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 beta2-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 percent) and 5 subjects of Group 2 (25 percent) 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.

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 microg/kg twice daily for 7 days and then 20 microg/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 microg 4 times daily) was administered during the first 3 days of the study and then as needed. At T0, 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.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children.

The effect over time of regular treatment with montelukast (MNT) in inhibiting exercise-induced bronchoconstriction (EIB) has never been evaluated in children. The aim of the present study was to examine the preventive effect of MNT against EIB in children at different time-points over a 4-week treatment period. Thirty-two asthmatic children (aged 6-12 yrs) were enrolled in a double-blinded, randomised, parallel group design to receive a 4-week treatment with MNT (5 mg chewable tablets administered once daily in the evening) or placebo. Exercise challenge was performed at baseline and after 3, 7 and 28 days of treatment, 20-24 h after dosing. MNT was significantly more protective than placebo against EIB at each time. The mean percentage drop of forced expiratory volume in one second (FEV1) was 24.6, 13.6, 12.0 and 11.6 for MNT, and 24.4, 22.4, 21.8 and 21.0 for placebo, at baseline and after 3, 7 and 28 days, respectively. For each drug, no significant difference in the percentage drop of FEV1 was found between different days. Regular treatment with montelukast provided significant protection against exercise-induced bronchoconstriction in asthmatic children over a 4-week period with no tolerance to the bronchoprotective effect.

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. METHODS: 1426 children referred to our Paediatric Asthma and Allergy Center because of allergic symptoms were examined. Bronchial asthma, allergic rhino-conjunctivitis, food allergy and atopic dermatitis were diagnosed with standardized methods. Atopy was diagnosed if at least one skin test was positive. RESULTS: Of the 1426 children examined, 629 (44%) were atopic and 769 (56%) were non-atopic. Asthma was diagnosed in the same proportion (i.e., 64%) of atopic and non-atopic children. However, after division into age groups, non-atopic asthma was significantly more prevalent (chi2 = 8.46) in children between 0 and 3 years old (group 1). On the other hand, atopy was significantly associated with asthma only in group 3 (odds ratio 1.85). Furthermore, a significant association with asthma symptoms was found for house dust mite (HDM) in group 3 (odds ratio 4.8). CONCLUSIONS: Asthma is related to atopy in pre-selected children only from the age of 7 years. House dust mite sensitization seems to be an important determinant of asthma in these "older" children.

[Treatment of bronchial asthma in chidren]. / Terapia dell'asma bronchiale in età pediatrica.

Asthma is a condition characterised by airways inflammation and bronchial hyperresponsiveness to specific and aspecific spasmogens associated with reversible airways obstruction. The bronchomotor tone is the result of an interaction between neurotransmitter release and local mediators. The efferent neurohumoral pathways to the muscular, vascular and glandular element include parasympathetic nerves, sympathetic nerves, and non-adrenergic non-cholinergic (NANC) neurotransmission. It is currently recognised that the alteration of these mechanisms can induce bronchial hyperresponsiveness that represents a characteristic feature of asthma. Asthma is common in children and its prevalence in this age group is increasing. The current therapy of asthma involves the use of anti-inflammatory drugs to control the underlying process (causal therapy) and the use of bronchodilators that provide rapid relief of bronchoconstriction (symptomatic therapy). The bronchodilators are represented by beta 2 adrenergic agonists, methylxanthines and anti-cholinergic drugs; the anti-inflammatory drugs are represented by corticosteroids, antileukotrienes and chromones. Other new therapies being studied include anti-immunoglobulin E, anti IL-5 agents, endothelin receptor antagonists, and others.

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 mug/day. Values for FEV(1), 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 mu/day). Authors conclude that NED could have a steroidsparing effect over long-term use.

Choroidal lacunae and Aicardi's syndrome.

Three children with flexion spasms and an ophthalmologic picture characterised by choroidal lacunae are described. Aicardi's syndrome was diagnosed in two cases. A diagnosis of Aicardi's syndrome should include CT scan and/or pneumoencephalographic findings of partial or total agenesis of the corpus callosum and/or other anomalies of the interhemispheric structures. Choroidal lacunae are not entirely pathognomonic.