therapeuticЮжно-Российский журнал терапевтической практикиSouth Russian Journal of Therapeutic Practice2712-81563033-8344РостГМУ10.21886/2712-8156-2025-6-4-28-42therapeutic-672Research ArticleОБЗОРЫREVIEWSМультиомика хронической обструктивной болезни лёгких: от генетических и метаболомных нарушений к персонализированной медицинеMulti-omics of chronic obstructive pulmonary disease: from genetic and metabolomic disorders to personalized medicinehttps://orcid.org/0000-0002-7722-5457НикитинаЛ. Ю.NikitinaL. Y.

Никитина Лидия Юрьевна, д.м.н., доцент, врач методист отдела анализа кадровой политики и мониторинга организации медицинской помощи Национального медицинского исследовательского центра по профилю «Пульмонология»

Москва

Lidiya Yu. Nikitina, Dr. Sci. (Med.), Associate Professor, Methodologist at the Department of Personnel Policy Analysis and Monitoring of Medical Care at the National Medical Research Center for Pulmonology

Moscow

nikitina_l_yu@staff.sechenov.ruhttps://orcid.org/0000-0002-2648-3245БуйкинС. В.BuikinS. V.

Буйкин Степан Вячеславович, к.м.н., доцент кафедры внутренних болезней Медицинского института

Великий Новгород

Stepan V. Buikin, Cand. Sci. (Med.), Associate Professor of the Department of Internal Diseases of the Medical Institute

Veliky Novgorod

buikin@mail2000.ruhttps://orcid.org/0000-0001-7854-0849ВеберВ. Р.WeberV. R.

Вебер Виктор Робертович, д.м.н., профессор, академик РАН, заведующий кафедрой внутренних болезней, научный руководитель Медицинского института

Великий Новгород

Viktor R. Weber, Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, Head of the Department of Internal Diseases, Scientific Director of the Medical Institute

Veliky Novgorod

viktor.Veber@novsu.ruhttps://orcid.org/0000-0001-5856-0404ГасановМ. З.GasanovM. Z.

Гасанов Митхат Зульфугарович, к.м.н., доцент, доцент кафедры госпитальной терапии, заместитель директора Медицинского института

Великий Новгород

Mithat Z. Hasanov, Cand. Sci. (Med.), Associate Professor, Associate Professor of the Department of Hospital Therapy, Deputy Director of the Medical Institute

Veliky Novgorod

mitkhat.gasanov@novsu.ruhttps://orcid.org/0000-0002-5999-2150АвдеевС. Н.AvdeevS. N.

Авдеев Сергей Николаевич, д.м.н., проф., акад. РАН, заведующий кафедрой пульмонологии, директор клиники пульмонологии и респираторной медицины, директор Национального медицинского исследовательского центра по профилю «пульмонология» 

Москва

Sergey N. Avdeev, Dr. Sci. (Med.), Professor, acad. RAS, Head of the Department of Pulmonology, Director of the Clinic of Pulmonology and Respiratory Medicine, Director of the National Medical Research Center for Pulmonology 

Moscow

serg_avdeev@list.ruФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian FederationФГБОУ ВО «Новгородский государственный университет им. Ярослава Мудрого»РоссияYaroslav the Wise Novgorod State UniversityRussian Federation202523122025642842Copyright © Никитина Л.Ю., Буйкин С.В., Вебер В.Р., Гасанов М.З., Авдеев С.Н., 20252025Никитина Л.Ю., Буйкин С.В., Вебер В.Р., Гасанов М.З., Авдеев С.Н.Nikitina L.Y., Buikin S.V., Weber V.R., Gasanov M.Z., Avdeev S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.therapeutic-j.ru/jour/article/view/672

Настоящий обзор посвящён современному представлению о генетических и метаболомных основах развития, особенностях течения и терапии хронической обструктивной болезни лёгких, одной из ведущих причин заболеваемости и смертности в мире. В нём проанализированы кандидатные гены заболевания, результаты полногеномных ассоциативных исследований, метаболомные изменения при ХОБЛ. Описаны методы метаболомного профилирования и варианты интегративных подходов в использовании этих данных в диагностике и лечении ХОБЛ.

This review is devoted to the modern understanding of the genetic and metabolomic basis of development, features of the course and therapy of chronic obstructive pulmonary disease, one of the leading causes of morbidity and mortality in the world. It analyzes candidate disease genes, results of genome-wide association studies, and metabolomic changes in COPD. It describes methods for metabolomic profiling and integrative approaches to using this data in the diagnosis and treatment of COPD.

хроническая обструктивная болезнь легкихХОБЛгены кандидатыметаболомикаChronic obstructive pulmonary diseaseCOPDcandidate genesmetabolomicsReferencesWerder RB, Zhou X, Cho MH, Wilson AA. Breathing new life into the study of COPD with genes identified from genome-wide association studies. Eur Respir Rev. 2024;33(172):240019. doi: 10.1183/16000617.0019-2024Werder RB, Zhou X, Cho MH, Wilson AA. Breathing new life into the study of COPD with genes identified from genome-wide association studies. Eur Respir Rev. 2024;33(172):240019. doi: 10.1183/16000617.0019-2024Cho MH, Hobbs BD, Silverman EK. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Respir Med. 2022;10(5):485-496. doi: 10.1016/S2213-2600(21)00510-5Cho MH, Hobbs BD, Silverman EK. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Respir Med. 2022;10(5):485-496. doi: 10.1016/S2213-2600(21)00510-5Буйкин С.В., Пузырев В.П. Альфа 1 антитрипсиновая недостаточность. Перспективы скрининга. Сообщение 1. Бюллетень Сибирского отделения Российской академии медицинских наук. 2004;(1):92–98. eLIBRARY ID: 9126426 EDN: HRSOHVBuikin S.V., Puzyrev V.P. Alpha1 antitrypsin deficiency. prospect screening. the first report. Byulleten' Sibirskogo otdeleniya Rossiyskoy akademii meditsinskikh nauk = Bulletin of the Siberian Branch of the Russian Academy of Medical Sciences. 2004;(1):92–98 (In Russ.). eLIBRARY ID: 9126426 EDN: HRSOHVPillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009;5(3):e1000421. doi: 10.1371/journal.pgen.1000421Pillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009;5(3):e1000421. doi: 10.1371/journal.pgen.1000421Генетика бронхолегочных заболеваний. Под ред. Огородова Л.М., Пузырёв В.П. М.: Атмосфера. 2010.Ogorodova LM, Puzyryov VP, eds. Genetika bronkholegochnykh zabolevanii. Moscow: Atmosfera. 2010 (In Russ.)Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, et al. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020;201(5):564-574. doi: 10.1164/rccm.201905-1017OCAllen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, et al. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020;201(5):564-574. doi: 10.1164/rccm.201905-1017OCPillai SG, Kong X, Edwards LD, Cho MH, Anderson WH, Coxson HO, et al. Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182(12):1498-1505. doi: 10.1164/rccm.201002-0151OCPillai SG, Kong X, Edwards LD, Cho MH, Anderson WH, Coxson HO, et al. Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182(12):1498-1505. doi: 10.1164/rccm.201002-0151OCYuan C, Chang D, Lu G, Deng X. Genetic polymorphism and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;12:1385-1393. doi: 10.2147/COPD.S134161Yuan C, Chang D, Lu G, Deng X. Genetic polymorphism and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;12:1385-1393. doi: 10.2147/COPD.S134161Wang S, Yue Y, Wang X, Tan Y, Zhang Q. SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation. Aging Cell. 2024;23(10):e14266. doi: 10.1111/acel.14266Wang S, Yue Y, Wang X, Tan Y, Zhang Q. SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation. Aging Cell. 2024;23(10):e14266. doi: 10.1111/acel.14266Yang Q, Huang W, Yin D, Zhang L, Gao Y, Tong J, et al. EPHX1 and GSTP1 polymorphisms are associated with COPD risk: a systematic review and meta-analysis. Front Genet. 2023;14:1128985. doi: 10.3389/fgene.2023.1128985Yang Q, Huang W, Yin D, Zhang L, Gao Y, Tong J, et al. EPHX1 and GSTP1 polymorphisms are associated with COPD risk: a systematic review and meta-analysis. Front Genet. 2023;14:1128985. doi: 10.3389/fgene.2023.1128985Gilowska I, Majorczyk E, Kasper Ł, Bogacz K, Szczegielniak J, Kasper M, et al. The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study. BMC Med Genet. 2019;20(1):19. doi: 10.1186/s12881-019-0751-9Gilowska I, Majorczyk E, Kasper Ł, Bogacz K, Szczegielniak J, Kasper M, et al. The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study. BMC Med Genet. 2019;20(1):19. doi: 10.1186/s12881-019-0751-9Kam MLW, Chong ST, Chan SH, Swigris JJ, Chew EL, Tan YH, et al. First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort. Respir Investig. 2024;62(3):348-355. doi: 10.1016/j.resinv.2024.02.004Kam MLW, Chong ST, Chan SH, Swigris JJ, Chew EL, Tan YH, et al. First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort. Respir Investig. 2024;62(3):348-355. doi: 10.1016/j.resinv.2024.02.004Maremanda KP, Sundar IK, Li D, Rahman I. Age-Dependent Assessment of Genes Involved in Cellular Senescence, Telomere, and Mitochondrial Pathways in Human Lung Tissue of Smokers, COPD, and IPF: Associations With SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis. Front Pharmacol. 2020;11:584637. doi: 10.3389/fphar.2020.584637Maremanda KP, Sundar IK, Li D, Rahman I. Age-Dependent Assessment of Genes Involved in Cellular Senescence, Telomere, and Mitochondrial Pathways in Human Lung Tissue of Smokers, COPD, and IPF: Associations With SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis. Front Pharmacol. 2020;11:584637. doi: 10.3389/fphar.2020.584637Zhu Y, Meng Y, Zhang Y, Karlsson IK, Hägg S, Zhan Y. Genetically determined telomere length and its association with chronic obstructive pulmonary disease and interstitial lung disease in biobank Japan: A Mendelian randomization study. Heliyon. 2023;10(1):e23415. doi: 10.1016/j.heliyon.2023.e23415Zhu Y, Meng Y, Zhang Y, Karlsson IK, Hägg S, Zhan Y. Genetically determined telomere length and its association with chronic obstructive pulmonary disease and interstitial lung disease in biobank Japan: A Mendelian randomization study. Heliyon. 2023;10(1):e23415. doi: 10.1016/j.heliyon.2023.e23415Córdoba-Lanús E, Montuenga LM, Domínguez-de-Barros A, Oliva A, Mayato D, Remírez-Sanz A, et al. Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers. Antioxidants (Basel). 2024;13(2):156. doi: 10.3390/antiox13020156Córdoba-Lanús E, Montuenga LM, Domínguez-de-Barros A, Oliva A, Mayato D, Remírez-Sanz A, et al. Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers. Antioxidants (Basel). 2024;13(2):156. doi: 10.3390/antiox13020156Córdoba-Lanús E, Cazorla-Rivero S, García-Bello MA, Mayato D, Gonzalvo F, Ayra-Plasencia J, et al. Telomere length dynamics over 10-years and related outcomes in patients with COPD. Respir Res. 2021;22(1):56. doi: 10.1186/s12931-021-01616-zCórdoba-Lanús E, Cazorla-Rivero S, García-Bello MA, Mayato D, Gonzalvo F, Ayra-Plasencia J, et al. Telomere length dynamics over 10-years and related outcomes in patients with COPD. Respir Res. 2021;22(1):56. doi: 10.1186/s12931-021-01616-zTacheva T, Zienolddiny-Narui S, Dimov D, Vlaykova D, Miteva I, Vlaykova T. The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease. Curr Issues Mol Biol. 2022;44(8):3757-3769. doi: 10.3390/cimb44080257Tacheva T, Zienolddiny-Narui S, Dimov D, Vlaykova D, Miteva I, Vlaykova T. The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease. Curr Issues Mol Biol. 2022;44(8):3757-3769. doi: 10.3390/cimb44080257Ruiz A, Flores-Gonzalez J, Buendia-Roldan I, Chavez-Galan L. Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases. Int J Mol Sci. 2021;23(1):425. doi: 10.3390/ijms23010425Ruiz A, Flores-Gonzalez J, Buendia-Roldan I, Chavez-Galan L. Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases. Int J Mol Sci. 2021;23(1):425. doi: 10.3390/ijms23010425Cagsin H, Uzan A, Tosun O, Rasmussen F, Serakinci N. Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2020;15:2751-2757. doi: 10.2147/COPD.S267799Cagsin H, Uzan A, Tosun O, Rasmussen F, Serakinci N. Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2020;15:2751-2757. doi: 10.2147/COPD.S267799Bowler RP, Jacobson S, Cruickshank C, Hughes GJ, Siska C, Ory DS, et al. Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Am J Respir Crit Care Med. 2015;191(3):275-284. doi: 10.1164/rccm.201410-1771OCBowler RP, Jacobson S, Cruickshank C, Hughes GJ, Siska C, Ory DS, et al. Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Am J Respir Crit Care Med. 2015;191(3):275-284. doi: 10.1164/rccm.201410-1771OCUbhi BK, Cheng KK, Dong J, Janowitz T, Jodrell D, Tal-Singer R, et al. Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD. Mol Biosyst. 2012;8(12):3125-3133. doi: 10.1039/c2mb25194aUbhi BK, Cheng KK, Dong J, Janowitz T, Jodrell D, Tal-Singer R, et al. Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD. Mol Biosyst. 2012;8(12):3125-3133. doi: 10.1039/c2mb25194aWang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3341-3348. doi: 10.2147/COPD.S176122Wang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3341-3348. doi: 10.2147/COPD.S176122Kanto N, Ohkawa Y, Kitano M, Maeda K, Shiida M, Ono T, et al. A highly specific antibody against the core fucose of the N-glycan in IgG identifies the pulmonary diseases and its regulation by CCL2. J Biol Chem. 2023;299(12):105365. doi: 10.1016/j.jbc.2023.105365Kanto N, Ohkawa Y, Kitano M, Maeda K, Shiida M, Ono T, et al. A highly specific antibody against the core fucose of the N-glycan in IgG identifies the pulmonary diseases and its regulation by CCL2. J Biol Chem. 2023;299(12):105365. doi: 10.1016/j.jbc.2023.105365Godbole S, Bowler RP. Metabolome Features of COPD: A Scoping Review. Metabolites. 2022;12(7):621. doi: 10.3390/metabo12070621Godbole S, Bowler RP. Metabolome Features of COPD: A Scoping Review. Metabolites. 2022;12(7):621. doi: 10.3390/metabo12070621Ran N, Pang Z, Gu Y, Pan H, Zuo X, Guan X, et al. An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease. Metabolites. 2019;9(6):111. doi: 10.3390/metabo9060111Ran N, Pang Z, Gu Y, Pan H, Zuo X, Guan X, et al. An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease. Metabolites. 2019;9(6):111. doi: 10.3390/metabo9060111Gillenwater LA, Pratte KA, Hobbs BD, Cho MH, Zhuang Y, Halper-Stromberg E, et al. Plasma Metabolomic Signatures of Chronic Obstructive Pulmonary Disease and the Impact of Genetic Variants on Phenotype-Driven Modules. Netw Syst Med. 2020;3(1):159-181. doi: 10.1089/nsm.2020.0009Gillenwater LA, Pratte KA, Hobbs BD, Cho MH, Zhuang Y, Halper-Stromberg E, et al. Plasma Metabolomic Signatures of Chronic Obstructive Pulmonary Disease and the Impact of Genetic Variants on Phenotype-Driven Modules. Netw Syst Med. 2020;3(1):159-181. doi: 10.1089/nsm.2020.0009Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, et al. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur Respir J. 2017;49(6):1602322. doi: 10.1183/13993003.02322-2016Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, et al. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur Respir J. 2017;49(6):1602322. doi: 10.1183/13993003.02322-2016Zhang Y, Ma X, Wu F, Sun Y, Mou H, Liu X, et al. The relationship between genetic prediction of 486 blood metabolites and the risk of COPD: mendelian randomization study. Sci Rep. 2025;15(1):7349. doi: 10.1038/s41598-025-92216-0Zhang Y, Ma X, Wu F, Sun Y, Mou H, Liu X, et al. The relationship between genetic prediction of 486 blood metabolites and the risk of COPD: mendelian randomization study. Sci Rep. 2025;15(1):7349. doi: 10.1038/s41598-025-92216-0Gillenwater LA, Helmi S, Stene E, Pratte KA, Zhuang Y, Schuyler RP, et al. Multi-omics subtyping pipeline for chronic obstructive pulmonary disease. PLoS One. 2021;16(8):e0255337. doi: 10.1371/journal.pone.0255337Gillenwater LA, Helmi S, Stene E, Pratte KA, Zhuang Y, Schuyler RP, et al. Multi-omics subtyping pipeline for chronic obstructive pulmonary disease. PLoS One. 2021;16(8):e0255337. doi: 10.1371/journal.pone.0255337Liang Y, Gai XY, Chang C, Zhang X, Wang J, Li TT. Metabolomic Profiling Differences among Asthma, COPD, and Healthy Subjects: A LC-MS-based Metabolomic Analysis. Biomed Environ Sci. 2019;32(9):659-672. doi: 10.3967/bes2019.085Liang Y, Gai XY, Chang C, Zhang X, Wang J, Li TT. Metabolomic Profiling Differences among Asthma, COPD, and Healthy Subjects: A LC-MS-based Metabolomic Analysis. Biomed Environ Sci. 2019;32(9):659-672. doi: 10.3967/bes2019.085Johnson RK, Brunetti T, Quinn K, Doenges K, Campbell M, Arehart C, et al. Discovering metabolite quantitative trait loci in asthma using an isolated population. J Allergy Clin Immunol. 2022;149(5):1807-1811.e16. doi: 10.1016/j.jaci.2021.11.002Johnson RK, Brunetti T, Quinn K, Doenges K, Campbell M, Arehart C, et al. Discovering metabolite quantitative trait loci in asthma using an isolated population. J Allergy Clin Immunol. 2022;149(5):1807-1811.e16. doi: 10.1016/j.jaci.2021.11.002

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