LABA Research Articles

USE OF INHALED CORTICOSTERIODS/LONG-ACTING BETA AGONIST (ICS-LABA) IN PATIENTS WITH BRONCHIOLITIS CAUSED BY SJÖGREN SYNDROME DECREASES NEED FOR ORAL STEROIDS

USE OF INHALED CORTICOSTERIODS/LONG-ACTING BETA AGONIST (ICS-LABA) IN PATIENTS WITH BRONCHIOLITIS CAUSED BY SJÖGREN SYNDROME DECREASES NEED FOR ORAL STEROIDS

CASE REPORT: BRONCHIAL THERMOPLASTY IN SEVERE PERSISTENT ASTHMA PATIENT

CASE REPORT: BRONCHIAL THERMOPLASTY IN SEVERE PERSISTENT ASTHMA PATIENT

Protocolo diagnóstico y terapéutico del asma de difícil control

Severe difficult-to-control or uncontrolled asthma is defined as the impossibility of controlling symptoms and exacerbations despite using high-dose inhaled corticosteroids and a long-acting beta2-agonist in the previous year, or oral glucocorticoids for six months or more of the last year. The first step to take with these patients is to rule out other concomitant diseases, verify their compliance with the indicated treatment, and differentiate which phenotype they have (T2 allergic or eosinophilic asthma or non-T2 asthma) according to their clinical and blood test characteristics. Based on said phenotype, biologic treatment can be administered via anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab, and benralizumab), or anti-IL-4/IL-13 (dupilumab) monoclonal antibodies in T2 asthma subtypes. To treat non-T2 type asthma, bronchial thermoplasty, systemic glucocorticoids, or even azithromycin can be considered.

INTRIGUING LUNG FUNCTION TESTS IN NEUROMUSCULAR WEAKNESS

INTRIGUING LUNG FUNCTION TESTS IN NEUROMUSCULAR WEAKNESS

The Effect of Glasthma Syrup in Asthma: a study protocol for a triple-blind randomized controlled trial.

ObjectivesAsthma is a chronic disease, and the demand for herbal medicines in this field has increased in recent years. The new findings highlight the role of the gut-lung axis in the pathophysiology of asthma. Hence, this study will evaluate the safety and efficacy of Glasthma syrup, an herbal formula based on Persian medicine, in improving asthma and regulating intestinal permeability. The formula consists of five herbal ingredients that have anti-inflammatory effects on the respiratory tract, also known as gut tonics.MethodsThe study will be conducted as a placebo-controlled, triple-blind, randomized trial. It will consist of a 4-week intervention followed by a 4-week follow-up period. The target sample size is 20 patients with moderate asthma aged 18 to 60 years. Eligible participants will be randomly assigned to either the experimental group or the control group in equal numbers. Patients in the experimental group will take Glasthma syrup (7.5 mL, twice a day), while patients in the control group will take a matching placebo. Both groups will receive a 4-week combination of a long-acting beta2 agonist and a leukotriene modulator as standard of care. Inhaled corticosteroids can be used as rescue medication as needed.ResultsThe primary outcomes are asthma symptom scale, lung function, and intestinal permeability. Secondary outcomes include quality of life, symptom recurrence rates, and blood tests. A safety assessment will also be conducted during the trial.ConclusionIn this trial, the effects of Glasthma syrup in patients with moderate asthma will be examined. The study will also assess the effects of the formulation on the gut-lung axis by simultaneously monitoring the gut permeability index, asthma symptoms, and lung function.

The Effect of Long-Acting Beta-2 Agonist Monotherapy and Long-Acting Anticholinergic Monotherapy to Quality-of-Life in Group B Stable COPD Patients

Background: Based on the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD), treatment for group B stable COPD patients is a long-acting beta-2 agonist (LABA) or long-acting anticholinergic (LAMA). Some studies experienced that LAMA was better than LABA but the opposite was also found in several studies. COPD patients often experience a decline in physical activity which causes a decrease in quality of life. We aimed to compare the effect of LABA or LAMA on quality of life in group B stable COPD patients.Methods: This was a study with case series design conducted on 50 COPD patients divided into two groups. The first group consisted of patients who used LABA for at least 3 months. The second group used LAMA for at least 3 months. All subjects filled in the SGRQ. The calculation of SGRQ was carried out using Microsoft Excel Calculator SGRQ.Results: A total 41 men and 9 women were enrolled in this study. There was no significant difference between the use of indacaterol monotherapy and tiotropium monotherapy on the quality of life although tiotropium showed a better quality of life (76%) than indacaterol monotherapy (64%).Conclusion: There was no significant difference in the use of indacaterol and tiotropium on the quality of life although in this case tiotropium showed better results (P=0.538).

Impact of pharmacotherapy with tiotropium/olodaterol on the pulmonary function in COPD patients depending on the Arg16Gly polymorphism of ADRB2 gene

Annotation. Chronic obstructive pulmonary disease (COPD) is a prevalent chronic disease. Endogenic or genetic factors play a significant role in the COPD development. The aim of our study was to investigate a response to the tiotropium/olodaterol treatment in patients with different ADRB2 gene polymorphism. 100 patients with the diagnosis of COPD were included into the study. Pulmonary function testing was performed during all study visits. All patients received treatment according to GOLD 2019, which included a combination of long-acting beta-2 agonists (LABA) and long-acting muscarinic antagonists (LAMA). According to the results of genetic testing all patients were divided into 3 groups: Arg16Arg – 23 patients (23%), Arg16Gly – 39 patients (39%), Gly16Gly – 38 patients (38%). Statistical processing of research materials was carried out using the SPSS statistical program package for Windows version 26.0. Descriptive statistics were determined for each interval variable and presented as mean ± standard deviation (SD). Kolmogorov-Smirnov test, Mann-Whitney test and T-test, Wilkson test, t-test, Kruskal-Wallis test were used as part of the one-way ANOVA analysis, as well as with the analysis of covariance (ANCOVA) followed by pairwise comparison of groups using Bonferroni corrections. Groups did not differ by sex, age, part of smokers, COPD duration. There was significant difference in RLM at the time of inclusion (p=0.01). There was a significant difference in the Pain value at the time of study completion (р=0.024). When comparing values of SGRQ questionnaire, there was a significant difference in the scales of Impact (р=0.006) and Total score (р=0.021). Thus, group Gly16Gly had better dynamics of SF-36 and SGRQ values during the study. Despite the absence of significant difference we can state, that Gly16Gly genotype has better response to treatment when compared to Arg16Arg, which is probably conditioned by the development of sensitization of ADRB2 receptor in Arg16Arg group.

Effect of camel milk in asthmatic children: A double-blind randomized pilot study.

Asthma is one of the prevalent diseases in children. There is some evidence regarding the benefits of camel milk in asthma. The present study was carried out to evaluate the effect of camel milk on asthmatic children. A randomized double-blind pilot study was operated in 2018 in a tertiary center. Sixty children aged more than 6 years with not well-controlled asthma were included. The intervention was consisting of 200-ml camel milk or placebo daily for 2 months. The medication regimen and spirometry parameters were assessed before and after the intervention. Data were analyzed using SPSS software. A total of 57 patients completed the trial. Patients were similar in demographic and baseline characteristics (p > 0.05). There was a significant difference between groups after intervention in use of inhaled corticosteroids (96.7% vs. 70.4%, p value = 0.01), short-acting beta-agonists (53.3% vs. 29.6%, p value = 0.0001) and long-acting beta-agonists (53.3% vs. 40.7%, p value = 0.04) in control and intervention, respectively. The percent of changes in forced expiratory volume (FEV1) in the control and intervention groups was 18.54 ± 14.89 and 21.89 ± 17.83, respectively (p = 0.19). The percent of changes in FEV1/forced vital capacity (FVC) in the control and intervention groups was 8.11 ± 7.12 and 11.11 ± 8.33, respectively (p = 0.14). In our pilot study, some children with asthma may benefit from camel milk. Further studies would be useful to evaluate this hypothesis.

Tiotropium for children and adolescents with severe asthma

Introduction An important proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, such as tiotropium bromide have been recommended for this subgroup of patients. The purpose of this study was to assess the cost-effectiveness of tiotropium as add-on therapies to ICS + LABA for children and adolescents with uncontrolled allergic asthma. Methods A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYS of two interventions including standard therapy (ICS + LABA), and add-on therapy with tiotropium, were calculated over a time horizon from 6 to 18 years. Probability sensitivity analyses were conducted. Results For a patient with severe asthma, our markov model showed that compared to standard therapy, add-on therapy with tiotropium was associated with higher treatment costs and QALY . The incremental cost-effectiveness ratio estimated was US$2,017 in the probabilistic model after Monte-Carlo simulation. Our base‐case results were robust to variations in all assumptions and parameters. The incremental net monetary benefit of US$327 with a 95% credible interval of US$396 to US425. Conclusion Add-on therapy with tiotropium was cost-effective when added to usual care in children and adolescents with severe asthma who remained uncontrolled despite treatment with medium or high-dose ICS/LABA. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Praktische Gesichtspunkte der Asthmatherapie mit Fixkombination und „single inhaler maintenance and reliever therapy“ (SMART) bei Kindern und Jugendlichen

The potential benefits and also possible problems of a fixed combination consisting of inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) as longer-term basic treatment and treatment as needed in exacerbation episodes in children and adolescents are presented under practical aspects. In the staged treatment recommended in the national treatment guidelines (NVL), in addition to the classical treatment of ICS plus bronchial dilators as needed, the single inhaler maintenance and reliever therapy (SMART) concept is also suggested as an alternative to short-acting betamimetics for treatment as needed over the age of 12 years. This means a needs-related inhalation treatment consisting of a fixed combination of ICS and rapid-acting beta‑2 agonists (RABA). This article touches on the potential as well as the problems of this treatment concept and the choice of substances for children and adolescents. Many of the combination substances available for children and adolescents, particularly for substances suitable for the SMART concept with a RABA, contain either a suboptimal ICS or LABA or are offered as a suboptimal device. There are also approval-related limitations for childhood and adolescence.

The Role of Dual Bronchodilation and the Conscientious Use of Inhaled Corticosteroid in COPD

Chronic obstructive pulmonary disease (COPD) is a global public health burden that stands out as a leading cause of mortality around the world, especially in less developed countries. COPD treatment should be centered on the individual necessities of each patient, integrating pharmacological therapy, immunization, nutritional support, pulmonary rehabilitation and control of comorbidities. Combining a long-acting antimuscarinic (LAMA) with a long-acting beta2-agonist (LABA) bronchodilator has proven to be more effective than monotherapy with LABA or LAMA, in terms of the functional improvement of forced expiratory volume (FEV1), symptoms and life quality and may be helpful in patients with progressive dyspnea. The eosinophil blood count is a simple biomarker that could guide personalized treatment strategies by identifying patients with greater clinical benefits of inhaled corticosteroid (ICS) treatment. However, one critical concern is the increased risk of pneumonia in individuals treated with ICS.

Risk Assessment of Acute Myocardial Infarction and Stroke Associated with Long-Acting Muscarinic Antagonists, Alone or in Combination, versus Long-Acting beta2-Agonists.

BackgroundThe long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safety study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists.PurposeTo estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA.Patients and MethodsThis population-based cohort study included patients with COPD aged ≥40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables.ResultsThe study included 11,121 new users of aclidinium, 4804 of aclidinium/formoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/formoterol) to 12.4 (LAMA/LABA), for stroke ranged from 4.8 (aclidinium/formoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/formoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95 [0.60–1.52], and highest for LAMA/LABA, 1.23 [0.91–1.67]), stroke (lowest for aclidinium/formoterol, 0.64 [0.39–1.06], and highest for tiotropium, 1.02 [0.81–1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75–1.16], and highest for LAMA/LABA, 1.24 [0.97–1.59]).ConclusionRisks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA.

Pharmacoeconomic analysis of the use of a fixed combination of tiotropium bromide and olodaterol as maintenance therapy in patients with chronic obstructive pulmonary disease in the Russian Federation

Objective: to evaluate the pharmacoeconomic effectiveness of the use of a fixed double combination of tiotropium bromide + olodаterol in order to treat chronic obstructive pulmonary disease (COPD) in comparison with less expensive monotherapy with long-acting beta-2-agonists (LABA) or long-acting anticholinergics (LAAC) with its insufficient effectiveness.Material and methods. The analysis of the impact on the health care system budget of the use of a fixed double chemical combination was carried out. The combination used was the one of tiotropium bromide + olodаterol in patients suffering from COPD who do not achieve effective disease control during LABA or LAAC monotherapy. We used published data on the distribution of patients into groups according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), also according to the therapy used and the frequency of exacerbations with hospitalization, obtained in a Russian epidemiological study. Direct and indirect costs associated with basic therapy and treatment of exacerbations requiring hospitalization were estimated as well.Results. Previously, it was shown that about 21.8% of patients with GOLD D severity of COPD receive therapy of insufficient efficacy (LABA monotherapy or long-acting M-cholinolytics). The use of a fixed combination of tiotropium bromide + olodaterol in such patients instead of monotherapy will reduce the direct costs of hospitalization by 21.1%, and the total costs (direct and indirect) – by 4.6%. On the scale of the Russian Federation, this will save 17.2 billion rubles a year.Conclusion. The results obtained showed that, despite the reasonably high cost of a fixed double combination in comparison with monopreparations, the use of double bronchodilating therapy allows to achieve more effective treatment and reduces both direct medical costs associated with hospitalization of patients with exacerbations of COPD, and direct non-medical and indirect costs associated with absenteeism of patients to work due to temporary disability as a result of hospitalization.

Determinants of asthma control and exacerbations in moderate to severe asthma

Determinants of asthma control and exacerbations in moderate to severe asthma

Assessment of Symptoms Control, Pulmonary Function and Related Quality of Life in Asthmatic Patients Treated with Extrafine Beclomethasone Dipropionate/Formoterol Fumarate 100/6 μg pMDI: Results of a Multicenter Observational Study in Romania (ALFRESCO Study).

IntroductionAsthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone. This is the first study done in Romania, which collected the real-world data on the effects of Foster® (extrafine beclomethasone dipropionate/formoterol fumarate BDP/FF in a pressurized metered-dose inhaler pMDI 100/6 μg formulation) in adult asthmatic population.ObjectiveWe aimed to assess the asthma symptoms control, pulmonary function and quality of life parameters in a heterogeneous Romanian asthmatic adult outpatient population, treated with extrafine BDP/FF 100/6 μg pMDI.MethodsThis was a prospective, multicenter, observational study involving 30 pulmonologists randomly selected from the Romanian healthcare system, which did not declare any competing interests. Recruitment period was Oct 2018 - Feb 2019, while the patients' observational period was 24 weeks. The study included poorly controlled and uncontrolled adult asthma outpatients treated with non-extrafine formulations medication, for which the treatment indication, according to Global Initiative for Asthma (GINA) 2018, was the use of an ICS-LABA combination. The study collected demographic data, smoking habits, comorbidities, data regarding asthma diagnosis, the evolution of asthma symptoms, spirometry, Asthma Control Questionnaire (ACQ-7) scoring test, current and concomitant treatment.ResultsOf 302 included patients, 290 completed the study. Pulmonary function parameters assessed during the trial (forced expiratory volume in one second - FEV1 and forced vital capacity - FVC) showed a significant improvement versus baseline (p<0.001). ACQ-7 score decreased significantly from 3.09±0.83 (visit 1) to 1.56±0.89 (visit 2) and to 1.09±0.81 (visit 3) (p<0.001). At the end of the study, 127 (43.79%) patients were well controlled (ACQ-7 score < 0.75).ConclusionThis observational study demonstrates the effectiveness and safety of extrafine fixed combination of BDP/FF (100/6 μg) pMDI in Romanian adult asthma patients uncontrolled with non-extrafine medication in a real-world setting, leading to clinically and statistically improvements in asthma control and pulmonary function.

Effectiveness of Maintenance and Reliever Therapy Using Inhaled Corticosteroid–Formoterol in Asthmatics

Real-world evidence on the effectiveness of maintenance and reliever therapy (MART) using inhaled corticosteroids plus long-acting beta-2 agonist (ICS-LABA) is sparse. This study aimed to evaluate the clinical effectiveness of MART (ICS-formoterol) by comparing its effectiveness with that of ICS-LABA plus as-needed short-acting beta-2 agonist (SABA) in adult asthmatics. We retrospectively retrieved data from the medical records of the Ajou University Medical Center, Korea, to compare clinical outcomes between patients treated with MART (the MART group) and those treated with ICS-LABA plus SABA (the non-MART group). Propensity score matching was performed and hazard ratios (HRs) with 95% confidence intervals were calculated using the Cox proportional hazards model. Severe asthma exacerbation (SAEx) was the primary end point, and asthma exacerbation (AEx), hospitalization, and pneumonia were secondary end points. Corticosteroid requirement was also analyzed. After propensity score matching, the MART and the non-MART groups included 231 and 512 adult asthmatics, respectively. The risk of SAEx and AEx was significantly lower in the MART group than in the non-MART group (HR [95% CI] 0.39 [0.18-0.77] and 0.61 [0.37-0.99], respectively). There was no significant difference in hospitalization and pneumonia risk between the 2 groups (HR [95% CI] 0.88 [0.55-1.37] and 0.63 [0.03-4.51], respectively). Corticosteroid requirements were lower in the MART group than in the non-MART group (median [interquartile range], 190.0 [97.9-420.0] and 411.0 [143.0-833.0] mg/person-year, respectively; P < .01). The MART strategy of ICS-formoterol was associated with lower risk of AEx and reduced corticosteroid requirement.

Regional variation in prevalence of difficult-to-treat asthma and oral corticosteroid use for patients in Australia: heat map analysis

Background In Australia, the regional prevalence of difficult-to-treat asthma is unknown. We aimed to describe regional variation in difficult-to-treat asthma prevalence and oral corticosteroid (OCS) use. Methods In this retrospective, observational, longitudinal study using data from March 2018–February 2019 in the NostraData longitudinal database, prescriptions dispensed for obstructive airway disease were processed through a high-level algorithm to identify patients with asthma. Difficult-to-treat asthma was defined by ≥2 high-dosage inhaled corticosteroids plus long-acting beta-agonist prescriptions over 6 months. Patients who additionally received OCS prescriptions sufficient to treat ≥2 exacerbations over 6 months were classified as having uncontrolled difficult-to-treat asthma. Patient-level data were analyzed across 340 geographic areas in Australia to determine regional prevalence of difficult-to-treat asthma, uncontrolled difficult-to-treat asthma, and OCS use. Results Of 1 851 129 people defined as having asthma, 440 800 (24%) were classified as having difficult-to-treat disease. Of those difficult-to-treat asthma patients, 96 338 (22%) were considered to have uncontrolled disease. Between 29% and 48% of patients had difficult-to-treat asthma in 49 geographic areas, most frequently located in Western Australia. Between 26% and 67% of patients had uncontrolled difficult-to-treat asthma in 29 geographic areas (mostly in Eastern Australia). Overall, a wide variability of asthma severity and control was observed among regions. Conclusions Despite global and national guidelines, regional differences in the prevalence of difficult-to-treat asthma and uncontrolled difficult-to-treat asthma and OCS use exist in Australia. Understanding these regional variations should inform policy and target management in the areas with the greatest unmet need.

Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?: Protocol of the randomised controlled OUTERSPACE trial

IntroductionMedication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to...

Cardiovascular events and all-cause mortality in patients with chronic obstructive pulmonary disease using olodaterol and other long-acting beta2-agonists.

PurposeWe examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all‐cause mortality compared with use of other long‐acting beta2‐agonists (LABAs). Channelling bias was also explored.MethodsThis Danish population‐based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias.ResultsThe IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n = 14 239) compared to users of other LABAs (n = 51 167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44–1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97–1.64) among LABA‐naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03–1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19–1.48) after applying overlap‐weights analysis.ConclusionsOlodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all‐cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

Effectiveness of Treatment With Dual Bronchodilation (LABA/LAMA) Compared With Combination Therapy (LABA/ICS) for Patients With COPD: A Population-Based Study

BackgroundInitiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations. MethodWe performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population. ResultsThe population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94–6.12) for LABA/ICS and 6.4 months (95%CI: 6.21–6.59) for LABA/LAMA; p<0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation. ConclusionInitiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care.