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Dose-response relationship of pre-ICU corticosteroids and influenza-associated pulmonary aspergillosis: a multicenter
Shengnan Xu1, Hongmei Liu1, Pengli Fan2
1Respiratory Intensive Care Unit, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Background:
Prior corticosteroid use is linked to influenza-associated pulmonary aspergillosis (IAPA) in critically ill patients, yet the dose-response relationship remains unclear.
Methods:
In this multicenter emulated target trial across 48 ICUs in Central China (January 2023-June 2025), we included critically ill, non-neutropenic adults with influenza. Using inverse probability of treatment weighting (IPTW) and restricted cubic splines, we modeled the dose-response association between pre-ICU corticosteroid exposure and IAPA, identifying risk thresholds via segmented regression. Effect modification by pre-specified patient characteristics was further assessed.
Results:
Among 2763 patients (74.2% exposed to corticosteroids; median dose 35 mg dexamethasone-equivalent), 191 (6.9%) developed IAPA during their ICU stay. Pre-ICU corticosteroid exposure was independently associated with IAPA (weighted HR = 2.11; 95% CI 1.25-3.56). A non-linear, J-shaped dose-response relationship was identified (P < 0.001). Risk increased continuously, with a 50% increase at 43.4 mg and doubling at 51.4 mg, followed by a steep inflection point at 63.7 mg (95% CI 62.8-64.7). Higher SOFA scores (>7) significantly amplified per-dose risk (P < 0.001), lowering thresholds to 35.2 mg for 50% increase and 39.5 mg for doubling.
Conclusions:
Pre-ICU corticosteroid exposure is associated with a nonlinear, dose-dependent increase in IAPA risk. Cumulative doses approaching 40-50 mg warrant heightened vigilance, particularly in severely ill patients. These findings support individualized, dose-aware corticosteroid stewardship in severe influenza.
