Adrenergic beta-2 Receptor Agonists

肾上腺素能 β 2 受体激动剂
  • 文章类型: Journal Article
    慢性阻塞性肺疾病(COPD)的特征是肺活量测定中的气流阻塞和症状,例如劳累时呼吸困难和痰产生的慢性咳嗽,从而使其成为全球范围内的重大医疗保健问题。与西方国家的患者相比,日本的COPD患者具有独特的特征,包括年龄较大和恶化频率较低。日本呼吸学会(JRS)于2022年6月发布了第6版COPD指南。本文介绍了COPD的管理目标,阐述了COPD稳定期的管理,如指南所述。管理目标包括改善现状,如症状,生活质量(QOL),运动耐受力,和身体活动,并通过预防恶化和抑制疾病进展来减少未来的风险,以防止缩短健康预期寿命。管理计划应包括避免致病物质,疾病严重程度的评估,个性化的治疗方案。使用吸入支气管扩张剂的药物治疗是治疗稳定COPD的关键组成部分。支气管扩张器,包括短效和长效扩张器,通常用于缓解症状和改善生活质量。吸入皮质类固醇(ICSs)与长效支气管扩张剂联合使用,特别是在哮喘和COPD重叠的患者中,或经常加重嗜酸性粒细胞增多症的患者。长效毒蕈碱拮抗剂(LAMA)的联合治疗,长效β2激动剂(LABA),与LAMA+LABA组合相比,ICS有望改善生活质量和呼吸功能,并降低死亡率和恶化。非药物治疗,包括戒烟和肺部康复,也应该考虑。
    Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction on spirometry and symptoms such as dyspnea on exertion and chronic cough with sputum production, thus making it a significant healthcare issue worldwide. Japanese patients with COPD have unique characteristics compared to patients in Western countries, including older age and lower exacerbation frequency. The Japanese Respiratory Society (JRS) published the 6th edition of the COPD guideline in June 2022. This article introduces the management goals of COPD and describes its management during the stable phase, as outlined in the guideline. Management goals include improving the current status, such as the symptoms, quality of life (QOL), exercise tolerance, and physical activity, and reducing future risks through prevention of exacerbation and suppression of disease progression to prevent shortening of healthy life expectancy. Management plans should include avoidance of causative substances, assessment of disease severity, and personalized treatment plans. Pharmacotherapy using inhalation bronchodilators is a key component of the treatment of stable COPD. Bronchodilators, including short- and long-acting dilators, are commonly used to relieve symptoms and improve QOL. Inhaled corticosteroids (ICSs) are used in combination with long-acting bronchodilators, especially in patients with asthma and COPD overlap, or those experiencing frequent exacerbation of eosinophilia. Combination therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta 2 agonist (LABA), and ICS is expected to improve QOL and respiratory function and reduce mortality and exacerbation compared to the LAMA + LABA combination. Non-pharmacological therapies, including smoking cessation and pulmonary rehabilitation, should also be considered.
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  • 文章类型: Meta-Analysis
    慢性阻塞性肺疾病患者的护理必须包括使用支气管扩张剂后肺活量测定法确认诊断。由于临床异质性以及肺活量测定法评估的气流阻塞仅部分反映疾病的严重程度,对患者进行全面的临床评估应包括评估症状负担和急性加重风险,以便实施循证药物和非药物干预措施.本指南提供了综合系统评价的建议,包括荟萃分析和专家知情的临床评论,以优化稳定COPD患者的维持药物治疗。以及自2019年更新加拿大胸科学会(CTS)指南以来的新证据,修订和实用的治疗途径。关键的临床问题是使用患者/人群(P),干预(I),比较/比较器(C),和结果(O)模型三个问题,重点是症状(呼吸困难)/健康状况的结果,急性加重,和死亡率。这项系统评价和荟萃分析的证据导致建议所有肺活量测定证实为COPD的有症状患者应接受长效支气管扩张剂维持治疗。那些中度至重度呼吸困难(改良医学研究理事会≥2)和/或健康状况受损(COPD评估测试≥10)且恶化风险较低的患者应接受长效毒蕈碱拮抗剂/长效+2-激动剂(LAMA/LABA)的联合治疗。对于中度/重度呼吸困难和/或健康状况受损且恶化风险高的患者,应使用三联疗法(LAMA/LABA/吸入糖皮质激素)阿奇霉素,罗氟司特或N-乙酰半胱氨酸被推荐用于特定人群;反对使用茶碱的建议,对所有COPD患者进行全身性口服皮质类固醇如泼尼松和吸入性皮质类固醇单药治疗.
    Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.
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  • 文章类型: Guideline
    吸入皮质类固醇和超长效β-激动剂(ICS/uLABA)组合是对抗阻塞性气道疾病(OAD)的最新进展。ICS/uLABA的组合有几个优点,为其利用创造有利的景观。糠酸氟替卡松/曲芬酯维兰特罗(FF/Vi)是ICS/uLABA的一个这样的实例。这两种药物都有几个好处,例如方便的每日一次给药方案;高亲脂性;糠酸氟替卡松的高受体亲和力以及高功能选择性和维兰特罗的快速起效。然而,与常规ICS/LABA相比,全球哮喘倡议(GINA)和全球慢性阻塞性肺疾病倡议(GOLD)指南没有明确界定ICS/uLABA的定位.有一些不确定的地方,特别是在哮喘中使用ICS/uLABA的适当缓解策略。目前的共识是计划与一组印度肺病学专家达成的,以更清楚地说明FF/Vi在哮喘和COPD中的潜在用途。与常规ICS/LABA相比,本共识手稿中强调的临床陈述解决了围绕FF/Vi的有效性和安全性的关键临床问题,并确定了理想的患者使用情况。这份共识文件还阐明了在哮喘中与FF/Vi一起使用的适当缓解剂以及在OAD中使用基于FF/Vi的三联疗法。本文中提到的专家建议将为肺科医师以及参与为OAD患者提供护理的顾问医师提供指导,并将帮助他们权衡在处方ICS/uLABA组合时需要考虑的各种因素。
    Inhaled corticosteroid and ultra-long-acting beta-agonist (ICS/uLABA) combination is a recent advancement in the armamentarium against obstructive airways diseases (OADs). The combination of ICS/uLABA has several advantages, creating a favorable landscape for its utilization. Fluticasone furoate/vilanterol trifenatate (FF/Vi) is one such example of an ICS/uLABA. It offers several benefits from both drugs, such as a convenient once daily dosing schedule; high lipophilicity; high receptor affinity of fluticasone furoate along with high functional selectivity and a quick onset of action of vilanterol. However, the Global Initiative for Asthma (GINA) as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines do not clearly define the positioning of ICS/uLABA compared to conventional ICS/LABAs. There are a few areas of uncertainty especially around the appropriate reliever strategy with ICS/uLABA in Asthma. The current consensus was planned with a group of Indian pulmonology experts to provide more clarity on the potential use of FF/Vi in Asthma and COPD. The clinical statements highlighted in this consensus manuscript address crucial clinical questions revolving around the efficacy and safety of FF/Vi as compared to conventional ICS/LABAs and identify the ideal patient profile for its use. This consensus paper also sheds light upon the appropriate reliever to be used along with FF/Vi in Asthma and the utilization of FF/Vi-based triple therapy in OADs. Expert recommendations mentioned in this paper will serve as guidance to pulmonologists as well as consultant physicians who are involved in providing care to OAD patients and will help them weigh the various factors that need to be taken into account while prescribing ICS/uLABA combination.
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  • DOI:
    文章类型: Editorial
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  • 文章类型: Journal Article
    在当代慢性阻塞性肺疾病(COPD)管理指南中,急性加重史对长期吸入疗法的选择具有重要作用.这项研究旨在评估充盈吸入处方在COPD时间过程中的人群水平趋势及其与恶化史的关系。
    我们使用了不列颠哥伦比亚省的行政健康数据库,加拿大(1997-2015),建立诊断为COPD患者的回顾性事件队列.我们在随访的每一年内对长效吸入药物处方进行了量化,并记录了它们在COPD时程中的趋势。使用广义线性模型,我们调查了频繁加重状态(前12个月内≥2次中度或≥1次重度加重)与就诊后按处方配药之间的关联.
    132,004例COPD患者(平均年龄68.6,49.2%为女性)。诊断第一年最常见的药物类别是吸入性皮质类固醇(ICS,使用率为49.9%),其次是长效β-2肾上腺素受体激动剂(LABA,31.8%)。长效毒蕈碱受体拮抗剂(LAMA)是最不常见的处方(10.4%)。在整个随访期间,ICS仍然是最常见的处方,每年约有50%的患者使用。39.0%的患者在诊断的第一年接受联合吸入疗法,ICS+LABA是最常见的(30.7%)。对于三联疗法,与恶化史的关联最明显,全科医生的比值比(OR)为2.68,专家为2.02(两者均p<0.001)。与专家相比,全科医生的这种协会通常更强,除了LABA或ICS的单一疗法。
    我们记录了单一疗法(特别是LAMA)的低利用率和联合疗法(特别是含ICS)的高利用率。与全科医生相比,专家在选择吸入疗法时不太可能考虑恶化史。
    BACKGROUND: In contemporary guidelines for the management of Chronic Obstructive Pulmonary Disease (COPD), the history of acute exacerbations plays an important role in the choice of long-term inhaled therapies. This study aimed at evaluating population-level trends of filled inhaled prescriptions over the time course of COPD and their relation to the history of exacerbations.
    METHODS: We used administrative health databases in British Columbia, Canada (1997-2015), to create a retrospective incident cohort of individuals with diagnosed COPD. We quantified long-acting inhaled medication prescriptions within each year of follow-up and documented their trend over the time course of COPD. Using generalized linear models, we investigated the association between the frequent exacerbator status (≥2 moderate or ≥1 severe exacerbation(s) in the previous 12 months) and filling a prescription after a physician visit.
    RESULTS: 132,004 COPD patients were included (mean age 68.6, 49.2% female). The most common medication class during the first year of diagnosis was inhaled corticosteroids (ICS, used by 49.9%), followed by long-acting beta-2 adrenoreceptor agonists (LABA, 31.8%). Long-acting muscarinic receptor antagonists (LAMA) were the least commonly prescribed (10.4%). ICS remained the most common prescription throughout follow-up, being used by approximately 50% of patients during each year. 39.0% of patients received combination inhaled therapies in their first year of diagnosis, with ICS+LABA being the most common (30.7%). The association with exacerbation history was the most pronounced for triple therapy with an odds ratio (OR) of 2.68 for general practitioners and 2.02 for specialists (p<0.001 for both). Such associations were generally stronger among GPs compared with specialists, with the exception of monotherapy with LABA or ICS.
    CONCLUSIONS: We documented low utilization of monotherapies (specifically LAMA) and high utilization of combination therapies (particularly ICS containing). Specialists were less likely to consider exacerbation history in the choice of inhaled therapies compared with GPs.
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  • 文章类型: Journal Article
    Asthma is a major public health problem worldwide and is associated with excess morbidity, mortality, and economic costs associated with lost productivity. The National Asthma Education and Prevention Program has released the 2020 Asthma Guideline Update with updated evidence-based recommendations for treatment of patients with asthma.
    To report updated recommendations for 6 topics for clinical management of adolescents and adults with asthma: (1) intermittent inhaled corticosteroids (ICSs); (2) add-on long-acting muscarinic antagonists; (3) fractional exhaled nitric oxide; (4) indoor allergen mitigation; (5) immunotherapy; and (6) bronchial thermoplasty.
    The National Heart, Lung, and Blood Advisory Council chose 6 topics to update the 2007 asthma guidelines based on results from a 2014 needs assessment. The Agency for Healthcare Research and Quality conducted systematic reviews of these 6 topics based on literature searches up to March-April 2017. Reviews were updated through October 2018 and used by an expert panel (n = 19) that included asthma content experts, primary care clinicians, dissemination and implementation experts, and health policy experts to develop 19 new recommendations using the GRADE method. The 17 recommendations for individuals aged 12 years or older are reported in this Special Communication.
    From 20 572 identified references, 475 were included in the 6 systematic reviews to form the evidence basis for these recommendations. Compared with the 2007 guideline, there was no recommended change in step 1 (intermittent asthma) therapy (as-needed short-acting β2-agonists [SABAs] for rescue therapy). In step 2 (mild persistent asthma), either daily low-dose ICS plus as-needed SABA therapy or as-needed concomitant ICS and SABA therapy are recommended. Formoterol in combination with an ICS in a single inhaler (single maintenance and reliever therapy) is recommended as the preferred therapy for moderate persistent asthma in step 3 (low-dose ICS-formoterol therapy) and step 4 (medium-dose ICS-formoterol therapy) for both daily and as-needed therapy. A short-term increase in the ICS dose alone for worsening of asthma symptoms is not recommended. Add-on long-acting muscarinic antagonists are recommended in individuals whose asthma is not controlled by ICS-formoterol therapy for step 5 (moderate-severe persistent asthma). Fractional exhaled nitric oxide testing is recommended to assist in diagnosis and monitoring of symptoms, but not alone to diagnose or monitor asthma. Allergen mitigation is recommended only in individuals with exposure and relevant sensitivity or symptoms. When used, allergen mitigation should be allergen specific and include multiple allergen-specific mitigation strategies. Subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with symptoms and sensitization to specific allergens. Sublingual immunotherapy is not recommended specifically for asthma. Bronchial thermoplasty is not recommended as part of standard care; if used, it should be part of an ongoing research effort.
    Asthma is a common disease with substantial human and economic costs globally. Although there is no cure or established means of prevention, effective treatment is available. Use of the recommendations in the 2020 Asthma Guideline Update should improve the health of individuals with asthma.
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  • 文章类型: Journal Article
    尽管临床试验提供了证据,关于三联吸入疗法的使用存在一些不确定性和争议.为了评估专门呼吸单位的临床实践,在西班牙使用1年后实施了一项关于使用单一吸入器固定剂量三联疗法的Delphi共识文件.
    COPD专家科学委员会定义了一个主题指数,指导了系统的文献综述,并帮助设计了德尔菲问卷。这是在2019年4月至6月期间发送给其他45名COPD专家的。使用李克特量表分两轮测试了对58项陈述的同意/分歧。当≥80%的小组成员同意时,答复被归类为共识;当达到≥66%的同意程度时,答复被归类为多数;如果协议<66%,则存在分歧。
    两轮过后,44.44%的声明达成共识,14.81%达到多数,40.74%出现分歧。小组成员一致认为,从双重支气管扩张升级应基于表型,旨在防止恶化,但不是为了改善症状。在吸入型皮质类固醇组合中添加抗毒蕈碱药物可改善肺功能,症状和恶化预防。主要的安全问题包括与支气管扩张剂治疗相比,肺炎的风险增加,具有类似的心血管效应。根据血液嗜酸性粒细胞计数或阻塞严重程度,对患者类型的反应没有达成共识。
    小组成员的共识程度低可能反映了严重COPD管理的复杂性。此处提供的信息可能对为COPD患者实施个性化医疗的临床医生有用。
    Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain.
    A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥80% of the panelists agreed; a majority when a degree of agreement of ≥66% was reached; and divergence if agreement was <66%.
    After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity.
    The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.
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    文章类型: Editorial
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  • 文章类型: Comparative Study
    Rationale: There is uncertainty on the optimal first-line therapy for symptomatic chronic obstructive pulmonary disease (COPD). Long-acting β2-receptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) have long been mainstays of treatment, though it is still not clear if dual therapy with LABA/LAMA is superior to monotherapy for symptomatic COPD.Objectives: To clarify the evidence landscape, we conducted a systematic review to answer the following question: in patients with COPD who complain of dyspnea and/or exercise intolerance, is LABA/LAMA combination therapy more effective and equally safe compared with LABA or LAMA monotherapy?Methods: A search of Medline, EMBASE, and the Cochrane Library databases was conducted by a medical librarian for randomized controlled trials enrolling patients with COPD who complain of dyspnea and/or exercise intolerance that compare LABA/LAMA combination therapy to LABA or LAMA monotherapy. A systematic approach was used to screen, abstract, and critically appraise the emerging study evidence. The Grading of Recommendations Assessment, Development, and Evaluation method was applied to rate the certainty and quality of the evidence.Results: A total of 24 studies were eligible for inclusion (n = 45,441). Pairwise random-effects meta-analysis revealed reductions in hospital admissions (11% reduction; P < 0.01) and acute exacerbations of COPD (20% reduction; P < 0.002), all in favor of LABA/LAMA dual therapy. Although there is reduced dyspnea (0.10 standardized mean difference; P < 0.001) and improved health-related quality of life (-0.13 standardized mean difference; P < 0.001), both values did not meet a clinical meaningful difference threshold. LABA/LAMA combination therapy showed no difference in treatment-emergent adverse effects (risk ratio, 0.99; P = 0.34) when compared with either LAMA or LABA monotherapy.Conclusions: Based on the reviewed evidence, in patients with symptomatic COPD who complain of dyspnea and/or exercise intolerance, dual LABA/LAMA therapy is superior to either LABA or LAMA monotherapy based on the reduced risk of exacerbations and hospitalizations.
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  • 文章类型: Journal Article
    With the help of a routine clinical case, we highlighted the difference between two of the best asthma guidelines available at the time regarding therapeutic suggestions for the so-called \"third step\" for school-age asthmatic children. We have analyzed the scientific evidence that each of the two guidelines brings to support their position. Finally, we have motivatedly solved the clinical scenario. However, the question of disagreement between two guidelines remains unresolved. This can lead to unjustified differences in the management of schoolchildren with persistent asthma.
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