The relationship between serum TIM4,LCN2 and SFRP1 expression and severity of the disease and lung function in children with respiratory syncytial virus pneumonia

Liu Xueru

Du Qing

Zhang Huiling

Wang Yanli

Department of Respiratory Medicine,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology

Abstract:Objective To investigate the expression levels of serum T-cell immunoglobulin and mucin domain containing protein 4(TIM4), lipocalin-2(LCN2), and secreted frizzled-related protein 1(SFRP1) in pediatric patients with respiratory syncytial virus(RSV) pneumonia, and to analyze their associations with disease severity and lung function. Methods A study cohort of 350 pediatric patients with RSV pneumonia admitted to the Department of Respiratory Medicine at Wuhan Children' s Hospital, Tongji Medical College, Huazhong University of Science and Technology between March 2024 and August 2025 was enrolled as the RSV pneumonia group. Based on disease severity, they were further categorized into a mild subgroup(263 cases) and a severe subgroup(87 cases). Additionally, 350 healthy children undergoing routine physical examinations during the same period served as the healthy control group. Serum TIM4, LCN2, and SFRP1 levels were measured using ELISA. Respiratory function parameters [tidal volume(TV), ratio of time to peak tidal expiratory flow to total expiratory time(TPTEF/TE), ratio of volume at peak tidal expiratory flow to expiratory tidal volume(VPEF/VE), respiratory rate(RR)]were assessed using a tidal flow spirometer. Spearman correlation analysis was performed to assess the relationships between serum TIM4, LCN2, SFRP1 levels and disease severity and pulmonary function. Logistic regression analysis was used to identify factors influencing disease progression in children with RSV pneumonia. ROC curve analysis was used to evaluate the predictive value of serum TIM4, LCN2, and SFRP1 levels for disease progression in children with RSV pneumonia. Results Serum TIM4, LCN2, and SFRP1 levels were significantly higher in the RSV pneumonia group than in the healthy control group(t/P =37.730/<0.001, 31.683/<0.001, 44.519/<0.001). Serum TIM4, LCN2, SFRP1 levels and RR were significantly higher in the severe subgroup than in the mild subgroup(t/P = 8.790/<0.001, 8.459/<0.001, 8.948/<0.001, 24.909/<0.001), while TV, TPTEF/TE, and VPEF/VE were significantly lower than those in the mild subgroup(t/P = 14.739/<0.001, 20.945/<0.001, 18.643/<0.001). Serum TIM4, LCN2, and SFRP1 levels were positively correlated with RSV pneumonia severity and RR(r/P = 0.586/<0.001, 0.562/<0.001, 0.513/<0.001, 0.623/<0.001, 0.598/<0.001, 0.565/<0.001), and negatively correlated with TV, TPTEF/TE,and VPEF/VE(r/P =-0.538/<0.001,-0.515/<0.001,-0.487/<0.001,-0.602/<0.001,-0.578/<0.001,-0.543/<0.001,-0.589/<0.001,-0.556/<0.001,-0.521/<0.001). Elevated TIM4, elevated LCN2, elevated SFRP1, prolonged disease duration, preterm birth, and low birth weight were independent risk factors for disease progression in children with RSV pneumonia [OR(95%CI) = 3.466(2.030-5.918), 3.415(1.703-6.848), 3.725(1.832-7.573), 4.107(2.308-7.308), 3.199(1.504-6.804), 1.546(1.104-2.166)], while breastfeeding was an independent protective factor [OR(95%CI) = 0.432(0.279-0.669)]. The AUCs for predicting RSV pneumonia progression using serum TIM4, LCN2, SFRP1, and their combination were 0.795, 0.793, 0.798,and 0.907, respectively. The AUC for combined prediction was significantly higher than those for individual predictions(Z/P =4.791/<0.001, 4.788/<0.001, 4.343/<0.001). Conclusion Serum levels of TIM4, LCN2, and SFRP1 are elevated in children with RSV pneumonia and correlate with disease progression and lung function impairment. Combined detection of these three markers demonstrates high predictive value for disease progression in pediatric RSV pneumonia patients.

Keyword:Respiratory syncytial virusT-cell immunoglobulin and mucin domain containing protein 4Lipocalin-2Secreted frizzled-related protein 1Lung functionPredictive value

Fund:Hubei Provincial Health Commission Scientific Research Project (WJ2021M262)