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Clinical manifestations and diagnosis of chronic pulmonary aspergillosis

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


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 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 pulmonary aspergillosis.

The pathophysiology, clinical manifestations, and diagnosis of chronic pulmonary aspergillosis will be reviewed here. The treatment of chronic pulmonary aspergillosis as well as allergic bronchopulmonary aspergillosis and invasive aspergillosis is discussed separately. (See "Treatment of chronic pulmonary aspergillosis" and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis" and "Epidemiology and clinical manifestations of invasive aspergillosis".)


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 [1,2].

Aspergilloma — An aspergilloma is a fungus ball composed of Aspergillus hyphae, fibrin, mucus, and cellular debris found within a pulmonary cavity [3]. Aspergillomas arise in preexisting pulmonary cavities that have become colonized with Aspergillus spp [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' below.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 11, 2017.
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  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. 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.
  3. Judson MA, Stevens DA. The treatment of pulmonary aspergilloma. Curr Opin Investig Drugs 2001; 2:1375.
  4. Muldoon EG, Sharman A, Page ID, et al. Aspergillus nodules; another presentation of chronic pulmonary aspergillosis. BMC Pulm Med 2016.
  5. 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.
  6. 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.
  7. Severo LC, Geyer GR, Porto Nda S, et al. Pulmonary Aspergillus niger intracavitary colonization. Report of 23 cases and a review of the literature. Rev Iberoam Micol 1997; 14:104.
  8. Pasqualotto AC, Denning DW. An aspergilloma caused by Aspergillus flavus. Med Mycol 2008; 46:275.
  9. Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J 2011; 37:865.
  10. Pena TA, Soubani AO, Samavati L. Aspergillus lung disease in patients with sarcoidosis: a case series and review of the literature. Lung 2011; 189:167.
  11. Sonnenberg P, Murray J, Glynn JR, et al. Risk factors for pulmonary disease due to culture-positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners. Eur Respir J 2000; 15:291.
  12. Lee JJ, Chong PY, Lin CB, et al. High resolution chest CT in patients with pulmonary tuberculosis: characteristic findings before and after antituberculous therapy. Eur J Radiol 2008; 67:100.
  13. Aspergilloma and residual tuberculous cavities--the results of a resurvey. Tubercle 1970; 51:227.
  14. Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. http://www.who.int/bulletin/volumes/89/12/11-089441.pdf (Accessed on January 24, 2012).
  15. Agarwal R, Denning DW, Chakrabarti A. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS One 2014; 9:e114745.
  16. Carvalho A, Pasqualotto AC, Pitzurra L, et al. Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis 2008; 197:618.
  17. Smith NL, Hankinson J, Simpson A, et al. A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis. Clin Microbiol Infect 2014; 20:O480.
  18. Smith NL, Hankinson J, Simpson A, et al. Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in Chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT. Clin Microbiol Infect 2014; 20:O960.
  19. Harrison E, Singh A, Morris J, et al. Mannose-binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis. Int J Immunogenet 2012; 39:224.
  20. Crosdale DJ, Poulton KV, Ollier WE, et al. Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis. J Infect Dis 2001; 184:653.
  21. Sambatakou H, Pravica V, Hutchinson IV, Denning DW. Cytokine profiling of pulmonary aspergillosis. Int J Immunogenet 2006; 33:297.
  22. Smith NL, Bromley MJ, Denning DW, et al. Elevated levels of the neutrophil chemoattractant pro-platelet basic protein in macrophages from individuals with chronic and allergic aspergillosis. J Infect Dis 2015; 211:651.
  23. Vaid M, Kaur S, Sambatakou H, et al. Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med 2007; 45:183.
  24. Sugino K, Hasegawa C, Sano G, et al. Pathophysiological study of chronic necrotizing pulmonary aspergillosis. Jpn J Infect Dis 2008; 61:450.
  25. Camuset J, Nunes H, Dombret MC, et al. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest 2007; 131:1435.
  26. Schweer KE, Bangard C, Hekmat K, Cornely OA. Chronic pulmonary aspergillosis. Mycoses 2014; 57:257.
  27. Desai SR, Hedayati V, Patel K, Hansell DM. Chronic Aspergillosis of the Lungs: Unravelling the Terminology and Radiology. Eur Radiol 2015; 25:3100.
  28. Roberts CM, Citron KM, Strickland B. Intrathoracic aspergilloma: role of CT in diagnosis and treatment. Radiology 1987; 165:123.
  29. Cucchetto G, Cazzadori A, Conti M, et al. Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series. Infection 2015; 43:277.
  30. Page ID, Richardson M, Denning DW. Antibody testing in aspergillosis--quo vadis? Med Mycol 2015; 53:417.
  31. Page ID, Richardson MD, Denning DW. Comparison of six Aspergillus-specific IgG assays for the diagnosis of chronic pulmonary aspergillosis (CPA). J Infect 2016; 72:240.
  32. Dumollard C, Bailly S, Perriot S, et al. Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis. J Clin Microbiol 2016; 54:1236.
  33. Fujiuchi S, Fujita Y, Suzuki H, et al. Evaluation of a Quantitative Serological Assay for Diagnosing Chronic Pulmonary Aspergillosis. J Clin Microbiol 2016; 54:1496.
  34. Kohno S, Kobayashi T, Kakeya H, Miyazaki Y. [Pulmonary aspergilloma, diagnosis and treatment]. Kekkaku 2003; 78:757.
  35. Wollschlager C, Khan F. Aspergillomas complicating sarcoidosis. A prospective study in 100 patients. Chest 1984; 86:585.
  36. Coleman RM, Kaufman L. Use of the immunodiffusion test in the serodiagnosis of aspergillosis. Appl Microbiol 1972; 23:301.
  37. Hagiwara E, Sekine A, Sato T, et al. [Clinical features of chronic necrotizing pulmonary aspergillosis treated with voriconazole in patients with chronic respiratory disease]. Nihon Kokyuki Gakkai Zasshi 2008; 46:864.
  38. 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.
  39. Park SY, Lee SO, Choi SH, et al. Serum and bronchoalveolar lavage fluid galactomannan assays in patients with pulmonary aspergilloma. Clin Infect Dis 2011; 52:e149.
  40. Izumikawa K, Yamamoto Y, Mihara T, et al. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol 2012; 50:811.
  41. 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.
  42. Shin B, Koh WJ, Jeong BH, et al. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect 2014; 68:494.
  43. Hope WW, Walsh TJ, Denning DW. The invasive and saprophytic syndromes due to Aspergillus spp. Med Mycol 2005; 43 Suppl 1:S207.