Abstract:

Objective

To explore the dynamic changes of heparin binding protein （HBP） and interleukin-6 （IL-6） levels in children with lobar pneumonia （LP）， and to analyze the correlation between HBP，IL-6 and disease severity.

Methods

The clinical data of 160 children with LP admitted to Suzhou Wujiang Distinct Children's Hospital from January 2022 to August 2023 were analyzed， retrospectively. According to the severity of pneumonia， they were divided into common pneumonia group （93 cases） and severe pneumonia group （67 cases）， and healthy children who underwent physical examination at the same time were selected as healthy control group （60 cases）. The general data and laboratory indicators of children of three groups were analyzed. HBP and IL-6 levels of children in normal pneumonia group and severe pneumonia group were analyzed before treatment and 3 d， 7 d， 14 d after treatment. The effects of gender， age， body mass index（BMI）， duration of fever， duration of hospitalization， lung lobe lesions and pathogen distribution on the levels of ΔHBP and ΔIL-6 were analyzed by hierarchical regression （Forward method）. The correlation between HBP and IL-6 levels between common pneumonia group and severe pneumonia group were analyzed by locally weighted regression （Lowess）. Logistic regression was used to analyze the independent correlation between HBP， IL-6 levels and disease severity. The diagnostic efficacy of HBP， IL-6 alone and in combination for the severity of LP were evaluated by the receiver operating characteristic curves （ROC）. The restricted cubic spline（RCS） model was established to analyze the dose-response relationship with associated strength between HBP level， IL-6 level and disease severity. The clinical practical value of HBP and IL-6 models were evaluated by decision curve analysis.

Results

The levels of white blood cell （WBC）， neutrophil （NEU）， lymphocyte （LYM），platelet （PLT）， neutrophil-lymphocyte ratio （NLR）， erythrocyte sedimentation rate （ESR）， C-reactive protein（CRP）， procalcitonin （PCT）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， immunoglobulin G （IgG），CD4⁺ T， CD8⁺ T and CD4⁺/CD8⁺ T among children in common pneumonia group， severe pneumonia group and healthy control group were all significantly different （F = 10.899， 68.235， 7.467， 24.068， 41.612， 151.070，283.137， 435.08， 73.047， 68.450， 59.703， 28.519， 32.398， 30.491； all P ＜ 0.001）. The duration of fever， duration of hospitalization， NEU， PLT， NLR， ESR， CRP， PCT， IgA， IgG， IgM， CD4⁺ T， CD8⁺ T， CD4⁺/CD8⁺ T （t = 7.681，8.628， 3.969， 4.125， 4.474， 5.551， 4.025， 11.996， 7.188， 6.208， 4.005， 3.151， 4.046， 4.463； all P ＜ 0.001）， HBP and IL-6 before treatment as well as 3 d， 7 d and 14 d after treatment in common pneumonia group and severe pneumonia group were all significantly different （HBP： t = 19.684， 17.632， 14.883， 6.72； all P ＜ 0.001. IL-6：t = 11.667， 10.454， 9.444， 18.424； all P ＜ 0.001）. The hierarchical regression model analysis showed that gender，age， body mass index （BMI）， lung lobe disease and pathogen distribution had significant positive effects on ΔHBP and ΔIL-6 （ΔHBP： F = 25.074， 21.935， 17.402， 14.333， 10.577； all P ＜ 0.001. ΔIL-6： F =14.512， 12.249，11.248， 18.218， 20.506； all P ＜ 0.001）. Lowess analysis showed that there was a significant linear positive correlation between HBP and IL-6 of common pneumonia group and severe pneumonia group （r = 0.50， 0.53；both P ＜ 0.001）. Logistic regression analysis showed that after adjusting covariates， HBP and IL-6 were still risk factors for the severity of LP （OR = 1.758， 95%CI： 1.622-1.891， P ＜ 0.001； OR = 1.207， 95%CI： 1.154-1.260，P = 0.001）， and there was an independent correlation with the severity of LP， the trend test of HBP and IL-6 from low to high quintile array was statistically significant （t = 13.002， 6.068； both P_trend ＜ 0.001）. The sensitivity analysis showed E value were 1.701 and 1.273， respectively. Subgroup analysis showed that there were statistical differences in HBP and IL-6 before treatment as well as 3 d， 7 d and 14 d after treatment between children with Mycoplasma pneumoniae infection and Streptococcus pneumoniae infection in common pneumonia group and severe pneumonia group （all P ＜ 0.001）. ROC curve analysis for diagnosing the severity of LP showed that the combined diagnostic effect of HBP and IL-6 was better， with an AUC of 0.991 （95%CI： 0.980-0.999， P ＜ 0.001），and the sensitivity， specificity and accuracy were 94.03%， 97.85% and 96.25%， which were significantly higher than those of single index diagnosis. RCS model analysis showed that strength association of both HBP and IL-6 levels were associated with the severity of LP in a dose-response relationship （P_fornonlinear = 0.331， 0.544）.The decision curve analysis showed that HBP and IL-6 prediction models had high clinical practical value.

Conclusions

HBP and IL-6 levels are significantly increased in children with LP， and independently correlated with the severity of the disease. They are important biomarkers for evaluating the disease and have important clinical value.

Key words: Heparin binding protein, Interleukin-6, Children, Lobar pneumonia, Dynamic change, Disease severity