Предикторы развития легочной гипертензии у пациентов с гиперчувствительным пневмонитом

Введение. Гиперчувствительный пневмонит (ГП) представляет собой интерстициальное заболевание легких (ИЗЛ), развивающееся у предрасположенных лиц в ответ на ингаляцию различных антигенов. Легочная гипертензия (ЛГ) является частым и прогностически неблагоприятным осложнением ГП, особенно при прогрессирующем фиброзном фенотипе заболевания. Неспецифичность клинической симптоматики и сложности диагностики существенно затрудняют своевременное выявление ЛГ у данной категории пациентов.

Цель. Оценить распространенность и выявить предикторы наличия ЛГ у пациентов с хроническим ГП.

Материалы и методы. Проведено наблюдательное продольное когортное исследование, в котором приняли участие 85 пациентов с установленным диагнозом «ГП». В ходе исследования проанализированы клинические показатели, данные компьютерной томографии грудной клетки высокого разрешения (ВРКТ), показатели газового состава артериальной крови, результаты теста с 6-минутной ходьбой (6МТХ), параметры функции внешнего дыхания и эхокардиографические характеристики.

Результаты. Пациенты были разделены на две группы с фиброзным (71,8%) и нефиброзным фенотипом (28,2%) ГП (фГП и нфГП соответственно). ЛГ была диагностирована у 42 (49,4%) пациентов: в подгруппе фГП – у 35 (57,4%) человек, в подгруппе нфГП – у 7 (29,2%). Наиболее значимыми предикторами развития ЛГ у пациентов с ГП были наличие фиброза легких по ВРКТ (ОШ 6,35 (95% ДИ 1,63–24,70), р = 0,008) и сердечно-сосудистые заболевания в анамнезе (ОШ 3,72 (95% ДИ 1,0–13,6), р = 0,050). Кроме того, риск наличия ЛГ увеличивался при возрасте старше 60 лет, SpO₂ дистанции в 6МТХ менее 390 м и при соотношении ФЖЕЛ/DLco > 1,5. в конце 6МТХ менее 85%,

Выводы. ЛГ является распространенным заболеванием у пациентов с хроническим ГП, особенно с фиброзным фенотипом. Раннее выявление предикторов ЛГ необходимо для своевременной диагностики этого осложнения среди пациентов с ГП.

1. Behr J, Ryu JH. Pulmonary hypertension in interstitial lung disease. Eur Respir J. 2008;31(6):1357–1367. https://doi.org/10.1183/09031936.00171307.

2. Dybowska M, Barańska I, Franczuk M, Skoczylas A, Szturmowicz M. Echocardiographic signs of pulmonary hypertension in patients with newly recognized hypersensitivity pneumonitis, prevalence and clinical predictors. J Thorac Dis. 2021;13(7):3988–3997. https://doi.org/10.21037/jtd-21-130.

3. Nadrous HF, Pellikka PA, Krowka MJ, Swanson KL, Chaowalit N, Decker PA, Ryu JH. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest. 2005;128(4):2393–2399. https://doi.org/10.1378/chest.128.4.2393.

4. Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006;129(3):746–752. https://doi.org/10.1378/chest.129.3.746.

5. Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007;132(3):998–1006. https://doi.org/10.1378/chest.06-3087.

6. Nathan SD, Stinchon MRJr, Atcheson S, Simone L, Nelson M. Shining a spotlight on pulmonary hypertension associated with interstitial lung disease care: The latest advances in diagnosis and treatment. J Manag Care Spec Pharm. 2025;31(1-а Suppl.):S2–S17. https://doi.org/10.18553/jmcp.2025.31.1-a.s2.

7. Hurdman J, Condliffe R, Elliot CA, Davies C, Hill C, Wild JM et al. ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre. Eur Respir J. 2012;39(4):945–955. https://doi.org/10.1183/09031936.00078411.

8. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J. 201924;53(1):1801914. https://doi.org/10.1183/13993003.01914-2018.

9. George PM, Mitchell JA. Defining a pathological role for the vasculature in the development of fibrosis and pulmonary hypertension in interstitial lung disease. Am J Physiol Lung Cell Mol Physiol. 2019;317(4):L431–L433. https://doi.org/10.1152/ajplung.00330.2019.

10. Papakosta D, Pitsiou G, Daniil Z, Dimadi M, Stagaki E, Rapti A et al. Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters. Lung. 2011;189:391–399. https://doi.org/10.1007/s00408-011-9304-5.

11. Castria D, Refini RM, Bargagli E, Mezzasalma F, Pierli C, Rottoli P. Pulmonary hypertension in idiopathic pulmonary fibrosis: prevalence and clinical progress. Int J Immunopathol Pharmacol. 2012;25(3):681–689. https://doi.org/10.1177/039463201202500314.

12. Heresi G, Dean B, Wu B, Lee H, Sketch MR, Stafkey-Mailey D et al. Burden of illness in patients with pulmonary hypertension due to interstitial lung disease: a real-world analysis. BMC Pulm Med. 2024;24(1):335. https://doi.org/10.1186/s12890-024-03141-3.

13. Kimura M, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O et al. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Respiration. 2013;85(6):456–463. https://doi.org/10.1159/000345221.

14. 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.

15. Oliveira RKF, Pereira CAC, Ramos RP, Ferreira EV, Messina CM, Kuranishi LT et al. A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis. Eur Respir J. 2014;44(2):415–424. https://doi.org/10.1183/09031936.00010414.

16. Elnady MA, Elkorashy R, Nabil A, Ibrahim EK. Predictors of pulmonary hypertension in patients with hypersensitivity pneumonitis. BMC Pulm Med. 2023;23:61. https://doi.org/10.1186/s12890-023-02347-1.

17. Koschel DS, Cardoso C, Wiedemann B, Höffken G, Halank M. Pulmonary hypertension in chronic hypersensitivity pneumonitis. Lung. 2012;190(3):295–302. https://doi.org/10.1007/s00408-011-9361-9

18. Tornyos A, Trinker M, Foris V, Pfeiffer S, Odler B, Douschan P et al. Pulmonary hypertension in hypersensitivity pneumonitis. Eur Respir J. 2016;48(Suppl. 60):PA2450. https://doi.org/10.1183/13993003.congress-2016.PA2450.

19. Wälscher J, Gross B, Morisset J, Johannson KA, Vasakova M, Bruhwyler J, Kreuter M. Comorbidities and survival in patients with chronic hypersensitivity pneumonitis. Respir Res. 2020;21:12. https://doi.org/10.1186/s12931-020-1283-8.

20. Zisman DA, Ross DJ, Belperio JA, Saggar R, Lynch JP 3rd, Ardehali A, Karlamangla AS. Prediction of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med. 2007;101(10):2153–2159. https://doi.org/10.1016/j.rmed.2007.05.012.

21. Rahaghi FF, Kolaitis NA, Adegunsoye A, de Andrade JA, Flaherty KR, Lancaster LH et al. Screening Strategies for Pulmonary Hypertension in Patients With Interstitial Lung Disease: A Multidisciplinary Delphi Study. Chest. 2022;162(1):145–155. https://doi.org/10.1016/j.chest.2022.02.012.

22. Ang HL, Schulte M, Chan RK, Tan HH, Harrison A, Ryerson CJ, Khor YH. Pulmonary Hypertension in Interstitial Lung Disease: A Systematic Review and Meta-Analysis. Chest. 2024;166(4):778–792. https://doi.org/10.1016/j.chest.2024.04.025.

23. Fiorentù G, Bernardinello N, Giulianelli G, Cocconcelli E, Balestro E, Spagnolo P. Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future. Adv Ther. 2025;42(4):1627–1641. https://doi.org/10.1007/s12325-025-03129-3.

24. Stanojevic S, Kaminsky DA, Miller M, Thompson B, Aliverti A, Barjaktarevic I et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60:2101499. https://doi.org/10.1183/13993003.01499-2021.

25. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984;70(4):657–662. https://doi.org/10.1161/01.cir.70.4.657.

26. Rudski LG, Lai WW, Afilalo J, Hua LQ, Handschumacher MD, Chandrasekaran K et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713. https://doi.org/10.1016/j.echo.2010.05.010.

27. Colalillo A, Hoffmann-Vold AM, Pellicano C, Romaniello A, Gabrielli A, Hachulla E et al. The role of TAPSE/sPAP ratio in predicting pulmonary hypertension and mortality in the systemic sclerosis EUSTAR cohort. Autoimmun Rev. 2023;22(4):103290. https://doi.org/10.1016/j.autrev.2023.103290.

28. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618–3731. https://doi.org/10.1093/eurheartj/ehac237.

29. Kazimierczyk R, Kazimierczyk E, Knapp M, Sobkowicz B, Malek LA, Blaszczak P et al. Echocardiographic Assessment of Right Ventricular-Arterial Coupling in Predicting Prognosis of Pulmonary Arterial Hypertension Patients. J Clin Med. 2021;10(13):2995. https://doi.org/10.3390/jcm10132995.

30. Tello K, Axmann J, Ghofrani HA, Naeije R, Narcin N, Rieth A et al. Relevance of the TAPSE/PASP ratio in pulmonary arterial hypertension. Int J Cardiol. 2018;266:229–235. https://doi.org/10.1016/j.ijcard.2018.01.053.

31. Tello K, Wan J, Dalmer A, Vanderpool R, Ghofrani HA, Naeije R et al. Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension. Circ Cardiovasc Imaging. 2019;12(9):e009047. https://doi.org/10.1161/circimaging.119.009047.

32. Fauvel C, Raitiere O, Boucly A, De Groote P, Renard S, Bertona J et al. Interest of TAPSE/sPAP ratio for noninvasive pulmonary arterial hypertension risk assessment. J Heart Lung Transplant. 2022;41(12):1761–1772. https://doi.org/10.1016/j.healun.2022.09.005.

33. Huston JH, Maron BA, French J, Huang S, Thayer T, Farber-Eger EH et al. Association of Mild Echocardiographic Pulmonary Hypertension With Mortality and Right Ventricular Function. JAMA Cardiol. 2019;4(11):1112–1121. https://doi.org/10.1001/jamacardio.2019.3345.

34. Kishaba T, Shimaoka Y, Fukuyama H, Nagano H, Nei Y, Yamashiro S, Tamaki H. Clinical characteristics of idiopathic pulmonary fibrosis patients with gender, age, and physiology staging at Okinawa Chubu Hospital. J Thorac Dis. 2015;7(5):843–849. https://doi.org/10.3978/j.issn.2072-1439.2015.04.54.

35. Lacedonia D, Correale M, Tricarico L, Scioscia G, Stornelli SR, Simone F et al. Survival of patients with idiopathic pulmonary fibrosis and pulmonary hypertension under therapy with nintedanib or pirfenidone. Intern Emerg Med. 2022;17(3):815–822. https://doi.org/10.1007/s11739-021-02883-w.

36. Parikh R, Konstantinidis I, O’Sullivan DM, Farber HW. Pulmonary hypertension in patients with interstitial lung disease: a tool for early detection. Pulm Circ. 2022;12:e12141. https://doi.org/10.1002/pul2.12141.

37. Nathan SD, Shlobin OA, Ahmad S, Urbanek S, Barnett SD. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007;131(3):657–663. https://doi.org/10.1378/chest.06-2485.

38. Steen VD. The lung in systemic sclerosis. J Clin Rheumatol. 2005;11(1):40–46. https://doi.org/10.1097/01.rhu.0000152147.38706.db.

39. Trad S, Amoura Z, Beigelman C, Haroche J, Costedoat N, Boutin le TH et al. Pulmonary arterial hypertension is a major mortality factor in diffuse systemic sclerosis, independent of interstitial lung disease. Arthritis Rheum. 2006;54(1):184–191. https://doi.org/10.1002/art.21538.

40. Sobiecka M, Lewandowska K, Kober J, Franczuk M, Skoczylas A, Tomkowski W et al. Can a new scoring system improve prediction of pulmonary hypertension in newly recognised interstitial lung diseases? Lung. 2020;198:547–554. https://doi.org/10.1007/s00408-020-00346-1.

41. Steen V, Chou M, Shanmugam V, Mathias M, Kuru T, Morrissey R. Exerciseinduced pulmonary arterial hypertension in patients with systemic sclerosis. Chest. 2008;134(1):146–151. https://doi.org/10.1378/chest.07-2324.

42. Sonti R, Gersten RA, Barnett S, Brown AW, Nathan SD. Multimodal noninvasive prediction of pulmonary hypertension in IPF. Clin Respir J. 2019;13(9):567–573. https://doi.org/10.1111/crj.13059.

43. Ruffenach G, Hong J, Vaillancourt M, Medzikovic L, Eghbali M. Pulmonary hypertension secondary to pulmonary fibrosis: clinical data, histopathology and molecular insights. Respir Res. 2020;21(1):303. https://doi.org/10.1186/s12931-020-01570-2.

44. Waxman AB, Elia D, Adir Y, Humbert M, Harari S. Recent advances in the management of pulmonary hypertension with interstitial lung disease. Eur Respir Rev. 2022;31(165):210220. https://doi.org/10.1183/16000617.0220-2021.

45. Nathan SD. Hypersensitivity pneumonitis and pulmonary hypertension: how the breeze affects the squeeze. Eur Respir J. 2014;44(2):287–288. https://doi.org/10.1183/09031936.00061214.

46. Shlobin OA, Adir Y, Barbera JA, Cottin V, Harari S, Jutant EM et al. Pulmonary hypertension associated with lung diseases. Eur Respir J. 2024;64(4):2401200. https://doi.org/10.1183/13993003.01200-2024.

47. Farkas L, Gauldie J, Voelkel NF, Kolb M. Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors. Am J Respir Cell Mol Biol. 2011;45(1):1–15. https://doi.org/10.1165/rcmb.2010-0365TR.