mvjrМедицинский вестник Юга РоссииMedical Herald of the South of Russia2219-80752618-7876The Rostov State Medical University10.21886/2219-8075-2022-13-2-91-101mvjr-1546Research ArticleПЕДИАТРИЯPAEDIATRICSБиомаркеры астмы у детей. Новые возможности, реальная практика и перспективыAsthma biomarkers in children. new opportunities, real practice and frontiershttps://orcid.org/0000-0001-5039-8473ПампураА. Н.PampuraN.

Пампура Александр Николаевич, д.м.н. заведующий отделом аллергологии и клинической иммунологии

Москва

Alexander N. Pampura, Dr. Sci. (Med.), Head of Allergy and Clinical Immunology Department

Moscow

apampura@pedklin.ruhttps://orcid.org/0000-0001-9654-3429КамаевА. В.KamaevA. V.

Камаев Андрей Вячеславович, к.м.н., доцент; кафедра общей практики (семейной медицины)

Санкт-Петербург

Andrey V. Kamaev, Cand. Sci. (Med.), associated professor; department of general practice (family medicine) 

Saint Petersburg

andykkam@mail.ruhttps://orcid.org/0000-0003-4525-1500ЛебеденкоА. А.LebedenkoA. A.

Лебеденко Александр Анатольевич, д.м.н., проф., заведующий кафедры детских болезней №2

Ростов-на-Дону

Alexander A. Lebedenko, Dr. Sci. (Med.), Professor, head of Department of childhood diseases № 2 

Rostov-on-Don

leb.rost@rambler.ruНаучно-исследовательский клинический институт педиатрии им. акад. Ю. Е. Вельтищева, Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; Российская медицинская академия непрерывного профессионального образования»; Морозовская детская городская клиническая больница ДЗМРоссияVeltischev Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional Education; Morozov Children’s Municipal Clinical HospitalRussian FederationПервый Санкт-Петербургский Государственный Медицинский Университет им. акад. И. П. ПавловаРоссияPavlov First Saint-Petersburg State Medical UniversityRussian FederationРостовский государственный медицинский университетРоссияRostov State Medical UniversityRussian Federation20220607202213291101Copyright © Пампура А.Н., Камаев А.В., Лебеденко А.А., 20222022Пампура А.Н., Камаев А.В., Лебеденко А.А.Pampura N., Kamaev A.V., Lebedenko A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medicalherald.ru/jour/article/view/1546

Персонализация ведения детей с хроническими воспалительными неинфекционными заболеваниями, в том числе и бронхиальной астмой (БА) исключительно активно разрабатывается в течение последнего десятилетия. Одним из наиболее важных условий разработки этого направления является выявление биомаркеров, обладающих высокой клинической информативностью. Возможности и эффективность использования биомаркеров определяются выбором цели, патогенетической обоснованностью параметра, адекватным выбором биоматериала, валидностью тестирования и т.д. В статье представлены характеристики наиболее перспективных биомаркеров БА, обозначены их преимущества и недостатки при использовании в педиатрической практике. Рациональное использование биомаркеров уже сегодня позволяет выделить группу риска по развитию БА, предложить рациональную профилактику, в ряде случаев обосновать диагноз и оценить тяжесть заболевания, оптимизировать противовоспалительную терапию, прогнозировать ответ на фармакотерапию, оценить вероятность развития будущих обострений, своевременно выделить детей с тяжелым течением БА, которым необходимо дифференцированно инициировать и провести биологическую терапию.

Personalized management of children with chronic inflammatory non-communicable diseases, including bronchial asthma, have been extremely elaborated last decade. Highly informative biomarkers exploring is one of important conditions of this management. Testing aim, molecule’s pathogeneticrole, adequate biomaterial choice and test validity determine possibility and effectiveness of biomarker application. The paper represents key features of most perspective asthma biomarkers and discuss advantages and disadvantages of their using in pediatric practice. with rational biomarkers implementation nowadays one can separate patients with asthma development risk, provide a rational prevention, confirm the diagnosis and evaluate severity in some cases, optimize anti-inflammatory treatment, prognose the treatment response, evaluate future exacerbation probability, devote children with severe asthma in-time to initiate and conduct biological therapy for them.

биомаркерыбронхиальная астмадетиImmunoCAPаллергочипISAC-обзорbiomarkersasthmachildrenImmunoCAPImmuno Solid-phase Allergy ChipsummaryReferencesKönig I.R, Fuchs O., Hansen G., von Mutius E., Kopp M.V. What is precision medicine? Eur. Respir J. 2017; 50(4):1700391. DOI: 10.1183/13993003.00391-2017König I.R, Fuchs O., Hansen G., von Mutius E., Kopp M.V. What is precision medicine? Eur. Respir J. 2017; 50(4):1700391. DOI: 10.1183/13993003.00391-2017Пампура А. Н. Проблемы и перспективы развития детской аллергологии. Российский вестник перинатологии и педиатрии. 2015. – Т. 60. – № 1. – С. 7-15. eLIBRARY ID: 23093968Pampura A. N. Development of pediatric allergology: Problems and prospects. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2015. – Vol. 60. – No. 1. – pp. 7-15. (In Russ.). eLIBRARY ID: 23093968Bousquet J., Hellings P.W., Agache I., Bedbrook A, Bachert C. et al. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle. Clin Transl Allergy. 2016; 30(6):47. DOI: 10.1186/s13601-016-0137-4.Bousquet J., Hellings P.W., Agache I., Bedbrook A, Bachert C. et al. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle. Clin Transl Allergy. 2016; 30(6):47.Raulf-Heimsoth, M., Wirtz, C., Papenfuss, F., Baur, X. Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2000; 30(1):110-121. doi:10.1046/j.1365-2222.2000.00690.xDOI: 10.1186/s13601-016-0137-4.Kaur R., Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. 2019;144(1):1-12. doi: 10.1016/j.jaci.2019.05.031.Raulf-Heimsoth, M., Wirtz, C., Papenfuss, F., Baur, X. Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2000; 30(1):110-121. doi:10.1046/j.1365-2222.2000.00690.xArron J.R., Izuhara K. Asthma biomarkers: what constitutes a 'gold standard?. Thorax. 2015;70(2):105-107. doi:10.1136/thoraxjnl-2014-206069Kaur R., Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. 2019;144(1):1-12. doi: 10.1016/j.jaci.2019.05.031.Breiteneder H., Peng Y.Q, Agache I., Diamant Z., Eiwegger T. et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy. 2020;75(12):3039-3068. doi: 10.1111/all.14582.Arron J.R., Izuhara K. Asthma biomarkers: what constitutes a 'gold standard?. Thorax. 2015;70(2):105-107. doi:10.1136/thoraxjnl-2014-206069Геппе Н.А., Иванова Н.А., Камаев А.В., Колосова Н.Г., Кондюрина Е.Г., Малахов А.Б. и др. Бронхиальная обструкция на фоне острой респираторной инфекции у детей дошкольного возраста: диагностика, дифференциальная диагностика, терапия и профилактика. М.: МедКом-Про; 2019, 63 с. ISBN 978-5-9500978-9-8. eLIBRARY ID: 37324018Breiteneder H., Peng Y.Q, Agache I., Diamant Z., Eiwegger T. et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy. 2020;75(12):3039-3068. doi: 10.1111/all.14582.Yaneva M., Darlenski R. The link between atopic dermatitis and asthma- immunological imbalance and beyond. Asthma Res Pract. 2021; 15;7(1):16. doi: 10.1186/s40733-021-00082-0.Geppe N.A., Ivanova N.A., Kamaev A.V., Kolosova N.G., Kondyurina E.G., Malakhov A.B. et al. Bronchial obstruction against the background of acute respiratory infection in preschool children: diagnosis, differential diagnosis, therapy and prevention. M.: MedCom-Pro. 2019, 63 p. ISBN 978-5-9500978-9-8. (In Russ.). eLIBRARY ID: 37324018Hallas H.W., Chawes B.L., Rasmussen M.A., Arianto L., Stokholm J. et al. Airway obstruction and bronchial reactivity from age 1 month until 13 years in children with asthma: A prospective birth cohort study. PLoS Med. 2019; 8;16(1):e1002722. doi: 10.1371/journal.pmed.1002722.Yaneva M., Darlenski R. The link between atopic dermatitis and asthma- immunological imbalance and beyond. Asthma Res Pract. 2021; 15;7(1):16. doi: 10.1186/s40733-021-00082-0.Puzzovio P.G., Levi-Schaffer F. Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis. Front Pharmacol. 2021; 30;12:747364. doi: 10.3389/fphar.2021.747364.Hallas H.W., Chawes B.L., Rasmussen M.A., Arianto L., Stokholm J. et al. Airway obstruction and bronchial reactivity from age 1 month until 13 years in children with asthma: A prospective birth cohort study. PLoS Med. 2019; 8;16(1):e1002722. doi: 10.1371/journal.pmed.1002722.Guerra S., Vasquez M.M., Spangenberg A., Halonen, M., Martin R.J. Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. J. Allergy Clin. Immunol. 2016; 138, 932–934.e1. doi.org/10.1016/j.jaci.2016.03.047Puzzovio P.G., Levi-Schaffer F. Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis. Front Pharmacol. 2021; 30;12:747364. doi: 10.3389/fphar.2021.747364.Ma Y.N., Wang, J., Lee Y.L., Ren W.H.; Lv X.-F. et al. Association of urine CC16 and lung function and asthma in Chinese children. Allergy Asthma Proc. 2015; 36, 59–64. doi.org/10.2500/aap.2015.36.3853Guerra S., Vasquez M.M., Spangenberg A., Halonen, M., Martin R.J. Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. J. Allergy Clin. Immunol. 2016; 138, 932–934.e1. doi.org/10.1016/j.jaci.2016.03.047Almuntashiri S., Zhu Y., Han Y., Wang X., Somanath P.R., Zhang D. Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases. J. Clin. Med. 2020, 9, 4039; doi:10.3390/jcm9124039Ma Y.N., Wang, J., Lee Y.L., Ren W.H.; Lv X.-F. et al. Association of urine CC16 and lung function and asthma in Chinese children. Allergy Asthma Proc. 2015; 36, 59–64. doi.org/10.2500/aap.2015.36.3853Kim H.J., Jung Y.J. The Emerging Role of Eosinophils as Multifunctional Leukocytes in Health and Disease. Immune Netw. 2020; 23;20(3):e24. doi: 10.4110/in.2020.20.e24.Almuntashiri S., Zhu Y., Han Y., Wang X., Somanath P.R., Zhang D. Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases. J. Clin. Med. 2020, 9, 4039; doi:10.3390/jcm9124039Korevaar D.A., Westerhof G.A., Wang J., Cohen J.F., Spijker R., Sterk P.J. et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290-300. Doi:10.1016/s2213-2600(15)00050-8Kim H.J., Jung Y.J. The Emerging Role of Eosinophils as Multifunctional Leukocytes in Health and Disease. Immune Netw. 2020; 23;20(3):e24. doi: 10.4110/in.2020.20.e24.Narendra D., Blixt J., Hanania N.A. Immunological biomarkers in severe asthma. Semin Immunol. 2019; 46:101332. doi: 10.1016/j.smim.2019.101332.Korevaar D.A., Westerhof G.A., Wang J., Cohen J.F., Spijker R., Sterk P.J. et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290-300. Doi:10.1016/s2213-2600(15)00050-8CastroRodriguez J.A., Cifuentes L., Martinez F.D. Predicting Asthma Using Clinical Indexes. Front Pediatr. 2019; 31;7:320. doi: 10.3389/fped.2019.00320.Narendra D., Blixt J., Hanania N.A. Immunological biomarkers in severe asthma. Semin Immunol. 2019; 46:101332. doi: 10.1016/j.smim.2019.101332.Anderson H.M., Lemanske R.F., Arron J.R., Holweg CTJ, Rajamanickam V. et al. Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol. 2017;139(3):790-796. doi: 10.1016/j.jaci.2016.05.033.CastroRodriguez J.A., Cifuentes L., Martinez F.D. Predicting Asthma Using Clinical Indexes. Front Pediatr. 2019; 31;7:320. doi: 10.3389/fped.2019.00320.Price D.B., Rigazio A., Campbell J.D., Bleecker E.R, Corrigan C.J. et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015; 3(11):849-58. doi: 10.1016/S2213-2600(15)00367-7.Anderson H.M., Lemanske R.F., Arron J.R., Holweg CTJ, Rajamanickam V. et al. Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol. 2017;139(3):790-796. doi: 10.1016/j.jaci.2016.05.033.Konradsen J.R., Skantz E., Nordlund B., Lidegran M., James A. et al. Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. Pediatr Allergy Immunol. 2015; 26:772–779. doi: 10.1111/pai.12457Price D.B., Rigazio A., Campbell J.D., Bleecker E.R, Corrigan C.J. et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015; 3(11):849-58. doi: 10.1016/S2213-2600(15)00367-7.Just J., Nicoloyanis N., Chauvin M., Pribil C., Grimfeld A, Duru G. Lack of eosinophilia can predict remission in wheezy infants? Clin Exp Allergy. 2008; 38:767–73. doi: 10.1111/j.1365-2222.2008.02966.x.Konradsen J.R., Skantz E., Nordlund B., Lidegran M., James A. et al. Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. Pediatr Allergy Immunol. 2015; 26:772–779. doi: 10.1111/pai.12457Fitzpatrick AM. Severe asthma in children: lessons learned and future directions. J Allergy Clin Immunol Pract. 2016; 4:11–19. doi: 10.1016/j.jaip.2015.10.008.Just J., Nicoloyanis N., Chauvin M., Pribil C., Grimfeld A, Duru G. Lack of eosinophilia can predict remission in wheezy infants? Clin Exp Allergy. 2008; 38:767–73. doi: 10.1111/j.1365-2222.2008.02966.x.Jabbal S., Lipworth B.J. Blood eosinophils: the forgotten man of inhaled steroid dose titration. Clin Exp Allergy. 2018; 48:93–95. doi: 10.1111/cea.13057.Fitzpatrick AM. Severe asthma in children: lessons learned and future directions. J Allergy Clin Immunol Pract. 2016; 4:11–19. doi: 10.1016/j.jaip.2015.10.008.Koh G.C-H., Shek L.P-C., Goh D.Y-T., Van Bever H., Koh D.S-Q. Eosinophil cationic protein: is it useful in asthma? A systematic review. Respir Med. 2007;101:696–705. doi: 10.1016/j.rmed.2006.08.012.]Jabbal S., Lipworth B.J. Blood eosinophils: the forgotten man of inhaled steroid dose titration. Clin Exp Allergy. 2018; 48:93–95. doi: 10.1111/cea.13057.Kato M., Yamada Y., Maruyama K., Hayashi Y. Serum eosinophil cationic protein and 27 cytokines/chemokines in acute exacerbation of childhood asthma. Int Arch Allergy Immunol. 2010;152(Suppl 1):62–66. doi: 10.1159/000312127].Koh G.C-H., Shek L.P-C., Goh D.Y-T., Van Bever H., Koh D.S-Q. Eosinophil cationic protein: is it useful in asthma? A systematic review. Respir Med. 2007;101:696–705. doi: 10.1016/j.rmed.2006.08.012.]Spahn J.D., Covar R.A., Jain N., Gleason M., Shimamoto R., Szefler S.J., et al. Effect of montelukast on peripheral airflow obstruction in children with asthma. Ann Allergy Asthma Immunol. 2006; 96:541–549. doi: 10.1016/S1081-1206(10)63548-XKato M., Yamada Y., Maruyama K., Hayashi Y. Serum eosinophil cationic protein and 27 cytokines/chemokines in acute exacerbation of childhood asthma. Int Arch Allergy Immunol. 2010;152(Suppl 1):62–66. doi: 10.1159/000312127].Fitzpatrick A.M. Biomarkers of asthma and allergic airway diseases. Ann Allergy Asthma Immunol. 2015;115:335–340. doi: 10.1016/j.anai.2015.09.003.Spahn J.D., Covar R.A., Jain N., Gleason M., Shimamoto R., Szefler S.J., et al. Effect of montelukast on peripheral airflow obstruction in children with asthma. Ann Allergy Asthma Immunol. 2006; 96:541–549. doi: 10.1016/S1081-1206(10)63548-XMeteran H., Sivapalan P., Stæhr Jensen J.U. Treatment Response Biomarkers in Asthma and COPD. Diagnostics. 2021, 11, 1668. doi.org/10.3390/diagnostics11091668Fitzpatrick A.M. Biomarkers of asthma and allergic airway diseases. Ann Allergy Asthma Immunol. 2015;115:335–340. doi: 10.1016/j.anai.2015.09.003.Dweik, R.A., Boggs P.B., Erzurum S.C., Irvin, C.G.; Leigh, M.W. 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, 602–615. doi.org/10.1164/rccm.9120-11stMeteran H., Sivapalan P., Stæhr Jensen J.U. Treatment Response Biomarkers in Asthma and COPD. Diagnostics. 2021, 11, 1668. doi.org/10.3390/diagnostics11091668Abe Y., Suzuki M., Kimura H., Shimizu K.; Makita, H. et al. Annual Fractional Exhaled Nitric Oxide Measurements and Exacerbations in Severe Asthma. J. Asthma Allergy. 2020, 13, 731–741. doi.org/10.21203/rs.3.rs-40852/v2Dweik, R.A., Boggs P.B., Erzurum S.C., Irvin, C.G.; Leigh, M.W. 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, 602–615. doi.org/10.1164/rccm.9120-11stJoshi A.Y., Iyer V.N., Boyce T.G., Hagan J.B., Park M.A., Abraham R.S. Elevated serum immunoglobulin E (IgE): When to suspect hyper-IgE syndrome—A 10-year pediatric tertiary care center experience. Allergy Asthma Proc 30:23–27, 2009; doi: 10.2500/aap.2009.30.3193Abe Y., Suzuki M., Kimura H., Shimizu K.; Makita, H. et al. Annual Fractional Exhaled Nitric Oxide Measurements and Exacerbations in Severe Asthma. J. Asthma Allergy. 2020, 13, 731–741. doi.org/10.21203/rs.3.rs-40852/v2Humbert M., Taillé C., Mala L., Le Gros V., Just J. et al. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018. Doi:10.1183/13993003.02523-2017.Joshi A.Y., Iyer V.N., Boyce T.G., Hagan J.B., Park M.A., Abraham R.S. Elevated serum immunoglobulin E (IgE): When to suspect hyper-IgE syndrome—A 10-year pediatric tertiary care center experience. Allergy Asthma Proc 30:23–27, 2009; doi: 10.2500/aap.2009.30.3193Moustaki M., Loukou I., Tsabouri S., Douros K. The Role of Sensitization to Allergen in Asthma Prediction and Prevention. Front Pediatr. 2017; 31;5:166. doi: 10.3389/fped.2017.00166.Humbert M., Taillé C., Mala L., Le Gros V., Just J. et al. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018. Doi:10.1183/13993003.02523-2017.Wickman M., Lupinek C., Andersson N. et al. Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence. EBioMedicine. 2017;26:91-99. doi.org/10.1016/j.ebiom.2017.11.009Moustaki M., Loukou I., Tsabouri S., Douros K. The Role of Sensitization to Allergen in Asthma Prediction and Prevention. Front Pediatr. 2017; 31;5:166. doi: 10.3389/fped.2017.00166.Garib V., Rigler E., Gastager F. et al. Determination of IgE and IgG reactivity to more than 170 allergen molecules in paper-dried blood spots. J Allergy Clin Immunol. 2019; 143(1):437-440. doi.org/10.1016/j.jaci.2018.08.047Wickman M., Lupinek C., Andersson N. et al. Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence. EBioMedicine. 2017;26:91-99. doi.org/10.1016/j.ebiom.2017.11.009Пампура А.Н. Значение липидных медиаторов воспаления при сочетанном атопическом поражении кожи и желудочно-кишечного тракта в обосновании терапии. Автореферат дис. кандидата медицинских наук / Моск. НИИ педиатрии и детской хирургии. Москва, 1995, 26с.Garib V., Rigler E., Gastager F. et al. Determination of IgE and IgG reactivity to more than 170 allergen molecules in paper-dried blood spots. J Allergy Clin Immunol. 2019; 143(1):437-440. doi.org/10.1016/j.jaci.2018.08.047Rabinovitch N., Graber N.J., Chinchilli V.M., Sorkness C.A., Zeiger R.S. et al. Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in childhood asthma. J. Allergy Clin Immunol. 2010;126:545–51. doi.org/10.1016/j.jaci.2010.07.008Pampura A.N. The importance of lipid mediators of inflammation in combined atopic lesions of the skin and gastrointestinal tract in the justification of therapy. Abstract of the dissertation of the Candidate of medical Sciences / Moscow. Research Institute of Pediatrics and Pediatric Surgery. Moscow, 1995, 26c. (In Russ.).Rabinovitch N., Mauger D.T., Reisdorph N., Covar R., Malka J., Lemanske R.F. et al. Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma. J. Allergy Clin Immunol. 2014;133:350–6. doi.org/10.1016/j.jaci.2013.07.039Rabinovitch N, Graber N.J., Chinchilli V.M., Sorkness C.A., Zeiger R.S., Strunk R.C.et al. Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in childhood asthma. J. Allergy Clin Immunol. 2010;126:545–51. doi.org/10.1016/j.jaci.2010.07.008Bochenek G., Stachura T., Szafraniec K., Plutecka H., Sanak M. et al. Diagnostic accuracy of urinary LTE4 measurement to predict aspirin-exacerbated respiratory disease in patients with asthma. J. Allergy Clin Immunol Pract. 2018;6:528–35. doi.org/10.1016/j.jaip.2017.07.001Rabinovitch N., Mauger D.T., Reisdorph N., Covar R., Malka J., Lemanske R.F.Hellings P.W., Steelant В. Epithelial barriers in allergy and asthma. J Allergy Clin Immunol. 2020;145:1499-509. doi: 10.1016/j.jaci.2020.04.010.et al. Predictors of asthma control and lung function responsiveness to stepIzuhara K., Nunomura S., Nanri Y., Ono J., Takai M., Kawaguchi A. Periostin: an emerging biomarker for allergic diseases. Allergy. 2019; 74:2116e28. doi.org/10.1111/all.13814therapy in children with uncontrolled asthma. J. Allergy Clin Immunol.Noguchi T., Nakagome K., Kobayashi T., Uchida Y., Soma T. et al. Periostin upregulates the effector functions of eosinophils. J. Allergy Clin Immunol. 2016; 138:1449e14452 e5. doi.org/10.1016/j.jaci.2016.05.020;133:350–6. doi.org/10.1016/j.jaci.2013.07.039Matsumoto H. Role of serum periostin in the management of asthma and its comorbidities. Respiratory Investigation. doi.org/10.1016/j.resinv.2020.02.003Bochenek G., Stachura T., Szafraniec K., Plutecka H., Sanak M. et al. Diagnostic accuracy of urinary LTE4 measurement to predict aspirin-exacerbated respiratory disease in patients with asthma. J. Allergy Clin Immunol Pract. 2018;6:528–35. doi.org/10.1016/j.jaip.2017.07.001Burgess J.K., Jonker M.R., Berg M., Ten Hacken N.T. et al. Periostin: contributor to abnormal airway epithelial function in asthma? Eur Respir J. 2020 Sep 9:2001286. doi: 10.1183/13993003.01286-2020.Hellings P.W., Steelant В. Epithelial barriers in allergy and asthma. J Allergy Clin Immunol. 2020;145:1499-509. doi: 10.1016/j.jaci.2020.04.010.James A., Janson C., Malinovschi A., Holweg C., Alving K. et al. Serum periostin relates to type-2 inflammation and lung function in asthma: data from the large population based cohort Swedish GA(2)LEN. Allergy. 2017;72:1753e60. doi.org/10.1111/all.13181Izuhara K., Nunomura S., Nanri Y., Ono J., Takai M., Kawaguchi A. Periostin: an emerging biomarker for allergic diseases. Allergy. 2019; 74:2116e28. doi.org/10.1111/all.13814Камаев, А. В. Периостин как предиктор неконтролируемого течения астмы и снижения показателей функции легких у пациентов разных возрастных групп. Ученые записки СПбГМУ им. акад. И.П. Павлова. 2020; Т. 27. № 4. С. 71-79. DOI:10.24884/1607-4181-2020-27-4-71-79.Noguchi T., Nakagome K., Kobayashi T., Uchida Y., Soma T. et al. Periostin upregulates the effector functions of eosinophils. J. Allergy Clin Immunol. 2016; 138:1449e14452 e5. doi.org/10.1016/j.jaci.2016.05.020Ziegler S.F. Thymic stromal lymphopoietin (TSLP) and allergic disease. J. Allergy Clin Immunol. 2012; 130(4): 845–852. doi:10.1016/j.jaci.2012.07.010.Matsumoto H. Role of serum periostin in the management of asthma and its comorbidities. Respiratory Investigation. doi.org/10.1016/j.resinv.2020.02.003Roan F., Obata-Ninomiya K., Ziegler S.F. Epithelial cell–derived cytokines: more than just signaling the alarm. J Clin Invest. 2019;129 (4):14411451. doi:10.1172/jci124606Burgess J.K., Jonker M.R., Berg M., Ten Hacken N.T. et al. Periostin: contributor to abnormal airway epithelial function in asthma? Eur Respir J. 2020 Sep 9:2001286. doi: 10.1183/13993003.01286-2020.Lin S.C., Cheng F.Y., Liu J.L., Ye Y.L. Expression and regulation of thymic stromal lymphopoietin and thymic stromal lymphopoietin receptor heterocomplex in the innate–adaptive immunity of pediatric asthma. Int. J. Mol. Sci. 2018, 19, 1231; doi:10.3390/ijms190412James A., Janson C., Malinovschi A., Holweg C., Alving K. et al. Serum periostin relates to type-2 inflammation and lung function in asthma: data from the large population based cohort Swedish GA(2)LEN. Allergy. 2017;72:1753e60. doi.org/10.1111/all.13181Ying S., O’Connor B., Ratoff J. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 2005;174(12):8183–8190. doi:10.4049/jimmunol.174.12.8183Kamaev A.V. Periostin as a predictor of uncontrolled asthma and decreased lung function in patients of different age groups. Scientific notes of the St. Petersburg State Medical University named after Academician I.P. Pavlov. 2020; Vol. 27. No. 4. pp. 71-79. (In Russ.). DOI:10.24884/1607-4181-2020-27-4-71-79.Зайнуллина О.Н., Печкуров Д.В., Хисматуллина З.Р., Ганковская Л.В. Пилотное исследование уровней Toll-подобного рецептора 2 и тимического стромального лимфопоэтина в сыворотке крови детей с атопическим дерматитом. Педиатрия им. Г.Н. Сперанского. 2021; 100 (2): 64–71. doi.org/10.24110/0031-403x-2021-100-2-64-71Ziegler S.F. Thymic stromal lymphopoietin (TSLP) and allergic disease. J. Allergy Clin Immunol. 2012; 130(4): 845–852. doi:10.1016/j.jaci.2012.07.010.Nejman-Gryz, P., Górska, K., Paplińska-Goryca, M., Proboszcz, M., Krenke, R. (2020). Periostin and Thymic Stromal Lymphopoietin-Potential Crosstalk in Obstructive Airway Diseases. Journal of clinical medicine. 2020;9(11):E3667. doi:10.3390/jcm9113667Roan F., Obata-Ninomiya K., Ziegler S.F. Epithelial cell–derived cytokines: more than just signaling the alarm. J Clin Invest. 2019;129 (4):14411451. doi:10.1172/jci124606Shikotra A., Choy D.F., Ohri C.M. et al. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J. Allergy Clin Immunol. 2012;129(1):104–111. doi:10.1016/j.jaci.2011.08.03124Lin S.C., Cheng F.Y., Liu J.L., Ye Y.L. Expression and regulation of thymic stromal lymphopoietin and thymic stromal lymphopoietin receptor heterocomplex in the innate–adaptive immunity of pediatric asthma. Int. J. Mol. Sci. 2018, 19, 1231; doi:10.3390/ijms190412Камаев А.В., Мизерницкий Ю.Л., Трусова О.В., Камаева И.А., Шапорова Н.Л. Зависимость концентрации тимического стромального лимфопоэтина от уровня контроля бронхиальной астмы и функциональных показателей легких у пациентов разных возрастных групп. Медицинский совет. 2022;16(1):319–326. doi.org/10.21518/2079-701X-2022-16-1-319-326.Ying S., O’Connor B., Ratoff J. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 2005;174(12):8183–8190. doi:10.4049/jimmunol.174.12.8183Ненашева Н.М. Т2-бронхиальная астма: характеристика эндотипа и биомаркеры. Пульмонология. 2019; 29 (2): 216–228. DOI: 10.18093/0869-0189-2019-29-2-216-228Zaynullina O.N., Pechkurov D.V., Hismatullina Z.R., Gankovskaya L.V.. The pilot study of Toll- like receptor level 2 and thymic stromal lymphopoietin in children with atopic dermatitis. PEDIATRIA. 2021; 100 (2): 64-71. (In Russ.). doi.org/10.24110/0031-403x-2021-100-2-64-71Runnstrom M., Pitner H., Xu J., Lee F.E., Kuruvilla M. Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma. J. Inflamm Res. 2022 Jan 11;15:241-249. doi: 10.2147/JIR.S269297. PMID: 35068937; PMCID: PMC8769207.Nejman-Gryz, P., Górska, K., Paplińska-Goryca, M., Proboszcz, M., Krenke, R. (2020). Periostin and Thymic Stromal Lymphopoietin-Potential Crosstalk in Obstructive Airway Diseases. Journal of clinical medicine. 2020;9(11):E3667. doi:10.3390/jcm9113667Cevhertas, L., Ogulur, I., Maurer, D. J., Burla, D., Ding, M. et al. (2020). Advances and Recent Developments in Asthma in 2020. Allergy 75, 3124–3146. doi:10.1111/all.14607.Shikotra A., Choy D.F., Ohri C.M. et al. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J. Allergy Clin Immunol. 2012;129(1):104–111. doi:10.1016/j.jaci.2011.08.03124Agache I., Akdis C.A., Akdis M., Canonica G.W, Casale T. et al. EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy. 2021;76(1):14-44. doi: 10.1111/all.14425.Kamaev A.V., Mizernitsky Yu.L., Trusova O.V., Kamaeva I.A., Shaporova N.L. Dependence of thymic stromal lymphopoietin serum concentration from bronchial asthma control level and lung function results in patients of different age groups. Medical Advice. 2022;16(1):319–326. (In Russ.). doi.org/10.21518/2079-701X-2022-16-1-319-326.Nenasheva N.M. T2-bronchial asthma: endotype characteristics and biomarkers. Pulmonology. 2019; 29 (2): 216–228. (In Russ.). DOI: 10.18093/0869-0189-2019-29-2-216-228Nenasheva N.M. T2-bronchial asthma: endotype characteristics and biomarkers. Pulmonology. 2019; 29 (2): 216–228. (In Russ.). DOI: 10.18093/0869-0189-2019-29-2-216-228Runnstrom M., Pitner H., Xu J., Lee F.E., Kuruvilla M. Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma. J. Inflamm Res. 2022 Jan 11;15:241-249. doi: 10.2147/JIR.S269297. PMID: 35068937; PMCID: PMC8769207.Runnstrom M., Pitner H., Xu J., Lee F.E., Kuruvilla M. Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma. J. Inflamm Res. 2022 Jan 11;15:241-249. doi: 10.2147/JIR.S269297. PMID: 35068937; PMCID: PMC8769207.Cevhertas, L., Ogulur, I., Maurer, D. J., Burla, D., Ding, M. et al. (2020). Advances and Recent Developments in Asthma in 2020. Allergy 75, 3124–3146. doi:10.1111/all.14607.Cevhertas, L., Ogulur, I., Maurer, D. J., Burla, D., Ding, M. et al. (2020). Advances and Recent Developments in Asthma in 2020. Allergy 75, 3124–3146. doi:10.1111/all.14607.Agache I., Akdis C.A., Akdis M., Canonica G.W, Casale T. et al. EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy. 2021;76(1):14-44. doi: 10.1111/all.14425.Agache I., Akdis C.A., Akdis M., Canonica G.W, Casale T. et al. EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy. 2021;76(1):14-44. doi: 10.1111/all.14425.

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