Diagnosis of Invasive Aspergillosis in Hematological Malignancy Patients Receiving Mold-Active Antifungals: Performance of Interleukins 6 and 8, Asp LFD, and Aspergillus PCR in Same-Day Blood and Bronchoalveolar Lavage Fluid Samples

Martin Hoenigl, MD,1,2 Sven Heldt, MD,3 Juergen Prattes, MD,4 Susanne Eigl, MD,1 Birgit Spiess, MD,5 Gemma Johnson, MD,6 Robert Krause, MD,4 and Dieter Buchheidt, Prof5

Author address: 

1Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria 2UCSD, San Diego, California 3Medizinische Universitaet Graz, Graz, Austria 4Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria 5Department of Hematology and Oncology, Mannheim University Hospital, Heidelberg University, Mannheim, Germany 6OLM Diagnostics, Newcastle-upon-Tyne, UK

Abstract: 

Background

Aspergillus spp. induce elevated levels of several cytokines, including Interleukin (IL)-6 and IL-8. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/molecular tests for invasive aspergillosis (IA) in patients receiving mold-active antifungals.

Methods

This cohort study included 106 prospectively enrolled (2014–2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, galactomannan, β-d-glucan, and cytokines that have shown significant associations with IA in our previous matched case–control analysis (including IL-6 and IL-8), for IA classified according to the revised EORTC/MSG criteria.

Results

Among the 106 cases, 11 had probable IA, 32 possible IA, and 63 no evidence for IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed significantly better performance in BALF compared with blood, with the exception of serum IL-8 which was highly specific for IA and proved to be the most reliable blood biomarkers. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) were highly sensitive and specific for differentiating probable IA from no IA.

Conclusion

High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

2018

Poster: 

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abstract No: 

2567

Full conference title: 

ID week 2018
    • ID Week 2018