medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-137medsovet-9050Research ArticleПУЛЬМОНОЛОГИЯ, ОТОЛАРИНГОЛОГИЯPULMONOLOGY, OTORHINOLARYNGOLOGYРетроспективное изучение предикторов прогрессирования легочного фиброза при гиперчувствительном пневмонитеRetrospective study of predictors of pulmonary fibrosis progression in hypersensitivity pneumonitishttps://orcid.org/0000-0002-0685-4133ТрушенкоН. В.TrushenkoN. V.

Трушенко Наталья Владимировна, к.м.н., доцент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского, Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет); научный сотрудник научно-методического центра мониторинга и контроля болезней органов дыхания, Научноисследовательский институт пульмонологии Федерального медико-биологического агентства

119991, Москва, ул. Трубецкая, д. 8, стр. 2,

115682, Москва, Ореховый бульвар, д. 28

Natalia V. Trushenko, Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Researcher, Scientific and Methodological Center for Monitoring and Control of Respiratory Diseases, Research Institute for Pulmonology of the Federal Medical Biological Agency

8, Bldg. 2, Trubetskaya St., Moscow, 119991, 

8, Orekhovy Boulevard, Moscow, 115682

trushenko.natalia@yandex.ruhttps://orcid.org/0000-0001-9661-7213СувороваО. А.SuvorovaO. A.

Суворова Ольга Александровна, ассистент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Olga A. Suvorova, Assistant, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine

8, Bldg. 2, Trubetskaya St., Moscow, 119991

olga.a.suvorova@mail.ruhttps://orcid.org/0000-0002-3952-6865ПершинаЕ. С.PershinaE. S.

Першина Екатерина Александровна, к.м.н., руководитель Центра лучевой диагностики

119049, Москва, Ленинский проспект, д. 8

Ekaterina S. Pershina, Cand. Sci. (Med.), Head of the Radiation Diagnostics Center

8, Leninsky Avenue, Moscow, 119049

pershina86@mail.ruhttps://orcid.org/0000-0002-9509-0867НеклюдоваГ. В.NekludovaG. V.

Неклюдова Галина Васильевна, д.м.н., ведущий научный сотрудник лаборатории функциональных и ультразвуковых методов исследования, Научно-исследовательский институт пульмонологии Федерального медико-биологического агентства; доцент кафедры пульмонологии института клинической медицины имени Н.В. Склифосовского, Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)

115682, Москва, Ореховый бульвар, д. 28,

119991, Москва, ул. Трубецкая, д. 8, стр. 2

 

Galina V. Nekludova, Dr. Sci. (Med.), Leading Researcher, Research Institute for Pulmonology of the Federal Medical Biological Agency; Associate Professor, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

8, Orekhovy Boulevard, Moscow, 115682,

8, Bldg. 2, Trubetskaya St., Moscow, 119991

nekludova_gala@mail.ruhttps://orcid.org/0000-0002-5536-9388ЧикинаС. Ю.ChikinaS. Yu.

Чикина Светлана Юрьевна, к.м.н., доцент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Svetlana Yu. Chikina, Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, N.V. Sklifosovskiy Institute of Clinical Medicine

8, Bldg. 2, Trubetskaya St., Moscow, 119991

svch@list.ruhttps://orcid.org/0000-0002-0928-2900ЛевинаЮ. А.LevinaI. A.

Левина Юлия Алексеевна, ординатор кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Iuliia A. Levina, Resident of the Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine

8, Bldg. 2, Trubetskaya St., Moscow, 119991

yu1999levina@gmail.comhttps://orcid.org/0000-0002-0158-7056ЧерняевА. Л.ChernyaevA. L.

Черняев Андрей Львович, д.м.н., профессор, заведующий отделом фундаментальной пульмонологии, Научно-исследовательский институт пульмонологии Федерального медико-биологического агентства; профессор кафедры патологической анатомии и клинической патологической анатомии лечебного факультета, Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; ведущий научный сотрудник лаборатории клинической морфологии, Научно-исследовательский институт морфологии человека имени академика А.П. Авцына Российского научного центра хирургии имени академика Б.В. Петровского

115682, Москва, Ореховый бульвар, д. 28,

117997, Москва, ул. Островитянова, д. 1,

117418, Москва, ул. Цюрупы, д. 3

Andrey L. Chernyaev, Dr. Sci. (Med.), Professor, Head of the Department of Fundamental Pulmonology, Research Institute for Pulmonology of the Federal Medical Biological Agency; Professor, Department of Pathological Anatomy and Clinical Pathological Anatomy, Faculty of Medicine, Pirogov Russian National Research Medical University; Leading Researcher, Laboratory of Clinical Morphology, Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

8, Orekhovy Boulevard, Moscow, 115682,

1, Ostrovityanov St., Moscow, 117997, 

3, Tsyurupa St., Moscow, 117418

cheral12@gmail.comhttps://orcid.org/0000-0001-8170-1260СамсоноваМ. В.SamsonovaM. V.

Самсонова Мария Викторовна, д.м.н., заведующая лабораторией патологической анатомии и иммунологии

115682, Москва, Ореховый бульвар, д. 28

Maria V. Samsonova, Dr. Sci. (Med.), Head of Laboratory of Pathological Anatomy and Immunology

8, Orekhovy Boulevard, Moscow, 115682

samary@mail.ruhttps://orcid.org/0000-0003-3931-1431ТюринИ. Е.TyurinI. E.

Тюрин Игорь Евгеньевич, д.м.н., профессор, заведующий кафедрой рентгенологии и радиологии

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Igor E. Tyurin, Dr. Sci. (Med.), Professor, Head of Department of Radiology

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

igortyurin@gmail.comhttps://orcid.org/0000-0001-7123-120XНадточийН. Б.NadtochiyN. B.

Надточий Никита Борисович, ассистент кафедры онкологии, лучевой диагностики и лучевой терапии

454092, Челябинск, ул. Воровского, д. 64

Nikita B. Nadtochiy, Assistant at the Department of Oncology, Radiation Diagnostics and Radiation Therapy

64, Vorovskiy St., Chelyabinsk, 454092

nnb77@bk.ruhttps://orcid.org/0000-0002-3174-5000МержоеваЭ. М.MerzhoevaZ. M.

Мержоева Замира Магомедовна, к.м.н., доцент кафедры пульмонологии

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Zamira M. Merzhoeva, Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine

8, Bldg. 2, Trubetskaya St., Moscow, 119991

zamira.merzhoeva@bk.ruhttps://orcid.org/0000-0002-5999-2150АвдеевС. Н.AvdeevS. N.

Авдеев Сергей Николаевич, д.м.н., профессор, академик Российской академии наук, заведующий кафедрой пульмонологии Института клинической медицины имени Н.В. Склифосовского, Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет); ведущий научный сотрудник, Научно-исследовательский институт пульмонологии Федерального медико-биологического агентства

119991, Москва, ул. Трубецкая, д. 8, стр. 2,

115682, Москва, Ореховый бульвар, д. 28

Sergey N. Avdeev, Dr. Sci. (Med.), Professor, Academician of Russian Academy of Sciences, Head of the Department of Pulmonology, N.V.Sklifosovsky Institute of Clinical Medicine, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Leading Researcher, Research Institute for Pulmonology of the Federal Medical Biological Agency

8, Bldg. 2, Trubetskaya St., Moscow, 119991, 

8, Orekhovy Boulevard, Moscow, 115682

serg_avdeev@list.ruПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет); Научно-исследовательский институт пульмонологии Федерального медико-биологического агентстваРоссияSechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Research Institute for Pulmonology of the Federal Medical Biological AgencyRussian FederationПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Russian FederationГородская клиническая больница №1 им. Н.И. Пирогова Департамента здравоохранения города МосквыРоссияPirogov City Clinical Hospital №1, Moscow Healthcare DepartmentRussian FederationНаучно-исследовательский институт пульмонологии Федерального медико-биологического агентства; Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; Научно-исследовательский институт морфологии человека имени академика А.П. Авцына Российского научного центра хирургии имени академика Б.В. ПетровскогоРоссияResearch Institute for Pulmonology of the Federal Medical Biological Agency; Pirogov Russian National Research Medical University; Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of SurgeryRussian FederationНаучно-исследовательский институт пульмонологии Федерального медико-биологического агентстваРоссияResearch Institute for Pulmonology of the Federal Medical Biological AgencyRussian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationЮжно-Уральский государственный медицинский университетРоссияSouth Ural State Medical UniversityRussian Federation202504052025056776Copyright © Трушенко Н.В., Суворова О.А., Першина Е.С., Неклюдова Г.В., Чикина С.Ю., Левина Ю.А., Черняев А.Л., Самсонова М.В., Тюрин И.Е., Надточий Н.Б., Мержоева Э.М., Авдеев С.Н., 20252025Трушенко Н.В., Суворова О.А., Першина Е.С., Неклюдова Г.В., Чикина С.Ю., Левина Ю.А., Черняев А.Л., Самсонова М.В., Тюрин И.Е., Надточий Н.Б., Мержоева Э.М., Авдеев С.Н.Trushenko N.V., Suvorova O.A., Pershina E.S., Nekludova G.V., Chikina S.Y., Levina I.A., Chernyaev A.L., Samsonova M.V., Tyurin I.E., Nadtochiy N.B., Merzhoeva Z.M., 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.med-sovet.pro/jour/article/view/9050Введение

Введение. Гиперчувствительный пневмонит (ГП) – иммуноопосредованное интерстициальное заболевание легких (ИЗЛ). Фибротический ГП ассоциирован с прогрессированием заболевания, ухудшением функции легких и неблагоприятным исходом.

Цель

Цель. Выявить факторы, повышающие риск прогрессирования легочного фиброза у пациентов с ГП.

Материалы и методы

Материалы и методы. Исследование является ретроспективным мультицентровым наблюдательным. Проанализированы данные 1355 пациентов регистра фиброзирующих ИЗЛ, выбраны 292 пациента с диагнозом хронического ГП на основании мультидисциплинарного консилиума. Были оценены клинические, функциональные и лабораторные данные, показатели теста 6-минутной ходьбы и ЭХО-кардиографии исходно и через 12 мес. На основании корреляционного и регрессионного анализов определены факторы риска прогрессирования. Проведен анализ данных ROC-кривых и функции выживаемости по методу Каплана-Мейера для оценки значимости показателей в отношении прогрессирования.

Результаты

Результаты. В исследование вошло 292 пациента с хроническим ГП, распространенность фиброза составила 91,8%, летальности – 14,5%. Выделены 2 группы пациентов: с прогрессирующим фиброзом (n = 92, 30,3%) и без признаков прогрессии (n = 200, 69,7%). В ходе регрессионного анализа выявлено, что наиболее значимыми предикторами прогрессирования были мужской пол (ОШ 1,68 (95% ДИ 1,02–2,76), р = 0,041), курение (ОШ 1,1 (95% ДИ 1,0–1,1), р = 0,002), индекс Чарльсона

(ОШ 1,48 (95% ДИ 1,03–2,12), р = 0,036), шкала GAP (OШ 1,57 (95% ДИ 1,1–2,3; р =0,015), DLco % должн. (ОШ 0,93 (95% ДИ

0,89–0,97; р = 0,001)

0,89–0,97; р = 0,001). При проведении ROC-анализа факторами прогрессирования стали DLco < 50% должн. (р = 0,0001), показатель GAP ≥ 4 баллов (р = 0,03), индекс Чарльсона ≥ 3 балла (р = 0,04).

Выводы

Выводы. Пациенты с фибротическим ГП характеризуются высокой частотой прогрессирования легочного фиброза. Основными предикторами прогрессирования являются мужской пол, курение, увеличение индекса Чарльсона, DLco < 50%, показатель GAP ≥ 4 баллов.

Introduction

Introduction. Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD). Fibrotic HP is associated with disease progression, impaired lung function, and poor clinical outcomes.

Aim

Aim. Identify factors that increase the risk of progression of pulmonary fibrosis in patients with HP.

Materials and methods

Materials and methods. We conducted a retrospective multicenter observational study analyzing data from a fibrosing ILD registry (n = 1355). The study included 292 patients with chronic HP confirmed by multidisciplinary discussion. We evaluated clinical, functional, and laboratory parameters, including 6-minute walk test results and echocardiography findings at baseline and 12-month follow-up. Risk factors for progression were identified through correlation and regression analyses. ROC curve analysis and Kaplan-Meier survival analysis were performed to assess the prognostic significance of various parameters.

Results

Results. Among 292 chronic HP patients, fibrosis prevalence was 91.8% with 14.5% mortality. Patients were stratified into progressive fibrosis (n = 92, 30.3%) and non-progressive (n = 200, 69.7%) groups. Regression analysis identified significant predictors of progression: male sex (OR 1.68, 95% CI 1.02–2.76, p = 0,041), smoking (OR 1.1, 95% CI 1.0–1.1, p = 0,002), Charlson Comorbidity Index (OR 1,48, 95% CI 1.03–2.12, p = 0.036), GAP score (OR 1.57, 95% CI 1.1–2.3, p = 0,015), and DLco % predicted (OR 0.93, 95% CI 0.89–0.97, p = 0.001). ROC analysis revealed DLco <50% predicted (p = 0.0001), GAP score ≥4 (p = 0.03), and Charlson Index ≥3 (p = 0.04) as significant progression factors.

Conclusion

Conclusion. Patients with fibrotic HP demonstrate high rates of pulmonary fibrosis progression. The main progression predictors include male sex, smoking, higher Charlson Comorbidity Index, DLco < 50% predicted, and GAP score ≥ 4.

интерстициальные заболевания легкихгиперчувствительный пневмонитлегочный фиброзпрогрессированиелетальностьinterstitial lung diseaseshypersensitivity pneumonitispulmonary fibrosisdisease progressionmortalityReferencesThomeer MJ, Costabel U, Rizzato G, Poletti V, Demedts M. Comparison of registries of interstitial lung diseases in three European countries. Eur Respir J Suppl. 2001;32:114s–118s. https://doi.org/10.1183/09031936.01.18s320114.Thomeer MJ, Costabel U, Rizzato G, Poletti V, Demedts M. Comparison of registries of interstitial lung diseases in three European countries. Eur Respir J Suppl. 2001;32:114s–118s. https://doi.org/10.1183/09031936.01.18s320114.Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M et al. Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(3):36–69. https://doi.org/10.1164/rccm.202005-2032st.Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M et al. Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(3):36–69. https://doi.org/10.1164/rccm.202005-2032st.Fernández Pérez ER, Travis WD, Lynch DA, Brown KK, Johannson KA, Selman M et al. Executive summary diagnosis and evaluation of hypersensitivity pneumonitis: CHEST guideline and expert panel report. Chest. 2021;160(2):595–615. https://doi.org/10.1016/j.chest.2021.03.067.Fernández Pérez ER, Travis WD, Lynch DA, Brown KK, Johannson KA, Selman M et al. Executive summary diagnosis and evaluation of hypersensitivity pneumonitis: CHEST guideline and expert panel report. Chest. 2021;160(2):595–615. https://doi.org/10.1016/j.chest.2021.03.067.Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Guideline. Am J Respir Crit Care Med. 2022;205(9):e18–e47. https://doi.org/10.1164/rccm.202202-0399st.Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Guideline. Am J Respir Crit Care Med. 2022;205(9):e18–e47. https://doi.org/10.1164/rccm.202202-0399st.Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718–1727. https://doi.org/10.1056/nejmoa1908681.Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718–1727. https://doi.org/10.1056/nejmoa1908681.Pérez-Padilla R, Salas J, Chapela R, Sánchez M, Carrillo G, Pérez R et al. Mortality in Mexican patients with chronic pigeon breeder’s lung compared with those with usual interstitial pneumonia. Am Rev Respir Dis. 1993;148(1):49–53. https://doi.org/10.1164/ajrccm/148.1.49.Pérez-Padilla R, Salas J, Chapela R, Sánchez M, Carrillo G, Pérez R et al. Mortality in Mexican patients with chronic pigeon breeder’s lung compared with those with usual interstitial pneumonia. Am Rev Respir Dis. 1993;148(1):49–53. https://doi.org/10.1164/ajrccm/148.1.49.Vasakova M, Selman M, Morell F, Sterclova M, Molina-Molina M, Raghu G. Hypersensitivity Pneumonitis: Current Concepts of Pathogenesis and Potential Targets for Treatment. Am J Respir Crit Care Med. 2019;200(3):301–308. https://doi.org/10.1164/rccm.201903-0541pp.Vasakova M, Selman M, Morell F, Sterclova M, Molina-Molina M, Raghu G. Hypersensitivity Pneumonitis: Current Concepts of Pathogenesis and Potential Targets for Treatment. Am J Respir Crit Care Med. 2019;200(3):301–308. https://doi.org/10.1164/rccm.201903-0541pp.Choe J, Chae EJ, Kim YJ, Do KH, Song JS, Song JW. Serial changes of CT findings in patients with chronic hypersensitivity pneumonitis: imaging trajectories and predictors of fibrotic progression and acute exacerbation. Eur Radiol. 2021;31(6):3993–4003. https://doi.org/10.1007/s00330-020-07469-2.Choe J, Chae EJ, Kim YJ, Do KH, Song JS, Song JW. Serial changes of CT findings in patients with chronic hypersensitivity pneumonitis: imaging trajectories and predictors of fibrotic progression and acute exacerbation. Eur Radiol. 2021;31(6):3993–4003. https://doi.org/10.1007/s00330-020-07469-2.Dasgupta S, Bhattacharya A, Abhijit RD, Roy Chowdhury S, Chaudhury K. Risk factors associated with mortality in hypersensitivity pneumonitis: a meta-analysis. Expert Rev Respir Med. 2022;16(7):801–811. https://doi.org/10.1080/17476348.2022.2100352.Dasgupta S, Bhattacharya A, Abhijit RD, Roy Chowdhury S, Chaudhury K. Risk factors associated with mortality in hypersensitivity pneumonitis: a meta-analysis. Expert Rev Respir Med. 2022;16(7):801–811. https://doi.org/10.1080/17476348.2022.2100352.Lewandowska KB, Barańska I, Sobiecka M, Radwan-Rohrenschef P, Dybowska M, Franczuk M et al. Factors Predictive for Immunomodulatory Therapy Response and Survival in Patients with Hypersensitivity Pneumonitis-Retrospective Cohort Analysis. Diagnostics. 2022;12(11):2767. https://doi.org/10.3390/diagnostics12112767.Lewandowska KB, Barańska I, Sobiecka M, Radwan-Rohrenschef P, Dybowska M, Franczuk M et al. Factors Predictive for Immunomodulatory Therapy Response and Survival in Patients with Hypersensitivity Pneumonitis-Retrospective Cohort Analysis. Diagnostics. 2022;12(11):2767. https://doi.org/10.3390/diagnostics12112767.Seixas E, Ferreira M, Serra P, Aguiar R, Cunha I, Ferreira PG. Criteria for progressive fibrotic hypersensitivity pneumonitis in a Portuguese patient cohort. Afr J Thorac Crit Care Med. 2022;28(4):e250. https://doi.org/10.7196/ajtccm.2022.v28i4.250.Seixas E, Ferreira M, Serra P, Aguiar R, Cunha I, Ferreira PG. Criteria for progressive fibrotic hypersensitivity pneumonitis in a Portuguese patient cohort. Afr J Thorac Crit Care Med. 2022;28(4):e250. https://doi.org/10.7196/ajtccm.2022.v28i4.250.Lobo LJ, Liu Y, Li P, Ramaswamy M, Swaminathan AC, Veeraraghavan S et al. Design and baseline characteristics of the ILD-PRO registry in patients with progressive pulmonary fibrosis. BMC Pulm Med. 2024;24(1):468. https://doi.org/10.1186/s12890-024-03247-8.Lobo LJ, Liu Y, Li P, Ramaswamy M, Swaminathan AC, Veeraraghavan S et al. Design and baseline characteristics of the ILD-PRO registry in patients with progressive pulmonary fibrosis. BMC Pulm Med. 2024;24(1):468. https://doi.org/10.1186/s12890-024-03247-8.Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R et al. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J. 2020;55(6):2000085. https://doi.org/10.1183/13993003.00085-2020.Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R et al. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J. 2020;55(6):2000085. https://doi.org/10.1183/13993003.00085-2020.Salisbury ML, Gu T, Murray S, Gross BH, Chughtai A, Sayyouh M et al. Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory. Chest. 2019;155(4):699–711. https://doi.org/10.1016/j.chest.2018.08.1076.Salisbury ML, Gu T, Murray S, Gross BH, Chughtai A, Sayyouh M et al. Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory. Chest. 2019;155(4):699–711. https://doi.org/10.1016/j.chest.2018.08.1076.Hanak V, Golbin JM, Hartman TE, Ryu JH. High-resolution CT findings of parenchymal fibrosis correlate with prognosis in hypersensitivity pneumonitis. Chest. 2008;134(1):133–138. https://doi.org/10.1378/chest.07-3005.Hanak V, Golbin JM, Hartman TE, Ryu JH. High-resolution CT findings of parenchymal fibrosis correlate with prognosis in hypersensitivity pneumonitis. Chest. 2008;134(1):133–138. https://doi.org/10.1378/chest.07-3005.Alberti ML, Malet Ruiz JM, Fernández ME, Fassola L, Caro F, Roldán IB, Paulin F. Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Pulmonology. 2020;26(1):3–9. https://doi.org/10.1016/j.pulmoe.2019.08.007.Alberti ML, Malet Ruiz JM, Fernández ME, Fassola L, Caro F, Roldán IB, Paulin F. Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Pulmonology. 2020;26(1):3–9. https://doi.org/10.1016/j.pulmoe.2019.08.007.Mooney JJ, Elicker BM, Urbania TH, Agarwal MR, Ryerson CJ, Nguyen MLT et al. Radiographic fibrosis score predicts survival in hypersensitivity pneumonitis. Chest. 2013;144(2):586–592. https://doi.org/10.1378/chest.12-2623.Mooney JJ, Elicker BM, Urbania TH, Agarwal MR, Ryerson CJ, Nguyen MLT et al. Radiographic fibrosis score predicts survival in hypersensitivity pneumonitis. Chest. 2013;144(2):586–592. https://doi.org/10.1378/chest.12-2623.Ojanguren I, Morell F, Ramón MA, Villar A, Romero C, Cruz MJ, Muñoz X. Long-term outcomes in chronic hypersensitivity pneumonitis. Allergy. 2019;74(5):944–952. https://doi.org/10.1111/all.13692.Ojanguren I, Morell F, Ramón MA, Villar A, Romero C, Cruz MJ, Muñoz X. Long-term outcomes in chronic hypersensitivity pneumonitis. Allergy. 2019;74(5):944–952. https://doi.org/10.1111/all.13692.Wang P, Jones KD, Urisman A, Elicker BM, Urbania T, Johannson KA et al. Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis. Chest. 2017;152(3):502–509. https://doi.org/10.1016/j.chest.2017.02.011.Wang P, Jones KD, Urisman A, Elicker BM, Urbania T, Johannson KA et al. Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis. Chest. 2017;152(3):502–509. https://doi.org/10.1016/j.chest.2017.02.011.Lima MS, Coletta EN, Ferreira RG, Jasinowodolinski D, Arakaki JS, Rodrigues SC et al. Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and survival. Respir Med. 2009;103(4):508–515. https://doi.org/10.1016/j.rmed.2008.12.016.Lima MS, Coletta EN, Ferreira RG, Jasinowodolinski D, Arakaki JS, Rodrigues SC et al. Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and survival. Respir Med. 2009;103(4):508–515. https://doi.org/10.1016/j.rmed.2008.12.016.Chung JH, Zhan X, Cao M, Koelsch TL, Manjarres DCG, Brown KK et al. Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography Predicts Survival in Chronic Hypersensitivity Pneumonitis. Ann Am Thorac Soc. 2017;14(10):1533–1538. https://doi.org/10.1513/AnnalsATS.201701-035OC.Chung JH, Zhan X, Cao M, Koelsch TL, Manjarres DCG, Brown KK et al. Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography Predicts Survival in Chronic Hypersensitivity Pneumonitis. Ann Am Thorac Soc. 2017;14(10):1533–1538. https://doi.org/10.1513/AnnalsATS.201701-035OC.Adegunsoye A, Oldham JM, Chung JH, Montner SM, Lee C, Witt LJ et al. Phenotypic Clusters Predict Outcomes in a Longitudinal Interstitial Lung Disease Cohort. Chest. 2018;153(2):349–360. https://doi.org/10.1016/j.chest.2017.09.026.Adegunsoye A, Oldham JM, Chung JH, Montner SM, Lee C, Witt LJ et al. Phenotypic Clusters Predict Outcomes in a Longitudinal Interstitial Lung Disease Cohort. Chest. 2018;153(2):349–360. https://doi.org/10.1016/j.chest.2017.09.026.Morisset J, Johannson KA, Vittinghoff E, Aravena C, Elicker BM, Jones KD et al. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis. Chest. 2017;151(3):619–625. https://doi.org/10.1016/j.chest.2016.10.029.Morisset J, Johannson KA, Vittinghoff E, Aravena C, Elicker BM, Jones KD et al. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis. Chest. 2017;151(3):619–625. https://doi.org/10.1016/j.chest.2016.10.029.Fiddler CA, Simler N, Thillai M, Parfrey H. Use of mycophenolate mofetil and azathioprine for the treatment of chronic hypersensitivity pneumonitis-A single-centre experience. Clin Respir J. 2019;13(12):791–794. https://doi.org/10.1111/crj.13076.Fiddler CA, Simler N, Thillai M, Parfrey H. Use of mycophenolate mofetil and azathioprine for the treatment of chronic hypersensitivity pneumonitis-A single-centre experience. Clin Respir J. 2019;13(12):791–794. https://doi.org/10.1111/crj.13076.Walsh SL, Sverzellati N, Devaraj A, Wells AU, Hansell DM. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants. Eur Radiol. 2012;22(8):1672–1679. https://doi.org/10.1007/s00330-012-2427-0.Walsh SL, Sverzellati N, Devaraj A, Wells AU, Hansell DM. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants. Eur Radiol. 2012;22(8):1672–1679. https://doi.org/10.1007/s00330-012-2427-0.Leuschner G, Klotsche J, Kreuter M, Prasse A, Wirtz H, Pittrow D et al. Idiopathic Pulmonary Fibrosis in Elderly Patients: Analysis of the INSIGHTS-IPF Observational Study. Front Med. 2020;7:601279. https://doi.org/10.3389/fmed.2020.601279.Leuschner G, Klotsche J, Kreuter M, Prasse A, Wirtz H, Pittrow D et al. Idiopathic Pulmonary Fibrosis in Elderly Patients: Analysis of the INSIGHTS-IPF Observational Study. Front Med. 2020;7:601279. https://doi.org/10.3389/fmed.2020.601279.Clarson LE, Bajpai R, Whittle R, Belcher J, Abdul Sultan A et al. Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction. Heart. 2020;106(12):916–922. https://doi.org/10.1136/heartjnl2019-315511.Clarson LE, Bajpai R, Whittle R, Belcher J, Abdul Sultan A et al. Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction. Heart. 2020;106(12):916–922. https://doi.org/10.1136/heartjnl2019-315511.Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–1294. https://doi.org/10.1016/j.jclinepi.2004.03.012.Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–1294. https://doi.org/10.1016/j.jclinepi.2004.03.012.Rittig AH, Hilberg O, Ibsen R, Løkke A. Incidence, comorbidity and survival rate of hypersensitivity pneumonitis: a national population-based study. ERJ Open Res. 2019;5(4):00259–2018. https://doi.org/10.1183/23120541.00259-2018.Rittig AH, Hilberg O, Ibsen R, Løkke A. Incidence, comorbidity and survival rate of hypersensitivity pneumonitis: a national population-based study. ERJ Open Res. 2019;5(4):00259–2018. https://doi.org/10.1183/23120541.00259-2018.Zhan X, Du Y, Luo J, Que Y, Hu C, Xu L et al. Features of transbronchial lung cryobiopsy-diagnosed fibrotic hypersensitivity pneumonitis. Clin Respir J. 2023;17(1):50–58. https://doi.org/10.1111/crj.13561.Zhan X, Du Y, Luo J, Que Y, Hu C, Xu L et al. Features of transbronchial lung cryobiopsy-diagnosed fibrotic hypersensitivity pneumonitis. Clin Respir J. 2023;17(1):50–58. https://doi.org/10.1111/crj.13561.Nizri E, Irony-Tur-Sinai M, Lory O, Orr-Urtreger A, Lavi E, Brenner T. Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses. J Immunol. 2009;183:6681–6688. https://doi.org/10.4049/jimmunol.0902212.Nizri E, Irony-Tur-Sinai M, Lory O, Orr-Urtreger A, Lavi E, Brenner T. Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses. J Immunol. 2009;183:6681–6688. https://doi.org/10.4049/jimmunol.0902212.Ryerson CJ, Vittinghoff E, Ley B, Lee JS, Mooney JJ, Jones KD et al. Predicting survival across chronic interstitial lung disease: the ILD-GAP model. Chest. 2014;145(4):723–728. https://doi.org/10.1378/chest.13-1474.Ryerson CJ, Vittinghoff E, Ley B, Lee JS, Mooney JJ, Jones KD et al. Predicting survival across chronic interstitial lung disease: the ILD-GAP model. Chest. 2014;145(4):723–728. https://doi.org/10.1378/chest.13-1474.Mendonça Almeida L, Fernandes AL, Gouveia Cardoso C, Lima B, Neves I, Novais-Bastos H et al. Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort. Ther Adv Respir Dis. 2022;16:17534666221135316. https://doi.org/10.1177/17534666221135316.Mendonça Almeida L, Fernandes AL, Gouveia Cardoso C, Lima B, Neves I, Novais-Bastos H et al. Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort. Ther Adv Respir Dis. 2022;16:17534666221135316. https://doi.org/10.1177/17534666221135316.Cano-Jiménez E, Villar Gómez A, Velez Segovia E, Aburto Barrenechea M, Sellarés Torres J, Francesqui J et al. Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study. ERJ Open Res. 2024;10(1):00405–02023. https://doi.org/10.1183/23120541.00405-2023.Cano-Jiménez E, Villar Gómez A, Velez Segovia E, Aburto Barrenechea M, Sellarés Torres J, Francesqui J et al. Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study. ERJ Open Res. 2024;10(1):00405–02023. https://doi.org/10.1183/23120541.00405-2023.Furusawa H, Peljto AL, Walts AD, Cardwell J, Molyneaux PL, Lee JS et al. Common idiopathic pulmonary fibrosis risk variants are associated with hypersensitivity pneumonitis. Thorax. 2022;77(5):508–510. https://doi.org/10.1136/thoraxjnl-2021-217693.Furusawa H, Peljto AL, Walts AD, Cardwell J, Molyneaux PL, Lee JS et al. Common idiopathic pulmonary fibrosis risk variants are associated with hypersensitivity pneumonitis. Thorax. 2022;77(5):508–510. https://doi.org/10.1136/thoraxjnl-2021-217693.

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