Distinguishing Invasive from Chronic Pulmonary Infections: Host Pentraxin 3 and Fungal Siderophores in
Radim Dobiáš1,2, Pavla Jaworská1, Valeria Skopelidou2
1Department of Bacteriology and Mycology, National Reference Laboratory for Mycological Diagnostics, Public Health Institute in Ostrava, 70200 Ostrava, Czech Republic.
Abstract:
The multiple forms of pulmonary aspergillosis caused by Aspergillus species are the most common respiratory mycoses. Although invasive, the analysis of diagnostic biomarkers in bronchoalveolar lavage fluid (BALF) is a clinical standard for diagnosing these conditions. The BALF samples from 22 patients with proven or probable aspergillosis were assayed for human pentraxin 3 (Ptx3), fungal ferricrocin (Fc), and triacetylfusarinine C (TafC) in a retrospective study. The infected group included patients with invasive pulmonary aspergillosis (IPA) and chronic aspergillosis (CPA). The BALF data were compared to a control cohort of 67 patients with invasive pulmonary mucormycosis (IPM), non-Aspergillus colonization, or bacterial infections. The median Ptx3 concentrations in patients with and without aspergillosis were 4545.5 and 242.0 pg/mL, respectively (95% CI, p < 0.05). The optimum Ptx3 cutoff for IPA was 2545 pg/mL, giving a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100, 98, 95, and 100%, respectively. The median Ptx3 concentration for IPM was high at 4326 pg/mL. Pentraxin 3 assay alone can distinguish IPA from CPA and invasive fungal disease from colonization. Combining Ptx3 and TafC assays enabled the diagnostic discrimination of IPM and IPA, giving a specificity and PPV of 100%.
Insights
Pentraxin 3 (Ptx3) in bronchoalveolar lavage fluid effectively diagnoses invasive pulmonary aspergillosis (IPA). Combining Ptx3 with triacetylfusarinine C (TafC) aids in distinguishing invasive fungal infections.
Area of Science:
- Medical Mycology
- Clinical Diagnostics
- Biomarker Discovery
Background:
- Pulmonary aspergillosis, caused by Aspergillus species, represents common respiratory mycoses.
- Accurate diagnosis of invasive pulmonary aspergillosis (IPA) and other fungal infections is critical for patient outcomes.
- Bronchoalveolar lavage fluid (BALF) analysis is a key diagnostic standard, necessitating improved biomarker identification.
Purpose of the Study:
- To evaluate the diagnostic utility of human pentraxin 3 (Ptx3) in BALF for differentiating pulmonary aspergillosis forms.
- To assess the combined diagnostic performance of Ptx3, ferricrocin (Fc), and triacetylfusarinine C (TafC) for invasive fungal diseases.
- To distinguish between invasive pulmonary aspergillosis (IPA), chronic aspergillosis (CPA), and invasive pulmonary mucormycosis (IPM).
Main Methods:
- Retrospective analysis of BALF samples from 22 patients with proven/probable aspergillosis and 67 controls.
- Assay of BALF for Ptx3, Fc, and TafC concentrations.
- Comparison of biomarker levels between patients with aspergillosis, mucormycosis, non-Aspergillus colonization, and bacterial infections.
Main Results:
- Significantly higher median Ptx3 concentrations in patients with aspergillosis (4545.5 pg/mL) versus controls (242.0 pg/mL) (p < 0.05).
- Ptx3 demonstrated high diagnostic performance for IPA (sensitivity 100%, specificity 98%, PPV 95%, NPV 100%) with a cutoff of 2545 pg/mL.
- Combined Ptx3 and TafC assays achieved 100% specificity and PPV for distinguishing IPM from IPA.
Conclusions:
- Ptx3 assay in BALF is a valuable tool for diagnosing IPA and differentiating it from CPA and fungal colonization.
- The combination of Ptx3 and TafC assays enables accurate discrimination between IPM and IPA.
- These biomarkers offer improved diagnostic accuracy for invasive fungal infections, guiding clinical management.
