Flow dependency and off-line measurement of exhaled NO in children

Levels of exhaled nitric oxide (eNO) are flow-dependent, and the choice of an optimal flow rate for off-line and on-line eNO measurement has raised much debate. Recently, a flow rate of 50 ml/s was recommended, but children younger than 5–6 years are not capable of stabilizing their expiratory flow at low flow rates. The power of off-line eNO values to discriminate between normal and atopic children was therefore evaluated at different exhalation flow rates. At flow rates of both 8.3 ml/s and of 350 ml/s, children (8–12 years) sensitive to house dust mite have two-fold higher eNO values (p < 0.001) as compared with children lacking such a sensitivity. The power of eNO to discriminate between normal and atopic subjects was similar at the two flow rates (no difference in AUC of receiver operation curves, p = 0.89). All children from 4.5 to 5 years of age (n = 29) could perform a single off-line exhalation manoeuvre at high (>350 ml/s) but not at low (8.3 ml/s) flow rates. At high exhalation flow rate, eNO was 7.1 ± 2.4 (mean ± SD) median, 6.5 p.p.b. with a mean variation coefficient of 5.5%. Depending on their developmental level, about half of the younger children (35–46 months of age) could perform an off-line exhalation manoeuvre at high flow rate with good reproducibility (mean variation coefficient of 6.6%). It is concluded that an exhalation flow rate of 350 ml/s is feasible to determine off-line eNO-values in children from 3.5 years of age, and that this high flow rate does not compromise the power of eNO to detect allergic disease.     

Exhaled nitric oxide and exercise-induced bronchoconstriction in young wheezy children – interactions with atopy

The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FE_NO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FE_NO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FE_NO by standard online technique. Although FE_NO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FE_NO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FE_NO and the severity of EIB was found ( r  = 0.44, p = 0.0004), and FE_NO was significantly predictive of EIB. No clear association between FE_NO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FE_NO levels. However, the association between the severity of EIB and FE_NO is present and FE_NO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze.     

Exhaled nitric oxide in asthmatic and non-asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smoke

Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3–14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin‐prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1‐l mylar bags (exhaled pressure 10 cmH₂O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non‐atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non‐atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7–1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non‐atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non‐atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2–3.9, p= 0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30–0.29), and with the sum of all wheals (r = 0.47) (p= 0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non‐atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1–2.3, p= 0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt‐sensitized subjects: 28.0 p.p.b.; Dpt‐unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5–3.5, p= 0.000). Non‐asthmatic Dpt‐sensitized subjects also had significantly higher eNO values than non‐asthmatic, non‐Dpt‐sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1–1.9, p= 0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house‐dust mite allergen.     

Exhaled nitric oxide in healthy young children during tidal breathing through a facemask

The aim of this study was to establish reference values and to examine day-to-day and within-day variations of exhaled nitric oxide (eNO) during tidal breathing in healthy children using a newly described method. Exhaled NO was measured on-line and off-line during tidal breathing through a facemask. In a subgroup of children measurements were repeated during the course of a single day and on the same time on three consecutive days. A total of 133 healthy children were included in the study and measurements were obtained from 121 children aged 2-7 yr (61 boys and 60 girls). The geometric mean eNO concentration and 95% CI was 3.9 (3.5-4.2) parts per billion (p.p.b.) for on-line measurements and 3.0 (2.7-3.3) p.p.b. for off-line measurements. Exhaled NO was independent of gender, age, height and weight. The 95% reference intervals (RI) for on-line and off-line measurements were 1.2-8.2 and 1.3-7.1 p.p.b. respectively. Twenty-three children completed measurements of within-day and day-to-day variations, none of which showed significant variation. In conclusion, the established reference values and data on variability within and between days may facilitate the clinical application for measurement of eNO during tidal breathing in young children.     

哮喘患儿呼出气一氧化氮及外周血嗜酸粒细胞的变化

目的：检测支气管哮喘（AS）,AS合并过敏性鼻炎（AS/AR）及慢性咳嗽变异性哮喘（CVA）患儿中呼出气一氧化氮（eNO）和外周血嗜酸粒细胞（EOS）的水平及两者的相关性,以探讨eNOS检测在AS儿童中的应用。方法：采用电化学法对5～14岁患有AS（n=12）、AS/AR（n=29）、CVA（n=10）的患儿进行eNO测定,同时测定EOS及一秒钟用力呼气容积占预计值百分比（FEV1％）。30例无特异性疾病史和家族过敏史,且近两周无急性呼吸道感染史的儿童作为对照组。结果：AS,AS/AR,CVA 3组eNO和EOS水平均高于对照组（P＜0.01）;AS/AR组eNO（50.3±6.7 ppb）和EOS水平（5.9±4.2×109）高于AS组（30.5±8.8 ppb,4.2±3.2×109）及CVA组（26.0±3.2 ppb,3.7±6.9×109）（均P＜0.05）,而AS、CVA组间差异无显著性;AS组eNO与EOS呈正相关（r＝0.51,P＜0.05）,但与FEV1无相关性（r＝0.144,P＞0.05）。结论：eNO在过敏性体质中高表达,且eNO可以反映AS患者气道嗜酸性炎症水平。［中国当代儿科杂志,2009,11（12）：986-988］     

NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children

Exhaled nitric oxide (FE_NO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FE_NO in adults with asthma and cystic fibrosis, was associated with the raised FE_NO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6–18 years) underwent measurements of FE_NO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FE_NO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FE_NO.     

Comparability of a hand-held nitric oxide analyser with online and offline chemiluminescence-based nitric oxide measurement

Practicability is crucial for successful implementation of fractional exhaled nitric oxide (FeNO) measurement into asthma management. The study aimed at comparing a conventional chemiluminescence NO analyser (EcoMedics^®) with a hand-held device (NIOX MINO^®) and offline FeNO measurement using a commercially available system in an unselected cohort of children aged 6–16 yr. A secondary objective was to confirm FeNO stability over time in 15 samples from adult volunteers obtained using the offline system. Sixty-six children (mean ± s.d. age 11.8 ± 3.0 yr) underwent single breath FeNO measurement in triplets with each device. Offline collected FeNO was measured after offline breath collection into a Mylar balloon and subsequent analysis using the chemiluminescence NO analyser. Variability and between-method agreement were assessed, and stability over time within the Mylar balloons was tested by repeated hourly measurements. FeNO levels ranged from 2 to 113 p.p.b. Intra-class correlation was excellent (r = 0.98, p <   0.001 for each pair). Bland–Altman plots and back-transformation of logarithmic mean differences revealed fair agreement between methods. Stability over time was confirmed over 10 h both at room temperature and when stored under cooling conditions. FeNO values obtained using the chemiluminescence NO analyser, the portable NIOX MINO^® system and the offline collection technique show between-method agreement within clinically acceptable range.     

Endogenous nitric oxide production in the airways of preterm and term infants

Few studies have measured endogenous nitric oxide exhaled from the respiratory system of newborn infants. We measured exhaled nitric oxide (eNO) in the first 48 h of life in 24 (13 preterm, 11 term) spontaneously breathing (online method) newborns using a chemoluminescence analyzer. There was a significant difference in the eNO concentration between term and preterm healthy infants in the first 2 days of life (repeated measures analysis of variance, p < 0.05). In term infants there is a peak eNO production in the first hours of life, suggesting a potential role in postnatal adaptation, while in preterm infants eNO production is almost absent at birth, and then gradually increases.     

在社区儿童哮喘诊断与管理中呼出气一氧化氮测定应用研究

目的 探讨呼出气一氧化氮（exhaled nitric oxide, eNO）体积分数在社区儿童的改变及对哮喘诊断与管理的价值。方法 2011年10月至2011年12月对来自北京西城区小学的7~12岁132例非哮喘儿童和93例哮喘儿童进行eNO测定、肺功能检测、过敏原皮肤点刺检查（skin prick test, SPT）以及病史询问和常规体检,观察eNO在社区非哮喘儿童和哮喘儿童的改变、影响因素及与临床情况的相关性。结果 非哮喘儿童与哮喘儿童eNO体积分数分别为（11.63±1.88）×10-9和（19.68±2.31）×10-9,其差异有统计学意义（P < 0.01）。在非哮喘儿童中,有鼻炎儿童的eNO为（17.49±2.02）×10-9,显著高于无鼻炎儿童（10.42±1.76）×10-9;特应性儿童的eNO为（16.12±1.98）×10-9,显著高于非特应性儿童（9.60±1.66）×10-9,差异均有统计学意义（P均 < 0.01）。在哮喘儿童中,伴有鼻炎与不伴有鼻炎儿童,其eNO水平分别为（19.54±2.31）×10-9、（20.09±2.25）×10-9,差异无统计学意义;但特应性儿童eNO水平显著高于非特应性儿童［分别为（23.06±2.18）×10-9、（8.75±1.86）×10-9,P < 0.01］;哮喘未控制儿童eNO为（25.09±2.31）×10-9,显著高于哮喘控制儿童［（17.21±2.22）×10-9,P < 0.05］;曾使用吸入激素与未曾使用吸入激素儿童,其eNO水平差异无统计学意义。无论是非哮喘儿童,还是哮喘儿童,其eNO水平与肺功能各参数间均无相关性。结论 eNO在社区特应性哮喘儿童中显著升高,并与哮喘控制与否有关。特应性是影响eNO水平的突出因素。在社区儿童中测定eNO有利于对儿童哮喘的进行早期诊断和分型,全面了解其过敏情况,从而改善哮喘的管理。     

Nitric oxide airway diffusing capacity and mucosal concentration in asthmatic schoolchildren

Asthmatic patients show increased concentrations of nitric oxide (NO) in exhaled air (Feno). The diffusing capacity of NO in the airways (Dawno), the NO concentrations in the alveoli and the airway wall, and the maximal airway NO diffusion rate have previously been estimated noninvasively by measuring Feno at different exhalation flow rates in adults. We investigated these variables in 15 asthmatic schoolchildren (8-18 y) and 15 age-matched control subjects, with focus on their relation to exhaled NO at the recommended exhalation flow rate of 0.05 L/s (Feno0.05), age, and volume of the respiratory anatomic dead space. NO was measured on-line by chemiluminescence according to the European Respiratory Society's guidelines, and the NO plateau values at three different exhalation flow rates (11, 99, and 382 mL/s) were incorporated in a two-compartment model for NO diffusion. The NO concentration in the airway wall (p < 0.001), Dawno (p < 0.01), and the maximal airway NO diffusion rate (p < 0.001) were all higher in the asthmatic children than in control children. In contrast, there was no difference in the NO concentration in the alveoli (p = 0.13) between the groups. A positive correlation was seen between the volume of the respiratory anatomic dead space and Feno0.05 (r = 0.68, p < 0.01), the maximal airway NO diffusion rate (r = 0.71, p < 0.01), and Dawno (r = 0.56, p < 0.01) in control children, but not in asthmatic children. Feno0.05 correlated better with Dawno in asthmatic children (r = 0.65, p < 0.01) and with the NO concentration in the airway wall in control subjects (r < 0.77, p < 0.001) than vice versa. We conclude that Feno0.05 increases with increasing volume of the respiratory anatomic dead space in healthy children, suggesting that normal values for Feno0.05 should be related to age or body weight in this age group. Furthermore, the elevated Feno0.05 seen in asthmatic children is related to an increase in both Dawno and NO concentration in the airway wall. Because Dawno correlates with the volume of the respiratory anatomic dead space in control subjects and Feno0.05 correlates with Dawno in asthmatic children, we suggest that Dawno partly reflects the total NO-producing surface area and that a larger part of the bronchial tree produces NO in asthmatic children than in control children.     

A methodology for measurements of nasal nitric oxide in children under 5 yr

Measurements of nasal nitric oxide (nNO) may give insight into respiratory conditions in children aged under 5 yr but no methodology has been described for this age-group. The present study aimed to establish the methodology and reproducibility for measuring nNO during tidal breathing in young children and to relate nNO to allergic conditions. Children and siblings aged under 5 yr attending hospital clinics were enrolled. On-line nNO measurements were obtained during tidal breathing using a chemiluminescence analyser. To establish our methodology, nNO was measured over 3, 5 or 10 s NO plateaus and nNO was also measured from left and right nostrils. nNO was then compared between children with and without allergic conditions. The reproducibility of nNO measurements over 24 h was studied in a separate group of children. Eighty-three children participated in the methodological part of the study and nNO was successfully measured in 57 (69%), mean (s.d.) age 3.4 (1.1) years, 14 with allergic conditions. Neither NO plateau duration nor choice of nostril influenced nNO values. The mean (s.d.) nNO for non-atopic children was 208 (103) parts per billion (ppb) and for atopic children was 284 (122), p = 0.032. Nasal NO values were not related to ambient NO, gender and passive smoke exposure; there was a non-significant trend for nNO to be positively related to age. Nasal NO measurements were reproducible in the 21 children tested, mean difference 9.6 ppb (limits of agreement-127, 146). We report a methodology for nNO measurement in young children. Further work is now required to establish the clinical utility of nNO in this age-group.     

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 ( t ₀) and immediately after ( t ₁) 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 t ₀ and t ₁, 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.     

哮喘儿童呼出气一氧化氮水平的测定

目的：　探讨哮喘儿童呼出气一氧化氮(exhalednitricoxide,eNO)水平及其意义。方法：　设定13～15cmH2O呼出气阻力以关闭软腭,用化学发光法测定34例6～14岁哮喘儿童和36名6～13岁非呼吸道疾病儿童单次呼吸的eNO浓度 ,同时测定一秒钟用力呼气容积占预计值百分比 (FEV1%)。结果：哮喘儿童的eNO浓度为 (89.4± 56 .4) ppb ,较非呼吸道疾病儿童eNO浓度 [(15 .8±5.8) ppb]显著增高 (P<0.01) ;哮喘儿童eNO浓度与FEV1%之间无显著相关性(r=0.06 ,P>0.05)。结论：　哮喘儿童eNO浓度高于正常,其变化与FEV1%无关。     

Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.     

Exhaled NO and breath condensate

A growing interest has recently directed toward non invasive methods, such as exhaled nitric oxide (FE(NO)) measurement and exhaled breath condensate (EBC) collection, for the assessment of asthmatic inflammation. FE(NO) is a reliable marker of eosinophilic airway inflammation and it can be measured by means of a standardized technique in children starting from the age of 4. FE(NO) may have useful applications both in asthma diagnosis and monitoring. EBC is obtained cooling exhaled air and its composition is believed to mirror the characteristics of airway lining fluid. The compounds detected in EBC are markers of inflammation and oxidative stress occurring in asthmatic lung. While EBC is still only a research tool, FENO measurement is closer to clinical practice and lately it has been included in some treatment algorithms for asthma.     

A single dose of nebulized budesonide decreases exhaled nitric oxide in children with acute asthma

This study was conducted to investigate whether a single dose of nebulized budesonide effectively decreased airway inflammation as demonstrated by exhaled nitric oxide (eNO) levels. A single dose of nebulized budesonide, but not nebulized terbutaline, rapidly decreased eNO levels in 6 hours. The decrease in eNO levels induced by nebulized budesonide was correlated to an increase in peak expiratory flow rate.     

Measurement of exhaled nitric oxide in young children during tidal breathing through a facemask

Measurement of exhaled nitric oxide (eNO) offers a non-invasive means for assessment of airway inflammation. The currently available methods are difficult to apply in preschool children. We evaluated four methods potentially applicable for eNO measurement during tidal breathing in young children. eNO was assessed during tidal breathing in 24 children, 2-7 yr old, using a facemask which separated nasal and oral airflow. Facemasks with and without a one-way valve allowing exhalation through the nose were used. Expiratory flow control was not attempted. Measurements of eNO were performed both on-line and off-line. In 11 children, 8-12 yr old, measurements were compared with the standard single breath on-line method. eNO was significantly lower applying the one-way valve in on-line and off-line measurements in comparison with measurements without the valve [4.6 and 3.9 parts per billion (ppb) vs. 6.9 ppb and 6.5 ppb]. The mean within subject coefficient of variation (CV) was significantly lower in on-line measurements with the one-way valve (9.6%) compared with the other three methods (18.8, 27.7 and 29.3% respectively). Measurements with a facemask fitted with a one-way valve yielded similar eNO levels as the standard single breath method (7.0 ppb vs. 6.9 ppb) and reproducibility (9.8% vs. 7.1%). In conclusion, reproducible measurements of eNO can be obtained without control of expiration flow using a facemask fitted with a one-way valve on the nasal compartment. The likely explanation to this is that the one-way valve reduces the admixture of nasal NO, thereby improving the reliability of eNO measurements.     

从美国胸科学会指南看呼出气一氧化氮测定的临床应用

近年来,随着对呼出气一氧化氮研究的增多,学术界对其临床应用价值的认识逐渐清晰。呼出气一氧化氮的测定已经标准化,但在实际临床工作中,如何在不同情况下选择使用此技术和解读其测定结果,很多医师仍感到困惑。美国胸科学会制定的关于呼出气一氧化氮临床应用的指南对有关问题进行了详细阐述,并给出了具体推荐意见。呼出气一氧化氮测定可用于确定嗜酸粒细胞性气道炎症,协助诊断哮喘,预测吸入皮质激素治疗的有效性,监测气道炎症状况。     

Montelukast decreased exhaled nitric oxide in children with perennial allergic rhinitis

BACKGROUND: Measurement of exhaled nitric oxide (eNO) is a simple and noninvasive method for assessment of inflammatory airway diseases. eNO is elevated in adolescent patients with perennial allergic rhinitis and related to bronchial hyperresponsiveness. The aim of this study was to investigate whether oral loratadine, montelukast, nasal budesonide or nasal sodium cromoglycate could reduce airway inflammation as indicated by decrease of eNO in children with perennial allergic rhinitis as demonstrated by eNO levels. METHODS: A randomized and investigator-blinded study was conducted in a hospital-based outpatient clinic. Children with perennial allergic rhinitis were divided into four groups and treated by loratadine, loratadine with nasal sodium cromoglycate, loratadine with oral montelukast, and loratadine with nasal budesonide, respectively. Allergic rhinitis scores, eNO and peak expiratory flow were measured before and 2, 4, 6 and 8 weeks after treatment. RESULTS: Results showed that eNO in children with perennial allergic rhinitis was reduced by nasal budesonide and oral montelukast within 2 weeks (24.56 +/- 14.42 vs 18.42 +/- 12.48, P < 0.001, in budesonide group; 27.81 +/- 13.4 vs 19.09 +/- 10.45, P < 0.001, in montelukast group), but not in the loratadine and cromoglycate groups. In contrast, loratadine or sodium cromoglycate also did not decrease eNO levels although they could decrease the symptom scores. CONCLUSIONS: It was concluded that four common treatment modalities could effectively release symptom scores, but decrease of airway inflammation as determined by decrease of eNO might be only achieved by nasal budesonide and montelukast, but not nasal sodium cromoglycate and loratadine. Children with perennial allergic rhinitis with high eNO levels may require oral montelukast or nasal budesonide treatment to prevent airway hyperresponsiveness.     

Increased bronchial NO output in severe atopic eczema in children and adolescents.

Atopic children have an increased risk for asthma, which is preceded by bronchial inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux, which reflect inflammation in lung periphery and central airways, respectively. Exhaled breath condensate is another non-invasive method to measure lung inflammation. The purpose of the present study was to find out if the severity of atopic eczema is associated with lung inflammation that can be observed with these non-invasive tests. We studied 81 patients (7-22 yr old) with atopic eczema and increased wheat-specific IgE (>or=0.4 kUA/l) and no diagnosis of asthma. Exhaled NO was measured at multiple exhalation flow rates, and bronchial NO flux and alveolar NO concentration were calculated. Cysteinyl-leukotriene concentrations were measured in exhaled breath condensate. The patients were divided into two groups according to the severity of atopic eczema. Patients with severe atopic eczema had enhanced bronchial NO output as compared with patients with mild eczema (2.1 +/- 0.5 vs. 0.9 +/- 0.1, p = 0.003). No statistically significant differences in alveolar NO concentrations were found between the groups. In the whole group of patients, the bronchial NO output correlated positively with serum eosinophil protein X (r(s) = 0.450, p < 0.001), serum eosinophil cationic protein (r(s) = 0.393, p < 0.001), serum total IgE (r(s) = 0.268, p = 0.016) and with urine eosinophil protein X (r(s) = 0.279, p = 0.012), but not with lung function. Alveolar NO concentration correlated positively with serum eosinophil protein X (r(s) = 0.444, p < 0.001) and with serum eosinophil cationic protein (r(s) = 0.362, p = 0.001). Measurable cysteinyl-leukotriene concentrations in exhaled breath condensate were found only in one-third of the patients, and there were no differences between the two groups. The results show that increased bronchial NO output is associated with eosinophilic inflammation and severe atopic eczema in patients without established asthma.