基于“肺-肠轴”分析小儿止咳平喘糖浆对痰热阻肺型哮喘患儿免疫炎症及肠道菌群的影响

Analysis of the Effects of Xiao’er Zhike Pingchuan Syrup on Immune Inflammation and Gut Microbiota in Children with Phlegm Heat Resistance Pulmonary Asthma Based on the “Lung Gut Axis”

关键词:  止咳平喘糖浆  痰热阻肺型哮喘  免疫炎症

Key words:  Xiao’er Zhike Pingchuan Syrup  Phlegm heat resistance pulmonary asthma  Immune inflammation.

摘要:

目的 基于“肺-肠轴”分析小儿止咳平喘糖浆对痰热阻肺型哮喘患儿免疫炎症及肠道菌群的影响。方法 选取2023年1月1号到2024年6月30号来我院就诊的80例急性哮喘患儿，随机数字表法分为中药治疗组（中药组）40例、安慰剂治疗组（安慰剂组）40例，中药组在常规治疗（孟鲁司特钠+布地奈德气雾剂）基础上叠加小儿止咳平喘糖浆治疗，安慰剂组在常规治疗基础上叠加安慰剂糖浆口服。比较两组临床疗效，哮喘控制测试（ACT）问卷、肺功能[测定1 s用力呼气容积(FEV1),1 s用力呼气容积肺活量(FVC),呼气峰值流速( PEF)]、免疫细胞含量（Th1、Th2、Treg、Th17、Th22）、血清细胞因子及介质（IFN-γ、IL-4、IL-10、Periostin、Eotaxin、ADAM33）；通过16S rRNA基因测序技术分析患者粪便样本中的肠道菌群组成，分析有益菌（如双歧杆菌、乳酸杆菌）和潜在有害菌（如拟杆菌、梭菌属）的变化。采用Pearson分析免疫炎症标志物与肠道菌群结构之间的相关性。结果 中药组总有效率90.00%明显高于安慰剂组的62.50%（P＜0.05）；治疗后两组ACT问卷明显升高，中药组ACT问卷评分明显高于安慰剂组（P＜0.05）；治疗后两组FEV1、FEV1/FVC比值指标明显升高，中药组FEV1、FEV1/FVC比值指标明显高于安慰剂组，治疗后两组PEF指标差异率明显降低，中药组PEF差异率指标明显降低（P＜0.05）；治疗后两组Th1、Treg水平明显升高，中药组Th1、Treg水平明显高于安慰剂组，治疗后Th2、Th17、Th22水平明显降低，中药组Th2、Th17、Th22水平明显低于安慰剂组（P＜0.05）；治疗后两组IFN-γ水平明显升高，中药组IFN-γ水平明显高于安慰剂组；治疗后两组IL-4、IL-10、Periostin、Eotaxin、ADAM33水平明显降低，中药组IL-4、IL-10、Periostin、Eotaxin、ADAM33水平明显低于安慰剂组（P＜0.05）；治疗后两组有益菌，包括双歧杆菌、乳酸杆菌菌群明显升高，中药组双歧杆菌、乳酸杆菌菌群明显高于安慰剂组，治疗后两组潜在潜在有害菌（属水平），包括拟杆菌（Bacteroides）、梭菌属（Clostridium）明显降低（P＜0.05）。Pearson分析结果显示， IFN-γ与拟杆菌、梭菌属菌群呈负相关，与双歧杆菌,乳酸杆菌菌群呈正相关(P<0.05)。IL-4、IL-10、Periostin、Eotaxin、ADAM33分别与拟杆菌、梭菌属菌群呈正相关，与双歧杆菌,乳酸杆菌菌群呈负相关(P<0.05)。结论 小儿止咳平喘糖浆治疗痰热阻肺型哮喘患儿临床效果显著，可能通过调节免疫炎症反应及肠道菌群进而改善临床症状，为哮喘的治疗提供了新的思路。

Abstract:

OBJECTIVE Based on the "lung gut axis" analysis, this study aims to investigate the effects of pediatric cough and asthma syrup on immune inflammation and gut microbiota in children with phlegm heat resistant pulmonary asthma. METHODS Eighty children with acute asthma who came to our hospital for treatment from January 1, 2023 to June 30, 2024 were randomly divided into a traditional Chinese medicine treatment group (TCM group) of 40 cases and a placebo treatment group (placebo group) of 40 cases using a random number table method. The TCM group was treated with Xiao’er Zhike Pingchuan Syrup, while the placebo group was treated with placebo syrup orally. Compare the clinical efficacy of two groups, including asthma control test (ACT) questionnaire, lung function [measuring forced expiratory volume (FEV1), forced expiratory volume vital capacity (FVC), peak expiratory flow rate (PEF)], immune cell content (Th1, Th2, Treg, Th17, Th22), serum cytokines and mediators (IFN - γ, IL-4, IL-10, Periostin, Eotaxin, ADAM33); Analyze the composition of gut microbiota in patient fecal samples using 16S rRNA gene sequencing technology, and analyze changes in beneficial bacteria (such as Bifidobacterium and Lactobacillus) and harmful bacteria (such as Bacteroides and Clostridium). Pearson analysis was used to investigate the correlation between immune inflammatory markers and gut microbiota structure. RESULTS The total effective rate of 90.00% (65.00% cured + 22.50% significant effect + 12.50% effective) in the traditional Chinese medicine group was significantly higher than the total effective rate of 62.50% (30.00% cured + 20.00% significant effect + 12.50% effective) in the placebo group (P < 0.05); the ACT questionnaire of the two groups was significantly elevated after treatment, and the score of the ACT questionnaire of the traditional Chinese medicine group was significantly higher than that of the placebo group (P < 0.05); FEV1 and FEV1/FVC ratio indexes were significantly higher in the two groups after treatment, and FEV1 and FEV1/FVC ratio indexes were significantly higher in the traditional Chinese medicine group than in the placebo group; the rate of difference in PEF indexes was significantly lower in the two groups after treatment, and the rate of difference in PEF indexes was significantly lower in the traditional Chinese medicine group (P < 0.05); the levels of Th1 and Treg were significantly higher in the two groups after treatment, and the levels of Th1 and Treg were significantly higher in the traditional Chinese medicine group than in the placebo group. Th1 and Treg levels were significantly higher in the group than in the placebo group, and the levels of Th2, Th17, and Th22 were significantly lower in the TCM group than in the placebo group after treatment (P < 0.05); the levels of IFN-γ were significantly higher in the two groups after treatment, and the levels of IFN-γ were significantly higher in the TCM group than in the placebo group; the levels of IL-4, IL-10 in the two groups after treatment were significantly lower, Periostin, Eotaxin, and ADAM33 levels were significantly lower in the traditional Chinese medicine group than in the placebo group (P < 0.05); beneficial bacteria, including Bifidobacteria and Lactobacillus colonies, were significantly higher in both groups after treatment, and Bifidobacteria and Lactobacillus colonies were significantly higher in the traditional Chinese medicine group than in the placebo group, and Bifidobacteria and Lactobacillus colonies were significantly higher in the traditional Chinese medicine group than in the placebo group after treatment, and Bifidobacteria and Lactobacillus colonies were significantly higher in the placebo group after treatment. Significantly higher than the placebo group; harmful bacteria, including Bifidobacterium and Clostridium spp. flora, were significantly lower in both groups after treatment, and Bifidobacterium and Clostridium spp. flora in the traditional Chinese medicine group were significantly lower than those in the placebo group (P<0.05).The results of the Pearson's analysis showed that IFN-γ was negatively correlated with the Bifidobacterium and Clostridium spp. flora and positively correlated with the Bifidobacterium,Lactobacillus spp. flora (P<0.05).The results of the IL-4, IL- 10, Periostin, Eotaxin, and ADAM33 were positively correlated with Bacteroides and Clostridium spp. and negatively correlated with Bifidobacterium,Lactobacillus spp. flora, respectively (P<0.05). CONCLUSION The clinical effect of pediatric cough and asthma syrup in treating children with phlegm heat resistance pulmonary asthma is significant. It may improve clinical symptoms by regulating immune inflammatory response and intestinal microbiota, providing new ideas for the treatment of asthma..