• 【在西班牙住院患者中按标签使用吸入性支气管扩张剂:一项多中心观察性研究。】 复制标题 收藏 收藏
    DOI:10.1136/ejhpharm-2019-002171 复制DOI
    作者列表:Villamañán E,Sobrino C,Bilbao C,Fernández J,Herrero A,Calle M,Alvaro D,Segura M,Picazo G,Rodríguez JM,Baldominos G,Ramirez MT,Larrubia Y,Llorente J,Martinez A,Alvarez-Sala R
    BACKGROUND & AIMS: BACKGROUND:Off-label prescription of inhaled bronchodilators (IB) is frequent, despite the fact that they can be ineffective and increase avoidable healthcare costs. OBJECTIVE:To analyse the frequency of off-label prescription of IB in hospitalised patients. Indications and level of evidence, involved drugs, medical specialties prescribing off-label IB and patients' adherence to IBs were also evaluated. METHOD:A descriptive, observational, cross-sectional study was performed in four tertiary hospitals in Spain. The main outcome measure was the number of patients prescribed off-label IBs. Prescriptions were checked against the European Medicines Agency-approved indications. The level of evidence supporting off-label prescription of IBs (according to MICROMEDEX 2.0) was also analysed. Patients were interviewed to test differences (off-label vs on-label) in adherence and knowledge about their inhaled therapy. RESULTS:217 patients were prescribed IBs, 92 of whom were givend off-label IBs (54.7% men, mean age 73.9±12.9 years). The most common off-label prescriptions for IBs were: unspecified dyspnoea (not related to COPD or asthma) (27.2%), respiratory infections (23.9%) and heart failure (22.8%). 76.8% of patients did not have evidence supporting them. Beta2-agonist+corticosteroids and anticholinergics were most commonly prescribed off-label. Internal Medicine was the main medical specialty involved. There were no differences between off-label and on-label users in terms of patients' knowledge about treatment and adherence. CONCLUSION:Off-label indications for IBs are common in hospitalised patients and are generally indicated without scientific support. Dyspnoea not related to COPD or asthma, respiratory infections and heart failure were the main off-label indications, most frequently treated with anticholinergics and beta2-agonists+corticosteroids, for which their efficacy and safety has not been proved. Our results show that prescribing needs to be improved to follow the evidence that exists. Moreover, further research focused on off-label indications is needed to clarify whether they are effective, safe and cost-effective.
    背景与目标: 背景:吸入性支气管扩张剂(IB)的标签外处方很常见,尽管它们可能无效并增加了可避免的医疗费用。
    目的:分析住院患者IB无处方处方的频率。还评估了适应症和证据水平,所用药物,开标签外IB的医学专业以及患者对IB的依从性。
    方法:在西班牙的四家三级医院进行了描述性,观察性横断面研究。主要结局指标是开出处方外IB的患者人数。按照欧洲药品管理局批准的适应症检查处方。还分析了支持IB的非处方处方的证据水平(根据MICROMEDEX 2.0)。采访患者以测试依从性和吸入疗法知识的差异(标签外与标签上)。
    结果:217例患者开了IBs,其中92例接受了不合格的IBs(54.7%的男性,平均年龄73.9±12.9岁)。最常见的IB处方外处方为:未明确的呼吸困难(与COPD或哮喘无关)(27.2%),呼吸道感染(23.9%)和心力衰竭(22.8%)。 76.8%的患者没有支持他们的证据。 Beta2激动剂皮质类固醇和抗胆碱能药最常在处方外使用。内科是其中涉及的主要医学专业。就患者对治疗和依从性的了解而言,标签外和标签外使用者之间没有差异。
    结论:IBs的标签外适应症在住院患者中很常见,并且通常在没有科学支持的情况下适应症。与COPD或哮喘无关的呼吸困难,呼吸道感染和心力衰竭是主要的禁忌证适应症,最常使用抗胆碱能药和β2-激动剂皮质类固醇治疗,但尚未证明其功效和安全性。我们的结果表明,必须遵循现有证据改进处方。此外,还需要针对标签外适应症的进一步研究,以阐明它们是否有效,安全和具有成本效益。
  • 【双重长效支气管扩张剂如何预防慢性阻塞性肺疾病的恶化?】 复制标题 收藏 收藏
    DOI:10.1164/rccm.201609-1794CI 复制DOI
    作者列表:Beeh KM,Burgel PR,Franssen FME,Lopez-Campos JL,Loukides S,Hurst JR,Fležar M,Ulrik CS,Di Marco F,Stolz D,Valipour A,Casserly B,Ställberg B,Kostikas K,Wedzicha JA
    BACKGROUND & AIMS: :Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.
    背景与目标: :减少加重发作的频率和严重程度是治疗慢性阻塞性肺疾病的主要目标之一。多项研究表明,长效支气管扩张剂可降低病情加重率和/或严重程度,另一些研究表明,长效β2-肾上腺素能激动剂(LABAs)和长效毒蕈碱拮抗剂(LAMAs)的组合可更大程度地降低病情加重在发生这些事件的低风险和高风险患者中,其比单组分或LABA /吸入皮质类固醇联合治疗的风险要高。在这篇综述中,一小组的专家严格地评估了可能导致LABA / LAMA组合比单用长效支气管扩张药或LABA /吸入皮质类固醇激素增加的益处增加的机制,这些机制可减轻病情加重。这些包括对肺过度充气和机械压力,炎症,粘液纤毛清除受损的过多粘液产生以及症状严重程度的影响。每组收集和分析的数据均经过所有作者的审查,并合并到本手稿中。现有的临床结果支持以下可能性:LABA / LAMA组合对恶性通货膨胀,纤毛纤毛清除和症状严重性的影响都可能导致病情加重。尽管临床前研究表明LABA和LAMA具有抗炎作用,但在慢性阻塞性肺疾病患者中尚未证明这种作用。
  • 【支气管扩张药和抗哮喘药的遗传毒性和致癌性研究。】 复制标题 收藏 收藏
    DOI:10.1111/bcpt.12054 复制DOI
    作者列表:Brambilla G,Mattioli F,Robbiano L,Martelli A
    BACKGROUND & AIMS: :This survey is a compendium of genotoxicity and carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.
    背景与目标: :该调查是支气管扩张剂和抗哮喘药的遗传毒性和致癌性信息的纲要。收集了来自46种上市药物的数据。在这46种药物中,有25种(54.3%)没有可检索的遗传毒性或致癌性数据。其余21个(45.7%)至少具有一项遗传毒性或致癌性测试结果。在这21种药物中,有10种具有至少一项阳性发现:三种在至少一种遗传毒性试验中呈阳性,至少八种在至少一种致癌性试验中呈阳性,其中一种在遗传毒性和致癌性试验中均呈阳性。关于长期致癌试验结果的遗传毒理学发现的可预测性,有15种药物同时具有遗传毒性和致癌性数据:其中7种(46.6%)既没有遗传毒性也不具有致癌性,其中6种(40.0%)既没有致癌性也没有致癌性。至少一种性别的小鼠或大鼠在遗传毒性试验中呈阴性,有1(6.7%)在遗传毒性试验中呈阳性,但无致癌性,另有1(6.7%)在遗传毒性和致癌性试验中均呈阳性反应。在所考虑的46种药物中,只有11种(23.9%)具有当前药物测试指南所要求的所有数据,但是其中很大一部分是在当前监管环境之前开发和销售的。
  • 【支气管扩张剂对COPD患者的支气管扩张剂随机,安慰剂对照试验。】 复制标题 收藏 收藏
    DOI:10.1378/chest.06-2308 复制DOI
    作者列表:Stolz D,Pollak V,Chhajed PN,Gysin C,Pflimlin E,Tamm M
    BACKGROUND & AIMS: BACKGROUND:In contrast to asthma, the indication for bronchodilators prior to bronchoscopy in patients with COPD has not been properly investigated. We therefore performed a randomized, double-blind, placebo-controlled trial to determine whether use of a short-acting bronchodilator provides a protective effect in patients with COPD undergoing bronchoscopy. METHODS:One hundred twenty patients undergoing bronchoscopy were included. Patients with COPD were randomized to receive either 200 mug of salbutamol (n = 40) or placebo (n = 40) before bronchoscopy. Control patients (n = 40) did not receive any inhaled medication. Spirometry was performed before and 2 h after bronchoscopy in all patients. Sedative drug requirements and hemodynamic parameters were recorded. RESULTS:Hemodynamic findings before, during, and after bronchoscopy were similar in patients with COPD randomized to either salbutamol or placebo (p = not significant for all). Compared to prebronchoscopy values, postbronchoscopy percentage of predicted FEV(1) decreased significantly in all three groups: salbutamol (median, - 4.7%; interquartile range [IQR], - 13.3 to 6.6); placebo (median, - 4.8%; IQR, - 19.9 to 8.4); and control subjects (median, - 10.0%; IQR, - 20.2 to - 3.3) [p = 0.023]. The decrease in FEV(1) was similar in all three patient groups (p = 0.432). The relative change in FEV(1) was inversely correlated to the increasing severity of COPD as expressed by Global Initiative for Chronic Obstructive Lung Disease stages (p = 0.01). CONCLUSIONS:Premedication with an inhaled short-acting beta-agonist cannot be recommended in patients with COPD undergoing bronchoscopy.
    背景与目标: 背景:与哮喘相反,COPD患者在支气管镜检查之前对支气管扩张药的适应症尚未得到适当研究。因此,我们进行了一项随机,双盲,安慰剂对照试验,以确定使用短效支气管扩张剂是否对接受支气管镜检查的COPD患者提供保护作用。
    方法:包括120例接受支气管镜检查的患者。患有COPD的患者在支气管镜检查前随机接受200杯沙丁胺醇(n = 40)或安慰剂(n = 40)。对照患者(n = 40)未接受任何吸入药物治疗。所有患者均在支气管镜检查之前和之后2小时进行肺活量测定。记录镇静药物需求和血液动力学参数。
    结果:在随机分配给沙丁胺醇或安慰剂的COPD患者中,支气管镜检查之前,期间和之后的血流动力学结果相似(p =对所有患者均无显着性)。与支气管镜检查前的值相比,所有三组支气管镜检查后的FEV(1)百分比均显着降低:沙丁胺醇(中位数,-4.7%;四分位间距[IQR],-13.3至6.6);沙丁胺醇(四分位数范围[IQR],-13.3至6.6);沙丁胺醇。安慰剂(中位数--4.8%; IQR--19.9至8.4);和对照组(中位数-10.0%; IQR--20.2至-3.3)[p = 0.023]。在所有三个患者组中,FEV(1)的下降均相似(p = 0.432)。 FEV(1)的相对变化与慢性阻塞性肺疾病全球倡议所表达的COPD严重程度呈负相关(p = 0.01)。
    结论:对于患有支气管镜检查的COPD患者,不建议使用吸入的短效β-激动剂进行药物治疗。
  • 【通过执行NICE细支气管炎指南,减少不必要的胸部X光检查,抗生素和支气管扩张剂。】 复制标题 收藏 收藏
    DOI:10.1007/s00431-017-3034-5 复制DOI
    作者列表:Breakell R,Thorndyke B,Clennett J,Harkensee C
    BACKGROUND & AIMS: :Chest X-rays (CXR), antibiotics and inhaled/nebulized therapy are overused in bronchiolitis, despite evidence-based guidelines suggesting supportive management only. This study investigates the effect of the implementation of the NICE bronchiolitis guideline in a secondary paediatric unit in England. We present a quality improvement project with a completed audit cycle (winter 2014-2015 and 2015-2016) pre- and post-implementation of the NICE bronchiolitis guideline. The educational intervention included sessions for raising awareness of appropriate and inappropriate management of bronchiolitis for both clinicians and nursing staff. As a result, the number of chest radiographs reduced fivefold (from 20 to 4% of patients, absolute reduction 16%), antibiotics reduced more than threefold (from 22 to 6% of patients, absolute reduction 16%) and inhaled/nebulised treatment up to twofold (from 30 to 16%, absolute reduction 14%). Overall NICE guideline compliance rose from 28 to 63%. CONCLUSION:Implementation of the NICE bronchiolitis guideline supported by a simple educational intervention can effectively reduce the number of inappropriate chest radiographs and antibiotic prescribing in bronchiolitis, and enhance compliance with the NICE guideline. What is Known: • Bronchiolitis management in paediatric units in the UK is variable, with poor evidence for existing guidance. Best available evidence was compiled into the NICE guideline, aiming to standardize care. • Some evidence exists for the effectiveness of quality improvement approaches to improve the management of bronchiolitis. What is New: • NICE guidance can be effectively applied to a department using simple educational tools. • Effective NICE implementation reduces the rates of unnecessary chest radiograph and antibiotic administration for patients admitted with bronchiolitis in District General Hospitals.
    背景与目标: 尽管有基于证据的指南仅建议进行支持性治疗,但在细支气管炎中仍过度使用胸腔X射线(CXR),抗生素和吸入/雾化疗法。这项研究调查了在英格兰的第二小儿科医院实施NICE细支气管炎指南的效果。我们提出了一个质量改进项目,在执行之前和之后执行NICE毛细支气管炎指南的审核周期均已完成(2014-2015年冬季和2015-2016年冬季)。该教育干预措施包括提高临床医生和护理人员对毛细支气管炎适当和不适当处理的认识的课程。结果,胸部X光片数量减少了五倍(从20%减少到4%的患者,绝对减少了16%),抗生素减少了三倍以上(从22%减少到6%的患者,绝对减少了16%),并且采用了吸入/雾化治疗高达两倍(从30%到16%,绝对减少14%)。 NICE指南的总体合规率从28%上升到63%。
    结论:通过简单的教育干预措施来实施NICE细支气管炎指南可有效减少细支气管炎的胸部X光片和抗生素处方的使用,并提高对NICE指南的依从性。众所周知:•英国小儿毛细支气管炎的治疗方法不一,现有指南的证据不充分。 NICE指南中汇集了最佳的可用证据,旨在使护理标准化。 •有一些证据表明质量改进方法可改善毛细支气管炎的治疗效果。新增功能:•NICE指南可以使用简单的教育工具有效地应用于部门。 •有效的NICE实施降低了地区综合医院收治的细支气管炎患者不必要的胸部X光检查和抗生素管理的比例。
  • 【磷酸二酯酶4D型基因多态性:与小儿哮喘患者对短效支气管扩张药的反应有关。】 复制标题 收藏 收藏
    DOI:10.1155/2011/301695 复制DOI
    作者列表:Labuda M,Laberge S,Brière J,Bérubé D,Beaulieu P,Pastinen T,Krajinovic M
    BACKGROUND & AIMS: :Short-acting b2-adrenergic receptor agonists are commonly used bronchodilators for symptom relief in asthmatics. The aim of this study was to test whether genetic variants in PDE4D gene, a key regulator of b2-adrenoceptor-induced cAMP turnover in airway smooth muscle cells, affect the response to short-acting b2-agonists. Bronchodilator responsiveness was assessed in 133 asthmatic children by % change in baseline forced expiratory volume in one second (FEV(1)) after administration of albuterol. The analyses were performed in patients with airway obstruction (FEV(1)/FVC ratio below 90%, n = 93). FEV(1)  % change adjusted for baseline FEV(1) values was significantly different between genotypes of rs1544791 G/A polymorphism (P = 0.006) and -1345 C/T (rs1504982) promoter variation (P = 0.03). The association remained significant with inclusion of age, sex, atopy, and controller medication into multivariate model (P = 0.004 and P = 0.02, resp.). Our work identifies new genetic variants implicated in modulation of asthma treatment, one of them (rs1544791) previously associated with asthma phenotype.
    背景与目标: :速效b2-肾上腺素能受体激动剂通常用于支气管扩张药,以缓解哮喘患者的症状。这项研究的目的是测试PDE4D基因(b2-肾上腺素受体诱导的气道平滑肌细胞cAMP转换的关键调节剂)的遗传变异是否影响对短效b2-激动剂的反应。通过在服用沙丁胺醇后一秒钟内基线强迫呼气量的百分比变化(FEV(1))对133名哮喘儿童的支气管扩张剂反应性进行了评估。该分析是在气道阻塞患者中进行的(FEV(1)/ FVC比率低于90%,n = 93)。 rs1544791 G / A多态性(P = 0.006)和-1345 C / T(rs1504982)启动子变异的基因型之间,经基线FEV(1)值调整的FEV(1)%变化显着不同(P = 0.03)。在将年龄,性别,特应性疾病和控制药物纳入多变量模型后,这种关联仍然很显着(分别为P = 0.004和P = 0.02)。我们的工作确定了与哮喘治疗调节有关的新遗传变异,其中之一(rs1544791)以前与哮喘表型有关。
  • 【用于COPD和哮喘的新型长效支气管扩张剂。】 复制标题 收藏 收藏
    DOI:10.1038/bjp.2008.284 复制DOI
    作者列表:Cazzola M,Matera MG
    BACKGROUND & AIMS: :An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily beta2-agonists or ultra long-acting beta2-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist-beta2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.
    背景与目标: :简化哮喘和慢性阻塞性肺疾病(COPD)管理并改善对处方疗法的依从性的重要步骤是将剂量频率降低到维持疾病控制所需的最低限度。因此,每天一次剂量的给药是改善依从性的重要策略,并且是大多数患者首选的治疗方案,这也可能导致依从性增强,并且可能具有导致整体临床结果改善的优势。正在开发每天一次的β2激动剂或超长效β2激动剂(LABA),例如卡莫特罗,茚达特罗,GSK-159797,GSK-597901,GSK-159802,GSK-642444和GSK-678007和COPD。另外,一些新的长效抗毒蕈碱剂(LAMAs),例如阿地铵,LAS-35201,GSK656398,GSK233705,NVA-237(甘草酸吡咯烷酸盐)和OrM3也正在开发中。无论如何,当前的观点是,开发包含几种长效支气管扩张药的组合的吸入器,以试图尽可能简化治疗方案将是有利的。因此,目前正在评估每日一次双作用的超LABA LAMA组合产品的几种选择。一种不同的方法是拥有同时存在两种药理作用的二聚体分子(这些分子被称为M3拮抗剂β2激动剂(MABA)支气管扩张剂)。成功的MABA产品的问世将彻底改变该领域,并为新的组合产品系列打开大门。
  • 【吸入的短效支气管扩张剂,用于处理儿童紧急哮喘:综述概述。】 复制标题 收藏 收藏
    DOI:10.1111/all.13039 复制DOI
    作者列表:Pollock M,Sinha IP,Hartling L,Rowe BH,Schreiber S,Fernandes RM
    BACKGROUND & AIMS: :International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist (SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic (SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice.
    背景与目标: :国际准则在急诊室(ED)中如何使用支气管扩张剂来管理儿童急性喘息病提出了相互矛盾的建议,而且在这些国家和地区之间,如何管理这些情况也存在差异。这可能反映出证据的不确定性。这份系统综述(SR)概述旨在合成,评估和呈现所有有关SR吸入短效支气管扩张剂治疗0-18岁儿童哮喘和喘息加重的有效性和安全性的所有SR证据。使用The Cochrane Collaboration推荐的方法进行了搜索,评论选择,数据提取和分析以及质量评估。纳入了13项SR,包括56项相关试验和5526例患者。结果表明,定量吸入器提供的短效β受体激动剂(SABA)作为一线治疗对年幼和较大儿童的疗效(年幼儿童的医院住院减少44%,ED住院时间减少33分钟在较大的孩子中)。对于严重情况下的大龄儿童,应在SABA中添加短效抗胆碱能(SAAC)(与单独使用SABA和SAAC相比,住院率分别降低了27%和74%)。常规实践中不建议进行连续雾化,向SABA中添加硫酸镁以及与沙丁胺醇相比的左旋沙丁胺醇。
  • 【校正至:长效支气管扩张剂可改善COPD患者的运动能力:系统评价和荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1186/s12931-018-0764-5 复制DOI
    作者列表:Di Marco F,Sotgiu G,Santus P,O'Donnell DE,Beeh KM,Dore S,Roggi MA,Giuliani L,Blasi F,Centanni S
    BACKGROUND & AIMS: :In the original publication [1] is an incorrect sentence in the abstract under Conclusions.
    背景与目标: :在原始出版物中,[1]是结论中摘要中的错误句子。
  • 【BRONCH-AHF研究:对诊断为急性心力衰竭的急诊科患者的雾化支气管扩张剂的近期预后影响。】 复制标题 收藏 收藏
    DOI:10.1002/ejhf.1028 复制DOI
    作者列表:Miró Ò,Tost J,Gil V,Martín-Sánchez FJ,Llorens P,Herrero P,Mebazaa A,Harjola VP,Ríos J,Marco-Hernández J,Collins SP,Peacock WF,Hollander JE,Lorca MT,Jacob J,ICA-SEMES Research Group.
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【支气管扩张剂在毛细支气管炎管理中的作用:一项临床试验。】 复制标题 收藏 收藏
    DOI:10.1080/02724936.1995.11747752 复制DOI
    作者列表:Chowdhury D,al Howasi M,Khalil M,al-Frayh AS,Chowdhury S,Ramia S
    BACKGROUND & AIMS: A randomized clinical trial was conducted on young children with bronchiolitis admitted to hospital with moderate illness to determine the efficacy of the bronchodilators Salbutamol and ipratropium bromide, either as a single drug or in combination, given as a nebulized solution, compared with a normal saline placebo. Eighty-nine patients, aged from 23 days to 11 months, were randomized into four groups, depending on administered drug or placebo, as followsgroup 1--Salbutamol (n = 20); group 2--ipratropium bromide (n = 23); group 3--combined Salbutamol and Ipratropium bromide (n = 24); group 4--normal saline (n = 22). The groups were identical with respect to age, sex, family history of atopy, respiratory syncytial virus (RSV) positivity and enrollment score. They were scored using the clinical parameters of wheezing, retractions and respiratory rate at enrollment, at 30 and 60 minutes after the first nebulization, and after 60 minutes following completion of subsequent nebulization at 6, 12, 24 and 36 hours. We did not find any significant difference in the rate of improvement and the final score (p = 0.49) in the four groups. The same finding was also noted in children aged more than 3 months (p = 0.35) and in those positive for RSV infection (p = 0.18). The lengths of hospitalization in the four groups were also similar (p = 0.79). It is concluded that there is no role for the nebulized bronchodilators Salbutamol and Ipratropium bromide, either as a single agent or in combination, compared with normal saline placebo in treating young children in hospital with bronchiolitis.

    背景与目标: 对入院中度疾病的毛细支气管炎的幼儿进行了一项随机临床试验,以确定与常规生理盐水安慰剂相比,支气管扩张药沙丁胺醇和异丙托溴铵作为雾化溶液作为单一药物或联合给药的疗效。年龄从23天到11个月不等的89例患者根据所用药物或安慰剂被随机分为四组,分别为1组-沙丁胺醇(n = 20)。 2-溴异丙托溴铵(n = 23);第3组:沙丁胺醇和异丙托溴铵合用(n = 24);第4组-生理盐水(n = 22)。两组在年龄,性别,特应性家族史,呼吸道合胞病毒(RSV)阳性和入组评分方面相同。在入组时,第一次雾化后30和60分钟,以及随后的雾化6、12、24和36小时后60分钟后,使用入院时的喘息,回缩和呼吸频率的临床参数对他们进行评分。在四组中,改善率和最终得分(p = 0.49)均未发现任何显着差异。在3个月以上的儿童(p = 0.35)和RSV感染阳性的儿童(p = 0.18)中也发现了相同的发现。四组的住院时间也相似(p = 0.79)。结论是,与生理盐水安慰剂相比,雾化的支气管扩张剂沙丁胺醇和溴化异丙托溴铵无论是单药还是联合用药,在治疗毛细支气管炎住院的幼儿中均没有作用。

  • 【机械通气期间吸入支气管扩张剂:给药技术,反应评估和成本效益。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hess D
    BACKGROUND & AIMS: :Inhaled beta 2 agonists can be administered by SVN or MDI during mechanical ventilation. MDI is an effective administration technique, it avoids the problems related to SVN, and it may be less expensive than SVN. A variety of techniques can be used to evaluate bronchodilator response during mechanical ventilation. Low-tech methods are also low cost, but may lack sensitivity. High-tech approaches to evaluate bronchodilator responsiveness may be more sensitive but are also more expensive. More work is needed to determine the most appropriate and cost-effective methods to evaluate bronchodilator response in mechanically ventilated patients.
    背景与目标: :吸入β2激动剂可以在机械通气期间通过SVN或MDI给药。 MDI是一种有效的管理技术,它避免了与SVN相关的问题,并且可能比SVN便宜。可以使用多种技术来评估机械通气期间的支气管扩张药反应。低技术含量的方法成本也较低,但可能缺乏敏感性。评估支气管扩张药反应性的高科技方法可能更敏感,但也更昂贵。需要更多的工作来确定评估机械通气患者支气管扩张药反应的最合适,最具成本效益的方法。
  • 【辣椒素类支气管扩张药的SAR研究。第1部分:邻苯二酚部分的重要性以及B环结构的各个方面。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmc.2007.11.055 复制DOI
    作者列表:Dalence-Guzmán MF,Berglund M,Skogvall S,Sterner O
    BACKGROUND & AIMS: :Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.
    背景与目标: :辣椒素及其衍生物和类似物是人类小气道收缩的一般抑制剂。从辣椒素结构的系统变化分为四个区域,建立了SAR。这部分涉及A-环的儿茶酚部分以及卡塞平的2,3,4,5-四氢-1H-2-氮杂环庚烷部分(B环)。结果表明,构象约束(作为稠合环)很重要,带有六元B环(作为1,2,3,4-四氢异喹啉)的化合物通常比相应的异吲哚啉2更有效。 1,3,4,5-四氢-1H-2-苯并ze庚因和2,3,4,5-四氢-1H-3-苯并ze庚因衍生物。
  • 【在没有药代动力学数据的情况下分析作用时程的非参数方法:应用于吸入性支气管扩张剂。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejps.2008.04.007 复制DOI
    作者列表:Agoram BM,Milligan PA,van der Graaf PH
    BACKGROUND & AIMS: :In spite of the extensive use of long-acting beta(2)-agonist (LABA) bronchodilators in asthma, the actual mechanism of their in vivo duration of action is not well understood, primarily due to limitations of standard pharmacokinetic-pharmacodynamic (PKPD) analysis methodologies. We have developed a novel method of analysing lung efficacy vs. time profiles for LABAs that can be used to provide comparative information on the lung PK. We hypothesised that for compounds that do not differ in their PK at the site of PD action, but differ in their in vivo potencies, the relationship between the area under the effect curve (AUEC) and the observed maximum effect (OME) at different doses is described by the same sigmoid curve. We have illustrated this property for standard PKPD models by obtaining analytical solution and through simulations. Anaesthetised dog in vivo effect vs. time profiles were gathered for six inhaled LABA candidates that differ in their in vitro potencies. Neither lung nor systemic PK was available for any compound. Analysis of the AUEC vs. OME data, derived from the efficacy profiles, using nonlinear mixed effects modelling indicated that for four compounds, the observed differences in in vivo duration of action was due to differences in their in vivo potencies and not because of lung PK differences. Therefore, it was concluded that for these compounds, characterisation of lung PK was unlikely to differentiate their PKPD characteristics. Thus, the proposed approach helped focus resources during translational research leading to lead candidate selection.
    背景与目标: :尽管在哮喘中广泛使用了长效β(2)-激动剂(LABA)支气管扩张剂,但其体内作用持续时间的实际机制仍未得到很好的了解,这主要是由于标准药代动力学-药效学(PKPD)的局限性)分析方法论。我们已经开发了一种新的分析LABA的时间与时间效率曲线的方法,可用于提供有关肺PK的比较信息。我们假设,对于在PD作用部位的PK不变但体内效力不同的化合物,在不同剂量下效应曲线下的面积(AUEC)与观察到的最大效应(OME)之间的关系用相同的S形曲线描述。我们已经通过获取解析解和仿真来说明了标准PKPD模型的这一特性。收集了六只吸入的LABA候选药物,它们的体外药效不同,麻醉后的狗体内效应与时间的关系曲线。肺和全身性PK均不可用于任何化合物。使用非线性混合效应模型对源自功效谱的AUEC与OME数据进行的分析表明,对于四种化合物,观察到的体内作用持续时间差异是由于其体内效力差异引起的,而不是由于肺部PK差异。因此,可以得出结论,对于这些化合物,肺部PK的表征不太可能区分其PKPD的特征。因此,所提出的方法有助于在翻译研究期间集中资源,从而导致候选者的选择。
  • 【使用体积描记法和示波法比较COPD患者的长效支气管扩张药。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2007.03013.x 复制DOI
    作者列表:Borrill ZL,Houghton CM,Tal-Singer R,Vessey SR,Faiferman I,Langley SJ,Singh D
    BACKGROUND & AIMS: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Forced expiratory volume in 1 s (FEV(1)) is the standard measurement used to measure drug effects in chronic obstructive pulmonary disease (COPD) clinical trials. Having previously shown that specific airway conductance (sGaw) measured using body plethysmography and impulse oscillometry (IOS) are more sensitive than FEV(1) for assessing short-acting bronchodilator effects in patients with COPD, we conducted the first randomized, placebo-controlled study to compare long-acting bronchodilators in COPD patients using these techniques. WHAT THIS STUDY ADDS:sGaw and IOS sensitively differentiated between the effects of tiotropium and salmeterol when FEV(1) measurements were similar. sGaw and IOS measurements are better than FEV(1) for sensitively assessing bronchodilator pharmacology and differentiating between treatments in COPD clinical trials. AIMS:Assessment of bronchodilator pharmacology in chronic obstructive pulmonary disease (COPD) may be improved by using more sensitive methods than spirometry, such as impulse oscillometry (IOS) and body plethysmography. We sought to compare salmeterol (S) and tiotropium (Tio) using these methods. METHODS:In this double-blind, randomized, four-way crossover study, 32 COPD patients received single doses of Tio (18 microg), S (50 and 100 microg) or placebo. Specific airway conductance (sGaw), forced expiratory volume in 1 s (FEV(1)) and IOS were measured pre- and up to 26 h postdose. Comparisons between treatments were analysed by weighted means (WM) between 0 and 12 (WM 0-12 h) and 12-24 h (WM 12-24 h) postdose. Data are expressed as mean difference (or geometric ratio for nonparametric data) with 95% confidence intervals. RESULTS:Tio and S100 significantly improved FEV(1), sGaw and IOS parameters up to 26 h and S50 up to 16 h. WM analysis showed no difference between Tio and S100 in FEV(1) for 0-12 h or 12-24 h. Maximum mid-expiratory flow (-0.06; -0.11, -0.01) and R35 (0.02; 0.01, 0.03) demonstrated superiority of S100 compared with Tio for WM 0-12 h sGaw (1.12; 1.02, 1.23), R5 (-0.06; -0.09, -0.02), R15 (-0.03; -0.05, -0.01), and resonant frequency (RF) (-2.30; -3.83, -0.77) showed superiority of Tio compared with S100 for WM 12-24 h. At 26 h, sGaw, R5, R15, X5 and RF also showed superiority of Tio compared with S100. CONCLUSIONS:sGaw and IOS parameters sensitively differentiated between the effects of Tio and S when FEV(1) measurements were similar. Clinical trials in patients with COPD should use IOS and sGaw to assess comprehensively bronchodilator pharmacology.
    背景与目标: 关于此对象的已知知识:1秒内的呼气量(FEV(1))是用于测量慢性阻塞性肺疾病(COPD)临床试验中药物作用的标准测量方法。先前已经表明,使用人体体积描记法和脉冲示波法(IOS)测量的比气道电导率(sGaw)比FEV(1)更敏感,以评估COPD患者的短效支气管扩张药效果,我们进行了首项随机,安慰剂对照研究比较使用这些技术的COPD患者中的长效支气管扩张剂。
    当FEV(1)测量相似时,sGaw和IOS在噻托铵和沙美特罗的作用之间有灵敏的区别。在敏感性评估COPD临床药理学和区分治疗方法方面,sGaw和IOS测量优于FEV(1)。
    目的:通过使用比肺活量测定法更灵敏的方法(例如脉冲示波法(IOS)和人体体积描记法),可以改善慢性阻塞性肺疾病(COPD)中支气管扩张药理学的评估。我们试图使用这些方法比较沙美特罗(S)和噻托溴铵(Tio)。
    方法:在这项双盲,随机,四向交叉研究中,有32名COPD患者接受了单剂量的Tio(18微克),S(50和100微克)或安慰剂。在服药前和服药后26小时内测量比气道电导率(sGaw),1 s内的呼气量(FEV(1))和IOS。在给药后0至12(WM 0-12h)至12-24h(WM 12-24h)之间通过加权平均值(WM)分析治疗之间的比较。数据表示为具有95%置信区间的平均差(或非参数数据的几何比率)。
    结果:Tio和S100显着改善了FEV(1),sGaw和IOS参数,最长可达26 h,而S50最长可达16 h。 WM分析显示FEV(1)中的Tio和S100在0-12小时或12-24小时之间没有差异。对于WM 0-12小时sGaw(1.12; 1.02,1.23),R5(-0.06),最大呼气中流量(-0.06; -0.11,-0.01)和R35(0.02; 0.01,0.03)显示出S100优于Tio。 ; -0.09,-0.02),R15(-0.03; -0.05,-0.01)和共振频率(RF)(-2.30; -3.83,-0.77)在WM 12-24小时内显示出优于S100的Tio。在26小时时,与S100相比,sGaw,R5,R15,X5和RF也显示出Tio的优越性。
    结论:当FEV(1)测量相似时,sGaw和IOS参数可以区分Tio和S的影响。 COPD患者的临床试验应使用IOS和sGaw来全面评估支气管扩张药理学。

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