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.     

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.     

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。     

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.     

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??Objective??To study the clinical value of the test of tidal breathing lung function and exhaled nitric oxide in asthmatic children aged 2 to 5. Methods??216 children with asthma treated from January 2012 to June 2015 in the Pediatric Department of Xijing Hospital of Fourth Military Medical University were listed in asthma group??and 128 normal children in the same period were selected as control group. Tidal breathing lung function and exhaled nitric oxide at the acute and remission stages of asthma were tested respectively??and compared with control group. Tidal breathing lung function were compared before and after bronchial dilation test. Correlation between exhaled nitric oxide level and tidal breath lung function parameters was analyzed. Results??The ratio of time to peak tidal expiratory flow to total expiratory time??TPEF/TE?? and ratio of volume to peak expiratory flow to total expiratory volume??VPEF/VE?? in acute stage of asthma group were significantly lower than those of the asthma group in the remission stage and the control group??P??0.05??. TPEF/TE and VPEF/VE had significantly improved in asthma group in remission stage??but were still significantly lower than those of the control group??P??0.05??. TPEF/TE and VPEF/VE had significantly improved after bronchial dilation test in the acute stage of asthma group??P??0.05??. Taking an improvement rate of ≥15% either for TPEF/TE or for VPEF/VE as an indicator of positive bronchial dilation test??thus the positive rate was 69.90%. The levels of FeNO in acute and remission stages of asthma group???35.50±14.13??×10-9????28.16±5.52??×10-9?? were significantly higher than those of the control group???12.77±7.00??×10-9??P??0.05?????and the levels of FeNO in acute stage of asthma group were significantly higher than those of asthma group in remission stage??P??0.05??. FeNO levels were not correlated with TPTEF/TE and VPEF/VE in acute or in remission stages of asthma group. Conclusion??Tidal breathing lung function??exhaled nitric oxide test and bronchial dilation test are complementary??combined applications can effectively improve the diagnosis and treatment in early childhood asthma.     

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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)...     

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。     

Daily ambulatory exhaled nitric oxide measurements in asthma

Exhaled NO (FENO) is a non-invasive, validated marker for asthmatic airway inflammation. Recently, a new hand-held NO-analyzer has been developed which makes it possible to monitor FENO at home. We assessed feasibility and analyzed variability of daily FENO home measurements. Twenty-one asthmatics (mean age 14.5 yr; range 8-25 yr) participated. Nineteen used a stable dose of inhaled corticosteroids and all of them were in a stable clinical condition. FENO was measured twice daily for 14 consecutive days. Measurements and symptom scores were recorded on a smart card in the analyzer. Symptom score items included well-being, wheeze, activity, and nocturnal symptoms. Measurements showed a success rate of 93%. We found a significant diurnal variation in FENO with geometric mean morning levels 14% higher than evening levels (95% CI: 4%-25%; p = 0.013). Individual subjects showed marked fluctuation of FENO. The mean intrasubject coefficient of variation of FENO was 40% for morning and 36% for evening values. FENO and cumulative symptom scores did not correlate. Home FENO measurements are feasible, and offer the possibility to asses airway inflammation on a daily basis. Further study is needed to interpret and evaluate possible benefits of FENO home monitoring.     

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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.     

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。     

Spirometry‐adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry‐adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry‐adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry‐adjusted fraction of exhaled NO/FEV₁ (AUC = 0.712; P = .010) and NO/FEF_25%‐75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non‐controlled asthma were 59% and 81%, respectively, for the cut‐off value of 9.7 ppb/L for exhaled NO/FEV₁, and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF_25%‐75%. Exhaled NO did not allow to identify childhood asthma. Spirometry‐adjusted fraction of exhaled NO performed better‐assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.     

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??Abstract: Objective To learn the level of exhaled nitric oxide??ENO?? in Jinan schoolchildren??setting up normal reference value range and analyzing associate influencing factors. Method A total of 473 school children in Jinan aged 7 to 13 years were included in this study. By means of filling out the questionnaire and site examination??we selected eligible children and then measured the exhaled nitric oxide and Peak Expiratory Flow ??PEF??. Result The 473 cases of healthy schoolchildren were selected??male 257??female 216??in this study and we concluded the geometric mean and the 95% CI was 7.780??4.656??13.002??× 109 mol/L. We found that ENO’s level of 10??13-years-old children significantly higher than 7??9 year-old children??P??0.05??. The geometric mean and the 95% CI were 8.680??5.936??12.692??× 109 mol/L and 6.710??3.588??12.546??× 109 mol/L.In our study we found that age had positive relation with ENO ??P??0.05??while gender??height??weight ??PEFR and passive smoking had no significant correlation with ENO??P??0.05??. Conclusion The geometric mean and the 95% CI of ENO in children aged 7??13 years in Jinan is 7.780??4.656??13.002??× 109 mol/L?? in which 10??13-year- old children was significantly higher than 7??9-years old children ??P??0.05?? and the geometric mean and the 95% CI are 8.680??5.936??12.692??× 109 mol/L and 6.710??3.588??12.546??× 109 mol/L. Gender is an independent influencing factor of ENO level.     

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.     

哮喘患儿呼出气一氧化氮与其他无创性检查的相关性研究进展

对于哮喘患儿呼吸道炎症过程的监测,呼出气一氧化氮(FeNO)水平现在被公认为是一个可靠的提示嗜酸性粒细胞性气道炎症的标志物,且其作为一个完全无创性的检测方法,简便易行.该文综述FeNO检测在儿童哮喘中的应用以及在哮喘的评估、诊断中,FeNO水平与其他无创性检查的相关性.     

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.     

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.     

FeNO与儿童哮喘关系的研究进展

支气管哮喘是一种异质性疾病,以气道高反应性、气道慢性炎症为特征,常伴有可逆性气流受限。目前儿童哮喘诊断的实验室检测方法主要以肺通气功能检测为主,由于儿童的不配合性,学龄前儿童肺通气功能检测具有挑战性。肺功能检测是瞬时指标,受患儿理解能力、精神因素等影响。肺功能检测不能评估气道炎症的严重程度。近年来一种无创、简单、客观评价气道炎症指标呼出气一氧化氮 （FeNO）逐渐在儿童中应用增多。该综述就FeNO的产生、实验参考值界定及其在不同年龄哮喘儿童的诊断、治疗、预测评估中的作用研究进展进行阐述。     

Environmental exposures and exhaled nitric oxide in children with asthma

OBJECTIVE: To evaluate the relation of environmental factors with exhaled nitric oxide (FENO) concentrations among asthmatic children. STUDY DESIGN: Cross-sectional analysis of 170 tobacco smoke-exposed children, ages 6 to 12 years, who have doctor-diagnosed asthma using measures of FENO, medication use, and exposures to settled indoor allergens and tobacco smoke. RESULTS: In multivariable analysis, child's age, uncarpeted flooring, not owning a cat, higher income, dust mite exposure, and being sensitized to any allergens were associated with higher FENO concentrations. Children who were sensitized to indoor allergens had an adjusted geometric mean FENO of 15.4 ppb (95% CI, 13.1, 18.2) compared with 10 ppb (95% CI, 8.2, 12.2) for unsensitized children. There was no statistically significant association of serum cotinine, hair cotinine, or reported corticosteroid therapy with FENO. CONCLUSIONS: FENO is higher among children who are sensitized to indoor allergens and exposed to dust mites. The results hold promise for the use of FENO as a tool to manage childhood asthma by using both pharmacologic and environmental treatments.     

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.