, Volume 174, Issue 2, pp 163–169 | Cite as

The Performance of Real-Time PCR, Galactomannan, and Fungal Culture in the Diagnosis of Invasive Aspergillosis in Ventilated Patients with Chronic Obstructive Pulmonary Disease (COPD)

  • Valério R. Aquino
  • Fabiano Nagel
  • Huander F. Andreolla
  • Fernanda de-Paris
  • Melissa O. Xavier
  • Luciano Z. Goldani
  • David W. Denning
  • Alessandro C. PasqualottoEmail author


Emerging reports have associated chronic pulmonary obstructive disease (COPD) with invasive aspergillosis (IA), particularly in patients treated with mechanical ventilation and/or corticosteroids. This is a multicentre study in which COPD patients demonstrating a new lung infiltrate while being mechanically ventilated were prospectively evaluated for the presence of IA. From the 47 patients studied, Aspergillus fumigatus was recovered in culture in two patients (4.2%). While serum galactomannan (GM) was negative for 94% of patients, GM levels in respiratory samples were >0.5, >1.0 and >1.5 for 74.5, 40.5, and 21.3% of patients, respectively. PCR was positive for 10 patients in the study but did not differentiate Aspergillus colonization from infection. The combination of PCR and GM in respiratory samples may be an interesting alternative to diagnose IA in COPD patients.


Aspergillosis Aspergillus fumigatus COPD Galactomannan PCR 



We are in debt with our ICU and infection control colleagues, for their help in recruiting patients for this study. We thank Prof. Arnaldo Colombo for his thoughts on this subject. This study was sponsored by independent research grants from Pfizer, Biometrix, and Myconostica.

Conflict of interest

Dr Denning holds founder shares in F2G Ltd a University of Manchester spin-out company and has received grant support from F2G as well as the Fungal Research Trust, the Wellcome Trust, the Moulton Trust, The Medical Research Council, The Chronic Granulomatous Disease Research Trust, the National Institute of Allergy and Infectious Diseases, National Institute of Health Research, the European Union, and AstraZeneca. He acts as an advisor/consultant to F2G and Myconostica (now part of Lab21 group) as well as other companies over the last 5 years including Pfizer, Schering Plough (now Merck), Nektar, Astellas, and Gilead. He has been paid for talks on behalf of Merck, Astellas, Novartis, Merck, Dainippon, and Pfizer. In the past 5 years, Dr Pasqualotto has received grant support from Pfizer, Merck, United Medical, Bagó, CAPES, CNPq, FAPERGS, The Fungal Research Trust, Sigma-Tau, and Myconostica. He has been a speaker to or has received travel grants from Pfizer, Schering-Plough (now Merck), Astellas, United Medical, Biometrix, Merck, and Bagó. All other authors have no conflict of interest to declare.


  1. 1.
    Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007;30:782–800.PubMedCrossRefGoogle Scholar
  2. 2.
    Guinea J, Torres-Narbona M, Gijón P, Muñoz P, Pozo F, Peláez T, de Miguel J, Bouza E. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect. 2010;16:870–7.PubMedGoogle Scholar
  3. 3.
    Gao X, Chen L, Hu G, Mei H. Invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease and the diagnostic value of combined serological tests. Ann Saudi Med. 2010;30:193–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Ader F. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: an emerging fungal disease. Curr Infect Dis Rep. 2010;12:409–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004;170:621–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, Spriet I, Verbeken E, Van Wijngaerden E. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177:27–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Anaissie EJ. A bad bug takes on a new role as a cause of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2008;177:1–2.PubMedCrossRefGoogle Scholar
  8. 8.
    Mortensen KL, Johansen HK, Fuursted K, Knudsen JD, Gahrn-Hansen B, Jensen RH, Howard SJ, Arendrup MC. A prospective survey of Aspergillus spp. in respiratory tract samples: prevalence, clinical impact and antifungal susceptibility. Eur J Clin Microbiol Infect Dis. 2011;30:1355–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Pasqualotto AC, Xavier MO, Sánchez LB, de Oliveira Costa CD, Schio SM, Camargo SM, Camargo JJ, Sukiennik TC, Severo LC. Diagnosis of invasive aspergillosis in lung transplant recipients by detection of galactomannan in the bronchoalveolar lavage fluid. Transplantation. 2010;90:306–11.PubMedCrossRefGoogle Scholar
  10. 10.
    D’Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L, Meersseman P, Meersseman W, Lagrou K, Maertens J. Galactomannan detection in bronchoalveolar lavage fluid of patients at risk of invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol. 2012. doi: 10.1128/JCM.06423-11
  11. 11.
    Kimura S, Odawara J, Aoki T, Yamakura M, Takeuchi M, Matsue K. Detection of sputum Aspergillus galactomannan for diagnosis of invasive pulmonary aspergillosis in haematological patients. Int J Hematol. 2009;90:463–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Moore CB, Bowyer P, Perlin DS. High frequency triazole resistance found in non-culturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011;52:1123–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Kirwan MB, Fraczek M, Martin J, Barber PV, Richardson MD, Moore CB, Denning DW. Comparison of Aspergillus diagnostic yields from bronchial aspirate, bronchoalveolar lavage and sputa by real-time polymerase chain reaction compared to standard fungal culture. In: 5th advances against Aspergillosis. 2012. Abstract 55.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Valério R. Aquino
    • 1
    • 2
  • Fabiano Nagel
    • 2
  • Huander F. Andreolla
    • 3
  • Fernanda de-Paris
    • 2
  • Melissa O. Xavier
    • 4
  • Luciano Z. Goldani
    • 1
    • 2
  • David W. Denning
    • 5
  • Alessandro C. Pasqualotto
    • 1
    • 3
    • 6
    Email author
  1. 1.Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Hospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Molecular Biology LaboratorySanta Casa de Porto AlegrePorto AlegreBrazil
  4. 4.Universidade Federal do Rio GrandeRio GrandeBrazil
  5. 5.Manchester Academic Health Science CentreThe University of ManchesterManchesterUK
  6. 6.Universidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil

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