UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of chronic pulmonary aspergillosis

Author
David W Denning, MBBS, FRCP, FRCPath, FMedSci
Section Editor
Carol A Kauffman, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Chronic pulmonary aspergillosis includes several disease manifestations, including aspergilloma, Aspergillus nodules, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. Subacute invasive pulmonary aspergillosis (formerly known as chronic necrotizing pulmonary aspergillosis) is on the spectrum between chronic and acute forms of pulmonary aspergillosis (see 'Definitions' below). A duration of disease longer than three months distinguishes chronic pulmonary aspergillosis from acute and subacute invasive pulmonary aspergillosis.

The treatment of chronic pulmonary aspergillosis will be reviewed here. The pathophysiology, clinical manifestations, and diagnosis of chronic pulmonary aspergillosis are discussed separately; the treatment of allergic bronchopulmonary aspergillosis and invasive aspergillosis are also reviewed elsewhere. (See "Clinical manifestations and diagnosis of chronic pulmonary aspergillosis" and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis" and "Treatment and prevention of invasive aspergillosis".)

DEFINITIONS

Chronic pulmonary aspergillosis describes several patterns of disease. However, the terminology that has been developed can be difficult to apply to a spectrum of disease entities that have considerable overlap and variation in severity. The following terminology will be used to describe the spectrum of disease; each entity is characterized by specific radiographic findings [1].

Aspergilloma — An aspergilloma is a fungus ball composed of Aspergillus hyphae, fibrin, mucus, and cellular debris found within a pulmonary cavity [2]. Aspergillomas arise in preexisting pulmonary cavities that have become colonized with Aspergillus spp or develop in chronic cavitary pulmonary aspergillosis [1].

If the aspergilloma is single, the cavity stable over months, and the patient has few symptoms (ie, a mild cough only) and little evidence of systemic inflammation, a simple aspergilloma may be diagnosed. We will use the term "simple aspergilloma" to distinguish this entity from the more complex forms of chronic pulmonary aspergillosis. (See "Diagnosis of invasive aspergillosis", section on 'Diagnostic modalities'.)

                          

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Sep 27 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003; 37 Suppl 3:S265.
  2. Judson MA, Stevens DA. The treatment of pulmonary aspergilloma. Curr Opin Investig Drugs 2001; 2:1375.
  3. Muldoon EG, Sharman A, Page I, et al. Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis. BMC Pulm Med 2016; 16:123.
  4. Baxter CG, Bishop P, Low SE, et al. Pulmonary aspergillosis: an alternative diagnosis to lung cancer after positive [18F]FDG positron emission tomography. Thorax 2011; 66:638.
  5. Farid S, Mohamed S, Devbhandari M, et al. Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence--a National Centre's experience. J Cardiothorac Surg 2013; 8:180.
  6. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J 2016; 47:45.
  7. Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1.
  8. Lejay A, Falcoz PE, Santelmo N, et al. Surgery for aspergilloma: time trend towards improved results? Interact Cardiovasc Thorac Surg 2011; 13:392.
  9. Chen QK, Jiang GN, Ding JA. Surgical treatment for pulmonary aspergilloma: a 35-year experience in the Chinese population. Interact Cardiovasc Thorac Surg 2012; 15:77.
  10. Moodley L, Pillay J, Dheda K. Aspergilloma and the surgeon. J Thorac Dis 2014; 6:202.
  11. Dupont B. Itraconazole therapy in aspergillosis: study in 49 patients. J Am Acad Dermatol 1990; 23:607.
  12. De Beule K, De Doncker P, Cauwenbergh G, et al. The treatment of aspergillosis and aspergilloma with itraconazole, clinical results of an open international study (1982-1987). Mycoses 1988; 31:476.
  13. Lebeau B, Pelloux H, Pinel C, et al. Itraconazole in the treatment of aspergillosis: a study of 16 cases. Mycoses 1994; 37:171.
  14. Campbell JH, Winter JH, Richardson MD, et al. Treatment of pulmonary aspergilloma with itraconazole. Thorax 1991; 46:839.
  15. Denning DW. Chronic aspergillosis. In: Aspergillus fumigatus and Aspergillosis, Latge JP, Steinbach WJ (Eds), ASM Press, Washington, DC 2009.
  16. Hammerman KJ, Christianson CS, Huntington I, et al. Spontaneous lysis of aspergillomata. Chest 1973; 64:679.
  17. Camuset J, Nunes H, Dombret MC, et al. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest 2007; 131:1435.
  18. Jain LR, Denning DW. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J Infect 2006; 52:e133.
  19. Sambatakou H, Dupont B, Lode H, Denning DW. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am J Med 2006; 119:527.e17.
  20. Felton TW, Baxter C, Moore CB, et al. Efficacy and safety of posaconazole for chronic pulmonary aspergillosis. Clin Infect Dis 2010; 51:1383.
  21. Al-Shair K, Atherton GT, Harris C, et al. Long-term antifungal treatment improves health status in patients with chronic pulmonary aspergillosis: a longitudinal analysis. Clin Infect Dis 2013; 57:828.
  22. Agarwal R, Vishwanath G, Aggarwal AN, et al. Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature. Mycoses 2013; 56:559.
  23. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347:408.
  24. Cucchetto G, Cazzadori A, Conti M, et al. Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series. Infection 2015; 43:277.
  25. Yoshida K, Kurashima A, Kamei K, et al. Efficacy and safety of short- and long-term treatment of itraconazole on chronic necrotizing pulmonary aspergillosis in multicenter study. J Infect Chemother 2012; 18:378.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. Kohno S, Izumikawa K, Yoshida M, et al. A double-blind 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.
  31. Caras WE, Pluss JL. Chronic necrotizing pulmonary aspergillosis: pathologic outcome after itraconazole therapy. Mayo Clin Proc 1996; 71:25.
  32. Kohno S, Masaoka T, Yamaguchi H, et al. A multicenter, open-label clinical study of micafungin (FK463) in the treatment of deep-seated mycosis in Japan. Scand J Infect Dis 2004; 36:372.
  33. Ashbee HR, Barnes RA, Johnson EM, et al. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother 2014; 69:1162.
  34. Pasqualotto AC, Denning DW. Generic substitution of itraconazole resulting in sub-therapeutic levels and resistance. Int J Antimicrob Agents 2007; 30:93.
  35. Saito W, Shishikura Y, Nishimaki K, et al. [Two cases of pulmonary aspergilosis, which deteriorated with generic itraconazole]. Kansenshogaku Zasshi 2014; 88:469.
  36. Newton PJ, Harris C, Morris J, Denning DW. Impact of liposomal amphotericin B therapy on chronic pulmonary aspergillosis. J Infect 2016.
  37. Koyama K, Ohshima N, Suzuki J, et al. Recurrence of chronic pulmonary aspergillosis after discontinuation of maintenance treatment by antifungal triazoles. J Infect Chemother 2014; 20:375.
  38. Baxter CG, Marshall A, Roberts M, et al. Peripheral neuropathy in patients on long-term triazole antifungal therapy. J Antimicrob Chemother 2011; 66:2136.
  39. Al-shair K, Atherton GT, 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.
  40. Tsubura E. [Multicenter clinical trial of itraconazole in the treatment of pulmonary aspergilloma. Pulmonary Aspergilloma Study Group]. Kekkaku 1997; 72:557.
  41. Hafeez I, Muers MF, Murphy SA, et al. Non-tuberculous mycobacterial lung infection complicated by chronic necrotising pulmonary aspergillosis. Thorax 2000; 55:717.
  42. Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 2011; 52:1123.
  43. Howard SJ, Cerar D, Anderson MJ, et al. Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 2009; 15:1068.
  44. Verweij PE, Howard SJ, Melchers WJ, Denning DW. Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist Updat 2009; 12:141.
  45. Takeda K, Imamura Y, Takazono T, et al. The risk factors for developing of chronic pulmonary aspergillosis in nontuberculous mycobacteria patients and clinical characteristics and outcomes in chronic pulmonary aspergillosis patients coinfected with nontuberculous mycobacteria. Med Mycol 2016; 54:120.
  46. Smith NL, Denning DW. Clinical implications of interferon-γ genetic and epigenetic variants. Immunology 2014; 143:499.
  47. Kelleher P, Goodsall A, Mulgirigama A, et al. Interferon-gamma therapy in two patients with progressive chronic pulmonary aspergillosis. Eur Respir J 2006; 27:1307.
  48. Regnard JF, Icard P, Nicolosi M, et al. Aspergilloma: a series of 89 surgical cases. Ann Thorac Surg 2000; 69:898.
  49. Kim YT, Kang MC, Sung SW, Kim JH. Good long-term outcomes after surgical treatment of simple and complex pulmonary aspergilloma. Ann Thorac Surg 2005; 79:294.
  50. Pratap H, Dewan RK, Singh L, et al. Surgical treatment of pulmonary aspergilloma: a series of 72 cases. Indian J Chest Dis Allied Sci 2007; 49:23.
  51. Brik A, Salem AM, Kamal AR, et al. Surgical outcome of pulmonary aspergilloma. Eur J Cardiothorac Surg 2008; 34:882.
  52. Daly RC, Pairolero PC, Piehler JM, et al. Pulmonary aspergilloma. Results of surgical treatment. J Thorac Cardiovasc Surg 1986; 92:981.
  53. Massard G, Roeslin N, Wihlm JM, et al. [Surgical treatment of pulmonary and bronchial aspergilloma]. Ann Chir 1993; 47:147.
  54. Lee JG, Lee CY, Park IK, et al. Pulmonary aspergilloma: analysis of prognosis in relation to symptoms and treatment. J Thorac Cardiovasc Surg 2009; 138:820.
  55. Shiraishi Y, Katsuragi N, Nakajima Y, et al. Pneumonectomy for complex aspergilloma: is it still dangerous? Eur J Cardiothorac Surg 2006; 29:9.
  56. Demir A, Gunluoglu MZ, Turna A, et al. Analysis of surgical treatment for pulmonary aspergilloma. Asian Cardiovasc Thorac Ann 2006; 14:407.
  57. Mohapatra B, Sivakumar P, Bhattacharya S, Dutta S. Surgical treatment of pulmonary aspergillosis: A single center experience. Lung India 2016; 33:9.
  58. Rivera C, Arame A, Pricopi C, et al. Pneumonectomy for benign disease: indications and postoperative outcomes, a nationwide study. Eur J Cardiothorac Surg 2015; 48:435.
  59. Jardin M, Remy J. Control of hemoptysis: systemic angiography and anastomoses of the internal mammary artery. Radiology 1988; 168:377.
  60. Swanson KL, Johnson CM, Prakash UB, et al. Bronchial artery embolization : experience with 54 patients. Chest 2002; 121:789.
  61. Corr P. Management of severe hemoptysis from pulmonary aspergilloma using endovascular embolization. Cardiovasc Intervent Radiol 2006; 29:807.
  62. Serasli E, Kalpakidis V, Iatrou K, et al. Percutaneous bronchial artery embolization in the management of massive hemoptysis in chronic lung diseases. Immediate and long-term outcomes. Int Angiol 2008; 27:319.
  63. Giron J, Poey C, Fajadet P, et al. CT-guided percutaneous treatment of inoperable pulmonary aspergillomas: a study of 40 cases. Eur J Radiol 1998; 28:235.
  64. Kravitz JN, Berry MW, Schabel SI, Judson MA. A modern series of percutaneous intracavitary instillation of amphotericin B for the treatment of severe hemoptysis from pulmonary aspergilloma. Chest 2013; 143:1414.
  65. Lee KS, Kim HT, Kim YH, Choe KO. Treatment of hemoptysis in patients with cavitary aspergilloma of the lung: value of percutaneous instillation of amphotericin B. AJR Am J Roentgenol 1993; 161:727.
  66. Aspergilloma and residual tuberculous cavities--the results of a resurvey. Tubercle 1970; 51:227.
  67. Jewkes J, Kay PH, Paneth M, Citron KM. Pulmonary aspergilloma: analysis of cavitating invasive pulmonary aspergillosis in immunocompromised patients. Ann Thorac Surg 1983; 53:621.
  68. Tomlinson JR, Sahn SA. Aspergilloma in sarcoid and tuberculosis. Chest 1987; 92:505.
  69. Ohba H, Miwa S, Shirai M, et al. Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir Med 2012; 106:724.
  70. Binder RE, Faling LJ, Pugatch RD, et al. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore) 1982; 61:109.
  71. Nam HS, Jeon K, Um SW, et al. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int J Infect Dis 2010; 14:e479.