Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients
Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking.
We performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.
There were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA.
Our results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.
- Barnes PD, Marr KA: Aspergillosis: spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am 2005, 20: 545–61. CrossRef
- Von Eiff M, Roos N, Schlten R, Hesse M, Zuhlsdorf M, Loo J: Pulmonary aspergillosis: early diagnosis improves survival. Respiration 1995, 62: 341–7. CrossRef
- De Pauw B, Walsh TH, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group: Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infections Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008, 46: 1813–21. CrossRef
- Hope WW, Walsh TJ, Denning DW: Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis 2005, 5: 609–22. CrossRef
- 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. CrossRef
- Musher B, Fredricks D, Leisenring W, Balajee SA, Smith C, Marr KA: Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J Clin Microbiol 2004, 42: 5517–22. CrossRef
- Nguyen MH, Jaber R, Leather HL, Wingard JR, Staley B, Wheat LJ: Use of bronchoalveolar lavage to detect galactomannan for diagnosis of pulmonary aspergillosis among nonimmunocompromised hosts. J Clin Microbiol 2007, 45: 2787–92. CrossRef
- Husain S, Paterson DL, Studer SM, Crespo M, Pilewski J, Durkin M, Wheat JL, Johnson B, McLaughlin L, Bentsen C, McCurry KR, Singh N: Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation 2007, 83: 1330–6. CrossRef
- Clancy CJ, Jaber RA, Leather HL, Wingard JR, Staley B, Wheat LJ, Cline CL, Rand KH, Schain D, Baz M, Nguyen MH: Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol 2007, 45: 1759–65. CrossRef
- Maertens J, Maertens V, Theunissen K, Meersseman W, Meersseman P, Meers S, Verbeken E, Verhoef G, Van Eldere J, Lagrou K: Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis 2009, 49: 1688–93. CrossRef
- Hope WW, Kruhlak MJ, Lyman CA, Petraitiene R, Petraitis V, Francesconi A, Kasai M, Mickiene D, Sein T, Peter J, Kelaher AM, Hughes JE, Cotton MP, Cotten CJ, Bacher J, Tripathi S, Bermudez L, Maugel TK, Zerfas PM, Wingard JR, Drusano GL, Walsh TJ: Pathogenesis of Aspergillus fumigatus and the kinetics of galactomannan in an in vitro model of early invasive pulmonary aspergillosis: implications for antifungal therapy. J Infect Dis 2007, 195: 455–66. CrossRef
- Slobbe L, Polinder S, Doorduijn JK, Lugtenburg PJ, el Barzouhi A, Steyerberg EW, Rijnders BJA: Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clin Infect Dis 2008, 47: 1507–12. CrossRef
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/10/44/prepub
- Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients
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BMC Infectious Diseases
- Online Date
- March 2010
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. Department of Medicine, National University Hospital, Singapore, 5 Lower Kent Ridge Road, 119074, Singapore
- 2. Division of Hematology, National University Cancer Institute, Singapore
- 3. Department of Laboratory Medicine, National University Hospital, Singapore