Projects & Grants

Early diagnosis of invasive lung aspergilosis of next generation
Project IdNU23-05-00095
Main solverMgr. Lenka Kramná, Ph.D.
Period5/2023 - 12/2026
ProviderAgentura zdravotnického výzkumu ČR
AnotationThe last decade has seen a significant increase in secondary Aspergillus infections, not only due to primary hypersensitivity, immunodeficiency based on oncological diseases and their therapy, but mainly due to a rise in severe respiratory infections (H1N1, COVID-19, bacterial infections). This is most evident in critically ill patients whose life is threatened by invasive pulmonary aspergillosis (IPA), with over 90% of cases being caused by Aspergillus fumigatus. In recent decades, various biomarkers with well-known limits of use (Aspergillus DNA, galactomannan, 1,3-ß-D-glucan) have been used for early diagnosis of IPA. However, the clinical need to clearly distinguish the onset of IPA from colonization is much more significant. The current biomarkers only provide "probable IPA" interpretation and the diagnosis is rarely confirmed. Based on our preliminary studies, the use of new low molecular weight substances (secondary metabolites) combined with acute-phase proteins (pentraxin 3) allows very reliable immediate confirmation of IPA. In tissue samples, bronchoalveolar lavage fluid, endotracheal aspirate, breath condensate, serum, and urine of critically ill patients, we will be able to recognize and confirm IPA in time using highly sensitive mass spectrometry detecting specific microbial siderophores in correlation with a significantly increased concentration of acute-phase host protein (pentraxin 3) within hours of the beginning of the invasion of lung tissue. Through a prospective multicenter study, we will evaluate the benefit of new biomarkers in non-invasive IPA confirmation, improve the IPA diagnostic algorithm and transfer the detection method to MALDI-TOF spectrometers widely used in clinical laboratories in the Czech Republic. The study results will contribute to a high clarity of IPA cases, the accurate introduction of antifungal therapy, and a better prognosis of survival of critically ill patients.