Dose-response relationship of pre-ICU corticosteroids and influenza-associated pulmonary aspergillosis: a multicenter target trial emulation.

Authors

Shengnan Xu, Hongmei Liu, Pengli Fan, Hao Dou, Leilei Guo, Bo Qiao, Yuanyuan Li, Yansheng Zhou, Xiufeng Hu, Yanyan Guo, Bin Hu, Sangang Zheng, Junping Liu, Jiangfeng Zhang, Junzhe Bao, Peng Li

Published in

Annals of intensive care. Volume 16. Pages 100132. Epub Aug 03, 2026.

Abstract

Prior corticosteroid use is linked to influenza-associated pulmonary aspergillosis (IAPA) in critically ill patients, yet the dose-response relationship remains unclear.
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.
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.
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.

PMID:
42604214
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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