Invasive pulmonary aspergillosis in the ICU: the corticosteroid link.

Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection traditionally associated with severely immunocompromised hosts, particularly those with hematologic malignancies. However, its epidemiological profile has shifted in recent years, with a rising incidence among critically ill patients in intensive care units (ICUs), many of whom lack classical risk factors. This change is driven by increased use of corticosteroids and immunomodulatory therapies, the growing prevalence of chronic lung disease, and severe viral pneumonias such as influenza and COVID-19. In these patients, airway epithelial injury, immune dysregulation, and mechanical ventilation facilitate fungal invasion even in the absence of profound immunosuppression. Corticosteroids play a central role in IPA pathogenesis. While they limit hyperinflammation, they simultaneously impair fungal clearance by suppressing NF-κB signaling, downregulating TNF-α production, and promoting IL-10 secretion, resulting in a Th2-skewed immune profile. Neutrophil recruitment persists but becomes dysregulated, contributing to tissue injury rather than effective pathogen elimination. Corticosteroids may also directly enhance Aspergillus growth, further compounding risk. Diagnosis of IPA in ICU patients remain challenging because radiological hallmarks such as the halo sign are uncommon, and distinguishing colonization from invasive disease is difficult. Serum and bronchoalveolar lavage galactomannan, β-D-glucan assays, and PCR can improve early detection, but no single test is definitive in this heterogeneous population. As much as possible, high-quality lower respiratory tract samples should be obtained. Furthermore, effective treatment requires not only timely diagnosis, but also careful selection of antifungal taking into consideration pharmacologic challenges of ICU patients and pharmacodynamics of antifungals. Recognition of high-risk patients such as those receiving corticosteroids, those with chronic lung disease, severe viral pneumonia, or requiring invasive ventilation is critical to improve outcomes. Mortality in this group can exceed that of neutropenic patients, underscoring the need for heightened clinical suspicion and timely antifungal therapy. A deeper understanding of the immunopathogenesis of IPA in non-neutropenic patients, particularly the dual effects of corticosteroids on inflammation and host defense, may inform risk stratification and guide earlier intervention. Enhanced surveillance, prompt diagnostic workup, and judicious use of immunomodulatory therapy represent key strategies to mitigate the rising burden of this devastating infection in ICU settings.