pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2025-35-4-491-499pulmo-4789Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESВозрастные особенности концентрации выдыхаемого оксида азота у пациентов с бронхиальной астмойAge-related differences in the fractional exhaled nitric oxide concentration in patients with asthmahttps://orcid.org/0000-0003-2123-8440МокроносоваМ. А.MokronosovaM. A.

Мокроносова Марина Адольфовна – д. м. н., профессор, ведущий научный сотрудник лаборатории аллергодиагностики 

105064, Москва, Малый Казенный пер., 5А

Marina A. Mokronosova, Doctor of Medicine, Professor, Leading Researcher, Laboratory of Allergy Diagnostics

Malyy Kazennyy per. 5A, Moscow, 105064

mmokronosova@mail.ruhttps://orcid.org/0000-0002-3623-4293КонищеваА. Ю.KonishchevaA. Yu.

Конищева Анна Юрьевна – к. м. н., ведущий научный сотрудник лаборатории аллергодиагностики 

105064, Москва, Малый Казенный пер., 5А

Anna Yu. Konishcheva, Candidate of Medicine, Leading Researcher, Laboratory of Allergy Diagnostics

Malyy Kazennyy per. 5A, Moscow, 105064

ankon81@list.ruhttps://orcid.org/0000-0003-4692-9897МазуринаС. А.MazurinaS. A.

Мазурина Светлана Александровна – к. б. н., ведущий научный сотрудник лаборатории аллергодиагностики 

105064, Москва, Малый Казенный пер., 5А

Svetlana A. Mazurina, Candidate of Biological Sciences, Leading Researcher, Laboratory of Allergy Diagnostics

Malyy Kazennyy per. 5A, Moscow, 105064

S.Mazurina@gmail.comhttps://orcid.org/0000-0001-5394-7132ЖелтиковаТ. М.ZheltikovaT. M.

Желтикова Татьяна Михайловна – д. б. н., профессор, заведующая лабораторией аллергодиагностики 

105064, Москва, Малый Казенный пер., 5А

Tatyana M. Zheltikova, Doctor of Biology, Professor, Head of Laboratory of Allergy Diagnostics

Malyy Kazennyy per. 5A, Moscow, 105064

t-zheltikova@yandex.ruФедеральное государственное бюджетное научное учреждение «Научно-исследовательский институт вакцин и сывороток имени И.И.Мечникова» Министерства науки и высшего образования Российской ФедерацииРоссияFederal State Budgetary Scientific Institution “I.I.Mechnikov Vaccine and Serum Research Institute” Ministry of Science and Higher Education of the Russian FederationRussian Federation202508082025354491499Copyright © Мокроносова М.А., Конищева А.Ю., Мазурина С.А., Желтикова Т.М., 20252025Мокроносова М.А., Конищева А.Ю., Мазурина С.А., Желтикова Т.М.Mokronosova M.A., Konishcheva A.Y., Mazurina S.A., Zheltikova T.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4789

Концентрация оксида азота (NO) в выдыхаемом воздухе (Fractional exhaled nitric oxide concentration – FeNO) является биомаркером эозинофильного воспаления дыхательных путей (ДП) и служит надежным предиктором эффективности терапии глюкокортикостероидами.

 Целью исследования явилась оценка FeNO у больных бронхиальной астмой (БА) различной степени тяжести в зависимости от возраста пациентов.

Материалы и методы

Материалы и методы. В исследовании приняли участие пациенты (n = 489) с аллергическими заболеваниями в возрасте 4–68 лет. На основании клинических признаков и данных лабораторно-инструментального обследования у 305 (62 %) пациентов диагностирована БА. Группу сравнения составили 184 (38 %) пациента. Все пациенты были распределены на 7 возрастных групп: до 7 лет, 8–10, 11–14, 15–18, 19–30, 31–55 и 56 лет и старше. Определение FeNO во выдыхаемом воздухе проводилось с помощью портативного ручного монитора окиси азота NOBreath (Bedfont Scientific Ltd, Великобритания) в соответствии с рекомендациями Европейского респираторного общества (European Respiratory Society – ERS) / Американского торакального общества (American Thoracic Society – ATS). Статистическая обработка количественных данных выполнялась с помощью статистических формул программы Microsoft Office Excel 2016 и Statistiсa 10.0.

Результаты

Результаты. Установлены возрастные особенности концентрации FeNO у пациентов с БА. Показано, что у детей до 7 лет независимо от наличия БА, а также тяжести ее течения концентрация FeNO не превышала 35 ppb, у больных БА старше 8 лет – в 2 раза выше, чем в молодом возрасте. У пациентов с БА в возрасте 19–68 лет показатели FeNO были сравнимы, при этом разброс значений FeNO (M; 95%-ный доверительный интервал) у лиц пожилого возраста (старше 55 лет) значительно шире, что может быть связано с большим числом коморбидных факторов и сопутствующих заболеваний. Среди взрослых пациентов с БА легкой степени превышение концентрации FeNO выявлялось в 1,6–2 раза реже, чем у пациентов с БА средней и тяжелой степени. У детей при этом наблюдались разнонаправленные тенденции.

Заключение

Заключение. Повышенная концентрация FeNO, особенно у маленьких детей, может служить чувствительным биомаркером, отражающим изменения в слизистой оболочке ДП.

Fractional exhaled nitric oxide concentration (FeNO) is a biomarker of eosinophilic airway inflammation and a reliable predictor of corticosteroid therapy.

The aim was to assess the concentration of FeNO in patients with asthma of different severity, depending on age. Methods. Our study involved 489 patients with asthma aged 4 to 68 years. 305 (62%) patients were diagnosed with asthma based on clinical symptoms and laboratory and instrumental diagnostics. The control group included 184 (38%) patients without asthma. All patients were divided into age groups: under 7 years, 8 – 10, 11 – 14, 15 – 18, 19 – 30, 31 – 55 years, and 56 years and older. FeNO level was measured according to the American Thoracic Society/European Respiratory Society recommendations using a portable hand-held nitric oxide monitor NOBreath (Bedfont Scientific Ltd, UK). Statistical processing of quantitative data was performed using Microsoft Office Excel 2016 and Statistiсa 10.0.

Results

Results. FeNO concentration in patients with asthma was age-related. It did not exceed 35 ppb regardless of the presence of asthma and its severity in children under 7 years of age. FeNO concentration was 2 times higher in patients with asthma over 8 years of age than in the younger patients. FeNO values were comparable in the patients aged 19 – 68 years, while the range of FeNO values (M; 95% CI) in elderly people (over 55 years) was significantly wider, which may be associated with many comorbid factors and concomitant diseases. Elevated FeNO concentrations were detected 1.6 – 2 times less frequently among adult patients with mild asthma than in patients with moderate and severe asthma. The opposite trends were observed in children.

Conclusion

Conclusion. Elevated FeNO levels in young children can serve as a sensitive biomarker reflecting changes in the respiratory mucosa.

оксид азота в выдыхаемом воздухеFeNOбронхиальная астмадетивзрослыеfractional exhaled nitric oxide (FeNO)bronchial asthmachildrenadultsReferencesGlobal Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Update 2024. Available at: https://ginasthma.org/2024-report/Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Update 2024. Available at: https://ginasthma.org/2024-report/Martinez F.D., Wright A.L., Taussig L.M. et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N. Engl. J. Med. 1995; 332 (3): 133–138. DOI: 10.1056/NEJM199501193320301.Martinez F.D., Wright A.L., Taussig L.M. et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N. Engl. J. Med. 1995; 332 (3): 133–138. DOI: 10.1056/NEJM199501193320301.Castro-Rodríguez J.A., Holberg C.J., Wright A.L., Martinez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing. Am. J. Respir. Crit. Care Med. 2000; 162 (4, Pt 1): 1403–1406. DOI: 10.1164/ajrccm.162.4.9912111.Castro-Rodríguez J.A., Holberg C.J., Wright A.L., Martinez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing. Am. J. Respir. Crit. Care Med. 2000; 162 (4, Pt 1): 1403–1406. DOI: 10.1164/ajrccm.162.4.9912111.Leonardi N.A., Spycher B.D., Strippoli M.P. et al. Validation of the asthma predictive index and comparison with simpler clinical prediction rules. J. Allergy Clin. Immunol. 2011; 127 (6): 1466–1472.e6. DOI: 10.1016/j.jaci.2011.03.001.Leonardi N.A., Spycher B.D., Strippoli M.P. et al. Validation of the asthma predictive index and comparison with simpler clinical prediction rules. J. Allergy Clin. Immunol. 2011; 127 (6): 1466–1472.e6. DOI: 10.1016/j.jaci.2011.03.001.Schneider A., Gindner L., Tilemann L. et al. Diagnostic accuracy of spirometry in primary care. BMC Pulm. Med. 2009; 9: 31. DOI: 10.1186/1471-2466-9-31.Schneider A., Gindner L., Tilemann L. et al. Diagnostic accuracy of spirometry in primary care. BMC Pulm. Med. 2009; 9: 31. DOI: 10.1186/1471-2466-9-31.Papi A., Brightling C., Pedersen S.E., Reddel H.K. Asthma. Lancet. 2018; 391 (10122): 783–800. DOI: 10.1016/S0140-6736(17)33311-1.Papi A., Brightling C., Pedersen S.E., Reddel H.K. Asthma. Lancet. 2018; 391 (10122): 783–800. DOI: 10.1016/S0140-6736(17)33311-1.Cavicchi M., Whittle B.J. Potentiation of cytokine induced iNOS expression in the human intestinal epithelial cell line, DLD-1, by cyclic AMP. Gut. 1999; 45 (3): 367–374. DOI: 10.1136/gut.45.3.367.Cavicchi M., Whittle B.J. Potentiation of cytokine induced iNOS expression in the human intestinal epithelial cell line, DLD-1, by cyclic AMP. Gut. 1999; 45 (3): 367–374. DOI: 10.1136/gut.45.3.367.Poljakovic M., Karpman D., Svanborg C., Persson K. Human renal epithelial cells express iNOS in response to cytokines but not bacteria. Kidney Int. 2002; 61 (2): 444–455. DOI: 10.1046/j.1523-1755.2002.00138.x.Poljakovic M., Karpman D., Svanborg C., Persson K. Human renal epithelial cells express iNOS in response to cytokines but not bacteria. Kidney Int. 2002; 61 (2): 444–455. DOI: 10.1046/j.1523-1755.2002.00138.x.George L., Brightling C.E. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther. Adv. Chronic Dis. 2016; 7 (1): 34–51. DOI: 10.1177/2040622315609251.George L., Brightling C.E. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther. Adv. Chronic Dis. 2016; 7 (1): 34–51. DOI: 10.1177/2040622315609251.Ricciardolo F.L., Sterk P.J., Gaston B., Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol. Rev. 2004; 84 (3): 731–765. DOI: 10.1152/physrev.00034.2003.Ricciardolo F.L., Sterk P.J., Gaston B., Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol. Rev. 2004; 84 (3): 731–765. DOI: 10.1152/physrev.00034.2003.Diamant Z., Vijverberg S., Alving K. et al. Toward clinically applicable biomarkers for asthma: an EAACI position paper. Allergy. 2019; 74 (10): 1835–1851. DOI: 10.1111/all.13806.Diamant Z., Vijverberg S., Alving K. et al. Toward clinically applicable biomarkers for asthma: an EAACI position paper. Allergy. 2019; 74 (10): 1835–1851. DOI: 10.1111/all.13806.Gustafsson L.E., Leone A.M., Persson M.G. et al. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem. Biophys. Res. Commun. 1991; 181 (2): 852–857. DOI: 10.1016/0006-291x(91)91268-h.Gustafsson L.E., Leone A.M., Persson M.G. et al. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem. Biophys. Res. Commun. 1991; 181 (2): 852–857. DOI: 10.1016/0006-291x(91)91268-h.American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide 2005. Am. J. Respir. Crit. Care Med. 2005; 171 (8): 912–930. DOI: 10.1164/rccm.200406-710ST.American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide 2005. Am. J. Respir. Crit. Care Med. 2005; 171 (8): 912–930. DOI: 10.1164/rccm.200406-710ST.Asthma: diagnosis and monitoring of asthma in adults, children and young people. London: National Institute for Health and Care Excellence (NICE); 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK469773/Asthma: diagnosis and monitoring of asthma in adults, children and young people. London: National Institute for Health and Care Excellence (NICE); 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK469773/Plaza V., Alobid I., Alvarez C. et al. [Translated article]. Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and controversies. Arch. Bronconeumol. 2022; 58 (2): T150–158. DOI: 10.1016/j.arbres.2021.05.032.Plaza V., Alobid I., Alvarez C. et al. [Translated article]. Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and controversies. Arch. Bronconeumol. 2022; 58 (2): T150–158. DOI: 10.1016/j.arbres.2021.05.032.Dweik R.A., Boggs P.B., Erzurum S.C. et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am. J. Respir. Crit. Care Med. 2011; 184 (5): 602–615. DOI: 10.1164/rccm.9120-11ST.Dweik R.A., Boggs P.B., Erzurum S.C. et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am. J. Respir. Crit. Care Med. 2011; 184 (5): 602–615. DOI: 10.1164/rccm.9120-11ST.Loewenthal L., Menzies-Gow A. FeNO in Asthma. Semin. Respir. Crit. Care Med. 2022; 43 (5): 635–645. DOI: 10.1055/s-0042-1743290.Loewenthal L., Menzies-Gow A. FeNO in Asthma. Semin. Respir. Crit. Care Med. 2022; 43 (5): 635–645. DOI: 10.1055/s-0042-1743290.Czubaj-Kowal M., Nowicki G.J., Kurzawa R. et al. Factors influencing the concentration of exhaled nitric oxide (FeNO) in school children aged 8–9-years-old in Krakow, with high FeNO values ≥ 20 ppb. Medicina (Kaunas). 2022; 58 (2): 146. DOI: 10.3390/medicina58020146.Czubaj-Kowal M., Nowicki G.J., Kurzawa R. et al. Factors influencing the concentration of exhaled nitric oxide (FeNO) in school children aged 8–9-years-old in Krakow, with high FeNO values ≥ 20 ppb. Medicina (Kaunas). 2022; 58 (2): 146. DOI: 10.3390/medicina58020146.Taylor E.S., Smith A.D., Cowan J.O. et al. Effect of caffeine ingestion on exhaled nitric oxide measurements in patients with asthma. Am. J. Respir. Crit. Care Med. 2004; 169 (9): 1019–1021. DOI: 10.1164/rccm.200310-1473OC.Taylor E.S., Smith A.D., Cowan J.O. et al. Effect of caffeine ingestion on exhaled nitric oxide measurements in patients with asthma. Am. J. Respir. Crit. Care Med. 2004; 169 (9): 1019–1021. DOI: 10.1164/rccm.200310-1473OC.Buchvald F., Baraldi E., Carraro S. et al. Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. J. Allergy Clin. Immunol. 2005; 115 (6): 1130–1136. DOI: 10.1016/j.jaci.2005.03.020.Buchvald F., Baraldi E., Carraro S. et al. Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. J. Allergy Clin. Immunol. 2005; 115 (6): 1130–1136. DOI: 10.1016/j.jaci.2005.03.020.Tsang K.W., Ip S.K., Leung R. et al. Exhaled nitric oxide: the effects of age, gender and body size. Lung. 2001; 179 (2): 83–91. DOI: 10.1007/s004080000050.Tsang K.W., Ip S.K., Leung R. et al. Exhaled nitric oxide: the effects of age, gender and body size. Lung. 2001; 179 (2): 83–91. DOI: 10.1007/s004080000050.Ekroos H., Tuominen J., Sovijärvi A.R. Exhaled nitric oxide and its long-term variation in healthy non-smoking subjects. Clin. Physiol. 2000; 20 (6): 434–439. DOI: 10.1046/j.1365-2281.2000.00277.x.Ekroos H., Tuominen J., Sovijärvi A.R. Exhaled nitric oxide and its long-term variation in healthy non-smoking subjects. Clin. Physiol. 2000; 20 (6): 434–439. DOI: 10.1046/j.1365-2281.2000.00277.x.Liu Y., Zhang H., Wang J. et al. Reference values for exhaled nitric oxide in healthy children aged 6–18 years in China: a cross-sectional, multicenter clinical study. Respir. Res. 2024; 25 (1): 340. DOI: 10.1186/s12931-024-02938-4.Liu Y., Zhang H., Wang J. et al. Reference values for exhaled nitric oxide in healthy children aged 6–18 years in China: a cross-sectional, multicenter clinical study. Respir. Res. 2024; 25 (1): 340. DOI: 10.1186/s12931-024-02938-4.Buchvald F., Bisgaard H. FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr. Am. J. Respir. Crit. Care Med. 2001; 163 (3, Pt 1): 699–704. DOI: 10.1164/ajrccm.163.3.2004233.Buchvald F., Bisgaard H. FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr. Am. J. Respir. Crit. Care Med. 2001; 163 (3, Pt 1): 699–704. DOI: 10.1164/ajrccm.163.3.2004233.Ghdifan S., Verin E., Couderc L. et al. Exhaled nitric oxide fractions are well correlated with clinical control in recurrent infantile wheeze treated with inhaled corticosteroids. Pediatr. Allergy Immunol. 2010; 21 (7): 1015–1020. DOI: 10.1111/j.1399-3038.2010.01076.x.Ghdifan S., Verin E., Couderc L. et al. Exhaled nitric oxide fractions are well correlated with clinical control in recurrent infantile wheeze treated with inhaled corticosteroids. Pediatr. Allergy Immunol. 2010; 21 (7): 1015–1020. DOI: 10.1111/j.1399-3038.2010.01076.x.van der Heijden H.H., Brouwer M.L., Hoekstra F. et al. Reference values of exhaled nitric oxide in healthy children 1–5 years using off-line tidal breathing. Pediatr. Pulmonol. 2014; 49 (3): 291–295. DOI: 10.1002/ppul.22796.van der Heijden H.H., Brouwer M.L., Hoekstra F. et al. Reference values of exhaled nitric oxide in healthy children 1–5 years using off-line tidal breathing. Pediatr. Pulmonol. 2014; 49 (3): 291–295. DOI: 10.1002/ppul.22796.van Mastrigt E., Gabriele C., de Jongste J.C. Exhaled nitric oxide in infants – what is a nice test like FeNO doing in a place like this? Semin. Respir. Crit. Care Med. 2007; 28 (3): 264–271. DOI: 10.1055/s-2007-981647.van Mastrigt E., Gabriele C., de Jongste J.C. Exhaled nitric oxide in infants – what is a nice test like FeNO doing in a place like this? Semin. Respir. Crit. Care Med. 2007; 28 (3): 264–271. DOI: 10.1055/s-2007-981647.Moeller A., Diefenbacher C., Lehmann A. et al. Exhaled nitric oxide distinguishes between subgroups of preschool children with respiratory symptoms. J. Allergy Clin. Immunol. 2008; 121 (3): 705–709. DOI: 10.1016/j.jaci.2007.11.008.Moeller A., Diefenbacher C., Lehmann A. et al. Exhaled nitric oxide distinguishes between subgroups of preschool children with respiratory symptoms. J. Allergy Clin. Immunol. 2008; 121 (3): 705–709. DOI: 10.1016/j.jaci.2007.11.008.Caudri D., Wijga A.H., Hoekstra M.O. et al. Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE. Thorax. 2010; 65 (9): 801–807. DOI: 10.1136/thx.2009.126912.Caudri D., Wijga A.H., Hoekstra M.O. et al. Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE. Thorax. 2010; 65 (9): 801–807. DOI: 10.1136/thx.2009.126912.Singer F., Luchsinger I., Inci D. et al. Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma. Allergy. 2013; 68 (4): 531–538. DOI: 10.1111/all.12127.Singer F., Luchsinger I., Inci D. et al. Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma. Allergy. 2013; 68 (4): 531–538. DOI: 10.1111/all.12127.Yang Q., Cai C., Xu Q. et al. Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children? Front. Pediatr. 2023; 11: 1189496. DOI: 10.3389/fped.2023.1189496.Yang Q., Cai C., Xu Q. et al. Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children? Front. Pediatr. 2023; 11: 1189496. DOI: 10.3389/fped.2023.1189496.Escamilla-Gil J.M., Fernandez-Nieto M., Acevedo N. Understanding the cellular sources of the fractional exhaled nitric oxide (FeNO) and its role as a biomarker of type 2 inflammation in asthma. Biomed. Res. Int. 2022; 2022: 5753524. DOI: 10.1155/2022/5753524.Escamilla-Gil J.M., Fernandez-Nieto M., Acevedo N. Understanding the cellular sources of the fractional exhaled nitric oxide (FeNO) and its role as a biomarker of type 2 inflammation in asthma. Biomed. Res. Int. 2022; 2022: 5753524. DOI: 10.1155/2022/5753524.

The authors declare that there are no conflicts of interest present.