Autopsy study of fatal invasive pulmonary aspergillosis: Often undiagnosed premortem

Invasive aspergillosis (IA) is a serious complication in immunocompromised and critically ill patients but is difficult to diagnose. We sought to examine how often cases go undiagnosed and to understand the presenting clinical and radiologic features associated with fatal IA. We reviewed cases of fatal IA confirmed at autopsy (N = 67) between 1999 and 2019 at a tertiary academic hospital. At autopsy, pulmonary involvement was present in 97% of cases--46% were limited to the lungs and 51% had concomitant extrapulmonary involvement. Immunosuppression with either glucocorticoids and/or other immunosuppressive agents was present in 85%. Among those not immunocompromised (15%), chronic lung disease was present in 70%, and a respiratory coinfection was found in 50%. Chest imaging abnormalities including consolidation, ground glass opacities, halo sign, cavitation, and air crescent sign were present in 49%, 49%, 37%, 22%, and 7% of cases, respectively. Diagnostic bronchoscopy was performed in 61% of cases and yielded aspergillus in 63% of those cases by either bronchoalveolar lavage (galactomannan and/or culture), bronchial washings, or transbronchial biopsy cultures. Either a respiratory coinfection or other systemic coinfection was diagnosed in 64%. The performance of diagnostic bronchoscopy was associated with accurate pre-mortem identification of IA (p = 0.001). Clinicians correctly identified IA as the cause of death in only 27% of fatal IA cases identified at autopsy. Complex presenting features, high rates of co-infections, and low rates of invasive diagnostic procedures may have led to missed diagnoses of IA.