Performance of Diagnostic Algorithms in Patients With Invasive Pulmonary Aspergillosis

Abstract

Background: Invasive pulmonary aspergillosis (IPA), once limited to immunocompromised patients, is now a severe complication in critically ill ICU patients without classic risk factors. Due to the difficulty of obtaining histological evidence, diagnosis relies on poorly tested algorithms in real-world settings.

Methods: We conducted a retrospective multicenter (n = 9) cohort study including 202 patients with IPA. Patients were classified using a multistep process based on the EuropeanOrganization- for-the-Research-and-Treatment-of-Cancer/Mycosis-Study Group (EORTC-MSG), Invasive-Fungal-Diseases-in-Adult-Patients-in-Intensive-Care-Unit (FUNDICU), Aspergillus-ICU (Asp-ICU), and Asp-ICU with biomarkers (Asp-ICU-BM) criteria. We then evaluated the predictive performance of these criteria against the clinical cohort and histologically proven cases.

Results: Among 202 patients, 78 had EORTC-MSG host factors and were classified accordingly, with EORTC-MSG criteria achieving 100% agreement in identifying clinical and histologically proven cases. In 112 ICU patients without EORTC-MSG host factors, overall agreement was 53% for FUNDICU, 4% for Asp-ICU, and 26% for Asp-ICU-BM versus the clinical cohort. Validation against histologically proven cases showed FUNDICU had 44% sensitivity and 75% specificity, Asp-ICU 6% sensitivity and 100% specificity, and Asp-ICU-BM 28% sensitivity and 63% specificity. Adding acute respiratory distress syndrome (ARDS) and post-cardiac surgery to the FUNDICU criteria improved sensitivity to 97% with a specificity of 63%. The remaining 12 patients lacked EORTC-MSG host factors and were not in the ICU, highlighting a novel classification system.

Conclusions: EORTC-MSG and FUNDICU IPA classification systems are useful for the assignment of most patients with IPA. Incorporating postoperative complications after cardiac surgery and ARDS enhanced the diagnostic accuracy of FUNDICU.

Keywords: ICU; IPA; classification; host factors; invasive pulmonary aspergillosis.

Graphical Abstract

Figure 1.

A–D, The figure summarizes the diagnostic performance of established algorithms for IPA compared with the novel proposed FUNDICU-clinical algorithm. The performance was evaluated against histologically proven cases, with AUROC used as the measure of accuracy. Abbreviations: ASP-ICU, Aspergillus in Intensive Care Units; ASP-ICU-BM, Aspergillus in Intensive Care Units with biomarkers; AUROC, area under the receiver operating characteristic curve; FUNDICU, Invasive Fungal Diseases in Adult Patients in Intensive Care Unit; IPA, invasive pulmonary aspergillosis.