Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion

Verweij, Paul E.; Rijnders, Bart J. A.; Brüggemann, Roger J. M.; Azoulay, Elie; Bassetti, Matteo; Blot, Stijn; Calandra, Thierry; Clancy, Cornelius J.; Cornely, Oliver A.; Chiller, Tom; Depuydt, Pieter; Giacobbe, Daniele Roberto; Janssen, Nico A. F.; Kullberg, Bart-Jan; Lagrou, Katrien; Lass-Flörl, Cornelia; Lewis, Russell E.; Liu, Peter Wei-Lun; Lortholary, Olivier; Maertens, Johan; Martin-Loeches, Ignacio; Nguyen, M. Hong; Patterson, Thomas F.; Rogers, Thomas R.; Schouten, Jeroen A.; Spriet, Isabel; Vanderbeke, Lore; Wauters, Joost; van de Veerdonk, Frank L.

PURPOSE: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. METHODS: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. RESULTS: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. CONCLUSION: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.