Alessandro Bodini

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.

Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.

Prevalence and risk factors for atopic dermatitis in preschool children.

Background  Atopic dermatitis (AD) is a common condition in infancy which usually disappears by 3 years of age in a significant proportion of children. The prognosis is mostly determined by severity and presence of atopic sensitization.

Exhaled air temperature in asthma: methods and relationship with markers of disease.

Background Exhaled breath temperature has been proposed as a surrogate marker for the evaluation of airway inflammation in asthmatic patients.

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children

Background:  The Childhood Asthma Control Test (C‐ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C‐ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function.

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

Cysteinyl leukotrienes (cys‐LTs), LTB4 and 8‐isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys‐LTs, LTB4 and 8‐isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756  m). Sputum eosinophil percentage and measurement of cys‐LTs, LTB4 and 8‐isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 ± 1.1% at T0 and 3.5 ± 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 ± 0.5% at T0 and 1.5 ± 1.0% at T1 (ns). Cys‐LTs mean level was 14.24 ± 4.53 pg/ml at T0 and 4.65 ± 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 ± 0.19 pg/ml at T0 and 2.41 ± 0.23 pg/ml at T1 (ns). 8‐Isoprostane level reduced from 17.47 ± 3.18 pg/ml at T0 to 7.36 ± 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys‐LTs and 8‐isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non‐invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Mite avoidance can reduce air trapping and airway inflammation in allergic asthmatic children

Background We investigated the effects of prolonged allergen avoidance in 18 house dust mite‐sensitized asthmatic children during a prolonged residential period at a high altitude, allergen‐free environment.

Flunisolide decreases exhaled nitric oxide and nitrotyrosine levels in asthmatic children.

Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects.

Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma

Airway inflammation is a characteristic of asthma. Exhaled nitric oxide (eNO) has been demonstrated to be related to actual levels of airway inflammation in asthmatic patients. The purpose of this study was to investigate whether the temperature of exhaled air is related to eNO levels. Temperature of exhaled air and eNO were measured in 52 asthmatic children with a cross-sectional design. A significant relationship was demonstrated between eNO and temperature of peak and plateau exhaled air temperature. The relationship between both the peak and the plateau values and eNO was more evident when it was corrected for environmental temperature. These results suggest a relationship between exhaled nitric oxide and the temperature of exhaled air in asthmatic patients not treated with systemic steroids.

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.