Association between Clonorchis sinensis infection and the risk of pulmonary fungal infection in patients with AECOPD: a retrospective propensity score matching study

Background Pulmonary fungal infection (PFI) is a severe complication in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Although helminth infections are increasingly recognized as potent modulators of host immunity, their influence on susceptibility to opportunistic fungal infections remains poorly understood. We investigated whether Clonorchis sinensis ( C. sinensis ) infection is associated with risk of PFI in AECOPD patients and explored potential immunological mechanisms underlying this association. Methods We conducted a retrospective cohort study including 2,523 patients hospitalized for AECOPD between January 2018 and December 2025. Following 1:4 propensity score matching (PSM), 217 patients with C. sinensis infection were matched to 840 controls. The primary outcome was in-hospital PFI. A five-tier causal inference framework incorporating PSM, multivariable conditional logistic regression, inverse probability of treatment weighting (IPTW), and doubly robust estimation was used to evaluate robustness of the association. Robustness was validated through sensitivity analyses adjusting for acute exacerbation severity (arterial blood gas parameters) and applying strictly defined PFI criteria. Causal mediation analyses assessed contributions from peripheral immune cells and clinical treatments. Results Post-matching, the C. sinensis group exhibited a significantly lower PFI incidence than controls (5.1% vs. 10.5%, P = 0.021). This association remained consistent across all primary causal inference models (Odds Ratio [OR] range: 0.455–0.465, all P < 0.05). These findings were further confirmed by sensitivity analyses adjusting for acute exacerbation severity (OR = 0.448, P = 0.018) and restricting the outcome to strictly defined PFI cases receiving ≥ 7 days of systemic antifungal therapy (OR = 0.376, P = 0.016; E-value = 4.76). Mediation analyses revealed that the quantitative preservation of peripheral absolute lymphocyte counts accounted for 12.11% of this association, while a reduced duration of systemic corticosteroids exposure mediated an additional 10.91%. Conclusions C. sinensis infection is independently associated with a substantially lower risk of PFI in hospitalized AECOPD patients. This association is partially mediated by two parallel pathways: the quantitative preservation of peripheral lymphocyte counts and a reduced duration of systemic corticosteroids exposure. These findings provide novel clinical evidence linking helminth-associated immune remodeling to altered host susceptibility to opportunistic infections.