呼出气一氧化氮在儿童呼吸系统过敏性疾病诊断和治疗中的应用

doi:10.12372/jcp.2022.23e0182

摘要/Abstract

摘要：

呼出气一氧化氮检测是一项无创气道炎症检测技术，反映嗜酸性粒细胞性气道炎症状态的指标，可以预测呼吸系统过敏性疾病对皮质类固醇治疗的反应性，主要用于呼吸系统过敏性疾病的诊断、鉴别诊断、治疗和相关预测、管理等。

Abstract:

Expiratory nitric oxide detection is a non-invasive method to assess the state of eosinophilic airway inflammation and can predict the responsiveness of respiratory allergic diseases to corticosteroid treatment. It is mainly used for the diagnosis, differential diagnosis, treatment, and predicting prognosis and management of respiratory allergic diseases.

Key words: exhaled nitric oxide, allergic disease, eosinophilic airway inflammation, child

吴巾红. 呼出气一氧化氮在儿童呼吸系统过敏性疾病诊断和治疗中的应用[J]. 临床儿科杂志, 2023, 41(5): 328-332.

WU Jinhong. Application of exhaled nitric oxide in the diagnosis and treatment of respiratory allergic diseases in children[J]. Journal of Clinical Pediatrics, 2023, 41(5): 328-332.

图/表 2

参考文献 43

[1]	Ricciardolo FL. Revisiting the role of exhaled nitric oxide in asthma[J]. Curr Opin Pulm Med, 2014, 20(1): 53-59. doi: 10.1097/MCP.0000000000000006 pmid: 24275926
[2]	Global Initiative of Asthma 2022. Global strategy for asthma management and prevention[EB/OL]. [2023-03-09]. https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf.
[3]	Louis R, Satia I, Ojanguren I, et al. European Respiratory Society Guidelines for the diagnosis of asthma in adults[J]. Eur Respir J, 2022: 2101585.
[4]	Pijnenburg MW, De Jongste JC. Exhaled nitric oxide in childhood asthma: a review[J]. Clin Exp Allergy, 2008, 38(2): 246-259. pmid: 18076708
[5]	Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls[J]. Cell, 1994, 78(6): 915-918. doi: 10.1016/0092-8674(94)90266-6 pmid: 7522969
[6]	Manna A, Montella S, Maniscalco M, et al. Clinical application of nasal nitric oxide measurement in pediatric airway diseases[J]. Pediatr Pulmonol, 2015, 50(1): 85-99.
[7]	Lane C, Knight D, Burgess S, et al. Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath[J]. Thorax, 2004, 59(9): 757-760. doi: 10.1136/thx.2003.014894 pmid: 15333851
[8]	Guo FH, Erzurum SC. Characterization of inducible nitric oxide synthase expression in human airway epithelium[J]. Environ Health Perspect, 1998, 106(Suppl 5): 1119-1124.
[9]	Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications[J]. Am J Respir Crit Care Med, 2011, 184(5): 602-615. doi: 10.1164/rccm.9120-11ST
[10]	张皓, 江文辉, 马春艳, 等. 中国6-18岁学龄儿童与青少年呼出气一氧化氮正常值的多中心研究[J]. 中华实用儿科临床杂志, 2020, 35(21): 1618-1623.
[11]	Kovesi T, Kulka R, Dales R. Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9- to 12-year-old children[J]. Chest, 2008, 133(1): 169-175. doi: 10.1378/chest.07-1177 pmid: 17925422
[12]	Cho HJ, Jung YH, Yang SI, et al. Reference values and determinants of fractional concentration of exhaled nitric oxide in healthy children[J]. Allergy Asthma Immunol Res, 2014, 6(2): 169-174. doi: 10.4168/aair.2014.6.2.169
[13]	Komlósi ZI, van de Veen W, Kovács N, et al. Cellular and molecular mechanisms of allergic asthma[J]. Mol Aspects Med, 2022, 85: 100995. doi: 10.1016/j.mam.2021.100995
[14]	Soma T, Iemura H, Naito E, et al. Implication of fraction of exhaled nitric oxide and blood eosinophil count in severe asthma[J]. Allergol Int, 2018, 67S: S3-S11.
[15]	Karrasch S, Linde K, Rücker G, et al. Accuracy of FENO for diagnosing asthma: a systematic review[J]. Thorax, 2017, 72(2): 109-116. doi: 10.1136/thoraxjnl-2016-208704 pmid: 27388487
[16]	Shen H, Hua W, Wang P, et al. A new phenotype of asthma: chest tightness as the sole presenting manifestation[J]. Ann Allergy Asthma Immunol, 2013, 111(3): 226-227. doi: 10.1016/j.anai.2013.06.016
[17]	Feng Y, Zhang S, Shang Y, et al. The use of exercise challenge testing and fractional exhaled nitric oxide in diagnosis of chest tightness variant asthma in children[J]. Int Arch Allergy Immunol, 2022, 183(7): 762-769. doi: 10.1159/000522062
[18]	Heaney LG, Busby J, Hanratty CE, et al. Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial[J]. Lancet Respir Med, 2021, 9(1): 57-68. doi: 10.1016/S2213-2600(20)30397-0 pmid: 32916135
[19]	Schneider A, Brunn B, Hapfelmeier A, et al. Diagnostic accuracy of FeNO in asthma and predictive value for inhaled corticosteroid responsiveness: a prospective, multicentre study[J]. EClinicalMedicine, 2022, 50: 101533. doi: 10.1016/j.eclinm.2022.101533
[20]	Chung KF. Increasing utility of FeNO as a biomarker of type-2 inflammation in severe asthma[J]. Lancet Respir Med, 2021, 9(10): 1083-1084. doi: 10.1016/S2213-2600(21)00170-3 pmid: 34181878
[21]	Busse WW, Wenzel SE, Casale TB, et al. Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled, moderate-to-severe asthma receiving placebo in the LIBERTY ASTHMA QUEST study: a post-hoc analysis[J]. Lancet Respir Med, 2021, 9(10): 1165-1173. doi: 10.1016/S2213-2600(21)00124-7 pmid: 34181876
[22]	Lipworth B, Kuo CR, Chan R. 2020 updated asthma guidelines: clinical utility of fractional exhaled nitric oxide (Feno) in asthma management[J]. J Allergy Clin Immunol, 2020, 146(6): 1281-1282. doi: 10.1016/j.jaci.2020.03.006
[23]	Hearn AP, Kavanagh J, D'Ancona G, et al. The relationship between Feno and effectiveness of mepolizumab and benralizumab in severe eosinophilic asthma[J]. J Allergy Clin Immunol Pract, 2021, 9(5): 2093-2096. doi: 10.1016/j.jaip.2021.01.008 pmid: 33486140
[24]	Pavord ID, Deniz Y, Corren J, et al. Baseline FeNO independently predicts the dupilumab response in patients with moderate-to-severe asthma[J]. J Allergy Clin Immunol Pract, 2022 : S2213- 2198(22)01303-4.
[25]	Petsky HL, Cates CJ, Kew KM, et al. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis[J]. Thorax, 2018, 73(12): 1110-1119. doi: 10.1136/thoraxjnl-2018-211540 pmid: 29858277
[26]	Fielding S, Pijnenburg M, de Jongste JC, et al. Change in FEV(1) and feno measurements as predictors of future asthma outcomes in children[J]. Chest, 2019, 155(2): 331-341. doi: S0012-3692(18)32590-X pmid: 30359613
[27]	Petsky HL, Kew KM, Chang AB. Exhaled nitric oxide levels to guide treatment for children with asthma[J/OL]. Cochrane Database Syst Rev, 2016, 11(11): CD011439.
[28]	Bose S, Bime C, Henderson RJ, et al. Biomarkers of type 2 airway inflammation as predictors of loss of asthma control during step-down therapy for well-controlled disease: the long-acting beta-agonist step-down study (LASST)[J]. J Allergy Clin Immunol Pract, 2020, 8(10): 3474-3481. doi: 10.1016/j.jaip.2020.06.067 pmid: 32693214
[29]	Singer F, Luchsinger I, Inci D, et al. Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma[J]. Allergy, 2013, 68(4): 531-538. doi: 10.1111/all.12127 pmid: 23414302
[30]	Bastain TM, Islam T, Berhane KT, et al. Exhaled nitric oxide, susceptibility and new-onset asthma in the children's health study[J]. Eur Respir J, 2011, 37(3): 523-531. doi: 10.1183/09031936.00021210 pmid: 20634264
[31]	Gibson PG, Fujimura M, Niimi A. Eosinophilic bronchitis: clinical manifestations and implications for treatment[J]. Thorax, 2002, 57(2): 178-182. pmid: 11828051
[32]	Asano T, Takemura M, Fukumitsu K, et al. Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status[J]. Allergol Int, 2017, 66(2): 344-350. doi: S1323-8930(16)30134-4 pmid: 27693513
[33]	Song WJ, Kim HJ, Shim JS, et al. Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: a systematic review and meta-analysis[J]. J Allergy Clin Immunol, 2017, 140(3): 701-709. doi: 10.1016/j.jaci.2016.11.037
[34]	Liu X, Wang X, Yao X, et al. Value of exhaled nitric oxide and FEF(25-75) in identifying factors associated with chronic cough in allergic rhinitis[J]. Allergy Asthma Immunol Res, 2019, 11(6): 830-845. doi: 10.4168/aair.2019.11.6.830
[35]	Spitale N, Popat N, McIvor A. Update on exhaled nitric oxide in pulmonary disease[J]. Expert Rev Respir Med, 2012, 6(1): 105-115. doi: 10.1586/ers.12.1
[36]	Taylor DR, Pijnenburg MW, Smith AD, et al. Exhaled nitric oxide measurements: clinical application and interpretation[J]. Thorax, 2006, 61(9): 817-827. doi: 10.1136/thx.2005.056093 pmid: 16936238
[37]	Bousquet J, Khaltaev N, Cruz AA, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)[J]. Allergy, 2008, 63(Suppl 86): 8-160. doi: 10.1111/all.2008.63.issue-s86
[38]	Kawamoto H, Takeno S, Yajin K. Increased expression of inducible nitric oxide synthase in nasal epithelial cells in patients with allergic rhinitis[J]. Laryngoscope, 1999, 109(12): 2015-2020. pmid: 10591366
[39]	Yoon J, Choi YJ, Lee E, et al. Allergic rhinitis in preschool children and the clinical utility of FeNO[J]. Allergy Asthma Immunol Res, 2017, 9(4): 314-321. doi: 10.4168/aair.2017.9.4.314
[40]	Sapsaprang S, Tanticharoenwiwat P, Kulalert P, et al. Comparison of exhaled nitric oxide levels in pediatric patients with allergic rhinitis[J]. Int J Pediatr Otorhinolaryngol, 2019, 126: 109603. doi: 10.1016/j.ijporl.2019.109603
[41]	Ciprandi G, Tosca MA, Capasso M. Exhaled nitric oxide in children with allergic rhinitis and/or asthma: a relationship with bronchial hyperreactivity[J]. J Asthma, 2010, 47(10): 1142-1147. doi: 10.3109/02770903.2010.527026 pmid: 20950134
[42]	Ambrosino P, Parrella P, Formisano R, et al. Clinical application of nasal nitric oxide measurement in allergic rhinitis: a systematic review and meta-analysis[J]. Ann Allergy Asthma Immunol, 2020, 125(4): 447-459. doi: 10.1016/j.anai.2020.07.003
[43]	Liu C, Zheng K, Liu X, et al. Use of nasal nitric oxide in the diagnosis of allergic rhinitis and nonallergic rhinitis in patients with and without sinus inflammation[J]. J Allergy Clin Immunol Pract, 2020, 8(5): 1574-1581. doi: S2213-2198(19)31051-7 pmid: 31891823

年龄	<切点（低值）	临界值	≥切点（高值）
>12岁	<25	25~50	>50
≤12岁	<20	20~35	>35
临床意义	非嗜酸粒细胞性气道炎症	结合临床	嗜酸粒细胞性气道炎症

FeNO	哮喘			慢性咳嗽治疗指导	变应性鼻炎诊断
FeNO	诊断	治疗指导	新发预测	慢性咳嗽治疗指导	变应性鼻炎诊断
<20~25 ppb	非过敏性哮喘或诊断有误	初始治疗提示糖皮质激素治疗效果不佳，哮喘治疗过程中提示近期控制良好	未来发生过敏性哮喘的可能性小	糖皮质激素治疗无效	非变应性鼻炎或诊断有误
临界值	结合临床
>35~50 ppb	过敏性哮喘	初始治疗提示糖皮质激素治疗有效，哮喘治疗过程中提示控制不佳，存在哮喘急性发作风险	未来发生过敏性哮喘的可能性大	糖皮质激素治疗有效	变应性鼻炎