Лекарственно-индуцированное интерстициальное заболевание легких (Л-ИЗЛ) может быть вызвано различными препаратами, включая антибиотики, амиодарон, противоопухолевые, ревматологические и нестероидные противовоспалительные средства.
Л-ИЗЛ включает реакции гиперчувствительности, организующуюся и неспецифическую интерстициальную пневмонии, эозинофильные заболевания легких, диффузное альвеолярное повреждение и альвеолярную гиповентиляцию. Для исключения других причин легочных заболеваний необходима оценка анамнеза, физикальных данных и результатов обследования, которые могут включать рентгенографию/мультиспиральную компьютерную томографию (МСКТ) грудной клетки, исследование функции легких и бронхоскопию с бронхоальвеолярным лаважом. Диагностика Л-ИЗЛ затруднена вследствие неоднородности клинических, рентгенологических и гистологических данных. Рентгенопатологический фенотип Л-ИЗЛ различается, не выявлено специфичного МСКТ-паттерна. Лечение включает отмену препарата и в некоторых случаях терапию глюкокортикоидами, хотя нет проспективных исследований по их влиянию на исход болезни. В этой статье приводятся различные лекарственные средства, которые вызывают ИЗЛ, подходы к их диагностике и лечению.
Drug-induced interstitial lung disease (D-ILD) can be caused by various drugs, including antibiotics, amiodarone, antitumor, rheumatological and non-steroidal anti-inflammatory drugs. D-ILD includes hypersensitivity reactions, organizing and non-specific interstitial pneumonia, eosinophilic lung diseases, diffuse alveolar damage and alveolar hypoventilation. To exclude other causes of pulmonary diseases, an assessment of the medical history, physical data and examination results, which may include chest X-ray/multispiral computed tomography (MSCT), lung function tests, and bronchoscopy with bronchoalveolar lavage, are necessary. Diagnosis of D-ILD is difficult due to the heterogeneity of clinical, radiological and histological data. The X-ray pathological phenotype of D-ILD is different; a specific MSCT pattern has not been identified. Treatment includes drug withdrawal and, in some cases, glucocorticoid therapy, although there are no prospective studies on their effect on the outcome of the disease. This article provides various drugs that cause ILD, approaches to their diagnosis and treatment.
1. Schreiber J. Drug-induced lung diseases. Dtsch med Wochenschr. 2011;136(13):631-4. doi: 10.1055/s-0031-1274553
2. Camus P, Bonniaud P, Fanton A, et al. Drug-induced and iatrogenic infiltrative lung disease. Clin Chest Med. 2004 Sep;25(3):479-519. doi: 10.1016/j.ccm.2004.05.006
3. Travis WD, Costabel U, Hansell DM, 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 Sep 15;188(6):733-48. doi: 10.1164/rccm.201308-1483ST
4. Amar RK, Jick SS, Rosenberg D, et al. Drug-/radiation-induced interstitial lung disease in the United Kingdom general population: Incidence, all-cause mortality and characteristics at diagnosis. Respirology. 2012 Jul;17(5):861-8. doi: 10.1111/j.1440-1843.2012.02187.x
5. Duchemann B, Annesi-Maesano I, de Jacobe NC, et al. Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris. Eur Respir J. 2017 Aug 3;50(2). pii: 1602419. doi: 10.1183/13993003.02419-2016
6. Roelandt M, Demedts M, Callebaut W, et al. Epidemiology of interstitial lung disease (ILD) in Flanders: Registration by pneumologists in 1992–1994. Working group on ILD, VRGT. Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding. Acta Clin Belg. 1995;50(5):260-8. doi: 10.1080/17843286.1995.11718459
7. Hyldgaard C, Hilberg O, Muller A, Bendstrup E. A cohort study of interstitial lung diseases in central Denmark. Respir Med. 2014 May;108(5):793-9. doi: 10.1016/j.rmed.2013.09.002
8. Skeoch S, Weatherley N, Swift AJ, et al. Drug-Induced Interstitial Lung Disease: A Systematic Review. J Clin Med. 2018 Oct 15;7(10). pii: E356. doi: 10.3390/jcm7100356
9. Kakugawa T, Yokota S, Ishimatsu Y, et al. Serum heat shock protein 47 levels in patients with drug-induced lung disease. Respir Res. 2013 Nov 20;14:133. doi: 10.1186/1465-9921-14-133
10. Ohnishi H, Yokoyama A, Yasuhara Y, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003 Oct;58(10):872-5. doi: 10.1136/thorax.58.10.872
11. Piciucchi S, Romagnoli M, Chilosi M, et al. Prospective evaluation of drug-induced lung toxicity with high-resolution CT and transbronchial biopsy. Radiol Med. 2011 Mar;116(2):246-63. doi: 10.1007/s11547-010-0608-y
12. Blum RH, Carter SK, Agre K. A clinical review of bleomycin – A new antineoplastic agent. Cancer. 1973 Apr;31(4):903-14. doi: 10.1002/1097-0142(197304)31:4<903::aid-cncr2820310422>3.0.co; 2-n
13. Stamatoullas A, Brice P, Bouabdallah R, et al. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: Frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. doi: 10.1111/bjh.13419
14. O’Sullivan JM, Huddart RA, Norman AR, et al. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003 Jan;14:91-6. doi: 10.1093/annonc/mdg020
15. Sahin IH, Geyer AI, Kelly DW, O’Reilly EM. Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma – An Infrequent Event: Elucidation of Risk Factors and Management Implications. Clin Colorectal Cancer. 2016 Mar;15(1):24-31. doi: 10.1016/j.clcc.2015.08.003
16. Kouroussis C, Mavroudis D, Kakolyris S, et al. High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: Results of a dose-finding study. Lung Cancer. 2004 Jun;44:363-8. doi: 10.1016/j.lungcan.2003.12.004
17. Hamada T, Yasunaga H, Nakai Y, et al. Interstitial lung disease associated with gemcitabine: A Japanese retrospective cohort study. Respirology. 2016 Feb;21(2):338-43. doi: 10.1111/resp.12665
18. Osawa M, Kudoh S, Sakai F, et al. Clinical features and risk factors of panitumumab-induced interstitial lung disease: A postmarketing all-case surveillance study. Int J Clin Oncol. 2015 Dec;20(6):1063-71. doi: 10.1007/s10147-015-0834-3
19. Gemma A, Kudoh S, Ando M, et al. Final safety and efficacy of erlotinib in the phase 4 POLARSTAR surveillance study of 10,708 Japanese patients with non-small-cell lung cancer. Cancer Sci. 2014 Dec;105(12):1584-90. doi: 10.1111/cas.12550
20. Boku N, Sugihara K, Kitagawa Y, et al. Panitumumab in Japanese patients with unresectable colorectal cancer: A post-marketing surveillance study of 3085 patients. Jpn J Clin Oncol. 2014 Mar;44(3):214-23. doi: 10.1093/jjco/hyt196
21. Solazzo A, Botta C, Nava F, et al. Interstitial Lung Disease After Kidney Transplantation and the Role of Everolimus. Transplant Proc. 2016 Mar;48(2):349-51. doi: 10.1016/j.transproceed.2015.12.039
22. White DA, Camus P, Endo M, et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC
23. Iacovelli R, Palazzo A, Mezi S, et al. Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy.
A meta-analysis of published trials. Acta Oncol. 2012 Sep;51(7):873-9. doi: 10.3109/0284186X.2012.705019
24. Delaunay M, Cadranel J, Lusque A, et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J. 2017 Aug 10;50(2). pii: 1700050. doi: 10.1183/13993003.00050-2017
25. Khunger M, Rakshit S, Pasupuleti V, et al. Incidence of Pneumonitis with Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer:A Systematic Review and Meta-Analysis of Trials. Chest. 2017 Aug;152(2):271-81. doi: 10.1016/j.chest.2017.04.177
26. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-56. doi: 10.1056/NEJMoa1709684
27. Conway R, Low C, Coughlan RJ, et al. Methotrexate and lung disease in rheumatoid arthritis:A meta-analysis of randomized controlled trials. Arthritis Rheumatol. 2014 Apr;66(4):803-12. doi: 10.1002/art.38322
28. Conway R, Low C, Coughlan RJ, et al. Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and inflammatory bowel disease: Systematic literature review and meta-analysis of randomised controlled trials. BMJ. 2015 Mar 13;350:h1269. doi: 10.1136/bmj.h1269
29. Alarcon GS, Kremer JM, Macaluso M, et al. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med. 1997 Sep 1;127(5):356-64. doi: 10.7326/0003-4819-127-5-199709010-00003
30. Imokawa S, Colby TV, Leslie KO, Helmers RA. Methotrexate pneumonitis: Review of the literature and histopathological findings in nine patients. Eur Respir J. 2000 Feb;15(2):373-81. doi: 10.1034/j.1399-3003.2000.15b25.x
31. Sawada T, Inokuma S, Sato T, et al. On Behalf of the Study Committee for Leflunomide-induced Lung Injury, Japan College of Rheumatology. Leflunomide-induced interstitial lung disease: Prevalence and risk factors in Japanese patients with rheumatoid arthritis. Rheumatology (Oxford). 2009 Oct;48(10):1265-8. doi: 10.1093/rheumatology/kep227
32. Conway R, Low C, Coughlan RJ, et al. Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials. J Rheumatol. 2016 May;43(5):855-60. doi: 10.3899/jrheum.150674
33. Roubille C, Haraoui B. Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review. Semin Arthritis Rheum. 2014 Apr;43(5):613-26. doi: 10.1016/j.semarthrit.2013.09.005
34. Herrinton LJ, Harrold LR, Liu L, et al. Association between anti-TNF-alpha therapy and interstitial lung disease. Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):394-402. doi: 10.1002/pds.3409
35. Hadjinicolaou AV, Nisar MK, Bhagat S, et al. Non-infectious pulmonary complications of newer biological agents for rheumatic diseases –
A systematic literature review. Rheumatology (Oxford). 2011 Dec;50(12):2297-305. doi: 10.1093/rheumatology/ker289
36. Liote H, Liote F, Seroussi B, et al. Rituximab-induced lung disease:
A systematic literature review. Eur Respir J. 2010 Mar;35(3):681-7. doi: 10.1183/09031936.00080209
37. Holmberg L, Boman G, Bottiger LE, et al. Adverse reactions to nitrofurantoin. Analysis of 921 reports. Am J Med. 1980 Nov;69(5):733-8. doi: 10.1016/0002-9343(80)90443-x
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1. Schreiber J. Drug-induced lung diseases. Dtsch med Wochenschr. 2011;136(13):631-4. doi: 10.1055/s-0031-1274553
2. Camus P, Bonniaud P, Fanton A, et al. Drug-induced and iatrogenic infiltrative lung disease. Clin Chest Med. 2004 Sep;25(3):479-519. doi: 10.1016/j.ccm.2004.05.006
3. Travis WD, Costabel U, Hansell DM, 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 Sep 15;188(6):733-48. doi: 10.1164/rccm.201308-1483ST
4. Amar RK, Jick SS, Rosenberg D, et al. Drug-/radiation-induced interstitial lung disease in the United Kingdom general population: Incidence, all-cause mortality and characteristics at diagnosis. Respirology. 2012 Jul;17(5):861-8. doi: 10.1111/j.1440-1843.2012.02187.x
5. Duchemann B, Annesi-Maesano I, de Jacobe NC, et al. Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris. Eur Respir J. 2017 Aug 3;50(2). pii: 1602419. doi: 10.1183/13993003.02419-2016
6. Roelandt M, Demedts M, Callebaut W, et al. Epidemiology of interstitial lung disease (ILD) in Flanders: Registration by pneumologists in 1992–1994. Working group on ILD, VRGT. Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding. Acta Clin Belg. 1995;50(5):260-8. doi: 10.1080/17843286.1995.11718459
7. Hyldgaard C, Hilberg O, Muller A, Bendstrup E. A cohort study of interstitial lung diseases in central Denmark. Respir Med. 2014 May;108(5):793-9. doi: 10.1016/j.rmed.2013.09.002
8. Skeoch S, Weatherley N, Swift AJ, et al. Drug-Induced Interstitial Lung Disease: A Systematic Review. J Clin Med. 2018 Oct 15;7(10). pii: E356. doi: 10.3390/jcm7100356
9. Kakugawa T, Yokota S, Ishimatsu Y, et al. Serum heat shock protein 47 levels in patients with drug-induced lung disease. Respir Res. 2013 Nov 20;14:133. doi: 10.1186/1465-9921-14-133
10. Ohnishi H, Yokoyama A, Yasuhara Y, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003 Oct;58(10):872-5. doi: 10.1136/thorax.58.10.872
11. Piciucchi S, Romagnoli M, Chilosi M, et al. Prospective evaluation of drug-induced lung toxicity with high-resolution CT and transbronchial biopsy. Radiol Med. 2011 Mar;116(2):246-63. doi: 10.1007/s11547-010-0608-y
12. Blum RH, Carter SK, Agre K. A clinical review of bleomycin – A new antineoplastic agent. Cancer. 1973 Apr;31(4):903-14. doi: 10.1002/1097-0142(197304)31:4<903::aid-cncr2820310422>3.0.co; 2-n
13. Stamatoullas A, Brice P, Bouabdallah R, et al. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: Frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. doi: 10.1111/bjh.13419
14. O’Sullivan JM, Huddart RA, Norman AR, et al. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003 Jan;14:91-6. doi: 10.1093/annonc/mdg020
15. Sahin IH, Geyer AI, Kelly DW, O’Reilly EM. Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma – An Infrequent Event: Elucidation of Risk Factors and Management Implications. Clin Colorectal Cancer. 2016 Mar;15(1):24-31. doi: 10.1016/j.clcc.2015.08.003
16. Kouroussis C, Mavroudis D, Kakolyris S, et al. High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: Results of a dose-finding study. Lung Cancer. 2004 Jun;44:363-8. doi: 10.1016/j.lungcan.2003.12.004
17. Hamada T, Yasunaga H, Nakai Y, et al. Interstitial lung disease associated with gemcitabine: A Japanese retrospective cohort study. Respirology. 2016 Feb;21(2):338-43. doi: 10.1111/resp.12665
18. Osawa M, Kudoh S, Sakai F, et al. Clinical features and risk factors of panitumumab-induced interstitial lung disease: A postmarketing all-case surveillance study. Int J Clin Oncol. 2015 Dec;20(6):1063-71. doi: 10.1007/s10147-015-0834-3
19. Gemma A, Kudoh S, Ando M, et al. Final safety and efficacy of erlotinib in the phase 4 POLARSTAR surveillance study of 10,708 Japanese patients with non-small-cell lung cancer. Cancer Sci. 2014 Dec;105(12):1584-90. doi: 10.1111/cas.12550
20. Boku N, Sugihara K, Kitagawa Y, et al. Panitumumab in Japanese patients with unresectable colorectal cancer: A post-marketing surveillance study of 3085 patients. Jpn J Clin Oncol. 2014 Mar;44(3):214-23. doi: 10.1093/jjco/hyt196
21. Solazzo A, Botta C, Nava F, et al. Interstitial Lung Disease After Kidney Transplantation and the Role of Everolimus. Transplant Proc. 2016 Mar;48(2):349-51. doi: 10.1016/j.transproceed.2015.12.039
22. White DA, Camus P, Endo M, et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC
23. Iacovelli R, Palazzo A, Mezi S, et al. Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy.
A meta-analysis of published trials. Acta Oncol. 2012 Sep;51(7):873-9. doi: 10.3109/0284186X.2012.705019
24. Delaunay M, Cadranel J, Lusque A, et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J. 2017 Aug 10;50(2). pii: 1700050. doi: 10.1183/13993003.00050-2017
25. Khunger M, Rakshit S, Pasupuleti V, et al. Incidence of Pneumonitis with Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer:A Systematic Review and Meta-Analysis of Trials. Chest. 2017 Aug;152(2):271-81. doi: 10.1016/j.chest.2017.04.177
26. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-56. doi: 10.1056/NEJMoa1709684
27. Conway R, Low C, Coughlan RJ, et al. Methotrexate and lung disease in rheumatoid arthritis:A meta-analysis of randomized controlled trials. Arthritis Rheumatol. 2014 Apr;66(4):803-12. doi: 10.1002/art.38322
28. Conway R, Low C, Coughlan RJ, et al. Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and inflammatory bowel disease: Systematic literature review and meta-analysis of randomised controlled trials. BMJ. 2015 Mar 13;350:h1269. doi: 10.1136/bmj.h1269
29. Alarcon GS, Kremer JM, Macaluso M, et al. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med. 1997 Sep 1;127(5):356-64. doi: 10.7326/0003-4819-127-5-199709010-00003
30. Imokawa S, Colby TV, Leslie KO, Helmers RA. Methotrexate pneumonitis: Review of the literature and histopathological findings in nine patients. Eur Respir J. 2000 Feb;15(2):373-81. doi: 10.1034/j.1399-3003.2000.15b25.x
31. Sawada T, Inokuma S, Sato T, et al. On Behalf of the Study Committee for Leflunomide-induced Lung Injury, Japan College of Rheumatology. Leflunomide-induced interstitial lung disease: Prevalence and risk factors in Japanese patients with rheumatoid arthritis. Rheumatology (Oxford). 2009 Oct;48(10):1265-8. doi: 10.1093/rheumatology/kep227
32. Conway R, Low C, Coughlan RJ, et al. Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials. J Rheumatol. 2016 May;43(5):855-60. doi: 10.3899/jrheum.150674
33. Roubille C, Haraoui B. Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review. Semin Arthritis Rheum. 2014 Apr;43(5):613-26. doi: 10.1016/j.semarthrit.2013.09.005
34. Herrinton LJ, Harrold LR, Liu L, et al. Association between anti-TNF-alpha therapy and interstitial lung disease. Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):394-402. doi: 10.1002/pds.3409
35. Hadjinicolaou AV, Nisar MK, Bhagat S, et al. Non-infectious pulmonary complications of newer biological agents for rheumatic diseases –
A systematic literature review. Rheumatology (Oxford). 2011 Dec;50(12):2297-305. doi: 10.1093/rheumatology/ker289
36. Liote H, Liote F, Seroussi B, et al. Rituximab-induced lung disease:
A systematic literature review. Eur Respir J. 2010 Mar;35(3):681-7. doi: 10.1183/09031936.00080209
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Авторы
Э.Х. Анаев
ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
________________________________________________
E.Kh. Anaev
Pirogov Russian National Research Medical University, Moscow, Russia