Pre-admission fine particulate matter exposure is associated with invasive pulmonary aspergillosis in patients with severe pneumonia, results from two multicenter cohort studies.

Background: Aspergillus, the causative pathogen of invasive pulmonary aspergillosis (IPA)-a highly lethal infectious disease-produces spores with diameters that fall within the fine particulate matter (PM_2.5) range and are frequently detected in ambient PM_2.5 samples. In this study, we investigated whether pre-admission exposure to PM_2.5 is associated with an increased risk of IPA in patients with severe pneumonia.

Methods: Daily PM_2.5 levels for the six months before admission were obtained from a multicenter retrospective cohort and a multicenter prospective cohort. Multivariable logistic regression was used to assess whether pre-admission PM_2.5 exposure is an independent risk factor of IPA in both cohorts. Pooled concentration-response curves determined the dose-response relationship. Mediation analysis was used to assess whether the presence of Aspergillus acts as a mediator between PM_2.5 exposure and 28-day mortality.

Findings: Among 2287 patients, higher average daily PM_2.5 exposure over six-month before admission was independently associated with an increased risk of IPA. For every 10 μg/m³ increase in average daily PM_2.5 exposure during the six months before admission, the risk of IPA increased by 21% (95% CI: 10%-32%). The dose-response relationship was linear, and results remained robust across subgroups and sensitivity analyses. Mediation analysis showed that Aspergillus positivity was found to mediate 21.26% (95% CI: 4.5%-48%; P = 0.008) of the relationship between daily PM_2.5 exposure in the 90 days preceding admission and 28-day mortality.

Interpretation: In this study, we evaluate the association between pre-admission PM_2.5 exposure and IPA. Our findings demonstrate that higher concentrations of PM_2.5 prior to admission are associated with an increased risk of IPA among ICU-admitted patients with severe pneumonia. In addition, our findings suggest that Aspergillus mediate the association between PM_2.5 exposure and mortality in this population.

Funding: This work was supported by National Science and Technology Major Project of China (2025ZD0549000), National Natural Science Foundation of China (grant no. 82202356, 82341109, and 82173645), the Zhejiang Provincial Natural Science Fund (grant no. LTGY24H190001), "Pioneer" and "Leading Goose" R&D Program of Zhejiang (grant no. 2025C02090).