目的

探究肝素结合蛋白（HBP）与白细胞介素-6（IL-6）水平在儿童大叶性肺炎（LP）中的动态变化，并分析HBP和IL-6与疾病严重程度的相关性。

方法

回顾性分析2022年1月至2023年8月苏州市吴江区儿童医院收治的160例LP患儿临床资料。根据肺炎病情分为普通肺炎组（93例）和重症肺炎组（67例），另选择同期体检的健康儿童作为健康对照组（60例）。比较3组儿童的一般资料和实验室指标，分析普通肺炎组和重症肺炎组患儿治疗前和治疗后3 d、7 d和14 d的HBP和IL-6水平。应用分层回归（前进法）分析性别、年龄、身体质量指数（BMI）、发热时间、住院时间、肺叶病变和病原体分布对ΔHBP和ΔIL-6的影响。应用局部加权回归（Lowess）分析普通肺炎组和重症肺炎组HBP与IL-6水平的相关性。采用Logistic回归分析HBP和IL-6水平与病情严重程度的独立相关性。应用受试者工作特征曲线（ROC）评估HBP、IL-6单独与二者联合对LP病情严重程度的诊断效能。采用限制性立方样条（RCS）模型分析HBP和IL-6水平与病情关联强度的剂量-反应关系。应用决策曲线分析评估HBP、IL-6模型的临床实用价值。

结果

普通肺炎组、重症肺炎组和健康对照组儿童白细胞（WBC）、中性粒细胞（NEU）、淋巴细胞（LYM）、血小板（PLT）、中性粒细胞/淋巴细胞比值（NLR）、红细胞沉降率（ESR）、C-反应蛋白（CRP）、降钙素原（PCT）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、免疫球蛋白G（IgG）、CD4⁺ T、CD8⁺ T和CD4⁺/CD8⁺ T淋巴细胞水平差异均有统计学意义（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，P均＜ 0.001）。普通肺炎组与重症肺炎组患儿发热时间、住院时间、NEU、PLT、NLR、ESR、CRP、PCT、IgA、IgG、IgM、CD4⁺ T、CD8⁺ T和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，P均＜ 0.001）以及治疗前、治疗后3 d、7 d和14 d的HBP和IL-6水平（HBP：t = 19.684、17.632、14.883、6.72，P均＜ 0.001；IL-6：t = 11.667、10.454、9.444、18.424，P均＜ 0.001）差异均有统计学意义。分层回归模型分析显示，性别、年龄、体质量指数（BMI）、肺叶病变和病原体分布对ΔHBP、ΔIL-6产生显著的正向影响（ΔHBP：F = 25.074、21.935、17.402、14.333、10.577，P均＜ 0.001；IL-6：F = 14.512、12.249、11.248、18.218、20.506，P均＜ 0.001）。Lowess分析结果显示，普通肺炎组和重症肺炎组患儿HBP与IL-6均呈显著线性正相关（r = 0.50、0.53，P均＜ 0.001）。Logistic回归分析结果显示，校正协变量后，HBP与IL-6仍是LP病情严重程度的危险因素（OR = 1.758、95%CI：1.622～1.891、P ＜ 0.001；OR = 1.207、95%CI：1.154～1.260、P = 0.001）；与LP病情严重程度存在独立相关性，HBP与IL-6从低到高五分位数组趋势性检验存在统计学意义（t = 13.002、6.068，P_趋势均＜ 0.001），敏感性分析显示E值分别为1.701和1.273。亚组分析显示，普通肺炎组和重症肺炎组中肺炎支原体感染与肺炎链球菌感染儿童在治疗前、治疗后3 d、7 d和14 d的HBP和IL-6水平差异均有统计学意义（P均＜ 0.001）。诊断LP病情严重程度的ROC曲线分析结果显示，HBP与IL-6联合诊断效果更优，AUC为0.991（95%CI：0.980～0.999、P ＜ 0.001），灵敏度、特异度和准确度较单一指标诊断均提高，分别为94.03%、97.85%和96.25%。RCS模型分析结果显示，HBP、IL-6水平与LP病情关联强度呈线性剂量-反应关系（P_非线性= 0.331、0.544）。决策曲线分析结果显示，HBP和IL-6预测模型临床实用价值较高。

结论

HBP和IL-6水平在儿童LP中显著升高，且与病情严重程度独立相关，是评估病情的重要生物标志物，具有较高的临床价值。

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.