Bronchial hyperresponsiveness to mannitol, airway inflammation and Asthma Control Test in atopic asthmatic children.

INTRODUCTION: The aim of this study was to evaluate the relationship between airway hyperresponsiveness (AHR) to mannitol and bronchial inflammation measured as exhaled nitric oxide (FeNO) and to assess whether asthma control correlates with AHR to mannitol and FeNO in atopic asthmatic children. MATERIAL AND METHODS: Allergy evaluation, the mannitol challenge test, FeNO levels and the Asthma Control Test (ACT) questionnaire were assessed in 40 children with intermittent and mild persistent allergic asthma. RESULTS: All the subjects showed positive AHR to mannitol. Pearson's correlation test revealed a significant inverse correlation between AHR (mannitol PD15) and FeNO (p = 0.020). There was also a significant positive correlation between ACT and PD15 (p = 0.020) and a significant negative correlation between ACT and FeNO levels (p = 0.003). The study population was divided into two groups according to FeNO levels (group A ≥ 16 ppb vs. group B < 16 ppb). In group A mannitol PD15 was significantly lower (p = 0.040) and ACT score values were significantly lower (p = 0.001) compared to group B. In group A, the ACT showed that 13.3% of subjects had well-controlled asthma, 80% had partially controlled asthma and 6.7% had uncontrolled asthma. In group B, the ACT showed that 72% of subjects had well-controlled asthma and 28% had partially controlled asthma. CONCLUSIONS: Our findings indicate that the degree of AHR to mannitol correlates with the degree of airway inflammation in asthmatic atopic children; moreover, better control of asthma correlates with a lower degree of AHR to both mannitol and FeNO.

Vitamin D supplementation modulates the immune system and improves atopic dermatitis in children.

BACKGROUND: Vitamin D seems to influence the evolution of atopic dermatitis (AD) in children. METHODS: We tested the vitamin D serum levels of 39 children with AD (AD group t0) and of 20 nonallergic healthy controls (C group). AD severity was evaluated using the AD scoring system (SCORAD index). Cytokine serum levels (IL-2, IL-4, IL-6, IFN-γ, TNF-α) and atopy biomarkers were also measured. The patients were then treated with vitamin D oral supplementation of 1,000 IU/day (25 mg/day) for 3 months. We then reevaluated the vitamin D serum levels, AD severity and cytokine serum levels in all of the treated children (AD group t1). RESULTS: The cross-sectional analysis on patients affected by AD (AD group t0) showed that the initial levels of all the tested cytokines except for TNF-α were higher than those of the healthy control group (C group), falling outside the normal range. After 3 months of supplementation the patients had significantly increased vitamin D levels (from 22.97 ± 8.03 to 29.41 ± 10.73 ng/ml; p = 0.01). A concomitant significant reduction of both the SCORAD index (46.13 ± 15.68 at the first visit vs. 22.57 ± 15.28 at the second visit; p < 0.001) and of all the altered cytokines (IL-2, IL-4, IL-6, IFN-γ) was also found. CONCLUSIONS: This study showed vitamin D supplementation to be an effective treatment in reducing AD severity in children through normalization of the Th1 and Th2 interleukin serum pattern.

Usefulness of nBos d 4, 5 and nBos d 8 Specific IgE Antibodies in Cow's Milk Allergic Children.

PURPOSE: The aim of study was to assess the value of recombinants in predicting the degree of symptoms in children with and without anaphylaxis to cow's milk. METHODS: The study included 79 children (70±40 months) referred to the Allergological Unit of the Pediatric Department between the years 2008-2012. Group A was composed of 17 children (78±49.6 months) with anaphylaxis after ingestion of milk. Group B was composed of 62 children (73.1±38.6 months) without a history of anaphylaxis, but with less severe symptoms (gastrointestinal and/or skin symptoms). All patients from Group B had a positive open challenge with cow's milk. All patients underwent an allergic evaluation and blood samples were collected to test for IgE to recombinans of milk (nBos d 4, 5, 8). RESULTS: A significant difference in nBos d 8 emerged with higher levels in Group A (median [IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there were no statistically significant differences for nBos d 4 and 5. The recombinants' sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85-7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the other recombinants in identifying children at risk for anaphylaxis, with an area under the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering a cutoff of 1.8 kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02 (95% C.I: 1.89-19.23). CONCLUSIONS: This study suggested 2 phenotypes of allergic children, "high-anaphylaxis-risk" and "milder-risk". These types can be differentiated through measuring the level of IgE to nBos d 8.

Evaluation of association between airway hyperresponsiveness, asthma control test, and asthma therapy assessment questionnaire in asthmatic children.

BACKGROUND: Achieving asthma control is a major challenge in children, otherwise symptoms perception remain poor especially at this age. The aim of this study is to evaluate the relationship between Asthma Control Test (ACTTM), Asthma Therapy Assessment Questionnaire (ATAQTM) and exercise-induced bronchospasm (EIB). METHODS: We studied 80 asthmatic children. Airways hyperresponsiveness (AHR) was assessed by exercise-induced bronchospasm (Balke Protocol). Asthma control was evaluated using two questionnaires in all subjects: ACT (composed by Childhood-ACT and ACT) and ATAQ. In addition the use of short acting beta 2 agonist agents (SABAs) was assessed for each patient. Non-parametric variables were compared by Chi Square Test. Binomial logistic regression was performed to estimate the two questionnaires Odds Ratio (OR) in finding AHR. RESULTS: We have found that ATAQ has a sensitivity and a specificity of 0.72 and 0.45 respectively; instead, ACT has a sensitivity and a specificity of 0.5 and 0.39 respectively in evaluating AHR. Patients with uncontrolled asthma according to ATAQ revealed a significant higher percentage of AHR compared with ACT (72% vs 50%, p < 0.01).Confirming this finding, patients declaring uncontrolled asthma to ATAQ have a significantly higher percentage (34%) of frequent SABAs use than the group with uncontrolled asthma to ACT (21%) (p <0.01).Binomial logistic regression shows how a test revealing uncontrolled asthma is associated with the increasing odds of having AHR according to ATAQ (OR = 3.8, p = 0.05), not to ACT (OR = 0.2, p = 0.1). CONCLUSIONS: Our results show that ATAQ reflects AHR and asthma control better than ACT. Children with uncontrolled asthma according to ATAQ have higher odds of having AHR and use of rescue medications (SABAs) compared to patients declaring uncontrolled asthma according to ACT. However both questionnaires are not sufficient alone to fully evaluate asthma control in children and it is always necessary to perform functional tests and investigate patients lifestyle, drug use and other important data that a simple questionnaire is not able to point out.

Sensitization to timothy grass pollen allergenic molecules in children.

BACKGROUND: Grass pollens are significant elicitors of IgE-mediated allergic disease in the world and timothy (Phleum pratense) is one of the most important pollens of the family. Molecular and biochemical characterization of Phleum pratense has revealed several allergen components: rPhl p 1 and rPhl p 5 have been shown to be "Species Specific Allergens", while the profilin rPhl p 12 and the calcium-binding protein rPhl p 7 are the principal Cross-Reactive components. METHODS: In this study the pattern of sensitization to rPhl p 1, rPhl p 5, rPhl p 7 and rPhl p 12 was analyzed in children with asthma and/or rhinoconjunctivitis and grass pollen allergy, in order to evaluate the frequency of sensitization to allergenic molecules of Phleum pratense among pediatric subjects allergic to grass pollen in a Mediterranean population. The correlation of sensitization to these Phleum allergenic molecules with IgE against grass pollen extract and its variation according to age and level of IgE against grass pollen extract were evaluated. RESULTS: IgE against to rPhl p 1 were found in 99% (205/207) of patients, to rPhl p 5 in 67% (139/207), to rPhl p 12 in 32% (66/207) and to rPhl p 7 only in 5% (10/207).Sensitization only to "Species Specific" (rPhl p1, rPhl p5) allergenic molecules of Phleum pratense was detected in 65% (135/207) of children. Our data show the predominant role of rPhl p 1 in pediatric populations as the most relevant sensitizing allergen detectable at all ages and at all levels of timothy grass pollen-specific IgE antibodies, while the importance of rPhl p 5 rises with the increase of patients' age and with grass pollen IgE levels. CONCLUSIONS: The assessment of sensitization to grass pollen allergenic molecules could help develop a better characterization of allergic sensitization in grass pollen allergy in children, which may be different in every patient. It could also enable clinicians to give more specific and effective immunotherapy, based on allergenic molecule sensitization.

Montelukast versus inhaled corticosteroids in the management of pediatric mild persistent asthma.

International guidelines recommend the use of inhaled corticosteroids (ICSs) as the preferred therapy, with leukotriene receptor antagonists (LTRAs) as an alternative, for the management of persistent asthma in children. Montelukast (MLK) is the first LTRA approved by the Food and Drug Administration for the use in young asthmatic children.Therefore, we performed an analysis of studies that compared the efficacy of MLK versus ICSs. We considered eligible for the inclusion randomized, controlled trials on pediatric populations with Jadad score > 3, with at least 4 weeks of treatment with MLK compared with ICS.Although it is important to recognize that ICSs use is currently the recommended first-line treatment for asthmatic children, MLK can have consistent benefits in controlling asthmatic symptoms and may be an alternative in children unable to use ICSs or suffering from poor growth. On the contrary, low pulmonary function and/or high allergic inflammatory markers require the corticosteroid use.

Growth failure in children with cystic fibrosis.

Poor linear growth and inadequate weight gain are very common problems in cystic fibrosis (CF) children. The most important factors involved in growth failure are undernutrition or malnutrition, chronic inflammation, lung disease, and corticosteroid treatment. Nutritional support and pharmacological therapy with recombinant human growth hormone are essential for a good management of children with CF, although these children are shorter and lighter than healthy children, and despite the catch-up growth observed after diagnosis, deficit in length/height and weight continues to be seen until adulthood. Early diagnosis is essential to ensure better nutritional status and growth, potentially associated with better respiratory function and prognosis. The aims of this review are try to explain etiology and pathogenetic mechanisms of growth failure in CF children and clarify their role in the disease morbidity and in clinical outcome, especially in relation to progressive decline of pulmonary function.

Relationship between exercise-induced bronchospasm (EIB) and asthma control test (ACT) in asthmatic children.

OBJECTIVE: Evaluate the relationship between Asthma Control Test™ (ACT) and exercise-induced bronchospasm (EIB) in 81 asthmatic children. METHODS: EIB was assessed in every patient by Balke protocol and asthma control was evaluated by ACT. Patients were divided into three groups: Group A (30 patients) with complete asthma control (ACT score = 25), Group B (37 patients) with partial asthma control (ACT score = 21-24), and Group C (14 patients) with poor asthma control (ACT score < 20). RESULTS: About 36% (11/30) of patients in Group A (with complete asthma control) tested positive for EIB, whereas 21% (8/37) in Group B (with partial asthma control) and 28% (4/14) in Group C (with poor asthma control) exhibited EIB. The percentage of positive EIB was very similar between the three groups with no differences between controlled, partially controlled, and uncontrolled asthma. Statistical evaluation by χ(2)-test between complete (ACT score = 25) and not complete asthma control (ACT score < 24) confirmed a statistically significant difference (p < .01) between the obtained data. CONCLUSIONS: It must be stated that ACT alone is not sufficient to evaluate asthma control in children correctly because it fails to detect EIB in a significant percentage of subjects.

FeNO as a Marker of Airways Inflammation: The Possible Implications in Childhood Asthma Management.

The aim of this study was to verify FeNO usefulness, as a marker of bronchial inflammation, in the assessment of therapeutic management of childhood asthma. We performed a prospective 1-year randomized clinical trial evaluating two groups of 32 children with allergic asthma: "GINA group", in which therapy was assessed only by GINA guidelines and "FeNO group", who followed a therapeutic program assessed also on FeNO measurements. Asthma Severity score (ASs), Asthma Exacerbation Frequency (AEf), and Asthma Therapy score (ATs) were evaluated at the start of the study (T1), 6 months (T2), and 1 year after (T3). ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 (p[T1-T2] = 0.0001, and p[T1-T3] = 0.01; p[T1-T2] = 0.0001; and p[T1-T3] < 0.0001, resp.). After six months of follow-up, we found a significant increase of patients under inhaled corticosteroid and/or antileukotrienes in the GINA group compared to the FeNO group (P = .02). Our data show that FeNO measurements, might be a very useful additional parameter for management of asthma, which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies, however, mantaining a treatment sufficient to obtain a meaningful improvement of asthma.

The reciprocal influences of asthma and obesity on lung function testing, AHR, and airway inflammation in prepubertal children.

Although asthma and obesity are among the major chronic disorders their reciprocal or independent influences on lung function testing, airways hyperresponsiveness (AHR) and bronchial inflammation has not been completely elucidated. In 118 pre-pubertal Caucasian children anthropometric measurements functional respiratory parameters (flow/volume curves at baseline and after 6-minute walk test [6MWT]) together with bronchial inflammatory index (FeNO) were assessed. The study population was divided into four groups according to BMI and the presence or absence of asthma: Obese asthmatic (ObA) Normal-weight asthmatic (NwA), Obese non-asthmatic (Ob), non-asthmatic normal-weight children (Nw). Baseline PEF and MEF(75) (%-expected) were significantly different across the four groups with significantly lower values of MEF(75) in ObA and Ob children when compared to Nw children (P = 0.004 and P = .0001, respectively) and this independent role of obesity on upper respiratory flows was confirmed by multiple analysis of covariance. After 6 MWT respiratory parameters decreased only in ObA and NwA children and 12 children presented a positive fall in FEV(1), in contrast no changes of respiratory function testing were detected in Ob and Nw children, and only 2 Ob children presented a significant fall in FEV(1). FeNO analysis demonstrated significantly higher values in ObA and NwA children when compared to Ob (P = 0.008 and P = 0.0002, respectively) and Nw children (P = 0.0001 and P = 0.0003, respectively), although a significant difference was found between Ob and Nw children (P = 0.0004). Multiple analysis of covariance confirmed an independent role of asthma on this parameter. In conclusion while AHR and airway inflammation are clearly associated with an asthmatic status, obesity seems to induce reduction of upper airways flows associated with a certain degree of pro-inflammatory changes.