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Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series

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Abstract

Purpose

Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung.

Methods

Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months.

Results

21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis (n = 8), chronic obstructive pulmonary disease (n = 7), corticosteroids (n = 14), chemo- or radio-therapy (n = 6), tracheostomy or endotracheal prosthesis (n = 5), smoking (n = 4), asthma (n = 3), and chronic liver disease (n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-β-d-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [18F]2-fluoro-2-deoxy-d-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity (n = 3), liver toxicity (n = 2) and severe mental disorder (n = 1). At 12 months’ follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease.

Conclusions

A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy.

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References

  1. Segal BH. Aspergillosis. N Engl J Med. 2009;360:1870–84.

    Article  CAS  PubMed  Google Scholar 

  2. Chotirmall SH, Al-Alawi M, Mirkovic B, et al. Aspergillus-associated airway disease, inflammation and the innate immune response. Biomed Res Int. 2013. doi:10.1155/2013/723129.

    PubMed Central  PubMed  Google Scholar 

  3. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;156–74.

  4. 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:S265–80.

    Article  PubMed  Google Scholar 

  5. Izumikawa K, Takazono T, Kohno S. Chronic aspergillus infections of the respiratory tract: diagnosis, management and antifungal resistance. Curr Opin Infect Dis. 2010;23:584–9.

    Article  CAS  PubMed  Google Scholar 

  6. 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;20:208–12.

    Article  PubMed  Google Scholar 

  7. Tashiro T, Izumikawa K, Tashiro M. A case series of chronic necrotizing pulmonary aspergillosis and a new proposal. Jpn J Infect Dis. 2013;66:312–6.

    PubMed  Google Scholar 

  8. Farid S, Mohamed S, Devbhandari M. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.

    Article  CAS  PubMed  Google Scholar 

  10. Jewkes J, Kay PH, Paneth M, Citron KM. Pulmonary aspergilloma: analysis of prognosis in relation to haemoptysis and survey of treatment. Thorax. 1983;38:572–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. 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:e479–82.

    Article  PubMed  Google Scholar 

  12. Nakamoto K, Takayanagi N, Kanauchi T, et al. Prognostic factors in 194 patients with chronic necrotizing pulmonary aspergillosis. Intern Med. 2013;52:727–34.

    Article  PubMed  Google Scholar 

  13. Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183:96–128.

    Article  CAS  PubMed  Google Scholar 

  14. Sambatakou H, Dupont B, Lode H, Denning DW. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am J Med. 2006;119:e17–24.

    Article  PubMed  Google Scholar 

  15. Kohno S, Izumikawa K, Ogawa K, et al. Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan. J Infect. 2010;61:410–8.

    Article  PubMed  Google Scholar 

  16. Cadranel J, Philippe B, Hennequin C, et al. Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial. Eur J Clin Microbiol Infect Dis. 2012;31:3231–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Saito T, Fujiuchi S, Sasaki Y, et al. Efficacy and safety of voriconazole in the treatment of chronic pulmonary aspergillosis: experience in Japan. Infection. 2012;40:661–7.

    Article  CAS  PubMed  Google Scholar 

  18. 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;57:828–35.

    Article  PubMed Central  PubMed  Google Scholar 

  19. SmPC voriconazole. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000387/WC500049756.pdf.

  20. Felton TW, Baxter C, Moore CB, et al. Efficacy and safety of posaconazole for chronic pulmonary aspergillosis. Clin Infect Dis. 2010;51:1383–91.

    Article  CAS  PubMed  Google Scholar 

  21. Barton RC, Hobson RP, McLoughlin H, Morris A, Datta B. Assessment of the significance of respiratory culture of Aspergillus in the non-neutropenic patient. A critique of published diagnostic criteria. Eur J Clin Microbiol Infect Dis. 2013;32:923–8.

    Article  CAS  PubMed  Google Scholar 

  22. Camuset J, Nunes H, Dombret MC, et al. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest. 2007;131:1435–41.

    Article  PubMed  Google Scholar 

  23. Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011;37:865–72.

    Article  CAS  PubMed  Google Scholar 

  24. Camara B, Reymond E, Saint-Raymond C, et al. Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry. Clin Respir J. 2014. doi:10.1111/crj.12105.

    PubMed  Google Scholar 

  25. Jhun BW, Jeon K, Eom JS, et al. Clinical characteristics and treatment outcomes of chronic pulmonary aspergillosis. Med Mycol. 2013;518:811–7.

    Article  Google Scholar 

  26. Gargani Y, Bishop P, Denning DW. Too many mouldy joints—marijuana and chronic pulmonary aspergillosis. Mediterr J Hematol Infect Dis. 2011;3:e2011005.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Cescon DW, Page AV, Richardson S, et al. Invasive pulmonary aspergillosis associated with marijuana use in man with colorectal cancer. J Clin Oncol. 2008;2613:2214–5.

    Article  Google Scholar 

  28. Verweij PE, Kerremans JJ, Voss A, Meis JF. Fungal contamination of tobacco and marijuana. JAMA. 2000;284:2875.

    Article  CAS  PubMed  Google Scholar 

  29. Zmeili OS, Soubani AO. Pulmonary aspergillosis: a clinical update. QJM. 2007;100:317–34.

    Article  CAS  PubMed  Google Scholar 

  30. 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;14:701–8.

    Article  PubMed  Google Scholar 

  31. Hachem RY, Kontoyiannis DP, Chemaly RF, et al. Utility of galactomannan enzyme immunoassay and (1,3)beta-d-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients. J Clin Microbiol. 2009;47:129–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006;42:1417–27.

    Article  CAS  PubMed  Google Scholar 

  33. 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;107:1094–100.

    Article  PubMed  Google Scholar 

  34. Shin B, Koh WJ, Jeong BH, et al. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect. 2014;68:494–9.

    Article  PubMed  Google Scholar 

  35. Ellis M, Al-Ramadi B, Finkelman M, et al. Assessment of the clinical utility of serial beta-D-glucan concentrations in patients with persistent neutropenic fever. J Med Microbiol. 2008;57:287–95.

    Article  CAS  PubMed  Google Scholar 

  36. Hot A, Maunoury C, Poiree S, et al. Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections. Clin Microbiol Infect. 2011;17:409–17.

    Article  CAS  PubMed  Google Scholar 

  37. Baxter CG, Bishop P, Low SE, Baiden-Amissah K, Denning DW. Pulmonary aspergillosis: an alternative diagnosis to lung cancer after positive [18F]FDG positron emission tomography. Thorax. 2011;66:638–40.

    Article  PubMed  Google Scholar 

  38. Baliko Z, Sarosi V, Illes MB, et al. PET-CT imaging and reality. Pathol Oncol Res. 2011;17:393–5.

    Article  PubMed  Google Scholar 

  39. 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;52:1123–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

Medical writing assistance was provided by Carmen Innes on behalf of Springer Healthcare Communications. An unrestricted grant for editorial assistance was provided by Pfizer, Italy. Pfizer has not been involved in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article.

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The authors declare that they have no conflicts of interest.

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Correspondence to G. Cucchetto.

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Cucchetto, G., Cazzadori, A., Conti, M. et al. Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series. Infection 43, 277–286 (2015). https://doi.org/10.1007/s15010-014-0711-4

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  • DOI: https://doi.org/10.1007/s15010-014-0711-4

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