Идиопатический легочный фиброз: федеральные клинические рекомендации по диагностике и лечению

Идиопатический легочный фиброз (ИЛФ) представляет собой особую форму хронической фиброзирующей интерстициальной пневмонии с прогрессирующим течением и плохим прогнозом. Распространенность ИЛФ в Российской Федерации составляет около 8–12 случаев на 100 тыс. населения. Основу терапии ИЛФ составляют препараты с антифибротическими свойствами.

Методология. Целевой аудиторией данных клинических рекомендаций являются врачи-терапевты, врачи общей практики, врачи-пульмонологи, врачи-патологоанатомы, врачи-рентгенологи и врачи по медицинской реабилитации. Каждый тезис-рекомендация по проведению диагностических и лечебных мероприятий оценивается по шкалам уровней достоверности доказательств от 1 до 5 и шкале оценки уровней убедительности рекомендаций – по категориям А, В, С. Клинические рекомендации содержат также комментарии и разъяснения к указанным тезисам-рекомендациям, алгоритмы по диагностике и лечению ИЛФ, справочные материалы.

Заключение. Представлены современные сведения об этиологии, патогенезе, клинических проявлениях, диагностике и лечении ИЛФ. Одобрены Научно-практическим советом Министерства здравоохранения Российской Федерации в 2021 г. 

1. Raghu G., Collard H.R., Egan J.J. et al. An official ATS/ERS/JRS/ ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am. J. Respir. Crit. Care Med. 2011; 183 (6): 788–824. DOI: 10.1164/rccm.2009-040GL.

2. Raghu G., Rochwerg B., Zhang Y. et al. An Official ATS/ERS/ JRS/ALAT clinical practice guideline: treatment of Idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am. J. Respir. Crit. Care Med. 2015; 192 (2): e3–19. DOI: 10.1164/rccm.201506-1063ST.

3. Travis W.D., Costabel U., Hansell D.M. et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013; 188 (6): 733–748. DOI: 10.1164/rccm.201308-1483ST.

4. Hodgson U., Pulkkinen V., Dixon M. et al. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis. Am. J. Hum. Genet. 2006; 79 (1): 149–154. DOI: 10.1086/504639.

5. Allen R.J., Porte J., Braybrooke R. et al. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respir. Med. 2017; 5 (11): 869–880. DOI: 10.1016/S2213-2600(17)30387-9.

6. Авдеев С.Н. Идиопатический фиброз легких: новая парадигма. Терапевтический архив. 2017; 89 (1): 112–122. DOI: 10.17116/terarkh2017891112-122

7. Taskar V.S., Coultas D.B. Is idiopathic pulmonary fibrosis an environmental disease. Proc. Am. Thorac. Soc. 2006; 3 (4): 293–298. DOI: 10.1513/pats.200512-131TK.

8. Bedard Methot D., Leblanc E., Lacasse Y. Meta-analysis of gastroesophageal reflux disease and idiopathic pulmonary fibrosis. Chest. 2019; 155 (1): 33–43. DOI: 10.1016/j.chest.2018.07.038.

9. Garcıa-Sancho Figueroa M.C., Carrillo G., Pérez-Padilla R. et al. Risk factors for idiopathic pulmonary fibrosis in a Mexican population: a case-control study. Respir. Med. 2010; 104 (2): 305–309. DOI: 10.1016/j.rmed.2009.08.013.

10. Oldham J.M., Kumar D., Lee C. et al. Thyroid disease is prevalent and predicts survival in patients with idiopathic pulmonary fibrosis. Chest. 2015; 148 (3): 692–700. DOI: 10.1378/chest.14-2714.

11. Stock C.J., Sato H., Fonseca C. et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax. 2013; 68 (5): 436–441. DOI: 10.1136/thoraxjnl-2012-201786.

12. El-Chemaly S., Ziegler S.G., Calado R.T. et al. Natural history of pulmonary fibrosis in two subjects with the same telomerase mutation. Chest. 2011; 139 (5): 1203–1209. DOI: 10.1378/chest.10-2048.

13. Tsang A.R., Wyatt H.D., Ting N.S.Y., Beattie T.L. hTERT mutations associated with idiopathic pulmonary fibrosis affect telomerase activity, telomere length, and cell growth by distinct mechanisms. Aging Cell. 2012; 11 (3): 482–490. DOI: 10.1111/j.1474-9726.2012.00810.x.

14. Fukuhara A., Tanino Y., Ishii T., et al. Pulmonary fibrosis in dyskeratosis congenita with TINF2 gene mutation. Eur. Respir. J. 2013; 42 (6): 1757–1759. DOI: 10.1183/09031936.00149113.

15. Kropski J.A., Mitchell D.B., Markin C. et al. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest. 2014; 146 (1): e1–7. DOI: 10.1378/chest.13-2224.

16. Alder J.K., Stanley S.E., Wagner C.L. et al. Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis. Chest. 2015; 147 (5): 1361–1368. DOI: 10.1378/chest.14-1947.

17. Чучалин А.Г., Авдеев С.Н., Айсанов З.Р. и др. Диагностика и лечение идиопатического легочного фиброза: Федеральные клинические рекомендации. Пульмонология. 2016; 26 (4): 399–419. DOI: 10.18093/0869-0189-2016-26-4-399-419.

18. Raghu G., Chen S.Y., Yeh W.S. et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11. Lancet Respir. Med. 2014; 2 (7): 566–572. DOI: 10.1016/S2213-2600(14)70101-8.

19. Raghu G., Weycker D., Edelsberg J. et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2006; 174 (7): 810–816. DOI: 10.1164/rccm.200602-163OC.

20. Coultas D.B., Zumwalt R.E., Black W.C., Sobonya R.E. The epidemiology of interstitial lung diseases. Am. J. Respir. Crit. Care Med. 1994; 150 (4): 967–972. DOI: 10.1164/ajrccm.150.4.7921471.

21. Nalysnyk L., Cid-Ruzafa J., Rotella P., Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur. Respir. Rev. 2012; 21 (126): 355–361. DOI: 10.1183/09059180.00002512.

22. Richeldi L., Rubin A.S., Avdeev S. et al. Idiopathic pulmonary fibrosis in BRIC countries: the cases of Brazil, Russia, India, and China. BMC Medicine. 2015; 13: 237. DOI: 10.1186/s12916-015-0495-0.

23. Raghu G., Remy-Jardin M., Myers J.L. et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am. J. Respir. Crit. Care Med. 2018; 198 (5): e44–68. DOI: 10.1164/rccm.201807-1255ST.

24. Lynch D.A., Sverzellati N., Travis W.D. et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir. Med. 2018; 6 (2): 138–153. DOI: 10.1016/S2213-2600(17)30433-2.

25. George R.B., Light R.W., Mattay M.A., Mattay R.A., eds. Chest Medicine: Essentials of Pulmonary and Critical Care Medicine. 5th edn. Philadelphia: Wolter Kluwers/Lippincott Williams & Wilkins; 2005.

26. Collard H.R., Ryerson C.J., Corte T.J. et al. Acute exacerbation of idiopathic pulmonary fibrosis: An international working group report. Am. J. Respir. Crit. Care Med. 2016; 194 (3): 265–275. DOI: 10.1164/rccm.201604-0801CI.

27. Gross T.J., Hunninghake G.W. Idiopathic pulmonary fibrosis. N. Engl. J. Med. 2001; 345 (7): 517–525. DOI: 10.1056/NEJMra003200.

28. King T.E., Tooze J.A., Schwarz M.I. et al. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am. J. Respir. Crit. Care Med. 2001; 164 (7): 1171–1181. DOI: 10.1164/ajrccm.164.7.2003140.

29. Авдеев С.Н. Обострение идиопатического легочного фиброза. Пульмонология. 2018; 28 (4): 469–482. DOI: 10.18093/0869-0189-2018-28-4-469-482.

30. Ambrosini V., Cancellieri A., Chilosi M. et al. Acute exacerbation of idiopathic pulmonary fibrosis: report of a series. Eur. Respir. J. 2003; 22 (5): 821–826. DOI: 10.1183/09031936.03.00022703.

31. Kim D.S., Park J.H., Park B.K. et al. Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur. Respir. J. 2006; 27 (1): 143–150. DOI: 10.1183/09031936.06.00114004.

32. Rajala K., Lehto J.T., Sutinen E. et al. mMRC dyspnoea scale indicates impaired quality of life and increased pain in patients with idiopathic pulmonary fibrosis. ERJ Open Res. 2017; 3 (4): 00084- 2017. DOI: 10.1183/23120541.00084-2017.

33. Ley B., Ryerson C.J., Vittinghoff E. et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann. Intern. Med. 2012; 156 (10): 684–691. DOI: 10.7326/0003-4819-156-10-201205150-00004.

34. Sgalla G., Walsh S.L.F., Sverzellati N. et al. “Velcro-type” crackles predict specific radiologic features of fibrotic interstitial lung disease. BMC Pulm. Med. 2018; 18 (1): 103. DOI: 10.1186/s12890-018-0670-0.

35. Collard H.R., King T.E. Jr, Bartelson B.B. et al. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2003; 168 (5): 538–542. DOI: 10.1164/rccm.200211-1311OC.

36. Wells A.U., Desai S.R., Rubens M.B. et al. Idiopathic pulmonary fibrosis: a composite physiologic index derived from disease extent observed by computed tomography. Am. J. Respir. Crit. Care Med. 2003; 167 (7): 962–969. DOI: 10.1164/rccm.2111053.

37. Mathieson J.R., Mayo J.R., Staples C.A., Muller N.L. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and chest radiography. Radiology. 1989; 171 (1): 111–116. DOI: 10.1148/radiology.171.1.2928513.

38. Remy-Jardin M., Campistron P., Amara A. et al. Usefulness of coronal reformations in the diagnostic evaluation of infiltrative lung disease. J. Comput. Assist. Tomogr. 2003; 27 (2): 266–273. DOI: 10.1097/00004728-200303000-00028.

39. Bankier A.A., O’Donnell C.R., Boiselle P.M. Quality initiatives. Respiratory instructions for CT examinations of the lungs: a handson guide. Radiographics. 2008; 28 (4): 919–931. DOI: 10.1148/rg.284085035.

40. Kim M., Lee S.M., Song J.W. et al. Added value of prone CT in the assessment of honeycombing and classification of usual interstitial pneumonia pattern. Eur. J. Radiol. 2017; 91: 66–70. DOI: 10.1016/j.ejrad.2017.03.018.

41. Gotway M.B., Lee E.S., Reddy G.P. et al. Low-dose, dynamic, expiratory thin-section CT of the lungs using a spiral CT scanner. J. Thorac. Imaging. 2000; 15 (3): 168–172. DOI: 10.1097/00005382-200007000-00003.

42. Lynch D.A., Godwin J.D., Safrin S. et al. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am. J. Respir. Crit. Care Med. 2005; 172 (4): 488–493. DOI: 10.1164/rccm.200412-1756OC.

43. Remy-Jardin M., Giraud F., Remy J. et al. Importance of groundglass attenuation in chronic diffuse infiltrative lung disease: pathologic-CT correlation. Radiology. 1993; 189 (3): 693–698. DOI: 10.1148/radiology.189.3.8234692.

44. Silva C.I., Müller N.L., Lynch D.A. et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. 2008; 246 (1): 288–297. DOI: 10.1148/radiol.2453061881.

45. Raghu G., Mageto Y.N., Lockhart D. et al. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study. Chest. 1999; 116 (5): 1168–1174. DOI: 10.1378/chest.116.5.1168.

46. Chung J.H., Chawla A., Peljto A.L. et al. CT scan findings of probable usual interstitial pneumonitis have a high predictive value for histologic usual interstitial pneumonitis. Chest. 2015; 147 (2): 450–459. DOI: 10.1378/chest.14-0976.

47. Cottin V., Nunes H., Brillet P.Y. et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur. Respir. J. 2005; 26 (4): 586–593. DOI: 10.1183/09031936.05.00021005.

48. Behr J., Kreuter M., Hoeper M.M. et al. Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry. Eur. Respir. J. 2015; 46 (1): 186–196. DOI: 10.1183/09031936.00217614.

49. Akagi T., Matsumoto T., Harada T. et al. Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis. Respir. Med. 2009; 103 (8): 1209–1215. DOI: 10.1016/j.rmed.2009.02.001.

50. Enright P.L. The Six-Minute Walk Test. Respir. Care. 2003; 48 (8): 783–785. Available at: http://rc.rcjournal.com/content/48/8/783.full.pdf

51. Lama V.N., Flaherty K.R., Toews G.B. et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am. J. Respir. Crit. Care Med. 2003; 168 (9): 1084–1090. DOI: 10.1164/rccm.200302-219OC.

52. du Bois R.M., Weycker D., Albera C. et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am. J. Respir. Crit. Care Med. 2011; 184 (12): 1382–1389. DOI: 10.1164/rccm.201105-0840OC.

53. Caminati A., Bianchi A., Cassandro R. et al. Walking distance on 6-MWT is a prognostic factor in idiopathic pulmonary fibrosis. Respir. Med. 2009; 103 (1): 117–123. DOI: 10.1016/j.rmed.2008.07.022.

54. Lederer D.J., Arcasoy S.M., Wilt J.S. et al. Six-minute-walk distance predicts waiting list survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2006; 174 (6): 659–664. DOI: 10.1164/rccm.200604-520OC.

55. Dowman L., Hill C.J., Holland A.E. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst. Rev. 2014; (10): CD006322. DOI: 10.1002/14651858.CD006322.pub3.

56. Mapel D.W., Samet J.M., Coultas D.B. Corticosteroids and the treatment of idiopathic pulmonary fibrosis: Past, present, and future. Chest. 1996; 110 (4): 1058–1067. DOI: 10.1378/chest.110.4.1058.

57. Hanson D., Winterbauer R.H., Kirtland S.H., Wu R. Changes in pulmonary function test results after 1 year of therapy as predictors of survival in patients with idiopathic pulmonary fibrosis. Chest. 1995; 108 (2): 305–310. DOI: 10.1378/chest.108.2.305.

58. Douglas W.W., Ryu J.H., Schroeder D.R. Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival. Am. J. Respir. Crit. Care Med. 2000; 161 (4, Pt 1): 1172–1178. DOI: 10.1164/ajrccm.161.4.9907002.

59. Raghu G., Depaso W.J., Cain K. et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am. Rev. Respir. Dis. 1991; 144 (2): 291–296. DOI: 10.1164/ajrccm/144.2.291.

60. Flaherty K.R., Toews G.B., Lynch J.P. et al. Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. Am. J. Med. 2001; 110 (4): 278–282. DOI: 10.1016/s0002-9343(00)00711-7.

61. Idiopathic Pulmonary Fibrosis Clinical Research Network; Martinez F.J., de Andrade J.A., Anstrom K.J. et al. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2014; 370 (22): 2093–2101. DOI: 10.1056/NEJMoa1401739.

62. Behr J., Maier K., Degenkolb B. et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis: adjunctive therapy to maintenance immunosuppression. Am. J. Respir. Crit. Care Med. 1997; 156 (6): 1897–1901. DOI: 10.1164/ajrccm.156.6.9706065.

63. Tomioka H., Kuwata Y., Imanaka K. et al. A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology. 2005; 10 (4): 449–455. DOI: 10.1111/j.1440-1843.2005.00725.x.

64. Oldham J.M., Ma S.F., Martinez F.J. et al. TOLLIP, MUC5B, and the response to N-acetylcysteine among individuals with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2015; 192 (12): 1475–1482. DOI: 10.1164/rccm.201505-1010OC.

65. Demedts M., Behr J., Buhl R. et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2005; 353 (21): 2229–2242. DOI: 10.1056/NEJMoa042976.

66. Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu G., Anstrom K.J., King T.E. Jr et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N. Engl. J. Med. 2012; 366 (21): 1968–1977. DOI: 10.1056/NEJMoa1113354.

67. Raghu G., Behr J., Brown K.K. et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann. Intern. Med. 2013; 158 (9): 641–649. DOI: 10.7326/0003-4819-158-9-201305070-00003.

68. Noth I., Anstrom K.J., Calvert S.B. et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2012; 186 (1): 88–95. DOI: 10.1164/rccm.201202-0314OC.

69. Lee J.S., Collard H.R., Anstrom K.J. et al. Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir. Med. 2013; 1 (5): 369–376. DOI: 10.1016/S2213-2600(13)70105-X.

70. Tran T., Suissa S. The effect of anti-acid therapy on survival in idiopathic pulmonary fibrosis: a methodological review of observational studies. Eur. Respir. J. 2018; 51 (6): 1800376. DOI: 10.1183/13993003.00376-2018.

71. Di Martino E., Provenzani A., Vitulo P., Polidori P. Systematic review and meta-analysis of pirfenidone, nintedanib, and pamrevlumab for the treatment of idiopathic pulmonary fibrosis. Ann. Pharmacother. 2021; 55 (6): 723–731. DOI: 10.1177/1060028020964451.

72. Lancaster L., Crestani B., Hernandez P. et al. Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: pooled data from six clinical trials. BMJ Open Respir. Res. 2019; 6 (1): e000397. DOI: 10.1136/bmjresp-2018-000397.

73. Skandamis A., Kani C., Markantonis S.L., Souliotis K. Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis. J. Drug Assess. 2019; 8 (1): 55–61. DOI: 10.1080/21556660.2019.1597726.

74. Richeldi L., Costabel U., Selman M. et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2011; 365 (12): 1079–1087. DOI: 10.1056/NEJMoa1103690.

75. Richeldi L., du Bois R.M., Raghu G. et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2014; 370 (22): 2071–2082. DOI: 10.1056/NEJMoa1402584.

76. Crestani B., Huggins J.T., Kaye M. et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. Lancet Respir. Med. 2019; 7 (1): 60–68. DOI: 10.1016/S2213-2600(18)30339-4.

77. Richeldi L., Cottin V., du Bois R.M. et al. Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the TOMORROW and INPULSIS(®) trials. Respir. Med. 2016; 113: 74–79. DOI: 10.1016/j.rmed.2016.02.001.

78. Авдеев С.Н. Новые возможности терапии идиопатического легочного фиброза. Пульмонология. 2017; 27 (4): 502–514. DOI: 10.18093/0869-0189-2017-27-4-502-514.

79. Авдеев С.Н., Трушенко Н.В. Антифибротическая терапия идиопатического легочного фиброза: соотношение эффективности и безопасности. Медицинский совет. 2018; (15): 131–136. DOI: 10.21518/2079-701X-2018-15-131-136.

80. Noble P.W., Albera C., Bradford W.Z. et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011; 377 (9779): 1760–1769. DOI: 10.1016/S0140-6736(11)60405-4.

81. King T.E., Bradford W.Z., Castro-Bernardini S. et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N. Engl. J. Med. 2014; 370 (22): 2083–2092. DOI: 10.1056/NEJMoa1402582.

82. Nathan S.D., Albera C., Bradford W.Z. et al. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir. Med. 2017; 5 (1): 33–41. DOI: 10.1016/S2213-2600(16)30326-5.

83. Авдеев С.Н., Чикина С.Ю., Нагаткина О.В. Идиопатический легочный фиброз: новые международные клинические рекомендации. Пульмонология. 2019; 29 (5): 525–552. DOI: 10.18093/0869-0189-2019-29-5-525-552.

84. Авдеев С.Н. Новые возможности терапии идиопатического легочного фиброза. Пульмонология. 2017; 27 (4): 502–514. DOI: 10.18093/0869-0189-2017-27-4-502-514.

85. Richeldi L., Cottin V., Flaherty K.R. et al. Design of the INPULSIS™ trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir. Med. 2014; 108 (7): 1023–1030. DOI: 10.1016/j.rmed.2014.04.011.

86. Birring S.S., Kavanagh J.E., Irwin R.S. et al. Treatment of interstitial lung disease associated cough: CHEST guideline and expert panel report. Chest. 2018; 154 (4): 904–917. DOI: 10.1016/j.chest.2018.06.038.

87. Nathan S.D., Costabel U., Albera C. et al. Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment. Respir. Med. 2019; 153: 44–51. DOI: 10.1016/j.rmed.2019.04.016.

88. Авдеев С.Н. Обострение идиопатического легочного фиброза. Пульмонология. 2018; 28 (4): 469–482. DOI: 10.18093/0869-0189-2018-28-4-469-482.

89. Polke M, Kondoh Y, Wijsenbeek M. et al. Management of acute exacerbation of idiopathic pulmonary fibrosis in specialised and non-specialised ILD centres around the world. Front. Med. (Lausanne). 2021; 8: 699644. DOI: 10.3389/fmed.2021.699644.

90. Kreuter M., Polke M., Walsh S.L.F. et al. Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation. Eur. Respir. J. 2020; 55 (4): 1901760. DOI: 10.1183/13993003.01760-2019.

91. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal oxygen therapy trial group. Ann. Intern. Med. 1980; 93 (3): 391–398. DOI: 10.7326/0003-4819-93-3-391.

92. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981; 317 (8222): 681–686. DOI: 10.1016/S0140-6736(81)91970-X.

93. Faverio P., De Giacomi F., Sardella L. et al. Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights. BMC Pulm. Med. 2018; 18 (1): 70. DOI: 10.1186/s12890-018-0643-3.

94. Dreher M., Ekkernkamp E., Schmoor C. et al. Pulmonary rehabilitation and noninvasive ventilation in patients with hypercapnic interstitial lung disease. Respiration. 2015; 89 (3): 208–213. DOI: 10.1159/000369862.

95. Stern J.B., Mal H., Groussard O. et al. Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure. Chest. 2001; 120 (1): 213–219. DOI: 10.1378/chest.120.1.213.

96. Al-Hameed F.M., Sharma S. Outcome of patients admitted to the intensive care unit for acute exacerbation of idiopathic pulmonary fibrosis. Can. Respir. J. 2004; 11 (2): 117–122. DOI: 10.1155/2004/379723.

97. Mollica C., Paone G., Conti V. et al. Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis. Respiration. 2010; 79 (3): 209–215. DOI: 10.1159/000225932.

98. Thabut G., Mal H., Castier Y. et al. Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J. Thorac. Cardiovasc. Surg. 2003; 126 (2): 469–475. DOI: 10.1016/s0022-5223(03)00600-7.

99. Hanada M., Kasawara K.T., Mathur S. et al. Aerobic and breathing exercises improve dyspnea, exercise capacity and quality of life in idiopathic pulmonary fibrosis patients: systematic review and meta-analysis. J. Thorac. Dis. 2020; 12 (3): 1041–1055. DOI: 10.21037/jtd.2019.12.27.

100. King T.E. Jr, Safrin S., Starko K.M. et al. Analyses of efficacy end points in a controlled trial of interferon-gamma1b for idiopathic pulmonary fibrosis. Chest. 2005; 127 (1): 171–177. DOI: 10.1378/chest.127.1.171.

101. Zappala C.J., Latsi P.I., Nicholson A.G. et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur. Respir. J. 2010; 35 (4): 830–836. DOI: 10.1183/09031936.00155108.

102. Zieliński M., Sitek P., Ziora D. Idiopathic pulmonary fibrosis coexisting with lung cancer – a review. Adv. Respir. Med. 2018; 86 (6): 319–326. DOI: 10.5603/ARM.a2018.0052.

103. Karampitsakos T., Tzilas V., Tringidou R. et al. Lung cancer in patients with idiopathic pulmonary fibrosis. Pulm. Pharmacol. Ther. 2017; 45: 1–10. DOI: 10.1016/j.pupt.2017.03.016.

104. Costabel U., Crestani B., Wells A., eds. Idiopathic Pulmonary Fibrosis: ERS Monograph. Plymouth: Latimer Trend and Company Limited; 2016. DOI: 10.1183/2312508X.erm7116.

105. Ghofrani H.A., Wiedemann R., Rose F. et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002; 360 (9337): 895–900. DOI: 10.1016/S0140-6736(02)11024-5.

106. Madden B.P., Allenby M., Loke T.K., Sheth A. A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul. Pharmacol. 2006; 44 (5): 372–376. DOI: 10.1016/j.vph.2006.01.013.

107. Collard H.R., Anstrom K.J., Schwarz M.I., Zisman D.A. Sildenafil improves walk distance in idiopathic pulmonary fibrosis. Chest. 2007; 131 (3): 897–899. DOI: 10.1378/chest.06-2101.

108. Olschewski H., Ghofrani H.A., Walmrath D. et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am. J. Respir. Crit. Care Med. 1999; 160 (2): 600–607. DOI: 10.1164/ajrccm.160.2.9810008.

109. Minai O.A., Sahoo D., Chapman J.T., Mehta A.C. Vaso-active therapy can improve 6-min walk distance in patients with pulmonary hypertension and fibrotic interstitial lung disease. Respir. Med. 2008; 102 (7): 1015–1020. DOI: 10.1016/j.rmed.2008.02.002.

110. Fulton B.G., Ryerson C.J. Managing comorbidities in idiopathic pulmonary fibrosis. Int. J. Gen. Med. 2015: 8: 309–318. DOI: 10.2147/IJGM.S74880.

111. Raghu G., Yang S.T., Spada C. et al. Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest. 2006; 129 (3): 794–800. DOI: 10.1378/chest.129.3.794.

112. Linden P.A., Gilbert R.J., Yeap B.Y. et al. Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation. J. Thorac. Cardiovasc. Surg. 2006; 131 (2): 438–446. DOI: 10.1016/j.jtcvs.2005.10.014.

113. Lee J.S., Ryu J.H., Elicker B.M. et al. Gastroesophageal reflux therapy is associated with longer survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2011; 184 (12): 1390–1394. DOI: 10.1164/rccm.201101-0138OC.

114. Savarino E., Bazzica M., Zentilin P. et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring. Am. J. Respir. Crit. Care Med. 2009; 179 (5): 408–413. DOI: 10.1164/rccm.200808-1359OC.

115. Cano-Jiménez E., Hernández González F., Peloche G.B. Comorbidities and complications in idiopathic pulmonary fibrosis. Med. Sci. 2018; 6 (3): 71. DOI: 10.3390/medsci6030071.

116. Kreuter M., Brunnemer E., Ehlers-Tenenbaum S. et al. Other comorbidities. In: Costabel U., Crestani B., Wells A., eds. Idiopathic pulmonary fibrosis: ERS Monograph. Plymouth: Latimer Trend and Company Limited; 2016: 186–195. DOI: 10.1183/2312508X.erm7116.

117. Mahler D.A., Wells C.K. Evaluation of clinical methods for rating dyspnea. Chest. 1988; 93 (3): 580–586. DOI: 10.1378/chest.93.3.580.