Prospective Evaluation of Clinical and Biological Markers To Predict the Outcome of Invasive Pulmonary Aspergillosis in Hematological Patients

Early diagnosis of invasive pulmonary aspergillosis (IPA) is crucial to prevent lethal disease in immunocompromized hosts. So far, lipopolysaccharide binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) levels have not been evaluated as biomarkers for IPA. IL-8, previously introduced as a biomarker for IPA, was also included in this study. Bronchoalveolar lavage fluid (BALF) of IPA patients and control patients with non-infectious lung disease was collected according to clinical indications. Measurements in BALF displayed significantly higher levels of LBP (p < 0.0001), BPI (p = 0.0002) and IL-8 (p < 0.0001) in IPA compared to control patients. Receiver operating characteristic curve analysis revealed higher AUC for LBP (0.98, 95% CI 0.95–1.00) than BPI (0.84, 95% CI 0.70–0.97; p = 0.0301). Although not significantly different, AUC of IL-8 (0.93, 95% CI 0.85–1.00) also tended to be higher than AUC for BPI (p = 0.0624). When the subgroup of non-hematological patients was analyzed, test performance of LBP (AUC 0.99, 95% CI 0.97–1.00), BPI (AUC 0.97, 95% CI 0.91–1.00) and IL-8 (AUC 0.96, 95% CI: 0.90–1.00) converged. In conclusion, LBP and—to a lesser extend—BPI displayed high AUCs that were comparable to those of IL-8 for diagnosis of IPA in BALF. Further investigations are worthwhile, especially in non-hematological patients in whom sensitive biomarkers for IPA are lacking.

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Bronchoalveolar lavage fluid and serum 1,3-β-d-glucan testing for invasive pulmonary aspergillosis diagnosis in hematological patients: the role of factors affecting assay performance

Scientific Reports ◽

10.1038/s41598-020-75132-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Barbora Weinbergerova ◽

Tomas Kabut ◽

Iva Kocmanova ◽

Martina Lengerova ◽

Zdenek Pospisil ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Bronchoalveolar Lavage Fluid ◽

Invasive Pulmonary Aspergillosis ◽

Lavage Fluid ◽

Complex Data ◽

Test Quality ◽

Pulmonary Aspergillosis ◽

Hematological Patients ◽

Assay Performance ◽

Diagnostic Time

Abstract Invasive fungal disease (IFD) early diagnosis improves hematological patient survival. Non-culture-based methods may reduce diagnostic time to identify IFD. As complex data on the value of 1,3-β-d-glucan (BDG) from bronchoalveolar lavage fluid (BALF) compared to serum for the most frequent invasive pulmonary aspergillosis (IPA) diagnosis are scarce, particularly including evaluation of potential factors adversely affecting BDG assay, we provided prospective single-center analysis evaluating 172 episodes of pulmonary infiltrates with BDG detection in BALF and serum samples collected in parallel among hematological patients from 2006 to 2015. Proven and probable IPA were documented in 13.4% of the episodes. Sensitivity (SEN), specificity (SPE), positive and negative predictive value (PPV; NPV), and diagnostic odds ratio (DOR) of the BDG assay using standard (80 pg/ml) cut-off for BALF were: 56.5%; 83.2%; 34.2%; 92.5%, and 6.5, respectively, and for serum were: 56.5%; 82.6%; 33.3%; 92.5%, and 6.2, respectively. The same BDG assay parameters employing a calculated optimal cut-off for BALF (39 pg/ml) were: 78.3%; 72.5%; 30.5%; 95.6%, and 9.5, respectively; and for serum (40 pg/ml) were: 73.9%; 69.1%; 27.0%; 94.5%, and 6.3, respectively. While identifying acceptable SEN, SPE, and DOR, yet low PPV of both BALF and serum BDG assay for IPA diagnosis, neither the combination of both materials nor the new optimal BDG cut-off led to significant test quality improvement. Absolute neutrophil count and aspirated BALF volume with a significant trend affected BDG assay performance. The BDG test did not outperform galactomannan assay.

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