Application of TLR2 and TLR4 in Peripheral Blood Mononuclear Cells and Serum TNF-α and IL-1β in Patients with Acute Exacerbation of COPD Complicated by Pulmonary Fungal Infection

WANG Jun; PAN Zhiyun; WU Yuying; YAO Zhi; WANG Han; ZHOU Xiaoni

doi:10.3639/j.issn.2095-3097.2025.11.005

Abstract：Objective To analyze the relationship between Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4)in peripheral blood mononuclear cells,serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and secondary pulmonary fungal infection(PFI)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and to explore their application significance so as to provide reference for the prevention and treatment of PFI.Methods A total of 98 patients with AECOPD admitted to Wuhan Pulmonary Hospital from February 2022 to January 2025 were selected.They were divided into the PFI group(18 cases)and the non-PFI group(80 cases)based on whether they had secondary PFI.General clinical data were compared between the two groups;TLR2,TLR4,TNF-α,IL-1β and pulmonary ventilation function indicators[including forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),FEV1/FVC]were compared between the two groups;Pearson correlation analysis was used to analyze the correlations between TLR2,TLR4,TNF-α,IL-1β and pulmonary ventilation function indicators;Multivariate Logistic regression analysis was used to analyze the risk factors for secondary PFI in patients with AECOPD;ROC curve analysis was used to analyze the predictive value of TLR2,TLR4,TNF-α,IL-1β for secondary PFI in patients with AECOPD.Results The detection rate of PFI in AECOPD patients was 18.37%(18/98).A total of 19 fungal strains were detected,predominantly Candida,among which Candida albicans accounted for the highest proportion,reaching 47.37%(9/19).Body mass index in the PFI group was lower than that in the non-PFI group,while the course of COPD,proportion of smokers,and proportion of invasive procedures were higher than those in the non-PFI group(P<0.05).Comparison of lung function grades between the two groups showed a statistically significant difference(P<0.05).Levels of TLR2,TLR4,TNF-α,and IL-1β in the PFI group were significantly higher than those in the non-PFI group,while FEV1,FVC,and FEV1/FVC were significantly lower than those in the non-PFI group(P<0.01).TLR2,TLR4,TNF-α,and IL-1β were all negatively correlated with FEV1/FVC(P<0.01).Multivariate logistic regression analysis showed that TLR4 and TNF-α were independent risk factors for secondary PFI in patients with AECOPD(OR=1.545,95%CI:1.036-2.304,P=0.034;OR=1.458,95%CI:1.121-1.896,P=0.005).ROC curve analysis showed that the AUC of the combination of TLR2,TLR4,TNF-α,and IL-1β for predicting secondary PFI in patients with AECOPD was 0.899,which was significantly better than that of individual predictions(0.758,0.768,0.714,0.768)(Z=1.835,1.690,2.336,1.355;P=0.066,0.091,0.019,0.175).The difference in AUC between the combined prediction and TNF-α alone was statistically significant(P<0.05).The sensitivity and specificity of the combined prediction were 87.23%and 84.69%,respectively.Conclusion TLR2 and TLR4 in peripheral blood mononuclear cells,as well as serum TNF-α and IL-1β,have high predictive value for secondary PFI in patients with AECOPD,and clinical monitoring is recommended.