Association between individual sensor behavior of an electronic nose and airways inflammation in children with asthma: a pilot study at alpine altitude climate.

BACKGROUND: Markers of airway inflammation can be helpful in the management of childhood asthma. Residential activities, such as intensive asthma camps at alpine altitude climate (AAC), can help reduce bronchial inflammation in patients who fail to achieve optimal control of the disease. Analysis of volatile organic compounds (VOCs) can be obtained using electronic devices such as e-Noses. We aimed to identify alterations in urinary e-Nose sensors among children with asthma participating in an intensive camp at AAC and to investigate associations between urinary e-Nose analysis and airway inflammation. METHODS: We analyzed data collected in children with asthma recruited between July and September 2020. All children were born and resided at altitudes below 600 m asl. Urinary VOCs (measured using the Cyranose 320® VOC analyzer), Fractional exhaled Nitric Oxide (FeNO) and spirometry were evaluated upon children's arrival at the Istituto Pio XII, Misurina (BL), Italy, at 1756 m asl (T0), and after 7 (T1) and 15 days (T2) of stay. RESULTS: Twenty-two patients (68.2% males; median age: 14.5 years) were enrolled. From T0 to T1 and T2, the negative trend for FeNO was significant (p < .001). Significant associations were observed between e-Nose sensors S7 (p = .002), S12 (p = .013), S16 (p = .027), S17 (p = .017), S22 (p = .029), S29 (p = .021), S31 (p = .009) and ΔFeNO at T0-T1. ΔFeNO at T0-T2 was significantly associated with S17 (p = .015), S19 (p = .004), S21 (p = .020), S24 (p = .012), S25 (p = .018), S26 (p = .008), S27 (p = .002), S29 (p = .007), S30 (p = .013). CONCLUSIONS: We showed that a decrease in FeNO levels after a short sojourn at AAC is associated with behaviors of individual urinary e-Nose sensors in children with asthma.

A positive effect of a short period stay in Alpine environment on lung function in asthmatic children.

Lung function is a central issue in diagnosis and determination of asthma severity and asthma control has been previously reported to improve after a stay in mountain environment for at least 2 weeks. No data are available for shorter periods of stay, in particular for small airways during a stay at altitude. The aim of this study is to focus on changes in respiratory function, regarding both the central airways and the peripheral airways in the first 2 weeks of stay in a mountain environment in asthmatic children. In this study, 66 asthmatic children (age: 14 ± 2.8 years) were evaluated through spirometric and oscillometric tests at the time of arrival at the Istituto Pio XII, Misurina (BL), Italy, 1756 m above sea level (T0), after 24 h (T1), and 168 h (T2) of stay. FEV1%, FEF25%-75%, and FEV1/FVC increased significantly from T0 value both at T1 and T2 (respectively, p = 0.0002, p < 0.0001, p = 0.0002). Oscillometry showed a significant improvement in R5, R20, and R5-20 at both T1 and T2 as compared to T0 (respectively, p = 0.0001, p = 0.0002, and p = 0.049). Reactance at 5 Hz (X5) improved significantly at T2 versus T0, p = 0.0022. The area under reactance curve between Fres and 5 Hz (AX) was significantly reduced (p = 0.0001) both at T1 and T2 as compared to T0. This study shows an improvement in respiratory indices as soon as after 24 h of stay at altitude, persisting in the following week.

Macrophage Phagocytosis and Allergen Avoidance in Children With Asthma.

Background and Objective: Airway macrophages perform the crucial functions of presenting antigens, clearing pathogens, and apoptotic cells. Macrophage phagocytosis is increased in adults with mild asthma and allergen exposure is known to activate macrophages. However, it is not clear whether the mechanism behind this is due to a primary defect or environmental factors such as allergen or lipopolysaccaride (LPS) exposure. Our aim was to assess the phagocytic function of airway macrophages in children with mild to moderate asthma after residence in a low allergen\LPS environment at high altitude. Methods: Sputum induction was performed in children with asthma at baseline and after residence for a 3 weeks' period at a high-altitude asthma center that has very low ambient allergen levels. The markers of eosinophilic inflammation (including percentage of macrophage cytoplasm with red hue) and phagocytosis of fluorescein isothiocyanate-labeled, heat-killed Staphylococcus aureus by airway macrophages was analyzed. Internalized bacteria were quantified using confocal microscopy. Results: The median bacterial count [mean (standard deviation)] per macrophage was significantly lower [39.55 (4.51) vs. 73.26 (39.42) (p = 0.006)] after residence at high altitude. No association was observed between markers of eosinophilic inflammation and bacterial phagocytosis. Conclusions: The results suggest that the mechanism behind the enhanced phagocytosis of bacteria in childhood asthma may be secondary to allergen or possibly LPS exposure.

Eosinophilic airway inflammation is increased in children with asthma and food allergies.

BACKGROUND: Asthma is associated with food allergies in a significant number of children, with evidence linking allergies to asthma severity and morbidity. In this study, we tested our hypothesis that the eosinophilic lower airway inflammation is higher in asthmatic children with food allergies. AIMS: The aims of the study were to compare the eosinophilic inflammatory markers in asthmatic children with and without food allergies. MATERIALS AND METHODS: Children with asthma, with (n = 22) and (n = 53) without food allergies were included. All subjects were classified according to the GINA guidelines (2009) and had received at least 3 months of anti-inflammatory therapy prior to testing. Fractional exhaled nitric oxide and sputum differential counts were performed using standard techniques. RESULTS: Children with asthma and food allergies had significantly higher fractional exhaled nitric oxide median (range) [(22.4 (6.1-86.9) vs. 10.3 (2.7-38.7) (p = 0.01)] and sputum eosinophil percentage [15.5 (5.0-53.0) vs. 2.0 (0-20) (p < 0.001)] compared with asthmatic children without allergies. CONCLUSION: These results suggest that the children with asthma and food allergies have increased eosinophilic inflammation of the airways.

Exhaled nitric oxide daily evaluation is effective in monitoring exposure to relevant allergens in asthmatic children.

BACKGROUND: Though asthma is an airway inflammatory disease, the assessment of treatment efficacy is mainly based on symptom monitoring and the evaluation of lung function parameters. This study was aimed to evaluate the feasibility of exhaled nitric oxide monitoring in allergic asthmatic children who were exposed to relevant allergens in their homes. METHODS: Twenty-two children allergic to mites underwent twice-daily fractional exhaled nitric oxide (FeNO) therapy using a portable device (NIOX MINO; Aerocrine AB; Stockholm, Sweden) and peak expiratory flow (PEF) measurements before, during, and after periods of natural exposure to mite allergens. The children were admitted to the study if they had lived in a mite-free environment for 3 months. They were observed in this environment for 10 days and then were moved to a site with natural mite exposure at sea level for 19 days. Finally, they were relocated to the mite-free environment for a period of 6 days for follow-up measurements. RESULTS: Significant differences were seen between the mite-free baseline FeNO level (26.4 parts per billion [ppb]; range, 19.3 to 36.2 ppb) and FeNO levels measured during natural mite exposure (37.3 ppb; 27.3 to 51 ppb) and after natural mite exposure (34.9 natural mite exposure; 25.2 to 48.2 ppb). Six children reported asthma symptoms during the mite exposure, and an increase in FeNO was observed in each case (p<0.031); PEF values showed no significant differences, whether between the different environments or between different periods. CONCLUSIONS: These data give further evidence for a possible role of frequent determinations of FeNO in order to promptly assess changes in the level of airway inflammation in asthmatic children.

Azithromycin reduces bronchial hyperresponsiveness and neutrophilic airway inflammation in asthmatic children: a preliminary report.

Macrolide antibiotics have immunomodulatory effects that may be beneficial to patients with chronic inflammatory pulmonary conditions. The aim of this study was to evaluate the effects of azithromycin on lung function, bronchial hyperresponsiveness (BHR), and airway inflammation in asthmatic children. Sixteen asthmatic children were treated with either azithromycin or placebo for 8 weeks. Lung function, BHR expressed as the dose-response slope (DRS) of forced expiratory volume in 1 second (FEV1) fall after hypertonic saline inhalation (DRS), and induced sputum were evaluated at baseline and after treatment. No significant change was observed in lung function before and after treatment. DRS (percent fall of FEV1/mL) decreased from (X +/- SD) 2.75 +/- 2.12 to 1.42 +/- 1.54 (p = 0.02) in azithromycin-treated children but not in the placebo group, which was 1.48 +/- 1.75 at baseline and 1.01 +/- 1.38 at the end of the study period. Neutrophil leukocytes decreased significantly in the azithromycin-treated group from 10 +/- 5.3% to 2.2 +/- 2.4% (p < 0.01) but not in the placebo group, with 7.2 +/- 4.2% at baseline and 3.3 +/- 3.6% at the end of the study. A short course of azithromycin is associated with amelioration of BHR and reduction in airway neutrophil infiltration in some children with asthma.

Passive smoking in asthmatic children: effect of a "smoke-free house" measured by urinary cotinine levels.

Environmental tobacco smoke (ETS) decreases pulmonary function and increases both airway reactivity and frequency of child asthma exacerbations. True exposure is related not only to parents smoking and to the number of cigarettes that they smoke, but also to involuntary smoking in public places. The aim of this study was to evaluate, by measuring urinary cotinine levels, the exposure to ETS in asthmatic children and the contribution of unapparent smoke exposure. Twenty asthmatic children (aged 7-12 years) were evaluated on the 1st day (TO) and after a week (T1) in a "smoke-free house." The mean level of urinary cotinine in children was 15.8 +/- 2.7 ng/mg of creatinine at TO and 4.2 +/- 0.6 ng/mg of creatinine at T1 (p < 0.0001). The urinary cotinine concentrations were higher in children living with smoking parents (21.8 +/- 3.4 ng/mg creatinine) compared with children not exposed to parental smoke (6.8 +/- 3.0 ng/mg creatinine; p = 0.017). The number of cigarettes smoked by parents correlates with the urinary cotinine levels (p = 0.005; r = 0.64). Urinary cotinine levels significantly decreased after the avoidance of ETS in children exposed to parental smoke (21.8 +/- 3.4 ng/mg at TO; 5.0 +/- 0.8 ng/mg at T1; p < 0.001) and also in children whose parents declared to be nonsmokers (6.8 +/- 1.2 ng/mg at TO; 3.0 +/- 0.8 ng/mg at T1; p = 0.006). Our data confirm the widespread indirect and undetected tobacco smoke exposure in children with chronic asthma and the relevance of an evaluation with an objective method of the exposure to second-hand smoke.

Montelukast versus formoterol as second-line therapy in asthmatic children exposed to relevant allergens.

In sensitive asthmatic children, the exposure to relevant allergens causes a deterioration of lung function and symptoms associated with an increase of inflammatory indices. The aim of this single-blind randomized add-on study was to compare the effects of montelukast or formoterol added to low-dose budesonide in asthmatic allergic children exposed to relevant allergens. Twenty children (5 female subjects and 15 male subjects, aged 6-12 years) were enrolled. Lung function and airway inflammatory indices (exhaled nitric oxide [eNO] and sputum eosinophils) were evaluated at T0 when children were not exposed to relevant allergens and at T1 after 15 days of natural effective allergen exposure. At T1, pulmonary function tests and sputum eosinophils remained stable in both of the groups, without significant differences in comparison with T0 at baseline. Furthermore, formoterol plus budesonide was effective in preventing the expected increase in eNO from 26.46 +/- 2.62 ppb at T0 to 29.33 +/- 9.28 ppb at T1 (not significant). However, in the group receiving montelukast plus budesonide, there was a significant decrease of eNO from baseline (30.78 +/- 6.87 ppb) to T1 (18.17 +/- 6.60 ppb) (p < .05). In allergic asthmatic children, the use of montelukast or formoterol combined with budesonide could offer a durable protective effect on symptoms, lung function, and inflammatory indices.

Improved bronchodilator effect of deep inhalation after allergen avoidance in asthmatic children.

BACKGROUND: In healthy adults and children, deep inhalation (DI) is able to reverse induced bronchoconstriction. This ability is impaired in asthma, but the reasons are still to be elucidated. OBJECTIVES: This study investigated whether the bronchodilator effect of DI during methacholine-induced bronchoconstriction can be improved by allergen avoidance in asthmatic children, and its relationship with airway inflammation. METHODS: The effect of DI on methacholine-induced bronchoconstriction was studied at the beginning and the end of a 3-month allergen avoidance period at high altitude in 14 allergic asthmatic children who had severe asthma attacks. Changes in airway caliber were inferred from the respiratory resistance (Rrs) measured by a forced oscillation technique. Results were related to the percentage of eosinophils in induced sputum and compared with those obtained in 9 age-matched nonasthmatic children. RESULTS: In asthmatic subjects, DI had no significant effect on methacholine-induced increase in Rrs before (P=.62) but significantly reversed it after (P <.01) allergen avoidance. However, the ability of DI to reverse a methacholine-induced increase in Rrs tended to remain less in asthmatic than nonasthmatic children even after allergen avoidance (P=.05). In the asthmatic children, the percentage of eosinophils in induced sputum was decreased at the end of the allergen avoidance period (P <.001), without any significant correlation between sputum eosinophils and airway responsiveness to methacholine or effect of DI. CONCLUSION: A short period of allergen avoidance may improve the ability of DI to reverse induced bronchoconstriction in some asthmatic children. This effect is associated, yet not correlated, with a reduction in airway inflammation.

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens.

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before (t0) and immediately after (t1) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t0 and t1, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.