The co-pathogenesis of severe influenza with invasive pulmonary aspergillosis.

 Influenza infection causes a severe global health burden annually, partly by leading to respiratory failure which necessitates admission to the intensive care unit in about 5-10% of all hospitalized patients. Over the last few years, reports on invasive pulmonary aspergillosis (IPA) complicating influenza infection in critically ill patients are increasing, reaching incidences of up to 23%, even in patients without typical risk factors for IPA such as congenital or acquired immunosuppression. We aim to investigate the pathophysiology of this superinfection of critically ill influenza patients, to better define the population at risk, ultimately leading to enhanced diagnosis and treatment options. We propose the research hypothesis that (a) an altered interaction of Aspergillus with the airway epithelium, (b) an altered fungal host response against Aspergillus, (c) the use of neuraminidase inhibitors as antiviral therapy and the use of corticosteroids at the ICU, and (d) the genetic profile of patients contribute all together to the development of influenza-associated aspergillosis (IAA). The present proposal has the potential to improve our understanding of precisely which patients with severe influenza develop IAA, and how and why they do so.