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.     

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.     

Consistently high levels of exhaled nitric oxide in children with asthma

Background: Exhaled nitric oxide (eNO) levels in children are unstable because they are regulated by many potent factors. The purpose of the current study was to evaluate the reliability of eNO levels between a long interval and other lung functions in normal and asthmatic children. Methods: Eighty‐three elementary school children (aged 11–12 years; male : female, 39 : 44) participated in this study. Lung function, airway resistance and eNO levels were measured twice: the first measurement was in autumn 2007, and the second was one year later. Results: There were 62 non‐asthmatic control children (male : female, 31 : 31) and 21 asthmatic children (male : female, 8 : 13). In both the first and the second examination, the levels of eNO in children with asthma were higher than those in children without asthma. The parameters of lung function and the respiratory resistance in children without asthma showed a good correlation between the results of the first and second examinations. The eNO level in non‐asthmatic children showed a good correlation between the two. On the other hand, the peripheral airway parameters of lung function and the respiratory resistance in children with asthma were not correlated between the first and the second examinations. The eNO level in these patients was well correlated between the two examinations. Conclusions: These data suggest that the eNO level showed good reproducibility in children with and without asthma. The eNO level is therefore considered to be a useful marker for reproducibly evaluating a subject's airway condition.     

特异质与慢性持续期哮喘儿童呼出气一氧化氮相关性研究

目的评估特异质对慢性持续期哮喘儿童呼出气一氧化氮(FeNO)水平的影响。方法选取同时完成皮肤点刺试验和FeNO检测的慢性持续期哮喘患儿52例,按皮肤点刺试验结果分为非特异质组和特异质组,按有无合并过敏性鼻炎分为鼻炎组和无鼻炎组;另选择78例健康儿童作为对照组,比较各组FeNO水平;并比较32例予吸入型糖皮质激素治疗3个月患儿的FeNO水平变化。结果 40例特异质组、12例非特异质组和对照组的FeNO水平差异有统计学意义(H=33.29,P=0.000);特异质组FeNO水平高于对照组和非特异质组,差异有统计学意义(P0.05)。11例无鼻炎组、41例鼻炎组和对照组的FeNO水平差异有统计学意义(H=30.63,P=0.000);鼻炎组FeNO水平高于对照组,差异有统计学意义(P0.05);鼻炎组与无鼻炎组差异无统计学意义(P0.05)。特异质组患儿FeNO水平与屋尘螨、粉尘螨皮肤点刺致敏风团直径无相关性(r=2.05、1.58,P均0.05)。32例患儿经吸入糖皮质激素治疗3个月后FeNO水平显著下降,与其治疗前第一次检测结果比较,差异有统计学意义(Z=2.05,P=0.041)。结论特异质对慢性持续期哮喘儿童FeNO水平有重要影响,吸入糖皮质激素可显著降低致敏哮喘儿童FeNO水平。     

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??Objective To explore the change of exhaled nitric oxide ??eNO?? in children from community and its importance in asthma management. Methods The study was conducted from October 2011 to December 2011. Totally 133 non-asthmatic children and 94 asthmatic children aged 7~12 years old from elementary schools in Beijing Xicheng District were included in the study. The eNO?? skin prick test ??SPT???? lung function and physical examination were carried out and information of medical history was collected in all children. The eNO level between non-asthmatic children and asthmatic children?? and its association with atopy?? rhinitis?? lung function and asthma control were analyzed. Results eNO levels of non-asthmatic children and asthmatic children were 11.63±1.88 ppb?? and 19.68±2.31 ppb respectively and the difference between them was statistically significant ??P<0.01??. In non-asthmatic children?? the level of eNO in children with rhinitis was significantly higher than in children without rhinitis ???17.49±2.02??×10-9 vs. ??10.42±1.76??×10-9?? P<0.01?? and eNO level in atopic children was higher than non-atopic children ???23.06±2.18??×10-9 vs. ??9.60±1.66??×10-9?? P<0.01??. In asthmatic children?? the difference in eNO level was not significant in children with rhinitis and without rhinitis ???19.58±2.34??×10-9 vs. ??20.09±2.25??×10-9??? but the eNO levels in atopic children ??23.06±2.18??×10-9 was significantly higher than non-atopic children ???8.75±1.86??×10-9?? P<0.01??. The level of eNO of uncontrolled asthmatic children was significantly higher than controlled asthmatic children ???25.09±2.31??×10-9 vs. ??17.21±2.22??×10-9?? P<0.05??. There was no significant difference in eNO level between children who used and those who did not use inhaled corticosteroid. The eNO level was not related to lung function parameters either in non-asthmatic or in asthmatic children. Conclusion The eNO level increases significantly in children with asthma or rhinitis and is associated with asthma control status. Atopy is an important factor on eNO level as well. Measuring eNO level would help improve the diagnosis of asthma and atopy and management of asthma and rhinitis in children from community.     

Exhaled nitric oxide in healthy children: Variability and a lack of correlation with atopy

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4–18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV ₁, MEF₂₅ and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.     

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.     

The effect of acute pain crisis on exhaled nitric oxide levels in children with sickle cell disease

Exhaled nitric oxide (FE(NO)) has been shown to be decreased in children with sickle cell disease. We sought to evaluate the effect of sickle cell vaso-occlusive crisis (VOC) on FE(NO) levels. We measured FE(NO) levels in 42 children with sickle cell disease, 29 in their baseline health and 13 during an acute VOC. There was no difference in FE(NO) levels between children at baseline (15.12 +/- 9.32 ppb) and those during an acute VOC (15.68 +/- 7.26 ppb; P = 0.794). FE(NO) is not a useful marker of acute VOC in children with sickle cell disease.     

以225名健康儿童建立呼出气一氧化氮正常值

目的：探讨6~14岁儿童呼出气一氧化氮（FeNO）正常值范围及其影响因素。方法：选取苏州市6~14岁在校儿童进行问卷调查及FeNO、肺功能、外周血嗜酸粒细胞（EOS）计数的检测,筛选出健康儿童建立FeNO正常值。FeNO的测定采用电化学法,根据美国胸科学会/欧洲呼吸学会指南进行操作。分析性别、年龄、身高、体重、外周血EOS计数、肺功能和FeNO的相关性。结果：参与调查的450名儿童中符合纳入标准者225名（男生107名,女生118名）进入分析。FeNO值呈偏态分布,经自然对数转换后呈正态分布。FeNO平均值为11 ppb(95%CI:5~28 ppb）,最小值<5 ppb,最大值为83 ppb。男生FeNO平均值为11 ppb(95%CI:5~31 ppb）,女生FeNO平均值为11 ppb(95%CI:5~25 ppb）。FeNO与外周血EOS计数相关性最为显著（r=0.291,P<0.001）,与身高（r=0.148, P=0.027）和FEV1（r=0.138, P=0.038）显著相关;>9岁儿童FeNO显著高于≤9岁儿童（P=0.002）;FeNO与性别、体重、BMI、FEV1/FVC无显著相关性。结论：苏州地区6~14岁儿童FeNO正常参考值为5~28 ppb;FeNO水平与外周血EOS计数、身高、FEV1显著相关。     

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??Abstract??The pathophysiology of wheezing in infants is yet to be fully understood, and approaches for a confirmatory diagnosis of this condition remain so far limited. Thus, a combination of medical history and laboratory investigations represents the most reliable source of clinical clues for diagnosis and differential diagnosis of infant wheezing.     

Exhaled nitric oxide fractions are well correlated with clinical control in recurrent infantile wheeze treated with inhaled corticosteroids

Ghdifan S, Verin E, Couderc L, Lubrano M, Michelet I, Marguet C. Exhaled nitric oxide fractions are well correlated with clinical control in recurrent infantile wheeze treated with inhaled corticosteroids.
Pediatr Allergy Immunol 2010: 21: 1015–1020.
© 2010 John Wiley & Sons A/S Fractional exhaled nitric oxide (FeNO) is a non‐invasive marker of bronchial inflammation in asthma. However, the interest of FeNO measurement remained limited in infantile wheeze. The aim of this prospective study was to evaluate the feasibility and reproducibility of FeNO off‐line measurement in very young children with recurrent wheeze and to assess whether clinical control of infantile wheeze correlates with FeNO levels. Two exhalation samples were collected in mylar balloon during quite tidal breathing. FeNO measurements were performed off‐line by a NO analyzer. The participating patients were aged ≤36 months, wheezes had started before the age of 24 months, and they were receiving maintenance treatment with inhaled corticosteroids for at least 3 months duration. The studied population comprised of 40 uncontrolled infants with persistent wheezy respiratory symptoms, median age 14.5 months, and 40 with optimal controlled infantile wheeze, median age 14 months. The reproducibility was excellent (r = 0.95; p < 0.0001). There was a significant difference in FeNO levels between the groups of persistent wheeze and well‐controlled infants: 19.8 (2.5–99.3) ppb vs. 7.7 (0.6–29.5) ppb, p < 0.0001. At a FeNO level >15 ppb, the predictive values for uncontrolled disease were as follows: positive predictive value = 65%, negative predictive value = 90%. FeN0 levels were not increased by atopy or passive tobacco. Off‐line assessment of FeNO is feasible, reproducible, and well accepted in wheezy very young children. Optimal clinical control of infantile wheeze appeared to be associated with the control of bronchial inflammation when evaluated by FeNO measurements.     

呼出气一氧化氮检测在幼儿支气管哮喘中的应用分析

目的分析各期支气管哮喘(AS)幼儿的呼出气一氧化氮(FeNO)浓度变化,探讨FeNO浓度与AS分期的相关性。方法选取2014年4~6月初次诊断为AS且处于急性发作期的1~3岁患儿58例为研究对象,依据治疗后病情转归情况分为慢性持续期(n=34)及临床缓解期(n=24),以同龄健康儿童30例为对照,对所有儿童行FeNO浓度、肺功能等检测。分析FeNO浓度与AS分期的相关性。利用受试者工作特征(ROC)曲线分析FeNO诊断AS的最佳诊断截点。结果各期AS患儿FeNO浓度均高于对照组儿童(P0.05)。急性发作期患儿Fe NO浓度高于慢性持续期和临床缓解期,且慢性持续期患儿FeNO浓度高于临床缓解期(均P0.05)。AS患儿FeNO浓度水平与AS分期相关(r=-0.382,P0.05)。ROC曲线分析显示FeNO诊断AS的最佳诊断截点为22.75 ppb,敏感度达0.933,但特异度仅为0.388。结论 AS幼儿FeNO浓度水平与AS分期相关;Fe NO浓度22.75 ppb可作诊断幼儿AS的界值。     

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目的评价呼出气一氧化氮(FeNO)监测在哮喘控制治疗中的评估指导作用。方法收集深圳市儿童医院哮喘专科门诊的41例患儿,根据抽签分组,20例进入FeNO组,21例进入对照组。控制治疗中,对照组根据儿童哮喘控制水平分级进行调整;FeNO组在此基础上结合FeNO检测结果进行调整。在10个月治疗后,观察两组之间哮喘症状、短效β受体激动剂使用情况、肺功能结果,吸入激素使用量,从而判断FeNO检测在哮喘控制治疗中的作用。结果 FeNO组使用短效β受体激动剂平均天数为(4.3±3)d,对照组为(3.7±2.8)d;FeNO组总发作次数9次,对照组为11次;第1秒用力呼气容积(FEV1)占预计值%在FeNO组为100.96±7.69,对照组为90.37±12.95;达50%用力肺活量时最大呼气流速(MEF50)占预计值%在FeNO组为95.77±9.32,对照组为87.01±13.84。以上指标比较均为P>0.05,差异无统计学意义。FeNO组平均吸入糖皮质激素量为(290±75)μg,对照组为(225±50)μg(P<0.01)。结论在哮喘控制治疗评估中,加入FeNO浓度检测,对吸入糖皮质激素(ICS)有指导作用,但未能显...     

The effect of spirometry and exercise on exhaled nitric oxide in asthmatic children.

American Thoracic Society (ATS) guidelines recommend to refrain from spirometry or exercise before measuring fractional exhaled nitric oxide (FENO) because forced breathing maneuvers might influence FENO values. However the few studies already reported in children have given conflicting results. The aim of the study was to observe to what extent spirometry or exercise could affect FENO in asthmatic children. Twenty-four asthmatic children (mean age 12.8 yr) were enrolled. Measurements of FENO were performed before and 5, 15, 30, 45 and 60 min after spirometry or a 6-min walk test, on two separate days in random order. Geometric mean FENO at baseline was 25.6 parts per billion (ppb) before spirometry and 23.5 ppb before exercise. A small drop of FENO to 24.2 and 23.7 ppb was found 5 and 15 min after spirometry (both p = 0.04). After exercise, FENO values showed a larger drop to 18.5 ppb after 5 min and 20.7 ppb after 15 min (p < 0.001; p = 0.004 respectively). Changes in FENO occurred after exercise irrespective of baseline FENO and values returned to baseline within 30 min. We conclude that both spirometry and exercise affect FENO in asthmatic children. As the changes after exercise may lead to erroneous interpretations, children should refrain from physical exercise during at least 30 min before FENO measurements.     

Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide ( FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho ≥ 0.30, p < 0.01, each correlation) and FeNO levels (Rho ≥ 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho ≥ 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.     

毛细支气管炎患儿呼出气一氧化氮检测应用价值

目的探讨毛细支气管炎患儿呼出气一氧化氮(FeNO)检测的意义及应用价值。方法以2018年1至9月收治的49例初发毛细支气管炎住院患儿为研究对象,根据呼吸道合胞病毒(RSV)检测结果分为RSV组(27例)和非RSV组(22例);另选取同期同年龄健康体检儿童17例作为健康对照组。对各组进行潮气呼吸法呼出气一氧化氮检测,RSV组和非RSV组患儿在缓解期(1～2周)和恢复期(4～6周)再次检测,比较检测结果。结果 RSV组、非RSV组以及健康对照组间性别、年龄差异无统计学意义(P0.05)。RSV组及非RSV组FeNO水平在急性期、缓解期和恢复期间的差异均有统计学意义(P0.05)。在恢复期,FeNO水平在RSV组、非RSV组和健康对照组间的差异有统计学意义(P0.05),以RSV组FeNO水平最高。在急性期和缓解期,FeNO水平在三组间的差异无统计学意义(P0.05)。结论毛细支气管炎(包括RSV感染和非RSV感染)患儿在急性期和缓解期的FeNO水平与健康同龄儿童无差异,在恢复期高于健康同龄儿童。     

呼出气一氧化氮在儿童呼吸道疾病中的应用进展

NO是人体内重要的信号因子,存在于正常人的呼出气中.各种呼吸道炎症性疾病均可导致呼出气NO增高,尤其是嗜酸性粒细胞性炎症.呼出气NO测定能直接反映气道炎症,具有无创、重复性好、易操作等优势,有助于临床对反复喘息、慢性咳嗽等呼吸道常见症状的病因鉴别,有助于对支气管哮喘等多种疾病的诊断、判断病情及预后,对于儿童呼吸道疾病的管理具有重要价值.     

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目的通过对哮喘儿童呼出气一氧化氮(FENO)水平的监测,为哮喘的临床诊断治疗及病情评估提供帮助。方法选择2007年10月至2009年8月于首都儿科研究所附属儿童医院门诊确诊的哮喘患儿共358例,根据其哮喘发作与治疗情况分为哮喘发作组与非发作组、治疗组与未治疗组。设计临床观察表记录各组患儿治疗、发作、肺部喘鸣音情况,并进行FENO及1秒用力呼气容积(FEV1)、用力肺活量(FVC)及最大用力呼气中段流量(MMEF)等肺功能指标的测定。结果 358例哮喘患儿的FENO值为28.5(15.5～55.0)×10-9,其中男性为29.0(15.0～49.8.0)×10-9,女性为28.0(16.0～58.6)×10-9,男女相比差别无统计学意义(Z=-1.006,P>0.05)。111例11岁以上哮喘儿童FENO为36.0(20.0～65.0)×10-9,其中男性为30.0(26.0～63.0)×10-9,女性为40.5(17.7～73.8)×10-9,与395例正常儿童相比FENO明显增高,差异具有统计学意义(Z=-11.352,P<0.001)。358例哮喘患儿FENO与年龄呈正相关(r=0.206,P<0.01)...