肺炎支原体肺炎患儿炎症细胞因子和免疫细胞与小气道功能的相关性分析

Correlation between cytokines, immune cells and small airway function in children with Mycoplasma pneumoniae pneumonia

目的 分析肺炎支原体肺炎(MPP)患儿炎症细胞因子和免疫细胞与小气道功能的相关性,了解炎症状态和免疫细胞对小气道功能损伤的影响。方法 选择2015年6月—2020年6月绍兴第二医院医共体总院儿科收治的诊断为MPP的患儿107例,其中31例出现喘息,同时选择同期体检健康的50例正常儿童作为对照组。检测所有患儿的肺功能,包括用力肺活量(FVC)、第1秒用力呼气量(FEV_(1))以及小气道功能指标[包括呼吸初期瞬间流量(FEF75%)、呼吸中期瞬间流量(FEF50%)、呼吸后期瞬间流量(FEF25%)及最大呼气中段流量(MMEF)]。采用酶联免疫吸附法检测所有儿童的炎症细胞因子水平,包括白细胞介素-4(IL-4)、白细胞介素-6(IL-6)及γ-干扰素(IFN-γ)。检测免疫细胞,包括CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞以及CD4^(+)/CD8^(+)T细胞比值。结果 喘息组儿童IL-4、IL-6及IFN-γ水平分别为(41.73±5.16)pg/ml、(26.93±3.32)pg/ml及(683.15±80.74)ng/L;未喘息组儿童IL-4、IL-6及IFN-γ水平分别为(26.91±4.47)pg/ml、(17.84±2.74)pg/ml及(406.18±78.16)ng/L;对照组儿童IL-4、IL-6及IFN-γ水平分别为(15.84±3.14)pg/ml、(7.43±1.08)pg/ml及(236.75±57.13)ng/L。3组儿童IL-4、IL-6及IFN-γ水平比较差异均有统计学意义(F=12.746,18.578,10.875,均P<0.05)。喘息组儿童IL-4、IL-6及IFN-γ水平均显著高于未喘息组和对照组,未喘息组儿童IL-4、IL-6及IFN-γ水平均显著高于对照组,差异均有统计学意义(均P<0.05)。3组儿童CD3^(+)T细胞水平比较差异有统计学意义(P<0.05),喘息组儿童CD3^(+)T细胞水平高于未喘息组和对照组,未喘息组儿童CD3^(+)T细胞水平高于对照组,差异均有统计学意义(P<0.05)。3组儿童FVC、FEV_(1)、FEF25%、FEF50%、FEF75%及MMEF水平比较差异均有统计学意义(均P<0.05)。喘息组儿童FVC、FEV_(1)、FEF25%、FEF50%、FEF75%及MMEF水平均显著低于未喘息组和对照组,未喘息组儿童FVC、FEV_(1)、FEF25%、FEF50%、FEF75%及MMEF水平均显著低于对照组,差异均有统计学意义(均P<0.05)。相关性分析结果显示:MPP患儿FEF25%、MMEF与IL-4、IL-6呈负线性相关,FEF25%、FEF50%、FEF75%、MMEF与IFN-γ呈负线性相关,与CD3^(+)T细胞呈正线性相关(均P<0.05)。结论 MPP患儿存在一定程度的小气道功能损伤,炎症细胞因子和免疫细胞功能紊乱参与了MPP患儿的发病过程,并与小气道损伤的严重程度具有相关性,临床通过监测相关指标水平变化,能够为MPP患儿病情、疗效及预后评估提供重要依据。

Objective To analyze the correlation between cytokines, immune cells and small airway function in children with Mycoplasma pneumoniae pneumonia(MPP), investigate the effects of inflammation state and immune cells on small airway injury. Methods From June 2015 to June 2020,107 children diagnosed as MPP in General Hospital of Medical Treatment Combination of the Second Hospital of Shaoxing were selected. Among them, 31 children had wheezing. Meanwhile, 50 healthy children in other hospital during the same period were selected as control group. Pulmonary function of all the children was tested, including forced vital capacity(FVC), forced expiratory volume in the first second(FEV_(1)), and small airway function indexes [including forced expiratory flow at 75% of FVC exhaled(FEF75%), forced expiratory flow at 50% of FVC exhaled(FEF50%), forced expiratory flow at 25% of FVC exhaled(FEF25%), and maximal mid-expiratory flow(MMEF)]. The levels of inflammatory cytokines in all the children were detected, including interleukin-4(IL-4), interleukin-6(IL-6), and gamma-interferon(IFN-γ). The levels of immune cells in all the children were detected, including CD3^(+)T cells, CD4^(+)T cells, CD8^(+)T cells, and CD4^(+)/CD8^(+)T cell ratio. Results The levels of IL-4,IL-6 and IFN-γ in wheezing group were(41.73±5.16)pg/ml,(26.93±3.32)pg/ml, and(683.15±80.74)ng/L, respectively;the levels of IL-4,IL-6 and IFN-γ in non-wheezing group were(26.91±4.47)pg/ml,(17.84±2.74)pg/ml, and(406.18±78.16)ng/L, respectively;the levels of IL-4,IL-6 and IFN-γ in control group were(15.84±3.14)pg/ml,(7.43±1.08)pg/ml, and(236.75±57.13)ng/L, respectively. There were statistically significant differences in the levels of IL-4,IL-6 and IFN-γ among the three groups(F=12.746,18.578,10.875,P<0.05). The levels of IL-4,IL-6 and IFN-γ in wheezing group were statistically significantly higher than those in non-wheezing group and control group, the levels of IL-4,IL-6 and IFN-γ in non-wheezing group were statistically significantly higher than those in control group(P<0.05). There was statistically significant difference in the level of CD3^(+)T cells among the three groups(P<0.05), the level of CD3^(+)T cells in wheezing group was statistically significantly higher than those in non-wheezing group and control group, the level of CD3^(+)T cells in non-wheezing group was statistically significantly higher than that in control group(P<0.05). There were statistically significant differences in the levels of FVC, FEV_(1), FEF25%, FEF50%, FEF75%, and MMEF among the three groups(P<0.05).The levels of FVC, FEV_(1), FEF25%, FEF50%, FEF75%, and MMEF in wheezing group were statistically significantly lower than those in non-wheezing group and control group, the levels of FEV_(1), FEF25%, FEF50%, FEF75%, and MMEF in non-wheezing group were statistically significantly lower than those in control group(P<0.05)Correlation analysis showed that FEF25% and MMEF were negatively linearly correlated with IL-4 and IL-6 in MPP children, FEF25%, FEF50%, FEF75%, and MMEF were negatively linearly correlated with IFN-γ and positively linearly correlated with CD3^(+)T cells(P<0.05). Conclusion There is a certain degree of impairment of small airway function in MPP children, and there is a certain correlation between the dysfunction of cellular immunity and inflammatory state and the decline of small airway function. The levels of inflammatory cytokines and immune cells can provide reference for disease condition, curative effect, and prognosis evaluation of children.