Influenza-associated pulmonary aspergillosis: new perspectives on the pathophysiological and clinical aspects to enable host-directed medicine

Influenza-associated pulmonary aspergillosis (IAPA) is a recently identified co-infection with high mortality, consisting of an invasive pulmonary infection caused by Aspergillus fumigatus in severe influenza patients admitted to the intensive care unit. Prospective clinical data on IAPA are lacking, while the pathophysiology still needs to be unraveled. Diagnosing the disease remains challenging in critically ill patients. To tackle these issues, this research proposal has the following objectives: (1) to define the epidemiology, clinical features and clinical risk factors as well as the outcome of IAPA in ICU patients; (2) to prospectively identify genetic factors associated with a higher risk of development of IAPA; (3) to investigate the role of the soluble pattern recognition receptor PTX3 in the pathophysiology of IAPA; (4) finally, to develop a zebrafish model of IAPA which will allow visualization of the interplay between the pathogens and the host immune system. To achieve these goals, this research project will make use of the embedding in an international, multicenter, prospective, observational study (part of H20202 HDM-FUN) for the clinical objective, while some of the samples obtained in this study will be used in both in vitro and in vivo studies for the other objectives.