Utility of bronchoalveolar lavage fluid galactomannan alone or in combination with PCR for the diagnosis of invasive aspergillosis in adult hematology patients: A systematic review and meta-analysis

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.