Objective To evaluate the anti-tussive effect of a total alkaloid agent extracted from Papaver Somniferum L. on simple chronic bronchitis of which the syndrome was counterflow ascent of lung qi according to traditional Chinese medicine (TCM). Methods Randomised, double blind method, placebo control and add on design were applied. Forty-five patients with counterflow ascent of lung qi of simple chronic bronchitis were randomly divided into two groups: treatment group (n=21) with alkaloid agent and control group (n=24) with placebo. Results The incidences of obvious coughing in treatment and control groups were 66.67% and 70.83% (P=0.763 3) respectively. The cough alleviation time of patients was 14.64±16.30 h and 15.12±15.28 h (P=0.795 6) respectively. The loss of cough rates on the third day was 28.57%, 16.67% (P=0.337 7) respectively. The average scores decreased were 4.29 and 2.88 (P=0.054 8) respectively. Conclusions The study indicates that total alkaloid agent extracted from Papaver somniferum L. has no significant anti-tussive effect on patients with counterflow ascent of lung qi of simple chronic bronchitis treated with cefaclor sustained release capsules simultaneously. The trial was interrupted by the advice from experts who disagreed with the selection of drug indication.
Objective To evaluate the effectiveness and safety of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis. Methods The randomized controlled trials (RCTs) of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis were searched in the following electronic databases: The Cochrane Library (Issue 1, 2010), PubMed (2000 to Jan. 2010), EMbase (1980 to Dec. 2009), CBM (2000 to Jan. 2010), and WanFang Data (2000 to Jan. 2010). Two reviewers independently screened the included studies, abstracted the data and assessed the quality. The RevMan 5.0 software was used to conduct meta-analyses. Results A total of four RCTs involving 2041 patients were included, and the Jadad scales of all studies were more than five. The results of meta-analyses showed that there was no significant difference between the extended-release formulation group and the immediate-release formulation group in aspects of the clinical cure rate (RR=0.93, 95%CI 0.96 to 1.03), the pathogen eradication rate (RR=0.99, 95%CI 0.94 to 1.04), and the adverse reaction incidence rate (RR=1.06, 95%CI 0.90 to 1.25). Conclusion As the present evidence shows, there is no significant difference in effectiveness and safety between the clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis.
Chinese medicine (CM) has significant clinical effects in the treatment of tracheal-bronchitis. It is of important clinical significance to formulate guidelines for the diagnosis and treatment of tracheal-bronchitis based on the characteristics of TCM syndrome differentiation. The Respiratory Disease Branch of China Association of Chinese Medicine and Respiratory Disease Branch of China Medical Association of Minorities organized and established a multi-disciplinary background working group, based on the World Health Organization Handbook for Guideline Development and the Guideline Development Handbook for Diagnosis and Therapy of Integrative Medicine to develop this guideline. It was developed through technical links such as clinical problem investigation, evidence collection and evaluation, Delphi consultation, and expert consensus meetings. Based on the current best evidence, CM intervention costs and expert experience, 25 recommendations were established to standardize the etiology and pathogenesis of tracheal-bronchitis, syndrome differentiation and treatment, prevention, and care, etc., which can be used by physicians at different levels of medical institutions.
目的 探讨诱导痰、痰、血清中的白介素(IL)-4、-6、-8在慢性支气管炎急性期的浓度阈值，确定其诊断意义，了解三种白介素在三种标本中的不同浓度对诊断慢性支气管炎急性期的意义。 方法 2001年1月-8月对77例慢性反复咳嗽患者按全国慢性支气管炎诊断标准确诊慢性支气管炎急性期48例，非慢性支气管炎29例，进行IL-4、-6、-8的诱导痰、痰、血清检测。采用受试者工作特征曲线(ROC曲线)鉴定三种白介素对三种标本的诊断价值。 结果 ①三种标本的三种白介素的诊断比值比(DOR)均＞3，95%可信区间的下限均＞1。②ROC曲线下面积显示：诱导痰及痰中IL-4、-8之间无差别(P＞0.05)，IL-4和IL-8分别与IL-6之间有统计学意义(P＜0.05)；血清中IL-4、-6、-8检测结果无差异(P＞0.05)。IL-4、-8的诱导痰及痰与血清有统计学意义(P＜0.05)，IL-6的诱导痰、痰、血清之间无差异(P＞0.05)。 结论 诱导痰及痰中的IL-4、-8诊断价值较好，可用于慢性支气管炎急性期的诊断。
嗜酸粒细胞性支气管炎(EB)是一种独立的疾病吗?答案是否定的，现有的证据也不支持。 广义的EB是指气管和支气管壁存在明显嗜酸粒细胞浸润的一种病理状态，为描记气道炎症特征的术语。作为一种常见的发病机制，EB参与多种呼吸系统疾病的发生。哮喘的基本特点就是EB，并与气道高反应性、气道重塑和可逆性气道阻塞密切相关 。除此之外，非哮喘性EB(nonasth— matic eosinophilic bronchitis)、COPD、上气道咳嗽综合征和胃食管反流性咳嗽等均可见EB改变，甚至无下呼吸道症状的变应性鼻炎或部分健康人也存在这种类型的气道炎症。因此，EB在临床上至少存在哮喘、非哮喘性EB、合并COPD 和无症状等表现形式。广义的EB并不是一种疾病，而是多种呼吸道疾病的共同病理过程。 狭义的EB即非哮喘I生EB，是指以咳嗽为唯一症状、肺通气功能和气道反应性正常、诱导痰中嗜酸粒细胞明显增多而皮质激素治疗有效者，是慢性咳嗽的常见病因。目前有观点认为，和咳嗽变异型哮喘相似，EB可能是极轻微的哮喘或哮喘的前期表现。研究发现，EB的病因和发病机制与哮喘很相似。如引起哮喘的环境职业因素和吸入过敏原均可导致EB，Th2炎症反应是两者嗜酸粒细胞气道炎症的主要基础。大部分研究显示介导EB和哮喘的嗜酸粒细胞气道炎症的细胞和细胞因子相同，或仅有程度上的差别。EB和哮喘一样也存在呼出气一氧化氮浓度增加，气道上皮基底膜增厚和上皮下纤维化，气道炎症及气道重塑改变程度两者也相似 。最大的不同在于肥大细胞在气道壁不同部位的浸润和激活。哮喘患者肥大细胞主要浸润支气管平滑肌层，而在EB则主要位于支气管黏膜层 。肥大细胞在气道壁的不同空间分布可以解释哮喘的气道高反应性和EB的咳嗽高敏感性，但不足于据此认为两者为不同的疾病。
Objective To investigate the causal relationship between 91 circulating inflammatory proteins and respiratory tract infection by bidirectional Mendelian randomization. Methods single nucleotide polymorphisms (SNPs) for 91 inflammatory circulating proteins were derived from GWAS data from a genome-wide association study of 14 824 subjects of European ancestry on the Olink Target platform, and SNPs for acute bronchitis, acute bronchiolitis, and acute laryngitis and tracheitis were derived from GWAS pooled data in the FinnGen database. Inverse variance weighting method was used as the main research method to conduct bidirectional Mendelian randomization analysis, and Cochran’ IVW Q test, MR-Egger regression method and one by one elimination method were used to conduct sensitivity tests to evaluate heterogeneity and horizontal pleiotropy. In order to reduce the incidence of Class I errors and improve the feasibility of the study, Bonferroni correction was performed.ResultsLevels of C hemokine C-X-C motif ligand 6 (CXCL6), matrix metalloproteinase-1 (MMP-1), hepatocyte growth factor (HGF), interleukin-10 (IL-10), chemokine C-X3-C motif ligand 1 (CX3CL1), and TNF-related activation-induced cytokine (TRANCE) were causally associated with acute bronchitis. MMP-1 level [OR: 1.239 0, 95%CI: 1.111 6-1.382 2, P<0.000 5] had a significant causal relationship with acute bronchitiss and played a promoting role. Levels of macrophage inflammatory protein-1α (MIP-1α), signaling lymphocyte activating molecules, and FMS-associated tyrosine kinase 3 ligand (FIt3L) were potentially causally associated with acute bronchiolitis. There was a potential causal relationship between C-X-C motif chemokine 5 (CXCL5), T cell surface glycoprotein CD6 subtype (CD6), fibroblast growth factor 19 (FGF-19), C-C motif chemokine 23 (CCL23), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor ligand superfamily member 12 (TNFSF12) levels and acute laryngitis and tracheitis. In reverse Mendelian randomization analysis, there were no positive results between acute bronchitis, acute bronchiolitis and 91 inflammatory factors. Acute laryngitis and tracheitis [OR: 1.076 3,95%CI: 1.012 9-1.143 7, P=0.017 6] were potentially causally associated with FGF-19 levels. Conclusions MMP-1 level have a significant causal relationship with acute bronchitis. The levels of other inflammatory factors such as CXCL6, HGF, MIP-1 alpha, FIt3L, CXCL5, FGF-19 are potentially causally associated with respiratory tract infections. MMP-1 may be an important target for the prediction or treatment of acute bronchitis.
Objective To evaluate and select essential medicine for acute exacerbation of chronic bronchitis (AECB) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines were included (four foreign guidelines, one domestic guideline; three based on evidence, two based on expert consensus). (2) Medicines recommended at least twice by the National Essential Medicine List (NEML, 2009 version) and Chinese National Formulary (CNF) contained: ipratropium bromide (four times), amoxicillin amp; clavulanate potassium (three times), and corticosteroid (three times), cefuroxime (twice), ciprofloxacin (twice), levofloxacin (twice), salbutamol (twice) and dextromethorphan (twice). (3) As for domestic study evidence, a result of one RCT indicated that amoxicillin amp; clavulanate potassium had efficiencies of 92.3% to 94.7% (n=77, low quality). A result of three RCTs (n=275, low quality) indicated that cefuroxime had efficiencies of 67.6% to 90% and an incidence of 5% as to adverse reaction that mainly included skin rashes, diarrhea, etc. A result of two RCTs (n=120, low quality) indicated that ciprofloxacin had efficiencies of 78.3% to 86.6%, bacterial clearance rates of 72.7% to 86.5% and the incidences of 8.7% to 16.2% as to adverse reaction that mainly included gastrointestinal reaction, skin rashes, etc. A result of seven RCTs (n=523, low quality) indicated that levofloxacin had efficiencies of 72.5% to 94.5%, bacterial clearance rates of 82.1% to 95.8% and the incidences of 5% to 7.5% as to adverse reaction. A result of two RCTs (n=239, low quality) indicated that salbutamol had efficiencies of 85.4% to 96.7%. A result of one RCT (n=95, low quality) indicated that ipratropium bromide had efficiencies of 98%. A result of five RCTs (n=466, low quality) indicated that the combined use of budesonide and bronchodilators had efficiencies of 93.4% to 97.8%. Conclusion (1) We offer a b recommendation for cefuroxime, amoxicillin amp; clavulanate potassium, ciprofloxacin and levofloxacin used in the treatment of AECB. (2) We offer a b recommendation for glucocorticoid (budesonide, aerosol) and anticholinergic bronchodilator (ipratropium bromide) and a weak recommendation for short-acting β2-agonist bronchodilator (salbutamol) and antitussive agent (dextromethorphan) for alleviating symptoms due to AECB. (3) We make a recommendation against mucolytic agents and theophylline as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies on AECB and outcome indicator should be improved in order to produce high-quality local evidence.
目的 评价酚妥拉明治疗小儿毛细支气管炎的疗效和安全性。 方法 计算机检索Cochrane图书馆，Medline（1950年－2013年），Embase（1980年－2013年），中国生物医学文献数据库（1978年－2013年）、中国知网（1979年－2013年）、万方（1986年－2013年）、维普（1989年－2013年），收集酚妥拉明联合常规方法对比仅用常规方法治疗小儿毛细支气管炎的随机对照试验（RCT），由两名研究者根据纳入与排除标准筛选文献、提取资料并评价质量后，采用RevMan 5.1软件进行Meta分析。 结果 共纳入13个RCT，1 186例患儿。Meta分析结果显示：在常规治疗基础上加用酚妥拉明，其总有效率[RR=1.30，95%CI（1.15，1.46），P＜0.000 1]、平均住院时间[MD=?2.15 d，95%CI（?2.78，?1.53） d，P＜0.000 01]、啰音消失的平均时间[MD=?1.62 d，95%CI（?2.02，?1.23） d，P＜0.000 01]，憋喘消失的平均时间[MD=?2.39 d，95%CI（?4.64，?0.13）d，P=0.04]差异有统计学意义，而气促消失的平均时间差异无统计学意义[MD=?0.62 d，95%CI（?1.31，0.07）d，P=0.08]。 结论 在常规治疗基础上加用酚妥拉明治疗小儿毛细支气管炎时，其疗效疗效优于仅采用常规治疗，在缓解啰音、憋喘等临床症状上起效更快。而在安全性方面证据不足，需要进一步的研究。
Objective To evaluate and select essential medicine for acute bronchitis using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Eight guidelines were included (seven foreign guidelines, one domestic guideline; five based on evidence, three based on expert consensus). (2) A result of six RCTs (n=816, low quality) indicated that pentoxyverine had efficiencies of 53% to 82% for cough relief. Among the six RCTs, a result of three RCTs (n=283) indicated that pentoxyverine was slightly less efficient than procaterol (RR=0.86, 95%CI 0.78 to 0.94, P=0.001); a result of two RCTs (n=233) indicated that pentoxyverine was slightly less efficient than Chinese medicinals decoction (RR=0.82, 95%CI 0.74 to 0.91, Plt;0.001). Adverse reaction of pentoxyverine (incidence: 0% to 2.4%) mainly covered nausea, palpitation, etc. Pentoxyverine cost 0.20 yuan (for adult) or 0.08 yuan (for child) daily, which was orally taken and applicable to the target population. (3) A result of six RCTs (n=403, low quality) indicated that the efficiencies of dextromethorphan for cough relief was 47.0% to 95.3%. Among the six RCTs, a result of one RCT (n=283) indicated that dextromethorphan hydrobromide (nasal drop) was more efficient than blank intervention (RR=3.71, 95%CI 1.91 to 7.21); a result of one RCT (n=43) indicated that dextromethorphan (for oral use) was more efficient than placebo (RR=1.74, 95%CI 1.13 to 2.66); a result of one RCT (n=300, moderate quality) indicated that dextromethorphan was more efficient than pentoxyverine (RR=1.16, 95%CI 1.07 to 1.26); a result of one observational study (n=121, low quality) indicated that dextromethorphan given for 5 days had an efficiency of 66.5%. Adverse reaction of dextromethorphan (incidence: 2% to 30%) mainly covered mouth dryness, dizziness, nausea, etc. Conclusion (1) We offer a b recommendation for dextromethorphan used in relieving dry cough due to acute bronchitis. (2) We offer a weak recommendation for pentoxyverine as symptomatic treatment for cough relief. (3) We make a recommendation against antibiotics, β2-agonist bronchodilators and mucolytic agents as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies of acute bronchitis in hopes of producing high-quality local evidence.