HIGH-SENSITIVITY MULTIPLEX ANALYSIS OF INTERLEUKINS IN EXHALED BREATH CONDENSATE FROM CHILDREN WITH BRONCHIAL ASTHMA: DIAGNOSTIC SIGNIFICANCE OF IL-13 AND IL-17A
- Authors: Tereshchenko S.Y.1, Gorbacheva N.N.1, Smolnikova M.V.1
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Affiliations:
- Scientific Research Institute of Medical Problems of the North – a separate division of Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
- Section: Immunological readings in Chelyabinsk
- Submitted: 12.05.2025
- Accepted: 25.05.2025
- URL: https://rusimmun.ru/jour/article/view/17272
- DOI: https://doi.org/10.46235/1028-7221-17272-HSM
- ID: 17272
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Full Text
Abstract
AbstractInterleukins play a key role in the formation of bronchial asthma endotypes, which determines the clinical course of the disease and the effectiveness of therapy. Exhaled breath condensate (EBC) represents a promising non-invasive material for assessing local airway inflammation in asthma; however, data on the possibility of detecting cytokines in EBC in children are limited. Aim: To establish the possibility of detection and diagnostic significance of IL-4, IL-5, IL-13, and IL-17A in EBC in children with asthma using high-sensitivity multiplex analysis. Methods: The study included 169 children aged 6-17 years (104 with asthma and 65 healthy controls). EBC was collected using RTube (Respiratory Research, США), samples were concentrated, and interleukin levels were determined by multiplex analysis on the MAGPIX (Luminex, USA) platform. Results: Analysis of interleukins in exhaled air condensate showed that children with bronchial asthma exhibit statistically significant changes compared to the control group. Children with asthma showed significantly increased detection rates of IL-13 (53.9% vs 30.8%, p=0.003) and IL-17A (57.7% vs 27.7%, p=0.001) compared to controls. The detection frequency of these cytokines progressively increased with disease severity, reaching 72.7% for IL-13 and 63.6% for IL-17A in severe asthma. Conclusion: Our results demonstrate the possibility of detecting key cytokines in exhaled air condensate in children with bronchial asthma using highly sensitive multiplex analysis after preliminary concentration of samples. Detection of IL-13 and IL-17A in EBC can be considered as potential non-invasive biomarkers of asthma severity in children. However, further studies with larger patient populations and standardization of sample concentration procedures are needed for clinical implementation of the method. The data obtained demonstrate the promise of using EBC for non-invasive assessment of local airway inflammation in children with bronchial asthma.
About the authors
Sergey Yurevich Tereshchenko
Scientific Research Institute of Medical Problems of the North – a separate division of Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
Email: legise@mail.ru
M.D. (Medicine), Professor, Head of the Clinical Department of Somatic and Mental Health of Children
Russian FederationNina Nikolaevna Gorbacheva
Scientific Research Institute of Medical Problems of the North – a separate division of Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
Email: n-n-gorbacheva@yandex.ru
senior researcher
Russian FederationMarina Victorovna Smolnikova
Scientific Research Institute of Medical Problems of the North – a separate division of Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
Author for correspondence.
Email: smarinv@yandex.ru
PhD, Head of the Molecular Genetic Research Group, Leading Researcher
Russian FederationReferences
- Сидоренко Г.И., Зборовский Э.И., Левина Д.И. Поверхностно-активные свойства конденсата выдыхаемого воздуха (новый способ исследования функций легких). // Терапевтический архив. – 1980. – Т.53, №.3. – С.:65–68. Sidorenko G.I., Zborovskiĭ E.I., Levina D.I. Surface-active properties of the exhaled air condensate (a new method of studying lung function). J. Ter Arkh., 1980, Vol. 52, no. 3, pp. 65-68. https://pubmed.ncbi.nlm.nih.gov/6892965/
- Global Asthma Report 2021. Global Asthma Network. Available At: https://Globalasthmareport.Org [Accessed: January 30.] - https://Globalasthmareport.Org
- Hao W., Li M., Zhang C., Zhang Y., Wang P. Inflammatory mediators in exhaled breath condensate and peripheral blood of healthy donors and stable COPD patients. J. Immunopharmacol Immunotoxicol, 2019, Vol. 41, no. 2, pp. 224-230. - https://www.tandfonline.com/doi/full/10.1080/08923973.2019.1609496 [doi: 10.1080/08923973.2019.1609496]
- Horváth I., Hunt J., Barnes P.J., Alving K., Antczak A., Baraldi E., Becher G., Van Beurden W.J., Corradi M., Dekhuijzen R., Dweik R.A., Dwyer T., Effros R., Erzurum S., Gaston B., Gessner C., Greening A., Ho L.P., Hohlfeld J., Jöbsis Q., Laskowski D., Loukides S., Marlin D., Montuschi P., Olin A.C., Redington A.E., Reinhold P., Van Rensen E.L., Rubinstein I., Silkoff P., Toren K., Vass G., Vogelberg C., Wirtz H. Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J., 2005, Vol. 26, no. 3, pp. 523-548. - https://publications.ersnet.org/content/erj/26/3/523
- [doi: 10.1183/09031936.05.00029705]
- Kasule G.W., Hermans S., Semugenze D., Wekiya E., Nsubuga J., Mwachan P., Kabugo J., Joloba M., García-Basteiro A.L., Ssengooba W. Non-sputum-based samples and biomarkers for detection of Mycobacterium tuberculosis: the hope to improve childhood and HIV-associated tuberculosis diagnosis. Eur J. Med Res., 2024, Vol. 29, no. 1, 502. - https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-02092-z
- [doi: 10.1186/s40001-024-02092-z]
- Kita K., Gawinowska M., Chełmińska M., Niedoszytko M. The Role of Exhaled Breath Condensate in Chronic Inflammatory and Neoplastic Diseases of the Respiratory Tract. Int J. Mol Sci., 2024, Vol. 25, no. 13, 7395. - https://www.mdpi.com/1422-0067/25/13/7395
- [doi: 10.3390/ijms25137395]
- Maison N., Omony J., Illi S., Thiele D., Skevaki C., Dittrich A.M., Bahmer T., Rabe K.F., Weckmann M., Happle C., Schaub B., Meyer M., Foth S., Rietschel E., Renz H., Hansen G., Kopp M.V., Von Mutius E., Grychtol R., Fuchs O., Roesler B., Welchering N., Kohistani-Greif N., Kurz J., Landgraf-Rauf K., Laubhahn K., Liebl C., Ege M., Hose A., Zeitlmann E., Berbig M., Marzi C., Schauberger C., Zissler U., Schmidt-Weber C., Ricklefs I., Diekmann G., Liboschik L., Voigt G., Sultansei L., Nissen G., König I.R., Kirsten A.M., Pedersen F., Watz H., Waschki B., Herzmann C., Abdo M., Biller H., Gaede K.I., Bovermann X., Steinmetz A., Husstedt B.L., Nitsche C., Veith V., Szewczyk M., Brinkmann F., Malik A., Schwerk N., Dopfer C., Price M., Jirmo A.C., Habener A., Deluca D.S., Gaedcke S., Liu B., Calveron M.R., Weber S., Schildberg T., Van Koningsbruggen-Rietschel S., Alcazar M. T2-high asthma phenotypes across lifespan. Eur Respir J., 2022, Vol. 60, no. 3, 2102288. - https://publications.ersnet.org/content/erj/60/3/2102288
- [doi: 10.1183/13993003.02288-2021]
- Montesi S.B., Mathai S.K., Brenner L.N., Gorshkova I.A., Berdyshev E.V., Tager A.M., Shea B.S. Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis. BMC Pulm Med., 2014, Vol. 14, 5. - https://bmcpulmmed.biomedcentral.com/articles/10.1186/1471-2466-14-5
- [doi: 10.1186/1471-2466-14-5]
- Nessen E., Toussaint B., Israëls J., Brinkman P., Maitland-Van Der Zee A.H., Haarman E. The Non-Invasive Detection of Pulmonary Exacerbations in Disorders of Mucociliary Clearance with Breath Analysis: A Systematic Review. J. Clin Med., 2024, Vol. 13, no. 12, 3372. - https://www.mdpi.com/2077-0383/13/12/3372
- [doi: 10.3390/jcm13123372]
- Pleil J.D., Wallace M.A.G., Madden M.C. Exhaled breath aerosol (EBA): the simplest non-invasive medium for public health and occupational exposure biomonitoring. J. Breath Res., 2018, Vol. 12, no. 2, 027110. - https://iopscience.iop.org/article/10.1088/1752-7163/aa9855
- [doi: 10.1088/1752-7163/aa9855]
- Steinke J.W., Lawrence M.G., Teague W.G., Braciale T.J., Patrie J.T., Borish L. Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma. J. Allergy Clin Immunol., 2021, Vol. 147, no. 2, pp. 686-693. - https://www.jacionline.org/article/S0091-6749(20)30809-5/fulltext
- [doi: 10.1016/j.jaci.2020.05.039]
- Stiegel M.A., Pleil J.D., Sobus J.R., Morgan M.K., Madden M.C. Analysis of inflammatory cytokines in human blood, breath condensate, and urine using a multiplex immunoassay platform. Biomarkers, 2015, Vol. 20, no. 1, pp. 35-46. - https://www.tandfonline.com/doi/full/10.3109/1354750X.2014.988646
- [doi: 10.3109/1354750x.2014.988646]
- Szunerits S., Dӧrfler H., Pagneux Q., Daniel J., Wadekar S., Woitrain E., Ladage D., Montaigne D., Boukherroub R. Exhaled breath condensate as bioanalyte: from collection considerations to biomarker sensing. J. Anal Bioanal Chem., 2023, Vol. 415, no. 1, pp. 27-34. - https://link.springer.com/article/10.1007/s00216-022-04433-5
- [doi: 10.1007/s00216-022-04433-5]
- Thomas P.S., Lowe A.J., Samarasinghe P., Lodge C.J., Huang Y., Abramson M.J., Dharmage S.C., Jaffe A. Exhaled breath condensate in pediatric asthma: promising new advance or pouring cold water on a lot of hot air? A systematic review. J. Pediatr Pulmonol., 2013, Vol. 48, no. 5, pp. 419-442. - https://pubmed.ncbi.nlm.nih.gov/23401497/
- [doi: 10.1002/ppul.22776]
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