Long-acting Antimuscarinic Agent Research Articles

Triple inhaled therapy for asthma in Canada

A significant number of patients with asthma have poor control on their current inhaled therapies, typically a combination of inhaled corticosteroids (ICS) and long-acting beta-2 adrenergic bronchodilators (LABA). Adding a long-acting antimuscarinic agent (LAMA) has been shown to improve asthma control and the availability of triple therapy formulations (ICS/LABA/LAMA) in a single inhaler device or single inhaler triple therapy (SITT) mitigates the adherence concerns associated with use of multiple inhaler devices. Here, we provide an overview of the pivotal data concerning the use of triple asthma therapy in patients with poor control on ICS-LABA treatment, and present our expert approach to their application in the routine clinical management of such patients as well the appropriate sequencing of initiating triple therapy and seeking a referral for consideration of more advanced therapies.

Revisiting asthma pharmacotherapy: where do we stand and where do we want to go?

Several current guidelines/strategies outline a treatment approach to asthma, which primarily consider the goals of improving lung function and quality of life and reducing symptoms and exacerbations. They suggest a strategy of stepping up or down treatment, depending on the patient's overall current asthma symptom control and future risk of exacerbation. While this stepwise approach is undeniably practical for daily practice, it does not always address the underlying mechanisms of this heterogeneous disease. In the last decade, there have been attempts to improve the treatment of severe asthma, such as the addition of a long-acting antimuscarinic agent to the traditional inhaled corticosteroid/long-acting β2-agonist treatment and the introduction of therapies targeting key cytokines. However, despite such strategies several unmet needs in this population remain, motivating research to identify novel targets and develop improved therapeutic and/or preventative asthma treatments. Pending the availability of such therapies, it is essential to re-evaluate the current conventional "one-size-fits-all" approach to a more precise asthma management. Although challenging, identifying "treatable traits" that contribute to respiratory symptoms in individual patients with asthma may allow a more pragmatic approach to establish more personalised therapeutic goals.

The Role of Long-Acting Antimuscarinic Agents in the Treatment of Asthma.

The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data.

Inhaled corticosteroids administration/withdrawal as a therapeutic continuum for patients with chronic obstructive pulmonary disease in real clinical practice

Chronic obstructive pulmonary disease (COPD) is a progressing disease. Each exacerbation impairs the patient’s prognosis and increases burden for the healthcare system. The most common maintenance treatment options for COPD include long-acting bronchodilators – β2-agonists (LABA) and long-acting antimuscarinic agents (LAMA), and inhaled glucocorticosteroids (ICS), in fixed/opened double and triple combinations. Triple therapy in subjects with exacerbation history is the most effective way to prevent negative outcomes of the disease. It can reduce the frequency of exacerbations, slow down the disease progression, improve quality of life, and reduce mortality in the long run. On the other hand, the response to triple therapy may change over the time depending on airways inflammation level, infection activity, and exacerbation frequency. Current COPD guidelines propose different indications for therapy escalation and de-escalation (ICS addition/withdrawal) for more personalized and safe treatment. At the same time, many practical issues of this process are still unclear, e.g. how often treatment regimens should be reviewed and what escalation/de-escalation criteria should be prioritized. The authors strongly believe that COPD therapy should adapt a holistic treatment approach (continuum) with quick responses to any changes in the patient’s condition.The aim of our work was to create an algorithm for ICS administration/ withdrawal for COPD patients on long-acting dual bronchodilators maintenance therapy and to establish a therapeutic continuum that takes into account exacerbation history, symptoms severity, blood eosinophilia level, and concomitant asthma.Conclusion. This instrument can be a useful and convenient tool for long-term patient management when access to specialized medical care might be restricted. It takes into account the main current recommendations for COPD management and is easy to apply in real clinical practice.

COPD and glycopyrronium responsiveness assessment: An appraisal.

ECR/159/Inst/WB/2013/RR-20. Glycopyrronium bromide (a long-acting antimuscarinic agent: LAMA) appears pharmacokinetically suitable for testing bronchodilator responsiveness as salbutamol (short-acting β2-agonist: SABA). Exploring the feasibility, acceptability, degree of reversibility with glycopyrronium, and its comparison with that of salbutamol may be intriguing. New, consecutive, and willing outpatient attendees in the same season of the two consecutive years with chronic obstructive pulmonary disease (FEV1/FVC <0.07; FEV1 <80% of predicted) were subjected to serial responsiveness with inhalation of salbutamol first followed by 50 μg dry powder glycopyrronium [Salbutamol- Glycopyrronium] (phase-1) in the first year and glycopyrronium followed by salbutamol [Glycopyrronium- Salbutamol] (phase-2) in the following year. We looked for the acceptability, adverse reactions, and degree of changes in FEV1, FVC, FEV1/FVC, and FEF25-75 with comparison between the two groups. The [Salbutamol- Glycopyrronium] group (n = 86) were similar in age, body mass index, and FEV1 to the [Glycopyrronium- Salbutamol] group (n = 88). Both the agents could make a significant (P <.0001) improvement in the parameters independently or as add-on when used serially in alternate orders. The intergroup difference at no stage was significant. The sensitive patients to salbutamol (n = 48), glycopyrronium (n = 44), and both (n = 12) have improvement of 165, 189, and 297 mL while a both-insensitive group (n = 70) had barely 44 mL of improvement. The protocol was universally accepted without any adverse events. Serial testing of salbutamol and glycopyrronium responsiveness in alternate orders provides an insight regarding the independent and the add-on effects of these two agents. About 40% of our chronic obstructive pulmonary disease patients had no clinically appreciable difference in FEV1 with the salbutamol + glycopyrronium combination inhalation.

Multi-omics analysis reveals the mechanisms of action and therapeutic regimens of traditional Chinese medicine, Bufei Jianpi granules: Implication for COPD drug discovery

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a serious public health challenge in the world. According to the treatment instructions by Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020, bronchiectasis combine with inhaled corticosteroids and long-acting anti-muscarinic agents were recommended as the main prescription. However, this symptomatic treatment still has ineluctable limits because it ignored the most pathogenesis mechanism of COPD. As an alternative traditional Chinese medicine (TCM) for COPD, Bufei Jianpi granules (BJG) can reduce the frequency and duration of acute exacerbation in COPD patients and improve their quality of life. The evidence demonstrated BJG acts as therapeutics that retarding the airway remodeling process, eliminating phlegm, thrombolysis and improving mitochondrial function. However, the detailed molecular mechanism is still urgently revealed. PurpuseIn this study, we aim to find out the active pharmacodynamic ingredients and reveal the treatment mechanism of active pharmacodynamic ingredients. MethodsBased on the pharmacodynamic evaluation and chemomic profiling of BJG in COPD rats, an integrated multi-omics analysis was performed, including molecular networking, metabonomics, proteomics and bioinformatics. Moreover, focus on the active compounds, we verified the molecular core mechanism by molecular biology methods. ResultsPachymic acid, shionone, peiminine and astragaloside A was verified as therapeutic agents for improving the condition of COPD by acting on the EGFR, ERK1, PAI-1 and p53 target, respectively. ConclusionIn this study, our findings indicated that some compounds in BJG alleviates the pathological process of COPD, which is related to regulating lung function, mucus production, pulmonary embolism and energy metabolism and this will be a benefit complementary to GOLD guidelines.

When single-inhaler triple therapy is a preferred option in asthma management?

Asthma control is the main goal of management. Unfortunately, most asthma patients with moderate-severe asthma remain uncontrolled despite receiving standard treatment of inhaled corticosteroids (ICS) with long-acting β2 agonists (LABA). The addition of long-acting antimuscarinic agents (LAMA) has been shown to improve different aspects of asthma control, including symptoms, lung functions, and probably exacerbations. Such an option could be considered for low-T2 asthma phenotype. Umeclidinium and glycopyrronium bromide are other LAMA agents that have been recently made available in combination with ICS and LABA in single-inhaler triple therapy (SITT) devices. Here, we discuss the position of SITT as a new novel therapeutic option in asthma management and its clinical benefits, potential cost saving, and improved compliance.

Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications.

A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long‐acting β2 adrenergic bronchodilators (LABA). The addition of long‐acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single‐inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS‐LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Evaluating revefenacin as a therapeutic option for chronic obstructive pulmonary disease

ABSTRACT Introduction In chronic obstructive pulmonary disease (COPD), inhaled long-acting antimuscarinic agents (LAMA) are effective maintenance therapies used across all severity stages of the disease. Most of them are administered via dry powder inhalers, but these devices require a potent inspiratory flow which cannot be effectively achieved by patients with advanced disease. In such patients, inhaled therapy via nebulization might be an option. Areas covered Revefenacin is a LAMA that was specifically formulated for once daily nebulization and which was authorized by the FDA as a maintenance therapy for COPD. In phase II and III clinical studies discussed in this review, revefenacin demonstrated its rapid onset of action and sustained effect on lung function on both a short- and long-term basis. Expert opinion Nebulized revefenacin with once daily use does not require any particular effort of administration and hence can be used by patients with severe airways obstruction or by those having milder cognitive deficits. Further studies are needed, however, to better document the long-term cardiovascular safety and its ability to reduce the exacerbation rate.

Update on the NAEPPCC Asthma Guidelines: The wait is over, or is it?

As an asthma specialist, one is often asked to discuss the asthma guidelines. The challenge that one faces is deciding which guidelines to use as a resource for discussion or presentation. It often comes down to the following questions: What is the question? What message does one want to deliver? Where is the most current information? and Who is the target audience? This commentary will help answer those questions as it guides the reader through the new update of the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program guidelines and then outlines differences between 2 widely used strategies for the management of asthma: the Global Initiative for Asthma and the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma.

Incorporating new evidence on inhaled medications in COPD. The latin American chest association (ALAT) 2019

This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting β2-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of < 300 cells/μl. All this evidence, categorized according to the severity of the obstruction, symptoms, and risk of exacerbations, has been used to generate an algorithm for the use of inhaled medication in COPD.

Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019

This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting β2-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of <300 cells/μl. All this evidence, categorized according to the severity of the obstruction, symptoms, and risk of exacerbations, has been used to generate an algorithm for the use of inhaled medication in COPD.

Which Step-Up Drug Combination Is Preferred for Chronic Obstructive Pulmonary Disease Patients?

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend the combination of a long-acting antimuscarinic (LAMA) agent and

Availability and affordability of medicines and diagnostic tests recommended for management of asthma and chronic obstructive pulmonary disease in sub-Saharan Africa: a systematic review

BackgroundEarly accurate diagnosis and sustainable availability of affordable medicines and diagnostic tests is fundamental in optimal management of asthma and chronic obstructive pulmonary disease (COPD). We systematically reviewed original research articles about availability and affordability of medicines and diagnostic tests recommended for management of asthma and COPD in sub-Saharan Africa (SSA).MethodsWe searched PubMed, Scopus and African Journal Online for original research articles conducted in SSA between 2000 and March 2018 containing information about availability and affordability of any recommended medicine and diagnostic test for asthma and COPD.ResultsThe search yielded 9 eligible research articles. Availability of short-acting beta agonists (SABA), inhaled corticosteroids (ICS) and short acting anti-muscarinic agents (SAMA) ranged between 19.9–100%, 0–45.5% and 0–14.3% respectively. Combination of ICS-long acting beta agonists (LABA) were available in 0–14.3% of facilities surveyed. There was absence of inhaled long acting anti-muscarinic agents (LAMA) and LAMA/LABA combinations. Spirometry and peak expiratory flow devices were available in 24.4–29.4% and 6.7–53.6% respectively. Affordability of SABA and ICS varied greatly, ranging from < 2 to 107 days’ wages while ICS–LABA combinations, SAMA and oral theophylline plus leukotriene receptor antagonists cost 6.4–17.1, 13.7 and 6.9 days’ wages respectively.ConclusionAvailability and affordability of medicines and diagnostics recommended for the management of asthma and COPD is a big challenge in SSA. Research about this subject in this region is still limited. More robustly performed studies are required to further understand the magnitude of inequity in access to these medicines and diagnostic tests in SSA and also to formulate simple pragmatic solutions to address this challenge.

Alignment of Inhaled Chronic Obstructive Pulmonary Disease Therapies with Published Strategies. Analysis of the Global Initiative for Chronic Obstructive Lung Disease Recommendations in SPIROMICS.

Despite awareness of chronic obstructive pulmonary disease (COPD) treatment recommendations, uptake is poor. The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) spans 2010-2016, providing an opportunity to assess integration of 2011 Global Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in a large observational cohort study. To evaluate how COPD treatment aligns with 2011 GOLD strategies and determine factors associated with failure to align with recommendations. Information on inhaled medication use collected via questionnaire annually for 4 years was compiled into therapeutic classes (long-acting antimuscarinic agent, long-acting β-agonist, inhaled corticosteroids [ICS], and combinations thereof). Medications were not modified by SPIROMICS investigators. 2011 GOLD COPD categories A, B, C, and D were assigned. Alignment of inhaler regimen with first-/second-line GOLD recommendations was determined, stratifying into recommendation aligned or nonaligned. Recommendation-nonaligned participants were further stratified into overuse and underuse categories. Of 1,721 participants with COPD, at baseline, 52% of regimens aligned with GOLD recommendations. Among participants with nonaligned regimens, 46% reported underuse, predominately owing to lack of long-acting inhalers in GOLD category D. Of the 54% reporting overuse, 95% were treated with nonindicated ICS-containing regimens. Among 431 participants with 4 years of follow-up data, recommendation alignment did not change over time. When we compared 2011 and 2017 recommendations, we found that 47% did not align with either set of recommendations, whereas 35% were in alignment with both recommendations. Among SPIROMICS participants with COPD, nearly 50% reported inhaler regimens that did not align with GOLD recommendations. Nonalignment was driven largely by overuse of ICS regimens in milder disease and lack of long-acting inhalers in severe disease.

Asthma Guidelines Priority Topic: Long-Acting Anti-Muscarinic Agents in Asthma Management as Add-On to Inhaled Corticosteroids

The National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma are slated to be updated on 6 topic areas. This review summarizes the findings for the cha...

Optimising treatment for severe asthma.

The treatment landscape in severe asthma is changing rapidly, with multiple new therapies emerging that promise to transform patient outcomes. In a patient who is not responding to conventional therapy with inhaled corticosteroids and long-acting β2-agonists, it is important to first consider if the diagnosis of asthma is correct and, second, to reflect on whether readily modifiable factors are contributing to poor asthma control. In selected patients it may be appropriate to consider a modified n-of-1 trial of add-on therapies such as long-acting anti-muscarinic agents, leukotriene blockers, theophylline or low dose macrolide antibiotics. A number of monoclonal antibodies are now available that target the molecular pathways that contribute to asthma pathogenesis, and more such agents are likely to emerge in the near future. These biologicals can be transformative in selected patients, markedly reducing the frequency of asthma exacerbations, and allowing many patients to reduce or eliminate their use of long term oral corticosteroids. If the promise of personalised treatment is to be fully realised, it is important that better methods are developed to target these new and expensive treatments to patients most likely to respond. The ultimate goal of inducing remission or cure of asthma is still some distance away.

Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective

BackgroundEquitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.MethodsData on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days’ wages it would cost the least paid public servant were analysed.ResultsThe availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days’ wages for inhaled salbutamol to 17.1 days’ wages for formoterol/budesonide inhalers and 27.8 days’ wages for spirometry.ConclusionMedicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent versus a long-acting β2-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.