Giorgio Piacentini

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting β2-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9–8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4–11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FENO levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

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.

Current evidence and future research needs for FeNO measurement in respiratory diseases

Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.

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.

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.

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.

Changes in nasal specific IgE to mites after periods of allergen exposure‐avoidance: a comparison with serum levels

Variations of serum and nasal specific IgE to Dermatophagoides pteronyssinus (Der p) during alternate periods of antigen avoidance exposure have been evaluated with an open design in a group of allergic children with asthma and rhinitis at the residential house Istituto Pio XII (Misurina, BL, Italy), at 1756 m. in the Italian Dolomites. A method based on direct incubation of allergen coupled substrate on the nasal mucosa has been employed to evaluate the levels of nasal IgE. Serum specific IgE decreased respectively from (median) 117‐89.3 kU/l (P < 0.001) during an initial period of 3 months of allergen avoidance and from 88.2 to 78.4 kU/l (P < 0.0002) during a subsequent period of allergen avoidance. No significant increase in serum specific IgE was, in contrast, observed during two periods, 22 and 9 days, of antigen exposure, changing respectively from 89.3 to 88.2 and from 78.4 to 89 1 kU/l. In contrast, nasal IgE has been significantly influenced by the alternate periods of antigen exposure‐avoidance, showing a decrease from 19.75 to 4.01 kU/l (P < 0.0001) after the initial period of avoidance, followed by an increase to 9.95 kU/l (P < 0.0001) after 22 days of exposure. A significant decrease to a value of 2.37 kU/l (P < 0.0001) was also observed during the subsequent period of avoidance, followed again by an increase to 7.87 kU/l (P < 0.002) after 9 days of exposure. The evaluation of the kinetics of changes in nasal specific IgE revealed a significant decrease (P < 0.01) as soon as antigen avoidance was implemented for 3 days. Nasal specific TgE, therefore, appears to be a more sensitive index of antigen exposure avoidance than serum IgE levels.

Time efficacy of a single dose of montelukast on exercise‐induced asthma in children

The aim of this study was to evaluate the timing of onset and the duration of action of a single oral‐dose treatment with montelukast in comparison to placebo on exercise‐induced asthma (EIA) in asthmatic children. Nineteen children (7–13 years) with stable asthma were evaluated. Patients undertook three consecutive treadmill exercise tests, respectively, 2, 12 and 24 h after a single‐dose administration. A double‐blind randomized, single‐dose, placebo‐controlled, crossover design was used. To assess bronchoconstriction after the exercise challenge, the maximal percentage fall in FEV1 (ΔFEV1) from the baseline value was considered. Two hours after dosing, ΔFEV1 was −15.33 ± 2.93 for placebo and −13.33 ± 2.03 for montelukast. At 12 h, ΔFEV1 was −18.69 ± 2.83 for placebo, −9.78 ± 1.85 for montelukast (p < 0.005). No difference was observed between placebo (ΔFEV1−10.21 ± 2.07) and montelukast (ΔFEV1−9.10 ± 2.02) at 24 h. Analysis of the degree of protection showed a significant efficacy of montelukast (p = 0.02) in comparison with placebo only at 12 h. Montelukast showed a significant protective effect 12 h after dosing, but no effect after 2 and 24 h. In mild asthmatics, the timing of administration of single dosage before exercise should be strictly considered in order to obtain the drug protective effects.

Monitoring asthma in children

The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence. ERS statement summarising and discussing the available literature on monitoring children with asthma http://ow.ly/H01NG