儿童呼出气一氧化氮检测的临床应用

呼出气一氧化氮检测可反映气道嗜酸性粒细胞性炎症,近年来被广泛用于辅助支气管哮喘的诊断、监测支气管哮喘患者气道炎症以及监测患者对治疗效果的反应.呼出气一氧化氮检测作为一种无创性检查,能够得到成人及5岁以上儿童的高度配合,但在5岁以下儿童中的应用存在很多问题,目前国内尚缺乏婴幼儿及新生儿呼出气一氧化氮检测的正常值及相关大样本研究.该文主要从儿童呼出气一氧化氮检测的原理及方法、正常参考值、影响因素、临床应用等方面进行综述.     

呼出气一氧化氮在儿童毛细支气管炎中的应用

近年来呼出气一氧化氮在呼吸系统疾病中的应用越来越广泛,特别是在监测气道炎症性疾病的发生、发展和评价方面被认为是最具有发展前景的呼出气标志物之一.该文综述呼出气一氧化氮在儿童毛细支气管炎中的相关文献,旨在探讨呼出气一氧化氮在儿童毛细支气管炎中可能的应用价值.     

呼出气一氧化氮检测在儿童气道疾病的临床应用

一氧化氮在气道和肺部多个生理和病理环节中发挥着重要作用,当气道和肺部发生疾病时,呼出气一氧化氮浓度会产生变化.近年来随着临床研究的深入及检测技术水平的不断提高,呼出气一氧化氮测定在儿童多种气道疾病中得到广泛应用,该检测技术提供了一种了解气道炎症类型、炎症部位、炎症程度的新方法.     

呼出气一氧化氮在儿童支气管哮喘诊治中的应用进展

支气管哮喘是以慢性气道炎症为主要特征的常见呼吸系统疾病.近年来,呼出气一氧化氮作为无创性气道炎症的评估检测方法,广泛应用于判断气道炎症性质、确定糖皮质激素治疗的反应性、临床诊断及鉴别诊断、调整激素治疗、判断预后等.该文对呼出气一氧化氮在儿童喘息及相关疾病的研究进展、产生及作用、正常值标准、临床应用等方面进行综述.     

呼出气一氧化氮测定与哮喘的气道炎症

哮喘是一种常见病和多发病,其病理基础是气道炎症,而对哮喘气道炎症的监测是防治哮喘的关键.NO是近年来研究较多的一种生物活性物质,已证实其与许多炎症介质相关,在哮喘的发病机制中具有重要作用.目前认为呼出气中NO测定是反映哮喘气道炎症的新型无创伤性及敏感的生物指标,因而呼出气中NO测定对哮喘的诊断、治疗、病情监控和预后评估均有十分重要的意义.呼出气中NO测定技术的开展具有广阔的临床应用前景.     

哮喘的炎症标志物

哮喘是一种慢性气道炎症性疾病.检测、评估气道炎症对于哮喘的早期诊断、病情严重程度的判断、药物种类和剂量的选择以及对已控制症状患者停药时机的选择等,均有重要的临床指导意义,故迫切需要能客观地反映气道炎症的检测技术来指导哮喘的诊断和治疗.目前研究较多的炎症标志物主要有呼出气一氧化氮、白三烯、呼出气冷凝液测定、骨膜蛋白、人软骨糖蛋白等.该文就上述炎症标志物的生物学特性及在哮喘临床中的应用进行阐述.     

儿童呼出气一氧化氮检测及临床应用专家共识(2021版)

呼出气一氧化氮(eNO)目前被认为是气道Ⅱ型炎症的生物标志物,在临床上得到了广泛的应用。近来欧洲呼吸学会推荐并规范了小气道eNO和上气道eNO的测定技术,而我国尚无相关的测定技术标准与临床应用指南。为此,中华医学会儿科学分会呼吸学组哮喘协作组组织相关专家,参考国内外最新循证医学研究结果,制定出本共识,以期为临床合理使用...     

支气管哮喘患儿血清一氧化氮、一氧化氮合酶水平变化临床研究

多年来已认识到哮喘是一种慢性气道变态反应性炎症性疾病。一氧化氮(NO)是几种最有希望成为气道炎症标志物的物质之一。检测呼出气NO需要精密昂贵的仪器设备，作者拟用血清NO、一氧化氮合酶(NOS)检测替代呼出气NO检测，以便于普遍推广，并为临床哮喘病情判断和疗效评价提供一定的参考依据。     

肺功能联合呼出气一氧化氮测定在儿童慢性咳嗽诊断中的研究进展

慢性咳嗽可以发生于各个年龄段儿童,发病率及就诊率逐年增高,明确病因是慢性咳嗽治疗的关键。目前,国内外对于慢性咳嗽的病因分析并没有简便、易于操作的统一标准,是临床上研究的热点问题。随着诊疗技术的发展,肺功能及呼出气一氧化氮测定在慢性咳嗽诊断中的作用逐渐引起关注。该文就肺功能联合呼出气一氧化氮测定在儿童慢性咳嗽病因分析中的...     

肺泡呼出气一氧化氮在儿童肺疾病中的应用进展

呼出气一氧化氮被认为是气道炎症的生物标志物,其中表征小气道炎症的肺泡呼出气一氧化氮(alveolar exhaled nitric oxide,CaNO)越来越多地被应用于呼吸系统疾病中。CaNO不仅可以应用于儿童支气管哮喘严重程度的评估、治疗方案的选择以及治疗效果的动态监测,还可以应用于间质性肺疾病的早期诊断及肺损害...     

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.     

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.     

Effects of montelukast on symptoms and eNO in children with mild to moderate asthma

BACKGROUND: Asthma is a chronic inflammatory airway disease. Exhaled nitric oxide (eNO) is a marker reflecting airway inflammation. This study was conducted to investigate whether montelukast, a leukotriene receptor antagonist, could be used for the management of asthma and how fast the montelukast sodium decreased airway inflammation as demonstrated by eNO levels. METHODS: Twenty children aged 6-14 years (mean age: 9.2 +/- 2.4 years; mean weight 30 +/- 4.6 kg) with mild to moderate asthma were recruited for the study. They received montelukast plus an inhaled short-acting beta2 agonist as open and uncontrolled therapy. Asthma score (AS) and peak expiratory flow rate (PEFR) and eNO concentrations were measured at pretreatment (0 week) and post-treatment (1 and 2 weeks) as well as 2 weeks after withdrawal of therapy. RESULTS: In one week, the eNO levels (33.3 +/- 15.5 p.p.b. vs 14.8 +/- 8.6 p.p.b.; P < 0.05), and AS (4.2 +/- 1.3 vs 1.8 +/- 1.3; P < 0.05) decreased rapidly, and PEFR (206.9 +/- 69.7 L/min vs 236.2 +/- 69.8 L/min; P < 0.05) increased. Concurrent beta2 agonist use decreased from a mean +/- SD of 2.2 +/- 0.4-1.3 +/- 0.3 puffs per weeks (P < 0.05). After the withdrawal of treatment for 2 weeks, the eNO levels (29.2 +/- 16.1 p.p.b) rebounded again, although the improvements in AS (1.1 +/- 1.3) and PEFR (245.0 +/- 91.3 L/min) persisted. CONCLUSION: Oral montelukast sodium treatment of these children with mild to moderate asthma effectively improved asthmatic symptoms and suppressed airway inflammation in 1 week, suggesting that this leukotriene antagonist combined with short-acting beta2 agonists may provide effective treatment option in mild to moderate childhood asthma. Larger, controlled, and double-blinded studies are needed to confirm these preliminary open uncontrolled observations.     

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.     

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.     

Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis

Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic children were recruited as controls. eNO levels (median) were significantly higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic asthma had higher eNO levels than children with allergic rhinitis. A significant positive correlation was found between eNO and total serum IgE (asthma, r = 0.42, p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE than with the number of positive skin prick tests. This correlation was independent of allergic sensitization. High total serum IgE represents a specific and predictive marker of eNO increase in children with asthma or allergic rhinitis. This finding adds further support to the hypothesis that increased serum IgE could be a marker itself of airway inflammation in patients with allergic disease.     

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］     

Suppression of plasma matrix metalloproteinase-9 following montelukast treatment in childhood asthma

BACKGROUND: Montelukast and ketotifen are commonly prescribed anti-inflammatory medications used in the treatment of childhood asthma. METHODS: To investigate the modulation effect of montelukast and ketotifen, the levels of exhaled nitric oxide (eNO) and plasma matrix metalloproteinase-9 (MMP-9) were analyzed in a group of 30 children with mild persistent asthma. RESULTS: Patients on montelukast therapy for 8 weeks had significantly decreased levels of eNO and plasma MMP-9, which were associated with improved symptoms and enhanced peak expiratory flow but not significantly associated with increased level of tissue inhibitor metalloproteinase-1 (TIMP-1). In contrast, treatment with ketotifen produced no significant changes in these parameters until 4-6 weeks into the therapy and no effect on plasma MMP-9. CONCLUSION: Leukotriene antagonists, such as montelukast, may be better non-steroidal anti-inflammatory drugs for preventing airway inflammation in mild childhood asthma.     

Surrogate markers of airway inflammation: inflammometry in paediatric respiratory medicine

Until recently, there has not been any practical way to assess airway inflammation non-invasively in paediatrics. Surrogate markers of airway inflammation are potentially of great importance in the diagnosis and monitoring of inflammatory airways disease in children. A large number of substances in blood, urine and exhaled air or induced sputum are currently under study to evaluate their possible usefulness as markers of airway inflammation. To be useful, a marker should be valid, preferably non-invasive, quick, reproducible, repeatable and cheap. In addition, markers should be studied in relation to their specific purpose because different markers may be useful for different types of airway inflammation. Few, if any, markers will fulfill all these requirements. Most research has focused on applications of markers in asthma, some data refer to cystic fibrosis, infections and ciliary dyskinesia. Of all surrogate markers, exhaled nitric oxide has been studied the most and seems to offer information that should be evaluated for its relevance to clinical practice. Before introducing markers of inflammation into daily practice, analysis of benefits and costs are needed. There is little doubt that 'inflammometry' will be a major step forward and will be useful in differentiating airways diseases and improving treatment.