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Effectiveness of Chinese herbal medicine combined with conventional medicine on acute exacerbation of chronic obstructive pulmonary disease:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2023年第2期43卷 212-220页

作者： GUO Wen LI Xuanlin ZHAO Hulei LEI Siyuan XIE Yang LI Jiansheng Co-construction Collaborative Innovation Center for Respiratory disease Diagnosis and Treatment&Chinese Medicine Development of Henan Province/Henan Key Laboratory of Chinese Medicine for Respiratory disease Henan University of Chinese MedicineZhengzhou 450046China Department of Respiratory diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 450000China

OBJECTIVE:To systematically evaluate the efficacy and safety of Chinese herbal medicine(CHM) combined with conventional Western Medicine(CWM) on acute exacerbation of chronic obstructive pulmonary disease(AECOPD) based on high-quality randomized placebocontrolled trials.METHODS:We searched PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure Database,Chinese Biomedical Literature Database,China Science and Technology Journal Database,and Wanfang databases for randomized placebo-controlled trials of CHM treatment for AECOPD from inception to June 4,2021.The Cochrane Collaboration’s tool and the Grading of Recommendations,Assessment,Development and Evaluation were used to assess the risk of bias and the evidence quality of the included studies.Revman 5.3 software was used for Meta-analysis.RESULTS:A total of 9 trials involving 1591 patients were included.The Meta-analysis showed that based on CWM treatment,CHM group had significant advantages over the placebo group in ameliorating clinical total effective rate [RR = 1.29,95% CI(1.07,1.56),P = 0.007,low quality] and TCM symptom scores [MD =-2.99,95% CI(-4.46,-1.53),P < 0.0001,moderate quality],improving arterial blood gas results [PaO_(2):MD = 4.51,95% CI(1.97,7.04),P = 0.0005,moderate quality;PaCO_(2):MD =-2.87,95% CI(-4.28,-1.46),P < 0.0001,moderate quality],reducing CAT scores [MD =-2.08,95% CI(-2.85,-1.31),P < 0.000 01,moderate quality],length of hospitalization [MD =-1.87,95% CI(-3.33,-0.42),P = 0.01,moderate quality],and acute exacerbation rate [RR = 0.60,95% CI(0.43,0.83),P = 0.002,moderate quality].No serious CHM-related adverse events were reported.CONCLUSIONS:The current evidence indicates that CHM is an effective and well-tolerated adjunct therapy for AECOPD patients receiving CWM.However,considering the high heterogeneity,this conclusion requires confirmation.

关键词： drugs Chinese herbal pulmonary disease chronic obstructive acute exacerbation systematic review Meta-analysis GRADE approach

Yinyanghuo(Herba Epimedii Brevicornus) and its components for chronic obstructive pulmonary disease:preclinical evidence and possible mechanisms

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Journal of Traditional Chinese Medicine 2023年第2期43卷 386-396页

作者： WANG Yide GAO Zhen Department of Respiration Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830000China Department of Integrative Medicine Huashan hospital of Fudan UniversityShanghai 200040China

OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pulmonary disease(COPD).METHODS:First,Meta-analysis was carried out.The Chinese and English literature of Yinyanghuo(Herba Epimedii Brevicornus) in treating COPD was searched using the systematic strategy of combining subject words with free words.The included studies were evaluated by the SYRCLE risk bias assessment tool,after which the review manager software was used to combine the effect quantities for statistical analysis.Then,based on bioinformatics technology,the active ingredients and their targets of Yinyanghuo(Herba Epimedii Brevicornus) were screened,and the intersection genes were obtained by mapping and comparing with the targets of COPD.The "medicinal materials-compounds-targets model" was constructed,and the key pathways were annotated.Finally,the core target was docked with important compounds.RESULTS:A total of 8 studies were included in the Metaanalysis.The results showed that the Yinyanghuo(Herba Epimedii Brevicornus) group could significantly downregulate pro-inflammatory factors such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B(pAKT) in the COPD model(all P < 0.05).A total of 23 active components and 102 corresponding target genes of Yinyanghuo(Herba Epimedii Brevicornus) were obtained by bioinformatics technology,among which 17 compounds and 63 targets were closely related to COPD.The results of enrichment analysis mainly included TNF signaling pathway,phosphoinositide 3-kinase(PI3K)/Akt signaling pathway,cancer signaling pathway,and other inflammatory reactions,oxidative stress,and tumorrelated pathways.The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such a

关键词： Yinyanghuo(Herba Epimedii Brevicornus) pulmonary disease chronic obstructive Meta-analysis computational biology

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease

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Chinese Medical Journal 2004年第5期117卷 661-667页

作者：肖丹王辰杜敏捷庞宝森张洪玉肖白刘敬忠翁心植苏丽 David C.Christiani Beijing Institute of Respiratory Medicine Research Center of Preclinical Medicine Occupational Health Program

Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD) However, only 10%-20% of chronic heavy cigarette smokers develop symptomatic disease COPD is most likely the result of complex interactions between environmental and genetic factors Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113→His), exon 4 (His139→Arg) and GSTP1 polymorphism in exon 5 (Ile105→Val) in 100 COPD patients and 100 age- and sex-matched healthy controls Results The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%) The odds ratio ( OR ) adjusted by age, sex, body mass index (BMI) and cigarette years was 2 96 (95% CI 1 24-7 09) There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1 00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1 00 There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls Conclusions mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China The interaction might exist between mEH genotype and smoke The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population

关键词： pulmonary disease chronic obstructive · microsomes · epoxide hydrolases · glutathione S-transferase P· polymorphism genetics

Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and therapeutic effects of glucocorticoids and N-acetylcysteine in rats

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Chinese Medical Journal 2004年第11期117卷 1611-1619页

作者：徐凌蔡柏蔷朱元珏 Department of Respiratory Medicine Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 China

Background T lymphocytes and matrix metalloproteinase (MMP) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-γ (IFN-γ), interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine.Methods Male Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. IL-4 and IFN-γ levels were then determined in bronchoalveolar lavage fluid and lung tissue samples by enzyme -linked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR. Results In comparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significa nt decrease in IFN-γ levels. In addition, the IL-4/ IFN-γ ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0.3 second to forced vital capacity (FEV 0.3/FVC) and dynamic compliance (C dyn) decreased and expiratory resistance (Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-γ increased. The IL-4/IFN-γ ratio returned to normal, though the MMP-12/TIMP-1 ratio remained unchanged. FEV 0.3/FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-γ increased and the IL-4/IFN-γ ratio decreased. The MMP-12/TIMP-1 ratio remained unchanged. Re and C dyn both improved obv

关键词： pulmonary disease chronic obstructive cytokine s· glucocorticiods N-acetylcysteine

Genetic polymorphism in matrix metalloproteinase-9 and the susceptibility to chronic obstructive pulmonary disease in Han population of south China

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Chinese Medical Journal 2004年第10期117卷 1481-1484页

作者：周敏黄绍光万欢英李彪邓伟吾李敏 Department of pulmonary MedicineRuijin Hospital Shanghai Second Medical University Shanghai 200025 China Department of Nuclear MedicineRuijin Hospital Shanghai Second Medical University Shanghai 200025 China

Background There are many candidate genes for chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase-9 (MMP-9) plays an essential role in tissue remodeling and repair associated with development of COPD. In this study we investigated the correlation between MMP-9 gene polymorphism and COPD susceptibility in the Han population of South China.Methods We examined the frequency of polymorphic genotypes of the MMP-9 promoter (-1562C/T) in 100 COPD patients and 98 healthy smokers by restriction fragment length polymorphism.Results The frequencies of polymorphic genotypes in promoters of MMP-9 were C/C 86%, C/T 14% in COPD group; and C/C 98%, C/T 2% in the control group. There were significant differences between the two groups (P<0.01). The allele frequencies were also significantly different between the COPD group and the control group (C allele frequency: 93% vs 99%, T allele frequency: 7% vs 1%, P<0.05 respectively).Conclusion The genetic polymorphism in promoters of MMP-9 gene is associated with the susceptibility to COPD in the Han population of South China.

关键词： pulmonary disease chronic obstructive matrix metalloproteinase-9 genetic polymorphism

Sugarcane bagasse dietary fiber as an adjuvant therapy for stable chronic obstructive pulmonary disease:a four-center,randomized,double-blind,placebo-controlled study

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Journal of Traditional Chinese Medicine 2016年第4期36卷 418-426页

作者： Liu Miao Zheng Fengjie Ni Lei Sun Yan Wu Ruohan Zhang Tianyu Zhang Jinchao Zhong Xianggen Li Yuhang School of Preclinical Medicine Beijing University of Chinese Medicine

OBJECTIVE:To evaluate the efficacy and safety of sugarcane bagasse dietary fiber as an adjuvant therapy for improving quality of life in patients with stable chronic obstructive pulmonary disease(COPD).METHODS:This was a multicenter,randomized,double-blind,placebo-controlled trial.A total of196 participants were randomized into a trial group(treated with 6 g/day sugarcane bagasse plus conventional treatment,n = 98) and a control group(treated with placebo plus conventional treatment,n = 98).All efficacy analyses were performed according to the intention-to-treat(ITT) principle.A per-protocol analysis set(PPS) was used to analyze the cases that completed the clinical trial with good compliance.The trial period was 30 days,with a 6-month follow-up.Pre-and post-treatmentpulmonary symptom scores(cough,sputum,wheezing,and dyspnea) were recorded for both groups.The St.George's Respiratory Questionnaire(SGRQ) and the modified Medical Research Council(m MRC) dyspnea scale were assessed before treatment and at the end of the 6-month follow-up.RESULTS:The ITT population was 178 and the PPS population was 166.Post-treatment pulmonary clinical symptoms and severity of dyspnea(m MRC and SGRQ evaluation) were significantly improved in both the trial group and the control group(ITT and PPS:P pulmonary symptoms and m MRC.There was a greater reduction in the SGRQ subscales of activity,effect and total score in the trial group compared with the control group(ITT and PPS:P < 0.01).There was no statistical difference in pre-and post-treatment safety variables in either group.CONCLUSION:Sugarcane bagasse combined with conventional treatment improved quality of life in patients with stable COPD.Sugarcane bagasse appears to be a safe herbal medicine with potential for treating patients with stable COPD when taken orally as an adjuvant therapy.

关键词： Saccharum pulmonary disease chronic obstructive Randomized clinical trial Medicine Chinese Traditional

Interleukin-32, not reduced by salmeterol/fluticasone propionate in smokers with chronic obstructive pulmonary disease

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中华医学杂志(英文版) 2014年第9期127卷 1613-1618页

作者： Du Yipeng Wang Wei Yang Wei He Bei Department of Respiratory Medicine Peking University Third Hospital

Background The interleukin(IL)-32/tumor necrosis factor(TNF) α pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease(COPD) inflammation. Inhaled corticosteroids(ICS) in combination with long-acting β2-agonists(LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain. Methods Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate(SF; Seretide, GlaxoSmithKline) Diskus(50/500 μg twice daily) or ipratropium bromide/salbutamol(IS; Combivent, Boehringer Ingelheim) MDI(42 μg/240 μg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-α, the number of neutrophils and eosinophils were measured.Results Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-α in sputum(P=0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance(P=0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George’s respiratory questionnaire in both the SF(P=0.004) and IS(P=0.030) treatment groups, but no evidence of improvement in lung function was observed in either group.Conclusion The sputum TNF-α and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.

关键词： interleukins pulmonary disease chronic obstructive anti-inflammatory agents interleukin 32 protein human

Correlation of HDEFB1 polymorphism and susceptibility to chronic obstructive pulmonary disease in Chinese Han population

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Chinese Medical Journal 2004年第11期117卷 1637-1641页

作者：胡瑞成徐永健张珍祥倪望陈仕新 Department of Respiratory Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Background Inherited factors are involved in the development of chronic obstructive pulmonary disease (COPD). This study was designed to investigate the relationship between polymorphisms of HDEFB1 668 C/G and 1654G/A loci and susceptibility to COPD in Chinese Han population.Methods After the process of extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers, the loci of genotypes 668C/G and 1654G/A were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and polymerase chain reaction-single strand conformation polymorphism analysis. Results With respect to HDEFB1 668 locus, the occurences of CC, CG, GG genotypes were 72.7%, 25.0%, 2.3% in COPD smokers and 53.2%, 38.3%, 8.5% in healthy smokers (P<0.05, respectively). The allele frequencies of 668 C and 668G were 85.2% and 14.8% in COPD smokers and 72.3% and 27.7% in healthy smokers (P<0.01, respectively, odds ratio was 2.32 with 95% confidence interval 1.37 to 3.72). As to HDEFB1 1654G/A locus, neither genotype distribution difference nor allele distribution difference was found when comparing COPD smokers with healthy smokers. Conclusion The polymorphism of HDEFB1 668C/G is associated with susceptibility to COPD in Chinese Han population; furthermore, the 668G allele represents relatively lower susceptibility to COPD.

关键词： pulmonary disease chronic obstructive susceptibility polymorphism (genetics) human beta defensin-1

Expression and role of adrenomedullm and its receptor in patients with chronic obstructive pulmonary disease

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Chinese Medical Journal 2003年第6期116卷 863-867页

作者：徐平戴爱国周厚德沈宏伟刘丽华宋卫东 Department of Respiratory Medicine Peking University Shenzhen HospitalShenzhen 518034China Department of Respiratory disease Research the Third Affiliated HospitalNanhua UniversityHengyang 421900China Institute of Endocrinology and Metabolism the Second Affiliated Hospital of Central South UniversityXiangya Medical CollegeChangsha 410007China Center Laboratory the Second Affiliated Hospital of Central South UniversityXiangya Medical CollegeChangsha 410007China

Objective To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).Methods Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n =12) and those with PH were placed in Group B (n =10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.Results The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD ( P pulmonary artery walls of control subjects . The expression levels were significantly higher in those of COPD sufferers ( P pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO2.Conclusion ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.

关键词： pulmonary disease chronic obstructive·adrenomedullin·receptor