Performance of the (1,3)-Beta- d -Glucan Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary A

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Performance of the (1,3)-Beta-D-Glucan Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis Kathleen A. Linder . Carol A. Kauffman . Shiwei Zhou . Blair J. Richards . Steve Kleiboeker . Marisa H. Miceli

Received: 4 July 2020 / Accepted: 14 July 2020 Ó Springer Nature B.V. 2020

Abstract Detection of (1,3)-beta-D-glucan (BDG), a component of the cell wall of many fungi, was studied in bronchoalveolar lavage fluid (BALF) as a possible aid for the diagnosis of proven/probable invasive pulmonary aspergillosis (IPA). BDG was measured on stored BALF from 13 patients with EORTC/ MSGERC defined proven/probable IPA and 26 matched control patients without IPA. The median BALF BDG was 80 pg/mL (range\ 45–8240 pg/mL) in the IPA cohort and 148 pg/mL (range

\ 45–5460 pg/mL) in the non-IPA cohort. Using a positive cutoff of C 80 pg/mL, sensitivity was 54% and specificity was 38%. Higher cutoff values led to improvement in specificity but a dramatic decrease in sensitivity. ROC/AUC analysis was unable to identify an optimal cutoff value at which test performance was enhanced: AUC 0.43, 95% CI 0.24–0.63. When the BDG assay was performed on BALF, neither sensitivity nor specificity was sufficient for use in the diagnosis of IPA.

Handling Editor: Vishnu Chaturvedi.

Keywords Aspergillosis  Pneumonia  Beta-Dglucan  Bronchoalveolar lavage

K. A. Linder  C. A. Kauffman Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA K. A. Linder  C. A. Kauffman  S. Zhou Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA B. J. Richards Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, USA S. Kleiboeker Viracor Eurofins Clinical Diagnostics, Lee’s Summit, MO, USA M. H. Miceli (&) Division of Infectious Diseases, University of Michigan Health System, F4005 University Hospital South, Ann Arbor, MI 48109-5378, USA e-mail: [email protected]

Introduction Non-culture-based methods have become an important tool for the diagnosis of invasive pulmonary aspergillosis (IPA), as culture-based methods cannot reliably identify invasive pulmonary infection [1]. Detection of (1,3)-beta-D-glucan (BDG), a component of the cell wall of many fungi, in serum has been reported to have sensitivity as high as 94–96% for the diagnosis of Pneumocystis jirovecii pneumonia and 85% for invasive candidiasis [2–4], but is less sensitive for the diagnosis of IPA [5, 6]. Bronchoalveolar lavage fluid (BALF) is frequently obtained from patients with IPA and is often used for other non-

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Mycopathologia

culture-based testing methodologies, including Aspergillus galactomannan (GM) testing. We sought to determine whether the BDG assay in BALF might prove useful in the diagnosis of IPA.

Materials and Methods This retrospective, single-center study was performed at the University of Michigan Health System and was approved by the Institutional Review Board. Residual BALF samples from bro