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.

Sublingual immunotherapy in children with allergic polysensitization.

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1.

Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype.

Pediatric asthma evaluation: what's to be considered?

The increasing evidence that asthma begins very early in childhood leads the need for having outcome's measures able to identify the early damage and its evolution both for research than for clinical purposes. The current available methods are clinical questionnaires, pulmonary function tests, airway reactivity tests and direct or indirect inflammation markers' measures. Among the first, ISAAC questionnaire, for epidemiological purpose, Asthma Control Test, for clinical monitoring and Health Related Quality of Life questionnaire are the most used. There are many pulmonary function tests that may be used in all age for functional evaluation, but airway responsiveness measures may be commonly performed only in school age children. As regards respiratory inflammation measures the only currently useful is the exhaled nitric oxide evaluation. The complexity of the pathogenic mechanisms, molecular, cellular and inflammatory that realize the asthmatic syndrome and the effects of the disease on respiratory function, on the activity of the child, on the quality of life of the family and on the economic costs to society show that there is no a single outcome measure that can evaluate all these effects simultaneously.

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.

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.

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.

Comparison of add-on therapy to inhaled fluticasone propionate in children with asthma: residual volume and exhaled nitric oxide as outcome measures.

The purpose of this study was to evaluate changes in lung function and fractional exhaled nitric oxide (FeNO) in children with mild to moderate persistent asthma treated with low-dose inhaled steroids but still manifesting significantly increased residual volume (RV). This was a crossover study evaluating lung function and FeNO before and after a 2-week crossover therapy period by adding either montelukast or salmeterol to inhaled fluticasone propionate in 12 children with asthma. Salmeterol increased forced expiratory volume at 1 second (FEV(1)) and decreased RV without effects on eNO. Addition of montelukast produced a statistically significant decrease both for RV (from 191.7 +/- 60.8% to 132.4 +/- 36.1%; p = 0.03) and for eNO (from 14.0 +/- 6.3 ppb to 8. 5+/- 5.0 ppb; p < 0.01). No effect was observed for the montelukast treatment period in FEV(1) and forced expiratory flow at 25-75%. Add-on therapy may reduce RV and decrease levels of FeNO, leading to consideration of a possible anti-inflammatory additive effect that could improve the control of the disease.

Functional assessment of allergic asthmatic children while asymptomatic.

The aim of this study was to detect the best test lung function to identify abnormalities in asthmatic children while asymptomatic. We studied 200 asthmatic children. Patients were evaluated by questionnaire to evaluate the presence of symptoms and drug consumption in the previous 3 months. Allergological evaluation by skin-prick tests and seric-specific IgE determination for relevant local inhalant allergens was made. Lung function was studied evaluating expiratory flows and measuring lung volumes by nitrogen washout technique. One hundred twenty-seven of 200 (63%) children showed functional abnormalities: 21 (10.5%) children had flow reductions, 56 (28%) children had volume modifications, and 50 (25%) children had either flow and lung volume alterations, respectively. We observed increased total lung capacity (TLC), residual volume (RV), and ratio RV/TLC values more often in patients with mild and moderate persistent asthma than in patients with intermittent asthma. No significant difference was detected considering expiratory flows. Measurements of lung volumes are an important tool to evaluate "air trapping" in asthmatic patients and this could be related to disease severity. According to the literature, our data suggest that an increase of RV, functional residual capacity RV/TLC could be the only functional airway dysfunction present in asthmatic children during asymptomatic period.