A.F. Capristo

Fractional Exhaled Nitric Oxide (FENO), Lung Function and Airway Hyperresponsiveness in Naïve Atopic Asthmatic Children

Background. Measurement of fractional exhaled nitric oxide (FENO) is a noninvasive, simple, well‐tolerated, and reproducible marker of airway inflammation. Asthmatic children with normal respiratory function could be affected by airway inflammation. The aim of this study was to assess the correlation between FENO and bronchial hyperesponsiveness (BHR) to methacholine, and between FENO and lung function in atopic children with intermittent asthma. Methods. Thirty‐seven children (21 male), aged 7.2–14.4 years (median: 10.9 years), suffering from mild intermittent atopic asthma with a physician‐diagnosed history of wheezing and/or chest tightness were studied. None had taken anti‐asthmatic therapy for at least three months before the study. No child had symptoms of respiratory tract infection in the month before the study. All subjects underwent FENO measurement, pulmonary function testing and the methacholine provocation tests. Results. The mean percentages of FEV1 and FEF25–27 were 91.9 ± 10.5 and 88.3 ± 11.8, respectively. The mean FENO was 62.2 ± 39.2 ppb and PC20 methacholine was 0.93 mg/ml ± 0.54. Significant correlations were identified between FENO and FEV1 (p < 0.0059, r = 0.468) and between FENO and FEF25–75 (p < 0.0098, r = 0.439). There was no correlation between FENO and logPC20 (p = 0.14). Conclusions. A single FENO measurement is probably of scarce prognostic and predictive value and it is not surprising to find discordance with BHR. We suggest that FENO measurement could represent a good marker of airway inflammation also in naïve atopic children with intermittent asthma. Repeated measurements over time are probably necessary to understand better the clinical implications of the data obtained in this study.

Atopy and house dust mite sensitization as risk factors for asthma in children

Background:Recent evidence suggests that asthma is not invariably related to atopy. The aim of this study was to evaluate the frequency of atopy, asthma and sensitization to eight common allergens in a large group of children with allergic symptoms.

Leukotriene modifiers in the treatment of asthma in children

Asthma is one of the most common respiratory disorders in clinical practice, affecting up to 13% of people worldwide. Inflammation is the most important component of asthma and inhaled corticosteroids (ICS) are recommended as the first line controller treatment for patients of all ages. Treatment with corticosteroids is often unable to fully control asthma symptoms and progression. Recently, leukotrienes have come to the forefront of research as they have been found play a pivotal role in the airway inflammatory process, and specific drugs have been developed to target them. Cysteiny leukotriene antagonists (LTRAs) have recently emerged as important therapeutic options that show a large potential clinical utility. Three specific LTRAs are licensed for clinical use: montelukast, zafirlukast and pranlukast, although montelukast is the only drug approved in the paediatric age range. It is well tolerated (although adverse effects such as headaches, abdominal pain, rashes, angioedema, pulmonary eosinophilia and arthralgia have been reported) and shows many positive effects in asthmatic patients. Current Global Initiative for Asthma guidelines recommend LTRAs as: (1) a second choice treatment to ICS for patients with mild persistent asthma, (2) an add-on therapy to reduce the dose of ICS in patients with moderate or severe asthma, due to the different and complementary mechanisms of action of these agents. LTRAs may be particularly appropriate choices in a number of clinical situations, including the following: patients with concomitant rhinitis; patients with viral-induced wheeze; patients with exercise-induced bronchoconstriction (EIB) and, in children aged 2-5 years, to reduce the frequency of asthma exacerbations.

Neutrophilic Cells in Sputum of Allergic Asthmatic Children

Airway inflammation is regarded as a central feature of asthma and is mostly sustained by eosinophilic infiltrate. Recent studies have shown that a co-activation of eosinophil- and neutrophil-dependent inflammatory mechanisms might explain why some asthmatics do not respond to conventional asthma therapy. The aim of our study is to determine whether neutrophilic inflammation was involved in 55 allergic children with mild-moderate persistent asthma and the relationship with the response to steroid treatment. Before the sputum analysis, all children underwent spirometry with the reversibility test, and were divided into two groups on the basis of the response (such as >12% of baseline FEV1): group 1 positive and group 2 negative. Eosinophil cationic protein concentrations were measured by radioimmunoassay and neutrophyl myeloperoxidase (MPO) concentrations were measured by an MPO-EIA. Ten healthy children of comparable ages served as control group. Total IgE, FEV1 and FEV/FVC values were similar in both groups. The sputum macrophage count was higher in controls than in allergic asthmatics, but there was no difference between groups 1 and 2 (59.6% vs 18.3% and 17%; p≤ 0.005). Sputum neutrophils were significantly higher in group 2 both vs controls (62% vs 34%; p≤ 0.005) and vs group 1 (62% vs 37%; p≤ 0.005). Our data suggest that neutrophils are involved in airway allergic inflammation in mild-moderate persistent childhood asthma and a high neutrophil count in sputum may be related to a lower responsiveness to inhaled corticosteroids.

High-dose inhaled flunisolide versus budesonide in the treatment of acute asthma exacerbations in preschool-age children.

The role of inhaled corticosteroids in asthma exacerbation is debated. We compared high doses of nebulized budesonide versus high doses of nebulized flunisolide, in association with a short-acting beta-2-agonist, in the treatment of moderate asthma exacerbation in preschool children. In this randomized, parallel group, simple blind study, 46 children aged between 3 and 5 years affected by an acute moderate asthma attack were treated with nebulized flunisolide (Group 1) 40 μg/kg twice daily for 7 days and then 20 μg/kg twice daily for 14 days, or with nebulized budesonide (Group 2) 0.5 mg twice daily for 7 days then 0.25 mg twice daily for 15 days. Inhaled salbutamol (MDI+ spacer − 200 μg 4 times daily) was administered during the first 3 days of the study and then as needed. At TO, T7 and T21 days, airway resistances were evaluated with the forced oscillation technique before and after inhalation of inhaled salbutamol (200 mcg). Parents recorded symptoms and drug use on a diary card. Forty children completed the study. Airway resistances were significantly reduced at T7 (p< 0.01 flunisolide; p< 0.05 budesonide) and T21 (p< 0.05 flunisolide; p< 0.05 budesonide) versus T0 in both groups, although at T7 the reduction occurred faster in group 1 than in group 2 (p<0.01). During the first 7 days of treatment, symptom scores decreased in both groups; however, the decrease was greater in group 1 (p< 0.05). High doses of inhaled flunisolide and budesonide are both effective in the management of moderate asthma exacerbations in pre-school-age children, but the flunisolide therapeutic effect was faster than budesonide.

Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use.

Evaluation of bronchial hyperreactivity with mannitol dry powder challenge test in a paediatric population with intermittent allergic asthma or allergic rhinitis.

We evaluated the bronchial hyperreactivity (BHR) with a new bronchial challenge test, mannitol dry powder, in a paediatric population with intermittent allergic asthma or allergic rhinitis who did not respond to an exercise challenge test. We selected 50 children, aged 9–16 years, with intermittent allergic bronchial asthma (Group 1) or allergic rhinitis without clinical manifestation of asthma for at least 12 months (Group 2). All patients performed the following tests in three different days (> 48 hours apart): Day 1: exhaled nitric oxide (FeNO) determination followed by baseline spirometry and reversibility to inhaled β2-agonists; Day 2: exercise challenge test followed by FeNO determination; Day 3: mannitol challenge test followed by FeNO determination. Forty children completed the study. Eighteen subjects of Group 1 (90%) and 5 subjects of Group 2 (25%) resulted positive to the mannitol test. Positive mannitol challenge subjects showed no statistically significant differences compared to negative subjects as regard baseline spirometry, reversibility to salbutamol and response to the exercise challenge test, but they had significantly higher FeNO values. In conclusion, the mannitol challenge test can be a diagnostic tool more useful than the exercise challenge test to identify BHR in a paediatric population with intermittent allergic asthma or allergic rhinitis because it is better reproducible, quick and easy to perform and well tolerated.