Predictive significance of peripheral blood IL-6 and FeNO in pediatric Mycoplasma pneumoniae infections accompanied by airway hyperresponsiveness.

Background: Mycoplasma pneumoniae (MP) is a common cause of pediatric pneumonia and may contribute to airway hyperresponsiveness (AHR). This study aimed to investigate the levels of evaluated peripheral blood interleukin-6 (IL-6) and fractional exhaled nitric oxide (FeNO) in pediatric patients with MP infection and AHR, and their predictive value for this co-occurrence. Methods: A total of 120 pediatric patients with MP infection admitted to our hospital from June 2021 to May 2023 were stratified into an AHR cohort (n=45) and a non-AHR cohort (n=75) based on the presence or absence of AHR. General patient information, IL-6 and FeNO levels, lung function indices [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) predicted values], and expression levels of molecules implicated in the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway were analyzed. The correlation of IL-6 and FeNO with lung function parameters and the HMGB1/TLR4/NF-κB pathway was analyzed. A multifactorial logistic regression model was utilized to analyze risk factors contributing to the co-occurrence of MP infection and AHR. The receiver operating characteristic (ROC) curves were plotted to evaluate the predictive power of IL-6, FeNO, and their combination for MP infection and AHR in children. Results: Proportions of the AHR cohort with fever duration ≥7 days (P=0.02) and antibiotic initiation ≥7 days (P=0.02) were significantly higher than those in the non-AHR cohort. The AHR cohort exhibited significantly higher levels of peripheral blood IL-6 (P<0.001), HMGB1 (P<0.001), TLR4 (P=0.01), NF-κB (P=0.01), and FeNO (P<0.001) and lower values of FEV1 (P=0.04), FVC (P<0.001), and PEF (P<0.001). Pearson correlation demonstrated that IL-6 and FeNO were positively correlated with HMGB1, TLR4, and NF-κB (r>0, P<0.001), and inversely correlated with FEV1, FVC, and PEF (r<0, P<0.001), while IL-6 exhibited a positive correlation with FeNO (r>0, P<0.001). Logistic regression revealed that fever duration (≥7 d) (P=0.02), initiation of antibiotic therapy (≥7 d) (P=0.01), and elevated levels of IL-6 (P<0.001), HMGB1 (P=0.009), TLR4 (P=0.02), and NF-κB (P=0.009) were independent risk factors for the co-occurrence of MP infection with AHR [odds ratio (OR) >1, P<0.05], while FEV1 (P=0.040), FVC (P=0.040), and PEF (P=0.040) were protective factors (OR <1, P<0.05). The area under the curve (AUC) of the ROC curves for IL-6, FeNO, and their combination in predicting the co-occurrence of MP infection with AHR was 0.859 [95% confidence interval (CI): 0.787-0.930], 0.873 (95% CI: 0.807-0.939), and 0.887 (95% CI: 0.824-0.950), respectively. Conclusions: Peripheral blood levels of IL-6 and FeNO were significantly elevated in children with MP infection and AHR. These markers were associated with lung function and the HMGB1/TLR4/NF-κB signaling pathway. Their combined assessment could effectively predict the co-incurrence of AHR in patients with MP infection.