pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2026-36-5-800-809pulmo-4993Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESПерспективы комбинированных индексов биомаркеров в диагностике прогрессирующего легочного фиброза у пациентов с гиперчувствительным пневмонитомProspects of combined biomarker indices for the diagnosis of progressive pulmonary fibrosis in patients with hypersensitivity pneumonitishttps://orcid.org/0000-0001-6257-354XБолотоваЕ. В.BolotovaE. V.

Болотова Елена Валентиновна – д. м. н., профессор, профессор кафедры терапии № 1

Author ID: 277732 

350063, Краснодар, ул. Митрофана Седина, 4  тел.: (961) 509-­79-­33 

Elena V. Bolotova, Doctor of Medicine, Professor, Professor, Department of Therapy No.1

Author ID: 277732 

ul. Mitrofana Sedina 4, Krasnodar, 350063  tel.: (961) 509-­79­33 

bolotowa_e@mail.ruhttps://orcid.org/0009-0001-0255-2533ЮрковаЮ. Г.YurkovaYu. G.

Юркова Юлия Геннадьевна – аспирант кафедры пульмонологии; врач­пульмонолог консультативно­диагностического центра

AuthorID: 1303568 

350063, Краснодар, ул. Митрофана Седина, 4  тел.: (908) 679­-27-32 

350086, Краснодар, ул. Первого Мая, 167 

Yulia G. Yurkova, Postgraduate Student, Department of Pulmonology; Pulmonologist, Consultative and Diagnostic Center

AuthorID: 1303568 

ul. Mitrofana Sedina 4, Krasnodar, 350063  tel.: (908) 679-­27­32 

ul. Pervogo Maya 167, Krasnodar, 360086

dr.yurkova.yu@yandex.ruhttps://orcid.org/0000-0002-9766-1811ГилевичИ. В.GilevichI. V.

Гилевич Ирина Валерьевна – к. м. н., заведующая лабораторией разработки и изучения новых технологий лечения заболеваний ; ассистент кафедры онкологии с курсом торакальной хирургии

AuthorID: 705356

350063, Краснодар, ул. Митрофана Седина, 4  тел.: (861) 252-­57­-61 

350086, Краснодар, ул. Первого Мая, 167 

Irina V. Gilevich, Candidate of Medicine, Head of the Laboratory for the Development and Study of New Technologies for the Treatment of Diseases; Assistant Professor, Department of Oncology with a course in thoracic surgery

AuthorID: 705356 

ul. Mitrofana Sedina 4, Krasnodar, 350063  tel.: (861) 252­57­-61 

ul. Pervogo Maya 167, Krasnodar, 360086

giliv@list.ruhttps://orcid.org/0000-0002-2110-0970ШульженкоЛ. В.Shul'zhenkoL. V.

Шульженко Лариса Владимировна – д. м. н., профессор, заведующая кафедрой пульмонологии; заведующая пульмонологическим отделением

Author ID: 725189 

350063, Краснодар, ул. Митрофана Седина, 4  тел.: (862) 252­-73-­93 

350086, Краснодар, ул. Первого Мая, 167 

Larisa V. Shul’zhenko, Doctor of Medicine, Professor, Head of Department of Pulmonology; Head of the Department of Pulmonology

ul. Mitrofana Sedina 4, Krasnodar, 350063  tel.: (862) 252-­73­93 

ul. Pervogo Maya 167, Krasnodar, 360086

larisa_shulzhenko@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Кубанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Educational Institution of Higher Education “Kuban State Medical University” of the Ministry of Health of the Russian FederationRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Кубанский государственный медицинский университет» Министерства здравоохранения Российской Федерации ; Государственное бюджетное учреждение здравоохранения «Научно-исследовательский институт – Краевая клиническая больница № 1 имени профессора С.В.Очаповского» Министерства здравоохранения Краснодарского краяРоссияFederal State Budgetary Educational Institution of Higher Education “Kuban State Medical University” of the Ministry of Health of the Russian Federation ; Federal Budgetary Healthcare Institution “Research Institute – Regional Hospital No.1 named after S.V.Ochapovskiy”Russian Federation202608102026365800809Copyright © Болотова Е.В., Юркова Ю.Г., Гилевич И.В., Шульженко Л.В., 20262026Болотова Е.В., Юркова Ю.Г., Гилевич И.В., Шульженко Л.В.Bolotova E.V., Yurkova Y.G., Gilevich I.V., Shul'zhenko L.V.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/4993

Гиперчувствительный пневмонит (ГП) – распространенное интерстициальное заболевание легких (ИЗЛ), для которого характерно развитие прогрессирующего легочного фиброза (ПЛФ). Наряду с общепризнанными диагностическими критериями ПЛФ в настоящее время продолжается поиск лабораторных маркеров для диагностики ПЛФ при ИЗЛ на ранних стадиях.

Целью исследования являлось составление математической модели биомаркеров для ранней диагностики ПЛФ у пациентов с ГП.

Материалы и методы

Материалы и методы. В исследование включены пациенты (n = 85) с ГП. ПЛФ установлен на основании критериев Американского торакального общества (American Thoracic Society – ATS), Европейского респираторного общества (European Respiratory Society – ERS), Японского респираторного общества (Japanese Respiratory Society – JRS), Латиноамериканского торакального общества (Latin American Thoracic Society – ALAT) (2022). Количественное определение уровней биомаркеров в сыворотке крови и бронхоальвеолярной лаважной жидкости (БАЛЖ) выполнено на автоматическом спектрофотометре Infinite M Nano (Tecan, Австрия). Статистическая обработка материалов исследования проведена с помощью программы SPSS Statistics 23. Построение математических моделей риска развития ПЛФ проводилось с помощью метода многофакторной логистической регрессии, соотношение чувствительности и специфичности биомаркеров и полученных моделей оценивались с помощью ROC­анализа (графический метод оценки качества бинарных классификаторов (Receiver Operating Characteristic)).

Результаты

Результаты. Показано, что у пациентов с ГП и ПЛФ значения точек отсечения бимаркеров БАЛЖ составили 6,37 нг / мл для матриксной металлопротеиназы (MMP)­7 и 521,29 пг / мл – для моноцитарного хемотаксического белка­1, или СС­хемокина лиганда­2 (MCP­1 / CCL2). Пороговые значения биомаркеров в сыворотке крови составили 6,79 нг / мл – для MMP­7, 17,56 нг / мл – для сурфактантного белка­D (SP­D), 643,59 пмоль / л – для периостина. Комбинированный индекс MMP­7 + MCP­1 (CCL2) БАЛЖ определяет риск развития ПЛФ с чувствительностью 87,5 % и специфичностью 83,0 %, комбинированный индекс MMP­7 + SP­D + периостина в сыворотке крови – с чувствительностью 84,4 % и специфичностью 92,5 %.

Заключение

Заключение. Комбинированные индексы MMP­7 + MCP­1 (CCL2) БАЛЖ и MMP­7 + SP­D + периостин в сыворотке крови являются чувствительными и специфичными методами ранней диагностики ПЛФ при ГП.

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILDs) and is characterized by the potential development of progressive pulmonary fibrosis (PPF). Alongside established diagnostic criteria for PPF, the search for laboratory biomarkers enabling early detection of PPF in patients with ILD remains an important area of research.

The aim to develop a biomarker­based predictive model for the early diagnosis of PPF in patients with HP.

Methods

Methods. The study included 85 patients with HP. PPF was diagnosed according to the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Society (2022) criteria. Quantitative measurements of biomarkers in serum and bronchoalveolar lavage fluid (BALF) were performed using an Infinite M Nano automated spectrophotometer (Tecan, Austria). Statistical analyses were conducted using SPSS Statistics version 23. Multivariable logistic regression analysis was used to develop predictive models for PPF risk, while the diagnostic performance of biomarkers and derived models was assessed using receiver operating characteristic (ROC) analysis.

Results

Results. In patients with HP and PPF, the optimal BALF biomarker cut­off values were 6.37 ng/mL for MMP­7 and 521.29 pg/mL for MCP­1 (CCL2). The serum biomarker cut­off values were 6.79 ng/mL for MMP­7, 17.56 ng/mL for SP­D, and 643.59 pmol/L for periostin. The combined BALF index consisting of MMP­7 and MCP­1 (CCL2) predicted the risk of PPF with a sensitivity of 87.5% and a specificity of 83.0%. The combined serum index including MMP­7, SP­D, and periostin demonstrated a sensitivity of 84.4% and a specificity of 92.5%.

Conclusion

Conclusion. The combined BALF biomarker index MMP­7 + MCP­1 (CCL2) and the combined serum biomarker index MMP­7 + SP­D + periostin are highly sensitive and specific tools for the early diagnosis of PPF in patients with HP.

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