Диагностика и лечение хронического легочного аспергиллеза: клинические рекомендации Европейского респираторного общества и Европейского общества клинической микробиологии и инфекционных заболеваний

Хронический легочный аспергиллез (ХЛА) – нечастое и труднодиагностируемое легочное заболевание, осложняющее многие другие респираторные заболевания. В настоящее время в Европе насчитывается около 240 тыс. больных ХЛА. Наиболее распространенной формой ХЛА является кавитарный ХЛА (ХКЛА) (с формированием полостей), который при отсутствии лечения может трансформироваться в хронический фиброзирующий ХЛА. К менее частым проявлениям ХЛА относятся аспергиллезные узлы и одиночная аспергиллема. Все перечисленные изменения встречаются у иммунонекомпрометированных пациентов с различными заболеваниями легких. Подострый инвазивный легочный аспергиллез (ранее называвшийся хроническим некротизирующим легочным аспергиллезом) – это быстропрогрессирующая (< 3 мес.) инфекция, обычно диагностируемая у больных с умеренным иммунодефицитом, которая должна лечиться как инвазивный аспергиллез. Диагностика и ведение больных ХЛА ранее рассматривалось в единичных клинических рекомендациях. В связи с этим была созвана группа экспертов для разработки клинических, рентгенологических и микробиологических рекомендаций. При диагностике ХЛА требуется сочетание следующих признаков: одна или несколько полостей с грибковым конгломератом внутри или без такового либо узлы при лучевом обследовании легких; прямое подтверждение аспергиллезной инфекции (путем микроскопии или посева биопсийного материала) или иммунологическая реакция на Aspergillus spp. при исключении альтернативного диагноза. Все признаки должны наблюдаться в течение ≥ 3 мес. Уровень антител к Aspergillus (преципитины) повышен у > 90 % больных. В случае технической возможности рекомендуется хирургическое удаление аспергиллемы, желательно методом видеоассистированной торакоскопии. При ХКЛА рекомендуется длительная пероральная противогрибковая терапия для улучшения состояния в целом и устранения респираторных симптомов, прекращения кровохарканья и предотвращения прогрессирования заболевания. Рекомендуется тщательное мониторирование сывороточной концентрации азола, лекарственного взаимодействия и возможных токсических эффектов. Кровохарканье и легочное кровотечение можно устранить с помощью транексамовой кислоты и эмболизации бронхиальных артерий, реже – с помощью хирургической резекции легкого. Кровохарканье может служить признаком неэффективности лечения и / или резистентности к противогрибковым препаратам. Больные с одиночным аспергиллезным узлом нуждаются в противогрибковой терапии только при невозможности резекции, а при множественных аспергиллезных узлах противогрибковая терапия может дать существенный терапевтический эффект. Такие больные нуждаются в тщательном наблюдении.

1. Bennett J. On the parasitic vegetable structures found growing in living animals. Trans Royal Soc. Edinburgh. 1842; 15: 277-279.

2. Kelmenson V.A. Treatment of pulmonary aspergillosis. Dis. Chest. 1959; 36: 442-443.

3. Deve F. Une nouvelle forme anatomoradiologique mycose pulmonaire primitive. Le megamycetome intrabron chiectasique [A new anatomical shape radiological primary pulmonary fungal infection. The megamycetoma intrabronchiectasique]. Arch. Med. Chir. Appar. Respir. 1938; 13: 337.

4. Finegold S.M., Will D., Murray J.F. Aspergillosis: a review and report of 12 cases. J. Med. 1959; 27: 463-482.

5. Longbottom J.L., Pepys J., Clive F.T. Diagnostic precipitin test in Aspergillus pulmonary mycetoma. Lancet. 1964; 1: 588-589.

6. Gefter W.B., Weingrad T.R., Epstein D.M. et al. «Semiinvasive» pulmonary aspergillosis: a new look at the spectrum of aspergillus infections of the lung. Radiology. 1981; 140: 313-321.

7. Binder R.E., Faling L.J., Pugatch R.D. et al. Chronic necrotizing pulmonary aspergillosis: a discrete clinicalentity. Medicine. 1982; 61: 109-124.

8. Battaglini J.W., Murray G.F., Keagy B.A. et al. Surgical management of symptomatic pulmonary aspergilloma. Ann. Thorac. Surg. 1985; 39: 512-516.

9. Daly R.C., Pairolero P.C., Piehler J.M. et al. Pulmonary aspergilloma. Results of surgical treatment. J. Thorac. Cardiovasc. Surg.1986; 92: 981-988.

10. Denning D.W., Riniotis K., Dobrashian R. et al. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin. Infect. Dis. 2003; 37 (Suppl. 3): S265-S280.

11. Godet C., Philippe B., Laurent F. et al. Chronic pulmonary aspergillosis: an update on diagnosis and treatment. Respiration. 2014; 88: 162-174.

12. Hope W.W., Walsh T.J., Denning D.W. The invasive and saprophytic syndromes due to Aspergillus spp. Med. Mycol. 2005; 43 (Suppl. 1): S207-S238.

13. Izumikawa K., Tashiro T., Tashiro M. et al. Pathogenesis and clinical features of chronic pulmonary aspergillosis - is it possible to distinguish CNPA and CCPA clinically? J. Infect. Chemother. 2014; 20: 208-212.

14. Kohno S., Izumikawa K., Ogawa K. et al. Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan. J. Infect. 2010; 61: 410-418.

15. Cadranel J., Philippe B., Hennequin C. et al. Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial. Eur. J. Clin. Microbiol. Infect. Dis. 2012; 31: 3231-3239.

16. Kohno S., Masaoka T., Yamaguchi H. et al. A multicenter, openlabel clinical study of micafungin (FK463) in the treatment of deepseated mycosis in Japan. Scand. J. Infect. Dis. 2004; 36: 372-379.

17. Denning D.W., Perlin D.S. Azole resistance in Aspergillus: a growing public health menace. Future Microbiol. 2011; 6: 1229-1232.

18. Denning D.W., Pleuvry A., Cole D.C. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med. Mycol. 2013; 51: 361-370.

19. Denning D.W., Pleuvry A., Cole D.C. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. Eur. Respir. J. 2013; 41: 621-626.

20. Stevens D.A., Kan V.L., Judson M.A. et al. Practice guide lines for diseases caused by Aspergillus. Clin. Infect. Dis. 2000; 30: 696-709.

21. Walsh T.J., Anaissie E.J., Denning D.W. et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 2008; 46: 327-360.

22. Ullmann A.J., Cornely O.A., Donnelly J.P. et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases. Clin. Microbiol. Infect. 2012; 18: Suppl. 7, 1-8.

23. Dai Z., Zhao H., Cai S. et al. Invasive pulmonary asper gillosis in nonneutropenic patients with and without underlying disease: a singlecentre retrospective analysis of 52 subjects. Respirology. 2013; 18: 323-331.

24. Kim S.Y., Lee K.S., Han J. et al. Semiinvasive pulmonary aspergillosis: CT and pathologic findings in six patients. Am. J. Roentgenol. 2000; 174: 795-798.

25. Kobashi Y., Fukuda M., Yoshida K. et al. Chronic necrotizing pulmonary aspergillosis as a complication of pulmonary Mycobacterium avium complex disease. Respirology. 2006; 11: 809-813.

26. Kosmidis C., Denning D.W. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015; 70: 270-277.

27. Denning D.W., Follansbee S., Scolaro M. et al. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N. Engl. J. Med. 1991; 324: 654-662.

28. Kono Y., Tsushima K., Yamaguchi K. et al. The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis. Respir. Med. 2013; 107: 1094-1100.

29. Uffredi M.L., Mangiapan G., Cadranel J. et al. Significance of Aspergillus fumigatus isolation from respiratory specimens of nongranulocytopenic patients. Eur. J. Clin. Microbiol. Infect. Dis. 2003; 22: 457-462.

30. Camuset J., Nunes H., Dombret M.C. et al. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest. 2007; 131: 1435-1441.

31. Nam H.S., Jeon K., Um S.W. et al. Clinical characteris tics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int. J. Infect. Dis. 2010; 14: e479-e482.

32. Horvath J.A., Dummer S. The use of respiratorytract cultures in the diagnosis of invasive pulmonary aspergillosis. Am. J. Med. 1996; 100: 171- 178.

33. McCarthy D.S., Pepys J. Allergic bronchopulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin. Allergy. 1971; 1: 415-432.

34. Chakrabarti A., Sethi S., Raman D.S.V. et al. Eightyear study of allergic bronchopulmonary aspergillosis in an Indian teaching hospital. Mycoses. 2002; 45: 295-299.

35. Pashley C.H., Fairs A., Morley J.P. et al. Routine processing procedures for isolating filamentous fungi from respiratory sputum samples may underestimate fungal prevalence. Med. Mycol. 2012; 50: 433-438.

36. Fraczek M.G., Kirwan M.B., Moore C.B. et al. Volume dependency for culture of fungi from respiratory secretions and increased sensitivity of Aspergillus quantitative PCR. Mycoses. 2014; 57: 69-78.

37. Howard S.J., Cerar D., Anderson M.J. et al. Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg. Infect. Dis. 2009; 15: 1068-1076.

38. Izumikawa K., Yamamoto Y., Mihara T. et al. Broncho alveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med. Mycol. 2012; 50: 811-817.

39. Shin B., Koh W.J., Jeong B.H. et al. Serum galactoman nan antigen test for the diagnosis of chronic pulmonary aspergillosis. J. Infect. 2014; 68: 494-499.

40. Franquet T., Mäller N.L., Giménez A. et al. Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings. Radiographics. 2001; 21: 825-837.

41. Tashiro T., Izumikawa K., Tashiro M. et al. A case series of chronic necrotizing pulmonary aspergillosis and a new proposal. Jpn. J. Infect. Dis. 2013; 66: 312-316.

42. van Toorenenbergen A.W. Betweenlaboratory quality control of automated analysis of IgG antibodies against Aspergillus fumigatus. Diagn. Microbiol. Infect. Dis. 2012; 74: 278-281.

43. Baxter C.G., Denning D.W., Jones A.M. et al. Perfor mance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis. Clin. Microbiol. Infect. 2013; 19: E197-E204.

44. Guitard J., Sendid B., Thorez S. et al. Evaluation of a recombinant antigenbased enzyme immunoassay for the diagnosis of noninvasive aspergillosis. J. Clin. Microbiol. 2012; 50: 762-765.

45. Aspergilloma and residual tuberculous cavities - the results of a resurvey. Tubercle. 1970; 51: 227-245.

46. Kitasato Y., Tao Y., Hoshino T. et al. Comparison of Aspergillus galactomannan antigen testing with a new cut off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirology. 2009; 14: 701-708.

47. Ohba H., Miwa S., Shirai M. et al. Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir. Med. 2012; 106: 724-729

48. Brouwer J. Detection of antibodies against Aspergillus fumigatus: comparison between double immunodiffusion, ELISA and immunoblot analysis. Int. Arch. Allergy Appl. Immunol.1988; 85: 244-249.

49. Schønheyder H. Pathogenetic and serological aspects of pulmonary aspergillosis. Scand. J. Infect. Dis. 1987; 51 (Suppl.): 1-62.

50. Ninomiya H., Harada S., Harada Y. et al. [Serological diagnosis of pulmonary aspergillosismeasurement of IgG, IgM and IgAantibodies against Aspergillus fumigatus by means of ELISA]. Kekkaku. 1990; 65: 263-272.

51. Agarwal R., Garg M., Aggarwal A.N. et al. Serologic aller gic bronchopulmonary aspergillosis (ABPAS): longterm outcomes. Respir. Med. 2012; 106: 942-947.

52. McCarthy D.S., Pepys J. Pulmonary aspergillomaclinical immunology. Clin. Allergy. 1973; 3: 57-70.

53. Brummund W., Resnick A., Fink J.N. et al. Aspergillus fumigatusspecific antibodies in allergic bronchopul monary aspergillosis and aspergilloma: evidence for a polyclonal antibody response. J. Clin. Microbiol. 1987; 25: 5-9.

54. Page I.D., Richardson M., Denning D.W. Antibody testing in aspergillosisquo vadis? Med. Mycol. 2015; 52: 417-439.

55. Greene R. The radiological spectrum of pulmonary aspergillosis. Med. Mycol. 2005; 43 (Suppl. 1): S147-S154.

56. Roberts C.M., Citron K.M., Strickland B. Intrathoracic aspergilloma: role of CT in diagnosis and treatment. Radiology. 1987; 165: 123-128.

57. Baxter C.G., Bishop P., Low S.E. et al. Pulmonary aspergillosis: an alternative diagnosis to lung cancer after positive [18F]FDG positron emission tomography. Thorax. 2011; 66: 638-640.

58. Kim J.Y., Yoo J.W., Oh M. et al. (18)Ffluoro2deoxy Dglucose positron emission tomography/computed tomography findings are different between invasive and noninvasive pulmonary aspergillosis. J. Comput. Assist. Tomogr. 2013; 37: 596-601.

59. Felton T.W., Baxter C., Moore C.B. et al. Efficacy and safety of posaconazole for chronic pulmonary aspergillosis. Clin. Infect. Dis. 2010; 51: 1383-1391.

60. Baliko Z., Sarosi V., Illes M.B. et al. PETCT imaging and reality. Pathol. Oncol. Res. 2011; 17: 393-395.

61. Patterson K.C., Strek M.E. Diagnosis and treatment of pulmonary aspergillosis syndromes. Chest. 2014; 146: 1358-1368.

62. Smith N.L., Denning D.W. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur. Respir. J. 2011; 37: 865- 872.

63. Kato T., Usami I., Morita H. et al. Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients. Chest. 2002; 121: 118-127.

64. Parakh U.K., Sinha R., Bhatnagar A.K. et al. Chronic necrotising pulmonary aspergillosis: a rare complication in a case of silicosis. Indian. J. Chest Dis. Allied. Sci. 2005; 47: 199-203.

65. Blanco J.J., Barcala F.J.G., Moure M.A.A. et al. Aspergilosis pulmonar necrotizante crónica como complicación de silicosis [Chronic necrotising pulmonary aspergillosis as a complication of silicosis]. An. Sist. Sanit. Navar. 2011; 34: 109-114.

66. Lachkar S., Dominique S., Thiberville L. et al. Aspergillose et sarcoїdose [Aspergillosis and sarcoidosis]. Rev. Mal. Respir. 2007; 24: 943-953.

67. Soubani A.O., Chandrasekar P.H. The clinical spectrum of pulmonary aspergillosis. Chest. 2002; 121: 1988-1999.

68. Huang C.W., Lee M.A., Lu R.H. et al. A case of pulmonary aspergilloma and actinomycosis. J. Med. Microbiol. 2011; 60: 543-546.

69. Bal A., Bagai M., Mohan H. et al. Aspergilloma in a pulmonary hydatid cyst: a case report. Mycoses. 2008; 51: 357-359.

70. Pimentel J.C. Pulmonary calcification in the tumorlike form of pulmonary aspergillosis: pulmonary aspergilloma. Am. Rev. Respir. Dis. 1966; 94: 208-216.

71. Park Y., Kim T.S., Yi C.A. et al. Pulmonary cavitary mass containing a mural nodule: differential diagnosis between intracavitary aspergilloma and cavitating lung cancer on contrastenhanced computed tomography. Clin. Radiol. 2007; 62: 227-232.

72. Gazzoni F.F., Severo L.C., Marchiori E. et al. Fungal diseases mimicking primary lung cancer: radiologicpathologic correlation. Mycoses. 2014; 57: 197-208.

73. Adeyemo A.O., Odelowo E.O., Makanjuola D.I. Management of pulmonary aspergilloma in the presence of active tuberculosis. Thorax. 1984; 39: 862-867.

74. Hafeez I., Muers M.F., Murphy S.A. et al. Nontuberculous mycobacterial lung infection complicated by chronic necrotising pulmonary aspergillosis. Thorax. 2000; 55: 717-719.

75. Yoon S.H., Park C.M., Goo J.M. et al. Pulmonary aspergillosis in immunocompetent patients without air meniscus sign and underlying lung disease: CT findings and histopathologic features. Acta. Radiol. 2011; 52: 756-761.

76. Lim J., Lyu J., Choi C.M. et al. Nontuberculous mycobacterial diseases presenting as solitary pulmonary nodules. Int. J. Tuberc. Lung Dis. 2010; 14: 1635-1640.

77. Baik J.J., Lee G.L., Yoo C.G. et al. Pulmonary actinomy cosis in Korea. Respirology. 1999; 4: 31-35.

78. McConnochie K., O’Sullivan M., Khalil J.F. et al. Aspergillus colonization of pulmonary rheumatoid nodule. Respir. Med. 1989; 83: 157-160.

79. Cavazza A., Paci M., Turrini E. et al. Fungus colonisation of pulmonary rheumatoid nodule. J. Clin. Pathol. 2003; 56: 636-637.

80. Denning D.W., Follansbee S.E., Scolaro M. et al. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N. Engl. J. Med. 1991; 324: 654-662.

81. Rajalingham S., Anshar F.M. Chronic necrotizing pulmonary aspergillosis presenting as bilateral pleural effusion: a case report. J. Med. Case Rep. 2012; 6: 62.

82. Schweer K.E., Wittersheim M., Bangard C. et al. Chronische pulmonale aspergilloses: vier klinische fall beispiele und uberblick uber die aktuelle literatur [Chronic pulmonary aspergillosis: four exemplary clinical cases and literature overview]. Dtsch. Med. Wochenschr. 2014; 139: 2242-2247.

83. Agarwal R., Vishwanath G., Aggarwal A.N. et al. Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature. Mycoses. 2013; 56: 559-570.

84. Jones P.W., Quirk F.H., Baveystock C.M. et al. A self complete measure of health status for chronic airflow limitation: the St. George’s Respiratory Questionnaire. Am. Rev. Respir. Dis. 1992; 145: 1321-1327.

85. Alshair K., Atherton G.T.W., Kennedy D. et al. Validity and reliability of the St. George’s Respiratory Questionnaire in assessing health status in patients with chronic pulmonary aspergillosis. Chest. 2013; 144: 623-631.

86. Dupont B. Itraconazole therapy in aspergillosis: study in 49 patients. J. Am. Acad. Dermatol. 1990; 23: 607-614.

87. De Beule K., De Doncker P., Cauwenbergh G. et al. The treatment of aspergillosis and aspergilloma with itracona zole, clinical results of an open international study (1982-1987). Mycoses. 1988; 31: 476-485.

88. Judson M.A., Stevens D.A. The treatment of pulmonary as pergilloma. Curr. Opin. Invest. Drugs. 2001; 2: 1375-1377.

89. Jain L.R., Denning D.W. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J. Infect. 2006; 52: e133-e137.

90. Sambatakou H., Dupont B., Lode H. et al. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am. J. Med. 2006; 119: 527.e17-e24.

91. Saito T., Fujiuchi S., Tao Y. et al. Efficacy and safety of voriconazole in the treatment of chronic pulmonary aspergillosis: experience in Japan. Infection. 2012; 40: 661-667.

92. Cucchetto G., Cazzadori A., Conti M. et al. Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series. Infection. 2015; 43: 277-286.

93. Caras W.E., Pluss J.L. Chronic necrotizing pulmonary aspergillosis: pathologic outcome after itraconazole therapy. Mayo Clin. Proc. 1996; 71: 25-30.

94. Saraceno J.L., Phelps D.T., Ferro T.J. et al. Chronic necrotizing pulmonary aspergillosis: approach to management. Chest. 1997; 112: 541-548.

95. Camuset J., Lavolé A., Wislez M. et al. [Infections aspergillaires bronchopulmonaires du sujet nonimmun odéprimé [Bronchopulmonary aspergillosis infections in the nonimmunocompromised patient]. Rev. Pneumol. Clin. 2007; 63: 155-166.

96. Yoshida K., Shoji H., Takuma T. et al. Iliopsoas abscess caused by Aspergillus fumigatus complicated by pulmonary aspergillosis. J. Infect. Chemother. 2012; 18: 569-575.

97. Kohno S., Izumikawa K., Yoshida M. et al. A doubleblind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis. Eur. J. Clin. Microbiol. Infect. Dis. 2013; 32: 387-397.

98. Yasuda S., Ohnishi R., Suzuki T. et al. [Shortterm efficacy evaluation of chronic pulmonary aspergillosis treated with micafangin and maintenance therapy of itraconazole]. Nihon Kokyuki Gakkai Zasshi. 2009; 47: 985-990.

99. Kohno S., Izumikawa K., Kakeya H. et al. Clinical efficacy and safety of micafungin in Japanese patients with chronic pulmonary aspergillosis: a prospective observational study. Med. Mycol. 2011; 49: 688-693.

100. Izumikawa K., Ohtsu Y., Kawabata M. et al. Clinical efficacy of micafungin for chronic pulmonary aspergillosis. Med. Mycol. 2007; 45: 273-278.

101. Newton P.J., Harris C., Denning D.W. The clinical response to a shortterm course of intravenous liposomal amphotericin B therapy in patients with chronic pulmonary aspergillosis. Available from: http://www.aspergillus.org. uk/content/clinicalresponseshorttermcourseintravenousliposomalamphotericinbtherapypatients

102. Keir G.J., Garfield B., Hansell D.M. et al. Cyclical caspo fungin for chronic pulmonary aspergillosis in sarcoidosis. Thorax. 2014; 69: 287-288.

103. Newton P.J., Harris C., Denning D.W. The clinical response to a shortterm course of intravenous liposomal amphotericin B therapy in patients with chronic pulmonary aspergillosis. Mycoses. 2013; 56 (Suppl. 3): 164.

104. Rumbak M., Kohler G., Eastrige C. et al. Topical treatment of life threatening haemoptysis from aspergillomas. Thorax. 1996; 51: 253-255.

105. Kravitz J.N., Berry M.W., Schabel S.I. et al. A modern series of percutaneous intracavitary instillation of amphotericin B for the treatment of severe hemoptysis from pulmonary aspergilloma. Chest. 2013; 143: 1414-1421.

106. Giron J., Poey C., Fajadet P. et al. CTguided percutaneous treatment of inoperable pulmonary aspergillomas: a study of 40 cases. Eur. J. Radiol. 1998; 28: 235-242.

107. Yamada H., Kohno S., Koga H. et al. Topical treatment of pulmonary aspergilloma by antifungals: relationship between duration of the disease and efficacy of therapy. Chest. 1993; 103: 1421-1425.

108. Hargis J.L., Bone R.C., Stewart J. et al. Intracavitary

109. amphotereicin B in the treatment of symptomatic pulmonary aspergillomas. Am. J. Med. 1980; 68: 389-394.

110. Lee K.S., Kim H.T., Kim Y.H. et al. Treatment of hemoptysis in patients with cavitary aspergilloma of the lung: value of percutaneous instillation of amphotericin B. Am. J. Roentgenol. 1993; 161: 727-731.

111. Shapiro M.J., Albelda S.M., Mayock R.L. et al. Severe hemoptysis associated with pulmonary aspergilloma: per cutaneous intracavitary treatment. Chest. 1988; 94: 1225-1231.

112. Munk P.L., Vellet A.D., Rankin R.N. et al. Intracavitary aspergilloma: transthoracic percutaneous injection of amphotericin gelatin solution. Radiology. 1993; 188: 821-823.

113. Jackson M., Flower C.D., Shneerson J.M. Treatment of symptomatic pulmonary aspergillomas with intracavitary instillation of amphotericin B through an indwelling catheter. Thorax. 1993; 48: 928-930.

114. Krakówka M., Traczyk K., Walczak J. et al. Local treatment of aspergilloma of the lung with a paste containing nystatin of amphotericin B. Tubercle. 1970; 51: 184-191.

115. Hendee W.R., Edwards F.M. ALARA and an integrated approach to radiation protection. Semin. Nucl. Med. 1986; 16: 142-150.

116. Rafferty P., Biggs B.A., Crompton G.K. et al. What happens to patients with pulmonary aspergilloma? Analysis of 23 cases. Thorax. 1983; 38: 579- 583.

117. Döffinger R., Harris C., Lear S. et al. Impaired Th1 and Th17 immunity in chronic pulmonary aspergillosis. In: NHS England National Commissiong Group Chronic Pulmonary Aspergillosis national service, The National Aspergillosis Centre Annual Report 2013-2014. NHS England, London; 2014. Available from: http://www.uhsm.nhs.uk/nac/news/Documents/NAC annual report 20134 web.pdf

118. Kelleher P., Goodsall A., Mulgirigama A. et al. Interferonγ therapy in two patients with progressive chronic pulmonary aspergillosis. Eur. Respir. J. 2006; 27: 1307-1310.

119. Prutsky G., Domecq J.P., Salazar C.A. et al. Antifibrinolytic therapy to reduce haemoptysis from any cause. Cochrane Database Syst. Rev. 2012; 4: CD008711.

120. Moen C.A., Burrell A., Dunning J. Does tranexamic acid stop haemoptysis? Interact. Cardiovasc. Thorac. Surg. 2013; 17: 991-994.

121. Jardin M., Remy J. Control of hemoptysis: systemic angiography and anastomoses of the internal mammary artery. Radiology. 1988; 168: 377- 383.

122. Swanson K.L., Johnson C.M., Prakash U.B.S. et al. Bronchial artery embolization: experience with 54 patients. Chest. 2002; 121: 789-795.

123. Corr P. Management of severe hemoptysis from pulmonary aspergilloma using endovascular embolization. Cardiovasc. Intervent. Radiol. 2006; 29: 807-810.

124. Serasli E., Kalpakidis V., Iatrou K. et al. Percutaneous bronchial artery embolization in the management of massive hemoptysis in chronic lung diseases. Immediate and longterm outcomes. Int. Angiol. 2008; 27: 319-328.

125. Brik A., Salem A.M., Kamal A.R. et al. Surgical outcome of pulmonary aspergilloma. Eur. J. Cardiothorac. Surg. 2008; 34: 882-885.

126. Farid S., Mohamed S., Devbhandari M. et al. Results of surgery for chronic pulmonary aspergillosis, optimal antifungal therapy and proposed high risk factors for recur rence - a National Centre’s experience. J. Cardiothorac. Surg. 2013; 8: 180.

127. Regnard J.F., Icard P., Nicolosi M. et al. Aspergilloma: a series of 89 surgical cases. Ann. Thorac. Surg. 2000; 69: 898-903.

128. Kim Y.T., Kang M.C., Sung S.W. et al. Good longterm outcomes after surgical treatment of simple and complex pulmonary aspergilloma. Ann. Thorac. Surg. 2005; 79: 294-298.

129. Pratap H., Dewan R.K., Singh L. et al. Surgical treatment of pulmonary aspergilloma: a series of 72 cases. Indian. J. Chest Dis. Allied. Sci. 2007; 49: 23-27.

130. Muniappan A., Tapias L.F., Butala P. et al. Surgical therapy of pulmonary aspergillomas: a 30year North American experience. Ann. Thorac. Surg. 2014; 97: 432-438.

131. Lejay A., Falcoz P.E., Santelmo N. et al. Surgery for aspergilloma: time trend towards improved results? Interact. Cardiovasc. Thorac. Surg. 2011; 13: 392-395.

132. Chen Q.K., Jiang G.N., Ding J.A. Surgical treatment for pulmonary aspergilloma: a 35year experience in the Chinese population. Interact. Cardiovasc. Thorac. Surg. 2012; 15: 77-80.

133. Chen Q.K., Chen C., Chen X.F. et al. Videoassisted thoracic surgery for pulmonary aspergilloma: a safe and effective procedure. Ann. Thorac. Surg. 2014; 97: 218-223.

134. Igai H., Kamiyoshihara M., Nagashima T. et al. Pulmonary aspergilloma treated by limited thoracoplasty with simultaneous cavernostomy and muscle transposition flap. Ann. Thorac. Cardiovasc. Surg. 2012; 18: 472- 474.

135. Grima R., Krassas A., Bagan P. et al. Treatment of complicated pulmonary aspergillomas with cavernostomy and muscle flap: interest of concomitant limited thoracoplasty. Eur. J. Cardiothorac. Surg. 2009; 36: 910-913.

136. Srivastava D.N., Jana M., Bhalla A. et al. Bronchial artery embolization in pulmonary diseases: current scenario. J. Int. Med. Sci. Acad. 2013; 26: 69-71.

137. Stather D.R., Tremblay A., MacEachern P. et al. Bron choscopic removal of a large intracavitary pulmonary aspergilloma. Chest. 2013; 143: 238-241.

138. Stather D., Tremblay A., MacEachern P. et al. Intra cavitary pulmonary aspergilloma removal using combined virtual, ultrathin, and rigid bronchoscopy - a case series. Chest. 2013; 144: 817A.

139. Akbari J.G., Varma P.K., Neema P.K. et al. Clinical profile and surgical outcome for pulmonary aspergilloma: a single center experience. Ann. Thorac. Surg. 2005; 80: 1067- 1072.

140. Sagan D., Goz′dziuk K. Surgery for pulmonary aspergilloma in immunocompetent patients: no benefit from adjuvant antifungal pharmacotherapy. Ann. Thorac. Surg. 2010; 89: 1603-1610.

141. Benhamed L., Woelffle D. Adjuvant antifungal therapy after pulmonary surgery for aspergilloma: is it useful? Interact. Cardiovasc. Thorac. Surg. 2014; 18: 835-837.

142. Muldoon E.G., Page I., Bishop P. et al. Aspergillus pulmonary nodules; presentation, radiology, and histology features. In: NHS England National Commissiong Group Chronic Pulmonary Aspergillosis national service, The National Aspergillosis Centre Annual Report 2013-2014. NHS England, London; 2014. Available from: http://www.uhsm.nhs.uk/nac/news/Documents/NAC annual re

143. port%2020134%20web.pdf