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Bronchoalveolar Lavage Fluid Galactomannan for Diagnosis of Pulmonary Aspergillosis
Abstract & Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Dr. Winslow serves as a consultant for Siemens Diagnostics, and is on the speaker's bureau for GSK and Cubist.
Synopsis: A retrospective analysis of the Platelia galactomannan (GM) assay was performed on bronchoalveolar lavage (BAL) fluid on 99 evaluable high-risk hematology patients, including 58 with proven or probable invasive pulmonary aspergillosis (IPA). Estimates of positive and negative predictive values of a positive BAL GM results for proven and probable IPA were 76% and 96%, respectively.
Source: Maertens J, et al. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2009;49:1688-1693.
All patients with hematologic disorders from a university teaching hospital in Belgium, who had BAL tested for galactomannan (GM) from 2005-2008, were reviewed. Only BAL samples obtained before the start of systemic antifungal therapy were used in the analysis. Two investigators, who were blinded to the results of the BAL GM, reviewed the medical records of the patients and classified them using revised EORTC/MSG case definitions as having proven, probable, possible, or no IA.
Using an EIA cutoff of 1.0 OD for proven IA vs. no IA, a positive predictive value of 77% and negative predictive value of 98% were obtained. For proven + probable IA vs. no IA, positive and negative predictive values of 76% and 96% were seen, respectively. BAL from 29 of 58 proven or probable IA cases were culture positive for Aspergillus species.
Despite the retrospective design of this study and the likelihood that pretest probability of IA was quite high in the group of patients studied, the results obtained have potential clinical significance. Early diagnosis of invasive fungal infections in patients with hematologic malignancies, and in patients following both hematopoietic stem cell transplantation and solid organ transplantation, remains problematic. The use of imaging studies such as high resolution CT scan has probably been the single most important advance in this area, but even this modality is lacking in both sensitivity and specificity. Serial serum GM assays in high-risk patients have been shown to be helpful in some, but not in all, studies. GM EIA, whether performed on serum or BAL fluid, often has low sensitivity, and false-positive results are common, and can result from airway colonization with Aspergillus in the absence of clinical and radiographic findings (what I would term a "true false positive") and in the presence of interfering substances such as piperacillin/tazobactam (a "false false positive"). Most importantly, a negative serum or BAL GM does not exclude invasive fungal infection due to non-Aspergillus organisms such as Zygomycetes.
Another interesting article looked at the diagnostic performance of the serum (1->3)-B-D-glucan (BG) assay in patients at high risk for invasive fungal infection.1 Using a cutoff of 80 pg/mL, sensitivities of 0.64 and specificity of 0.84, respectively, were seen. This assay has the advantage of being able to detect this antigen, which is common to essentially all pathogenic fungi (including Pneumocystis, where it has almost 100% sensitivity).
Clearly, newer diagnostic modalities, including GM, BG, and fungal PCR assays, currently in development, need to be studied in large, prospective clinical trials in order for their appropriate use to be defined. These studies should include looking at their sensitivities and specificities when run on both serum/plasma and BAL fluid.