Dual Bronchodilator Research Articles

Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.

Benefit of dual bronchodilator therapy on exacerbations in former and current smokers with chronic obstructive pulmonary disease in real-world clinical practice: a multicenter validation study (TOReTO)

BackgroundDual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups.MethodsThe TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed.ResultsData from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study.ConclusionsThe three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution.

Emulating Randomized Trials by Observational Database Studies: The RCT-DUPLICATE Initiative in COPD and Asthma.

Observational studies are increasingly used to provide real-world evidence in regulatory decision-making. The RCT-DUPLICATE initiative conducted observational studies emulating two trials in patients with asthma and three in COPD. For each trial, new-user cohorts were constructed from two US healthcare claims databases, comparing initiators of the study and comparator drugs, matched on propensity scores. Proportional hazards models were used to compare the treatments on study outcomes. The observational studies involved more subjects than the corresponding trials, with treatment arms well-matched on baseline characteristics. An asthma example involved emulation of the 26-week FDA-mandated D5896 trial. With 6,494 asthma patients per arm, the hazard ratio (HR) of a serious asthma-related event with budesonide-formoterol versus budesonide was 1.29 (95% CI: 0.63-2.65), compared with 1.07 (95% CI: 0.70-1.65) in the trial. A COPD example is the emulation of the one-year IMPACT trial. With 4,365 COPD patients per arm, the HR of a COPD exacerbation with triple therapy versus dual bronchodilators was 1.08 (95% CI: 1.00-1.17), compared with 0.84 (95% CI: 0.78-0.91) in the trial. We found mainly discordant results between observational analyses and randomized trials, likely from the forced discontinuation of treatments prior to randomization in the trials, not mimicable in the observational analyses.

DElaying disease Progression In COPD with early escalation to Triple therapy – A Modelling Study (DEPICT-2)

IntroductionIn patients with chronic obstructive pulmonary disease (COPD), dual bronchodilator (long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA)) and triple therapy (inhaled corticosteroid (ICS)/LAMA/LABA) reduce risk of exacerbations and lung function decline in short-mid-term, but their long-term impact is unknown. This modelling study explores long-term impact of these therapies on lung function decline, quality of life (QoL) and all-cause mortality.MethodsThis modelling approach used a longitudinal non-parametric superposition model using published data regarding exacerbations, QoL (assessed by St. George's Respiratory Questionnaire (SGRQ)), and mortality. The model simulated disease progression from 40 to 75 years of age and assessed the impact of initiating dual bronchodilator at age 45 years (“LAMA/LABA only” group) and escalation to triple therapy at age 50 years (“Escalation to triple” group) on forced expiratory volume in 1 s (FEV1) decline, QoL, and mortality.ResultsModel simulation predicted that by 75 years of age: “LAMA/LABA only” preserves 159.1 mL of FEV1versusno treatment, “Escalation to triple” preserves an additional 376.5 mL and 217.3 mL of FEV1versusno pharmacotherapy and “LAMA/LABA only”, respectively. In “LAMA/LABA only”, SGRQ score reduces (−3.2)versusno treatment, which further reduces to −7.5 therapy in “Escalation to triple”. In “LAMA/LABA only”, mortality reduces by 5.4% by 75 yearsversusno treatment, while the “Escalation to triple” shows further decrease in mortality by 12.0%.ConclusionEarly pharmacotherapy initiation and escalation from dual bronchodilator to triple therapy could slow disease progression by preserving lung function and improving QoL and survival in patients with COPD.

Treatment patterns in patients with newly diagnosed COPD in the USA

BackgroundPrompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA.MethodsThis retrospective, noninterventional study used de-identified data from the Inovalon Insights’ database (Commercial, Medicaid Managed Care, and Medicare Advantage–insured individuals) between January 1, 2015, and December 31, 2021. The “patient journey” from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns.ResultsThe cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4).ConclusionsMost patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.

Dynamic chest radiographic evaluation of the effects of tiotropium/olodaterol combination therapy in chronic obstructive pulmonary disease: the EMBODY study protocol for an open-label, prospective, single-centre, non-controlled, comparative study

IntroductionTo date, there is limited evidence on the effects of bronchodilators on respiratory dynamics in chronic obstructive pulmonary disease (COPD). Dynamic chest radiography (DCR) is a novel radiographic modality that...

Clinical case of indacaterol / glycopyrronium bromide prescription in a patient with severe copd and concomitant pathology

Combinations of inhaled glucocorticosteroids (IHGC) and long-acting bronchodilator inhalers (LABA inhalers) have been widely used to treat chronic obstructive pulmonary disease (COPD) over the past two decades. Prescription of these drugs was based on large studies showing that this therapeutic regimen was more effective compared to placebo and monotherapy. The article presents a clinical case report of a patient with severe course of COPD and coronary heart disease (CHD). Up-to-date concepts of using dual bronchodilator therapy when switching from combinations of inhaled glucocorticosteroids and long-acting bronchodilator inhalers (IHGC/LABA) is discussed. A patient with COPD and coronary artery disease, atrial fibrillation while using IHGC/LABA had progressive respiratory failure, frequent exacerbations, and acute symptomatology. As there is evidence that the use of IHGC/LABA has a number of limitations in the combined course of COPD and cardiovascular diseases, first of all in coronary artery disease and arrhythmias, it was recommended to replace therapy with a combination of dual bronchodilators – a long-acting muscarinic antagonist (LAMA) and a long-acting β agonist (LABA). The therapy resulted in stabilization of the condition, reduction of clinical symptoms, and absence of cardiovascular complications. It has been concluded that the dual bronchodilator therapy with a combination of glycopyrronium bromide and indacaterol is prioritized in COPD, including COPD combined with cardiovascular pathology; no increase in cardiovascular events in patients with COPD combined with coronary artery disease is observed; Breezhaler inhaler is user-friendly for the patients and has advantages over other delivery devices.

Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies

The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. Several prospective, randomized, placebo-controlled studies have shown areduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, areduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with ablood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is apossible option for the eosinophilic phenotype in the near future.

Systemic Manifestations of COPD and the Impact of Dual Bronchodilation with Tiotropium/Olodaterol on Cardiac Function and Autonomic Integrity.

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 μg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests' results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests' results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m2 (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study.

Real-World Effectiveness of Single-Inhaler Triple Therapy for COPD: Impact of Diabetes Comorbidity

Background Type 2 diabetes is a frequent comorbidity in chronic obstructive pulmonary disease (COPD) patients, with the GOLD treatment recommendations asserting that the presence of diabetes be disregarded in the choice of treatment. Methods In a cohort of COPD patients with frequent exacerbations, initiators of single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, adjusted by propensity score weighting and stratified by type 2 diabetes. Results The COPD cohort included 1,114 initiators of triple inhalers and 4,233 of dual bronchodilators (28% with type 2 diabetes). The adjusted hazard ratio (HR) of exacerbation with triple therapy was 1.04 (95% CI: 0.86–1.25) among COPD patients with type 2 diabetes and 0.74 (0.65–0.85) in those without. The incidence of severe pneumonia was elevated with triple therapy among patients with type 2 diabetes (HR 1.77; 1.14–2.75). Conclusion Triple therapy in COPD is effective among those without, but not those with, type 2 diabetes. Future therapeutic trials in COPD should consider diabetes comorbidity.

Cardiovascular Events with the Use of Long-Acting Muscarinic Receptor Antagonists: An Analysis of the FAERS Database 2020–2023

PurposeThis study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium, and umeclidinium alone or in combination with a LABA and, in the context of triple therapy, with the addition of an ICS, and submitted to the food and drug administration adverse event reporting system (FAERS).MethodsA retrospective disproportionality analysis was conducted utilizing CV AE reports submitted to the FAERS from January 2020 to 30 September 2023. Disproportionality was measured by calculating the reporting odds ratio.ResultsCompared with ipratropium, tiotropium was associated with fewer reports of CV AEs. Compared with tiotropium, other LAMAs were more likely to be associated with reports of CV AEs. Combinations of glycopyrronium with indacaterol or formoterol and umeclidinium with vilanterol significantly reduced reports of CV AEs compared with the respective LAMA. The addition of an ICS to these combinations further reduced the risk of CV AE reports.ConclusionOur study suggests that inhaled LAMAs are not free from cardiac AE risks. This risk may be more evident when the newer LAMAs are used, but it is generally significantly reduced when COPD patients are treated with dual bronchodilators or triple therapy. However, these results do not prove that LAMAs cause CV AEs, as FAERS data alone are not indicative of a drug’s safety profile. Given the frequency with which COPD and cardiovascular disease co-exist, a large study in the general population could shed light on this very important issue.

Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History.

Chronic obstructive pulmonary disease (COPD) is one of the major causes of disability and death. Maintenance use of inhaled bronchodilator(s) is the cornerstone of COPD pharmacological therapy, but inhaled corticosteroids (ICSs) are also commonly used. This narrative paper reviews the role of ICSs as maintenance treatment in combination with bronchodilators, usually in a single inhaler, in stable COPD subjects. The guidelines strongly recommend the addition of an ICS in COPD subjects with a history of concomitant asthma or as a step-up on the top of dual bronchodilators in the presence of hospitalization for exacerbation or at least two moderate exacerbations per year plus high blood eosinophil counts (≥300/mcl). This indication would only involve some COPD subjects. In contrast, in real life, triple inhaled therapy is largely used in COPD, independently of symptoms and in the presence of exacerbations. We will discuss the results of recent randomized controlled trials that found reduced all-cause mortality with triple inhaled therapy compared with dual inhaled long-acting bronchodilator therapy. ICS use is frequently associated with common local adverse events, such as dysphonia, oral candidiasis, and increased risk of pneumonia. Other side effects, such as systemic toxicity and unfavorable changes in the lung microbiome, are suspected mainly at higher doses of ICS in elderly COPD subjects with comorbidities, even if not fully demonstrated. We conclude that, contrary to real life, the use of ICS should be carefully evaluated in stable COPD patients.

Baseline patient demographics for TETRIS: a prospective, noninterventional study to characterize the use of triple therapy for COPD in Germany.

Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2-48 weeks. For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. https://clinicaltrials.gov/study/NCT04657211.

Comparative effectiveness and safety of escalating to triple therapy versus switching to dual bronchodilators after discontinuing LABA/ICS in patients with COPD: a retrospective cohort study.

The latest guidelines discourage the use of long-acting beta2-agonists/inhaled corticosteroids (LABA/ICS) for chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the optimal subsequent treatment after discontinuing LABA/ICS. To compare the effectiveness and safety of switching from LABA/ICS to triple therapy (LABA/long-acting muscarinic antagonists (LAMA)/ICS) or to dual bronchodilators (LABA/LAMA) in COPD patients. This was a new-user, active-comparator, and propensity score-matched cohort study analyzing the Taiwanese nationwide healthcare insurance claims. We recruited COPD patients switching from LABA/ICS to triple therapy or to dual bronchodilators from 2015 to 2019. The primary effectiveness outcome was the annual rate of exacerbations, and safety outcomes included severe pneumonia and all-cause mortality. Stratification by prior exacerbations was conducted. After matching, each group comprised 1892 patients, 55% of whom experienced no exacerbations in the prior year. Treatment with LABA/LAMA/ICS versus LABA/LAMA showed comparable annual rate of moderate-to-severe exacerbations (incidence rate ratio, 1.04; 95% confidence interval (CI), 0.91-1.19). However, switching to LABA/LAMA/ICS was associated with increased risks of severe pneumonia (hazard ratio (HR), 1.65; 95% CI, 1.30-2.09) and all-cause death (HR, 1.39; 95% CI, 1.09-1.78). In patients with⩾2 prior exacerbations, LABA/LAMA/ICS versus LABA/LAMA was related to a 21% reduced rate of exacerbations but with a twofold increased pneumonia risk and a 49% elevated risk of all-cause mortality. Switching from LABA/ICS to triple therapy versus dual bronchodilators in COPD patients was associated with similar rates of annual exacerbations but was related to elevated risks of severe pneumonia and all-cause mortality. Among frequent exacerbators, triple therapy was associated with lower rates of exacerbation but was accompanied by increased risks of pneumonia and mortality compared to LABA/LAMA. Careful consideration of the examined safety events is necessary when switching from LABA/ICS to triple therapy in COPD management.

Применение тройного комбинированного препарата будесонид/гликопиррония бромид/формотерол у больных хронической обструктивной болезнью легких в реальной клинической практике (первый отечественный опыт)

Background: the Global Initiative for Chronic Obstructive Lung Disease (COPD) recommends triple therapy as an initial treatment for patients of "group E" (eosinophil count ≥ cells/μL) or as maintenance therapy for patients with frequent exacerbations. Triple therapy combines three types of inhaled medications that help improve lung function, manage symptoms and prevent exacerbations. The use of a single inhaler helps to increase patients' adherence to therapy. Aim: to evaluate the efficacy of the triple combination drug — budesonide/glycopyrronium bromide/formoterol (BUD/GLI/FOR) – and the patients' adherence to the ongoing inhalation therapy of COPD in real clinical practice. Materials and Methods: 30 patients with severe COPD (mean age 65.55±5.98 years) receiving basic therapy in accordance with clinical recommendations during remission were examined. After the initial examination, patients were recommended therapy with a combination of BUD/GLI/FOR 160/7.2/5 μg 2 inhalations twice a day. Patients received the prescribed therapy for 3 months, after which the assessments of therapy adherence and satisfaction with it, the changes concerning the severity of dyspnea (mMRC scale), COPD symptoms (CAT-test), spirometry exams were conducted. Results: after 3 months of therapy with BUD/GLI/FOR, none of the patients had an exacerbation of COPD. During treatment, there was a tendency to decrease the disease severity. No significant changes in spirometry have been established. In 83,3% of cases, patients performed inhalation without errors while reproducing the correct technique. All patients were satisfied with the therapy and were ready to continue treatment. Conclusion: the results obtained serve as the basis for further treatment of patients with COPD with the drug used in real clinical practice and are encouraging in achieving the clinical and functional efficacy announced in randomized clinical trials. KEYWORDS: COPD, triple combination, phospholipids, aerosphere, adherence, inhaled glucocorticosteroid, dual bronchodilator therapy. FOR CITATION: Titova O.N., Kuzubova O.A., Sklyarova D.B. Triple combination drug — budesonide/glycopyrronium bromide/formoterol in patients with chronic obstructive pulmonary disease in real clinical practice (the first domestic experience). Russian Medical Inquiry. 2024;8(8):459–463 (in Russ.). DOI: 10.32364/2587-6821-2024-8-8-3.

Experience of clinicians with dual bronchodilator therapy in COPD (EXPAND) in Nepal

Introduction: Combination of bronchodilators, particularly long-acting muscarinic antagonists (LAMAs) and long-acting β2 agonists (LABAs) have become the mainstay of pharmacological therapy for COPD. COPD is now a common non communicable disease in Nepal. Objective: The study evaluated the current perception and experience of the clinicians in Nepal on diagnosis and management of COPD with focus on use of dual bronchodilator therapy. Method: This cross-sectional, observational survey evaluated experiences of clinicians (n=96; pulmonologist-13, physician-57, general practitioner-26) in Nepal on diagnosis, management trends, and current perceptions on the use of dual bronchodilator therapy in COPD management. Result: 93% of clinicians were practising in an urban setting for an average of 10 years and an average of 35% of their patients are of COPD. 61% of clinicians use mMRC with (34%) or without (27%) CAT score. 92% of clinicians perceived that most of their patients had 1 (32%) or >1 (59%) exacerbation/year. 54% of clinicians performed spirometry on all their patients with suspected COPD. 49% of clinicians measured blood EOS in their patients with severe COPD before adding ICS. 93% of clinicians preferred dual therapy (separate inhalers or a combination) for their COPD patients, but 83% of clinicians preferred LABA + LAMA in a single inhaler over inhalers given separately. 57% of clinicians preferred LABA + LAMA and 82% preferred the Tiotropium + Formoterol combination. 81% of clinicians stepped up or stepped down their treatment. 56% of patients were taking LABA + LAMA + ICS and 55% of clinicians co-prescribed ICS + LABA with LABA + LAMA. 80% of clinicians checked the inhalation technique at every visit and an average of 54% of their COPD patients were adherent (>80%) to the prescribed inhalation therapy. 78% of clinicians felt that dryness of mouth was the most common side effect of LABA + LAMA. 94% of clinicians believed that managing COPD better could improve cardiovascular outcomes in their patients with coexistent COPD. Conclusion: In the EXPAND survey, Formoterol + Tiotropium was preferred by most clinicians in Nepal amongst the LABA + LAMA combination. There is a good scope for improvement in the utilization of tools like spirometry, mMRC, CAT, and blood EOS in the daily practice of clinicians in Nepal.

Delphi Consensus on Clinical Applications of GOLD 2023 Recommendations in COPD Management: How Aligned are Recommendations with Clinical Practice?

The objective of this Delphi study was to understand and assess the level of consensus among respiratory experts on the clinical application of GOLD 2023 recommendations in management of patients with chronic obstructive pulmonary disease (COPD). The study comprised two online surveys and a participant meeting with 34 respiratory experts from 16 countries. Responses of 73 questions were recorded using a Likert scale ranging from 0 (disagreement) to 9 (agreement). The consensus threshold was 75%. Survey 1 and survey 2 had 34 and 32 participants, respectively; and 25 attended the participant meeting. Consensus was reached on survey 1: 28/42; survey 2: 18/30 close-ended questions. A consensus was reached on the clinical relevance of most updates in definitions and diagnosis of COPD. Mixed results for the treatment recommendations by GOLD were noted: 74% agreed with the recommendation to initiate treatment with dual bronchodilators for group E patients; 63% agreed for including inhaled corticosteroids (ICS)/long-acting β2 agonist(LABA)/ Long-acting muscarinic receptor antagonists (LAMA) as a treatment option for GOLD B patients. Also, consensus lacked on removing ICS + LABA as an initial therapeutic option, in countries with challenges in access to other treatment option;. 88% agreed that they use GOLD recommendations in their daily clinical practice. This Delphi study demonstrated a high level of consensus regarding key concepts of GOLD 2023 report, with most participants favoring recent updates in definitions, diagnosis, management, and prevention of COPD. More evidence on the etiotype based management and treatment options for group B and E are required which could further strengthen clinical application of the GOLD report.

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed. The benefits of dual bronchodilation in symptomatic patients with COPD at low exacerbation risk, and its duration of efficacy and cost effectiveness in this population, are not yet fully established. Questions remain on the impact of baseline symptom severity, prior treatment, degree of reversibility to bronchodilators, and smoking status on responses to dual bronchodilator treatment. Using evidence from EMAX (NCT03034915), a 6-month trial comparing the LAMA/LABA combination umeclidinium/vilanterol with umeclidinium and salmeterol monotherapy in symptomatic patients with COPD at low exacerbation risk who were inhaled corticosteroid-naïve, we describe how these findings can be applied in primary care.

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

IntroductionBronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung...

Clinical Implications of Peak Inspiratory Flow in COPD: Post Hoc Analyses of the TRONARTO Study.

In patients with COPD, inhalation ability should be assessed when considering inhaler choice. To evaluate whether the soft mist inhaler (SMI) is suitable for COPD patients irrespective of inhalation ability, the TRONARTO study investigated the efficacy of dual long-acting bronchodilator therapy delivered via the Respimat® SMI on lung function in patients with COPD stratified by inhalation ability. Tiotropium/olodaterol delivered via the SMI was effective both in patients with peak inspiratory flow (PIF) <60L/min and PIF ≥60L/min, measured against medium-low resistance. This congress compilation summarizes post hoc analyses from the TRONARTO study presented at the annual American Thoracic Society 2022 and European Respiratory Society 2022 meetings. These analyses evaluated PIF in over 200 patients, with PIF measurements taken daily at home for 4weeks, and in the clinic at baseline, Weeks 2 and 4. Overall, 57.9% of patients had a PIF range (difference between lowest and highest PIF measurements) <20 L/min (12.4% of patients had PIF range <10 L/min). At-home PIF range decreased over the study period, suggesting that inhaler training/repeated PIF measurements may help to make patients' inspiratory effort more consistent. Some patient characteristics correlated with lower PIF (female gender, shorter stature, more severe disease, worse airflow obstruction) and lower PIF range (more severe disease). PIF measurements differed between medium-low and high-resistance settings, highlighting the importance of measuring PIF at the resistance of a patient's inhaler. PIF correlated poorly with spirometry measurements. As indicated in COPD management guidelines, choice of inhaler is essential to optimize pharmacologic therapies for COPD. Poor inspiratory ability should be viewed as a treatable trait that can help to inform inhaler choice. Inhaler training and consideration of PIF (if patients use a dry powder inhaler) can reduce patient-to-inhaler mismatch, with potential consequences for health status and exacerbation risk.