens in children with AD were mites and grass pollen. Rhinitis symptoms and wheezing were present in 32.2% and 24.2%, respectively, of children with AD. Allergic sensitization to egg, cat, grass pollen and mites, as well as the presence of symptoms of rhinitis, and a positive family history of atopy were all significant risk factors for AD. CONCLUSIONS: The study demonstrates a high prevalence of AD and a close relationship with rhinitis symptoms. Significant risk factors for AD were sensitization to food or inhalant allergens as well as parental history of atopy.