Galactomannan Testing in Bronchoalveolar Lavage Fluid Facilitates the Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Hematologic Malignancies and Stem Cell Transplant Recipients

Abstract

Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.

Detection of Galactomannan in Bronchoalveolar Lavage Fluid Samples of Patients at Risk for Invasive Pulmonary Aspergillosis: Analytical and Clinical Validity

“…Hence, for daily clinical practice, a lower OD index cutoff value (0.8) seems to be much more appropriate, as evidenced by the ROC analysis. This lower cutoff is also in line with previously published experiences (24). Of note, at these lower values, the pretest probability of disease remains crucially important for determining the posttest probability (Fig.…”

“…Hence, a culture-independent method may increase the yield of BAL fluid samples. Recently, the clinical utility of GM EIA detection using BAL fluid samples has been explored in a variety of adult and pediatric populations; these studies, which use various OD cutoff indices for positivity, have reported high sensitivities in hematology patients (2,3,7,13,19,22,24,26,28,30), most solid-organ transplant recipients (4), critically ill patients (21), and nonimmunocompromised patients (23). However, significantly lower sensitivities have been reported in lung transplant recipients (4,15,18,27).…”

Invasive fungal infections in acute leukemia

“…due to the use of mold-active antifungal prophylaxis and corticosteroids) are possible [Marr et al 2005[Marr et al , 2004Mennink-Kersten et al 2004]. Furthermore, GM assay in BAL specimen has shown promising results and adds to the sensitivity of the serum GM assay [Nguyen et al 2010;Meersseman et al 2008].…”

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“…Bronchoalveolar lavage galactomannan was positive in all patients who had invasive fungal infection and were on active antifungal therapy for < 3 days. 53 Serum galactomannan can be falsely elevated in patients with gastrointestinal GVHD and those receiving beta lactams such as piperacillintazobactam. 54 Elevated serum 1,3-beta-D-glucan assay levels may be useful in the diagnosis but is not well defined in patients with IPA.…”