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Abstract
Background: The clinical utility of bronchoalveolar lavage (BAL) fluid galactomannan (GM) for the early diagnosis of invasive aspergillosis (IA) varies widely across studies mainly due to heterogeneity of the studied populations. Methods: We conducted a systematic review and meta-analysis of 16 studies involving 783 adults with hematological malignancies to derive summary estimates of the overall accuracy of BAL-GM for diagnosing IA. Findings: Summary estimates of BAL-GM using an optical density (OD) index cutoff value of 1.5 for proven and probable IA were: sensitivity 0.92 (95% CI = 0.48–0.99), specificity 0.98 (95% CI = 0.78–1.00), positive likelihood ratio 53.7 (95% CI = 3.7–771.8), and negative likelihood ratio 0.08 (95% CI = 0.01–0.83). Comparing serum GM and Aspergillus PCR testing on BAL fluid, BAL-GM conferred greater sensitivity, but lower specificity than the serum GM test, and similar specificity as the PCR assay. The use of BAL-GM with serum GM or BAL-PCR tests increased the sensitivity moderately when a positive result was defined by either assay. Interpretation: GM quantification in BAL fluid at an OD index cutoff value of 1.5 has excellent sensitivity and specificity to assist clinical decision-making in confirming or excluding a diagnosis of IA when results are interpreted with clinical findings. Additional research investigating the effects of antifungal agents, optimal timing and processing of BAL sampling are needed to improve the diagnostic accuracy of BAL-GM testing.
Acknowledgements
Heng SC is the recipient of an Endeavour Postgraduate Award. This study was not supported by funding from any sponsor.
Declaration of interest
M.A.S. and S.C.A.C. have sat on advisory boards for and received research funding (not related to the current work) from Pfizer, MSD and Gilead Sciences. C.O.M. has been a member of advisory boards for, received investigator-initiated grants from (not related to the current work), and given lectures for Gilead Sciences, Pfizer, MSD, and Orphan Australia. D.C.M.K. has sat on an advisory board for Pfizer and receives financial support (not related to the current work) from Pfizer, MSD, Novartis and Gilead Sciences. All other authors: no conflicts of interest.